From 53a5495583c027965cedcf561faaaea602fb46cc Mon Sep 17 00:00:00 2001 From: Rafael Soler Date: Thu, 23 Jul 2026 01:08:22 +0200 Subject: [PATCH] feat(depmap): publish and wire DepMap Public 26Q1 evidence Publish the sanitized real DepMap Public 26Q1 evidence bundle and integrate it into the v0.5.0 reporting workflow. Add portable release loading, reproducibility metadata, checksums, inventories, 331 Markdown cards, 331 HTML reports, the discovery overlay, and authoritative three-intent baseline rankings. Preserve the deterministic 300-target baseline and keep DepMap as an optional post-ranking research-preview evidence layer requiring human review. Closes #74. --- .gitignore | 17 + CHANGELOG.md | 11 + README.md | 9 +- .../depmap/DepMap_Public_26Q1/README.md | 9 + .../activation_readiness_summary.json | 1 + .../artifact_compatibility.json | 1 + .../baseline_preservation.json | 1 + .../benchmark_coverage.json | 1 + .../DepMap_Public_26Q1/benchmark_report.md | 3 + .../DepMap_Public_26Q1/benchmark_universe.tsv | 57 + .../DepMap_Public_26Q1/candidate_overlay.tsv | 301 + .../depmap/DepMap_Public_26Q1/checksums.json | 1 + .../dependency_profile_summary.tsv | 332 + .../dependency_report_evidence.jsonl | 331 + .../DepMap_Public_26Q1/discovery_universe.tsv | 332 + .../integration_gate_decision.json | 1 + .../DepMap_Public_26Q1/integration_report.md | 7 + .../publication_inventory.tsv | 108 + .../publication_manifest.json | 1 + .../release_closure_manifest.json | 1 + .../DepMap_Public_26Q1/release_preflight.json | 1 + .../DepMap_Public_26Q1/release_readiness.json | 1 + .../DepMap_Public_26Q1/release_report.md | 5 + 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examples/target_cards/depmap_26q1/TBL1XR1.md create mode 100644 examples/target_cards/depmap_26q1/TBX3.md create mode 100644 examples/target_cards/depmap_26q1/TCL1A.md create mode 100644 examples/target_cards/depmap_26q1/TENT5C.md create mode 100644 examples/target_cards/depmap_26q1/TERT.md create mode 100644 examples/target_cards/depmap_26q1/TET1.md create mode 100644 examples/target_cards/depmap_26q1/TET2.md create mode 100644 examples/target_cards/depmap_26q1/TFE3.md create mode 100644 examples/target_cards/depmap_26q1/TFEB.md create mode 100644 examples/target_cards/depmap_26q1/TGFB1.md create mode 100644 examples/target_cards/depmap_26q1/TGFBR1.md create mode 100644 examples/target_cards/depmap_26q1/TIGIT.md create mode 100644 examples/target_cards/depmap_26q1/TMEM127.md create mode 100644 examples/target_cards/depmap_26q1/TNFRSF17.md create mode 100644 examples/target_cards/depmap_26q1/TNFRSF18.md create mode 100644 examples/target_cards/depmap_26q1/TP53.md create mode 100644 examples/target_cards/depmap_26q1/TP63.md create mode 100644 examples/target_cards/depmap_26q1/TRAF7.md create mode 100644 examples/target_cards/depmap_26q1/TREM2.md create mode 100644 examples/target_cards/depmap_26q1/TRRAP.md create mode 100644 examples/target_cards/depmap_26q1/TSC1.md create mode 100644 examples/target_cards/depmap_26q1/TSC2.md create mode 100644 examples/target_cards/depmap_26q1/TYR.md create mode 100644 examples/target_cards/depmap_26q1/TYRP1.md create mode 100644 examples/target_cards/depmap_26q1/U2AF1.md create mode 100644 examples/target_cards/depmap_26q1/UBR5.md create mode 100644 examples/target_cards/depmap_26q1/USP6.md create mode 100644 examples/target_cards/depmap_26q1/WAS.md create mode 100644 examples/target_cards/depmap_26q1/WNT5A.md create mode 100644 examples/target_cards/depmap_26q1/WRN.md create mode 100644 examples/target_cards/depmap_26q1/ZBTB16.md create mode 100644 examples/target_cards/depmap_26q1/ZFHX3.md create mode 100644 examples/target_cards/depmap_26q1/ZNF331.md create mode 100644 scripts/13_publish_depmap_v050.py create mode 100644 targetintel/functional_dependency/publication.py create mode 100644 targetintel/functional_dependency/report_loader.py create mode 100644 tests/test_depmap_html_publication.py create mode 100644 tests/test_depmap_pipeline_wiring.py create mode 100644 tests/test_depmap_report_loader.py create mode 100644 tests/test_depmap_v050_publication.py create mode 100644 tests/test_v050_release.py diff --git a/.gitignore b/.gitignore index 6d2479e..ce3c970 100644 --- a/.gitignore +++ b/.gitignore @@ -1,4 +1,21 @@ # Byte-compiled / optimized / DLL files +CRISPRGeneEffect* +CRISPRGeneDependency* +Model.csv +ScreenGeneEffect* +ScreenGeneDependency* +dependency_profiles.jsonl +*.parquet +*.h5 +*.h5ad +*.rds +*.loom +*.mtx +*.tar +*.tar.gz +*.zip +raw/ +cache/ __pycache__/ *.py[codz] *$py.class diff --git a/CHANGELOG.md b/CHANGELOG.md index 28a7a82..bfbf4be 100644 --- a/CHANGELOG.md +++ b/CHANGELOG.md @@ -2,6 +2,17 @@ All notable changes to TargetIntel-IO are documented in this file. +## v0.5.0 — DepMap Public 26Q1 publication interface + +- Added an offline, checksum-validating portable DepMap report-evidence loader. +- Added the optional `targetintel run --depmap-snapshot` report-decoration path; + it does not change productive scores, ranks, roles, or activation. +- Added a fail-closed publication command and official-source documentation for + validated DepMap Public 26Q1 aggregate bundles. +- Added a DepMap functional-dependency research-preview section to HTML indexes + when a portable snapshot is explicitly supplied. +- Single-cell and spatial evidence integration is planned for v0.6.0. + ## v0.2.0 — Common Evidence Layer Issue 208 completed with 183 passing tests; the final release may contain additional tests. diff --git a/README.md b/README.md index 901b5ec..cc5e962 100644 --- a/README.md +++ b/README.md @@ -16,7 +16,7 @@ TargetIntel-IO helps research teams distinguish possible therapeutic targets, bi | Target feasibility | Complete | Offline modality-specific feasibility and coverage | | Functional dependency | Research preview | DepMap/CRISPR evidence, closure, portable reporting and human review | -The project has progressed through v0.1.3 deterministic therapeutic-intent baseline, v0.2.0 Common Evidence Layer, v0.3.0 grounded evidence and human-review infrastructure, v0.4.0 target feasibility, and v0.5.0 DepMap/CRISPR functional-dependency architecture. v0.5.0 implementation and reporting architecture are complete; real DepMap Public 26Q1 repository snapshot publication is pending Issue 512. +The project has progressed through v0.1.3 deterministic therapeutic-intent baseline, v0.2.0 Common Evidence Layer, v0.3.0 grounded evidence and human-review infrastructure, v0.4.0 target feasibility, and v0.5.0 DepMap/CRISPR functional-dependency architecture. A sanitized, portable DepMap Public 26Q1 aggregate bundle and versioned research-preview reports are published. The validated closure captures the authoritative antibody/IO baseline score and rank used by the bounded overlay; it does not contain the other two full productive score tables, so reports do not infer them. The former “real DepMap Public 26Q1 repository snapshot publication is pending Issue 512” status is superseded by this publication. ## Biological problem and framing @@ -90,16 +90,19 @@ The normal deterministic workflow does not require a local DepMap release. targetintel run targetintel run --validate targetintel run --refresh +targetintel run --depmap-snapshot data/releases/depmap/DepMap_Public_26Q1 targetintel run --help python -m pytest -q ``` ## Outputs -The productive workflow writes a deterministic feature table, therapeutic-intent ranked targets, Markdown cards, HTML reports and figures. Optional reviewed evidence, feasibility, and functional-dependency sections decorate matching reports only. Portable aggregate DepMap snapshots are a separate research-preview artifact; real 26Q1 repository publication artifacts are pending Issue 512. +The productive workflow writes a deterministic feature table, therapeutic-intent ranked targets, Markdown cards, HTML reports and figures. Optional reviewed evidence, feasibility, and functional-dependency sections decorate matching reports only. A portable aggregate DepMap Public 26Q1 snapshot is a separate research-preview artifact and never changes scores, ranks, roles, or activation. Versioned examples include [HTML reports](examples/html_reports/), [figures](examples/figures/), the [benchmark snapshot](examples/benchmark/README.md), and [sensitivity outputs](examples/sensitivity/README.md). +Single-cell and spatial evidence integration is planned for v0.6.0. + ## Validation and reproducibility TargetIntel-IO uses deterministic rule application and tie-breaking, versioned configuration and benchmark material, immutable evidence contracts, and offline regression tests. Run `targetintel run --validate` for the existing workflow validation and `python -m pytest -q` for the test suite. The 56-target benchmark remains an internal consistency check, not independent validation or clinical performance evidence. @@ -153,7 +156,7 @@ This layer requires mandatory human review and does not alter deterministic scor ## Scientific limitations -TargetIntel-IO does not make treatment recommendations, validate targets or biomarkers, establish causality, or predict patient response. Missing evidence is not negative evidence. DepMap cell-line profiles do not reproduce the complete tumor microenvironment, and broad dependency can reflect general essentiality. Optional DepMap infrastructure is implemented, while real 26Q1 snapshot publication remains pending Issue 512. Future research directions include single-cell/spatial integration, clinical-response research models, and knowledge-graph expansion. +TargetIntel-IO does not make treatment recommendations, validate targets or biomarkers, establish causality, or predict patient response. Missing evidence is not negative evidence. DepMap cell-line profiles do not reproduce the complete tumor microenvironment, and broad dependency can reflect general essentiality. The real 26Q1 portable aggregate publication is available under `data/releases/depmap/DepMap_Public_26Q1`, with reports under `examples/html_reports/depmap_26q1` and `examples/target_cards/depmap_26q1`. Future research directions include single-cell/spatial integration, clinical-response research models, and knowledge-graph expansion. ## Repository map diff --git a/data/releases/depmap/DepMap_Public_26Q1/README.md b/data/releases/depmap/DepMap_Public_26Q1/README.md new file mode 100644 index 0000000..1802c26 --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/README.md @@ -0,0 +1,9 @@ +# Portable DepMap report snapshot + +This repository-safe derived snapshot records `DepMap_Public_26Q1` for melanoma anti-PD-1 context (`melanoma_anti_pd1:v1`). Configuration identity: `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`. Release manifest identity: `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`. Scientific closure identity: `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`. + +The original productive baseline contains 300 genes and remains unchanged. The discovery universe contains 331 identities; 18,531 genes were used only as background, and no 18,531-gene productive ranking was generated. Production activation is disabled and human review is mandatory. + +DepMap cell-line dependency is not clinical anti-PD-1 response evidence. Absence of tumor-cell dependency does not invalidate an immune target. General dependency may reflect broad essentiality, and cell lines do not reproduce the full tumor microenvironment. Full matrices and `dependency_profiles.jsonl` are excluded. + +Files: `release_summary.json` records validated closure state; the three Markdown reports preserve sanitized aggregate reports; `candidate_overlay.tsv` and `dependency_profile_summary.tsv` are derived aggregate tables; `selected_target_profiles.tsv` contains only requested descriptive profiles; `checksums.json` verifies the other eight files. diff --git a/data/releases/depmap/DepMap_Public_26Q1/activation_readiness_summary.json b/data/releases/depmap/DepMap_Public_26Q1/activation_readiness_summary.json new file mode 100644 index 0000000..551dcbb --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/activation_readiness_summary.json @@ -0,0 +1 @@ +{"approved_authorization_emitted":false,"candidate_activation_readiness":"blocked","human_review_required":true,"integration_state":"blocked_insufficient_evidence","module_release_state":"ready_research_preview_human_review"} diff --git a/data/releases/depmap/DepMap_Public_26Q1/artifact_compatibility.json b/data/releases/depmap/DepMap_Public_26Q1/artifact_compatibility.json new file mode 100644 index 0000000..66bdeb4 --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/artifact_compatibility.json @@ -0,0 +1 @@ +{"compatible":true,"expected_context_identity":"melanoma_anti_pd1:v1","metrics":{"background_count":18531,"baseline_fingerprint":"20cb7436b457d916d803d68f8335784291b8a36589b91605ec55291259d5a804","baseline_preserved":true,"baseline_ranking_id":"blr_20cb7436b457d916d803d68f8335784291b8a36589b91605ec55291259d5a804","benchmark_count":56,"benchmark_coverage":1.0,"development_count":null,"discovery_count":331,"holdout_count":null,"holdout_coverage":1.0,"integration_artifacts_compatible":true,"integration_state":null,"profile_run_id":"dmpr_6235f463ba983887eaaafaee391a220fd96d6a64ac8fc1e0dc8348e0bc345ab4","unresolved_count":0,"unresolved_fraction":0.0}} diff --git a/data/releases/depmap/DepMap_Public_26Q1/baseline_preservation.json b/data/releases/depmap/DepMap_Public_26Q1/baseline_preservation.json new file mode 100644 index 0000000..fcbcca6 --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/baseline_preservation.json @@ -0,0 +1 @@ +{"baseline_file_bytes_unchanged":true,"baseline_fingerprint_after":"20cb7436b457d916d803d68f8335784291b8a36589b91605ec55291259d5a804","baseline_fingerprint_before":"20cb7436b457d916d803d68f8335784291b8a36589b91605ec55291259d5a804","baseline_ranks_retained_exactly":true,"baseline_scores_retained_exactly":true,"default_profile_unchanged":true,"global_profile_registered":false,"production_ranking_configurations_unchanged":true,"production_scoring_configuration_fingerprints_after":{"scoring_antibody_io.yaml":"e86b929fd57a2520148f3708d5d9bebbf45bf1d89568f85e15610621911a0a15","scoring_biomarker.yaml":"96ab2815b3604ff2e9bb6e83eef715872f3187e76fea61d1815254cb32c58550","scoring_small_molecule.yaml":"3c86c056c92d177809937c67189e4dc104bbfe644695fc9d22bd0e8180cfc66e"},"production_scoring_configuration_fingerprints_before":{"scoring_antibody_io.yaml":"e86b929fd57a2520148f3708d5d9bebbf45bf1d89568f85e15610621911a0a15","scoring_biomarker.yaml":"96ab2815b3604ff2e9bb6e83eef715872f3187e76fea61d1815254cb32c58550","scoring_small_molecule.yaml":"3c86c056c92d177809937c67189e4dc104bbfe644695fc9d22bd0e8180cfc66e"},"production_scoring_configurations_unchanged":true} diff --git a/data/releases/depmap/DepMap_Public_26Q1/benchmark_coverage.json b/data/releases/depmap/DepMap_Public_26Q1/benchmark_coverage.json new file mode 100644 index 0000000..01b0024 --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/benchmark_coverage.json @@ -0,0 +1 @@ +{"profiled_target_count":56,"ranked_target_count":25,"reconciliation_counts":{"profiled_not_ranked":31,"ranked_and_profiled":25},"total_benchmark_targets":56} diff --git a/data/releases/depmap/DepMap_Public_26Q1/benchmark_report.md b/data/releases/depmap/DepMap_Public_26Q1/benchmark_report.md new file mode 100644 index 0000000..9515d06 --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/benchmark_report.md @@ -0,0 +1,3 @@ +# Dependency benchmark (analysis only) + +This offline synthetic analysis is exploratory, not clinical or causal validation. It does not enable a production dependency-aware ranking. Human review is required. diff --git a/data/releases/depmap/DepMap_Public_26Q1/benchmark_universe.tsv b/data/releases/depmap/DepMap_Public_26Q1/benchmark_universe.tsv new file mode 100644 index 0000000..a07fa3e --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/benchmark_universe.tsv @@ -0,0 +1,57 @@ +benchmark_class benchmark_limitations canonical_identity curation_rationale curation_version entry_format_version entry_id evidence_source_key expected_qualitative_behaviour inclusion_source_ids inclusion_sources inclusion_status limitations original_identifier partition rejection_reason resistance_axes resolution_status role role_annotation universe_type +known_positive "[""Translation is context dependent.""]" symbol:ARG1|entrez:383 Existing internal metabolic benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_e7acda184048f92df16f9e61de329e81515a234db0a1a84fbc13028fda9b3dd2 configs/benchmark_targets.yaml:metabolic_enzymatic_small_molecule curated metabolic-immune-suppression behaviour "[""tus_cc5d1639a9ad69cb55b47276b06ff2ab104def4eb7c1e348b98a442192ad56e2""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:metabolic_enzymatic_small_molecule""}]" included [] ARG1 holdout "[""metabolic_immune_suppression""]" resolved_exact metabolic immune-suppression target metabolic immune-suppression target benchmark +context_dependent "[""State marker does not establish a direct dependency.""]" symbol:AXL|entrez:558 Existing internal plasticity benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_7764c015b33d2ca2292ac1e8578e50349c334b200a3404e513b36b4aecb07a7b configs/benchmark_targets.yaml:melanoma_plasticity_small_molecule curated melanoma-plasticity behaviour "[""tus_c56358690cc163bcfda2ce23b980afc7379be9dd8aa914c5675e1d6bc785788a""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:melanoma_plasticity_small_molecule""}]" included [] AXL development "[""melanoma_plasticity""]" resolved_exact melanoma plasticity / resistance-associated marker melanoma plasticity / resistance-associated marker benchmark +biomarker_not_intervention_target "[""Often not a direct intervention target.""]" symbol:B2M|entrez:567 Existing internal antigen-presentation benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_7b12e53f6a2f7df4f15d8b187aee17cd65c13195129ea82943362391d9dd2651 configs/benchmark_targets.yaml:antigen_presentation_loss curated antigen-presentation biomarker behaviour "[""tus_cecee6666da014e2d199cc5352bcb4690e2de6b299784b49c55bd051ca5e92c0""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:antigen_presentation_loss""}]" included [] B2M development "[""antigen_presentation_loss""]" resolved_exact antigen-presentation resistance biomarker antigen-presentation resistance biomarker benchmark +challenging_control "[""Control class is not a therapeutic conclusion.""]" symbol:BAP1|entrez:8314 Existing internal poor-direct-target control. targetintel_io_internal_v0_1 v0.5.0 tue_9b46718b5f320bde4d3c76ed70d1c9ce9b6b3e46725160d44b6d1429308fa45d configs/benchmark_targets.yaml:poor_direct_targets curated poor-direct-target control behaviour "[""tus_bd4fc12d9cd1cbdce55304ddecd539d811be164d10aa7f2fec9d1f674dd9bf76""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:poor_direct_targets""}]" included [] BAP1 development "[""other_unresolved""]" resolved_exact tumor-intrinsic driver / poor direct therapeutic target tumor-intrinsic driver / poor direct therapeutic target benchmark +known_positive "[""Does not imply anti-PD-1 combination suitability.""]" symbol:BRAF|entrez:673 Existing internal tumor-intrinsic benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_9a433ff4846a6f3cd5120b874adb5e8b6a2fbda3188dd3d8a70f90e6b224832d configs/benchmark_targets.yaml:tumor_intrinsic_small_molecule curated tumor-intrinsic intervention behaviour "[""tus_8396c368a175a8de8d820d75ef1f76670691d25a3c39e5429c2c74e24e5f6a5f""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:tumor_intrinsic_small_molecule""}]" included [] BRAF development "[""tumor_intrinsic_driver""]" resolved_exact tumor-intrinsic driver / small-molecule target tumor-intrinsic driver / small-molecule target benchmark +known_positive "[""Internal rule-based curation; not independent validation.""]" symbol:CD274|entrez:29126 Existing internal checkpoint benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_f1cfccd51f74e9150c6ed0e453763965db2b2ec5b9c0e1393a02622e7c4df2ee configs/benchmark_targets.yaml:checkpoint_combination curated checkpoint-combination behaviour "[""tus_931a390a0533a345be5ed785f8a7aa6582c00de9d24964013cfb737043e22f72""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:checkpoint_combination""}]" included [] CD274 development "[""checkpoint_redundancy""]" resolved_exact anti-PD-1 combination target anti-PD-1 combination target benchmark +biomarker_not_intervention_target "[""Immune abundance marker rather than direct target.""]" symbol:CD8A|entrez:925 Existing internal immune-context benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_f2a082e317c16ec81dc9df415a88934b1412a591ac0f191e6838a8987db5d986 configs/benchmark_targets.yaml:immune_context curated immune-context biomarker behaviour "[""tus_7f29a60add00fd7eb92ea9662f4cdc7e5d928195fdf17bc3ef76646622abac7e""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:immune_context""}]" included [] CD8A development "[""immune_cold_state""]" resolved_exact immune-context marker immune-context marker benchmark +known_positive "[""Does not imply anti-PD-1 combination suitability.""]" symbol:CDK4|entrez:1019 Existing internal tumor-intrinsic benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_beb9450d970d255328b0e8877b866bae6dd4382a70ca5137742465d03b27e384 configs/benchmark_targets.yaml:tumor_intrinsic_small_molecule curated tumor-intrinsic intervention behaviour "[""tus_8396c368a175a8de8d820d75ef1f76670691d25a3c39e5429c2c74e24e5f6a5f""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:tumor_intrinsic_small_molecule""}]" included [] CDK4 holdout "[""other_unresolved""]" resolved_exact tumor-intrinsic driver / small-molecule target tumor-intrinsic driver / small-molecule target benchmark +challenging_control "[""Control class is not a therapeutic conclusion.""]" symbol:CDKN2A|entrez:1029 Existing internal poor-direct-target control. targetintel_io_internal_v0_1 v0.5.0 tue_80675543beda3ccc5fcd6a9a186fd9d24a6df596abe2e710323130a4c01e9795 configs/benchmark_targets.yaml:poor_direct_targets curated poor-direct-target control behaviour "[""tus_bd4fc12d9cd1cbdce55304ddecd539d811be164d10aa7f2fec9d1f674dd9bf76""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:poor_direct_targets""}]" included [] CDKN2A development "[""tumor_intrinsic_driver""]" resolved_exact tumor-intrinsic driver / poor direct therapeutic target tumor-intrinsic driver / poor direct therapeutic target benchmark +known_positive "[""Myeloid biology is context dependent.""]" symbol:CSF1R|entrez:1436 Existing internal myeloid benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_0bd5ff645ac4aa5f5f6a7580d3dd65c91c8e266848ecabd4ddc7566f3c7a8bc3 configs/benchmark_targets.yaml:myeloid_suppression curated myeloid-combination behaviour "[""tus_cdd532c8c92399da14dfbcb38978ca97e7923ea10afc936f77b362a5db74c5a7""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:myeloid_suppression""}]" included [] CSF1R development "[""myeloid_suppression""]" resolved_exact myeloid/TME anti-PD-1 combination target myeloid/TME anti-PD-1 combination target benchmark +known_positive "[""Internal rule-based curation; not independent validation.""]" symbol:CTLA4|entrez:1493 Existing internal checkpoint benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_d8dc69364aa33b8b34003a92773119ef9964ae77a78cd61d35d21d769c1bb359 configs/benchmark_targets.yaml:checkpoint_combination curated checkpoint-combination behaviour "[""tus_931a390a0533a345be5ed785f8a7aa6582c00de9d24964013cfb737043e22f72""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:checkpoint_combination""}]" included [] CTLA4 development "[""checkpoint_redundancy"", ""treg_suppression""]" resolved_exact anti-PD-1 combination target anti-PD-1 combination target benchmark +context_dependent "[""Stromal biology is heterogeneous and safety sensitive.""]" symbol:CXCL12|entrez:6387 Existing internal stromal benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_26c4b03c66392ab595f1d941d326d09ea1cbd80055e8551352a8c89749ff13a0 configs/benchmark_targets.yaml:stromal_ligand_io curated stromal-exclusion behaviour "[""tus_284790cd9dcf778a8224d791a7701cc4ba4b2ebf21e4d576e4eeba83c4ee7b40""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:stromal_ligand_io""}]" included [] CXCL12 development "[""tgfb_caf_exclusion""]" resolved_exact immune-exclusion / stromal-resistance candidate immune-exclusion / stromal-resistance candidate benchmark +biomarker_not_intervention_target "[""Immune abundance marker rather than direct target.""]" symbol:CXCL9|entrez:4283 Existing internal immune-context benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_3d5bf66e4d30e07fc24946b6280fad21cd8de9ae3a6026cd42f22feebfa51ef6 configs/benchmark_targets.yaml:immune_context curated immune-context biomarker behaviour "[""tus_7f29a60add00fd7eb92ea9662f4cdc7e5d928195fdf17bc3ef76646622abac7e""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:immune_context""}]" included [] CXCL9 development "[""immune_cold_state""]" resolved_exact immune-context marker immune-context marker benchmark +context_dependent "[""Stromal biology is heterogeneous and safety sensitive.""]" symbol:CXCR4|entrez:7852 Existing internal stromal benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_36c568135aa2ee8f584fcc8424af18a0b714259fd2a586fe7c514abcd2ff1f09 configs/benchmark_targets.yaml:stromal_receptor_small_molecule curated stromal-exclusion behaviour "[""tus_eda976bf4dc79998275df7691cfeae6dd00a4848fbd0a9c52576a7321faacfd7""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:stromal_receptor_small_molecule""}]" included [] CXCR4 holdout "[""tgfb_caf_exclusion""]" resolved_exact immune-exclusion / stromal-resistance candidate immune-exclusion / stromal-resistance candidate benchmark +known_positive "[""Translation is context dependent.""]" symbol:ENTPD1|entrez:953 Existing internal metabolic benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_387372e8eaa965552e5b9c7253b582cc36bba832751959fd1cf6397ad53618dc configs/benchmark_targets.yaml:metabolic_surface_io curated metabolic-immune-suppression behaviour "[""tus_4d6e20d76d4dffcaf9d953d5cc09adec937bb2bbfe690f594239475a918a596c""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:metabolic_surface_io""}]" included [] ENTPD1 development "[""metabolic_immune_suppression""]" resolved_exact metabolic immune-suppression target metabolic immune-suppression target benchmark +context_dependent "[""Treg targeting can affect immune tolerance.""]" symbol:FOXP3|entrez:50943 Existing internal Treg benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_9157b2b1d90b891ee8e0c1c0ac742ea92cc91ffecdb370b591a290ee6982ea43 configs/benchmark_targets.yaml:treg_suppression curated Treg-suppression behaviour "[""tus_278c749faa4d960664196012386e128a53909fcd77c15ec90b7128210f9df0ca""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:treg_suppression""}]" included [] FOXP3 development "[""treg_suppression""]" resolved_exact Treg-suppression marker / possible IO-combination target Treg-suppression marker / possible IO-combination target benchmark +negative_control "[""Unresolved axis is explicit and not a biological negative claim.""]" symbol:GNA11|entrez:2767 Existing internal context-control representative. targetintel_io_internal_v0_1 v0.5.0 tue_d7313c4c6ad60470805ed8f4e1c5171a701f8d0f8948709fe12b4c5ade9206fb configs/benchmark_targets.yaml:context_controls curated context-control behaviour "[""tus_7ecf4e7621e60df6e5c1e790d8696ce68c009072e645b9f63c56cf8d50c06e21""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:context_controls""}]" included [] GNA11 holdout "[""other_unresolved""]" resolved_exact unclear / low-confidence candidate unclear / low-confidence candidate benchmark +negative_control "[""Unresolved axis is explicit and not a biological negative claim.""]" symbol:GNAQ|entrez:2776 Existing internal context-control representative. targetintel_io_internal_v0_1 v0.5.0 tue_8f18890404a5c006a0f5007ecfd240f746c618e804af2c762e424adcca9a2611 configs/benchmark_targets.yaml:context_controls curated context-control behaviour "[""tus_7ecf4e7621e60df6e5c1e790d8696ce68c009072e645b9f63c56cf8d50c06e21""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:context_controls""}]" included [] GNAQ development "[""other_unresolved""]" resolved_exact unclear / low-confidence candidate unclear / low-confidence candidate benchmark +biomarker_not_intervention_target "[""Immune abundance marker rather than direct target.""]" symbol:GZMB|entrez:3002 Existing internal immune-context benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_341a088d45a3ac136e91003ecc6e79c8035048ad906ed09323d5d58aacf955d2 configs/benchmark_targets.yaml:immune_context curated immune-context biomarker behaviour "[""tus_7f29a60add00fd7eb92ea9662f4cdc7e5d928195fdf17bc3ef76646622abac7e""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:immune_context""}]" included [] GZMB development "[""immune_cold_state""]" resolved_exact immune-context marker immune-context marker benchmark +known_positive "[""Internal rule-based curation; not independent validation.""]" symbol:HAVCR2|entrez:84868 Existing internal checkpoint benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_582a0e2d5efea102058ddd3bce634f32aa485ca56cbef13cdc50f506cb98eb55 configs/benchmark_targets.yaml:checkpoint_combination curated checkpoint-combination behaviour "[""tus_931a390a0533a345be5ed785f8a7aa6582c00de9d24964013cfb737043e22f72""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:checkpoint_combination""}]" included [] HAVCR2 development "[""checkpoint_redundancy""]" resolved_exact anti-PD-1 combination target anti-PD-1 combination target benchmark +biomarker_not_intervention_target "[""Often not a direct intervention target.""]" symbol:HLA-A|entrez:3105 Existing internal antigen-presentation benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_b6ae8a2ab491175fe20f23925783ec2ba84be2d1d0007910c760b9adb9e677e4 configs/benchmark_targets.yaml:antigen_presentation_loss curated antigen-presentation biomarker behaviour "[""tus_cecee6666da014e2d199cc5352bcb4690e2de6b299784b49c55bd051ca5e92c0""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:antigen_presentation_loss""}]" included [] HLA-A development "[""antigen_presentation_loss""]" resolved_exact antigen-presentation resistance biomarker antigen-presentation resistance biomarker benchmark +biomarker_not_intervention_target "[""Often not a direct intervention target.""]" symbol:HLA-B|entrez:3106 Existing internal antigen-presentation benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_b783ffec34337be2fb575076017d5895ce04054766afa9054cd249579cc899bf configs/benchmark_targets.yaml:antigen_presentation_loss curated antigen-presentation biomarker behaviour "[""tus_cecee6666da014e2d199cc5352bcb4690e2de6b299784b49c55bd051ca5e92c0""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:antigen_presentation_loss""}]" included [] HLA-B holdout "[""antigen_presentation_loss""]" resolved_exact antigen-presentation resistance biomarker antigen-presentation resistance biomarker benchmark +known_positive "[""Translation is context dependent.""]" symbol:IDO1|entrez:3620 Existing internal metabolic benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_95480446fb2f412dc6a64cbc4ad307cb3daf1362c72c861c973b9d19ff0888ed configs/benchmark_targets.yaml:metabolic_enzymatic_small_molecule curated metabolic-immune-suppression behaviour "[""tus_cc5d1639a9ad69cb55b47276b06ff2ab104def4eb7c1e348b98a442192ad56e2""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:metabolic_enzymatic_small_molecule""}]" included [] IDO1 development "[""metabolic_immune_suppression""]" resolved_exact metabolic immune-suppression target metabolic immune-suppression target benchmark +mechanism_control "[""Mechanism association does not establish direct tractability.""]" symbol:IFNGR1|entrez:3459 Existing internal interferon-resistance benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_06885770a0a77d76a2349a36c2970363069d16219a906f4663cbdf486e62676b configs/benchmark_targets.yaml:ifng_resistance curated interferon-resistance mechanism behaviour "[""tus_a75c9cf0c5154f0a700f7bd157adc31ae824fd2c794d51656e36f8b911df2694""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:ifng_resistance""}]" included [] IFNGR1 development "[""ifng_resistance""]" resolved_exact IFN-gamma resistance mechanism / biomarker IFN-gamma resistance mechanism / biomarker benchmark +context_dependent "[""Treg targeting can affect immune tolerance.""]" symbol:IL2RA|entrez:3559 Existing internal Treg benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_e5c243162ea8423238b4becf0e377aad9f7636fdca2b5084174e274f276efed3 configs/benchmark_targets.yaml:treg_suppression curated Treg-suppression behaviour "[""tus_278c749faa4d960664196012386e128a53909fcd77c15ec90b7128210f9df0ca""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:treg_suppression""}]" included [] IL2RA holdout "[""treg_suppression""]" resolved_exact Treg-suppression marker / possible IO-combination target Treg-suppression marker / possible IO-combination target benchmark +mechanism_control "[""Mechanism association does not establish direct tractability.""]" symbol:IRF1|entrez:3659 Existing internal interferon-resistance benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_3c3f038f4baf47934b8c381bb5cadd23be3f9fbbfa043ab2579757276da99760 configs/benchmark_targets.yaml:ifng_resistance curated interferon-resistance mechanism behaviour "[""tus_a75c9cf0c5154f0a700f7bd157adc31ae824fd2c794d51656e36f8b911df2694""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:ifng_resistance""}]" included [] IRF1 development "[""ifng_resistance""]" resolved_exact IFN-gamma resistance mechanism / biomarker IFN-gamma resistance mechanism / biomarker benchmark +mechanism_control "[""Mechanism association does not establish direct tractability.""]" symbol:JAK1|entrez:3716 Existing internal interferon-resistance benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_da03f55ea76c0fcb42743cb7e47fc6a8899cc9b47ec13649cbd42c89159b2950 configs/benchmark_targets.yaml:ifng_resistance curated interferon-resistance mechanism behaviour "[""tus_a75c9cf0c5154f0a700f7bd157adc31ae824fd2c794d51656e36f8b911df2694""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:ifng_resistance""}]" included [] JAK1 development "[""ifng_resistance""]" resolved_exact IFN-gamma resistance mechanism / biomarker IFN-gamma resistance mechanism / biomarker benchmark +mechanism_control "[""Mechanism association does not establish direct tractability.""]" symbol:JAK2|entrez:3717 Existing internal interferon-resistance benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_fcdf22315a611983db4966d2de7f51f20d9910e4ac66400f9bde805189755076 configs/benchmark_targets.yaml:ifng_resistance curated interferon-resistance mechanism behaviour "[""tus_a75c9cf0c5154f0a700f7bd157adc31ae824fd2c794d51656e36f8b911df2694""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:ifng_resistance""}]" included [] JAK2 development "[""ifng_resistance""]" resolved_exact IFN-gamma resistance mechanism / biomarker IFN-gamma resistance mechanism / biomarker benchmark +known_positive "[""Does not imply anti-PD-1 combination suitability.""]" symbol:KIT|entrez:3815 Existing internal tumor-intrinsic benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_dd427cf1f39269a754475dde8852cebd8656b8a9fe69a457a1aa995e163d9d2a configs/benchmark_targets.yaml:tumor_intrinsic_small_molecule curated tumor-intrinsic intervention behaviour "[""tus_8396c368a175a8de8d820d75ef1f76670691d25a3c39e5429c2c74e24e5f6a5f""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:tumor_intrinsic_small_molecule""}]" included [] KIT development "[""other_unresolved""]" resolved_exact tumor-intrinsic driver / small-molecule target tumor-intrinsic driver / small-molecule target benchmark +known_positive "[""Internal rule-based curation; not independent validation.""]" symbol:LAG3|entrez:3902 Existing internal checkpoint benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_5c2bce30b63a22d1d15bcb82ae4fa83a98fd5ed3ab2bf0f5f562ad5c804f41e8 configs/benchmark_targets.yaml:checkpoint_combination curated checkpoint-combination behaviour "[""tus_931a390a0533a345be5ed785f8a7aa6582c00de9d24964013cfb737043e22f72""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:checkpoint_combination""}]" included [] LAG3 development "[""checkpoint_redundancy""]" resolved_exact anti-PD-1 combination target anti-PD-1 combination target benchmark +known_positive "[""Myeloid biology is context dependent.""]" symbol:LILRB1|entrez:10859 Existing internal myeloid benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_5e035fbc4349605694b51d6e002ccb578ba69999b1fe7b3020a89b6732242966 configs/benchmark_targets.yaml:myeloid_suppression curated myeloid-combination behaviour "[""tus_cdd532c8c92399da14dfbcb38978ca97e7923ea10afc936f77b362a5db74c5a7""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:myeloid_suppression""}]" included [] LILRB1 development "[""myeloid_suppression""]" resolved_exact myeloid/TME anti-PD-1 combination target myeloid/TME anti-PD-1 combination target benchmark +known_positive "[""Myeloid biology is context dependent.""]" symbol:LILRB2|entrez:10288 Existing internal myeloid benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_fd78868c8f54228d61cdbefd87807ec6930a748e2f2b5e44aa8169ab966bf6c9 configs/benchmark_targets.yaml:myeloid_suppression curated myeloid-combination behaviour "[""tus_cdd532c8c92399da14dfbcb38978ca97e7923ea10afc936f77b362a5db74c5a7""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:myeloid_suppression""}]" included [] LILRB2 holdout "[""myeloid_suppression""]" resolved_exact myeloid/TME anti-PD-1 combination target myeloid/TME anti-PD-1 combination target benchmark +known_positive "[""Does not imply anti-PD-1 combination suitability.""]" symbol:MAP2K1|entrez:5604 Existing internal tumor-intrinsic benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_e21d6d74a7ad6a0f012b0514c35ef3ca96e6dba4e77a2ce4c76e2a1399368655 configs/benchmark_targets.yaml:tumor_intrinsic_small_molecule curated tumor-intrinsic intervention behaviour "[""tus_8396c368a175a8de8d820d75ef1f76670691d25a3c39e5429c2c74e24e5f6a5f""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:tumor_intrinsic_small_molecule""}]" included [] MAP2K1 development "[""tumor_intrinsic_driver""]" resolved_exact tumor-intrinsic driver / small-molecule target tumor-intrinsic driver / small-molecule target benchmark +known_positive "[""Does not imply anti-PD-1 combination suitability.""]" symbol:MAP2K2|entrez:5605 Existing internal tumor-intrinsic benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_2f3e0dbc89c9d3f9f939ade71622b0aa79cabe46338feeeb972e4e32408920ef configs/benchmark_targets.yaml:tumor_intrinsic_small_molecule curated tumor-intrinsic intervention behaviour "[""tus_8396c368a175a8de8d820d75ef1f76670691d25a3c39e5429c2c74e24e5f6a5f""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:tumor_intrinsic_small_molecule""}]" included [] MAP2K2 development "[""other_unresolved""]" resolved_exact tumor-intrinsic driver / small-molecule target tumor-intrinsic driver / small-molecule target benchmark +known_positive "[""Myeloid biology is context dependent.""]" symbol:MARCO|entrez:8685 Existing internal myeloid benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_721c6d4c6beae154057c4a27ff2c0ce228a9079575e2987436f87383debcafd7 configs/benchmark_targets.yaml:myeloid_suppression curated myeloid-combination behaviour "[""tus_cdd532c8c92399da14dfbcb38978ca97e7923ea10afc936f77b362a5db74c5a7""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:myeloid_suppression""}]" included [] MARCO development "[""myeloid_suppression""]" resolved_exact myeloid/TME anti-PD-1 combination target myeloid/TME anti-PD-1 combination target benchmark +known_positive "[""Myeloid biology is context dependent.""]" symbol:MERTK|entrez:10461 Existing internal myeloid benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_ad3fb272d42ea9c5fc161d88877a37b243b58b992cf8d6d69873236d0cbbe82c configs/benchmark_targets.yaml:myeloid_suppression curated myeloid-combination behaviour "[""tus_cdd532c8c92399da14dfbcb38978ca97e7923ea10afc936f77b362a5db74c5a7""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:myeloid_suppression""}]" included [] MERTK development "[""myeloid_suppression""]" resolved_exact myeloid/TME anti-PD-1 combination target myeloid/TME anti-PD-1 combination target benchmark +biomarker_not_intervention_target "[""Biomarker role does not imply direct intervention suitability.""]" symbol:MITF|entrez:4286 Existing internal tumor-intrinsic biomarker representative. targetintel_io_internal_v0_1 v0.5.0 tue_4f1eacf2a4142ce352b9affc9449e8381404e2b195c958e3648b541002d7c2ab configs/benchmark_targets.yaml:tumor_intrinsic_biomarkers curated tumor-intrinsic biomarker behaviour "[""tus_9b17b0d84afc0fc6619e94172403a52c453d27203b6e60f8f99938fbd7c3126a""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:tumor_intrinsic_biomarkers""}]" included [] MITF development "[""other_unresolved""]" resolved_exact tumor-intrinsic driver / biomarker tumor-intrinsic driver / biomarker benchmark +challenging_control "[""Control class is not a therapeutic conclusion.""]" symbol:NF1|entrez:4763 Existing internal poor-direct-target control. targetintel_io_internal_v0_1 v0.5.0 tue_cb8bcf01155c3953497f2733806eef2c293ac2c1ec72e4198b3dcd71134a4f1c configs/benchmark_targets.yaml:poor_direct_targets curated poor-direct-target control behaviour "[""tus_bd4fc12d9cd1cbdce55304ddecd539d811be164d10aa7f2fec9d1f674dd9bf76""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:poor_direct_targets""}]" included [] NF1 development "[""tumor_intrinsic_driver""]" resolved_exact tumor-intrinsic driver / poor direct therapeutic target tumor-intrinsic driver / poor direct therapeutic target benchmark +context_dependent "[""State marker does not establish a direct dependency.""]" symbol:NGFR|entrez:4804 Existing internal plasticity benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_3765a4f2cb98b66368e2a71692cf67caa485a158d61dfd3d71d81aae1182e717 configs/benchmark_targets.yaml:melanoma_plasticity_biomarker curated melanoma-plasticity behaviour "[""tus_fa6fb1e779c5532e743c947c56d3cc50216fc59f2940c5acc5f07362275e113c""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:melanoma_plasticity_biomarker""}]" included [] NGFR holdout "[""melanoma_plasticity""]" resolved_exact melanoma plasticity / resistance-associated marker melanoma plasticity / resistance-associated marker benchmark +biomarker_not_intervention_target "[""Biomarker role does not imply direct intervention suitability.""]" symbol:NRAS|entrez:4893 Existing internal tumor-intrinsic biomarker representative. targetintel_io_internal_v0_1 v0.5.0 tue_c4bec1944e642b5067a74a987e813e27df68cb9321b7cd2d6a40dc9c262f8ced configs/benchmark_targets.yaml:tumor_intrinsic_biomarkers curated tumor-intrinsic biomarker behaviour "[""tus_9b17b0d84afc0fc6619e94172403a52c453d27203b6e60f8f99938fbd7c3126a""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:tumor_intrinsic_biomarkers""}]" included [] NRAS development "[""tumor_intrinsic_driver""]" resolved_exact tumor-intrinsic driver / biomarker tumor-intrinsic driver / biomarker benchmark +known_positive "[""Translation is context dependent.""]" symbol:NT5E|entrez:4907 Existing internal metabolic benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_6fb0e851d8a8059e961e865788cd06591352c452866cc44102860723893ad644 configs/benchmark_targets.yaml:metabolic_surface_io curated metabolic-immune-suppression behaviour "[""tus_4d6e20d76d4dffcaf9d953d5cc09adec937bb2bbfe690f594239475a918a596c""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:metabolic_surface_io""}]" included [] NT5E development "[""metabolic_immune_suppression""]" resolved_exact metabolic immune-suppression target metabolic immune-suppression target benchmark +known_positive "[""Internal rule-based curation; not independent validation.""]" symbol:PDCD1|entrez:5133 Existing internal checkpoint benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_83c60a076cb3cc4553a8f9ada0c27e6a9cc61f7b167bd0725f6d44b39afc6442 configs/benchmark_targets.yaml:checkpoint_combination curated checkpoint-combination behaviour "[""tus_931a390a0533a345be5ed785f8a7aa6582c00de9d24964013cfb737043e22f72""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:checkpoint_combination""}]" included [] PDCD1 development "[""checkpoint_redundancy""]" resolved_exact anti-PD-1 combination target anti-PD-1 combination target benchmark +biomarker_not_intervention_target "[""Immune abundance marker rather than direct target.""]" symbol:PRF1|entrez:5551 Existing internal immune-context benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_94718c7144289e9b612d7c3b3ea333146f65bae2272969122b651d1a1a7e66c5 configs/benchmark_targets.yaml:immune_context curated immune-context biomarker behaviour "[""tus_7f29a60add00fd7eb92ea9662f4cdc7e5d928195fdf17bc3ef76646622abac7e""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:immune_context""}]" included [] PRF1 holdout "[""immune_cold_state""]" resolved_exact immune-context marker immune-context marker benchmark +challenging_control "[""Control class is not a therapeutic conclusion.""]" symbol:PTEN|entrez:5728 Existing internal poor-direct-target control. targetintel_io_internal_v0_1 v0.5.0 tue_920597631e385f44d693addafae07b1dee04b8c113c23da678d86893a50a67c6 configs/benchmark_targets.yaml:poor_direct_targets curated poor-direct-target control behaviour "[""tus_bd4fc12d9cd1cbdce55304ddecd539d811be164d10aa7f2fec9d1f674dd9bf76""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:poor_direct_targets""}]" included [] PTEN holdout "[""tumor_intrinsic_driver""]" resolved_exact tumor-intrinsic driver / poor direct therapeutic target tumor-intrinsic driver / poor direct therapeutic target benchmark +negative_control "[""Unresolved axis is explicit and not a biological negative claim.""]" symbol:SLC24A5|entrez:283652 Existing internal context-control representative. targetintel_io_internal_v0_1 v0.5.0 tue_4aaed7a8fcbf2909e0ae9c53b1c06525992a24526ef172ef3c64478bb6257ae4 configs/benchmark_targets.yaml:context_controls curated context-control behaviour "[""tus_7ecf4e7621e60df6e5c1e790d8696ce68c009072e645b9f63c56cf8d50c06e21""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:context_controls""}]" included [] SLC24A5 development "[""other_unresolved""]" resolved_exact unclear / low-confidence candidate unclear / low-confidence candidate benchmark +mechanism_control "[""Mechanism association does not establish direct tractability.""]" symbol:STAT1|entrez:6772 Existing internal interferon-resistance benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_25f543dec9e5f893dab8e3c21e3982ca74ecfeeb839539ae36b297288921dd17 configs/benchmark_targets.yaml:ifng_resistance curated interferon-resistance mechanism behaviour "[""tus_a75c9cf0c5154f0a700f7bd157adc31ae824fd2c794d51656e36f8b911df2694""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:ifng_resistance""}]" included [] STAT1 holdout "[""ifng_resistance""]" resolved_exact IFN-gamma resistance mechanism / biomarker IFN-gamma resistance mechanism / biomarker benchmark +biomarker_not_intervention_target "[""Often not a direct intervention target.""]" symbol:TAP1|entrez:6890 Existing internal antigen-presentation benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_2dedb150768f697879ded0ac1edc85bce582ad511382b8152d8e00cabf76cdbc configs/benchmark_targets.yaml:antigen_presentation_loss curated antigen-presentation biomarker behaviour "[""tus_cecee6666da014e2d199cc5352bcb4690e2de6b299784b49c55bd051ca5e92c0""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:antigen_presentation_loss""}]" included [] TAP1 development "[""antigen_presentation_loss""]" resolved_exact antigen-presentation resistance biomarker antigen-presentation resistance biomarker benchmark +biomarker_not_intervention_target "[""Often not a direct intervention target.""]" symbol:TAP2|entrez:6891 Existing internal antigen-presentation benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_f2315f8bbad98c9714e9b80fafd04ad5784ce846fd0b0c4f1ff41c68c3e3f664 configs/benchmark_targets.yaml:antigen_presentation_loss curated antigen-presentation biomarker behaviour "[""tus_cecee6666da014e2d199cc5352bcb4690e2de6b299784b49c55bd051ca5e92c0""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:antigen_presentation_loss""}]" included [] TAP2 development "[""antigen_presentation_loss""]" resolved_exact antigen-presentation resistance biomarker antigen-presentation resistance biomarker benchmark +biomarker_not_intervention_target "[""Biomarker role does not imply direct intervention suitability.""]" symbol:TERT|entrez:7015 Existing internal tumor-intrinsic benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_aadfc9bb17861f478950475181bac5d71bd81461440992f87db6c6337438aa12 configs/benchmark_targets.yaml:tumor_intrinsic_biomarkers curated tumor-intrinsic biomarker behaviour "[""tus_9b17b0d84afc0fc6619e94172403a52c453d27203b6e60f8f99938fbd7c3126a""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:tumor_intrinsic_biomarkers""}]" included [] TERT holdout "[""other_unresolved""]" resolved_exact tumor-intrinsic driver / biomarker tumor-intrinsic driver / biomarker benchmark +context_dependent "[""Stromal biology is heterogeneous and safety sensitive.""]" symbol:TGFB1|entrez:7040 Existing internal stromal benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_5110f5b9e17830ce383ffab7071c51b8e54788ee5a0158bfea8e5106748ea417 configs/benchmark_targets.yaml:stromal_ligand_io curated stromal-exclusion behaviour "[""tus_284790cd9dcf778a8224d791a7701cc4ba4b2ebf21e4d576e4eeba83c4ee7b40""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:stromal_ligand_io""}]" included [] TGFB1 development "[""tgfb_caf_exclusion""]" resolved_exact immune-exclusion / stromal-resistance candidate immune-exclusion / stromal-resistance candidate benchmark +context_dependent "[""Stromal biology is heterogeneous and safety sensitive.""]" symbol:TGFBR1|entrez:7046 Existing internal stromal benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_8a6b416b8b04211d28f3bf5068e6c18ddba12df75ec88c93e811d6d73678f4f9 configs/benchmark_targets.yaml:stromal_receptor_small_molecule curated stromal-exclusion behaviour "[""tus_eda976bf4dc79998275df7691cfeae6dd00a4848fbd0a9c52576a7321faacfd7""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:stromal_receptor_small_molecule""}]" included [] TGFBR1 development "[""tgfb_caf_exclusion""]" resolved_exact immune-exclusion / stromal-resistance candidate immune-exclusion / stromal-resistance candidate benchmark +known_positive "[""Internal rule-based curation; not independent validation.""]" symbol:TIGIT|entrez:201633 Existing internal checkpoint benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_5392635025040f46f6f98b38a013750363bebdada3e98d88fac1c36f7120874d configs/benchmark_targets.yaml:checkpoint_combination curated checkpoint-combination behaviour "[""tus_931a390a0533a345be5ed785f8a7aa6582c00de9d24964013cfb737043e22f72""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:checkpoint_combination""}]" included [] TIGIT development "[""checkpoint_redundancy""]" resolved_exact anti-PD-1 combination target anti-PD-1 combination target benchmark +context_dependent "[""Treg targeting can affect immune tolerance.""]" symbol:TNFRSF18|entrez:8784 Existing internal Treg benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_fa6b101eb34fad666f08143e1661a64d137c636f3924f80649ad29d67532ed47 configs/benchmark_targets.yaml:treg_suppression curated Treg-suppression behaviour "[""tus_278c749faa4d960664196012386e128a53909fcd77c15ec90b7128210f9df0ca""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:treg_suppression""}]" included [] TNFRSF18 development "[""treg_suppression""]" resolved_exact Treg-suppression marker / possible IO-combination target Treg-suppression marker / possible IO-combination target benchmark +challenging_control "[""Control class is not a therapeutic conclusion.""]" symbol:TP53|entrez:7157 Existing internal poor-direct-target control. targetintel_io_internal_v0_1 v0.5.0 tue_abc58183ea3c69e70d0ca2d2047bfd0b815ff4b353f2672042ec7477fa3d111d configs/benchmark_targets.yaml:poor_direct_targets curated poor-direct-target control behaviour "[""tus_bd4fc12d9cd1cbdce55304ddecd539d811be164d10aa7f2fec9d1f674dd9bf76""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:poor_direct_targets""}]" included [] TP53 development "[""other_unresolved""]" resolved_exact tumor-intrinsic driver / poor direct therapeutic target tumor-intrinsic driver / poor direct therapeutic target benchmark +known_positive "[""Myeloid biology is context dependent.""]" symbol:TREM2|entrez:54209 Existing internal myeloid benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_f616dec4686584fae0af61e3eaa33843ed6175ce8b3edccdc1a6749f82027070 configs/benchmark_targets.yaml:myeloid_suppression curated myeloid-combination behaviour "[""tus_cdd532c8c92399da14dfbcb38978ca97e7923ea10afc936f77b362a5db74c5a7""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:myeloid_suppression""}]" included [] TREM2 development "[""myeloid_suppression""]" resolved_exact myeloid/TME anti-PD-1 combination target myeloid/TME anti-PD-1 combination target benchmark +context_dependent "[""State marker does not establish a direct dependency.""]" symbol:WNT5A|entrez:7474 Existing internal plasticity benchmark representative. targetintel_io_internal_v0_1 v0.5.0 tue_26c6b30abc0bcc160766c94af67620d33fd5bf226a37473a07aa81aa097157bb configs/benchmark_targets.yaml:melanoma_plasticity_biomarker curated melanoma-plasticity behaviour "[""tus_fa6fb1e779c5532e743c947c56d3cc50216fc59f2940c5acc5f07362275e113c""]" "[{""dataset_version"": ""targetintel_io_internal_v0_1"", ""inclusion_rule"": ""curated benchmark entry"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""configs/benchmark_targets.yaml:melanoma_plasticity_biomarker""}]" included [] WNT5A development "[""melanoma_plasticity""]" resolved_exact melanoma plasticity / resistance-associated marker melanoma plasticity / resistance-associated marker benchmark diff --git a/data/releases/depmap/DepMap_Public_26Q1/candidate_overlay.tsv b/data/releases/depmap/DepMap_Public_26Q1/candidate_overlay.tsv new file mode 100644 index 0000000..ad07e52 --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/candidate_overlay.tsv @@ -0,0 +1,301 @@ +original_target_identifier canonical_target_identity baseline_rank baseline_score candidate_rank dependency_signal dependency_component_count profile_available +CTLA4 symbol:CTLA4|entrez:1493 1 0.8534 10 0.22424242424242424 3 True +PDCD1 symbol:PDCD1|entrez:5133 2 0.8274 4 0.8545454545454545 3 True +CD274 symbol:CD274|entrez:29126 3 0.8249 9 0.29090909090909095 3 True +LAG3 symbol:LAG3|entrez:3902 4 0.8218 7 0.42424242424242425 3 True +IL2RA symbol:IL2RA|entrez:3559 5 0.6726 6 0.6484848484848486 3 True +NRAS symbol:NRAS|entrez:4893 6 0.3009 3 0.8787878787878789 3 True +BRAF symbol:BRAF|entrez:673 7 0.269 1 0.993939393939394 3 True +MAP2K1 symbol:MAP2K1|entrez:5604 8 0.2621 2 0.9696969696969697 3 True +B2M symbol:B2M|entrez:567 9 0.2272 5 0.7000000000000001 3 True +JAK2 symbol:JAK2|entrez:3717 10 0.2149 8 0.3 3 True +JAK1 symbol:JAK1|entrez:3716 11 0.2139 19 0.0212121212121212 3 True +CDKN2A symbol:CDKN2A|entrez:1029 12 0.0 18 0.33030303030303027 3 True +BAP1 symbol:BAP1|entrez:8314 13 0.0 13 0.8606060606060607 3 True +MAP2K2 symbol:MAP2K2|entrez:5605 14 0.0 12 0.903030303030303 3 True +PTEN symbol:PTEN|entrez:5728 15 0.0 16 0.609090909090909 3 True +MITF symbol:MITF|entrez:4286 16 0.0 11 0.9696969696969697 3 True +NF1 symbol:NF1|entrez:4763 17 0.0 17 0.4515151515151515 3 True +CDK4 symbol:CDK4|entrez:1019 18 0.0 14 0.8424242424242424 3 True +GNAQ symbol:GNAQ|entrez:2776 19 0.0 15 0.7696969696969697 3 True +ARID2 symbol:ARID2|entrez:196528 20 0.0 20 0 False +KIT symbol:KIT|entrez:3815 21 0.0 21 0.8242424242424242 3 True +RAC1 symbol:RAC1|entrez:5879 22 0.0 22 0 False +TERT symbol:TERT|entrez:7015 23 0.0 24 0.4151515151515152 3 True +GNA11 symbol:GNA11|entrez:2767 24 0.0 23 0.693939393939394 3 True +POT1 symbol:POT1|entrez:25913 25 0.0 25 0 False +MBD4 symbol:MBD4|entrez:8930 26 0.0 26 0 False +TP53 symbol:TP53|entrez:7157 27 0.0 27 0.11818181818181817 3 True +SF3B1 symbol:SF3B1|entrez:23451 28 0.0 28 0 False +PPP6C symbol:PPP6C|entrez:5537 29 0.0 29 0 False +IRF4 symbol:IRF4|entrez:3662 30 0.0 30 0 False +BRCA2 symbol:BRCA2|entrez:675 31 0.0 31 0 False +RAF1 symbol:RAF1|entrez:5894 32 0.0 32 0 False +KDR symbol:KDR|entrez:3791 33 0.0 33 0 False +PDGFRA symbol:PDGFRA|entrez:5156 34 0.0 34 0 False +ATM symbol:ATM|entrez:472 35 0.0 35 0 False +LRP1B symbol:LRP1B|entrez:53353 36 0.0 36 0 False +FLT4 symbol:FLT4|entrez:2324 37 0.0 37 0 False +CSF3R symbol:CSF3R|entrez:1441 38 0.0 38 0 False +PDGFRB symbol:PDGFRB|entrez:5159 39 0.0 39 0 False +TET2 symbol:TET2|entrez:54790 40 0.0 40 0 False +POLE symbol:POLE|entrez:5426 41 0.0 41 0 False +DDX3X symbol:DDX3X|entrez:1654 42 0.0 42 0 False +FOXP1 symbol:FOXP1|entrez:27086 43 0.0 43 0 False +PBRM1 symbol:PBRM1|entrez:55193 44 0.0 44 0 False +SETD2 symbol:SETD2|entrez:29072 45 0.0 45 0 False +CCND1 symbol:CCND1|entrez:595 46 0.0 46 0 False +ERBB4 symbol:ERBB4|entrez:2066 47 0.0 47 0 False +MET symbol:MET|entrez:4233 48 0.0 48 0 False +STK11 symbol:STK11|entrez:6794 49 0.0 49 0 False +ROS1 symbol:ROS1|entrez:6098 50 0.0 50 0 False +MTOR symbol:MTOR|entrez:2475 51 0.0 51 0 False +H3-3B symbol:H3-3B|entrez:3021 52 0.0 52 0 False +TRRAP symbol:TRRAP|entrez:8295 53 0.0 53 0 False +MC1R symbol:MC1R|entrez:4157 54 0.0 54 0 False +IKZF1 symbol:IKZF1|entrez:10320 55 0.0 55 0 False +FAT1 symbol:FAT1|entrez:2195 56 0.0 56 0 False +DICER1 symbol:DICER1|entrez:23405 57 0.0 57 0 False +MDM2 symbol:MDM2|entrez:4193 58 0.0 58 0 False +IFNAR1 symbol:IFNAR1|entrez:3454 59 0.0 59 0 False +MECOM symbol:MECOM|entrez:2122 60 0.0 60 0 False +WRN symbol:WRN|entrez:7486 61 0.0 61 0 False +CHEK2 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explicitly_absent reference_unavailable 0 5 valid +ACKR3 resolved_exact_symbol sufficient_complete_coverage 56 56 0.051971504824438984 0.05145549169103937 0.0005160131333996135 56 0.012531187649904931 0.0 0.0 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +ACVR1B resolved_exact_symbol sufficient_complete_coverage 56 56 -0.08515877044475642 -0.09349962650204376 0.008340856057287335 56 0.04447697969775254 0.0 0.019097222222222224 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +AFDN resolved_exact_symbol sufficient_complete_coverage 56 56 -0.09824333463123369 -0.05034653465070568 -0.04789679998052801 56 0.04490595607597833 0.0 0.033854166666666664 66.66666666666667 explicitly_absent reference_unavailable 0 5 valid +AFF4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.05939864471942567 -0.04846659657785693 -0.010932048141568743 56 0.03392475612734393 0.0 0.006076388888888889 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +AKT1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.0046377124629188235 -0.06178562151511162 0.06642333397803044 56 0.020344346257189568 0.0 0.04513888888888889 3.7037037037037037 explicitly_absent reference_unavailable 0 5 valid +AKT2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.007401318928414405 -0.061827372969298654 0.05442605404088425 56 0.020804451087822785 0.0 0.03298611111111111 14.814814814814815 explicitly_absent reference_unavailable 0 5 valid +ALK resolved_exact_symbol sufficient_complete_coverage 56 56 -0.09243115642296142 -0.08370200343847614 -0.008729152984485275 56 0.0461958733533957 0.0 0.006944444444444444 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +AMER1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.08276667476476582 0.055715421836088755 0.027051252928677064 56 0.009990647380253341 0.0 0.0 14.814814814814815 explicitly_absent reference_unavailable 0 5 valid +APC resolved_exact_symbol sufficient_complete_coverage 56 56 -0.3380178346085523 -0.35856163479934966 0.02054380019079738 56 0.27761769575678924 0.3392857142857143 0.3151041666666667 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +APOBEC3B resolved_exact_symbol sufficient_complete_coverage 56 56 0.005793906262137797 0.0054438496451189875 0.0003500566170188098 56 0.019179227319746587 0.0 0.005208333333333333 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +AR resolved_exact_symbol sufficient_complete_coverage 56 56 0.09918225274948897 0.0995889074224145 -0.00040665467292552715 56 0.007519158470395323 0.0 0.0026041666666666665 25.925925925925927 explicitly_absent reference_unavailable 0 5 valid +ARG1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.11451918046801807 0.15923861473765064 -0.04471943426963257 56 0.006837278753817717 0.0 0.0 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +ARHGAP35 resolved_exact_symbol sufficient_complete_coverage 56 56 0.1631803821345646 0.14921332134714987 0.01396706078741472 56 0.004719702771807059 0.0 0.0 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +ARHGEF12 resolved_exact_symbol sufficient_complete_coverage 56 56 0.034871420237681874 0.06702959068101953 -0.03215817044333766 56 0.015320245248807533 0.0 0.004340277777777778 77.77777777777777 explicitly_absent reference_unavailable 0 5 valid +ARID1A resolved_exact_symbol sufficient_complete_coverage 56 56 -0.2619302515505961 -0.1987028561249499 -0.06322739542564623 56 0.1554943077693044 0.25 0.19791666666666666 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +ARID1B resolved_exact_symbol sufficient_complete_coverage 56 56 -0.04386019774725303 -0.046217279840372535 0.0023570820931195086 56 0.032552869087177506 0.017857142857142856 0.046875 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +ARID2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.2207698686925888 -0.39568018024793095 0.17491031155534215 56 0.15054546566780236 0.25 0.3975694444444444 18.51851851851852 explicitly_absent reference_unavailable 0 5 valid +ARNT resolved_exact_symbol sufficient_complete_coverage 56 56 -0.20315562003917215 -0.029467086741976636 -0.17368853329719552 56 0.11103222682700858 0.17857142857142858 0.046875 88.88888888888889 explicitly_absent reference_unavailable 0 5 valid +ASPSCR1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.1028582496030106 -0.16502016861226537 0.062161919009254774 56 0.05442591831673187 0.0 0.019965277777777776 7.407407407407407 explicitly_absent reference_unavailable 0 5 valid +ATF1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.23658966248001567 -0.18135627841219829 -0.05523338406781739 56 0.14648723614834475 0.05357142857142857 0.044270833333333336 92.5925925925926 explicitly_absent reference_unavailable 0 5 valid +ATM resolved_exact_symbol sufficient_complete_coverage 56 56 0.08719509887627361 -0.03271177994171204 0.11990687881798565 56 0.007002239522950301 0.0 0.017361111111111112 7.407407407407407 explicitly_absent reference_unavailable 0 5 valid +ATP2B3 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.036856086964585304 -0.006210743477298063 -0.03064534348728724 56 0.03490888626221475 0.0 0.004340277777777778 74.07407407407408 explicitly_absent reference_unavailable 0 5 valid +ATR resolved_exact_symbol sufficient_complete_coverage 56 56 -1.172755189115312 -1.0938521815748763 -0.07890300754043578 56 0.9904158847911251 1.0 0.9722222222222222 77.77777777777777 explicitly_present reference_unavailable 1 5 valid +ATRX resolved_exact_symbol sufficient_complete_coverage 56 56 -0.3302554609174006 -0.16595772427626249 -0.16429773664113811 56 0.30795028110934963 0.32142857142857145 0.12065972222222222 88.88888888888889 explicitly_absent reference_unavailable 0 5 valid +AXIN1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.08289157811043477 0.04256362679826843 0.040327951312166335 56 0.009616196179705327 0.03571428571428571 0.029513888888888888 29.62962962962963 explicitly_absent reference_unavailable 0 5 valid +AXL resolved_exact_symbol sufficient_complete_coverage 56 56 -0.05461535624294615 -0.02503393031568872 -0.029581425927257432 56 0.03594859224302639 0.017857142857142856 0.012152777777777778 77.77777777777777 explicitly_absent reference_unavailable 0 5 valid +B2M resolved_exact_symbol sufficient_complete_coverage 56 56 0.015821163143747298 0.03622048456187049 -0.020399321418123194 56 0.0164348942055268 0.0 0.0 88.88888888888889 explicitly_absent reference_unavailable 0 5 valid +BACH2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.039909660670576906 0.041516359374421816 -0.0016066987038449096 56 0.013053911679737119 0.0 0.004340277777777778 55.55555555555556 explicitly_absent reference_unavailable 0 5 valid +BAP1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.5909145722746947 -0.5100347991107175 -0.08087977316397721 56 0.7153010101416735 0.6607142857142857 0.5598958333333334 77.77777777777777 explicitly_absent reference_unavailable 0 5 valid +BCL11A resolved_exact_symbol sufficient_complete_coverage 56 56 -0.056271293868629293 -0.043674201784329805 -0.012597092084299488 56 0.033069240860764355 0.017857142857142856 0.012152777777777778 59.25925925925926 explicitly_absent reference_unavailable 0 5 valid +BCL11B resolved_exact_symbol sufficient_complete_coverage 56 56 0.019832171594732825 0.026445756140667742 -0.0066135845459349175 56 0.018108339873370675 0.0 0.015625 70.37037037037037 explicitly_absent reference_unavailable 0 5 valid +BCL2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.025311452898357994 -0.002304872932074549 -0.023006579966283445 56 0.02454383022252416 0.0 0.03819444444444445 74.07407407407408 explicitly_absent reference_unavailable 0 5 valid +BCL9 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.23320556013071192 -0.17785031241584626 -0.05535524771486566 56 0.14987003186885173 0.19642857142857142 0.13802083333333334 77.77777777777777 explicitly_absent reference_unavailable 0 5 valid +BCL9L resolved_exact_symbol sufficient_complete_coverage 56 56 -0.08759133713750625 -0.0917593873692542 0.004168050231747947 56 0.03968158389728285 0.017857142857142856 0.0546875 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +BCOR resolved_exact_symbol sufficient_complete_coverage 56 56 0.025163160100960116 0.036174782854716786 -0.01101162275375667 56 0.01380619756232246 0.017857142857142856 0.025173611111111112 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +BCORL1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.10564126028540002 0.078574067475421 0.027067192809979018 56 0.007299775968082389 0.03571428571428571 0.006076388888888889 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +BIRC3 resolved_exact_symbol sufficient_complete_coverage 56 56 0.0066408270165531635 0.047385018388796066 -0.0407441913722429 56 0.01746802168718406 0.0 0.003472222222222222 88.88888888888889 explicitly_absent reference_unavailable 0 5 valid +BRAF resolved_exact_symbol sufficient_complete_coverage 56 56 -1.2347703095627218 -0.08618464573448142 -1.1485856638282403 56 0.9910996581121145 0.7857142857142857 0.06163194444444445 100.0 explicitly_absent reference_unavailable 0 5 valid +BRCA1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.6447037480808876 -0.45976625838565904 -0.18493748969522855 56 0.7565224518784195 0.7678571428571429 0.4930555555555556 92.5925925925926 explicitly_present reference_unavailable 1 5 valid +BRCA2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.5458386512220574 -0.5148152083770121 -0.031023442845045324 56 0.6356233831085945 0.625 0.5789930555555556 62.96296296296296 explicitly_present reference_unavailable 1 5 valid +BRD3 resolved_exact_symbol sufficient_complete_coverage 56 56 0.08710923930845982 0.0926341403288816 -0.005524901020421788 56 0.0076650310535126605 0.0 0.0 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +BRD4 resolved_exact_symbol sufficient_complete_coverage 56 56 -1.107477935554086 -1.0208121016059204 -0.08666583394816563 56 0.9859241206511045 0.9642857142857143 0.9513888888888888 77.77777777777777 explicitly_present reference_unavailable 1 5 valid +BTK resolved_exact_symbol sufficient_complete_coverage 56 56 0.021314724552192434 -0.007330588091896811 0.028645312644089246 56 0.014886149558598682 0.0 0.0078125 18.51851851851852 explicitly_absent reference_unavailable 0 5 valid +BUB1B resolved_exact_symbol sufficient_complete_coverage 56 56 -1.1239831043751725 -1.2084487939933954 0.08446568961822298 56 0.9837485018692456 0.9821428571428571 0.9826388888888888 22.22222222222222 explicitly_present reference_unavailable 0 5 valid +CACNA1D resolved_exact_symbol sufficient_complete_coverage 56 56 -0.019408167580945213 -0.03793979768108344 0.018531630100138224 56 0.02156477750214402 0.0 0.001736111111111111 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +CARD11 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.00843369100614956 -0.051334760222822906 0.042901069216673346 56 0.022444793911606052 0.0 0.006076388888888889 7.407407407407407 explicitly_absent reference_unavailable 0 5 valid +CARS1 resolved_exact_symbol sufficient_complete_coverage 56 56 -1.5980364353584418 -1.6918204316248233 0.09378399626638156 56 0.9999665853145443 1.0 0.9982638888888888 22.22222222222222 explicitly_present reference_unavailable 0 5 valid +CASP8 resolved_exact_symbol sufficient_complete_coverage 56 56 0.04398793623669359 0.0791425560186391 -0.035154619781945506 56 0.010841974401337703 0.0 0.0008680555555555555 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +CBFA2T3 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.01977128242853117 0.006295977022699727 -0.026067259451230895 56 0.02561603909201212 0.0 0.006076388888888889 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +CBL resolved_exact_symbol sufficient_complete_coverage 56 56 0.019575406859070273 0.024448993073224557 -0.004873586214154284 56 0.015865046905975483 0.0 0.004340277777777778 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +CBLB resolved_exact_symbol sufficient_complete_coverage 56 56 -0.0034065031597723177 -0.014833401787283557 0.011426898627511239 56 0.020538144383673726 0.0 0.0 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +CCND1 resolved_exact_symbol sufficient_complete_coverage 56 56 -1.828765775143998 -1.0402667593534412 -0.7884990157905569 56 1.0 0.9642857142857143 0.734375 85.18518518518519 explicitly_present reference_unavailable 1 5 valid +CCND2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.08633474069631311 -0.09905938266767858 0.012724641971365469 56 0.04813965995942092 0.0 0.0703125 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +CD274 resolved_exact_symbol sufficient_complete_coverage 56 56 0.1863639156999815 0.18292940359540852 0.00343451210457299 56 0.0035318069749596765 0.0 0.0 25.925925925925927 explicitly_absent reference_unavailable 0 5 valid +CD79A resolved_exact_symbol sufficient_complete_coverage 56 56 0.1100920547426244 0.1502631834284648 -0.04017112868584041 56 0.0069261069107548695 0.0 0.011284722222222222 88.88888888888889 explicitly_absent reference_unavailable 0 5 valid +CD8A resolved_exact_symbol sufficient_complete_coverage 56 56 0.03928974584334112 0.009326868105865534 0.029962877737475586 56 0.011938528707279468 0.0 0.001736111111111111 11.11111111111111 explicitly_absent reference_unavailable 0 5 valid +CDH1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.07204685958685368 -0.07780743771436863 0.005760578127514945 56 0.04375955195407501 0.03571428571428571 0.044270833333333336 25.925925925925927 explicitly_absent reference_unavailable 0 5 valid +CDK12 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.47096900533770847 -0.40197460651605 -0.06899439882165848 56 0.4693828317812654 0.44642857142857145 0.3680555555555556 85.18518518518519 explicitly_present reference_unavailable 1 5 valid +CDK4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.7802086880629331 -0.555203482310257 -0.22500520575267613 56 0.8640150958074966 0.7857142857142857 0.6371527777777778 66.66666666666667 explicitly_present reference_unavailable 1 5 valid +CDK6 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.4741396489201388 -0.5301172743335945 0.055977625413455634 56 0.5298570181549593 0.5178571428571429 0.5434027777777778 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +CDKN2A resolved_exact_symbol sufficient_complete_coverage 56 56 0.16082152009903888 0.1537404477867926 0.007081072312246278 56 0.0038283808957741555 0.0 0.001736111111111111 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +CDKN2B resolved_exact_symbol sufficient_complete_coverage 56 55 0.15881718146129087 0.09646482950727868 0.06235235195401219 55 0.005092649083602317 0.0 0.0009009009009009009 11.11111111111111 explicitly_absent reference_unavailable 0 5 valid +CDX2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.059264623715066425 -0.0901389591725308 0.030874335457464375 56 0.03842983462576611 0.0 0.026909722222222224 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +CHD4 resolved_exact_symbol sufficient_complete_coverage 56 56 -1.2512662213227028 -1.0955285224412754 -0.1557376988814274 56 0.9929567916053474 1.0 0.9670138888888888 70.37037037037037 explicitly_present reference_unavailable 1 5 valid +CHEK2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.3224042378144514 0.19688098835968726 0.12552324945476412 56 0.0006560276296503497 0.0 0.0 7.407407407407407 explicitly_absent reference_unavailable 0 5 valid +CIC resolved_exact_symbol sufficient_complete_coverage 56 56 -0.0724818295618623 -0.047195734884763044 -0.02528609467709926 56 0.041316844193587124 0.08928571428571429 0.0234375 74.07407407407408 explicitly_absent reference_unavailable 0 5 valid +CIITA resolved_exact_symbol sufficient_complete_coverage 56 56 0.01143269694703151 0.05172624755968459 -0.040293550612653085 56 0.016486777927961806 0.0 0.0008680555555555555 74.07407407407408 explicitly_absent reference_unavailable 0 5 valid +CLPTM1L resolved_exact_symbol sufficient_complete_coverage 56 56 0.11157894179367531 0.09135273401014984 0.020226207783525463 56 0.006899426529077324 0.0 0.001736111111111111 11.11111111111111 explicitly_absent reference_unavailable 0 5 valid +CLTC resolved_exact_symbol sufficient_complete_coverage 56 56 -1.5407053756609363 -1.5906811690883584 0.04997579342742209 56 0.999767927569396 0.9821428571428571 0.9878472222222222 62.96296296296296 explicitly_present reference_unavailable 0 5 valid +CNOT3 resolved_exact_symbol sufficient_complete_coverage 56 56 -1.5936584691809363 -1.5482596359662053 -0.04539883321473104 56 0.9998302256586487 1.0 0.9913194444444444 55.55555555555556 explicitly_present reference_unavailable 1 5 valid +CNOT9 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.4553898880376292 -0.5151796029638729 0.05978971492624369 56 0.5364384999804481 0.5178571428571429 0.5807291666666666 44.44444444444444 explicitly_present reference_unavailable 0 5 valid +CREB1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.0970478339479603 -0.09810468437499631 0.0010568504270360157 56 0.04475869080138886 0.017857142857142856 0.036458333333333336 37.03703703703704 explicitly_absent reference_unavailable 0 5 valid +CREBBP resolved_exact_symbol sufficient_complete_coverage 56 56 0.12434295478017252 -0.05535208762838778 0.1796950424085603 56 0.006852358906610696 0.017857142857142856 0.12586805555555555 25.925925925925927 explicitly_absent reference_unavailable 0 5 valid +CRLF2 resolved_exact_symbol insufficient_measured_context_models 56 4 0.10345284711544935 0.08640211093370642 4 0.005901815316236432 0.0 0.0 26.666666666666668 explicitly_absent reference_unavailable 0 5 valid +CSF1R resolved_exact_symbol sufficient_complete_coverage 56 56 0.016248024381766507 -0.012633329523399704 0.02888135390516621 56 0.018261184417227513 0.0 0.0 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +CSF3R resolved_exact_symbol sufficient_complete_coverage 56 56 -0.1036037219983435 -0.10573413036973203 0.0021304083713885313 56 0.05600813177010951 0.017857142857142856 0.010416666666666666 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +CTLA4 resolved_exact_symbol sufficient_complete_coverage 56 56 0.005832932383737247 -0.006802665948114025 0.012635598331851272 56 0.01842904351594934 0.0 0.0 37.03703703703704 explicitly_absent reference_unavailable 0 5 valid +CTNNB1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.20773415732109757 -0.1360022774360092 -0.07173187988508836 56 0.13451455384394487 0.07142857142857142 0.13368055555555555 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +CUX1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.04287214215173468 0.0869825007527967 -0.04411035860106202 56 0.010248060779731664 0.0 0.005208333333333333 55.55555555555556 explicitly_absent reference_unavailable 0 5 valid +CXCL12 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.022205827285089998 -0.022014651192065398 -0.00019117609302459967 56 0.020696994642275326 0.0 0.001736111111111111 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +CXCL9 resolved_exact_symbol sufficient_complete_coverage 56 56 0.05281410370015513 0.055645480717740975 -0.0028313770175858455 56 0.012647935195006565 0.0 0.0 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +CXCR4 resolved_exact_symbol sufficient_complete_coverage 56 56 0.05891644317724552 0.03551528037284271 0.02340116280440281 56 0.012532064623048806 0.0 0.0 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +CYLD resolved_exact_symbol sufficient_complete_coverage 56 56 -0.08653479539938982 -0.09590282432788348 0.009368028928493657 56 0.04655640165652187 0.017857142857142856 0.028645833333333332 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +CYP1B1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.09166972667834505 0.07704917027985958 0.014620556398485474 56 0.008242491577905423 0.0 0.0 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +DAXX resolved_exact_symbol sufficient_complete_coverage 56 56 -0.383732915488141 -0.32781716907898456 -0.05591574640915642 56 0.4007934163278375 0.42857142857142855 0.2994791666666667 70.37037037037037 explicitly_absent reference_unavailable 0 5 valid +DDR2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.020729125875991173 -0.02499213293873221 0.004263007062741037 56 0.022905507258844444 0.0 0.0008680555555555555 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +DDX3X resolved_exact_symbol sufficient_complete_coverage 56 56 -0.6607130262900589 -0.9204754845756884 0.2597624582856295 56 0.7872151954624422 0.6785714285714286 0.7838541666666666 18.51851851851852 explicitly_absent reference_unavailable 0 5 valid +DICER1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.6573228251847951 -0.5333495378258184 -0.12397328735897672 56 0.8229355663334141 0.7678571428571429 0.6041666666666666 88.88888888888889 explicitly_present reference_unavailable 1 5 valid +DNMT3A resolved_exact_symbol sufficient_complete_coverage 56 56 0.18235534714872575 0.16913275721791513 0.01322258993081063 56 0.0035343347073587836 0.0 0.0 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +EGFR resolved_exact_symbol sufficient_complete_coverage 56 56 -0.08543314878433285 -0.1329829304084583 0.047549781624125445 56 0.05061839110667351 0.017857142857142856 0.19791666666666666 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +ENTPD1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.03958058875364162 0.04175603185707605 -0.002175443103434427 56 0.014386164975697509 0.0 0.0 55.55555555555556 explicitly_absent reference_unavailable 0 5 valid +EP300 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.3520231118620166 -0.31374602852517774 -0.03827708333683888 56 0.30719246495550195 0.375 0.3585069444444444 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +ERBB2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.246206895071223 -0.2765318958763646 0.03032500080514161 56 0.1734088090428273 0.10714285714285714 0.20572916666666666 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +ERBB3 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.2064135944999752 -0.1589272115709494 -0.047486382929025794 56 0.13126533178718724 0.07142857142857142 0.0920138888888889 85.18518518518519 explicitly_absent reference_unavailable 0 5 valid +ERBB4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.08133237680604319 -0.07965460318059267 -0.0016777736254505182 56 0.04663575266879736 0.0 0.005208333333333333 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +ERCC2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.8344001265829372 -1.0164946290135148 0.18209450243057768 56 0.9417257675715691 0.9285714285714286 0.9487847222222222 3.7037037037037037 explicitly_present reference_unavailable 0 5 valid +ERCC3 resolved_exact_symbol sufficient_complete_coverage 56 56 -1.0257305946001085 -1.0099328935587977 -0.01579770104131084 56 0.9767427569343496 0.9821428571428571 0.9791666666666666 55.55555555555556 explicitly_present reference_unavailable 1 5 valid +ERCC4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.312962794264828 -0.28260245550413393 -0.03036033876069405 56 0.25032416264247376 0.16071428571428573 0.2048611111111111 74.07407407407408 explicitly_absent reference_unavailable 0 5 valid +ERCC5 resolved_exact_symbol sufficient_complete_coverage 56 56 0.02281300196535606 0.004754426576597483 0.018058575388758574 56 0.016749164858456053 0.0 0.0 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +ESR1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.00802662620138481 -0.035072393707524414 0.027045767506139604 56 0.02133572171212511 0.0 0.014756944444444444 25.925925925925927 explicitly_absent reference_unavailable 0 5 valid +EZH2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.0320485927146671 -0.01615439674972201 0.04820298946438911 56 0.01521772005739586 0.0 0.0842013888888889 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +FANCA resolved_exact_symbol sufficient_complete_coverage 56 56 -0.2676352166799574 -0.2268793023270395 -0.040755914352917866 56 0.18706360909548436 0.21428571428571427 0.16493055555555555 74.07407407407408 explicitly_absent reference_unavailable 0 5 valid +FANCD2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.24333725518628152 -0.2527791299461499 0.009441874759868407 56 0.16569585838507817 0.08928571428571429 0.17274305555555555 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +FANCE resolved_exact_symbol sufficient_complete_coverage 56 56 -0.19399076273649424 -0.1834007591965154 -0.010590003539978826 56 0.12078053526514522 0.05357142857142857 0.07899305555555555 74.07407407407408 explicitly_absent reference_unavailable 0 5 valid +FANCF resolved_exact_symbol sufficient_complete_coverage 56 56 -0.31555455536594124 -0.26618972538303864 -0.04936482998290259 56 0.24263160040327705 0.23214285714285715 0.17881944444444445 70.37037037037037 explicitly_absent reference_unavailable 0 5 valid +FAS resolved_exact_symbol sufficient_complete_coverage 56 56 -0.11478192715046522 -0.12435506063257856 0.009573133482113347 56 0.05203040919741203 0.0 0.004340277777777778 37.03703703703704 explicitly_absent reference_unavailable 0 5 valid +FAT1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.04713508116369999 0.06842656748864713 -0.021291486324947137 56 0.013016969463129585 0.0 0.0 66.66666666666667 explicitly_absent reference_unavailable 0 5 valid +FAT4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.023054746641925847 -0.03392017626805029 0.01086542962612444 56 0.026496833584941027 0.0 0.0 37.03703703703704 explicitly_absent reference_unavailable 0 5 valid +FBXO11 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.03427403620395675 -0.1713673283895495 0.13709329218559274 56 0.029319765084054497 0.08928571428571429 0.1918402777777778 11.11111111111111 explicitly_absent reference_unavailable 0 5 valid +FBXW7 resolved_exact_symbol sufficient_complete_coverage 56 56 0.08885012160126604 0.010205989215357245 0.0786441323859088 56 0.00790827217292547 0.0 0.05555555555555555 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +FCRL4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.10620558769013834 -0.08730315492360355 -0.01890243276653479 56 0.05680147102116183 0.0 0.003472222222222222 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +FGFR1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.04514236242722311 -0.08807460915298418 0.04293224672576107 56 0.030469376280351304 0.017857142857142856 0.1293402777777778 29.62962962962963 explicitly_absent reference_unavailable 0 5 valid +FGFR2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.05163254238200452 -0.05039978034208241 -0.0012327620399221126 56 0.03537906820870254 0.017857142857142856 0.020833333333333332 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +FGFR3 resolved_exact_symbol sufficient_complete_coverage 56 56 0.04922997969645476 0.051745889423516794 -0.0025159097270620323 56 0.015458308668818171 0.0 0.006076388888888889 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +FGFR4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.0050449308179600395 0.0027003004871381017 -0.007745231305098141 56 0.01975265020738414 0.0 0.006944444444444444 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +FH resolved_exact_symbol sufficient_complete_coverage 56 56 -0.3487538509937572 -0.2650427948104634 -0.08371105618329383 56 0.293119690869387 0.2857142857142857 0.1987847222222222 85.18518518518519 explicitly_absent reference_unavailable 0 5 valid +FLG resolved_exact_symbol sufficient_complete_coverage 56 56 0.053553678456244605 0.07752310352602157 -0.023969425069776965 56 0.012053492803449247 0.0 0.0 66.66666666666667 explicitly_absent reference_unavailable 0 5 valid +FLT3 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.13862055477951635 -0.14433146252465615 0.005710907745139798 56 0.08088979303060306 0.017857142857142856 0.010416666666666666 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +FLT4 resolved_exact_symbol sufficient_complete_coverage 56 56 0.029329758113223747 0.022611161855231363 0.006718596257992385 56 0.016517954870417618 0.0 0.0008680555555555555 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +FMN1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.13594679027128903 0.0793384023090912 0.05660838796219783 56 0.005465761799348213 0.017857142857142856 0.001736111111111111 11.11111111111111 explicitly_absent reference_unavailable 0 5 valid +FOXP1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.006684601879123767 0.03267808225302871 -0.025993480373904948 56 0.018906366489225244 0.0 0.004340277777777778 59.25925925925926 explicitly_absent reference_unavailable 0 5 valid +FOXP3 resolved_exact_symbol sufficient_complete_coverage 56 56 0.06163214472920807 0.08439257079983098 -0.02276042607062291 56 0.01160893644614088 0.0 0.0 66.66666666666667 explicitly_absent reference_unavailable 0 5 valid +FUBP1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.19477172807427562 -0.18567123240310301 -0.009100495671172604 56 0.10461075385553599 0.05357142857142857 0.1032986111111111 55.55555555555556 explicitly_absent reference_unavailable 0 5 valid +GATA2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.05691850044409493 0.05055920094207224 0.006359299502022693 56 0.012027009295317814 0.0 0.0234375 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +GNA11 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.1566551127202881 -0.13426614724950947 -0.02238896547077862 56 0.09407439748766974 0.017857142857142856 0.0078125 59.25925925925926 explicitly_absent reference_unavailable 0 5 valid +GNAQ resolved_exact_symbol sufficient_complete_coverage 56 56 -0.3311970646804885 -0.303722568914944 -0.027474495765544504 56 0.27679032897507927 0.23214285714285715 0.15711805555555555 74.07407407407408 explicitly_absent reference_unavailable 0 5 valid +GNAS resolved_exact_symbol sufficient_complete_coverage 56 56 -0.0395043305663757 -0.029135792389810813 -0.010368538176564888 56 0.032055853208135324 0.017857142857142856 0.005208333333333333 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +GRIN2A resolved_exact_symbol sufficient_complete_coverage 56 56 -0.08077181172218598 -0.10362275852250574 0.022850946800319766 56 0.04293536851828147 0.0 0.003472222222222222 18.51851851851852 explicitly_absent reference_unavailable 0 5 valid +GZMB resolved_exact_symbol sufficient_complete_coverage 56 56 -0.06917978710613715 -0.09065186099510326 0.021472073888966117 56 0.034480980287158486 0.0 0.03298611111111111 14.814814814814815 explicitly_absent reference_unavailable 0 5 valid +H3-3A resolved_exact_symbol sufficient_complete_coverage 56 55 -1.346906237251263 -1.4274413527694203 0.08053511551815729 55 0.995866238899257 1.0 0.9990328820116054 22.22222222222222 explicitly_present reference_unavailable 0 5 valid +H3-3B resolved_exact_symbol sufficient_complete_coverage 56 56 -0.33933172423069585 -0.33294586043375146 -0.006385863796944391 56 0.3108532559759873 0.2857142857142857 0.20572916666666666 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +H3C2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.20958209107011988 -0.15030042508751462 -0.05928166598260526 56 0.13346229752303382 0.03571428571428571 0.0390625 96.29629629629629 explicitly_absent reference_unavailable 0 5 valid +HAVCR2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.021078887581460377 0.02068223283461549 0.0003966547468448878 56 0.014689188029942131 0.0 0.0008680555555555555 59.25925925925926 explicitly_absent reference_unavailable 0 5 valid +HGF resolved_exact_symbol sufficient_complete_coverage 56 56 0.11360474924188933 0.10693466782056527 0.006670081421324067 56 0.007790645531783854 0.0 0.0008680555555555555 59.25925925925926 explicitly_absent reference_unavailable 0 5 valid +HLA-A resolved_exact_symbol sufficient_complete_coverage 56 56 -0.17280744614212706 -0.17130900334938684 -0.0014984427927402233 56 0.09981467563830992 0.03571428571428571 0.020833333333333332 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +HLA-B resolved_exact_symbol sufficient_complete_coverage 56 56 -0.07423159504405025 -0.06003423347479433 -0.014197361569255919 56 0.04113581826807637 0.0 0.013020833333333334 66.66666666666667 explicitly_absent reference_unavailable 0 5 valid +HNF1A resolved_exact_symbol sufficient_complete_coverage 56 56 -0.04778355491386431 -0.08873691102912343 0.04095335611525912 56 0.03521909600150257 0.017857142857142856 0.03819444444444445 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +HRAS resolved_exact_symbol sufficient_complete_coverage 56 56 -0.15093706759740222 -0.1723323947059019 0.021395327108499673 56 0.09876526486851311 0.07142857142857142 0.03125 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +IDH1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.07154041810566106 -0.0894757637733739 0.01793534566771285 56 0.03720868827740238 0.03571428571428571 0.006076388888888889 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +IDO1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.05843457057831062 0.07991012915554735 -0.02147555857723673 56 0.012181418582402407 0.0 0.0 59.25925925925926 explicitly_absent reference_unavailable 0 5 valid +IFNAR1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.10365599503808863 0.0905500778876211 0.013105917150467536 56 0.00683742314520901 0.0 0.0008680555555555555 29.62962962962963 explicitly_absent reference_unavailable 0 5 valid +IFNAR2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.04386869337198644 0.05345392875817253 -0.009585235386186088 56 0.012610739619383672 0.017857142857142856 0.0008680555555555555 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +IFNGR1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.08379368461486343 0.09999498361763992 -0.01620129900277649 56 0.008325044038448394 0.0 0.001736111111111111 77.77777777777777 explicitly_absent reference_unavailable 0 5 valid +IKBKB resolved_exact_symbol sufficient_complete_coverage 56 56 -0.035178888153201554 -0.05102159812064679 0.01584270996744524 56 0.032710880080595445 0.0 0.04513888888888889 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +IKZF1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.08862815619119767 0.04951864707054353 0.03910950912065414 56 0.008626052643370095 0.0 0.030381944444444444 3.7037037037037037 explicitly_absent reference_unavailable 0 5 valid +IKZF3 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.08258590755905212 -0.08543510902941406 0.0028492014703619395 56 0.047431048431888424 0.0 0.033854166666666664 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +IL2RA resolved_exact_symbol sufficient_complete_coverage 56 56 0.02141508360816008 0.03506792351978908 -0.013652839911629001 56 0.01744431698994827 0.0 0.001736111111111111 77.77777777777777 explicitly_absent reference_unavailable 0 5 valid +IL2RB resolved_exact_symbol sufficient_complete_coverage 56 56 0.0038683297949551783 0.02439620727691242 -0.02052787748195724 56 0.020888460567987405 0.0 0.0008680555555555555 55.55555555555556 explicitly_absent reference_unavailable 0 5 valid +IL2RG resolved_exact_symbol sufficient_complete_coverage 56 56 0.0675100811958824 0.07178624857086237 -0.004276167374979975 56 0.010681045947869647 0.0 0.003472222222222222 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +IL7R resolved_exact_symbol sufficient_complete_coverage 56 56 0.06426875135630919 0.0540259277490285 0.01024282360728069 56 0.010212835631815064 0.0 0.0008680555555555555 25.925925925925927 explicitly_absent reference_unavailable 0 5 valid +IRF1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.021794338384010233 -0.05149455915614158 0.029700220772131348 56 0.02736019181396147 0.0 0.004340277777777778 18.51851851851852 explicitly_absent reference_unavailable 0 5 valid +IRF4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.23865970092198735 -0.10271057116576726 -0.1359491297562201 56 0.1569832292049153 0.32142857142857145 0.059895833333333336 85.18518518518519 explicitly_absent reference_unavailable 0 5 valid +IRS4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.07806148005826202 -0.10738684343815279 0.029325363379890765 56 0.0474389800368865 0.0 0.012152777777777778 29.62962962962963 explicitly_absent reference_unavailable 0 5 valid +JAK1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.02114251550731768 -0.06171786636938264 0.08286038187670032 56 0.020298339745821688 0.0 0.042534722222222224 7.407407407407407 explicitly_absent reference_unavailable 0 5 valid +JAK2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.14140384507405612 0.13554410657570745 0.005859738498348671 56 0.005546648360096902 0.0 0.006944444444444444 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +JUN resolved_exact_symbol sufficient_complete_coverage 56 56 -0.17296392891862877 -0.2215204526435342 0.04855652372490543 56 0.08893106341563362 0.10714285714285714 0.2092013888888889 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +KAT6A resolved_exact_symbol sufficient_complete_coverage 56 56 -0.10723105858661139 -0.06841728941848245 -0.03881376916812894 56 0.0533855412738906 0.10714285714285714 0.046875 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +KAT6B resolved_exact_symbol sufficient_complete_coverage 56 56 -0.027627318543472862 -0.017488846530694255 -0.010138472012778607 56 0.02764718556997526 0.0 0.006944444444444444 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +KDM5A resolved_exact_symbol sufficient_complete_coverage 56 56 -0.08145184435535191 -0.123397791469151 0.04194594711379909 56 0.043825408803144034 0.05357142857142857 0.0703125 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +KDR resolved_exact_symbol sufficient_complete_coverage 56 56 -0.0387256781978957 -0.10628614925239364 0.06756047105449794 56 0.03446964505050472 0.0 0.0078125 25.925925925925927 explicitly_absent reference_unavailable 0 5 valid +KEAP1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.3844446143597566 -0.12876419291117772 -0.25568042144857883 56 0.37728663389576456 0.42857142857142855 0.20225694444444445 92.5925925925926 explicitly_absent reference_unavailable 0 5 valid +KIT resolved_exact_symbol sufficient_complete_coverage 56 56 -0.11187987261054008 -0.049520046569690335 -0.06235982604084975 56 0.05726951313842029 0.0 0.006944444444444444 77.77777777777777 explicitly_absent reference_unavailable 0 5 valid +KLF4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.045825769626115405 -0.03577309204374583 -0.010052677582369572 56 0.02931121522718555 0.0 0.011284722222222222 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +KLF6 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.05126217030720511 0.05671932324115789 -0.107981493548363 56 0.03244514830539762 0.03571428571428571 0.022569444444444444 70.37037037037037 explicitly_absent reference_unavailable 0 5 valid +KMT2A resolved_exact_symbol sufficient_complete_coverage 56 56 -0.13474643688042431 -0.1774936735376852 0.04274723665726088 56 0.0731199024889937 0.03571428571428571 0.14583333333333334 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +KMT2C resolved_exact_symbol sufficient_complete_coverage 56 56 0.08688860720869607 0.02716414390798371 0.059724463300712356 56 0.00790666231691314 0.017857142857142856 0.0234375 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +KMT2D resolved_exact_symbol sufficient_complete_coverage 56 56 -0.2813972812521446 -0.35788817100046905 0.07649088974832446 56 0.1829714967357441 0.30357142857142855 0.3645833333333333 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +KNL1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.6974565079231971 -0.6403867521469886 -0.05706975577620854 56 0.83423638852549 0.875 0.8142361111111112 44.44444444444444 explicitly_present reference_unavailable 1 5 valid +KRAS resolved_exact_symbol sufficient_complete_coverage 56 56 -0.4270863694795695 -0.5281858748391903 0.10109950535962081 56 0.4738799422322064 0.48214285714285715 0.5807291666666666 22.22222222222222 explicitly_present reference_unavailable 0 5 valid +KRT5 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.03875848753631785 -0.04773393398761376 0.008975446451295908 56 0.027358384042971286 0.0 0.001736111111111111 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +LAG3 resolved_exact_symbol sufficient_complete_coverage 56 56 0.006693995382591952 -0.003618027317403587 0.01031202269999554 56 0.02026514620529634 0.0 0.0008680555555555555 70.37037037037037 explicitly_absent reference_unavailable 0 5 valid +LATS2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.02532013141759792 -0.045542199828101974 0.07086233124569989 56 0.023948406020125466 0.017857142857142856 0.010416666666666666 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +LCK resolved_exact_symbol sufficient_complete_coverage 56 56 -0.015814512461379424 -0.004169732479268769 -0.011644779982110654 56 0.022171372889984876 0.0 0.0008680555555555555 88.88888888888889 explicitly_absent reference_unavailable 0 5 valid +LILRB1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.051821418581015924 0.07242996722054487 -0.020608548639528948 56 0.013681127550983843 0.0 0.0008680555555555555 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +LILRB2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.10414190586983159 -0.08313150725415695 -0.021010398615674636 56 0.054768936757054784 0.017857142857142856 0.018229166666666668 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +LPP resolved_exact_symbol sufficient_complete_coverage 56 56 0.052278005196747614 0.06052204046355543 -0.008244035266807816 56 0.012845188877211793 0.0 0.0 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +LRP1B resolved_exact_symbol sufficient_complete_coverage 56 56 -0.1145412718983222 -0.14613541027687557 0.03159413837855338 56 0.0526553283158261 0.03571428571428571 0.03125 14.814814814814815 explicitly_absent reference_unavailable 0 5 valid +LZTR1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.032631692394577985 -0.0040996041084022244 -0.02853208828617576 56 0.027297324657613566 0.0 0.008680555555555556 74.07407407407408 explicitly_absent reference_unavailable 0 5 valid +MAP2K1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.38895098205912615 -0.13536923650240806 -0.2535817455567181 56 0.38746891216194834 0.39285714285714285 0.03732638888888889 100.0 explicitly_absent reference_unavailable 0 5 valid +MAP2K2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.27913492073021595 -0.16844031673292117 -0.11069460399729478 56 0.210854567680023 0.26785714285714285 0.028645833333333332 85.18518518518519 explicitly_absent reference_unavailable 0 5 valid +MAP2K4 resolved_exact_symbol sufficient_complete_coverage 56 56 0.007155568370856763 0.0915090254067388 -0.08435345703588204 56 0.02000527970907914 0.017857142857142856 0.013020833333333334 88.88888888888889 explicitly_absent reference_unavailable 0 5 valid +MAP3K1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.18106151480989618 -0.10070370508995352 -0.08035780971994266 56 0.08325360586789075 0.017857142857142856 0.013020833333333334 92.5925925925926 explicitly_absent reference_unavailable 0 5 valid +MAP3K13 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.07585580490508761 -0.05665283244493447 -0.019202972460153143 56 0.04505395114891765 0.0 0.001736111111111111 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +MAPK1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.8129894142767058 -0.1353199435650762 -0.6776694707116295 56 0.8931882816760448 0.7857142857142857 0.1111111111111111 100.0 explicitly_absent reference_unavailable 0 5 valid +MARCO resolved_exact_symbol sufficient_complete_coverage 56 56 -0.07657305576587008 -0.04465436759431944 -0.031918688171550635 56 0.04508515552169046 0.0 0.0008680555555555555 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +MAX resolved_exact_symbol sufficient_complete_coverage 56 56 -0.688268648265024 -0.8024281149461636 0.11415946668113963 56 0.8762894271334364 0.875 0.8949652777777778 22.22222222222222 explicitly_present reference_unavailable 0 5 valid +MBD4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.08875452151828409 -0.0997614701925298 0.011006948674245717 56 0.04888988821268317 0.0 0.005208333333333333 29.62962962962963 explicitly_absent reference_unavailable 0 5 valid +MC1R resolved_exact_symbol sufficient_complete_coverage 56 56 -0.014394286830063385 -0.013703472453153571 -0.0006908143769098138 56 0.024505635992432086 0.03571428571428571 0.0078125 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +MDM2 resolved_exact_symbol sufficient_complete_coverage 56 56 -1.3485460927811548 -0.417231037590648 -0.9313150551905067 56 0.9964251033261587 0.75 0.4401041666666667 88.88888888888889 explicitly_present reference_unavailable 1 5 valid +MDM4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.1410025896159544 -0.05954959215537305 -0.08145299746058135 56 0.07119109464846649 0.125 0.12152777777777778 88.88888888888889 explicitly_absent reference_unavailable 0 5 valid +MECOM resolved_exact_symbol sufficient_complete_coverage 56 56 0.06243448810213843 0.03967563605699685 0.02275885204514158 56 0.01239713433525657 0.0 0.024305555555555556 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +MED12 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.6930691904602218 -0.5640423641245395 -0.1290268263356823 56 0.8357673700031603 0.7142857142857143 0.5902777777777778 70.37037037037037 explicitly_absent reference_unavailable 0 5 valid +MERTK resolved_exact_symbol sufficient_complete_coverage 56 56 -0.10690991997138019 -0.07365396552581074 -0.03325595444556945 56 0.05270852886247373 0.0 0.006944444444444444 88.88888888888889 explicitly_absent reference_unavailable 0 5 valid +MET resolved_exact_symbol sufficient_complete_coverage 56 56 0.010664057636821479 -0.014175308731316144 0.024839366368137623 56 0.01757639754618848 0.0 0.028645833333333332 14.814814814814815 explicitly_absent reference_unavailable 0 5 valid +MITF resolved_exact_symbol sufficient_complete_coverage 56 56 -0.4283536938090401 -0.0484782221745169 -0.3798754716345232 56 0.48643645267493163 0.44642857142857145 0.009548611111111112 96.29629629629629 explicitly_absent reference_unavailable 0 5 valid +MN1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.1147031423956377 0.10314709611451522 0.011556046281122473 56 0.0071448822915313025 0.0 0.0 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +MRTFA resolved_exact_symbol sufficient_complete_coverage 56 56 -0.12423974962740286 -0.13625769956788214 0.012017949940479278 56 0.05987725158027763 0.017857142857142856 0.018229166666666668 18.51851851851852 explicitly_absent reference_unavailable 0 5 valid +MSH2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.19916068457846808 -0.20475934254402095 0.005598657965552867 56 0.12392476588127996 0.03571428571428571 0.018229166666666668 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +MTAP resolved_exact_symbol sufficient_complete_coverage 56 56 0.001765919917108864 0.01988151731387778 -0.018115597396768914 56 0.01798254575130081 0.0 0.0 77.77777777777777 explicitly_absent reference_unavailable 0 5 valid +MTOR resolved_exact_symbol sufficient_complete_coverage 56 56 -1.2341950136618125 -1.2530843119942268 0.01888929833241426 56 0.991899482877697 1.0 0.9809027777777778 33.333333333333336 explicitly_present reference_unavailable 0 5 valid +MUTYH resolved_exact_symbol sufficient_complete_coverage 56 56 -0.06371844317038643 -0.06157007029515675 -0.002148372875229676 56 0.0372447418479774 0.0 0.0008680555555555555 66.66666666666667 explicitly_absent reference_unavailable 0 5 valid +MX2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.06322339592467445 0.06426324660462712 -0.0010398506799526724 56 0.010155243511429223 0.0 0.0 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +MYB resolved_exact_symbol sufficient_complete_coverage 56 56 -0.2383668513811943 -0.29944825875516784 0.06108140737397355 56 0.1759008399302746 0.03571428571428571 0.19618055555555555 7.407407407407407 explicitly_absent reference_unavailable 0 5 valid +MYCL resolved_exact_symbol sufficient_complete_coverage 56 56 -0.02694371489350945 -0.01981635049396331 -0.00712736439954614 56 0.02648200137173792 0.0 0.003472222222222222 77.77777777777777 explicitly_absent reference_unavailable 0 5 valid +MYCN resolved_exact_symbol sufficient_complete_coverage 56 56 -0.10231313440314074 -0.09697903595641764 -0.005334098446723098 56 0.04657996803044029 0.0 0.03819444444444445 59.25925925925926 explicitly_absent reference_unavailable 0 5 valid +MYH9 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.16774301545077763 -0.5430034403950423 0.3752604249442647 56 0.09881359449198113 0.21428571428571427 0.5607638888888888 0.0 explicitly_absent reference_unavailable 0 5 valid +NCOR1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.06479063151622333 -0.1194923433545593 0.05470171183833597 56 0.03644019619439713 0.017857142857142856 0.07118055555555555 11.11111111111111 explicitly_absent reference_unavailable 0 5 valid +NCOR2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.08617660679431993 -0.08045753395661871 -0.0057190728377012195 56 0.04143923631202472 0.017857142857142856 0.03819444444444445 37.03703703703704 explicitly_absent reference_unavailable 0 5 valid +NF1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.0019771339155402017 0.009506354566937518 -0.007529220651397316 56 0.019721964712171004 0.0 0.017361111111111112 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +NF2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.24139439051277362 0.210186534758799 0.03120785575397461 56 0.0025437083249686757 0.07142857142857142 0.036458333333333336 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +NFE2L2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.14924719674865072 -0.20714206629685664 0.05789486954820591 56 0.08432932917261374 0.05357142857142857 0.14149305555555555 7.407407407407407 explicitly_absent reference_unavailable 0 5 valid +NFKB2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.07291431839673687 -0.14911904088057587 0.076204722483839 56 0.039965302273933655 0.017857142857142856 0.057291666666666664 18.51851851851852 explicitly_absent reference_unavailable 0 5 valid +NFKBIE resolved_exact_symbol sufficient_complete_coverage 56 56 -0.3591398799415844 -0.4018719812845659 0.0427321013429815 56 0.3441621104153567 0.26785714285714285 0.4036458333333333 25.925925925925927 explicitly_present reference_unavailable 0 5 valid +NGFR resolved_exact_symbol sufficient_complete_coverage 56 56 -0.24041421960464082 -0.22750036261103532 -0.012913856993605505 56 0.1667282415797557 0.03571428571428571 0.03993055555555555 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +NKX2-1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.03133446214879327 -0.0067478861706825105 -0.02458657597811076 56 0.02987755063188091 0.0 0.018229166666666668 85.18518518518519 explicitly_absent reference_unavailable 0 5 valid +NOTCH1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.008586282728026395 0.006396218141302518 0.002190064586723877 56 0.015886080712783135 0.0 0.006076388888888889 55.55555555555556 explicitly_absent reference_unavailable 0 5 valid +NOTCH2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.034328145661024975 -0.05592751851732836 0.021599372856303388 56 0.025783870960812194 0.0 0.011284722222222222 37.03703703703704 explicitly_absent reference_unavailable 0 5 valid +NRAS resolved_exact_symbol sufficient_complete_coverage 56 56 -0.19958349119150692 -0.14580495301355656 -0.053778538177950364 56 0.11160490099703885 0.19642857142857142 0.0798611111111111 85.18518518518519 explicitly_absent reference_unavailable 0 5 valid +NT5E resolved_exact_symbol sufficient_complete_coverage 56 56 -0.008866378941955744 -0.010633835887351333 0.0017674569453955888 56 0.0211052075698444 0.0 0.0 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +NTRK1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.026272854423689842 0.0019428068125859747 0.024330047611103866 56 0.01863576450281533 0.0 0.0008680555555555555 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +NTRK2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.08551856745146294 0.11012805030019948 -0.02460948284873654 56 0.007605478950701532 0.0 0.0 66.66666666666667 explicitly_absent reference_unavailable 0 5 valid +NTRK3 resolved_exact_symbol sufficient_complete_coverage 56 56 0.00021986816198801135 0.029825131448152367 -0.029605263286164356 56 0.019114279173136295 0.0 0.0 70.37037037037037 explicitly_absent reference_unavailable 0 5 valid +NUP98 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.8055598197254084 -0.7858585933258144 -0.01970122639959393 56 0.9185618693763015 0.9464285714285714 0.9244791666666666 51.851851851851855 explicitly_present reference_unavailable 1 5 valid +NUTM1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.01540965770348755 -0.010114591962301623 -0.005295065741185927 56 0.023444423153857114 0.0 0.0026041666666666665 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +OCA2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.024477812493177965 -0.04837117404353246 0.023893361550354493 56 0.025337616392692195 0.0 0.0 18.51851851851852 explicitly_absent reference_unavailable 0 5 valid +PARP1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.20900614511179944 -0.1966899483893725 -0.012316196722426925 56 0.13645456881846418 0.05357142857142857 0.05642361111111111 55.55555555555556 explicitly_absent reference_unavailable 0 5 valid +PATZ1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.1391172000683189 -0.12116391877644954 -0.017953281291869364 56 0.0798356188482517 0.0 0.019097222222222224 59.25925925925926 explicitly_absent reference_unavailable 0 5 valid +PAX5 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.014464371335449124 -0.055350805488638084 0.04088643415318896 56 0.023559907731496195 0.0 0.04079861111111111 11.11111111111111 explicitly_absent reference_unavailable 0 5 valid +PBRM1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.04422832147235136 -0.1316982764726614 0.08746995500031005 56 0.025873981311805343 0.017857142857142856 0.0998263888888889 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +PDCD1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.01957298536283847 0.03332451189767327 -0.05289749726051174 56 0.02164243704516978 0.0 0.0 100.0 explicitly_absent reference_unavailable 0 5 valid +PDCD1LG2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.09145888055795778 0.103002820737755 -0.011543940179797221 56 0.007611086135415668 0.0 0.0 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +PDGFRA resolved_exact_symbol sufficient_complete_coverage 56 56 -0.18362142417989624 -0.16961968844526118 -0.014001735734635062 56 0.10237428471529833 0.05357142857142857 0.07118055555555555 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +PDGFRB resolved_exact_symbol sufficient_complete_coverage 56 56 -0.07629056372993706 -0.07162163718064343 -0.004668926549293628 56 0.04135928988080292 0.0 0.028645833333333332 59.25925925925926 explicitly_absent reference_unavailable 0 5 valid +PER1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.09976442986895973 0.13557826823363162 -0.03581383836467189 56 0.00844002980337798 0.0 0.0 74.07407407407408 explicitly_absent reference_unavailable 0 5 valid +PHOX2B resolved_exact_symbol sufficient_complete_coverage 56 56 0.09159221551687652 0.1141949979993373 -0.02260278248246078 56 0.009699743764547134 0.0 0.008680555555555556 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +PIK3CA resolved_exact_symbol sufficient_complete_coverage 56 56 -0.2939677758894327 -0.4561301766459492 0.1621624007565165 56 0.20917938968000044 0.14285714285714285 0.484375 14.814814814814815 explicitly_present reference_unavailable 0 5 valid +PIK3CB resolved_exact_symbol sufficient_complete_coverage 56 56 -0.16430375541703418 -0.08330221026338015 -0.08100154515365403 56 0.08159559753139387 0.19642857142857142 0.04513888888888889 85.18518518518519 explicitly_absent reference_unavailable 0 5 valid +PIK3R1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.07693671363161786 -0.015540592043400196 0.09247730567501805 56 0.009912816186445288 0.0 0.0390625 3.7037037037037037 explicitly_absent reference_unavailable 0 5 valid +PLCG1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.02301043378246097 0.02419500120026994 -0.001184567417808969 56 0.01620788943023691 0.0 0.015625 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +PLXNB2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.07287237929257996 0.10058493461462178 -0.027712555322041824 56 0.010539954198750902 0.0 0.0 70.37037037037037 explicitly_absent reference_unavailable 0 5 valid +PMEL resolved_exact_symbol sufficient_complete_coverage 56 56 -0.13772450645851692 -0.08696670078141512 -0.050757805677101794 56 0.07252845996137892 0.017857142857142856 0.001736111111111111 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +PMS2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.11394202876623996 0.11741983946404981 -0.0034778106978098494 56 0.005788126840964296 0.0 0.0 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +POLD1 resolved_exact_symbol sufficient_complete_coverage 56 56 -2.0748283180612623 -2.2009152860172185 0.1260869679559562 56 1.0 1.0 1.0 22.22222222222222 explicitly_present reference_unavailable 0 5 valid +POLE resolved_exact_symbol sufficient_complete_coverage 56 56 -1.512475654018234 -1.5813166861643115 0.06884103214607751 56 0.9994873578486327 1.0 0.9965277777777778 33.333333333333336 explicitly_present reference_unavailable 0 5 valid +POLQ resolved_exact_symbol sufficient_complete_coverage 56 56 -0.2878340309311357 -0.3354516196277339 0.04761758869659821 56 0.2125326319656341 0.17857142857142858 0.2760416666666667 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +POT1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.42293149499519567 -0.41623893481081464 -0.0066925601843810245 56 0.4805480850355817 0.48214285714285715 0.4427083333333333 70.37037037037037 explicitly_absent reference_unavailable 0 5 valid +POU2AF1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.010038770990871998 -0.007804775346166002 0.017843546337038 56 0.02258460016959892 0.0 0.04513888888888889 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +PPP2R1A resolved_exact_symbol sufficient_complete_coverage 56 56 -1.471863264456811 -1.1122473426836132 -0.3596159217731978 56 0.9991692822150705 0.9821428571428571 0.8541666666666666 88.88888888888889 explicitly_present reference_unavailable 1 5 valid +PPP6C resolved_exact_symbol sufficient_complete_coverage 56 56 -0.781903782242473 -0.4894286085851235 -0.29247517365734954 56 0.8982627669210668 0.75 0.5373263888888888 100.0 explicitly_absent reference_unavailable 0 5 valid +PRDM1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.008524764962677182 -0.030787463811943288 0.022262698849266106 56 0.02097438411360496 0.0 0.020833333333333332 18.51851851851852 explicitly_absent reference_unavailable 0 5 valid +PRDM16 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.09204657993987507 -0.08420739754723304 -0.00783918239264203 56 0.04697655942427176 0.0 0.011284722222222222 48.148148148148145 explicitly_absent reference_unavailable 0 5 valid +PREX2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.11155773430019963 0.12467928818372082 -0.013121553883521181 56 0.007049386132260232 0.0 0.0 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +PRF1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.0047451788481697 -0.010633916647433368 0.015379095495603068 56 0.02139926937725605 0.0 0.0 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +PTCH1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.018151218696463505 0.0247345840198514 -0.006583365323387894 56 0.020825055662632826 0.0 0.001736111111111111 25.925925925925927 explicitly_absent reference_unavailable 0 5 valid +PTEN resolved_exact_symbol sufficient_complete_coverage 56 56 0.3093834287818784 0.3424338799920227 -0.03305045121014427 56 0.0016319869133616688 0.017857142857142856 0.013888888888888888 55.55555555555556 explicitly_absent reference_unavailable 0 5 valid +PTK6 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.12026321213311797 -0.13326680094787496 0.013003588814756994 56 0.05169764005554711 0.017857142857142856 0.019965277777777776 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +PTPN11 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.22336959724687172 -0.7670813324996104 0.5437117352527387 56 0.15755716577163256 0.14285714285714285 0.7317708333333334 3.7037037037037037 explicitly_present reference_unavailable 0 5 valid +PTPN13 resolved_exact_symbol sufficient_complete_coverage 56 56 0.0242865690164243 0.04244292382368918 -0.01815635480726488 56 0.015851864845906453 0.0 0.001736111111111111 59.25925925925926 explicitly_absent reference_unavailable 0 5 valid +PTPRB resolved_exact_symbol sufficient_complete_coverage 56 56 -0.005419265839015835 -0.003032941042676718 -0.0023863247963391166 56 0.022612690169484462 0.0 0.0 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +PTPRC resolved_exact_symbol insufficient_measured_context_models 56 7 -0.1839674851282336 -0.10900363877047652 7 0.10142439265024349 0.0 0.0398936170212766 65.0 explicitly_absent reference_unavailable 0 5 valid +PTPRK resolved_exact_symbol sufficient_complete_coverage 56 56 0.11574090709819299 0.12022499097216345 -0.004484083873970465 56 0.007097817765832145 0.0 0.0 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +PTPRT resolved_exact_symbol sufficient_complete_coverage 56 56 -0.04661431473671101 -0.06314951684378767 0.01653520210707666 56 0.03077532270482216 0.0 0.004340277777777778 14.814814814814815 explicitly_absent reference_unavailable 0 5 valid +QKI resolved_exact_symbol sufficient_complete_coverage 56 56 -0.021443690625028444 -0.012262478887139099 -0.009181211737889345 56 0.02434871601799806 0.03571428571428571 0.026041666666666668 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +RAC1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.9644656313374076 -0.7451652685013221 -0.21930036283608545 56 0.9718981505657296 0.9821428571428571 0.7864583333333334 92.5925925925926 explicitly_present reference_unavailable 1 5 valid +RAD51C resolved_exact_symbol sufficient_complete_coverage 56 56 -0.811587320321768 -0.7475824057944447 -0.06400491452732326 56 0.8957799704120795 0.9107142857142857 0.8342013888888888 88.88888888888889 explicitly_present reference_unavailable 1 5 valid +RAF1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.02220851631360249 -0.07938596753238451 0.057177451218782024 56 0.02468474918939307 0.16071428571428573 0.10590277777777778 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +RANBP2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.5210149465256304 -0.5048284426200854 -0.01618650390554499 56 0.6193692604611463 0.6785714285714286 0.5894097222222222 59.25925925925926 explicitly_present reference_unavailable 1 5 valid +RB1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.20375104048983378 0.16453840788700114 0.03921263260283264 56 0.003501129077626756 0.017857142857142856 0.0008680555555555555 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +RET resolved_exact_symbol sufficient_complete_coverage 56 56 -0.07167217571962779 -0.10983917890358519 0.038167003183957396 56 0.04047103264540877 0.0 0.001736111111111111 3.7037037037037037 explicitly_absent reference_unavailable 0 5 valid +RICTOR resolved_exact_symbol sufficient_complete_coverage 56 56 -0.39783708129546663 -0.42860231358913625 0.03076523229366962 56 0.38868919644309075 0.35714285714285715 0.4375 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +ROS1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.12383389748495374 0.10590995083832916 0.017923946646624583 56 0.005657972826808763 0.0 0.0008680555555555555 11.11111111111111 explicitly_absent reference_unavailable 0 5 valid +RPL5 resolved_exact_symbol sufficient_complete_coverage 56 56 -2.0634465911044617 -2.3033679256554587 0.23992133455099696 56 1.0 1.0 1.0 25.925925925925927 explicitly_present reference_unavailable 0 5 valid +RRM1 resolved_exact_symbol sufficient_complete_coverage 56 56 -3.527279701684648 -3.268997723440182 -0.2582819782444661 56 1.0 1.0 1.0 100.0 explicitly_present reference_unavailable 1 5 valid +RRM2 resolved_exact_symbol sufficient_complete_coverage 56 56 -2.8483434965014958 -2.6467259603749254 -0.2016175361265704 56 1.0 1.0 0.9982638888888888 74.07407407407408 explicitly_present reference_unavailable 1 5 valid +RRM2B resolved_exact_symbol sufficient_complete_coverage 56 56 0.006488471619161884 0.003594131329540177 0.0028943402896217073 56 0.017595754218379635 0.0 0.0008680555555555555 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +RUNX1T1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.04714232020834208 -0.032589026610729495 -0.014553293597612586 56 0.03193243688624428 0.0 0.006076388888888889 37.03703703703704 explicitly_absent reference_unavailable 0 5 valid +SALL4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.05751971111293863 -0.07580809559290991 0.018288384479971276 56 0.036589651850089416 0.0 0.0078125 14.814814814814815 explicitly_absent reference_unavailable 0 5 valid +SETBP1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.020794089042544255 0.010837397892716812 0.009956691149827442 56 0.016776289101935012 0.0 0.0026041666666666665 25.925925925925927 explicitly_absent reference_unavailable 0 5 valid +SETD2 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.3280383584112302 -0.4084966647293849 0.0804583063181547 56 0.26696470082025603 0.32142857142857145 0.4071180555555556 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +SF3B1 resolved_exact_symbol sufficient_complete_coverage 56 56 -1.4947664924641337 -1.4373399099802928 -0.057426582483840916 56 0.9993767217839019 1.0 0.9965277777777778 74.07407407407408 explicitly_present reference_unavailable 1 5 valid +SLC24A5 resolved_exact_symbol sufficient_complete_coverage 56 56 0.04566657198688534 0.04404512747811383 0.0016214445087715107 56 0.012767474299341924 0.0 0.0 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +SLC45A2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.11861136448699858 0.06570325358802152 0.052908110898977054 56 0.006829464645826495 0.0 0.0 11.11111111111111 explicitly_absent reference_unavailable 0 5 valid +SMAD2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.020857726704379374 0.024634716706733818 -0.003776990002354444 56 0.019602222042527484 0.0 0.0026041666666666665 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +SMAD3 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.019242661334844407 -0.01789867056678154 -0.0013439907680628665 56 0.026968181859627394 0.0 0.001736111111111111 59.25925925925926 explicitly_absent reference_unavailable 0 5 valid +SMARCA4 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.40356272875642973 -0.31767283574775484 -0.08588989300867489 56 0.3939739872865238 0.4642857142857143 0.34375 70.37037037037037 explicitly_absent reference_unavailable 0 5 valid +SMO resolved_exact_symbol sufficient_complete_coverage 56 56 -0.016674116349569723 -0.08750244279607522 0.0708283264465055 56 0.025248343352956944 0.0 0.003472222222222222 11.11111111111111 explicitly_absent reference_unavailable 0 5 valid +SPEN resolved_exact_symbol sufficient_complete_coverage 56 56 -0.1069708047403998 0.030554897115655802 -0.13752570185605562 56 0.051609868437919544 0.017857142857142856 0.009548611111111112 96.29629629629629 explicitly_absent reference_unavailable 0 5 valid +SPOP resolved_exact_symbol sufficient_complete_coverage 56 56 -0.0011139874447977718 -0.06776801291012384 0.06665402546532606 56 0.021659335715944927 0.03571428571428571 0.017361111111111112 3.7037037037037037 explicitly_absent reference_unavailable 0 5 valid +STAT1 resolved_exact_symbol sufficient_complete_coverage 56 56 0.03441501730713435 0.034154773729614785 0.00026024357751956717 56 0.015444040039196624 0.0 0.0 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +STAT5B resolved_exact_symbol sufficient_complete_coverage 56 56 -0.11715704066883736 -0.15940249496985368 0.04224545430101631 56 0.059652060425314735 0.0 0.029513888888888888 3.7037037037037037 explicitly_absent reference_unavailable 0 5 valid +STK11 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.14109773350213328 -0.17737948283947755 0.036281749337344266 56 0.07264424891737002 0.14285714285714285 0.22395833333333334 44.44444444444444 explicitly_absent reference_unavailable 0 5 valid +STN1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.3320372797448661 -0.4231674721858706 0.09113019244100451 56 0.2679704032719562 0.30357142857142855 0.4592013888888889 37.03703703703704 explicitly_absent reference_unavailable 0 5 valid +SUFU resolved_exact_symbol sufficient_complete_coverage 56 56 0.05071099091677807 0.03946241725055476 0.01124857366622331 56 0.012147568247679989 0.017857142857142856 0.004340277777777778 55.55555555555556 explicitly_absent reference_unavailable 0 5 valid +SUZ12 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.33607475463804537 -0.3978726020463404 0.061797847408295026 56 0.28560992279472086 0.3392857142857143 0.4201388888888889 33.333333333333336 explicitly_absent reference_unavailable 0 5 valid +SYK resolved_exact_symbol sufficient_complete_coverage 56 56 0.008529689252564848 0.02714536697506613 -0.01861567772250128 56 0.018472304540237433 0.0 0.020833333333333332 70.37037037037037 explicitly_absent reference_unavailable 0 5 valid +TAP1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.07247945665159533 -0.12772717441396145 0.055247717762366116 56 0.0447208452197298 0.03571428571428571 0.008680555555555556 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +TAP2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.034986271431895845 0.058494450908196424 -0.02350817947630058 56 0.012748389342080056 0.0 0.001736111111111111 85.18518518518519 explicitly_absent reference_unavailable 0 5 valid +TBL1XR1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.33277910671051136 -0.32759591051601034 -0.005183196194501027 56 0.27129473782400343 0.26785714285714285 0.3541666666666667 37.03703703703704 explicitly_absent reference_unavailable 0 5 valid +TBX3 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.144887275560554 -0.08829038233687257 -0.05659689322368143 56 0.07955915571703014 0.07142857142857142 0.041666666666666664 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +TCL1A resolved_exact_symbol sufficient_complete_coverage 56 56 -0.000812838632041863 0.002780478045225047 -0.00359331667726691 56 0.02026722678410809 0.0 0.001736111111111111 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +TENT5C resolved_exact_symbol sufficient_complete_coverage 56 56 0.021952823430253073 0.03127656538377186 -0.009323741953518788 56 0.018800263137722335 0.0 0.0008680555555555555 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +TERT resolved_exact_symbol sufficient_complete_coverage 56 56 -0.04819403767771936 -0.046616592552625125 -0.0015774451250942373 56 0.03060298315596087 0.0 0.018229166666666668 59.25925925925926 explicitly_absent reference_unavailable 0 5 valid +TET1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.01236085251979058 -0.014266890181381182 0.001906037661590601 56 0.024035437041026612 0.0 0.0008680555555555555 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +TET2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.08659371212470038 0.11314935110904266 -0.02655563898434228 56 0.007554157730363114 0.0 0.0 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +TFE3 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.010454951169714191 0.03296252298346187 -0.04341747415317606 56 0.020410044427780348 0.0 0.0 81.48148148148148 explicitly_absent reference_unavailable 0 5 valid +TFEB resolved_exact_symbol sufficient_complete_coverage 56 56 0.0019224156039644225 0.0014476013747156938 0.0004748142292487288 56 0.01872188394700413 0.0 0.003472222222222222 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +TGFB1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.0584569922925765 -0.061696369974447524 0.0032393776818710265 56 0.03879322257892474 0.0 0.0026041666666666665 40.74074074074074 explicitly_absent reference_unavailable 0 5 valid +TGFBR1 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.04561856834087192 -0.12180796060214177 0.07618939226126986 56 0.03221306181112013 0.03571428571428571 0.0842013888888889 11.11111111111111 explicitly_absent reference_unavailable 0 5 valid +TIGIT resolved_exact_symbol sufficient_complete_coverage 56 56 -0.026380581032389563 -0.07111866194902111 0.04473808091663155 56 0.029299535174605706 0.0 0.0008680555555555555 7.407407407407407 explicitly_absent reference_unavailable 0 5 valid +TMEM127 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.2801840245311775 -0.27617043866279734 -0.004013585868380187 56 0.1948213468608736 0.17857142857142858 0.15711805555555555 55.55555555555556 explicitly_absent reference_unavailable 0 5 valid +TNFRSF17 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.07182926242556906 -0.08347379630619953 0.01164453388063047 56 0.04088511534774647 0.0 0.0008680555555555555 22.22222222222222 explicitly_absent reference_unavailable 0 5 valid +TNFRSF18 resolved_exact_symbol sufficient_complete_coverage 56 56 0.0031678861143592326 0.002761574411370651 0.00040631170298858175 56 0.020690473212946793 0.0 0.0 51.851851851851855 explicitly_absent reference_unavailable 0 5 valid +TP53 resolved_exact_symbol sufficient_complete_coverage 56 56 0.8202592324433257 0.22739095457705163 0.592868277866274 56 2.371112152923413e-07 0.0 0.004340277777777778 14.814814814814815 explicitly_absent reference_unavailable 0 5 valid +TP63 resolved_exact_symbol sufficient_complete_coverage 56 56 0.06069628975320457 -0.006515289977900816 0.06721157973110539 56 0.012420727182457592 0.017857142857142856 0.0954861111111111 7.407407407407407 explicitly_absent reference_unavailable 0 5 valid +TRAF7 resolved_exact_symbol sufficient_complete_coverage 56 56 -0.13475684387968312 -0.12945310511060099 -0.005303738769082134 56 0.06819388689452299 0.05357142857142857 0.058159722222222224 62.96296296296296 explicitly_absent reference_unavailable 0 5 valid +TREM2 resolved_exact_symbol sufficient_complete_coverage 56 56 0.0323268773346124 0.015628711378444307 0.01669816595616809 56 0.014501080563188398 0.0 0.0026041666666666665 29.62962962962963 explicitly_absent 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group.","gene_effect_context_minus_non_context_mean":-0.03085347126791045,"gene_effect_context_minus_non_context_median":-0.03387072477789323},"coverage_fraction":0.9821428571428571,"coverage_status":"sufficient_complete_coverage","dependency_aware_candidate_rank":210,"dependency_interpretation_state":"valid","dependency_probability":{"available":true,"first_quartile":0.008564060822250814,"interquartile_range":0.02700284675819572,"maximum":0.23484293062520295,"mean":0.03819658296592888,"measured_model_count":55,"median":0.019485636278314837,"minimum":0.0010067610165416245,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":0.03556690758044653,"threshold_fractions":[{"denominator":55,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":55,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56},"evidence_id":"drep_93922b07a6fc0f657cd41e36eccc7c393dcf72c6e91455b1ed87ac8e4ca265a5","format_version":"v1","gene_effect":{"available":true,"first_quartile":-0.06146208289047472,"interquartile_range":0.14758793421665212,"maximum":0.2881461102807952,"mean":0.007927014410996538,"measured_model_count":55,"median":0.007593842404380845,"minimum":-0.33029884415193866,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":0.08612585132617741,"threshold_fractions":[],"total_model_count":56},"gene_symbol":"ZFHX3","human_review_required":true,"integration_state":"blocked_insufficient_evidence","limitations":["Acral and drug-adapted models are excluded from the primary profile and retained separately.","Baseline: unchanged 300-target TargetIntel antibody-IO ranking.","Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.","DepMap Public 26Q1 cell-line dependency evidence.","Dependency is treated as explanatory evidence, not as clinical validation.","Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.","Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.","No automatic target activation or release.","No clinical anti-PD-1 response inference.","Primary context contains 56 reviewed cutaneous melanoma cell-line models.","Primary context: 56 reviewed cutaneous melanoma models.","Thresholds were fixed before inspecting benchmark outcomes.","Unmapped resistance-axis annotations are represented by the controlled value other_unresolved."],"missing_value_state":"target_resolved_both_matrices","model_count":2154,"production_activation_enabled":false,"profile_available":true,"provenance":{"source_artifact_names":["candidate_overlay.tsv","selected_target_profiles.tsv"]},"rank_delta":0,"reference_model_count":2098,"release_identifier":"DepMap_Public_26Q1","release_manifest_id":"dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1","scientific_closure_identity":"v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4","selectivity":{"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777},"unavailable_reason":null} +{"approved_authorization_emitted":false,"available_context_observations":56,"available_reference_observations":1152,"baseline_preserved":true,"baseline_rank":246,"candidate_activation_readiness":"blocked","canonical_gene_identity":"symbol:ZNF331|entrez:55422","configuration_id":"v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6","context_identity":"melanoma_anti_pd1:v1","context_model_count":56,"context_reference_comparison":{"context_minus_pan_cancer":{"dependency_probability_median":0.000887099880134024,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.04234439864678727,"gene_effect_median":-0.04372457184518963},"dependency_probability_context_minus_non_context_median":0.0009410321401466981,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.04440280691433923,"gene_effect_context_minus_non_context_median":-0.045076343973518174},"coverage_fraction":1.0,"coverage_status":"sufficient_complete_coverage","dependency_aware_candidate_rank":246,"dependency_interpretation_state":"valid","dependency_probability":{"available":true,"first_quartile":0.001704372331237138,"interquartile_range":0.005424707330500494,"maximum":0.10954958289983124,"mean":0.009442167813529304,"measured_model_count":56,"median":0.003587808287988493,"minimum":1.0645838207346946e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.007129079661737632,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56},"evidence_id":"drep_b5f3ff40e6903a84cec95adb93e101202320c5ee12b31a232b62549d7b70917b","format_version":"v1","gene_effect":{"available":true,"first_quartile":0.1254636788972895,"interquartile_range":0.14498040321724526,"maximum":0.7050101742014865,"mean":0.19150820508534952,"measured_model_count":56,"median":0.19280092244168862,"minimum":-0.15201787565274216,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.27044408211453475,"threshold_fractions":[],"total_model_count":56},"gene_symbol":"ZNF331","human_review_required":true,"integration_state":"blocked_insufficient_evidence","limitations":["Acral and drug-adapted models are excluded from the primary profile and retained separately.","Baseline: unchanged 300-target TargetIntel antibody-IO ranking.","Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.","DepMap Public 26Q1 cell-line dependency evidence.","Dependency is treated as explanatory evidence, not as clinical validation.","Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.","Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.","No automatic target activation or release.","No clinical anti-PD-1 response inference.","Primary context contains 56 reviewed cutaneous melanoma cell-line models.","Primary context: 56 reviewed cutaneous melanoma models.","Thresholds were fixed before inspecting benchmark outcomes.","Unmapped resistance-axis annotations are represented by the controlled value other_unresolved."],"missing_value_state":"target_resolved_both_matrices","model_count":2154,"production_activation_enabled":false,"profile_available":true,"provenance":{"source_artifact_names":["candidate_overlay.tsv","selected_target_profiles.tsv"]},"rank_delta":0,"reference_model_count":2098,"release_identifier":"DepMap_Public_26Q1","release_manifest_id":"dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1","scientific_closure_identity":"v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4","selectivity":{"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148},"unavailable_reason":null} diff --git a/data/releases/depmap/DepMap_Public_26Q1/discovery_universe.tsv b/data/releases/depmap/DepMap_Public_26Q1/discovery_universe.tsv new file mode 100644 index 0000000..c24e684 --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/discovery_universe.tsv @@ -0,0 +1,332 @@ +canonical_identity entry_format_version entry_id inclusion_source_ids inclusion_sources inclusion_status limitations original_identifier rejection_reason resistance_axes resolution_status role_annotation universe_type +symbol:ABL1|entrez:25 v0.5.0 tue_55f7bae0f091f5135960237d2160c85107a77b0d196f3030c054044ff58a1d7f "[""tus_b5500e784769b5ffb6e8197d270b0071227922e08a69244294eaea01a3571ab7""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000097007""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ABL1 "[""other_unresolved""]" resolved_exact discovery +symbol:ACKR3|entrez:57007 v0.5.0 tue_49f603e31fae705539dfc312ad872571895b89c44053fb2b4ff830c8c2fe233c "[""tus_bcc79c9d33a994862014e3fc489b20feef032ed0d79ec94fe54c2821b8f9a5ca""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000144476""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ACKR3 "[""other_unresolved""]" resolved_exact discovery +symbol:ACVR1B|entrez:91 v0.5.0 tue_483f2222ab485047f6e1ad4f66519726ad109387d8b7936645c9a875aedbdddf "[""tus_03aefc83b676ce9c5d2f8d8cf52ff5af7b3840d58bcd66c5c9ab581925f11795""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000135503""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ACVR1B "[""other_unresolved""]" resolved_exact discovery +symbol:AFDN|entrez:4301 v0.5.0 tue_1a43fce352ce29bd1a590cf3a7bc2460df84ec0d6d813d0f0922cf415fca9c75 "[""tus_159eef9a44a6baa7d190899e40170ca67ed60c121a4b6d3ef2d51771b1be4497""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000130396""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" AFDN "[""other_unresolved""]" resolved_exact discovery +symbol:AFF4|entrez:27125 v0.5.0 tue_3058368777a5279dea818622bf9a4485c09efb1bdf0aab3c6c5a59c3887bcf77 "[""tus_ec2e77d0ed0f331287dce8500f5617f6d1e5bb6bc88d37c9d900997590cc2d53""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000072364""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" AFF4 "[""other_unresolved""]" resolved_exact discovery +symbol:AKT1|entrez:207 v0.5.0 tue_568430c0e5de7694592fe5b1e8645755511fd0879c4b5886a63489c4b15861d0 "[""tus_ca91678234ebb8362db560656962de9370ee636513d32646703cb3bf508b9b06""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000142208""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" AKT1 "[""other_unresolved""]" resolved_exact discovery +symbol:AKT2|entrez:208 v0.5.0 tue_2d61f535360383fa87fb5b899c56799edde4d1e9dfe0cb72e49666f60acd8d48 "[""tus_0151dcd3340e4c04631d69da23a34d705d04e83db3d3354e2becc764cbf5944f""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000105221""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" AKT2 "[""other_unresolved""]" resolved_exact discovery +symbol:ALK|entrez:238 v0.5.0 tue_b5941cd8192dd7d934f37cc209bfae642968c7c2dace95c07e13525097d61666 "[""tus_cf0c45a9aa1efee978b98e9106b467ea6208a5ae1af4aa5ea2c9a59538a249ed""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000171094""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ALK "[""other_unresolved""]" resolved_exact discovery +symbol:AMER1|entrez:139285 v0.5.0 tue_e260c02cfde1c72af331db30b9240e0f0fbd44de459fec28fe500e11b0abd0f0 "[""tus_121305eca6f38ebf2365fd24f905d990ae6a2f58cc8330862e6a659ee0f1f695""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000184675""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" AMER1 "[""other_unresolved""]" resolved_exact discovery +symbol:APC|entrez:324 v0.5.0 tue_9e0d582535d4998c6c5cef5035a28c817938a26f8e2f0eb8b8e9b644e3efc0e1 "[""tus_55fdc775383107d6c81ad363effae86de9ec6494c2adb70b755953ca5e67c2b3""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000134982""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" APC "[""other_unresolved""]" resolved_exact discovery +symbol:APOBEC3B|entrez:9582 v0.5.0 tue_9a471d98999c6b1a09e426607d141873f77c6b871984e99b57c1f98b1bb289fc "[""tus_8803ad27b4e313e36ba7d0e54001adc3fef0308adab6af7c55be626915533554""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000179750""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" APOBEC3B "[""other_unresolved""]" resolved_exact discovery +symbol:ARG1|entrez:383 v0.5.0 tue_3326f1c120173a3ee3a2539b236ee446b8af032e72f456571343a193bed04d59 "[""tus_455344767e5ac59169f1bf73a58341f02b66f1024885972db4def56f02f4c49a""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:ARG1|entrez:383""}]" included [] ARG1 "[""metabolic_immune_suppression""]" resolved_exact metabolic immune-suppression target discovery +symbol:ARHGAP35|entrez:2909 v0.5.0 tue_048ad038e178ce7f06c4602c12b5b3c3f42d1d9c8a959eee8225f37aef3fab1b "[""tus_f6330f226d041722ce7c4a5b248c7818a15478e7280993c88090619076ec307e""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000160007""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ARHGAP35 "[""other_unresolved""]" resolved_exact discovery +symbol:ARHGEF12|entrez:23365 v0.5.0 tue_e3d5b95a9d6e306ee8e2fbe1f3c5bd7acc179cc23175295a700e67b6f269c3d7 "[""tus_a81fb66891c6ba89122c62ccd7dec054b32618ec05b0646f15406687694ea69c""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000196914""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ARHGEF12 "[""other_unresolved""]" resolved_exact discovery +symbol:ARID1A|entrez:8289 v0.5.0 tue_28626265beb699a14243897bc93051e0d219093052fd24886bb11de2817dbb20 "[""tus_d40ec3e9de4d0e9152d0c509677d3e1279777eab927a088f6a7f18cd549d10a3""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000117713""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ARID1A "[""other_unresolved""]" resolved_exact discovery +symbol:ARID1B|entrez:57492 v0.5.0 tue_6ad6b59b2d3ef9c20e0e96631bc0f247ec7c8ce1c21d84bbd57c1a76d2fdbab6 "[""tus_2b50c4ec0197197358a8d2fe5f9c740b8ed0a834ae213d47fd3472679101ce18""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000049618""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ARID1B "[""other_unresolved""]" resolved_exact discovery +symbol:ARID2|entrez:196528 v0.5.0 tue_1fdf2e944599318e5e932464224e71eb931ce741651f87557b59d3444e277f37 "[""tus_9bf5c03214868a02a52eb6dc1e5330f3bf720ec5b3bc7c860124939b2afac313""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000189079""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ARID2 "[""other_unresolved""]" resolved_exact discovery +symbol:ARNT|entrez:405 v0.5.0 tue_eaf389f560525650198d0ad66dd6cb021ba84f5170f0d9aef7bd7d0111440711 "[""tus_7e97282c2435886d83e2b4fbbe0665312656c8700dbd1df891e5437331d4dc60""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000143437""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ARNT "[""other_unresolved""]" resolved_exact discovery +symbol:AR|entrez:367 v0.5.0 tue_3e62701c840a1037c026da8fc65dc15f630edb868759429f91f95e245837eb8b "[""tus_f2ccc09190b1e30ad3f380ff8cd4058c2e8c4a573622e120444fa16586d9a653""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000169083""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" AR "[""other_unresolved""]" resolved_exact discovery +symbol:ASPSCR1|entrez:79058 v0.5.0 tue_3c9868b7cb6279abde2157eeac2e1733b48f6b41a932ab84910eeeec549a4092 "[""tus_551b10099abaf3ba7be626daae062e0db18434fc1bec4d9e07767ab293b98886""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000169696""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ASPSCR1 "[""other_unresolved""]" resolved_exact discovery +symbol:ATF1|entrez:466 v0.5.0 tue_834ac9ae356aeffcdf06d8a0adbcf2746cad461031a60749a414ac4a0ab21436 "[""tus_67063725b74617f452da2e62a9792a6b53b10723449d93af709050d729d71335""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000123268""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ATF1 "[""other_unresolved""]" resolved_exact discovery +symbol:ATM|entrez:472 v0.5.0 tue_a892355b54596014e95f77f67d1a54cfb14d3a12e5da7dcde989965b488cb296 "[""tus_38017e0c6c0576a2257ce49d37091124be9664cfae2433d02c7da1828e4e5391""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000149311""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ATM "[""other_unresolved""]" resolved_exact discovery +symbol:ATP2B3|entrez:492 v0.5.0 tue_17c5962122aca7cdae373b5c774e144335c9120152067c3518822c3ce0214eb1 "[""tus_f59edf1b5f42cc119f4722de57a7f9d3ef6f26a618fbd64dcfdd709b60fc7ddc""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000067842""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ATP2B3 "[""other_unresolved""]" resolved_exact discovery +symbol:ATRX|entrez:546 v0.5.0 tue_56b6e7f346b4daf83ecef00b0e68a61a1831a62b66bf5d53f63b8f4d4ca2d873 "[""tus_8a00d84070634a7fc8b943ae5a93bc68044143d3facb643fa426bef200172037""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000085224""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ATRX "[""other_unresolved""]" resolved_exact discovery +symbol:ATR|entrez:545 v0.5.0 tue_f2efdf1a1f43b801557250daf38ffa5318aa9477331a61d13afb180158f8361e "[""tus_7f4420dbd8fcd788575fb20214f39682ec439a802e151d0d98f91fec68f51b00""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000175054""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ATR "[""other_unresolved""]" resolved_exact discovery +symbol:AXIN1|entrez:8312 v0.5.0 tue_4fd6cdc43e73aa5a2e6198330f8b3f3200aea96563c1bc5eb691189ad1b70c02 "[""tus_79473195d36f8c0f783fa9e1bba036da8034c97460066b9641f12c6184c80e76""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000103126""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" AXIN1 "[""other_unresolved""]" resolved_exact discovery +symbol:AXL|entrez:558 v0.5.0 tue_f4df6e8c9000ec2492f28ed487acf0a34ae94a647126e7dbf06aec9ada3196d5 "[""tus_097eced9a30898a566261a5f91811d9e51bd874e48d6aad821edd4f96f6b742c""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:AXL|entrez:558""}]" included [] AXL "[""melanoma_plasticity""]" resolved_exact melanoma plasticity / resistance-associated marker discovery +symbol:B2M|entrez:567 v0.5.0 tue_a7574de048c566cbc6140ece35caccc64ed29883025913949c75dce33303c511 "[""tus_6a9818aea76119b44a27cce311eb281659a15e2241a0426be5260b9ccda00a2a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000166710""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" B2M "[""antigen_presentation_loss""]" resolved_exact discovery +symbol:BACH2|entrez:60468 v0.5.0 tue_fc11ae0517f1b98cce561cbd46dbb3447b1a6b506172102b18d7d065a8010527 "[""tus_51db7706f0937c0dcd48dfd2ac1ed7d772f0ec9f29d06c77838d1f858bf23b06""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000112182""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BACH2 "[""other_unresolved""]" resolved_exact discovery +symbol:BAP1|entrez:8314 v0.5.0 tue_24dc8aa6fe792dd7fc3f6333437926ee1c853f5e7ad85da0bbd0a373fab50b93 "[""tus_ece6655a4126263d5a8667ddd317af520af4f82396f332d1af6e41fd36865212""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000163930""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BAP1 "[""other_unresolved""]" resolved_exact discovery +symbol:BCL11A|entrez:53335 v0.5.0 tue_e2734e3d55bd6ec636b80b872dacde01963999cc14cabffbc9c17ab076727764 "[""tus_4636976d1ef05186f8b4984f34068dc31ab32654f945de5dfd1d6af3520e2bd2""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000119866""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BCL11A "[""other_unresolved""]" resolved_exact discovery +symbol:BCL11B|entrez:64919 v0.5.0 tue_dac6bb54d1f76c36524f94e7f88bf2827aefeb29c5a22f7e4fb2cda7727513f7 "[""tus_44d7a02d6c6d4e224c1b9b2eb99a74b2addc5ce48aed046d941a8f1c93e2a5c9""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000127152""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BCL11B "[""other_unresolved""]" resolved_exact discovery +symbol:BCL2|entrez:596 v0.5.0 tue_ea19d253eb088257d388dd587676e8a8d83bafb14f8834a90d8003923e15c269 "[""tus_25bf7b26ca489a0a282ceb89c926951976ff194041ba4e2ec1ec4e0706fa6e62""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000171791""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BCL2 "[""other_unresolved""]" resolved_exact discovery +symbol:BCL9L|entrez:283149 v0.5.0 tue_8ebe99ff38faa974b4cff59529ac2d8e1ac54bb9507d478d3d6891a9600dc01e "[""tus_093deb8f616de9c33137cfca40907a34bb00addc515393004260f594841d2377""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000186174""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BCL9L "[""other_unresolved""]" resolved_exact discovery +symbol:BCL9|entrez:607 v0.5.0 tue_b6648b5c7fe3fda5d5a181c311497d57408d4f978d8366ebcac14a368e43d1de "[""tus_af401d2563ad7d3f8dd589197fa9eb248942c2a88e102277b3be2f27497cff3c""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000116128""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BCL9 "[""other_unresolved""]" resolved_exact discovery +symbol:BCORL1|entrez:63035 v0.5.0 tue_6fefe7587b7ced11502fb481867d0dc59982509c6fc4af9c337d0707e1a6734d "[""tus_0ac3f7f304a30b9601b58435ac31d6ffeab53695c8dff7db209a646152eb19cd""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000085185""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BCORL1 "[""other_unresolved""]" resolved_exact discovery +symbol:BCOR|entrez:54880 v0.5.0 tue_4c38ea71515592ad1800a4714b18398894a65b5cfaa0d0c0d81304f3e2354060 "[""tus_da528d68110e2aaf0c9accbc17becac676d1e18734940a1527ceb2a150281843""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000183337""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BCOR "[""other_unresolved""]" resolved_exact discovery +symbol:BIRC3|entrez:330 v0.5.0 tue_8ce378360ce5b2e73096aaed7480b7aa10f809d21283ad95880b6ad4a6b00919 "[""tus_7449e4aeb1b5f475fe9a74c2c2c80f00db5cb91696c455c699bf4180f8966c9d""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000023445""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BIRC3 "[""other_unresolved""]" resolved_exact discovery +symbol:BRAF|entrez:673 v0.5.0 tue_ac171e1df24d8963ddc2d3be7517def0545c1573010a7efe81d3a694820fac0e "[""tus_17c9bcf3e77cb863a86948a6cf4388d77334a13fadc81a38b14c5d678a63dc84""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000157764""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" BRAF "[""tumor_intrinsic_driver""]" resolved_exact discovery +symbol:BRCA1|entrez:672 v0.5.0 tue_8bea5a3d202f2f19a81ddbd89448a218998e6b1bbcdd582236034e622aefc593 "[""tus_6ac5fda35322cefa4144d843cdfd6e4d31aaf6ed44a2e0516f15a004c877cd96""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000012048""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BRCA1 "[""other_unresolved""]" resolved_exact discovery +symbol:BRCA2|entrez:675 v0.5.0 tue_b6faf095d2d5b9203b544ddf7643e4fb0ea3caf2aeddc8ab83081c919b70dcf3 "[""tus_53075289f79d2bae3005cd1554ba9dd091d30d5b4eed12958d0a40be16b2d421""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000139618""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BRCA2 "[""other_unresolved""]" resolved_exact discovery +symbol:BRD3|entrez:8019 v0.5.0 tue_7deeff6aa1f8ea9da478f27fc1b4f6e25f84cf8c586d01b67be97b6c5ef3de7c "[""tus_75039c8b1b075ec27ccd9b9f627a54523fe977996783b8e1748247ac66da3032""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000169925""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BRD3 "[""other_unresolved""]" resolved_exact discovery +symbol:BRD4|entrez:23476 v0.5.0 tue_fbbbd6e4e4130e19a0120c3ac5a8f9902f8ee5b2b021aac33fade88f5c2ab89a "[""tus_c9d5f194e1f811cdf67e5aa431edd6eaa180b0f37edffa497a8cde3cb5a93b1a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000141867""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BRD4 "[""other_unresolved""]" resolved_exact discovery +symbol:BTK|entrez:695 v0.5.0 tue_3f07742b14d986d349e9c21404b287df556a0339cfa6d68b1488336a1f32b6d4 "[""tus_d85f45fd262d1df9279abc5eea4676600df63dd12e99fde8c4e99de316bd6008""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000010671""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BTK "[""other_unresolved""]" resolved_exact discovery +symbol:BUB1B|entrez:701 v0.5.0 tue_f5ed87ae406fd9b176388c158b42a1a8fe52244678198226e612ff787405f3d2 "[""tus_9a751615c9789d694d05c29ff449dcac9d5c7bd09040c6292b22920ffe4e3071""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000156970""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" BUB1B "[""other_unresolved""]" resolved_exact discovery +symbol:CACNA1D|entrez:776 v0.5.0 tue_e2a843cd32bfc4fec16cf60a47705cf9ec784e75c540fde40bbd9bb7580c196a "[""tus_995ccae2a3dc0965d060a515656dc4f543d4990748fbdc579500fc8d6983f8a6""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000157388""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CACNA1D "[""other_unresolved""]" resolved_exact discovery +symbol:CARD11|entrez:84433 v0.5.0 tue_8a4f140e1130a09e81aa7f2b1af7e1262518ca202bbffc836e55f8e7284c95a7 "[""tus_e1f7814a44ed00bcad68e724af91007467fdb668d375f981f840cdb31d707657""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000198286""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CARD11 "[""other_unresolved""]" resolved_exact discovery +symbol:CARS1|entrez:833 v0.5.0 tue_552cd6ec5fe288554f8647d863fed9f473f5ce333209d97c278fce2884299bf6 "[""tus_7e5c0396514edc4eb44a20b06e5fe0851b74e1f3b783cefeae8a65eddd9e03c8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000110619""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CARS1 "[""other_unresolved""]" resolved_exact discovery +symbol:CASP8|entrez:841 v0.5.0 tue_9045c379418273b97a8ee80b3c89f3bdf8ae7432796612fbe695ab07a6adbd26 "[""tus_c4e6ff44b675dcbbedf96ad52cefe136519cd510d1da2ffdbf58a74a79c06dcb""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000064012""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CASP8 "[""other_unresolved""]" resolved_exact discovery +symbol:CBFA2T3|entrez:863 v0.5.0 tue_8dec81f5a2ce4439c2f8f521801a7c9813fed45341990056288552b402b3fbd9 "[""tus_9d1a8f13caeabc3e88c1aa57cbebd127af5b7979cf9eaccfc3af56ad481f4830""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000129993""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CBFA2T3 "[""other_unresolved""]" resolved_exact discovery +symbol:CBLB|entrez:868 v0.5.0 tue_53980ffaa4a956c983a8f48b1fc1e1d41b751fd8b7ab34883f5bb4a7a3338ee7 "[""tus_7c3cef49072cac93e227c3d316f3c7f7802f6199fa08c387b00ce882760a333c""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000114423""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CBLB "[""other_unresolved""]" resolved_exact discovery +symbol:CBL|entrez:867 v0.5.0 tue_0f232ec4786b912802248e47faa4ea187bd0c063e4d967ad12d77542016c0600 "[""tus_a639817a956aa0447fcf8f65a70ace93d4789bd2369a9c27447b37c4941a20ba""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000110395""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CBL "[""other_unresolved""]" resolved_exact discovery +symbol:CCND1|entrez:595 v0.5.0 tue_8e91a74a34b4430ab325d43a99da056b9b53be34802116856d1ffaad2937d8e1 "[""tus_bcef30d8f57c1ad57c30e73fdfa6f1641d11e7e3e7d82975565a7b3572849649""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000110092""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CCND1 "[""other_unresolved""]" resolved_exact discovery +symbol:CCND2|entrez:894 v0.5.0 tue_28eb0ce885ba72bdefa2398d20494c56db55698b139fc45d15b15e2079b1749f "[""tus_e2f99e6025acaf92ed3f9585b6a3e89395624c46761b934dec67f75aeb46a7d3""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000118971""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CCND2 "[""other_unresolved""]" resolved_exact discovery +symbol:CD274|entrez:29126 v0.5.0 tue_3f1c2939d30cd99d328beda3fb1dfd44c129c9e6d37dc06dc23fa253a1d46afb "[""tus_9741a75171e86fc876c1fb8a264a88f0ce4ab570e6f839ce28e2ecfa92668f98""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000120217""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" CD274 "[""checkpoint_redundancy""]" resolved_exact discovery +symbol:CD79A|entrez:973 v0.5.0 tue_8bdd977b9395c25cc71dc720a56e4b05d7ed382d7f9fac20b977aa8ffbcffd30 "[""tus_c9211f6d02d5aa131a4cdf92c1d00ac43f47422006d359b7868371e319ebbc7f""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000105369""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CD79A "[""other_unresolved""]" resolved_exact discovery +symbol:CD8A|entrez:925 v0.5.0 tue_93080a29f4f28b149712efe8205fc20b95cde7934ca2e064e65d1292d338383e "[""tus_118441a554619d8ed068b79a4c59f77c592238fa643918ba47eb8b118c30fb53""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:CD8A|entrez:925""}]" included [] CD8A "[""immune_cold_state""]" resolved_exact immune-context marker discovery +symbol:CDH1|entrez:999 v0.5.0 tue_d78dc10e618538f9810b8c4557f6009e88386f1dd40a40cca7cabee377c95cd6 "[""tus_9988b2661182f4a21ba3921789786c92db7d842e8d94d4b3c7202ebb88c1d421""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000039068""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CDH1 "[""other_unresolved""]" resolved_exact discovery +symbol:CDK12|entrez:51755 v0.5.0 tue_df2c9491f02e06851d0a174cab27d7aceeb969ec982ba7175c3ef1da0671934f "[""tus_8644219d54497fe43ec65dda6b6081873d4e4c7373fb40528b843884bdce3b61""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000167258""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CDK12 "[""other_unresolved""]" resolved_exact discovery +symbol:CDK4|entrez:1019 v0.5.0 tue_f16bca7ac8c2b1dd031ec399d8809bef4f0ece258836a27bcf955968f5ed1366 "[""tus_d17846b58f680a0edef60b3881c2268ee14a81ca7c235d48d37ef7ac672e0f43""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000135446""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CDK4 "[""other_unresolved""]" resolved_exact discovery +symbol:CDK6|entrez:1021 v0.5.0 tue_d9f8f5597afdf704d49be63e233fedb08c1e3c2e02c67db30352164f4b5d4819 "[""tus_2d5f08a6c44c1678d76b033b6a3138381c146df635bbda526bd0376dea1e466a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000105810""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CDK6 "[""other_unresolved""]" resolved_exact discovery +symbol:CDKN2A|entrez:1029 v0.5.0 tue_df8e411406fdff40a5d6af267cf4994db21a5e3f52e833deb38a8cde90368b4e "[""tus_fbbc3903306af6a7dc5e30477bf2cc28d54e4a3a0f95d90355888cc9842cfdd2""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000147889""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" CDKN2A "[""tumor_intrinsic_driver""]" resolved_exact discovery +symbol:CDKN2B|entrez:1030 v0.5.0 tue_3119f4d21e0e02eb023e5c543c103ffadcc2a343b0578ed1afd4533246739060 "[""tus_9a7b8ed2ac9cdfc6ef79e5ddb6ce915ea8158ecf8da6017dfb7d6462f854b784""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000147883""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CDKN2B "[""other_unresolved""]" resolved_exact discovery +symbol:CDX2|entrez:1045 v0.5.0 tue_a9b19c519e49f31e7cbefc0bf6687eb7c1781c4784fde57837ce73942d1e317d "[""tus_dea2b148a888be1545251a32d651ac8461125180fb96cd34923a6f6c7409f594""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000165556""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CDX2 "[""other_unresolved""]" resolved_exact discovery +symbol:CHD4|entrez:1108 v0.5.0 tue_95103999805f672853836cfd0070bdc470e34a032f9f43c8d320e4d18f519443 "[""tus_f40a1ff7210f4861b937cb7401ef4c7f5c04337a151269e09eaac95c9baa888d""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000111642""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CHD4 "[""other_unresolved""]" resolved_exact discovery +symbol:CHEK2|entrez:11200 v0.5.0 tue_b3d1fbc0ba234512ae8c91fda3e0564c2c4ed7bb43908dbbe91a5ee701d1c51b "[""tus_398674505be2c6fb0d73efca5f4cba1725a298c9173fc67829dd7fd55e3315de""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000183765""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CHEK2 "[""other_unresolved""]" resolved_exact discovery +symbol:CIC|entrez:23152 v0.5.0 tue_94cb5e8822230d6286a2fe85f342604339b65797ec4209955e42678a607da7dd "[""tus_8f414c0c42c9455cea12f333664d6490f0c4a6e57c4bb6841bcaecb36a954796""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000079432""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CIC "[""other_unresolved""]" resolved_exact discovery +symbol:CIITA|entrez:4261 v0.5.0 tue_60639ee158769b2069448241c5e46e9e2ed44b5639ac98891357c37f40655750 "[""tus_a909a17dce3f8ec367f595bdc1c97d8c71dc6a95e9d2468306c0cc315df5b4e5""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000179583""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CIITA "[""other_unresolved""]" resolved_exact discovery +symbol:CLPTM1L|entrez:81037 v0.5.0 tue_76c10a6688bdb872993e094e8eaacbdb8b86b0bbd26d59d8109205a18d54cdc4 "[""tus_c5dd66da46f0d236f9279f2c78678edf2099a8f225bd2d8e9e7defe032f14939""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000049656""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CLPTM1L "[""other_unresolved""]" resolved_exact discovery +symbol:CLTC|entrez:1213 v0.5.0 tue_a0e10485b33d609ad0a6ab33fe29485cce9c3519365459929df4c4016e787c93 "[""tus_c3a5969e2ec0bbac02da4db029531dcd897f719786a1ac70f42e747ca76f01c9""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000141367""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CLTC "[""other_unresolved""]" resolved_exact discovery +symbol:CNOT3|entrez:4849 v0.5.0 tue_8204a669a2cedf0ef8627665be7af1d5f6b4c72891322a9552eb02b012b9f07d "[""tus_af3ec2b8591ef04be4687765aba8e58d80e1532ef99f6a0379760ab2ebc6d8ba""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000088038""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CNOT3 "[""other_unresolved""]" resolved_exact discovery +symbol:CNOT9|entrez:9125 v0.5.0 tue_3feaf1caffa8aa01f753c1a2a9a684f21716406f3a162c213f2dca47e6ea4216 "[""tus_1a10583412a3cd743d06b464c3eb6eb6bd07a25831caf4211834ebab7fc8022a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000144580""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CNOT9 "[""other_unresolved""]" resolved_exact discovery +symbol:CREB1|entrez:1385 v0.5.0 tue_d74fc2995df44bbfb5a02ce4399676f038859e10acbdee178e0806f3ca6e3368 "[""tus_ba3ab33fc03590f7847a5d7e3b92267b84ca4b14acb8ed1bce76d76603a33a59""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000118260""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CREB1 "[""other_unresolved""]" resolved_exact discovery +symbol:CREBBP|entrez:1387 v0.5.0 tue_ece46cc4dda1a2f8e7fb9dbd618ad5ee53e0c3013ccfebaecf63d30b2964da32 "[""tus_3e641f4b80af2053940399860a181a771c94c750c30b1ee33179e405a18707b6""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000005339""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CREBBP "[""other_unresolved""]" resolved_exact discovery +symbol:CRLF2|entrez:64109 v0.5.0 tue_ccc135b2c1c5e0d5b6d60387350496dfb2e2173324d67be84d0a70d9f6bd615f "[""tus_29c7fbd36bbf8d8f10cbbba1137a0c3fa4df2ba6084143f88bacef8d01f0c5d8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000205755""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CRLF2 "[""other_unresolved""]" resolved_exact discovery +symbol:CSF1R|entrez:1436 v0.5.0 tue_0993340d9f75d80c28af997633166ed8d66d4843e5d2501132b0880bf78a4d6b "[""tus_5742504603534a37eac54a4f02af5f34f3f43700c48905884740c4417b9a5955""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:CSF1R|entrez:1436""}]" included [] CSF1R "[""myeloid_suppression""]" resolved_exact myeloid/TME anti-PD-1 combination target discovery +symbol:CSF3R|entrez:1441 v0.5.0 tue_31e2a384835429e6c27a28fe2a585694d391bcea62c249d1bb5bd51ef816680f "[""tus_211a068cf9918be0918df1140f20988caf83e4afedd1c8dc2354529c64019952""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000119535""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CSF3R "[""other_unresolved""]" resolved_exact discovery +symbol:CTLA4|entrez:1493 v0.5.0 tue_fa63c72428eccb9b2156d160f5e0b9f5d9876ced5b78a1b33dda27459d8d1cd0 "[""tus_26736cbef3695ac4bee264be6916a99cd4a4d8ebd1d53b9fc1013b6102f49db9""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Multiple resistance axes originally separated by semicolon were canonicalized as pipe-separated controlled values."", ""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000163599""}]" included "[""Multiple resistance axes originally separated by semicolon were canonicalized as pipe-separated controlled values."", ""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" CTLA4 "[""checkpoint_redundancy"", ""treg_suppression""]" resolved_exact discovery +symbol:CTNNB1|entrez:1499 v0.5.0 tue_54c75aaec038b8da3d892ea598b0c41fa524b517dd7a5dcd8a5bbb37c67235e9 "[""tus_4249641a0396a93cb84080a1b21bde60370ad4c305e1d88d9b2e75d2391ab21a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000168036""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CTNNB1 "[""other_unresolved""]" resolved_exact discovery +symbol:CUX1|entrez:1523 v0.5.0 tue_f07eab2c412e2d87c985b9ffd8a528453e012ab82de50c9eab5584c7dba9d06b "[""tus_380a423702e6b5428578e5feddde61d460035972d6a5736b41e8b593496332bb""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000257923""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CUX1 "[""other_unresolved""]" resolved_exact discovery +symbol:CXCL12|entrez:6387 v0.5.0 tue_ead29d16042c89cd21ce239cf96a32d486769d402692dc2c4a726df83da128aa "[""tus_a0fb43950c7e820a1a62c55864fcf4a8caf40c24fb03736fdf83dca85faf7c05""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:CXCL12|entrez:6387""}]" included [] CXCL12 "[""tgfb_caf_exclusion""]" resolved_exact immune-exclusion / stromal-resistance candidate discovery +symbol:CXCL9|entrez:4283 v0.5.0 tue_a61399f2bb42068837412e69afc6b77804d6f31a01cb1f8a63e7b78a74c887e3 "[""tus_b9deddc8a9443c105970094351a5d8bdf9f3cefb8ec93190326fc255d2bd49cc""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:CXCL9|entrez:4283""}]" included [] CXCL9 "[""immune_cold_state""]" resolved_exact immune-context marker discovery +symbol:CXCR4|entrez:7852 v0.5.0 tue_be187f05e2fa038925c961d711f041652140b21da3426f44b431a7f537b9363b "[""tus_bc559d968f6ec8b84b82705d632fbf730c6c6ee7fccc88fb3cd9adcd21ed7b0f""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:CXCR4|entrez:7852""}]" included [] CXCR4 "[""tgfb_caf_exclusion""]" resolved_exact immune-exclusion / stromal-resistance candidate discovery +symbol:CYLD|entrez:1540 v0.5.0 tue_ae16f19f28c634ef27e4f72e50abbc979b9856014d4b4e8852cdd32126f72fea "[""tus_c96bccce01a2b53582322d5df519675ec0e0002c9ba04494ce09ea68126214dd""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000083799""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CYLD "[""other_unresolved""]" resolved_exact discovery +symbol:CYP1B1|entrez:1545 v0.5.0 tue_c5fe0b0ec545175bb928205be17aa790ef3e2f90bb997f3776ffab90cc446239 "[""tus_bc4f04c78fd252f7daf16e214e8bff7537cc69bbf3dc9cd89a4fdbc643c1f715""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000138061""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" CYP1B1 "[""other_unresolved""]" resolved_exact discovery +symbol:DAXX|entrez:1616 v0.5.0 tue_a653b3d7897c634893a59ffafeac9d5a14d3274cc5d8a021136e711b10492518 "[""tus_6903e399ff9b44b6f168d0c1654a2e359f3faf42a8404dedc11ece79ea905968""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000204209""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" DAXX "[""other_unresolved""]" resolved_exact discovery +symbol:DDR2|entrez:4921 v0.5.0 tue_0761a69485fa148af2fd4ee31d44ccbb171bf65187eb82dc1d5321e7258f1c79 "[""tus_5fc56c5b42f5e407662c009565de6d1952d0170bf166d99bcdbdbc5226e2df79""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000162733""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" DDR2 "[""other_unresolved""]" resolved_exact discovery +symbol:DDX3X|entrez:1654 v0.5.0 tue_952f03c77af11feb020856605e9a0eb51f3a9c631fbd04552caa279e6a6b4a95 "[""tus_de88f2b7da7853934b9d239fb1b455f2656d1c1f58fdcdb563e28b72b105dff6""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000215301""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" DDX3X "[""other_unresolved""]" resolved_exact discovery +symbol:DICER1|entrez:23405 v0.5.0 tue_192e30431b981bce3a20458e86ddbda0a6e4a77502b23f06c6a5241341c577c6 "[""tus_cf9d9456679654dce367ebeac9c3e3e124de2389354456b84217e5eec8811f69""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000100697""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" DICER1 "[""other_unresolved""]" resolved_exact discovery +symbol:DNMT3A|entrez:1788 v0.5.0 tue_2256c201f9d4f52f2d879352b60d6c8caca236b919b155776b0b201a391a2798 "[""tus_5da5f700a0bb61fb9334d885e124e8d5b36f72cf17aa26c8ec3d2eed001ea93e""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000119772""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" DNMT3A "[""other_unresolved""]" resolved_exact discovery +symbol:EGFR|entrez:1956 v0.5.0 tue_a9c867c548ad816cf19f67884ed6d9f356992e1a3116aa71b6b554946d96d9eb "[""tus_5212eb7f4664a34abd4840bf87722a35330dcf849efa2c9cc8a5276f15f72d83""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000146648""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" EGFR "[""other_unresolved""]" resolved_exact discovery +symbol:ENTPD1|entrez:953 v0.5.0 tue_8d75f8389fc5d6642fddaeb69025155536df48f70ea3f2c4a222ca164561b18a "[""tus_7607ab5744469c1b44b2858ad0153530fc44b0808e9ebaa63c700b5aa6066da0""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:ENTPD1|entrez:953""}]" included [] ENTPD1 "[""metabolic_immune_suppression""]" resolved_exact metabolic immune-suppression target discovery +symbol:EP300|entrez:2033 v0.5.0 tue_f867cbc203d8e0539e8ff67184b4261cbcdd61ebb74eca3cfbbaaa24786c3ee7 "[""tus_a40756722ce84c614116ce184caeef674410e7179c20b05d53eef432ae5c1ee1""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000100393""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" EP300 "[""other_unresolved""]" resolved_exact discovery +symbol:ERBB2|entrez:2064 v0.5.0 tue_9dff0dd5c206b783d52fbbec15045c8c173ff8a430ea9c8d524318d5e28fd4cc "[""tus_794eaf4daeda9ccc586889cab13dcd72156ccf28dbc08bcc0482fa22250eceb3""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000141736""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ERBB2 "[""other_unresolved""]" resolved_exact discovery +symbol:ERBB3|entrez:2065 v0.5.0 tue_544f7f69ab467487a17a24769e6102723d17dbf795bc5a15a2af069d020e5d53 "[""tus_e556a944eda0f3eca86025b5c6c190bac6c39cfd0ae46fc02a29295625ab3866""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000065361""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ERBB3 "[""other_unresolved""]" resolved_exact discovery +symbol:ERBB4|entrez:2066 v0.5.0 tue_7257352ca250f343aa4373338925912d02f8c11de8b08d9553e548531d092721 "[""tus_369fd0abbe9378492af25431a1979f62ffabdcc32e1ea55f11d3fb1846f2c4dd""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000178568""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ERBB4 "[""other_unresolved""]" resolved_exact discovery +symbol:ERCC2|entrez:2068 v0.5.0 tue_172c5613234b5d7e2e485809c97e19a8d92b420bfe558d1f73132d9cc64baf42 "[""tus_c09e7a8cb029db6d5ff2a77d3ef3ff770f3390bcc801e6aaca34a52cf5e32622""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000104884""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ERCC2 "[""other_unresolved""]" resolved_exact discovery +symbol:ERCC3|entrez:2071 v0.5.0 tue_885c3efc755f8d5185dd9ff8d8dd4f69ad06830a7c202ec5d128b309072625b6 "[""tus_aec65a9b10813ecd51b1cda036ab7e9cad7788b600c6952b932d6f1013eb99bd""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000163161""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ERCC3 "[""other_unresolved""]" resolved_exact discovery +symbol:ERCC4|entrez:2072 v0.5.0 tue_de260975aa8b7258d781a34ff0a96864a2f6bf7ff9654d362f9ddabf7137c905 "[""tus_2567ddd1b6b92cd515c724b10616dc59cae32fb82d36e2ed62c543f8473f9cd7""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000175595""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ERCC4 "[""other_unresolved""]" resolved_exact discovery +symbol:ERCC5|entrez:2073 v0.5.0 tue_c831485df5f360278edcf73906efeacba8484d1c1d88db5e9e53fb98be014073 "[""tus_ce67396b382712e39485d50a719122e5f3049618eed5df8d0a5281cb6b1d0635""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000134899""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ERCC5 "[""other_unresolved""]" resolved_exact discovery +symbol:ESR1|entrez:2099 v0.5.0 tue_0b093888d93b7f0033728e6d16fde4ac3f6bef36aefed08ae3987c682495c051 "[""tus_0a2053bcfb4ec4777ef58ceb3c9942758fa0dc5f07c77ec65b9585e0ff6a0c0d""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000091831""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ESR1 "[""other_unresolved""]" resolved_exact discovery +symbol:EZH2|entrez:2146 v0.5.0 tue_1ebfacd6fdeaf0fae234fca3c4e2bedb3d5973ceda43524fcd565216e11ffd8a "[""tus_a778639f16c3d898a8bee3747f9009558f57517aa3f2dfd8baae8f381d276290""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000106462""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" EZH2 "[""other_unresolved""]" resolved_exact discovery +symbol:FANCA|entrez:2175 v0.5.0 tue_17592bc11b37355373eff4eaa3dce7ab6379c24654e1030d1d2370daf4291215 "[""tus_201bc36938437ecd3fa603911335327e37443a1ec338bfc8f9a20ab552343fc4""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000187741""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FANCA "[""other_unresolved""]" resolved_exact discovery +symbol:FANCD2|entrez:2177 v0.5.0 tue_d01845077557a5fe67d013e2b3ce9de7c0b963349f671313522bad7ef7812963 "[""tus_8a4212e5b740904a38b0703892b2cf5f3fddaec5b74f79ec857a6388e06f6c11""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000144554""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FANCD2 "[""other_unresolved""]" resolved_exact discovery +symbol:FANCE|entrez:2178 v0.5.0 tue_0c87ad14094865e653825158232f4c50f053b183e8c445eee85bb14377605a57 "[""tus_6b09048612fcb63f5e1a968cc1743de036210c8d3d32a0a9cc70a74a06ad7ae6""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000112039""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FANCE "[""other_unresolved""]" resolved_exact discovery +symbol:FANCF|entrez:2188 v0.5.0 tue_6bfcc45def6f765f2e938b68be68f5ff46956d87b0364e06f938e52cadb6cf40 "[""tus_9863c3ba79b4209afc69c346b084320c5f3d895deb1ca6a5f5595327cb26bae9""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000183161""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FANCF "[""other_unresolved""]" resolved_exact discovery +symbol:FAS|entrez:355 v0.5.0 tue_edc05a206fede0c4bd8da0624deb4de3e955fdc9aaa027d2478a948ff9dec46e "[""tus_f8bc2652c49261e6e12c2e5d0b27a134ecae265f8e2b4b2fd380442f05a8595c""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000026103""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FAS "[""other_unresolved""]" resolved_exact discovery +symbol:FAT1|entrez:2195 v0.5.0 tue_3eb088b2e66d026a562dfb32ced45d61fe42e27bf85c28f8f5a64d2e83f85d72 "[""tus_bab5050b1aba58224536022772514534aa202514f6777e329fa56985554d74d5""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000083857""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FAT1 "[""other_unresolved""]" resolved_exact discovery +symbol:FAT4|entrez:79633 v0.5.0 tue_bbdd9b1f5a9a7db3c1ccf444d2678974ee41d2836db614ad7c0437e2cfe2837d "[""tus_4b43d37b2042edb4977940951de9e775bb45383f6611dabc9e4671ffbd6e5380""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000196159""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FAT4 "[""other_unresolved""]" resolved_exact discovery +symbol:FBXO11|entrez:80204 v0.5.0 tue_347c0334457ca3c20a7dc43a07a7e963629dbb768d54872ecef5c05f65f930ef "[""tus_f12da2d54e312eac5d199f35819f06bacc30b8dbbe12262d800ad3a50c062dd0""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000138081""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FBXO11 "[""other_unresolved""]" resolved_exact discovery +symbol:FBXW7|entrez:55294 v0.5.0 tue_f25852a50ede95840fc04c01a5f4ada25145456550902a6f408124f68485b196 "[""tus_062a53c2292fbe4183c1fa6421fe8d3396ca7263bd2785060dba272cf79cb661""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000109670""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FBXW7 "[""other_unresolved""]" resolved_exact discovery +symbol:FCRL4|entrez:83417 v0.5.0 tue_11b1518c50427abe7c4c5e5ad3189784f304133444958fa8cb02e20716a20986 "[""tus_066613e0c2c1e9279e781c01d151517f95c70a1aab9803263540517d974011ce""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000163518""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FCRL4 "[""other_unresolved""]" resolved_exact discovery +symbol:FGFR1|entrez:2260 v0.5.0 tue_fe7a9a06b287da74c893a547242a3889f633ffab70cf7678b4040fbaa039bba2 "[""tus_99eeafc820d9fbce63b1c8a7d7d994f42c1f4727bf0ed8c4de1e656b8d22c370""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000077782""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FGFR1 "[""other_unresolved""]" resolved_exact discovery +symbol:FGFR2|entrez:2263 v0.5.0 tue_5fb23966d7b8967185c5867201509e174194e8a697aa4b3d7e12701b14b9fce8 "[""tus_4734777aa95cb66772ebde20e6849ffa6242ca1c8e342caae42858c18e73de2d""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000066468""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FGFR2 "[""other_unresolved""]" resolved_exact discovery +symbol:FGFR3|entrez:2261 v0.5.0 tue_4c57958f9754d416cdfc2a95d5627a9bf03f805d6402675e6e12a7310eecf7f6 "[""tus_a79a131c9a072a092cb9d37cf020c10b92012765e5e8fee90eeb5c53084f185d""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000068078""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FGFR3 "[""other_unresolved""]" resolved_exact discovery +symbol:FGFR4|entrez:2264 v0.5.0 tue_f3d854fb3b2e4cb531365011db36a7c0a498f52bbf43eb9e5139a99e3d830318 "[""tus_97cbd79c55dbf7f5e6a31f333b3ac8df2e4002ad5c6059c075a5b50945f05e12""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000160867""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FGFR4 "[""other_unresolved""]" resolved_exact discovery +symbol:FH|entrez:2271 v0.5.0 tue_662d1e44fbfe2926a818b02be5f7a44af1a4ed219710510f971e09fd42a6e474 "[""tus_850becd686f2cbbc8c87b5aabec3f9b220930044f9479231f81438b87bd0b0d1""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000091483""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FH "[""other_unresolved""]" resolved_exact discovery +symbol:FLG|entrez:2312 v0.5.0 tue_71283c5e10e5add184cc7215403551484eacb441bd536984f92c9275978c0764 "[""tus_f97f1855dd927b8c9d031b3ec91bf1a7f65e2ba4afca97ace7af6133ff8fd084""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000143631""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FLG "[""other_unresolved""]" resolved_exact discovery +symbol:FLT3|entrez:2322 v0.5.0 tue_f94032f6a773fcb53fb323e62c10553ab9ec2ccab13d60e8e2ac9c99b24dccd5 "[""tus_dd393a6254972b423a6f02bf3de5d05cb44d899f37c2bb437620d36635eccb5b""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000122025""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FLT3 "[""other_unresolved""]" resolved_exact discovery +symbol:FLT4|entrez:2324 v0.5.0 tue_1cff78e5111198af63d995b437b0d36763d9f9b0599ae747e7462f7df91432c5 "[""tus_39846b1f00a506a1442a5580bf153fc801d61a619a691bd821b21483610b24ab""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000037280""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FLT4 "[""other_unresolved""]" resolved_exact discovery +symbol:FMN1|entrez:342184 v0.5.0 tue_1a2d49e79203b6af379647902a2f0d946050f68da23bd43661c1fe9abbd0f697 "[""tus_d4101d525627c23b74672177d40644c65b330195febe0c31d3168e2ddb49b212""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000248905""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FMN1 "[""other_unresolved""]" resolved_exact discovery +symbol:FOXP1|entrez:27086 v0.5.0 tue_370a051063e57ad3b4ffa33c828c0b4ae2f82a3832c3b8a757682e967d65b0c6 "[""tus_a71db237d51018916e8c8dbfe8949fd1d80127b7a4c1b49227f9fe0ecec214e5""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000114861""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FOXP1 "[""other_unresolved""]" resolved_exact discovery +symbol:FOXP3|entrez:50943 v0.5.0 tue_f48e72dc23aee41f7d353cfd53eb2baddb83b498e05d8792fcd1dc57c09d9b29 "[""tus_6a08875435969714f5cbdfa29fb81251487b2aa6511121433027985e2091780c""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:FOXP3|entrez:50943""}]" included [] FOXP3 "[""treg_suppression""]" resolved_exact Treg-suppression marker / possible IO-combination target discovery +symbol:FUBP1|entrez:8880 v0.5.0 tue_379351e585e1be4615ea24a6d5dfa0c4786d3911adee0d2f5f85d4899cfaf9c0 "[""tus_f54b707e86b5836598e38d3bb9c7409f50e910b2811216ce74e783a855cb91b4""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000162613""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" FUBP1 "[""other_unresolved""]" resolved_exact discovery +symbol:GATA2|entrez:2624 v0.5.0 tue_e7c72d0ed8fc2710828b32505df2dba7e90a32a1bba4ec39df423bec6d8a80f3 "[""tus_c795f18d26ab9b0cf43181562d24f9b6b5ec19bb1d63f8399677b7e0f99943e0""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000179348""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" GATA2 "[""other_unresolved""]" resolved_exact discovery +symbol:GNA11|entrez:2767 v0.5.0 tue_c1e908bf5a7ba57f0fe3cc1c1ce33d0f21beeb995aef908bc3bbdc6cdbb964b1 "[""tus_a0ab346c4b12e05948af4e59e7af27a2b9d78b58cae64d1c1a45954dd89fc7bd""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000088256""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" GNA11 "[""other_unresolved""]" resolved_exact discovery +symbol:GNAQ|entrez:2776 v0.5.0 tue_15bc8ea2e00b829e37061ef42e8db1adebb7744cde6388842e11315691522014 "[""tus_336d068bbd6bf0b02d67963f01a41f9d380207af44b1f428bd29227039598409""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000156052""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" GNAQ "[""other_unresolved""]" resolved_exact discovery +symbol:GNAS|entrez:2778 v0.5.0 tue_27e5c70654a49199ff200692e0d8cc7ff933cb9633fee74eea5acbfc9ac225ce "[""tus_eb30b4e24ecbcc12ae9ae2d37fc2b293a0b9074de1240c18c26ef3e59e61eec5""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000087460""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" GNAS "[""other_unresolved""]" resolved_exact discovery +symbol:GRIN2A|entrez:2903 v0.5.0 tue_8d3e7ea22201668188aca400f02388c2f7db071b52af256ca4d480a9a5be8f96 "[""tus_82c86f9c6d08d265c4269b5c2b0e521576b858d670d6a37165d609e2c75cf761""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000183454""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" GRIN2A "[""other_unresolved""]" resolved_exact discovery +symbol:GZMB|entrez:3002 v0.5.0 tue_e4777a3af0ec638e92b24b6adb2d2c1c266946d6b80eae3ea79378e5d02f45ad "[""tus_8c46f4c4ca54607a6b32d3f3a5f1db770b3c55dbc05f4dcb32414dfcdeb94ed6""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:GZMB|entrez:3002""}]" included [] GZMB "[""immune_cold_state""]" resolved_exact immune-context marker discovery +symbol:H3-3A|entrez:3020 v0.5.0 tue_1376771794ba9bb8e8a14c72266e77c7abdfe451fe895d66a1a962954bf37d7c "[""tus_ea2dcd26d5384837bb41602f8e4e6ccda4c6fb1246e05d4f3fa86c6cdf855e48""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000163041""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" H3-3A "[""other_unresolved""]" resolved_exact discovery +symbol:H3-3B|entrez:3021 v0.5.0 tue_25eae0a2bc02e3d559d169164bdf9253f9b672e9423cbc13443dbdcdcdbd3ece "[""tus_cb626926f199a1000e98fb8862de5283e83d3c950f0f926acf4585cd4cd370ee""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000132475""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" H3-3B "[""other_unresolved""]" resolved_exact discovery +symbol:H3C2|entrez:8358 v0.5.0 tue_c7690258e9bad2e7f5cbca2e09fc42fba799ba5ec6b76aa473b30d66a79e9c83 "[""tus_f5798a4da3c76c8f587aa9dc831afb40d0ece06f43b9a00b7bbaed1ffd307c12""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000286522""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" H3C2 "[""other_unresolved""]" resolved_exact discovery +symbol:HAVCR2|entrez:84868 v0.5.0 tue_96d498fb0744b0d3617269cf63e6e0177d926389b7df7ea647f23563f82085d5 "[""tus_a98806a3d986c379309e9c468374ec1419cce7251b416794eb7ba3508b2761e1""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:HAVCR2|entrez:84868""}]" included [] HAVCR2 "[""checkpoint_redundancy""]" resolved_exact anti-PD-1 combination target discovery +symbol:HGF|entrez:3082 v0.5.0 tue_151351fc6faf55764666191553868bb699b77915f027fa615a08f19c0c2fbb60 "[""tus_07230adff44da3cccb5d849c0e56b5bdc6ccb72e3cc0192304f1f5f83b2110ea""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000019991""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" HGF "[""other_unresolved""]" resolved_exact discovery +symbol:HLA-A|entrez:3105 v0.5.0 tue_e622b4cd09811d352e9e9e17d55e18ebe4268122bd8611f4edb400620ed39386 "[""tus_89e68d8945f12a9bcf088277c2962a9d56c88281af21ba4f3882b8a9bea4c0fd""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:HLA-A|entrez:3105""}]" included [] HLA-A "[""antigen_presentation_loss""]" resolved_exact antigen-presentation resistance biomarker discovery +symbol:HLA-B|entrez:3106 v0.5.0 tue_1cf03ff3c9fee00512b930a59a178d159b25dbdff70ba2baa187456eb286fc8d "[""tus_d3d2d93f5a7dd51e0e23d1656afb97388e97c57d678fc2a6b17259cc4229617b""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:HLA-B|entrez:3106""}]" included [] HLA-B "[""antigen_presentation_loss""]" resolved_exact antigen-presentation resistance biomarker discovery +symbol:HNF1A|entrez:6927 v0.5.0 tue_1f8b75b001df7f9fb10167aa447383344ccf27780a7cadc2857d92b4be4dc542 "[""tus_fa495086d782ef54f4aaa4512aeb1f19dfbb1bb9cf490f54a86ab5ef3b10a897""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000135100""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" HNF1A "[""other_unresolved""]" resolved_exact discovery +symbol:HRAS|entrez:3265 v0.5.0 tue_fa6d3f61ca0d77976402d1bc89fbb50aa00e28a8abc3b7869105985971950cc6 "[""tus_5191abeacee4bec67a4482404bd3ad50d309494447ec08329b17c45388ccadae""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000174775""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" HRAS "[""other_unresolved""]" resolved_exact discovery +symbol:IDH1|entrez:3417 v0.5.0 tue_8d6d356736ac80fb84e20c262e506cadf8fec02166a5f778f56d02f0b1e0393d "[""tus_f0154b357ee2038a226241f949c7dca71005185374ecdd94f7c02978a6c040cc""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000138413""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" IDH1 "[""other_unresolved""]" resolved_exact discovery +symbol:IDO1|entrez:3620 v0.5.0 tue_e6950209daf8ded1ab32dd77e90d3d555da672cba38085551f51be9a4624c877 "[""tus_ca508d6ac63b2433f9301369d668a19e45a50327afdeef933c69b80681102695""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:IDO1|entrez:3620""}]" included [] IDO1 "[""metabolic_immune_suppression""]" resolved_exact metabolic immune-suppression target discovery +symbol:IFNAR1|entrez:3454 v0.5.0 tue_ea7747ec7d01ad4d01154f4f7a7b2c9ee82435201107cdde8b7c075295712f09 "[""tus_39fe39474beef9abdf9a7b0b7b6f5e9cab8b3c554451802ca627970ae8f6b722""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000142166""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" IFNAR1 "[""other_unresolved""]" resolved_exact discovery +symbol:IFNAR2|entrez:3455 v0.5.0 tue_f1aceee5c947967260dd297f0929c0abd62f13d4667a977530d4c5622b50c9e8 "[""tus_ce562b9d1fd1a9fafd5977bc1aa55d41aa488f2951b7c826f41775d3245a527b""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000159110""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" IFNAR2 "[""other_unresolved""]" resolved_exact discovery +symbol:IFNGR1|entrez:3459 v0.5.0 tue_0fff99bc533df1435723fbfccc5daf9f9ed52104c4c2f11ae0b209e98138701b "[""tus_da6dc18c3b2475d8a558848bae810ac535f04ca47d4bf0ff024ab9561eaa74c4""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:IFNGR1|entrez:3459""}]" included [] IFNGR1 "[""ifng_resistance""]" resolved_exact IFN-gamma resistance mechanism / biomarker discovery +symbol:IKBKB|entrez:3551 v0.5.0 tue_cda6b4177730ee0ed6b2ea22363124775a42f9e3bd8c371d64a68ab68b3f74fe "[""tus_380a220c6c50f4b589359964c7db279ec94b5435340c916c216f72b73de9be69""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000104365""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" IKBKB "[""other_unresolved""]" resolved_exact discovery +symbol:IKZF1|entrez:10320 v0.5.0 tue_dc560306f153752b86c9c630bc1ccc63ad2fd631938ca87c8ded868058680218 "[""tus_039b70ecc57e6e7dc12dc31f9dc8afc1576a700370ba056a3dbc8695e1a226ed""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000185811""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" IKZF1 "[""other_unresolved""]" resolved_exact discovery +symbol:IKZF3|entrez:22806 v0.5.0 tue_444aa16947ff3d6821a5a3dc0625eaa53f6a3e044b7fc4fd8bc1e926e28e7b6a "[""tus_58609604d9f2b50fdb089d0ff191e01109a240b59c4f49d64d539b32177e8c9a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000161405""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" IKZF3 "[""other_unresolved""]" resolved_exact discovery +symbol:IL2RA|entrez:3559 v0.5.0 tue_b5eefc2cf351bd868a774c141fadb7deeeade1d4476ba8121063103838a54168 "[""tus_45e21ab5bb6f5614f8760e2a16311a8b9a6f2253e2f3d957a2c63442ce297f45""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000134460""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" IL2RA "[""treg_suppression""]" resolved_exact discovery +symbol:IL2RB|entrez:3560 v0.5.0 tue_aa0410bd620ed8c35b2f1336c46ff0fa3f07fa5dce4bf60ea61beb971e2f9189 "[""tus_b1b69eb651095f74157a1226c39f871f2d5461ebf2e125c81f710f35a66910c5""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000100385""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" IL2RB "[""other_unresolved""]" resolved_exact discovery +symbol:IL2RG|entrez:3561 v0.5.0 tue_2bcce8ecd69b4be57ec2b29c8eaefd5ac9f2c1e9f8dd3bb788006aa5ceac81ec "[""tus_1683e092a555aabfba8fd3d966fd6a3f5fbaf12ba491b32276b8a910c9ca35d2""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000147168""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" IL2RG "[""other_unresolved""]" resolved_exact discovery +symbol:IL7R|entrez:3575 v0.5.0 tue_44472c7554eb5738c809f43b06f78edef873a5f18d5504cee388c9b386d21a95 "[""tus_2332ee9e14699115dc8015ceb17a1b6a7f9dcc82afc7e7795ff505be02663ccf""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000168685""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" IL7R "[""other_unresolved""]" resolved_exact discovery +symbol:IRF1|entrez:3659 v0.5.0 tue_be997e187cae091c582d25ccbf4731d8999436e0fa703d7ed69ee5d7416511f4 "[""tus_5741ad4e868c27afa1db909ec354702f74dcba0234f171e5c96948073c3f989e""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:IRF1|entrez:3659""}]" included [] IRF1 "[""ifng_resistance""]" resolved_exact IFN-gamma resistance mechanism / biomarker discovery +symbol:IRF4|entrez:3662 v0.5.0 tue_220f818d4fe733858186e64e29ee7c28b5c32396ed8a5b486fa9c26b5cfec7bd "[""tus_5d1271b3fe86e57c3713ca612979605084b1db703f3dfb3c124d72b1b68ad979""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000137265""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" IRF4 "[""other_unresolved""]" resolved_exact discovery +symbol:IRS4|entrez:8471 v0.5.0 tue_d9ed2745a05f9191510eb6b14ff9ab177a8c5c19582c0933d3a6f45e1c931b36 "[""tus_9cada6244111c9c1feafc3090049a18db37430d2238be982ce6e6b4963fb986a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000133124""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" IRS4 "[""other_unresolved""]" resolved_exact discovery +symbol:JAK1|entrez:3716 v0.5.0 tue_617a32b7fe11ee2853ea66edd20cbef5eeb5fa27bb08582254391285ef990e04 "[""tus_e4da7b05a1ac8545e133b8f0a2cae635b31e71c97559f2ce9e7718d37593f5bd""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000162434""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" JAK1 "[""ifng_resistance""]" resolved_exact discovery +symbol:JAK2|entrez:3717 v0.5.0 tue_f374ddfb5f1e4f301f19d0bf44329f5f0d9fe0567bbf8c25c6cfb622c67c02b0 "[""tus_fd1b4509ceb6ae2ef11e2caf1713d73ce59488260a1bd79d9de58a5db550e648""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000096968""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" JAK2 "[""ifng_resistance""]" resolved_exact discovery +symbol:JUN|entrez:3725 v0.5.0 tue_122178ce8f17925ce02ed2ae9fb79a651ee8d23a4f9cd8e8b9a0a1af1a48f120 "[""tus_809d48c3cfe667fe11ae2b096c28b23a5845cb7d7616fb192b70611a5563839b""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000177606""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" JUN "[""other_unresolved""]" resolved_exact discovery +symbol:KAT6A|entrez:7994 v0.5.0 tue_3cd202ae6e9d8c0eea23e337f159712eb2928716242b71e52ddeec149ae6f22b "[""tus_267e63da914bceb5adead207b42c10cf7a80e5de50f8f3748e74d7d00ac0caf1""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000083168""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KAT6A "[""other_unresolved""]" resolved_exact discovery +symbol:KAT6B|entrez:23522 v0.5.0 tue_54e6efdf2f1b36414a59fe1d3c11616fcb8ef9df21ee344f7010e428bcd747eb "[""tus_49bcc20d05568f40993e713def7545dc9995447d1862429ae815374ba8b08169""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000156650""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KAT6B "[""other_unresolved""]" resolved_exact discovery +symbol:KDM5A|entrez:5927 v0.5.0 tue_b6e72447c623ecfc6b8586a5ca7b515d975d501782abb97a73d331c65b9cbaac "[""tus_08d28ccaccb51174f33744f4f5d881508103c9cea34fc5e5498b999094a12755""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000073614""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KDM5A "[""other_unresolved""]" resolved_exact discovery +symbol:KDR|entrez:3791 v0.5.0 tue_25bca6826e515dd9b2c715a0506c7c873f07f241e788a67cf51c0186e36cfdbe "[""tus_c2a3034fc19ac7cf142edfde05ad2c89cf23be0d55dab0a5f026fb8bde3c7dce""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000128052""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KDR "[""other_unresolved""]" resolved_exact discovery +symbol:KEAP1|entrez:9817 v0.5.0 tue_c08c262d951cf1bcc5859a0d320398be235ecdd6372316192dbdeef5258ffda4 "[""tus_742c26b973ac243df06b255826767bdab4e6caa29becc078ad25254f7c636658""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000079999""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KEAP1 "[""other_unresolved""]" resolved_exact discovery +symbol:KIT|entrez:3815 v0.5.0 tue_87288a925f80f8d303b9c510582ab03ade2318d6523d6211e8b26a72122c244f "[""tus_67248d33fd3654a8b59202c6ed977426808b419b216aa4b32c5c900a15fe5e35""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000157404""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KIT "[""other_unresolved""]" resolved_exact discovery +symbol:KLF4|entrez:9314 v0.5.0 tue_110da68b992cd5265668d4a827611994648725f40f1a0faa5a25612c736b6301 "[""tus_4973f41d090facc66d426256396e1fd3d9c6aed23ad6bca8e6e3a22039273854""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000136826""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KLF4 "[""other_unresolved""]" resolved_exact discovery +symbol:KLF6|entrez:1316 v0.5.0 tue_c3f382cd68c355fb0e0e9fde3f93fcc29d3547d8bea04118ac3f8d54429fb01d "[""tus_e3aac393e6830ca41c58b36b69251ebd63b1b292609fc68f2f60c06cb7cab975""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000067082""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KLF6 "[""other_unresolved""]" resolved_exact discovery +symbol:KMT2A|entrez:4297 v0.5.0 tue_0c5b321760d591c62f2200fe8d2c0e6035ef73c381a6ea3756446c501e5cdf7c "[""tus_dac5a0ad25cdc5485fba54121370cc7e3d6d30f6a63a6e78d4226eade4f8683d""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000118058""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KMT2A "[""other_unresolved""]" resolved_exact discovery +symbol:KMT2C|entrez:58508 v0.5.0 tue_8b7cd8828852bf413c5ad10af96ebe1ada12b1b7211ee79cda1d4ab96475d94e "[""tus_75a37dd49deca06d0592d3c56d385d0b61fb8143a792cbbe5af7b40b1c32cab5""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000055609""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KMT2C "[""other_unresolved""]" resolved_exact discovery +symbol:KMT2D|entrez:8085 v0.5.0 tue_275519bc9920e66332bf1c3c632ea612b9c42affa121f0e85649832e28ac6e3e "[""tus_e7047c5eb863fce528340076a80a6e863f4f144e09f45a890052e2692dbc0346""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000167548""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KMT2D "[""other_unresolved""]" resolved_exact discovery +symbol:KNL1|entrez:57082 v0.5.0 tue_57ade1cd12e47077956f5bbd30f3e7c454aecfa4d5e99d499be31dab7647da1f "[""tus_b469b8ba5a269e6bbde967d0bb57ffbd704ccbb9c9b559e20aa79da36ae5ee99""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000137812""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KNL1 "[""other_unresolved""]" resolved_exact discovery +symbol:KRAS|entrez:3845 v0.5.0 tue_338217eef50860310f6a5e97e184187a012429a578559b236ca1a092b636f788 "[""tus_41f4b1ae3fe3d070fd0eae52b59590552905d1fcdec959539591318a4c9404bc""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000133703""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KRAS "[""other_unresolved""]" resolved_exact discovery +symbol:KRT5|entrez:3852 v0.5.0 tue_051b36bb07733eb62b6e6b81959fdf80f487174d079f0d87ad54fea6d6d61109 "[""tus_4659c1bc4920b5debe1c02bbcd680a0c9956c21315bdc3a45478fb22ab019666""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000186081""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" KRT5 "[""other_unresolved""]" resolved_exact discovery +symbol:LAG3|entrez:3902 v0.5.0 tue_9d2f7f6b30913a552ffe38d23dd55c3d15d1af3f105c200fc699f3bcb3a7a06b "[""tus_4dcce76d2ed8c158c91fb72d17299d080a5a31ee11b0bec3eaaeaba96358e038""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000089692""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" LAG3 "[""checkpoint_redundancy""]" resolved_exact discovery +symbol:LATS2|entrez:26524 v0.5.0 tue_94e200425b0ccbca9b13b57e863b501531fdb12c8a6ec6bb8bd97ba4d8ff2c35 "[""tus_83ae85b4119cf73963650702d9b6a97c707709de997b96f3c5d44a2425d299fa""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000150457""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" LATS2 "[""other_unresolved""]" resolved_exact discovery +symbol:LCK|entrez:3932 v0.5.0 tue_22ef6d2646d77bc36fc7ded0494b5298ff19e4291e26542aeaf33040989ed86b "[""tus_c9ed7f1ed4633f981ac9504a70ffdead27ddf752259c95d6286833506f6faa78""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000182866""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" LCK "[""other_unresolved""]" resolved_exact discovery +symbol:LILRB1|entrez:10859 v0.5.0 tue_03a0300782ffa74cab6efa34b7db92fa38b97ecede8de720fe774365808315fe "[""tus_8f4a8fd5b91f3311355ea5f206d83f7039ae29dcc415f0b5578b4185afba38f6""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:LILRB1|entrez:10859""}]" included [] LILRB1 "[""myeloid_suppression""]" resolved_exact myeloid/TME anti-PD-1 combination target discovery +symbol:LILRB2|entrez:10288 v0.5.0 tue_bb6ae918ffbc5dce49436b1f9280d366dc4dad1db43a9ef3385a5626cfd1d923 "[""tus_a5d45c646d5eebe70c9346f76515829394def483c1dc831ff5a61e503d4fd259""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:LILRB2|entrez:10288""}]" included [] LILRB2 "[""myeloid_suppression""]" resolved_exact myeloid/TME anti-PD-1 combination target discovery +symbol:LPP|entrez:4026 v0.5.0 tue_865b9bb7a19376c7bc2b941039db2774232cba73690914a180d4b4fa72b01e38 "[""tus_b855815790f4d2af61760b73f16358e4e55e9717423a54b5647dc9026515839e""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000145012""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" LPP "[""other_unresolved""]" resolved_exact discovery +symbol:LRP1B|entrez:53353 v0.5.0 tue_73b166542a0a2f57f3c27d01efb95935d447540d51a39b10d8362af993a9ab3b "[""tus_4559fe338de69a9bc9217269cb5e82e07be5f013368e83e05f674ff0a8d99a25""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000168702""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" LRP1B "[""other_unresolved""]" resolved_exact discovery +symbol:LZTR1|entrez:8216 v0.5.0 tue_d28e1d022c269b2709b1b9bb3f07639445a46f7a18d192683d31c443b97e6725 "[""tus_d406ceb74b78188812f2baa33a29a8fea02f23f5c09aa188ad53eca8ff81a2b7""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000099949""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" LZTR1 "[""other_unresolved""]" resolved_exact discovery +symbol:MAP2K1|entrez:5604 v0.5.0 tue_839d478c5b82104543e9deb6520e60bfe0f738ba37840af15aa6978733a5f736 "[""tus_e07cc0b967a3f0ad15c2a3f67a9378e079177284a8032964a34d26ed8c77a294""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000169032""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" MAP2K1 "[""tumor_intrinsic_driver""]" resolved_exact discovery +symbol:MAP2K2|entrez:5605 v0.5.0 tue_91b38b457f6500396b474f8c3ab0a64b2a5284d1d515e998b271d44d7791b5d7 "[""tus_632185dc1430ca65f3d8f8e15d463eaade0b824b3fb9f79338363d14d873874d""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000126934""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MAP2K2 "[""other_unresolved""]" resolved_exact discovery +symbol:MAP2K4|entrez:6416 v0.5.0 tue_a820d259ea71ca6fd3cbe3284d925fecd2f3069d0cfb421eeced60fad2692977 "[""tus_c10257523ebde9fce2b1894794cef57085804d44bca3a6daeb7979bd89ff9be8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000065559""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MAP2K4 "[""other_unresolved""]" resolved_exact discovery +symbol:MAP3K13|entrez:9175 v0.5.0 tue_135e755137b5ab96f83e2f8474715580cacee58aec703f4905b22ac12aad9487 "[""tus_06157510379f1a5e6fb78c6dcf7ed83aeb59db95b6e87178c8227b6dbe5513ea""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000073803""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MAP3K13 "[""other_unresolved""]" resolved_exact discovery +symbol:MAP3K1|entrez:4214 v0.5.0 tue_f8472f18de3b23fa87be9a089bf3eaa2a9ca22e6b89a970631e946fbc4487938 "[""tus_23dc5c60e671a275172ae20f266f35bf057174dbc1e42ea4f80942323aa63da8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000095015""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MAP3K1 "[""other_unresolved""]" resolved_exact discovery +symbol:MAPK1|entrez:5594 v0.5.0 tue_6f697d376dbc961f4e8cef57b08f156dcf6a7360f2d35069bbf1627f5bf2b212 "[""tus_f2a4884cb9c29d2a46af5a4b16a25e399d9c99adafc260ce7428c0193be3ce3a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000100030""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MAPK1 "[""other_unresolved""]" resolved_exact discovery +symbol:MARCO|entrez:8685 v0.5.0 tue_529e465fb37e04c031e159a57bd64579811ff87d1c330e6b0db8b7c2253bc8a0 "[""tus_6f663f5eb9242ba2f41a5c312805415a74bec1e57e50577bc7a7c916344d127d""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:MARCO|entrez:8685""}]" included [] MARCO "[""myeloid_suppression""]" resolved_exact myeloid/TME anti-PD-1 combination target discovery +symbol:MAX|entrez:4149 v0.5.0 tue_2a66ce30905702040baa4bfef20f34feac60d4f351b4497429aef09daea71957 "[""tus_7f4d918ea104f2e20f7a015811fc4f1f1a77041c4c6c9bd5c9aaf9514de22f1d""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000125952""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MAX "[""other_unresolved""]" resolved_exact discovery +symbol:MBD4|entrez:8930 v0.5.0 tue_3edad00fec4a6fe7cb82f448e0ead93f9d1beee9f2291b4a6af580fa13da9833 "[""tus_4ac17abf1e5c547750d28f4f12c50cb1a52c050af5ed5f1fda8811c56269990d""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000129071""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MBD4 "[""other_unresolved""]" resolved_exact discovery +symbol:MC1R|entrez:4157 v0.5.0 tue_f3fae9452c50040ada79ae6186538cde8696a50ae4599a54c5953a722120f5d8 "[""tus_e8f7dd12e9b59cfb05a570d65aeb614a99c8ff864dd80c2328b8c232887352d7""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000258839""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MC1R "[""other_unresolved""]" resolved_exact discovery +symbol:MDM2|entrez:4193 v0.5.0 tue_a0120c163cdf3f9724e7599bbc23c367e84ec4051f37dcf5538d668192733299 "[""tus_351f0c09f25a84b383135938a18af1f22064c9381d751f80eb7575d8f8ad6e4c""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000135679""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MDM2 "[""other_unresolved""]" resolved_exact discovery +symbol:MDM4|entrez:4194 v0.5.0 tue_4dc15b85db55d5ed07a378ee074e86981ff45eda1e5f33b9024b9a89d6f2aa27 "[""tus_2d0fe2bf2cab4cbd869db571071b81b3591ba2c32f637a228f755e2a300053d1""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000198625""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MDM4 "[""other_unresolved""]" resolved_exact discovery +symbol:MECOM|entrez:2122 v0.5.0 tue_9e51de2827fd619394fb3315580140d93c2dbd564f758cdeca99dbd970a93eb6 "[""tus_c20936c7ce975da18a5807c6c7c71d7377491b3afb182ff34e117341a2691b3a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000085276""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MECOM "[""other_unresolved""]" resolved_exact discovery +symbol:MED12|entrez:9968 v0.5.0 tue_14139809d59f8b5ebb9679b6895341a33d2b288f05cf95f5d72d8a2df72ef351 "[""tus_248a101296f79d8590a5066402d8b87f2fd561d9adfeccaf79875730a208a34f""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000184634""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MED12 "[""other_unresolved""]" resolved_exact discovery +symbol:MERTK|entrez:10461 v0.5.0 tue_89a7524710333d18a54406a78073292028dee1df72479bddbffd27ca7293d42e "[""tus_4be80c0f0b9ddc9b28718775620c3fd6383ac2866f295fa72fad9ed30e059cb4""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:MERTK|entrez:10461""}]" included [] MERTK "[""myeloid_suppression""]" resolved_exact myeloid/TME anti-PD-1 combination target discovery +symbol:MET|entrez:4233 v0.5.0 tue_565c6417805e05285a388961f19c0a6a03f76b583135c318390e59abd8e65492 "[""tus_a2b0ee6e50ed238bfa60576525e02403e870e2d0a8b230cdc8afbae7836859db""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000105976""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MET "[""other_unresolved""]" resolved_exact discovery +symbol:MITF|entrez:4286 v0.5.0 tue_7a6c4667fc685e9e8e03bccba608450fbcb68a3580571b24520d4ea6e375cd6e "[""tus_d8e2a7fec7617baf9bcdcd21007d330315a4a2fb351e4654967f00b790654276""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000187098""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MITF "[""other_unresolved""]" resolved_exact discovery +symbol:MN1|entrez:4330 v0.5.0 tue_71a25bd609175b05bac5c675c0d18acc5ec2587c45870b4613eab3439af75024 "[""tus_6b0e8b35ef98bd23f20579797dc206aceb82c43df26eb7ce04e637f39f5bf1a7""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000169184""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MN1 "[""other_unresolved""]" resolved_exact discovery +symbol:MRTFA|entrez:57591 v0.5.0 tue_df94fc4e268108ca9e3f2d4a6610f66d5e386499ad8a56687b9d2c6093b5f25e "[""tus_451f4e0361a3c7aea70bcaa19822fb55f02716b2b4a5168808a8a11a30b2d616""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000196588""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MRTFA "[""other_unresolved""]" resolved_exact discovery +symbol:MSH2|entrez:4436 v0.5.0 tue_3f433ee5396a3e07df6dfc2b872257a5dcef120913268fcc773639a130a02c3b "[""tus_6bc15fc9e92b86831ea759586e623e35411e190ea040545b6f005f13f32db535""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000095002""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MSH2 "[""other_unresolved""]" resolved_exact discovery +symbol:MTAP|entrez:4507 v0.5.0 tue_b54df79f0096808b58734824c5478e32f2df66d978e990ab59afbc32d46f06bb "[""tus_9e47b04076180f9b31eedd006c7a84f79563921aefaedac34a160aaa6fa97e79""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000099810""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MTAP "[""other_unresolved""]" resolved_exact discovery +symbol:MTOR|entrez:2475 v0.5.0 tue_5e8ff9b4c92c773ccd3fa1e017ff1e4ca641fc2195ff5c45bebd0538360abaa6 "[""tus_ed3ff460611c93b274ee626b83acf8f8827dd5897cec878a5feb896b3eabc06b""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000198793""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MTOR "[""other_unresolved""]" resolved_exact discovery +symbol:MUTYH|entrez:4595 v0.5.0 tue_c8c2a84c0c40aff4684680621d7e9ee6fb8a72d3a3f884687c8bc878a8ba47b6 "[""tus_a3e4f2e92fa5715a57cb981e50228b811dd65df408b57220619416b1e3e25081""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000132781""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MUTYH "[""other_unresolved""]" resolved_exact discovery +symbol:MX2|entrez:4600 v0.5.0 tue_1cadcc971b89a18638652c9e9e372fea6193ba6216fc4d7672285e3a67e66a92 "[""tus_bc524985c640709bd4e591a70c613f032c4d5ba3666966ce49ddd56232c5f27c""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000183486""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MX2 "[""other_unresolved""]" resolved_exact discovery +symbol:MYB|entrez:4602 v0.5.0 tue_6dbd6d62ba144b07706e4601798229f9f07ac1cf0df587c13703bbbbc1fe84ad "[""tus_3d96ea0e305891b6853980f55db0744ef0af02a105924d101c69a78b70891b02""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000118513""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MYB "[""other_unresolved""]" resolved_exact discovery +symbol:MYCL|entrez:4610 v0.5.0 tue_f1ee212e4254557102d3ddf9303b50676190cbb25bbd89f5938aad54ecce3911 "[""tus_241e2bda2b46bc2fbad247b19ce8483c01cf60fb8150dfc8185aa57c007bd375""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000116990""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MYCL "[""other_unresolved""]" resolved_exact discovery +symbol:MYCN|entrez:4613 v0.5.0 tue_2e0b8b852965bf2e6bf8d483943bef420908b6c0855140ac30af74206364af3a "[""tus_f7c9c9edd331051b00c05e763f534a0d84a1fd8d4daebe49bfd719d499ce2b52""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000134323""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MYCN "[""other_unresolved""]" resolved_exact discovery +symbol:MYH9|entrez:4627 v0.5.0 tue_4365b0be5beedc352bf6f430dbad34712be25af3291ad942c56697fecccd0e91 "[""tus_f7571dcef217fb4d0c8a686960e4e000e335310b94576095fc2043f8d66382cd""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000100345""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" MYH9 "[""other_unresolved""]" resolved_exact discovery +symbol:NCOR1|entrez:9611 v0.5.0 tue_10569cb68dfa1e7929537938c1c8190430cdf0f52d1313da1e23ad52adda4112 "[""tus_9e2bad6d8a6673e0d23a237b006005307091c0609f7a747e9aadc360b38e3624""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000141027""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NCOR1 "[""other_unresolved""]" resolved_exact discovery +symbol:NCOR2|entrez:9612 v0.5.0 tue_7f52682dd49ca3e7524d227f9f91e8cade610b43b00cb2f3762788a700b63f35 "[""tus_7169d56a7caf2d05c5f9aeaaeafc6d08fac5254d2eb64825f8168c3b4ab90ad6""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000196498""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NCOR2 "[""other_unresolved""]" resolved_exact discovery +symbol:NF1|entrez:4763 v0.5.0 tue_7b1852a893e51e1a755f24ced66fa39a87df65262ae5cb53edc745629d7d6945 "[""tus_877b7f1e689b250094aa89e917179b073fdf06032ad42ce1074ae2e0b9f6f767""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000196712""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" NF1 "[""tumor_intrinsic_driver""]" resolved_exact discovery +symbol:NF2|entrez:4771 v0.5.0 tue_e24d043caddf58d396c0d140655d9979db0e3b5a01aaaf7dcf9935a1e46fb420 "[""tus_d57f1f10ff7c4bdf1e67fbf6f2a5a1763faed099aeaae51060eebbfed403e35e""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000186575""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NF2 "[""other_unresolved""]" resolved_exact discovery +symbol:NFE2L2|entrez:4780 v0.5.0 tue_88b280bc99b26273d1283cb2383396dc178c871d8ba3c63a91f1016c1db4174d "[""tus_a20785365363840316b4ae1164d5774f02a2b96a2994e64fb90435ecc9d178ce""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000116044""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NFE2L2 "[""other_unresolved""]" resolved_exact discovery +symbol:NFKB2|entrez:4791 v0.5.0 tue_c15998e73048ae46af3cb0b1b53961ac21b49c046150a00c239d0b9d22df5195 "[""tus_71aa436d3b5e0181d5068d806308e78adfde2863b32fe24291ff2bf997cbfcb1""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000077150""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NFKB2 "[""other_unresolved""]" resolved_exact discovery +symbol:NFKBIE|entrez:4794 v0.5.0 tue_d35ac6dce4d0e3f899e208c62efd5dbe5cfe6a21f58ebee96d2d0a9723a8ebda "[""tus_808f8af51b8dfd752680e986e0365be606e8770fea8210c55456afa942892553""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000146232""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NFKBIE "[""other_unresolved""]" resolved_exact discovery +symbol:NGFR|entrez:4804 v0.5.0 tue_151cd7ea74cb79de4007233d616b84e4267ff5d06b2062803f61b4d2a32c8210 "[""tus_66fe783ea851b2a35c2d9ebed6675715a28c3f3748a3823d7d18d1c1f52c13b3""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:NGFR|entrez:4804""}]" included [] NGFR "[""melanoma_plasticity""]" resolved_exact melanoma plasticity / resistance-associated marker discovery +symbol:NKX2-1|entrez:7080 v0.5.0 tue_0c29a75fd1616356ae666478e8d973febe06727ed1cbbf0270b5e0ad03a12cf6 "[""tus_3e6ff404d539a83b10ed68e2b98d47832741e5de294725651c03f2120745037f""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000136352""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NKX2-1 "[""other_unresolved""]" resolved_exact discovery +symbol:NOTCH1|entrez:4851 v0.5.0 tue_447f37762e5776f3a2cadccc99217ea2f70c5ec6823008590ce1048407f649d2 "[""tus_bf063195ca6dd07bda6b36a416a04fa32ab446f5046807261c11b69c3fe70a83""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000148400""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NOTCH1 "[""other_unresolved""]" resolved_exact discovery +symbol:NOTCH2|entrez:4853 v0.5.0 tue_03afa0e08ece3ffd76d348484879561d99eff2657b1b44badbd6da7f2fdde3bc "[""tus_50097275c67066a4ab41eecd7a0db91af25c24777f61adcd3295a3360354d2f8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000134250""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NOTCH2 "[""other_unresolved""]" resolved_exact discovery +symbol:NRAS|entrez:4893 v0.5.0 tue_04d4707cefc5ade4366c483b877cd500ca4fe1c172465edc4be64c6c781b660b "[""tus_625f17e63d62b4a743ce7ea8d278ea99a21bb9928c42ce90bc6a03acadffbec1""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000213281""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" NRAS "[""tumor_intrinsic_driver""]" resolved_exact discovery +symbol:NT5E|entrez:4907 v0.5.0 tue_311d933fa0d667d143f6bddcae199ef21656fa52f631df685158616a64531e1e "[""tus_ff7f613385a4244f73b6126c6cefbcf461639d5d5bf2fd5f06c5ba38f93dc533""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:NT5E|entrez:4907""}]" included [] NT5E "[""metabolic_immune_suppression""]" resolved_exact metabolic immune-suppression target discovery +symbol:NTRK1|entrez:4914 v0.5.0 tue_66a1d7a2259bd165dcc4929e0361c386dfeb4c54edf398d5fb97508073514a96 "[""tus_20d3b613e3279da79dc244e0b2ef7f2e10f33bea1410638492dba342f77c6926""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000198400""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NTRK1 "[""other_unresolved""]" resolved_exact discovery +symbol:NTRK2|entrez:4915 v0.5.0 tue_a97dbbf7ced98d829a699b97f584851fefb88ced04598ef6cc45d3a8715c0d4b "[""tus_dc4d3a3d9281abe0816bb497567b6cb9977dd907484a7ddb5d615710192330ee""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000148053""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NTRK2 "[""other_unresolved""]" resolved_exact discovery +symbol:NTRK3|entrez:4916 v0.5.0 tue_7be2fa3da78f6deac63570fab92972b66d3209dadcdf3c70eab8925b80c14ea7 "[""tus_e8c2963e575ebff4c56d22dc4833ef2612b23bd1842defe88d71dd155d73b143""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000140538""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NTRK3 "[""other_unresolved""]" resolved_exact discovery +symbol:NUP98|entrez:4928 v0.5.0 tue_0e86a95621df50f0b0737915d5474492e5ce5362bbb68cd2cf660e879f56ea62 "[""tus_8c9e90bef4fdd40eb90a4a18882e2823f38c96022c2b1794d8d1ea6eaaf171bd""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000110713""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NUP98 "[""other_unresolved""]" resolved_exact discovery +symbol:NUTM1|entrez:256646 v0.5.0 tue_a5db00fede873f979bcbbe3b0217d7fe22abf8d9567916b7bec62faa5f967cbb "[""tus_7a2da48beef02c11e284838d99facb91be29478d2512de5b7e9647165c1559ce""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000184507""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" NUTM1 "[""other_unresolved""]" resolved_exact discovery +symbol:OCA2|entrez:4948 v0.5.0 tue_bc4c32fa71c0067850fe641830e19a0f851c0a52ea27145b0f170631dad44673 "[""tus_7490b069a8302da995a90604755f64bffa21f7a39ffe9f88dfabaaf19ce8acba""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000104044""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" OCA2 "[""other_unresolved""]" resolved_exact discovery +symbol:PARP1|entrez:142 v0.5.0 tue_28aad8ec5316e798fcc934731d489eda5e561d2d999b53dd93968d709fb94ace "[""tus_88a1454854f51b1823cbe8936ea894495213444cde506a72add75dc6c7ec3055""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000143799""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PARP1 "[""other_unresolved""]" resolved_exact discovery +symbol:PATZ1|entrez:23598 v0.5.0 tue_98d293bcf07e132102752a523e58655ce335367c34151200460985bea58b5900 "[""tus_79f48b6198a24c9c5143c4653f9c45d9dd4aeb6af4e794e733b134c679882d77""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000100105""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PATZ1 "[""other_unresolved""]" resolved_exact discovery +symbol:PAX5|entrez:5079 v0.5.0 tue_b9f9422b24f77a9af0c3fe2e897e0f2c9ec96a364c14abf8645f55495a65a091 "[""tus_17a80ba8d0652021c137cd7384f92ea078dde39f77df0f26451637ee769eeb14""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000196092""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PAX5 "[""other_unresolved""]" resolved_exact discovery +symbol:PBRM1|entrez:55193 v0.5.0 tue_221389093efc5989a6b22cfac95ab582285c3774b493191246578bc23882799a "[""tus_5c38012b22ad21e73fed705021dbe11b5c700d10a4145e48ba505b888713aa66""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000163939""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PBRM1 "[""other_unresolved""]" resolved_exact discovery +symbol:PDCD1LG2|entrez:80380 v0.5.0 tue_49b5d6882134d634b237d9fb57a24e84c420cdec603cd8f81ba672308c39b181 "[""tus_076119c7453f7881af45bd302a020ad4c2e33ba68ecb4a2e76076b73d02aea14""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000197646""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PDCD1LG2 "[""other_unresolved""]" resolved_exact discovery +symbol:PDCD1|entrez:5133 v0.5.0 tue_f7f244f801bde700e4cca1b7eabbf581f402a86fa482d870e386a8148b87a3cc "[""tus_8aa5d72673485a1ce9add56c25aaf7935e31943efed11d59aa0ad9aa3ffe7155""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000188389""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" PDCD1 "[""checkpoint_redundancy""]" resolved_exact discovery +symbol:PDGFRA|entrez:5156 v0.5.0 tue_cf5f144e02f8f5579b645764b18639cb8d64acc84a4b4b907a9a4541c11e7a4a "[""tus_59c22e596279bdcd9da39f0d9129897003f617e61299eac341679713a5cd3475""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000134853""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PDGFRA "[""other_unresolved""]" resolved_exact discovery +symbol:PDGFRB|entrez:5159 v0.5.0 tue_1be36ae60fb87854ce1f5c9121bd9a550416df79e7270379ffe0625cbf192aed "[""tus_5a1f6e5b5fa58f21bcc7ee097f90b4f1644ad55737e96343b469175892bfad5a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000113721""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PDGFRB "[""other_unresolved""]" resolved_exact discovery +symbol:PER1|entrez:5187 v0.5.0 tue_fc2baa84becad2876c96a602201381f249d2d51607a025fdd2aeb42c08edba07 "[""tus_eafcfb66fcddb4a538ed6cd310f155120de8448685c46648f8dea9d6b0495c2c""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000179094""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PER1 "[""other_unresolved""]" resolved_exact discovery +symbol:PHOX2B|entrez:8929 v0.5.0 tue_f54a9d86b88e2704a5816b24eec53b4047e1453e672d8ade8273dac412f5f37c "[""tus_95f61049eb48b60fd613bbc3a4964e715f8304483fc1a969ff9aa85c562e45a8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000109132""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PHOX2B "[""other_unresolved""]" resolved_exact discovery +symbol:PIK3CA|entrez:5290 v0.5.0 tue_e2c84d4d267f969b3957a888dba3296e2add197e49652078ef157f0e9edfd4d2 "[""tus_a5f58badfd20031e48694dcf71265f88d614fff00e6f339252a246d87e7cd9af""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000121879""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PIK3CA "[""other_unresolved""]" resolved_exact discovery +symbol:PIK3CB|entrez:5291 v0.5.0 tue_d63f267351a6b48cb36fd65da2dbf6f467aa0c2546b564367101f4274915cf78 "[""tus_e73eeb30ab3edc2441c9ab2559c7bc7802ea70205912477a00b3a12f41861572""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000051382""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PIK3CB "[""other_unresolved""]" resolved_exact discovery +symbol:PIK3R1|entrez:5295 v0.5.0 tue_72882406c99a4cf824e5a412faf441b1bcc32d1e1d3ae1f0cd60bc5499d9a807 "[""tus_0fc48df2be9491ef8380b3cf94ff924a1b9acac452ceb151f04162fee8fd9b80""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000145675""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PIK3R1 "[""other_unresolved""]" resolved_exact discovery +symbol:PLCG1|entrez:5335 v0.5.0 tue_757a68ee7e9228ec8b10c2478795325f71b6d5d7e3c263bebcf5390a44aedf3b "[""tus_1dea8f39c38ed467de6f970f564baf82cdfa077b90628a12152ac806a1bfa7a8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000124181""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PLCG1 "[""other_unresolved""]" resolved_exact discovery +symbol:PLXNB2|entrez:23654 v0.5.0 tue_11aa1b09f2a20738009c5bce9d30294409c93f76048c6679c19b815470746892 "[""tus_617513394b2f55676e2967ed10034464436141be3c8284c43770a36b7da4ca7a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000196576""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PLXNB2 "[""other_unresolved""]" resolved_exact discovery +symbol:PMEL|entrez:6490 v0.5.0 tue_3f86eb43480a380de3dec89ce2f84e0a461da3ff9a7ac1d64f356c6a2ab0206f "[""tus_c20935fd4d2e5bec5b5246f58ce9f2b80d2d0764816f2d6cc75842f9764f3d62""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000185664""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PMEL "[""other_unresolved""]" resolved_exact discovery +symbol:PMS2|entrez:5395 v0.5.0 tue_573e3236f1351154444cf1ab0ae8dc2da335021b5f1e693ad412926ee5a40823 "[""tus_301ed6b2c2c937d215503da8e99fd4a010a06a81ce98015bebb5fa5b697725ad""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000122512""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PMS2 "[""other_unresolved""]" resolved_exact discovery +symbol:POLD1|entrez:5424 v0.5.0 tue_2908b6148baaef26f71bb7feb176fd32b44c990af6d913ef086cfa5e2fe3a8c6 "[""tus_4c271841060e4b96174d75f5e2f0046078b44693dcaa3d7505ba60b7e9587307""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000062822""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" POLD1 "[""other_unresolved""]" resolved_exact discovery +symbol:POLE|entrez:5426 v0.5.0 tue_a62a6c9f39916f79faed00f3f281022e44edefb7533b9ffdfbed737940a4e0aa "[""tus_9ea9f93df6afec83a55836ea9a9cef79d7f93a28396d63584232389281c1d9d8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000177084""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" POLE "[""other_unresolved""]" resolved_exact discovery +symbol:POLQ|entrez:10721 v0.5.0 tue_8a5529aa671997000cdb0c6bb3a1ee84a8b143be76d764b42a560c281d33c874 "[""tus_8ef8371840c3139e8ffd98b4bbb0e46f10f84a0ed0ba9b7be1965c569967db46""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000051341""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" POLQ "[""other_unresolved""]" resolved_exact discovery +symbol:POT1|entrez:25913 v0.5.0 tue_e1866dc41d6cc3cf8483b1e6859726b2a29079a6d25315ac89e5e962136ec1ce "[""tus_bad9eaf92eeacc4c66b41f472835c79c00b4d7a90e5d2fced6399d456952ec17""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000128513""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" POT1 "[""other_unresolved""]" resolved_exact discovery +symbol:POU2AF1|entrez:5450 v0.5.0 tue_8098ddb7995e0e1660980df25f3cca4fc27afcc280111c4f27f6a27bfcfafee7 "[""tus_2e778fe833a4529a7393243b9064729552fe96471ba1e12a4c8d1e02247e048f""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000110777""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" POU2AF1 "[""other_unresolved""]" resolved_exact discovery +symbol:PPP2R1A|entrez:5518 v0.5.0 tue_93f0c416ffd9196e733aab37b459ea029eb6b3479cff8a858eb0fd02fbb7b72b "[""tus_1bf8fd239c41b9d9a94577f89ddf4db2540329a10e155fe1327e2a17a05cf904""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000105568""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PPP2R1A "[""other_unresolved""]" resolved_exact discovery +symbol:PPP6C|entrez:5537 v0.5.0 tue_9d48bdb507fddb4ad22a5a135002209ce2776fdec493b65e4a3bd2309806a89c "[""tus_e59021d945d2d63dd91c4fc739da8677d79a7b7051942f9b09c1bdf093c6c87c""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000119414""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PPP6C "[""other_unresolved""]" resolved_exact discovery +symbol:PRDM16|entrez:63976 v0.5.0 tue_0330af5e8e5ee24b602f9e9fca500b7baa33f94bf354e2b63c33847ca859bde7 "[""tus_1b9f43b969e76057df584b3c43b5f14f9d922828e774e36948e438b826ac1800""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000142611""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PRDM16 "[""other_unresolved""]" resolved_exact discovery +symbol:PRDM1|entrez:639 v0.5.0 tue_9d770659064edfd087a263d031bae8e87e59ee261f7bc0b24502dec9494a82f5 "[""tus_b908002d1deb42fb6c73621ce588c0a5adef108d8b0a6c600d40ca38c7251fc8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000057657""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PRDM1 "[""other_unresolved""]" resolved_exact discovery +symbol:PREX2|entrez:80243 v0.5.0 tue_7bb67d651df294fa56ca451167fdadab1b34055100e3efda7c5f6693968ea384 "[""tus_ae20734ce07758f063480f742a1e1b3a1ac657f763e7ae6fb8d909b841acc7d7""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000046889""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PREX2 "[""other_unresolved""]" resolved_exact discovery +symbol:PRF1|entrez:5551 v0.5.0 tue_cd462a2e6326e868679bc8557832e244b1dcc9e5e0a30fd46ee898b486792264 "[""tus_a6c9c43dd157d243d21a0aa28f36ca50a94da7aac1fae1266e318bbb131885b1""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000180644""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" PRF1 "[""immune_cold_state""]" resolved_exact discovery +symbol:PTCH1|entrez:5727 v0.5.0 tue_16176e486e3fc57a284e1706ed0d21b42ed10dc38296c8a52abc76e30a0ac74e "[""tus_bff48267b79f23bf3e7c2d63850e00b9e6744e5b1c64bcf99476eb66d550d0fe""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000185920""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PTCH1 "[""other_unresolved""]" resolved_exact discovery +symbol:PTEN|entrez:5728 v0.5.0 tue_b981fbb88aa91cd10bd4658ef253fb867e83275a7412e1ac15d53abd1d06f7b0 "[""tus_fbb6f28bc4c3829f43c2c1367adcb14328a9210aa556118c308bcbbdba268dde""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000171862""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation.""]" PTEN "[""tumor_intrinsic_driver""]" resolved_exact discovery +symbol:PTK6|entrez:5753 v0.5.0 tue_c571a45e0e9b9f2cbd7e88972c7b673346a17fe093c3c279c4210d75f5ee6f51 "[""tus_09e79de8d0efb2e8eee64177dbe0509efd9078815ba0c14747737b016e50d681""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000101213""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PTK6 "[""other_unresolved""]" resolved_exact discovery +symbol:PTPN11|entrez:5781 v0.5.0 tue_83a01212f89c9ac241a4fb0bcae36591dda68ec5d496990b3a6b903f6a8d97df "[""tus_79e09ed4b54047051d32c0130647480454f22fc9e463758da1384a67a591c87a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000179295""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PTPN11 "[""other_unresolved""]" resolved_exact discovery +symbol:PTPN13|entrez:5783 v0.5.0 tue_3ca08291bb8776858a8230d9c27d4e2f9ca85ae3a86c04a6f0f15cac0355ef97 "[""tus_9858852a65375a56dc54e7af024ccdede032a5dab8d931b8e95b6c637f41e6b8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000163629""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PTPN13 "[""other_unresolved""]" resolved_exact discovery +symbol:PTPRB|entrez:5787 v0.5.0 tue_9d9e1e1f3ad0e3a5d9a5b99ce995fd5e6a2a3526e51e995b75c54fd9f4d6ea25 "[""tus_54ffdb46636f380988b1a94a29ef672f960e68f8b6644ce58d5d8e1d6e262bbb""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000127329""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PTPRB "[""other_unresolved""]" resolved_exact discovery +symbol:PTPRC|entrez:5788 v0.5.0 tue_84aec2eabde75e728a0e5151ff91c3e0bbb7aadc10c492e2b26a125fa5c3eb45 "[""tus_cf2096a7c3f87f64dadd990c9ad993b01395a68149df5edf1168f07451de8e3c""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000081237""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PTPRC "[""other_unresolved""]" resolved_exact discovery +symbol:PTPRK|entrez:5796 v0.5.0 tue_6e783bf14251bee7059ce30cb70dc1e55ab507e3a5a66f3f9340a8a22e96d3e4 "[""tus_2ab681e22b6e1615438ea9e2b3e9e296128aab2ea4be20a0d4c2ee03d0d6be4a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000152894""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PTPRK "[""other_unresolved""]" resolved_exact discovery +symbol:PTPRT|entrez:11122 v0.5.0 tue_fe25a54bc1f167a184323e98476cfe18c5990d08dd39d79125bb7c1911ac6205 "[""tus_b31d47cc6f59edcfed5ec2350965c0de077e8968afe4493d6fea24a3c1d41eed""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000196090""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" PTPRT "[""other_unresolved""]" resolved_exact discovery +symbol:QKI|entrez:9444 v0.5.0 tue_49f998227928b8b62e76c7e405981dffc155a3a109d891894c4bc0f231cd877c "[""tus_1d6f3eb644b54f986ed4d8d59acf02dc620ea5224e868d962b9384c2bf5874a2""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000112531""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" QKI "[""other_unresolved""]" resolved_exact discovery +symbol:RAC1|entrez:5879 v0.5.0 tue_870ae0de46389de1dbf064306367d689f7e6dc6236ed39dd0455a87e4792177f "[""tus_e58fd1f342dbacb7431258366b33e85ac57d796a2b13ec8d2a41bfa49be70a06""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000136238""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" RAC1 "[""other_unresolved""]" resolved_exact discovery +symbol:RAD51C|entrez:5889 v0.5.0 tue_51a67122d4a0ecfba4e312e6a5bb399cbf523e51646e0a810d70e42ab8e61502 "[""tus_cb911f778501fcedaf55dc42d00c96121570b7c8dcb0fac040b6bf9a50271be3""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000108384""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" RAD51C "[""other_unresolved""]" resolved_exact discovery +symbol:RAF1|entrez:5894 v0.5.0 tue_e14145af24990e5e98d2d460a3c6a2d5c533e28b3c9c7c8a6599db40258329c5 "[""tus_0a80cfae09fcb03e73a69dbf02ac26930de41a5fe2e4196ce117297feec14a1a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000132155""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" RAF1 "[""other_unresolved""]" resolved_exact discovery +symbol:RANBP2|entrez:5903 v0.5.0 tue_939c979411992fdbb7bba7b87e19c8f9e3781a88dc94e412981aeb76c5db9194 "[""tus_def7227f53c9ad793ecf0c6f324f7d9d5560461b1bf18418148b13c5c596c91f""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000153201""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" RANBP2 "[""other_unresolved""]" resolved_exact discovery +symbol:RB1|entrez:5925 v0.5.0 tue_4fc91c744fa5ef2fb28514f7fac97240ffa258e6799124727e9fff5fb3bb7683 "[""tus_4ed4aca7fe5f1ef49efe9d3d3ced58458f6b916d5d879d23e929b0575323aca0""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000139687""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" RB1 "[""other_unresolved""]" resolved_exact discovery +symbol:RET|entrez:5979 v0.5.0 tue_0dcea47ae41c65f191471418616d6d17f1841571a0a1373e46144404778d03ec "[""tus_d184456c88add3e18f134dd9bda010726bcbf3f137f9807859f18e4857e44f43""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000165731""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" RET "[""other_unresolved""]" resolved_exact discovery +symbol:RICTOR|entrez:253260 v0.5.0 tue_9988ba10176ac2fcfd82f55a540fccc7ca852a3a526f9c6c722d6d813ae4fa0f "[""tus_2e531c59d91ee634ae4630e0c4ea3b74bb03aff27fa837e3538407e3f312e4d2""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000164327""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" RICTOR "[""other_unresolved""]" resolved_exact discovery +symbol:ROS1|entrez:6098 v0.5.0 tue_3175ae3a4566be2ffc5abae65566b887f93bb4c4da432ff86fa507d2f3f62af9 "[""tus_d7b2c1d629ac182fea3cbd6f230ecae1b1814e6574634a157a7df1999b125657""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000047936""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ROS1 "[""other_unresolved""]" resolved_exact discovery +symbol:RPL5|entrez:6125 v0.5.0 tue_02d0499f97a202d6a091e5d917f4489e360b6861af0bd340eae58dc089b27dd7 "[""tus_bfb88bf5bbae0e7292f72fbf54ca938c63000d2dd2cfe26c62dd1b6fa9b96261""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000122406""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" RPL5 "[""other_unresolved""]" resolved_exact discovery +symbol:RRM1|entrez:6240 v0.5.0 tue_c33a06e1efd125ab4bbbe5c451f5954d9478e692b73bfdc714919de36f9a1dd3 "[""tus_1a26b5b43faa603ac2840bfff0f90c1842f7e32b4cb1a98988401e5a867f3fbf""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000167325""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" RRM1 "[""other_unresolved""]" resolved_exact discovery +symbol:RRM2B|entrez:50484 v0.5.0 tue_05559447610af551e79968dbf82bb2668a06dbf6850567a39fbfa60e03db4451 "[""tus_34dfa2039d02f5e2f872a3c7b8b2a23f7dad9fd6636ce34c9d51be2f65645df2""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000048392""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" RRM2B "[""other_unresolved""]" resolved_exact discovery +symbol:RRM2|entrez:6241 v0.5.0 tue_31014a34a22f137e45acdd698c075224fda92f4d20b2eb8308869d5a5b18d48a "[""tus_3e8caa52e90f1aa285e4d21e204cafbaa02057c62d0e7b1fe41abad77fcab230""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000171848""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" RRM2 "[""other_unresolved""]" resolved_exact discovery +symbol:RUNX1T1|entrez:862 v0.5.0 tue_7e283a4cb836a03c363bd524a5e1afa1d4b7cc9a1ffa05a46efa6e9adf1a01f4 "[""tus_4030f75e726e261ec541c2e46ad9ab1b422a24288c4ddc8b5b75d4f7ed5dd82b""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000079102""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" RUNX1T1 "[""other_unresolved""]" resolved_exact discovery +symbol:SALL4|entrez:57167 v0.5.0 tue_0c55689bc39f20bafdd62022a2c485d29e8f6ea44580fc57164d8a596e6b1bea "[""tus_af29c56e6745d543de67899ea816e416184fb044360388738d65ae6871c8ac3e""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000101115""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SALL4 "[""other_unresolved""]" resolved_exact discovery +symbol:SETBP1|entrez:26040 v0.5.0 tue_98f6b131c4d481b78e0e0415a5d81ef389b76725e3515ad988c8cb16ff46f888 "[""tus_37c12841fdd1a77b6c2054c00f71403e6c3c2c7d8fc5b4506dc904a74edf69da""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000152217""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SETBP1 "[""other_unresolved""]" resolved_exact discovery +symbol:SETD2|entrez:29072 v0.5.0 tue_d9bcc9fbdbefb45e88a1d41f9098be0337d8f5884df448540b0f4ac7a510fda4 "[""tus_c035de1941bf7bce3d51351aba4c84f8fde4a40e662cd75fb076c4cea8930483""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000181555""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SETD2 "[""other_unresolved""]" resolved_exact discovery +symbol:SF3B1|entrez:23451 v0.5.0 tue_7311dc4b161231b0ea07e1a628e915b875804e6c9de4ab279071a91860f2f30c "[""tus_b1591b13c70e201e5931be9db977f8e7b10261c19a5b8fe50e7eb9afd0d8c3d9""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000115524""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SF3B1 "[""other_unresolved""]" resolved_exact discovery +symbol:SLC24A5|entrez:283652 v0.5.0 tue_35a2703c667abcdef6341898b912051afe0db8883b2e24eedf62a2ceab9b25dc "[""tus_d61cc905f4615c468e5220dd0e76fec4620612f562153680062c8f0c54a03bdb""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000188467""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SLC24A5 "[""other_unresolved""]" resolved_exact discovery +symbol:SLC45A2|entrez:51151 v0.5.0 tue_0f5e9491e78a0f60f285bee45ecc29bce050473853cb8ee2aa789eb4e21e8568 "[""tus_30d7ea5c732d7088e53622d5c04cc2e04377405c540db67120810577bd2db69f""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000164175""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SLC45A2 "[""other_unresolved""]" resolved_exact discovery +symbol:SMAD2|entrez:4087 v0.5.0 tue_0f2b63d89d1a578ac2aae9f659488ad9dc183cf9cee99b1b4e451452a99a2adc "[""tus_2007a73bb303cf0387aa2c3917c176655b51bb4c6910d37f21c2c9246e76ffdb""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000175387""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SMAD2 "[""other_unresolved""]" resolved_exact discovery +symbol:SMAD3|entrez:4088 v0.5.0 tue_7ab508dc467db65f5f1c1f279dfffb20b88caaf350c1dda17dd8a3e179991915 "[""tus_37ac5e851973cccd08c6643a3f2cdf8d6c683d1531676e3b1db18e1edb3f929a""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000166949""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SMAD3 "[""other_unresolved""]" resolved_exact discovery +symbol:SMARCA4|entrez:6597 v0.5.0 tue_677f1f6787053195baa3700e6f70641ebee53619b6dbad6560acb81a6bc8b415 "[""tus_e6d8269a4b0700cf2c57a2118fe54e15f65a09736d7b709599f5eb7ce4fb7327""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000127616""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SMARCA4 "[""other_unresolved""]" resolved_exact discovery +symbol:SMO|entrez:6608 v0.5.0 tue_bfc8fbd353c8dc58fc291a38631024f88be20ba6b715025061e0b92f8de0d700 "[""tus_867048b6054399357fc5ab876505a1345c39dbdd44981307a04fef4135afb94b""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000128602""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SMO "[""other_unresolved""]" resolved_exact discovery +symbol:SPEN|entrez:23013 v0.5.0 tue_b78f789b34f841d8449fe641ba0a703dec6ea2912ec9b1c7ac81a4f432bedfb4 "[""tus_79783fe62be0f77b3fd01b1aa30cff2c44531bb13105ccf61e9d418e0acb18aa""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000065526""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SPEN "[""other_unresolved""]" resolved_exact discovery +symbol:SPOP|entrez:8405 v0.5.0 tue_c7ac61aeb8bc8336a58ec2fc54692333e7e1e786c1a07abe90164aa6fb0a02ef "[""tus_aad8af72fa3fcb51e58276978714a92b0032321259c3e97b657acc35a6c17d3d""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000121067""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SPOP "[""other_unresolved""]" resolved_exact discovery +symbol:STAT1|entrez:6772 v0.5.0 tue_c2eabf28150d8bded8c44f10dafe351107fbcde8751912a5804a3b1d4433c8a6 "[""tus_d8b60d2cb9fbf15e14f7688b082b916ad3b9be65dbc1af18aaed6d954bc1e422""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:STAT1|entrez:6772""}]" included [] STAT1 "[""ifng_resistance""]" resolved_exact IFN-gamma resistance mechanism / biomarker discovery +symbol:STAT5B|entrez:6777 v0.5.0 tue_09e13ffdb2f8cbf2fa3ee15fbf551073f8e4e7c345b43613b4c186dadbc9448c "[""tus_a416f69f7a8edfb070f38a59eccf74e9f97a14461b32b406b14ceb6b37e0936f""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000173757""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" STAT5B "[""other_unresolved""]" resolved_exact discovery +symbol:STK11|entrez:6794 v0.5.0 tue_c39515f151377bf6237499ecbd0d54eaa31dbb0240c0db5587b997d25bc446fe "[""tus_158567276bd5a206779c961e692294256a1fa1dc25b93d331f69f57d3e567a05""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000118046""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" STK11 "[""other_unresolved""]" resolved_exact discovery +symbol:STN1|entrez:79991 v0.5.0 tue_1fc02efbb4b543ca9795cc275905cb2a46bb8ff87113b1145f02ddc971ed37c5 "[""tus_df1357237535c3a8aa643c4081b1d1bf6ae1b7fb87eb6e375e917f723a69c702""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000107960""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" STN1 "[""other_unresolved""]" resolved_exact discovery +symbol:SUFU|entrez:51684 v0.5.0 tue_c0e5785b62af0b3788551d8f9eadbcecf385ff2ce595c176a258dabb7fb333fe "[""tus_648774096ca06f69ff6b24bbaa020bb7042df0ceb92d78cde1bc0de5f0400998""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000107882""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SUFU "[""other_unresolved""]" resolved_exact discovery +symbol:SUZ12|entrez:23512 v0.5.0 tue_e5112062c145db5ed2fbec4760429369b78a1485cf6982dbe63a8f2d336e97db "[""tus_551ce0b24aded3df4e9359a215337446f9cc9be16c2d8c182653ea39d6fd92a6""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000178691""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SUZ12 "[""other_unresolved""]" resolved_exact discovery +symbol:SYK|entrez:6850 v0.5.0 tue_fcaaf10887bdb8700669e3ab34d83b7535ebe43b5dabacba021f5ec1ed59b64c "[""tus_b66645df5f681542232d84f8cab7aaaef4d34c49894bdcd90f358ffcd4234c05""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000165025""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" SYK "[""other_unresolved""]" resolved_exact discovery +symbol:TAP1|entrez:6890 v0.5.0 tue_9b47dd3738e1114769e9170ef31c58906463394c3f276a7ed1e374a5c0608bcb "[""tus_c0b3448466d841bbc17c54a3e91af689b534f9b6c17d0e8a2ec93a6d50b755ed""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:TAP1|entrez:6890""}]" included [] TAP1 "[""antigen_presentation_loss""]" resolved_exact antigen-presentation resistance biomarker discovery +symbol:TAP2|entrez:6891 v0.5.0 tue_fb96e82f3d45c6d475ba74d15991cd20cdf3c57efc42cfd174c8bff8564b72a9 "[""tus_de275f37696c196da6850d6c8e39c7a06b48f29d172bc49bd5f4b872a2aa7b71""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:TAP2|entrez:6891""}]" included [] TAP2 "[""antigen_presentation_loss""]" resolved_exact antigen-presentation resistance biomarker discovery +symbol:TBL1XR1|entrez:79718 v0.5.0 tue_16239f9e35cc0c0dfe83f993495862c2fce3a6e000b3258a3d67c292bf2a722a "[""tus_df57c81724088452a6842b3303d6686f355c706ce4914193572f6152bbd7c4ae""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000177565""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TBL1XR1 "[""other_unresolved""]" resolved_exact discovery +symbol:TBX3|entrez:6926 v0.5.0 tue_378228ede891ee9f9c995191bcb84a5f10561e0648fbe0e1f1a2e25427548070 "[""tus_effae29686da2340b3709606868b6d6932a61d70872f3af83f55ac460991cb6d""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000135111""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TBX3 "[""other_unresolved""]" resolved_exact discovery +symbol:TCL1A|entrez:8115 v0.5.0 tue_dec81e8de630557f73b24a8204bda131e291eb368f6e42ad3c2dcb71dd259955 "[""tus_c254f3bbefe70776ecb53c89b1fe6d7de66385d912a4eb6f520870f39aa678d1""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000100721""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TCL1A "[""other_unresolved""]" resolved_exact discovery +symbol:TENT5C|entrez:54855 v0.5.0 tue_626c8a4c53f19145d49d0432b6d9faba141cccd3c7278b5524cffaf5852fb71e "[""tus_201832bf8f43a3c05ddcc4df4ed47143b907545c5a7076d58ae817528abf8215""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000183508""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TENT5C "[""other_unresolved""]" resolved_exact discovery +symbol:TERT|entrez:7015 v0.5.0 tue_f864df1ffcb14f69cb5713c235641749a61413ce0213bec40b64b0cd30cd11e0 "[""tus_987017500ddf561ea8234993c4ff6bae1bd828cbf08da614856b1fa9ca1f8bb8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000164362""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TERT "[""other_unresolved""]" resolved_exact discovery +symbol:TET1|entrez:80312 v0.5.0 tue_39fee935106d1dfd71998b55f555c608cc4938ea8584e3693fce005f4be92bd4 "[""tus_ab26d8474b745c31376fd4c627ffbdd5e94a98a339dfa6d2fc8776a09de6efa8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000138336""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TET1 "[""other_unresolved""]" resolved_exact discovery +symbol:TET2|entrez:54790 v0.5.0 tue_58e6812c8528bed0199c0d2edd482e10e1102fa95d25dbe1e56bc1599b1ca2f2 "[""tus_eef90b2649fb94cdda73c9afcf5db50591809e97e6ab8d988b669636246cfb12""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000168769""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TET2 "[""other_unresolved""]" resolved_exact discovery +symbol:TFE3|entrez:7030 v0.5.0 tue_618e074028a918d23ecd7428ee92bfb2f6854e01d3ff49587d800a7035140b29 "[""tus_98cd9b1fd3244b9e6264e0e3f790a4aad0adbb50c093540b0f9e2b6d45922991""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000068323""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TFE3 "[""other_unresolved""]" resolved_exact discovery +symbol:TFEB|entrez:7942 v0.5.0 tue_d146dbb0b42137e725b2852c7620808d7b8727d98e14f65451d40de969ceaaf0 "[""tus_da6bcf045a9e43f47999d9928cb014180b81307400dc6d423c021a1073669ab7""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000112561""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TFEB "[""other_unresolved""]" resolved_exact discovery +symbol:TGFB1|entrez:7040 v0.5.0 tue_1c38db8c49a2b8439e57dd9382e8db0282d689239f3e8deba3b4e61448f0b7be "[""tus_8e167326d653f5b914568970ffe5e090558b1a30fcecbad3b2906bd089bd45df""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:TGFB1|entrez:7040""}]" included [] TGFB1 "[""tgfb_caf_exclusion""]" resolved_exact immune-exclusion / stromal-resistance candidate discovery +symbol:TGFBR1|entrez:7046 v0.5.0 tue_5b7f8c4cfe86b66fcf7120f510f40bd357f345ca8134226a1aebf24e55bde242 "[""tus_dee1343e38f253d39548ee51277c98d58f24af3436a82ad1618280fafeaa98e3""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:TGFBR1|entrez:7046""}]" included [] TGFBR1 "[""tgfb_caf_exclusion""]" resolved_exact immune-exclusion / stromal-resistance candidate discovery +symbol:TIGIT|entrez:201633 v0.5.0 tue_2b3d7f687a0496266baa729c787629e3f346859f3ce5c2bd45083fafb89dd057 "[""tus_22327cf9c2e896cf80692f57d710f5c0a532b6cc74c943c189a5a3932aa46a1b""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:TIGIT|entrez:201633""}]" included [] TIGIT "[""checkpoint_redundancy""]" resolved_exact anti-PD-1 combination target discovery +symbol:TMEM127|entrez:55654 v0.5.0 tue_b719b54e27a4a671b9b5f3b5e476a3d0a13f52e6c3d9e35e1a0c408dc777e52f "[""tus_68e5dcf92b330522910f0c02c692abf474addbfbde91d03c20610026afee8077""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000135956""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TMEM127 "[""other_unresolved""]" resolved_exact discovery +symbol:TNFRSF17|entrez:608 v0.5.0 tue_f2b8bed412fcc3dddd6450da04b4834bd08fcda55d6f2f7b8c0ac841230b7178 "[""tus_2559c74573bd701b525f14993f79acc1d6d7f028fc6199d10a5cab87bbc1d75d""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000048462""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TNFRSF17 "[""other_unresolved""]" resolved_exact discovery +symbol:TNFRSF18|entrez:8784 v0.5.0 tue_04e1272d23a3b8b4bcf30f0e9a258446552336cb7400012abfc595fb6b1cff91 "[""tus_7874c9e3add0f4aa4f5f5556b13e6ebf11913e66fd22b6ba01fde2e0e64d0e67""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:TNFRSF18|entrez:8784""}]" included [] TNFRSF18 "[""treg_suppression""]" resolved_exact Treg-suppression marker / possible IO-combination target discovery +symbol:TP53|entrez:7157 v0.5.0 tue_f1a84f48b4bad06761ba93f9ba2d779f5399bd055b6d09669096cf5fadb59788 "[""tus_7f41fa9c65c2f355ea09a0ff146473a20fd5df58ec9afd8017fcb35152594a20""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000141510""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TP53 "[""other_unresolved""]" resolved_exact discovery +symbol:TP63|entrez:8626 v0.5.0 tue_cdd41b5d039cdd77beb661faf7b6c5b1a79ca42cf88a2a698b2b1bbd88b32d6c "[""tus_ef69acff776ea97a1850e114f215176ae7dc1d22b591010965545d6b8ec7e956""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000073282""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TP63 "[""other_unresolved""]" resolved_exact discovery +symbol:TRAF7|entrez:84231 v0.5.0 tue_bfb10e21c3d1048c8a8597d92396e0eb2bad410f1148144a075dd6225f68c3ee "[""tus_df9146094164ad3b6c32fd56e166447fbc6e04099d70f6a8c7c5be2f071cf724""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000131653""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TRAF7 "[""other_unresolved""]" resolved_exact discovery +symbol:TREM2|entrez:54209 v0.5.0 tue_475a8c94c74ea71cb2e9d1af4dbd1b5a8b2bc7bb6064dfdc3a33bc2dc5c29d9a "[""tus_354a0ddd0932f1455be96ec3c2b1539cd4c50a01c5ae9946c7cf687eb4fe7872""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:TREM2|entrez:54209""}]" included [] TREM2 "[""myeloid_suppression""]" resolved_exact myeloid/TME anti-PD-1 combination target discovery +symbol:TRRAP|entrez:8295 v0.5.0 tue_a39c26a1ed4643dc58777c3fd07bf13d2aa241b282b1d4b9e7f76026da71fce7 "[""tus_892fd2a635ef3979b6c00e25c846e363c6718683adc3d3813da62c438b111b72""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000196367""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TRRAP "[""other_unresolved""]" resolved_exact discovery +symbol:TSC1|entrez:7248 v0.5.0 tue_74f0bb1d9283ad358d68262fe4931aa2a8c415019c20b20ff22a0027e1b2b7f7 "[""tus_7c49c2a02f9dde9ce4e0aeb76e154bcdd8e9f3e12c67c927c7d471efaabf16a6""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000165699""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TSC1 "[""other_unresolved""]" resolved_exact discovery +symbol:TSC2|entrez:7249 v0.5.0 tue_49e71d95d4e9cf690a53823ddea28d10d42c7f12a1b055e8c412921b41de54f6 "[""tus_93723e328928b134aef818daa256de56a0f92be2270a861f81b153eb60cef37c""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000103197""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TSC2 "[""other_unresolved""]" resolved_exact discovery +symbol:TYRP1|entrez:7306 v0.5.0 tue_688dbce4aeae77e1bd4b3388a82ac10293d48aae1855732323234d6f95bf4c29 "[""tus_70f5ffcab44e18a63906ddb2df0c1445527179a11220b12534e906f711c1cd0b""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000107165""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TYRP1 "[""other_unresolved""]" resolved_exact discovery +symbol:TYR|entrez:7299 v0.5.0 tue_2144d485bc29feea7225a043a2fd2284794444a03e04d5e62f4d99cc3671859d "[""tus_6e3586bbc3187f549c8449d2bc95b2a89a01fa38501e6ecbf94e83120c618c93""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000077498""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" TYR "[""other_unresolved""]" resolved_exact discovery +symbol:U2AF1|entrez:7307 v0.5.0 tue_4258800d37563c44d97322530b2f0c9f07eb4325e75fcaf35908291b1f66df9d "[""tus_b43f646dacd30aa465e3c0341d1bd3b909205714653cbbd63b32b88d1166081e""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000160201""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" U2AF1 "[""other_unresolved""]" resolved_exact discovery +symbol:UBR5|entrez:51366 v0.5.0 tue_d730991755ed778912024a044e25aa21937bcfbd0b58b2cfe171379172b66ad4 "[""tus_4a32138ca1a6333c8aa6b958e1fa90e7dc1abe398ebd80e4b8b67128f62a6de8""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000104517""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" UBR5 "[""other_unresolved""]" resolved_exact discovery +symbol:USP6|entrez:9098 v0.5.0 tue_fc7df00fa8d64cf91d96a25f238203a93b8563a7bfa5ad38dcdcb06c8789f85b "[""tus_b3eea38c1f7a2df69f119deb3ba92f1ab5cc5a2f256b0580354093127f1636ed""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000129204""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" USP6 "[""other_unresolved""]" resolved_exact discovery +symbol:WAS|entrez:7454 v0.5.0 tue_7555d45ca2b08bc60bb985013f847de0dce0a06b6216e69dcea293fe51404a60 "[""tus_537242d2dc3a69b2d46d499f34d8d9b990e16afa96dd45ca9b9243dbcf4854ae""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000015285""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" WAS "[""other_unresolved""]" resolved_exact discovery +symbol:WNT5A|entrez:7474 v0.5.0 tue_048d7709565951081ff7a47a9aa409653e14726bf542ca65d832ff888a8b5741 "[""tus_2d21530176e2479a0e22bb0e193687973d0d23636c961e5701758554bb4139c0""]" "[{""dataset_version"": ""benchmark_v1"", ""inclusion_rule"": ""policy-required benchmark union"", ""limitations"": [], ""source_class"": ""benchmark_union"", ""source_record_id"": ""symbol:WNT5A|entrez:7474""}]" included [] WNT5A "[""melanoma_plasticity""]" resolved_exact melanoma plasticity / resistance-associated marker discovery +symbol:WRN|entrez:7486 v0.5.0 tue_91435b4d56e1521e52722ecf270e92aafaee0101650f5aba44063857fc5f8d81 "[""tus_835b669ed1e35c2aa7803410d23a33a772c30b8e7103e7c833fc45030e6a53f1""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000165392""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" WRN "[""other_unresolved""]" resolved_exact discovery +symbol:ZBTB16|entrez:7704 v0.5.0 tue_bb5bd88084c39ee3821a4a538af610cf5d6badded7cfb509e1a69f4da7aaa596 "[""tus_07732daf4dee9f3e046cd32248e95561a02e2337da48bdb08480f3e5c9ea6b67""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000109906""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ZBTB16 "[""other_unresolved""]" resolved_exact discovery +symbol:ZFHX3|entrez:463 v0.5.0 tue_daa67c64b7ffb2a803838790239d1022a9957a013ca6f4712a10b13b5611dd89 "[""tus_34d1b24650a465fc993fb4a0dfc14ead304a1fcbe3970f619cd244eb21c39f4f""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000140836""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ZFHX3 "[""other_unresolved""]" resolved_exact discovery +symbol:ZNF331|entrez:55422 v0.5.0 tue_5b8a3a4debb8001972085ef8ff7bc0cef1d9cf266dc6393dbcae35d34c3faf04 "[""tus_68f36580ecf29d1476633681c76596176c5237d9c700ed6c5872da7a8e56c3aa""]" "[{""dataset_version"": ""TargetIntel-IO:d6e7a5748b7c"", ""inclusion_rule"": ""Frozen membership in the pre-DepMap Open Targets-derived 300-target melanoma association universe used by TargetIntel."", ""limitations"": [""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""], ""source_class"": ""opentargets_candidate"", ""source_record_id"": ""ENSG00000130844""}]" included "[""Open Targets-derived universe subsequently annotated by TargetIntel; membership was frozen before DepMap evaluation."", ""Original axis value unmapped was normalized to the controlled ontology value other_unresolved.""]" ZNF331 "[""other_unresolved""]" resolved_exact discovery diff --git a/data/releases/depmap/DepMap_Public_26Q1/integration_gate_decision.json b/data/releases/depmap/DepMap_Public_26Q1/integration_gate_decision.json new file mode 100644 index 0000000..ecb8072 --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/integration_gate_decision.json @@ -0,0 +1 @@ +{"candidate_id":"dmapc_6ef49ad2486dc5f4954288bc0b0b9c77273c569123d7bc0f5c7920f409f825ae","criteria":[{"comparison_operator":"==","criterion_id":"evidence_scope_activation_eligible","description":"Evidence scope permits possible future activation.","limitations":[],"mandatory":true,"observed_value":true,"result":"pass","source_artifact":"gate_input","source_field":"evidence_scope","threshold":true},{"comparison_operator":">=","criterion_id":"benchmark_coverage","description":"Profile coverage meets the predeclared minimum.","limitations":[],"mandatory":true,"observed_value":1.0,"result":"pass","source_artifact":"benchmark_coverage.json","source_field":"profiled_target_count/total_benchmark_targets","threshold":0.8},{"comparison_operator":">=","criterion_id":"holdout_coverage","description":"Holdout profile coverage meets the predeclared minimum.","limitations":[],"mandatory":true,"observed_value":1.0,"result":"pass","source_artifact":"integration_evidence.json","source_field":"criteria.minimum_holdout_coverage.observed","threshold":0.8},{"comparison_operator":">=","criterion_id":"eligible_target_count","description":"Eligible benchmark target count meets the predeclared minimum.","limitations":[],"mandatory":true,"observed_value":24.0,"result":"fail","source_artifact":"partition_metrics.tsv","source_field":"combined/bounded_overlay_rank/eligible_target_count","threshold":30},{"comparison_operator":">=","criterion_id":"positive_control_recall_non_degradation","description":"Bounded overlay Recall@K does not degrade versus baseline.","limitations":[],"mandatory":true,"observed_value":0.0,"result":"pass","source_artifact":"partition_metrics.tsv","source_field":"combined Recall@K","threshold":0},{"comparison_operator":"<=","criterion_id":"negative_control_top_k_non_worsening","description":"Bounded overlay does not add negative controls to top K.","limitations":[],"mandatory":true,"observed_value":0.0,"result":"pass","source_artifact":"partition_metrics.tsv","source_field":"combined negative_top_k_count","threshold":0},{"comparison_operator":">=","criterion_id":"bounded_overlay_stability","description":"Bounded overlay stability meets the predeclared threshold.","limitations":[],"mandatory":true,"observed_value":0.9980159573146244,"result":"pass","source_artifact":"candidate_metrics.json","source_field":"rank_stability.bounded_overlay.spearman_rank_correlation","threshold":0.9},{"comparison_operator":"==","criterion_id":"zero_band_violations","description":"Bounded overlay has no band violations.","limitations":[],"mandatory":true,"observed_value":0,"result":"pass","source_artifact":"candidate_metrics.json","source_field":"rank_stability.bounded_overlay.band_violations","threshold":0},{"comparison_operator":"<=","criterion_id":"median_rank_displacement","description":"Median candidate displacement remains within threshold.","limitations":[],"mandatory":true,"observed_value":2,"result":"pass","source_artifact":"candidate_metrics.json","source_field":"rank_stability.bounded_overlay.median_absolute_rank_change","threshold":5.0},{"comparison_operator":">=","criterion_id":"source_ablation_robustness","description":"Every predeclared ablation retains sufficient top-K overlap.","limitations":[],"mandatory":true,"observed_value":0.25,"result":"fail","source_artifact":"ablation_metrics.tsv","source_field":"top_k_jaccard_vs_baseline","threshold":0.7},{"comparison_operator":"<=","criterion_id":"permitted_missing_profile_fraction","description":"Missing profile fraction remains permitted.","limitations":[],"mandatory":true,"observed_value":0.0,"result":"pass","source_artifact":"benchmark_coverage.json","source_field":"profiled_target_count/total_benchmark_targets","threshold":0.2},{"comparison_operator":"==","criterion_id":"candidate_overlay_matches_issue505","description":"The candidate overlay exactly matches Issue 505's bounded-overlay ranks for shared targets.","limitations":["This cross-check covers effective band construction, component eligibility, tie handling, and movement behavior."],"mandatory":true,"observed_value":true,"result":"pass","source_artifact":"rank_comparison.tsv","source_field":"bounded_overlay_rank","threshold":true},{"comparison_operator":"==","criterion_id":"compatible_identities","description":"All required artifact identities are compatible.","limitations":[],"mandatory":true,"observed_value":true,"result":"pass","source_artifact":"dependency_benchmark_manifest.json","source_field":"identity fields","threshold":true},{"comparison_operator":"==","criterion_id":"baseline_preservation","description":"The baseline artifact and production defaults remain unchanged.","limitations":[],"mandatory":true,"observed_value":true,"result":"pass","source_artifact":"baseline_preservation.json","source_field":"all preservation checks","threshold":true}],"decision_format_version":"v0.5.0","decision_id":"dmid_43ed63e59eebaa5c9559314d8bb036a67bd0b0427b66303c1731b365b555678a","decision_state":"blocked_insufficient_evidence","evidence_scope":"local_real_data","human_review_required":true,"limitations":["No production profile is registered or selected by this gate."],"policy_id":"dmip_1dbe37b4c9add183cc48464edb794798956610fae4c19265cb8a7f9d85a41bda","production_activation_enabled":false} diff --git a/data/releases/depmap/DepMap_Public_26Q1/integration_report.md b/data/releases/depmap/DepMap_Public_26Q1/integration_report.md new file mode 100644 index 0000000..b6cd9b4 --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/integration_report.md @@ -0,0 +1,7 @@ +# Dependency integration gate + +This is an offline, analysis-only candidate overlay. It does not alter TargetIntel production scoring, ranking, roles, configuration, or defaults. + +- Decision: `blocked_insufficient_evidence` +- Evidence scope: `local_real_data` +- Human review remains required. diff --git a/data/releases/depmap/DepMap_Public_26Q1/publication_inventory.tsv b/data/releases/depmap/DepMap_Public_26Q1/publication_inventory.tsv new file mode 100644 index 0000000..f1776b1 --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/publication_inventory.tsv @@ -0,0 +1,108 @@ +"source_artifact_name" "artifact_category" "source_size" "source_checksum" "publication_action" "exclusion_reason" "published_relative_path" "published_checksum" +"README.md" "derived_aggregate" "1419" "9f62b8dc88775bb4a2b15b3109474e36d815cc51188314104fdaa6098d13c0b2" "published" "" "README.md" "9f62b8dc88775bb4a2b15b3109474e36d815cc51188314104fdaa6098d13c0b2" +"activation_readiness_summary.json" "derived_aggregate" "226" "d6be4d9744f54294ff267b198c12d1d1025e1d6faddffbdea91d8e51c4db4812" "published" "" "activation_readiness_summary.json" "d6be4d9744f54294ff267b198c12d1d1025e1d6faddffbdea91d8e51c4db4812" +"artifact_compatibility.json" "derived_aggregate" "655" "944c804ca623c0a000ea13ea7badc9355a323f2ee41570bc5ad2d8dceb6e6050" "published" "" "artifact_compatibility.json" "944c804ca623c0a000ea13ea7badc9355a323f2ee41570bc5ad2d8dceb6e6050" +"baseline_preservation.json" "derived_aggregate" "1159" "106cfab62d1fce2039dff7a17e1a924a7902a44fc2e46fd9b638a0f3bf3b3950" "published" "" "baseline_preservation.json" "106cfab62d1fce2039dff7a17e1a924a7902a44fc2e46fd9b638a0f3bf3b3950" +"benchmark_coverage.json" "derived_aggregate" "159" "f69f4591f7c466dda5c8017443e81d6d091c521d2fb3406d6ecd563f8c46f221" "published" "" "benchmark_coverage.json" "f69f4591f7c466dda5c8017443e81d6d091c521d2fb3406d6ecd563f8c46f221" +"benchmark_report.md" "derived_aggregate" "207" "ceecc72c69ff8f719d3b52fab3a0c1a2ecac719118d19ead12e21547cafa8307" "published" "" "benchmark_report.md" "ceecc72c69ff8f719d3b52fab3a0c1a2ecac719118d19ead12e21547cafa8307" +"benchmark_universe.tsv" "derived_aggregate" "48228" "4e7ba3da08576e0425a780c34e778cf95a63defebf336402bf87793f36d1c54b" "published" "" "benchmark_universe.tsv" "4e7ba3da08576e0425a780c34e778cf95a63defebf336402bf87793f36d1c54b" +"candidate_overlay.tsv" "derived_aggregate" "15871" "fd4253001338d77d5d7909980c566002ac74fd5020bd968b52351bf1463cab27" "published" "" "candidate_overlay.tsv" "fd4253001338d77d5d7909980c566002ac74fd5020bd968b52351bf1463cab27" +"checksums.json" "derived_aggregate" "1008" "d116865f492f7925cc4f4e0f8978ead232d73ecc986be8e3df09958fd92f3ffc" "published" "" "checksums.json" "d116865f492f7925cc4f4e0f8978ead232d73ecc986be8e3df09958fd92f3ffc" +"dependency_profile_summary.tsv" "derived_aggregate" "81025" "ab70ae55251219113c7cc988e54fded7dc0b289310bcc8f21ce31a65438af983" "published" "" "dependency_profile_summary.tsv" "ab70ae55251219113c7cc988e54fded7dc0b289310bcc8f21ce31a65438af983" +"dependency_report_evidence.jsonl" "derived_aggregate" "1520298" "178ef20f7103a2109ce7cd578633db7a9cbd6e3fa05e0fa3f9fb1841fbb6386e" "published" "" "dependency_report_evidence.jsonl" "178ef20f7103a2109ce7cd578633db7a9cbd6e3fa05e0fa3f9fb1841fbb6386e" +"discovery_universe.tsv" "derived_aggregate" "314023" "03f7a5c679f3692cce6d3d7fddcfcd93785e05509c090d16f144923dfdc6f698" "published" "" "discovery_universe.tsv" "03f7a5c679f3692cce6d3d7fddcfcd93785e05509c090d16f144923dfdc6f698" +"integration_gate_decision.json" "derived_aggregate" "5276" "4d0b3599436dc500fc188329fa0c5c1a86672533aab76a823c73725f0efbb357" "published" "" "integration_gate_decision.json" "4d0b3599436dc500fc188329fa0c5c1a86672533aab76a823c73725f0efbb357" +"integration_report.md" "derived_aggregate" "292" "4bcfbd244336e1c50b8c1df1a2637520e8e74fefbc840f748d2a757e5031bfa7" "published" "" "integration_report.md" "4bcfbd244336e1c50b8c1df1a2637520e8e74fefbc840f748d2a757e5031bfa7" +"publication_manifest.json" "derived_aggregate" "583" "27341a9892790c6e80370d114d962ca69121b7a6ce806cef794beef21d7126ac" "published" "" "publication_manifest.json" "27341a9892790c6e80370d114d962ca69121b7a6ce806cef794beef21d7126ac" +"release_closure_manifest.json" "derived_aggregate" "425" "d591c6ca1b557292eb701a7bee2e6bc59d41d3c4f104fb7bdc2696b43cb09d0e" "published" "" "release_closure_manifest.json" "d591c6ca1b557292eb701a7bee2e6bc59d41d3c4f104fb7bdc2696b43cb09d0e" +"release_preflight.json" "derived_aggregate" "1482" "80d6e451afd810e1dcf241bd2b59ace4fd91539af3e39a160b0415422a55500b" "published" "" "release_preflight.json" "80d6e451afd810e1dcf241bd2b59ace4fd91539af3e39a160b0415422a55500b" +"release_readiness.json" "derived_aggregate" "3102" "42343990be9f6596c1b1ba7673d9e7da0100a4703dd51c9cbe7dc6141f37d22c" "published" "" "release_readiness.json" "42343990be9f6596c1b1ba7673d9e7da0100a4703dd51c9cbe7dc6141f37d22c" +"release_report.md" "derived_aggregate" "211" "d4d79fa24b4272794a67115102256544706f77a08c99c1093827634390f5565d" "published" "" "release_report.md" "d4d79fa24b4272794a67115102256544706f77a08c99c1093827634390f5565d" +"release_summary.json" "derived_aggregate" "4945" "842eeaf93ae93fd0d949defdad0257f475602f78dc2f74ea725d8344cb8d1e25" "published" "" "release_summary.json" "842eeaf93ae93fd0d949defdad0257f475602f78dc2f74ea725d8344cb8d1e25" +"reproducibility_summary.json" "derived_aggregate" "9550" "9934bdf6c52ad9f78b18d932b0f867d8e7fc6837d230193de907f7f315c8b3a8" "published" "" "reproducibility_summary.json" "9934bdf6c52ad9f78b18d932b0f867d8e7fc6837d230193de907f7f315c8b3a8" +"selected_target_profiles.tsv" "derived_aggregate" "844159" "d23691b944502d178d359f2e69c2bd78155c0e50b6db8c44435cff7f47666162" "published" "" "selected_target_profiles.tsv" "d23691b944502d178d359f2e69c2bd78155c0e50b6db8c44435cff7f47666162" +"source_manifest.json" "derived_aggregate" "1801" "a6feed7a2c15498f129d93b604cdcfe4f2abe08c862841d23973f9236fef4e5c" "published" "" "source_manifest.json" 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diff --git a/data/releases/depmap/DepMap_Public_26Q1/selected_target_profiles.tsv b/data/releases/depmap/DepMap_Public_26Q1/selected_target_profiles.tsv new file mode 100644 index 0000000..ebd4264 --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/selected_target_profiles.tsv @@ -0,0 +1,332 @@ +target canonical_gene_identity profile_available coverage_status context_model_count reference_model_count gene_effect dependency_probability context_reference_comparison selectivity interpretation_state portable_provenance +ABL1 symbol:ABL1|entrez:25 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.05206080637452079, ""interquartile_range"": 0.13179040761692934, ""maximum"": 0.28090126723303777, ""mean"": 0.0004447170999685991, ""measured_model_count"": 56, ""median"": 0.016656009569385857, ""minimum"": -0.39424595195096673, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.07972960124240855, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.008384728233917674, ""interquartile_range"": 0.028339679307337506, ""maximum"": 0.3238668973345923, ""mean"": 0.038111215003978426, ""measured_model_count"": 56, ""median"": 0.018554196815730083, ""minimum"": 0.0019480816982328645, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.03672440754125518, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.005268596799601434, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.011589403973509934, ""pan_cancer_fraction"": 0.011589403973509934, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.009105960264900662, ""pan_cancer_fraction"": 0.009105960264900662, ""threshold"": 0.8}], ""gene_effect_mean"": 0.028025674336998208, ""gene_effect_median"": 0.029341478281553125}, ""dependency_probability_context_minus_non_context_median"": -0.0058653162345687, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.012152777777777778, ""non_context_fraction"": 0.012152777777777778, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.009548611111111112, ""non_context_fraction"": 0.009548611111111112, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.02938803350615787, ""gene_effect_context_minus_non_context_median"": 0.031052462802977448}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 29.62962962962963}" valid candidate_overlay.tsv;selected_target_profiles.tsv +ACKR3 symbol:ACKR3|entrez:57007 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.04688567353100497, ""interquartile_range"": 0.17672355876386034, ""maximum"": 0.3406804666190274, ""mean"": 0.044219612203129, ""measured_model_count"": 56, ""median"": 0.051971504824438984, ""minimum"": -0.248858520923774, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.12983788523285536, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.00480346215672851, ""interquartile_range"": 0.022247043897867892, ""maximum"": 0.1649058271995307, ""mean"": 0.023943900342633655, ""measured_model_count"": 56, ""median"": 0.012531187649904931, ""minimum"": 0.0007241920367250855, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.027050506054596402, 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signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 44.44444444444444}" valid candidate_overlay.tsv;selected_target_profiles.tsv +AFDN symbol:AFDN|entrez:4301 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.18632748263487175, ""interquartile_range"": 0.15100015383667187, ""maximum"": 0.194234342399614, ""mean"": -0.10401314871474741, ""measured_model_count"": 56, ""median"": -0.09824333463123369, ""minimum"": -0.3508544694256321, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.03532732879819988, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.02930714986928311, ""interquartile_range"": 0.08549755078471634, ""maximum"": 0.3273106965579132, ""mean"": 0.08008016796975555, ""measured_model_count"": 56, ""median"": 0.04490595607597833, ""minimum"": 0.002530139433360224, ""missing_fraction"": 0.0, ""missing_model_count"": 0, 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candidate_overlay.tsv;selected_target_profiles.tsv +AMER1 symbol:AMER1|entrez:139285 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.009345387043821714, ""interquartile_range"": 0.12788514596415662, ""maximum"": 0.4383787682074304, ""mean"": 0.07528086605188714, ""measured_model_count"": 56, ""median"": 0.08276667476476582, ""minimum"": -0.19040979327961766, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.13723053300797833, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.005306404228444668, ""interquartile_range"": 0.01706158235075618, ""maximum"": 0.149077231539901, ""mean"": 0.018513075756905417, ""measured_model_count"": 56, ""median"": 0.009990647380253341, ""minimum"": 0.00021627471873552294, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.022367986579200846, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, 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56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.03646513983227573, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.25, ""difference"": 0.049668874172185434, ""pan_cancer_fraction"": 0.20033112582781457, ""threshold"": 0.5}, {""context_fraction"": 0.16071428571428573, ""difference"": 0.06054872280037844, ""pan_cancer_fraction"": 0.10016556291390728, ""threshold"": 0.8}], ""gene_effect_mean"": -0.0924020779430966, ""gene_effect_median"": -0.0586934200985495}, ""dependency_probability_context_minus_non_context_median"": 0.04286844721026127, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.25, ""difference"": 0.05208333333333334, ""non_context_fraction"": 0.19791666666666666, ""threshold"": 0.5}, {""context_fraction"": 0.16071428571428573, ""difference"": 0.0634920634920635, ""non_context_fraction"": 0.09722222222222222, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect 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eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 40.74074074074074}" valid candidate_overlay.tsv;selected_target_profiles.tsv +ARID2 symbol:ARID2|entrez:196528 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.4704228591773787, ""interquartile_range"": 0.40651398153145546, ""maximum"": 0.3411982550552147, ""mean"": -0.26655617429891615, ""measured_model_count"": 56, ""median"": -0.2207698686925888, ""minimum"": -0.996786364696395, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.0639088776459232, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.03116399473948154, ""interquartile_range"": 0.46389475167534294, ""maximum"": 0.9745826114257009, ""mean"": 0.27967584939597845, ""measured_model_count"": 56, ""median"": 0.15054546566780236, ""minimum"": 0.0022844621532051974, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 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sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.31199003147965054, ""interquartile_range"": 0.19505157988805688, ""maximum"": 0.20303160162622352, ""mean"": -0.2070263048606922, ""measured_model_count"": 56, ""median"": -0.23658966248001567, ""minimum"": -0.6261219152697686, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.11693845159159365, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.06743848309059797, ""interquartile_range"": 0.17343780682176396, ""maximum"": 0.7946224472456699, ""mean"": 0.1843216141685337, ""measured_model_count"": 56, ""median"": 0.14648723614834475, ""minimum"": 0.004121566474625243, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.24087628991236193, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.05357142857142857, ""numerator"": 3, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, 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sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.037343116083035185, ""interquartile_range"": 0.26661108518976745, ""maximum"": 0.9196883699197242, ""mean"": 0.08748785591226547, ""measured_model_count"": 56, ""median"": 0.08289157811043477, ""minimum"": -0.7764618367290135, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.22926796910673228, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.001998134253073587, ""interquartile_range"": 0.0260986272540997, ""maximum"": 0.8778227499507888, ""mean"": 0.06161891085070346, ""measured_model_count"": 56, ""median"": 0.009616196179705327, ""minimum"": 0.0, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.028096761507173287, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.03571428571428571, ""numerator"": 2, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.017857142857142856, 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true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 77.77777777777777}" valid candidate_overlay.tsv;selected_target_profiles.tsv +B2M symbol:B2M|entrez:567 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.03419536124041851, ""interquartile_range"": 0.13539073572534133, ""maximum"": 0.222441908549175, ""mean"": 0.02537352064559218, ""measured_model_count"": 56, ""median"": 0.015821163143747298, ""minimum"": -0.26075783687617665, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.10119537448492283, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.006961531439831104, ""interquartile_range"": 0.02038009892374358, ""maximum"": 0.23444542085876965, ""mean"": 0.025135791460166153, ""measured_model_count"": 56, ""median"": 0.0164348942055268, ""minimum"": 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"{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 55.55555555555556}" valid candidate_overlay.tsv;selected_target_profiles.tsv +BAP1 symbol:BAP1|entrez:8314 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.7617301000041377, ""interquartile_range"": 0.39215821877949375, ""maximum"": -0.027665093614035463, ""mean"": -0.580660108206857, ""measured_model_count"": 56, ""median"": -0.5909145722746947, ""minimum"": -1.1970868602866886, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.3695718812246439, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.30705277763360284, ""interquartile_range"": 0.5817669754730993, ""maximum"": 0.9966187017789548, ""mean"": 0.6221644187853995, ""measured_model_count"": 56, ""median"": 0.7153010101416735, 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"{""available"": true, ""first_quartile"": -0.11420819046622246, ""interquartile_range"": 0.16659082868984246, ""maximum"": 0.43518189292339327, ""mean"": -0.045648604296433484, ""measured_model_count"": 56, ""median"": -0.056271293868629293, ""minimum"": -0.5045098076749046, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.052382638223619986, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.013988075492537793, ""interquartile_range"": 0.044676824510456764, ""maximum"": 0.6734265664462808, ""mean"": 0.060102345993402966, ""measured_model_count"": 56, ""median"": 0.033069240860764355, ""minimum"": 0.0008709175060067826, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.058664900002994555, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.017857142857142856, ""numerator"": 1, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.0013133876807193273, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.017857142857142856, ""difference"": 0.005439924314096499, ""pan_cancer_fraction"": 0.012417218543046357, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0024834437086092716, ""pan_cancer_fraction"": 0.0024834437086092716, ""threshold"": 0.8}], ""gene_effect_mean"": 0.0032663000309570214, ""gene_effect_median"": -0.012237703308827015}, ""dependency_probability_context_minus_non_context_median"": 0.0013133876807193273, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.017857142857142856, ""difference"": 0.005704365079365078, ""non_context_fraction"": 0.012152777777777778, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0026041666666666665, ""non_context_fraction"": 0.0026041666666666665, 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0.07829039804553907, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.007893891610742113, ""interquartile_range"": 0.023567574776098024, ""maximum"": 0.2051689240725753, ""mean"": 0.024793767381785202, ""measured_model_count"": 56, ""median"": 0.018108339873370675, ""minimum"": 0.0026566262890120834, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.03146146638684014, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.0008022985700595793, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.014900662251655629, ""pan_cancer_fraction"": 0.014900662251655629, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 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lineages."", ""eligible_lineage_count"": 28, ""value"": 70.37037037037037}" valid candidate_overlay.tsv;selected_target_profiles.tsv +BCL2 symbol:BCL2|entrez:596 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.08696651149816556, ""interquartile_range"": 0.14561016392955564, ""maximum"": 0.2680923594186532, ""mean"": -0.016920171192513926, ""measured_model_count"": 56, ""median"": -0.025311452898357994, ""minimum"": -0.25176194650284295, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.05864365243139008, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.012691998621583553, ""interquartile_range"": 0.03380030655700515, ""maximum"": 0.161056642128686, ""mean"": 0.03713254238273757, ""measured_model_count"": 56, ""median"": 0.02454383022252416, ""minimum"": 0.0023418864731136555, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 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-0.23320556013071192, ""minimum"": -0.9150034496838594, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.0518927469686651, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.03469806330531005, ""interquartile_range"": 0.2717156659809888, ""maximum"": 0.9363484371526809, ""mean"": 0.24510724830209973, ""measured_model_count"": 56, ""median"": 0.14987003186885173, ""minimum"": 6.792628342980656e-05, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.30641372928629884, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.19642857142857142, ""numerator"": 11, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.07142857142857142, ""numerator"": 4, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.04722901062703447, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.19642857142857142, ""difference"": 0.055700094607379375, ""pan_cancer_fraction"": 0.14072847682119205, ""threshold"": 0.5}, {""context_fraction"": 0.07142857142857142, ""difference"": 0.029210028382213808, ""pan_cancer_fraction"": 0.042218543046357616, ""threshold"": 0.8}], ""gene_effect_mean"": -0.05197525956023036, ""gene_effect_median"": -0.0496702568894708}, ""dependency_probability_context_minus_non_context_median"": 0.0495749823570763, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.19642857142857142, ""difference"": 0.05840773809523808, ""non_context_fraction"": 0.13802083333333334, ""threshold"": 0.5}, {""context_fraction"": 0.07142857142857142, ""difference"": 0.030629960317460313, ""non_context_fraction"": 0.04079861111111111, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", 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0.09072755309577211, ""maximum"": 0.8980221838973915, ""mean"": 0.08478326576217181, ""measured_model_count"": 56, ""median"": 0.03968158389728285, ""minimum"": 0.0014820722411286198, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.10769860422679713, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.017857142857142856, ""numerator"": 1, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.017857142857142856, ""numerator"": 1, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.01015602430234061, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.017857142857142856, ""difference"": -0.03512298959318827, ""pan_cancer_fraction"": 0.052980132450331126, ""threshold"": 0.5}, {""context_fraction"": 0.017857142857142856, ""difference"": 0.0004730368968779569, ""pan_cancer_fraction"": 0.0173841059602649, ""threshold"": 0.8}], ""gene_effect_mean"": 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33.333333333333336}" valid candidate_overlay.tsv;selected_target_profiles.tsv +BCOR symbol:BCOR|entrez:54880 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.09843137692846265, ""interquartile_range"": 0.3024111110874371, ""maximum"": 0.5123476618974896, ""mean"": 0.043399310001232275, ""measured_model_count"": 56, ""median"": 0.025163160100960116, ""minimum"": -0.46608548605258826, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.2039797341589745, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.004385523455098974, ""interquartile_range"": 0.049122236208953576, ""maximum"": 0.5695078292114721, ""mean"": 0.04532958920474263, ""measured_model_count"": 56, ""median"": 0.01380619756232246, ""minimum"": 0.00015610740691107978, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.05350775966405255, ""threshold_fractions"": [{""denominator"": 56, 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0.10564126028540002, ""minimum"": -0.6082875411667698, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.22835437659217828, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0023587471886702166, ""interquartile_range"": 0.011221787353487667, ""maximum"": 0.7004279011526633, ""mean"": 0.04059999544600247, ""measured_model_count"": 56, ""median"": 0.007299775968082389, ""minimum"": 0.00014814138376582694, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.013580534542157883, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.03571428571428571, ""numerator"": 2, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.003567309948364188, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.03571428571428571, ""difference"": 0.028263954588457898, ""pan_cancer_fraction"": 0.0074503311258278145, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.8}], ""gene_effect_mean"": 0.019726784915498313, ""gene_effect_median"": 0.0258835663828344}, ""dependency_probability_context_minus_non_context_median"": -0.003764269348550839, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.03571428571428571, ""difference"": 0.029637896825396824, ""non_context_fraction"": 0.006076388888888889, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.020685725848890543, ""gene_effect_context_minus_non_context_median"": 0.027067192809979018}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 40.74074074074074}" valid candidate_overlay.tsv;selected_target_profiles.tsv +BIRC3 symbol:BIRC3|entrez:330 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.053832945649035846, ""interquartile_range"": 0.17211190378930316, ""maximum"": 0.29394174579102555, ""mean"": 0.021754678809343127, ""measured_model_count"": 56, ""median"": 0.0066408270165531635, ""minimum"": -0.27705052981998146, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.11827895814026732, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.006081698993193586, ""interquartile_range"": 0.0270064902459861, ""maximum"": 0.2690632218111069, ""mean"": 0.029979679761486938, ""measured_model_count"": 56, ""median"": 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[{""context_fraction"": 0.0, ""difference"": -0.003472222222222222, ""non_context_fraction"": 0.003472222222222222, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.02624571880988088, ""gene_effect_context_minus_non_context_median"": -0.0407441913722429}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 88.88888888888889}" valid candidate_overlay.tsv;selected_target_profiles.tsv +BRAF symbol:BRAF|entrez:673 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -1.6227668727162368, ""interquartile_range"": 0.9795415688905247, ""maximum"": -0.015881149663220406, ""mean"": -1.1769393408178332, ""measured_model_count"": 56, ""median"": -1.2347703095627218, ""minimum"": -2.6355354158678552, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.6432253038257121, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.8542815144561293, ""interquartile_range"": 0.14570215220149452, ""maximum"": 1.0, ""mean"": 0.7983333399564246, ""measured_model_count"": 56, ""median"": 0.9910996581121145, ""minimum"": 0.018849964783263323, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.9999836666576238, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.7857142857142857, ""numerator"": 44, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.75, ""numerator"": 42, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.941093110695153, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.7857142857142857, ""difference"": 0.690515610217597, ""pan_cancer_fraction"": 0.09519867549668874, ""threshold"": 0.5}, {""context_fraction"": 0.75, ""difference"": 0.6846026490066225, ""pan_cancer_fraction"": 0.06539735099337748, ""threshold"": 0.8}], ""gene_effect_mean"": -0.9973071133238599, ""gene_effect_median"": -1.1421352404225718}, ""dependency_probability_context_minus_non_context_median"": 0.943697459010603, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.7857142857142857, ""difference"": 0.7240823412698413, ""non_context_fraction"": 0.06163194444444445, ""threshold"": 0.5}, {""context_fraction"": 0.75, ""difference"": 0.7178819444444444, ""non_context_fraction"": 0.03211805555555555, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -1.0457873202215475, ""gene_effect_context_minus_non_context_median"": -1.1485856638282403}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 100.0}" valid candidate_overlay.tsv;selected_target_profiles.tsv +BRCA1 symbol:BRCA1|entrez:672 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.8334513137692443, ""interquartile_range"": 0.3666416803437246, ""maximum"": 0.062275150039045934, ""mean"": -0.6446669874885088, ""measured_model_count"": 56, ""median"": -0.6447037480808876, ""minimum"": -1.4679161979282245, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.46680963342551973, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.5092257497253594, ""interquartile_range"": 0.4183593833250353, ""maximum"": 0.9994909191982082, ""mean"": 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symbol:BRCA2|entrez:675 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.6488829996539245, ""interquartile_range"": 0.2518526421601791, ""maximum"": -0.11644136524611565, ""mean"": -0.5194239412699343, ""measured_model_count"": 56, ""median"": -0.5458386512220574, ""minimum"": -0.9883316064136789, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.3970303574937454, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.3920368984175355, ""interquartile_range"": 0.4198271479602616, ""maximum"": 0.9795182103056468, ""mean"": 0.5793265400728955, ""measured_model_count"": 56, ""median"": 0.6356233831085945, ""minimum"": 0.047399772777465814, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.8118640463777971, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.625, ""numerator"": 35, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.2857142857142857, ""numerator"": 16, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.041063484097139114, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.625, ""difference"": 0.04387417218543044, ""pan_cancer_fraction"": 0.5811258278145696, ""threshold"": 0.5}, {""context_fraction"": 0.2857142857142857, ""difference"": 0.00011825922421948576, ""pan_cancer_fraction"": 0.2855960264900662, ""threshold"": 0.8}], ""gene_effect_mean"": -0.0015668993950327392, ""gene_effect_median"": -0.029499749646440088}, ""dependency_probability_context_minus_non_context_median"": 0.044335610678987836, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.625, ""difference"": 0.04600694444444442, ""non_context_fraction"": 0.5789930555555556, ""threshold"": 0.5}, {""context_fraction"": 0.2857142857142857, ""difference"": 0.0001240079365079083, 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""missing_model_count"": 0, ""third_quartile"": 0.12685067575195583, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.00500462514257108, ""interquartile_range"": 0.013542976338508669, ""maximum"": 0.07572924687956509, ""mean"": 0.014028321936522852, ""measured_model_count"": 56, ""median"": 0.0076650310535126605, ""minimum"": 0.0008221952078158884, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.01854760148107975, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.0017194904093865027, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 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valid candidate_overlay.tsv;selected_target_profiles.tsv +BRD4 symbol:BRD4|entrez:23476 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -1.248457530692548, ""interquartile_range"": 0.31380168154055843, ""maximum"": -0.23565820283589978, ""mean"": -1.077419296229426, ""measured_model_count"": 56, ""median"": -1.107477935554086, ""minimum"": -1.7448082336119686, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.9346558491519896, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.955950792547962, ""interquartile_range"": 0.03830238730638025, ""maximum"": 0.9999959988125812, ""mean"": 0.9347159273213392, ""measured_model_count"": 56, ""median"": 0.9859241206511045, ""minimum"": 0.16171450657858166, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.9942531798543423, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.9642857142857143, 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-0.21445633651626686, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.07444228946938104, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.009506480463942741, ""interquartile_range"": 0.01914368707509713, ""maximum"": 0.17509651908925622, ""mean"": 0.022697174251634644, ""measured_model_count"": 56, ""median"": 0.014886149558598682, ""minimum"": 0.0014470532586933651, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.02865016753903987, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.007619040350417529, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.0074503311258278145, ""pan_cancer_fraction"": 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""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 18.51851851851852}" valid candidate_overlay.tsv;selected_target_profiles.tsv +BUB1B symbol:BUB1B|entrez:701 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -1.3026861749001495, ""interquartile_range"": 0.34471355076042975, ""maximum"": -0.35062174656503176, ""mean"": -1.1293619487648725, ""measured_model_count"": 56, ""median"": -1.1239831043751725, ""minimum"": -1.9513382130061605, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.9579726241397197, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.9661276307634157, ""interquartile_range"": 0.027854131010518257, ""maximum"": 1.0, ""mean"": 0.9478580814276604, ""measured_model_count"": 56, ""median"": 0.9837485018692456, ""minimum"": 0.27364189485863244, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.9939817617739339, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.9821428571428571, ""numerator"": 55, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.9285714285714286, ""numerator"": 52, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.004764787764668599, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.9821428571428571, ""difference"": -0.00047303689687805406, ""pan_cancer_fraction"": 0.9826158940397351, ""threshold"": 0.5}, {""context_fraction"": 0.9285714285714286, ""difference"": -0.02838221381267736, ""pan_cancer_fraction"": 0.956953642384106, ""threshold"": 0.8}], ""gene_effect_mean"": 0.09650160394376806, ""gene_effect_median"": 0.08149630964729271}, ""dependency_probability_context_minus_non_context_median"": -0.0049250007582350985, 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"{""available"": true, ""first_quartile"": -0.06948366200968034, ""interquartile_range"": 0.12410483739837593, ""maximum"": 0.22152661199200682, ""mean"": -0.013247144110869868, ""measured_model_count"": 56, ""median"": -0.019408167580945213, ""minimum"": -0.3736384929932119, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.054621175388695584, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.01215263379668628, ""interquartile_range"": 0.02561710835008954, ""maximum"": 0.3270060202736238, ""mean"": 0.037954791056176954, ""measured_model_count"": 56, ""median"": 0.02156477750214402, ""minimum"": 0.0011308355940113652, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.03776974214677582, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.008126721128793965, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.0016556291390728477, ""pan_cancer_fraction"": 0.0016556291390728477, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.8}], ""gene_effect_mean"": 0.023986554352201293, ""gene_effect_median"": 0.017300102971426506}, ""dependency_probability_context_minus_non_context_median"": -0.008561961886107583, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.001736111111111111, ""non_context_fraction"": 0.001736111111111111, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.02515256741098892, ""gene_effect_context_minus_non_context_median"": 0.018531630100138224}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 33.333333333333336}" valid candidate_overlay.tsv;selected_target_profiles.tsv +CARD11 symbol:CARD11|entrez:84433 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.09562676156794828, ""interquartile_range"": 0.19020488634525662, ""maximum"": 0.404261290756003, ""mean"": -0.01514292880487186, ""measured_model_count"": 56, ""median"": -0.00843369100614956, ""minimum"": -0.54090902690978, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.09457812477730834, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 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candidate_overlay.tsv;selected_target_profiles.tsv +CARS1 symbol:CARS1|entrez:833 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -1.8026753461573768, ""interquartile_range"": 0.3885820681187324, ""maximum"": -0.8250676982589952, ""mean"": -1.6092899115753092, ""measured_model_count"": 56, ""median"": -1.5980364353584418, ""minimum"": -2.3420142033697706, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -1.4140932780386444, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.9965804422428789, ""interquartile_range"": 0.0034195577571211055, ""maximum"": 1.0, ""mean"": 0.9922324381369838, ""measured_model_count"": 56, ""median"": 0.9999665853145443, ""minimum"": 0.8994039933591144, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 1.0, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 1.0, ""numerator"": 56, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 1.0, ""numerator"": 56, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -1.52871546978961e-05, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 1.0, ""difference"": 0.0016556291390728006, ""pan_cancer_fraction"": 0.9983443708609272, ""threshold"": 0.5}, {""context_fraction"": 1.0, ""difference"": 0.004966887417218513, ""pan_cancer_fraction"": 0.9950331125827815, ""threshold"": 0.8}], ""gene_effect_mean"": 0.08020409235119175, ""gene_effect_median"": 0.08857204807747632}, ""dependency_probability_context_minus_non_context_median"": -1.6309468427122553e-05, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 1.0, ""difference"": 0.0017361111111111605, ""non_context_fraction"": 0.9982638888888888, ""threshold"": 0.5}, {""context_fraction"": 1.0, ""difference"": 0.00520833333333337, ""non_context_fraction"": 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-0.0008278145695364238, ""pan_cancer_fraction"": 0.0008278145695364238, ""threshold"": 0.8}], ""gene_effect_mean"": -0.0277111166708659, ""gene_effect_median"": -0.03366897379591392}, ""dependency_probability_context_minus_non_context_median"": 9.028752303627194e-05, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.0008680555555555555, ""non_context_fraction"": 0.0008680555555555555, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0008680555555555555, ""non_context_fraction"": 0.0008680555555555555, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.029058184842366372, ""gene_effect_context_minus_non_context_median"": -0.035154619781945506}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 62.96296296296296}" valid candidate_overlay.tsv;selected_target_profiles.tsv +CBFA2T3 symbol:CBFA2T3|entrez:863 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.136964140758632, ""interquartile_range"": 0.16167139541119036, ""maximum"": 0.21418474445863944, ""mean"": -0.05229143749802029, ""measured_model_count"": 56, ""median"": -0.01977128242853117, ""minimum"": -0.4116048408666105, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.02470725465255836, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.015136985019785953, ""interquartile_range"": 0.05489342649673515, ""maximum"": 0.3112207868780006, ""mean"": 0.05585963773120791, ""measured_model_count"": 56, ""median"": 0.02561603909201212, ""minimum"": 0.0020054058447227492, ""missing_fraction"": 0.0, ""missing_model_count"": 0, 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[{""context_fraction"": 0.0, ""difference"": -0.0041390728476821195, ""pan_cancer_fraction"": 0.0041390728476821195, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0008278145695364238, ""pan_cancer_fraction"": 0.0008278145695364238, ""threshold"": 0.8}], ""gene_effect_mean"": 0.004217348259192944, ""gene_effect_median"": -0.004799686634262463}, ""dependency_probability_context_minus_non_context_median"": -0.00069776111089127, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.004340277777777778, ""non_context_fraction"": 0.004340277777777778, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0008680555555555555, ""non_context_fraction"": 0.0008680555555555555, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 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""maximum"": -0.05330788682190524, ""mean"": -1.8967774740528005, ""measured_model_count"": 56, ""median"": -1.828765775143998, ""minimum"": -3.3354607159421072, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -1.1986866801237686, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.9930169828579302, ""interquartile_range"": 0.006983017142069836, ""maximum"": 1.0, ""mean"": 0.9517735651535275, ""measured_model_count"": 56, ""median"": 1.0, ""minimum"": 0.045554294167438766, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 1.0, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.9642857142857143, ""numerator"": 54, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.9107142857142857, ""numerator"": 51, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.01699677125141008, 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group."", ""gene_effect_context_minus_non_context_mean"": -0.6824975150977388, ""gene_effect_context_minus_non_context_median"": -0.7884990157905569}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 85.18518518518519}" valid candidate_overlay.tsv;selected_target_profiles.tsv +CCND2 symbol:CCND2|entrez:894 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.15579197515311352, ""interquartile_range"": 0.17786015005357908, ""maximum"": 0.37138012941204834, ""mean"": -0.05966427508651161, ""measured_model_count"": 56, ""median"": -0.08633474069631311, ""minimum"": -0.22837474318280288, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.022068174900465552, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.013285731471925577, ""interquartile_range"": 0.06560912247822459, ""maximum"": 0.1904888154369347, ""mean"": 0.05466906017495544, ""measured_model_count"": 56, ""median"": 0.04813965995942092, ""minimum"": 0.0008839430891336923, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.07889485395015017, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.00577555222621233, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.06705298013245033, ""pan_cancer_fraction"": 0.06705298013245033, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.048841059602649006, ""pan_cancer_fraction"": 0.048841059602649006, ""threshold"": 0.8}], ""gene_effect_mean"": 0.10164960237461951, ""gene_effect_median"": 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symbol:CD274|entrez:29126 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.1219432529423023, ""interquartile_range"": 0.14942892394873147, ""maximum"": 0.5564732732340494, ""mean"": 0.19436573097880774, ""measured_model_count"": 56, ""median"": 0.1863639156999815, ""minimum"": -0.07863180936507297, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.27137217689103377, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.001499226517437284, ""interquartile_range"": 0.0064206254383672645, ""maximum"": 0.036701970754130495, ""mean"": 0.006382432047991671, ""measured_model_count"": 56, ""median"": 0.0035318069749596765, ""minimum"": 8.135797076424987e-05, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.007919851955804549, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, 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the context group."", ""gene_effect_context_minus_non_context_mean"": 0.01527799278063105, ""gene_effect_context_minus_non_context_median"": 0.00343451210457299}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 25.925925925925927}" valid candidate_overlay.tsv;selected_target_profiles.tsv +CD79A symbol:CD79A|entrez:973 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.059678830445944894, ""interquartile_range"": 0.09997205789462581, ""maximum"": 0.26466406443135215, ""mean"": 0.1122462807561854, ""measured_model_count"": 56, ""median"": 0.1100920547426244, ""minimum"": -0.02926449099631112, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.1596508883405707, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.003938865463013505, 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candidate_overlay.tsv;selected_target_profiles.tsv +CD8A symbol:CD8A|entrez:925 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.027430912377545535, ""interquartile_range"": 0.13942569209925004, ""maximum"": 0.46165860344769677, ""mean"": 0.045785073452028605, ""measured_model_count"": 56, ""median"": 0.03928974584334112, ""minimum"": -0.26540822030616257, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.11199477972170452, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.007483582094896921, ""interquartile_range"": 0.017911250672013962, ""maximum"": 0.201806266723021, ""mean"": 0.02445228992923763, ""measured_model_count"": 56, ""median"": 0.011938528707279468, ""minimum"": 0.0002748136637528369, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.02539483276691088, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, 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0.00343379789740067, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0180917185977245, ""interquartile_range"": 0.06286002234786717, ""maximum"": 0.874379672670159, ""mean"": 0.10329287088429209, ""measured_model_count"": 56, ""median"": 0.04375955195407501, ""minimum"": 0.0028271732493434652, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.08095174094559167, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.03571428571428571, ""numerator"": 2, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.03571428571428571, ""numerator"": 2, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -6.01063460411444e-05, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.03571428571428571, ""difference"": -0.008159886471144753, ""pan_cancer_fraction"": 0.043874172185430466, ""threshold"": 0.5}, {""context_fraction"": 0.03571428571428571, ""difference"": 0.010879848628192999, ""pan_cancer_fraction"": 0.024834437086092714, ""threshold"": 0.8}], ""gene_effect_mean"": -0.007372814336056799, ""gene_effect_median"": 0.005760578127514945}, ""dependency_probability_context_minus_non_context_median"": -6.01063460411444e-05, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.03571428571428571, ""difference"": -0.008556547619047623, ""non_context_fraction"": 0.044270833333333336, ""threshold"": 0.5}, {""context_fraction"": 0.03571428571428571, ""difference"": 0.011408730158730156, ""non_context_fraction"": 0.024305555555555556, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.007731215032948366, ""gene_effect_context_minus_non_context_median"": 0.005760578127514945}" 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56 2098 "{""available"": true, ""first_quartile"": -1.1460787729249597, ""interquartile_range"": 0.6487242724872709, ""maximum"": 0.14819456849436097, ""mean"": -0.9690295177076944, ""measured_model_count"": 56, ""median"": -0.7802086880629331, ""minimum"": -2.6012252653565273, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.4973545004376888, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.5276778197266463, ""interquartile_range"": 0.46063984426021753, ""maximum"": 1.0, ""mean"": 0.7625651007343259, ""measured_model_count"": 56, ""median"": 0.8640150958074966, ""minimum"": 0.0044507692556070445, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.9883176639868638, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.7857142857142857, ""numerator"": 44, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.5892857142857143, ""numerator"": 33, ""threshold"": 0.8}], 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candidate_overlay.tsv;selected_target_profiles.tsv +CLPTM1L symbol:CLPTM1L|entrez:81037 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.03365827977140918, ""interquartile_range"": 0.15583008785031374, ""maximum"": 0.37251074770739345, ""mean"": 0.12263371690035856, ""measured_model_count"": 56, ""median"": 0.11157894179367531, ""minimum"": -0.1922015107403494, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.18948836762172291, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0033575428305555734, ""interquartile_range"": 0.009723968496991963, ""maximum"": 0.07590534725685125, ""mean"": 0.011504028916612676, ""measured_model_count"": 56, ""median"": 0.006899426529077324, ""minimum"": 0.00046431606993314206, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.013081511327547536, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, 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candidate_overlay.tsv;selected_target_profiles.tsv +CREBBP symbol:CREBBP|entrez:1387 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.12137022065317296, ""interquartile_range"": 0.35378815047690215, ""maximum"": 0.7647019650205802, ""mean"": 0.07497423361604329, ""measured_model_count"": 56, ""median"": 0.12434295478017252, ""minimum"": -0.6954204183084232, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.23241792982372922, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0021103076008664352, ""interquartile_range"": 0.04964725377051653, ""maximum"": 0.8631610740408037, ""mean"": 0.06300891143216202, ""measured_model_count"": 56, ""median"": 0.006852358906610696, ""minimum"": 2.812680241471588e-07, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.05175756137138296, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 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most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 33.333333333333336}" valid candidate_overlay.tsv;selected_target_profiles.tsv +CSF3R symbol:CSF3R|entrez:1441 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.171973299240679, ""interquartile_range"": 0.12121511297415707, ""maximum"": 0.18391648947435318, ""mean"": -0.11817486019417255, ""measured_model_count"": 56, ""median"": -0.1036037219983435, ""minimum"": -0.6312179909842395, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.050758186266521926, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.030544914905776988, ""interquartile_range"": 0.05752607440635536, ""maximum"": 0.6352167069178504, ""mean"": 0.08797870213130601, ""measured_model_count"": 56, ""median"": 0.05600813177010951, ""minimum"": 0.004903090995091903, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 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most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 37.03703703703704}" valid candidate_overlay.tsv;selected_target_profiles.tsv +CTNNB1 symbol:CTNNB1|entrez:1499 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.30307444434386505, ""interquartile_range"": 0.2000363522550953, ""maximum"": 0.05464336452334989, ""mean"": -0.22538887888625375, ""measured_model_count"": 56, ""median"": -0.20773415732109757, ""minimum"": -0.7761741014319005, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.10303809208876974, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.04604754552361335, ""interquartile_range"": 0.21650665079839038, ""maximum"": 0.8885074947332431, ""mean"": 0.192631362342245, ""measured_model_count"": 56, ""median"": 0.13451455384394487, ""minimum"": 0.010324586920754095, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 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sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.03134505628584463, ""interquartile_range"": 0.14056117568087112, ""maximum"": 0.24029992912418896, ""mean"": 0.04110868821178555, ""measured_model_count"": 56, ""median"": 0.05281410370015513, ""minimum"": -0.21141841880282625, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.10921611939502648, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.00658768123852596, ""interquartile_range"": 0.022355271394094645, ""maximum"": 0.10831268763368852, ""mean"": 0.0204631377324164, ""measured_model_count"": 56, ""median"": 0.012647935195006565, ""minimum"": 0.001717118643636866, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.028942952632620606, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, 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"{""available"": true, ""first_quartile"": -0.544977811841365, ""interquartile_range"": 0.26742254574989294, ""maximum"": 0.106113115533227, ""mean"": -0.4087807091327999, ""measured_model_count"": 56, ""median"": -0.383732915488141, ""minimum"": -1.3662485543529452, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.277555266091472, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.21600580895105526, ""interquartile_range"": 0.40819467544094223, ""maximum"": 0.9983879181677233, ""mean"": 0.42374344131493585, ""measured_model_count"": 56, ""median"": 0.4007934163278375, ""minimum"": 0.006374091952721311, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.6242004843919975, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.42857142857142855, ""numerator"": 24, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.10714285714285714, ""numerator"": 6, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.11380922710420216, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.42857142857142855, ""difference"": 0.12310785241248817, ""pan_cancer_fraction"": 0.3054635761589404, ""threshold"": 0.5}, {""context_fraction"": 0.10714285714285714, ""difference"": -0.023651844843897832, ""pan_cancer_fraction"": 0.13079470198675497, ""threshold"": 0.8}], ""gene_effect_mean"": -0.03430155764609022, ""gene_effect_median"": -0.053760835452685674}, ""dependency_probability_context_minus_non_context_median"": 0.12201466100433733, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.42857142857142855, ""difference"": 0.12909226190476186, ""non_context_fraction"": 0.2994791666666667, ""threshold"": 0.5}, {""context_fraction"": 0.10714285714285714, ""difference"": -0.02480158730158731, ""non_context_fraction"": 0.13194444444444445, 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""value"": 33.333333333333336}" valid candidate_overlay.tsv;selected_target_profiles.tsv +DDX3X symbol:DDX3X|entrez:1654 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.9698286536882877, ""interquartile_range"": 0.7569406323261909, ""maximum"": 0.3339853718118322, ""mean"": -0.6088234854143035, ""measured_model_count"": 56, ""median"": -0.6607130262900589, ""minimum"": -2.0147135010407675, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.21288802136209684, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.14926781403958722, ""interquartile_range"": 0.8089440313140834, ""maximum"": 1.0, ""mean"": 0.6154656913017502, ""measured_model_count"": 56, ""median"": 0.7872151954624422, ""minimum"": 0.001289807589254826, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.9582118453536707, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 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""maximum"": 0.2660120139862773, ""mean"": -0.0768374949690435, ""measured_model_count"": 56, ""median"": -0.08543314878433285, ""minimum"": -0.46622495115702955, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.06211244927086508, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.013536831847736476, ""interquartile_range"": 0.07782264300434415, ""maximum"": 0.5606370090600415, ""mean"": 0.08069588416595065, ""measured_model_count"": 56, ""median"": 0.05061839110667351, ""minimum"": 0.0011475887843435738, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.09135947485208062, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.017857142857142856, ""numerator"": 1, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 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true, ""first_quartile"": -0.6301650470635833, ""interquartile_range"": 0.4709206521961253, ""maximum"": 0.44756105949178754, ""mean"": -0.3907983166708622, ""measured_model_count"": 56, ""median"": -0.3520231118620166, ""minimum"": -1.34610578400845, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.15924439486745806, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0690136792815241, ""interquartile_range"": 0.6549061339214883, ""maximum"": 0.994735297730019, ""mean"": 0.4060882923478336, ""measured_model_count"": 56, ""median"": 0.30719246495550195, ""minimum"": 0.00014797171299792128, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.7239198132030125, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.375, ""numerator"": 21, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.23214285714285715, ""numerator"": 13, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.04992797303338542, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.375, ""difference"": 0.01572847682119205, ""pan_cancer_fraction"": 0.35927152317880795, ""threshold"": 0.5}, {""context_fraction"": 0.23214285714285715, ""difference"": 0.009460737937559138, ""pan_cancer_fraction"": 0.222682119205298, ""threshold"": 0.8}], ""gene_effect_mean"": -0.03225721062927511, ""gene_effect_median"": -0.03480287000380533}, ""dependency_probability_context_minus_non_context_median"": 0.05588253082748845, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.375, ""difference"": 0.01649305555555558, ""non_context_fraction"": 0.3585069444444444, ""threshold"": 0.5}, {""context_fraction"": 0.23214285714285715, ""difference"": 0.009920634920634941, ""non_context_fraction"": 0.2222222222222222, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect 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56}" "{""available"": true, ""first_quartile"": 0.10583038909718276, ""interquartile_range"": 0.14106667753996144, ""maximum"": 0.669070278252544, ""mean"": 0.21661886597937663, ""measured_model_count"": 56, ""median"": 0.1734088090428273, ""minimum"": 0.011341833442620627, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.2468970666371442, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.10714285714285714, ""numerator"": 6, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.02793739386262034, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.10714285714285714, ""difference"": -0.09401608325449386, ""pan_cancer_fraction"": 0.201158940397351, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.09850993377483444, ""pan_cancer_fraction"": 0.09850993377483444, 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28, ""value"": 33.333333333333336}" valid candidate_overlay.tsv;selected_target_profiles.tsv +ERBB3 symbol:ERBB3|entrez:2065 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.29677275810467674, ""interquartile_range"": 0.15902387121322126, ""maximum"": 0.10539895655935005, ""mean"": -0.2172892726108315, ""measured_model_count"": 56, ""median"": -0.2064135944999752, ""minimum"": -0.5667130081211204, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.13774888689145548, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0701533166345286, ""interquartile_range"": 0.14491007038238968, ""maximum"": 0.6026137920472711, ""mean"": 0.16367057810715754, ""measured_model_count"": 56, ""median"": 0.13126533178718724, ""minimum"": 0.01069996622191269, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.2150633870169183, ""threshold_fractions"": 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+ERCC3 symbol:ERCC3|entrez:2071 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -1.1181967186257906, ""interquartile_range"": 0.21936811054409455, ""maximum"": -0.1968165974284698, ""mean"": -0.9861971850757215, ""measured_model_count"": 56, ""median"": -1.0257305946001085, ""minimum"": -1.2003431761784857, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.8988286080816961, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.9546022888982366, ""interquartile_range"": 0.035122029420819545, ""maximum"": 0.9976916871199579, ""mean"": 0.9395766573450544, ""measured_model_count"": 56, ""median"": 0.9767427569343496, ""minimum"": 0.15568980756884207, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.9897243183190562, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.9821428571428571, ""numerator"": 55, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.9642857142857143, ""numerator"": 54, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.002812007009274531, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.9821428571428571, ""difference"": 0.002838221381267658, ""pan_cancer_fraction"": 0.9793046357615894, ""threshold"": 0.5}, {""context_fraction"": 0.9642857142857143, ""difference"": 0.033822138126773926, ""pan_cancer_fraction"": 0.9304635761589404, ""threshold"": 0.8}], ""gene_effect_mean"": 0.03186839973649114, ""gene_effect_median"": -0.01496544170922709}, ""dependency_probability_context_minus_non_context_median"": 0.002916995705352421, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.9821428571428571, ""difference"": 0.0029761904761904656, ""non_context_fraction"": 0.9791666666666666, ""threshold"": 0.5}, {""context_fraction"": 0.9642857142857143, 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true, ""first_quartile"": -0.39440710682115865, ""interquartile_range"": 0.2515883236857389, ""maximum"": 0.12296597316977459, ""mean"": -0.27177681109686624, ""measured_model_count"": 56, ""median"": -0.2676352166799574, ""minimum"": -0.8702254040849512, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.14281878313541974, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.06949355765826927, ""interquartile_range"": 0.39275603779407636, ""maximum"": 0.9139864368396176, ""mean"": 0.2615344748466097, ""measured_model_count"": 56, ""median"": 0.18706360909548436, ""minimum"": 0.00882008373465794, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.4622495954523456, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.21428571428571427, ""numerator"": 12, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.017857142857142856, ""numerator"": 1, ""threshold"": 0.8}], 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candidate_overlay.tsv;selected_target_profiles.tsv +FAT1 symbol:FAT1|entrez:2195 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.010190119994076867, ""interquartile_range"": 0.1327527813060256, ""maximum"": 0.3239877898348623, ""mean"": 0.05787560641765308, ""measured_model_count"": 56, ""median"": 0.04713508116369999, ""minimum"": -0.1477656314088705, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.12256266131194873, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.006042510039561404, ""interquartile_range"": 0.01801475636113281, ""maximum"": 0.12678724791693652, ""mean"": 0.019558783916784724, ""measured_model_count"": 56, ""median"": 0.013016969463129585, ""minimum"": 0.0013710596238751416, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.024057266400694215, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, 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context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.01308695176463142, ""gene_effect_context_minus_non_context_median"": -0.021291486324947137}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 66.66666666666667}" valid candidate_overlay.tsv;selected_target_profiles.tsv +FAT4 symbol:FAT4|entrez:79633 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.08010063621579745, ""interquartile_range"": 0.13017968110048778, ""maximum"": 0.21669532988519838, ""mean"": -0.025541252959918388, ""measured_model_count"": 56, ""median"": -0.023054746641925847, ""minimum"": -0.47842898548034124, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.050079044884690324, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.01326244371222652, ""interquartile_range"": 0.033213141154614684, ""maximum"": 0.3959491092740444, ""mean"": 0.039079867410627044, ""measured_model_count"": 56, ""median"": 0.026496833584941027, ""minimum"": 0.0022160403622951044, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.0464755848668412, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.0035919121449942, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.8}], ""gene_effect_mean"": 0.011374350608281528, 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sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.15074818038210167, ""interquartile_range"": 0.281308577050804, ""maximum"": 0.42220203584434846, ""mean"": -0.04560795363310931, ""measured_model_count"": 56, ""median"": -0.03427403620395675, ""minimum"": -0.6741261622322151, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.1305603966687023, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.007285169440329596, ""interquartile_range"": 0.09745011838978633, ""maximum"": 0.7905134474847286, ""mean"": 0.10611223844677944, ""measured_model_count"": 56, ""median"": 0.029319765084054497, ""minimum"": 0.0004413568234268305, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.10473528783011593, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.08928571428571429, ""numerator"": 5, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, 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""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.15758967119915746, ""gene_effect_context_minus_non_context_median"": 0.13709329218559274}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 11.11111111111111}" valid candidate_overlay.tsv;selected_target_profiles.tsv +FBXW7 symbol:FBXW7|entrez:55294 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.10168761872706197, ""interquartile_range"": 0.31951626522136356, ""maximum"": 0.7477705375903348, ""mean"": 0.07512290288357788, ""measured_model_count"": 56, ""median"": 0.08885012160126604, ""minimum"": -0.42999840215935103, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.21782864649430156, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0023602908105894663, ""interquartile_range"": 0.04698617022723407, ""maximum"": 0.3990660245341544, ""mean"": 0.048686281727830724, ""measured_model_count"": 56, ""median"": 0.00790827217292547, ""minimum"": 7.339235394045013e-07, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.04934646103782354, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.010836419724310722, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.052980132450331126, ""pan_cancer_fraction"": 0.052980132450331126, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 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most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 22.22222222222222}" valid candidate_overlay.tsv;selected_target_profiles.tsv +FCRL4 symbol:FCRL4|entrez:83417 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.182975187793387, ""interquartile_range"": 0.13243973999157846, ""maximum"": 0.14030049532262745, ""mean"": -0.11330662488132592, ""measured_model_count"": 56, ""median"": -0.10620558769013834, ""minimum"": -0.451675523595505, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.05053544780180854, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.03271037791063712, ""interquartile_range"": 0.057892317786895325, ""maximum"": 0.4302335386003559, ""mean"": 0.07745410574824914, ""measured_model_count"": 56, ""median"": 0.05680147102116183, ""minimum"": 0.003675204351939972, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 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0.003472222222222222, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0008680555555555555, ""non_context_fraction"": 0.0008680555555555555, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.020643988012623682, ""gene_effect_context_minus_non_context_median"": -0.01890243276653479}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 62.96296296296296}" valid candidate_overlay.tsv;selected_target_profiles.tsv +FGFR1 symbol:FGFR1|entrez:2260 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.10585312617805011, ""interquartile_range"": 0.1474329702619552, ""maximum"": 0.24676378195924795, ""mean"": -0.04075960883877906, ""measured_model_count"": 56, ""median"": -0.04514236242722311, ""minimum"": -0.45737015923785884, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.04157984408390509, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.013136544667759788, ""interquartile_range"": 0.042445470736148155, ""maximum"": 0.5845513123281094, ""mean"": 0.05509342663926976, ""measured_model_count"": 56, ""median"": 0.030469376280351304, ""minimum"": 0.0018396455361303317, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.05558201540390795, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.017857142857142856, ""numerator"": 1, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.01369994659970368, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 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symbol:FGFR3|entrez:2261 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.05194312301230575, ""interquartile_range"": 0.17413908661637087, ""maximum"": 0.3363122041950665, ""mean"": 0.03525864250811891, ""measured_model_count"": 56, ""median"": 0.04922997969645476, ""minimum"": -0.46980050826203773, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.12219596360406512, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.005922891813622169, ""interquartile_range"": 0.023690854120683086, ""maximum"": 0.37901610456587304, ""mean"": 0.036640727013179324, ""measured_model_count"": 56, ""median"": 0.015458308668818171, ""minimum"": 0.0005398320917780566, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.029613745934305255, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, 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22.22222222222222}" valid candidate_overlay.tsv;selected_target_profiles.tsv +H3-3B symbol:H3-3B|entrez:3021 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.48313503447175277, ""interquartile_range"": 0.21974635922869223, ""maximum"": -0.012604660993106698, ""mean"": -0.3755518963514822, ""measured_model_count"": 56, ""median"": -0.33933172423069585, ""minimum"": -0.830902835454018, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.26338867524306053, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.19076786329106843, ""interquartile_range"": 0.3226438251221172, ""maximum"": 0.9130818463893109, ""mean"": 0.36860403231261063, ""measured_model_count"": 56, ""median"": 0.3108532559759873, ""minimum"": 0.019520162834314427, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.5134116884131856, ""threshold_fractions"": [{""denominator"": 56, 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51.851851851851855}" valid candidate_overlay.tsv;selected_target_profiles.tsv +IDH1 symbol:IDH1|entrez:3417 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.15448357052904954, ""interquartile_range"": 0.1485721977747924, ""maximum"": 0.20896505721913816, ""mean"": -0.09337330784363378, ""measured_model_count"": 56, ""median"": -0.07154041810566106, ""minimum"": -1.0350852467755454, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.005911372754257127, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.02007757384147797, ""interquartile_range"": 0.06085228289583204, ""maximum"": 0.9942833245620363, ""mean"": 0.08093502900778993, ""measured_model_count"": 56, ""median"": 0.03720868827740238, ""minimum"": 0.0038582797922045104, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.08092985673731001, ""threshold_fractions"": [{""denominator"": 56, 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than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 59.25925925925926}" valid candidate_overlay.tsv;selected_target_profiles.tsv +IFNAR1 symbol:IFNAR1|entrez:3454 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.02072702775838113, ""interquartile_range"": 0.15827098898244746, ""maximum"": 0.6503786890171347, ""mean"": 0.12145333029466691, ""measured_model_count"": 56, ""median"": 0.10365599503808863, ""minimum"": -0.16933916992926473, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.1789980167408286, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.003956222562329722, ""interquartile_range"": 0.01411125018501198, ""maximum"": 0.07902273935717684, ""mean"": 0.013110592051675965, ""measured_model_count"": 56, ""median"": 0.00683742314520901, ""minimum"": 9.673493890419153e-06, ""missing_fraction"": 0.0, ""missing_model_count"": 0, 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means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 44.44444444444444}" valid candidate_overlay.tsv;selected_target_profiles.tsv +IFNGR1 symbol:IFNGR1|entrez:3459 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.03662359372573171, ""interquartile_range"": 0.08240767601439589, ""maximum"": 0.5871211700580072, ""mean"": 0.0897245542698267, ""measured_model_count"": 56, ""median"": 0.08379368461486343, ""minimum"": -0.1744025104314158, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.1190312697401276, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.005404275629848286, ""interquartile_range"": 0.008713219530913212, ""maximum"": 0.06268986152833818, ""mean"": 0.01167419637458284, ""measured_model_count"": 56, ""median"": 0.008325044038448394, ""minimum"": 0.000290948338437609, 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symbol:IKZF3|entrez:22806 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.15225471866134643, ""interquartile_range"": 0.1450957650450127, ""maximum"": 0.5687894421280447, ""mean"": -0.07457440753634013, ""measured_model_count"": 56, ""median"": -0.08258590755905212, ""minimum"": -0.4283817472108195, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.00715895361633373, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.020035342674531775, ""interquartile_range"": 0.06675520347815952, ""maximum"": 0.4832088876731502, ""mean"": 0.06720851685893349, ""measured_model_count"": 56, ""median"": 0.047431048431888424, ""minimum"": 0.00014254418116806933, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.0867905461526913, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, 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context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 77.77777777777777}" valid candidate_overlay.tsv;selected_target_profiles.tsv +IL2RB symbol:IL2RB|entrez:3560 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.06167574734909529, ""interquartile_range"": 0.11419653118966835, ""maximum"": 0.4361428141068317, ""mean"": -0.00577974216374198, ""measured_model_count"": 56, ""median"": 0.0038683297949551783, ""minimum"": -0.31092525578047747, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.052520783840573064, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.011368937411090727, ""interquartile_range"": 0.02233347339096224, ""maximum"": 0.24466414856941635, ""mean"": 0.03389348922793028, ""measured_model_count"": 56, ""median"": 0.020888460567987405, ""minimum"": 0.0003780927747437147, ""missing_fraction"": 0.0, ""missing_model_count"": 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"{""available"": true, ""first_quartile"": -0.09754301210474758, ""interquartile_range"": 0.12296515702841573, ""maximum"": 0.26037306954494316, ""mean"": -0.03541258134233933, ""measured_model_count"": 56, ""median"": -0.021794338384010233, ""minimum"": -0.4899942974308896, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.025422144923668153, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.013848609180153479, ""interquartile_range"": 0.03581323489428311, ""maximum"": 0.49436318873189083, ""mean"": 0.04739429910381706, ""measured_model_count"": 56, ""median"": 0.02736019181396147, ""minimum"": 0.0011200409618568816, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.04966184407443659, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], 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85.18518518518519}" valid candidate_overlay.tsv;selected_target_profiles.tsv +IRS4 symbol:IRS4|entrez:8471 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.18839419052946696, ""interquartile_range"": 0.1798390999941063, ""maximum"": 0.21201552366845364, ""mean"": -0.09293988067528866, ""measured_model_count"": 56, ""median"": -0.07806148005826202, ""minimum"": -0.38768029787152425, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.00855509053536067, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.018429753510722652, ""interquartile_range"": 0.07826150665683715, ""maximum"": 0.4219517244413161, ""mean"": 0.0786677639842874, ""measured_model_count"": 56, ""median"": 0.0474389800368865, ""minimum"": 0.003356154467398746, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.0966912601675598, ""threshold_fractions"": [{""denominator"": 56, 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negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 7.407407407407407}" valid candidate_overlay.tsv;selected_target_profiles.tsv +JAK2 symbol:JAK2|entrez:3717 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.09372960195593227, ""interquartile_range"": 0.09638480604756475, ""maximum"": 0.4345972003497355, ""mean"": 0.14725027992853618, ""measured_model_count"": 56, ""median"": 0.14140384507405612, ""minimum"": -0.10783153860797157, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.19011440800349702, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0034333194534452273, ""interquartile_range"": 0.0042969091439646915, ""maximum"": 0.044572665063286214, ""mean"": 0.007047471137138419, ""measured_model_count"": 56, ""median"": 0.005546648360096902, ""minimum"": 0.0003687940884532363, ""missing_fraction"": 0.0, 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77.77777777777777}" valid candidate_overlay.tsv;selected_target_profiles.tsv +KLF4 symbol:KLF4|entrez:9314 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.0866160725632556, ""interquartile_range"": 0.09094159645890684, ""maximum"": 0.29033441321163894, ""mean"": -0.036429378374868294, ""measured_model_count"": 56, ""median"": -0.045825769626115405, ""minimum"": -0.18846226428060717, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.0043255238956512385, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.01830988808607737, ""interquartile_range"": 0.031197954431363674, ""maximum"": 0.12728694959590328, ""mean"": 0.03673849894871195, ""measured_model_count"": 56, ""median"": 0.02931121522718555, ""minimum"": 0.0015769843027852257, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.049507842517441045, ""threshold_fractions"": [{""denominator"": 56, 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candidate_overlay.tsv;selected_target_profiles.tsv +KMT2C symbol:KMT2C|entrez:58508 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.002613878383379797, ""interquartile_range"": 0.22930347633925058, ""maximum"": 0.7588941965548464, ""mean"": 0.08533586436646227, ""measured_model_count"": 56, ""median"": 0.08688860720869607, ""minimum"": -0.5393806663773176, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.2266895979558708, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0032623542350772366, ""interquartile_range"": 0.023637002199571364, ""maximum"": 0.7548851600875993, ""mean"": 0.047657468264772414, ""measured_model_count"": 56, ""median"": 0.00790666231691314, ""minimum"": 3.015181277604221e-06, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.0268993564346486, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.017857142857142856, ""numerator"": 1, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.008378037643394922, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.017857142857142856, ""difference"": -0.005321665089877012, ""pan_cancer_fraction"": 0.023178807947019868, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0033112582781456954, ""pan_cancer_fraction"": 0.0033112582781456954, ""threshold"": 0.8}], ""gene_effect_mean"": 0.07308581728239892, ""gene_effect_median"": 0.056357339633505504}, ""dependency_probability_context_minus_non_context_median"": -0.00913467488608257, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.017857142857142856, ""difference"": -0.005580357142857144, ""non_context_fraction"": 0.0234375, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.003472222222222222, ""non_context_fraction"": 0.003472222222222222, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.07663860006696002, ""gene_effect_context_minus_non_context_median"": 0.059724463300712356}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 22.22222222222222}" valid candidate_overlay.tsv;selected_target_profiles.tsv +KMT2D symbol:KMT2D|entrez:8085 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.5054747400504007, ""interquartile_range"": 0.43801977053473673, ""maximum"": 0.4453175128783058, ""mean"": -0.27953827290798855, ""measured_model_count"": 56, ""median"": -0.2813972812521446, 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-0.05818353831598866, ""pan_cancer_fraction"": 0.3617549668874172, ""threshold"": 0.5}, {""context_fraction"": 0.16071428571428573, ""difference"": -0.021404919583727505, ""pan_cancer_fraction"": 0.18211920529801323, ""threshold"": 0.8}], ""gene_effect_mean"": 0.11216053843555868, ""gene_effect_median"": 0.07237576799848949}, ""dependency_probability_context_minus_non_context_median"": -0.13011903737267616, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.30357142857142855, ""difference"": -0.06101190476190477, ""non_context_fraction"": 0.3645833333333333, ""threshold"": 0.5}, {""context_fraction"": 0.16071428571428573, ""difference"": -0.022445436507936484, ""non_context_fraction"": 0.1831597222222222, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.11761278683173171, 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""dependency_probability_context_minus_non_context_median"": 0.04473365357168113, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.875, ""difference"": 0.06076388888888884, ""non_context_fraction"": 0.8142361111111112, ""threshold"": 0.5}, {""context_fraction"": 0.5357142857142857, ""difference"": 0.0530753968253968, ""non_context_fraction"": 0.4826388888888889, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.009350919945992131, ""gene_effect_context_minus_non_context_median"": -0.05706975577620854}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 44.44444444444444}" valid candidate_overlay.tsv;selected_target_profiles.tsv +KRAS symbol:KRAS|entrez:3845 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.6390363697007047, ""interquartile_range"": 0.3255914225769023, ""maximum"": 0.037107045533280814, ""mean"": -0.4615597662300834, ""measured_model_count"": 56, ""median"": -0.4270863694795695, ""minimum"": -0.9671398918289789, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.31344494712380233, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.2804397654477754, ""interquartile_range"": 0.4166743169804551, ""maximum"": 0.9882225371239182, ""mean"": 0.48315218978865904, ""measured_model_count"": 56, ""median"": 0.4738799422322064, ""minimum"": 0.012521637812168088, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.6971140824282305, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.48214285714285715, ""numerator"": 27, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.17857142857142858, ""numerator"": 10, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.11562974175001095, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.48214285714285715, ""difference"": -0.09401608325449379, ""pan_cancer_fraction"": 0.5761589403973509, ""threshold"": 0.5}, {""context_fraction"": 0.17857142857142858, ""difference"": -0.16248817407757807, ""pan_cancer_fraction"": 0.34105960264900664, ""threshold"": 0.8}], ""gene_effect_mean"": 0.2633418509692072, ""gene_effect_median"": 0.08983073184763496}, ""dependency_probability_context_minus_non_context_median"": -0.1300421110614044, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.48214285714285715, ""difference"": -0.09858630952380948, ""non_context_fraction"": 0.5807291666666666, ""threshold"": 0.5}, {""context_fraction"": 0.17857142857142858, ""difference"": -0.17038690476190474, ""non_context_fraction"": 0.3489583333333333, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.2761431909468766, ""gene_effect_context_minus_non_context_median"": 0.10109950535962081}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 22.22222222222222}" valid candidate_overlay.tsv;selected_target_profiles.tsv +KRT5 symbol:KRT5|entrez:3852 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.1162600050798901, ""interquartile_range"": 0.16026986264477588, ""maximum"": 0.3326259306248558, ""mean"": -0.03271996044744329, ""measured_model_count"": 56, ""median"": -0.03875848753631785, ""minimum"": -0.4083100273302143, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.04400985756488579, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.013107390885123485, ""interquartile_range"": 0.04935434074536283, ""maximum"": 0.34081918050850224, ""mean"": 0.05037789993099017, ""measured_model_count"": 56, ""median"": 0.027358384042971286, ""minimum"": 0.0012650511761817924, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.062461731630486315, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.005669141450315225, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.0016556291390728477, ""pan_cancer_fraction"": 0.0016556291390728477, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0008278145695364238, ""pan_cancer_fraction"": 0.0008278145695364238, ""threshold"": 0.8}], ""gene_effect_mean"": 0.018647943378540567, ""gene_effect_median"": 0.008795443937758655}, ""dependency_probability_context_minus_non_context_median"": -0.0059289590279801505, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.001736111111111111, ""non_context_fraction"": 0.001736111111111111, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0008680555555555555, ""non_context_fraction"": 0.0008680555555555555, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.019554440626108442, ""gene_effect_context_minus_non_context_median"": 0.008975446451295908}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 33.333333333333336}" valid candidate_overlay.tsv;selected_target_profiles.tsv +LAG3 symbol:LAG3|entrez:3902 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.05881633966392029, ""interquartile_range"": 0.12893561937780812, ""maximum"": 0.37914429966497276, ""mean"": 0.003600261025976661, ""measured_model_count"": 56, ""median"": 0.006693995382591952, ""minimum"": -0.31014322945440886, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.07011927971388784, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.010007862547405266, ""interquartile_range"": 0.025780908070300368, ""maximum"": 0.2736649589269115, ""mean"": 0.03207975191250165, ""measured_model_count"": 56, ""median"": 0.02026514620529634, ""minimum"": 0.0006578282366709314, 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-0.0008680555555555555, ""non_context_fraction"": 0.0008680555555555555, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.01226224338686388, ""gene_effect_context_minus_non_context_median"": 0.01031202269999554}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 70.37037037037037}" valid candidate_overlay.tsv;selected_target_profiles.tsv +LATS2 symbol:LATS2|entrez:26524 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.1556578421689475, ""interquartile_range"": 0.346068833316306, ""maximum"": 0.6812382978063686, ""mean"": 0.020232855958764978, 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[{""context_fraction"": 0.017857142857142856, ""difference"": 0.007095553453169347, ""pan_cancer_fraction"": 0.01076158940397351, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0008278145695364238, ""pan_cancer_fraction"": 0.0008278145695364238, ""threshold"": 0.8}], ""gene_effect_mean"": 0.04324556828627929, ""gene_effect_median"": 0.06935077629481798}, ""dependency_probability_context_minus_non_context_median"": -0.007375489439448841, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.017857142857142856, ""difference"": 0.00744047619047619, ""non_context_fraction"": 0.010416666666666666, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0008680555555555555, ""non_context_fraction"": 0.0008680555555555555, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", 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candidate_overlay.tsv;selected_target_profiles.tsv +LILRB1 symbol:LILRB1|entrez:10859 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.01109020400994214, ""interquartile_range"": 0.1398087266452999, ""maximum"": 0.4433027675302377, ""mean"": 0.05536551565827964, ""measured_model_count"": 56, ""median"": 0.051821418581015924, ""minimum"": -0.2138537031730067, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.12871852263535774, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.006022954802638753, ""interquartile_range"": 0.017556262760780754, ""maximum"": 0.11051920534037452, ""mean"": 0.01924822092948011, ""measured_model_count"": 56, ""median"": 0.013681127550983843, ""minimum"": 0.00023616078642564348, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.023579217563419505, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, 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-0.01126878239771938, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.023619920694685523, ""interquartile_range"": 0.06576945252265654, ""maximum"": 0.5581267752985244, ""mean"": 0.0736724021976837, ""measured_model_count"": 56, ""median"": 0.054768936757054784, ""minimum"": 0.0008249314826466763, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.08938937321734206, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.017857142857142856, ""numerator"": 1, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.008650022490033216, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.017857142857142856, ""difference"": -0.0003547776726584677, ""pan_cancer_fraction"": 0.018211920529801324, ""threshold"": 0.5}, {""context_fraction"": 0.0, 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negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 81.48148148148148}" valid candidate_overlay.tsv;selected_target_profiles.tsv +LPP symbol:LPP|entrez:4026 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.008783199593916918, ""interquartile_range"": 0.10063549851005911, ""maximum"": 0.39512059249409137, ""mean"": 0.0501342135041537, ""measured_model_count"": 56, ""median"": 0.052278005196747614, ""minimum"": -0.28660592592022155, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.09185229891614219, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.00715624060802497, ""interquartile_range"": 0.014590503911784831, ""maximum"": 0.14433042014147968, ""mean"": 0.01906680258772825, ""measured_model_count"": 56, ""median"": 0.012845188877211793, ""minimum"": 0.0007890807311014471, ""missing_fraction"": 0.0, 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true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 14.814814814814815}" valid candidate_overlay.tsv;selected_target_profiles.tsv +LZTR1 symbol:LZTR1|entrez:8216 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.09712302034637581, ""interquartile_range"": 0.12603647569734755, ""maximum"": 0.39835316383447017, ""mean"": -0.023218800975575663, ""measured_model_count"": 56, ""median"": -0.032631692394577985, ""minimum"": -0.31250394234035345, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.028913455350971732, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.013866497890610329, ""interquartile_range"": 0.03558430953541362, ""maximum"": 0.22804494863519476, ""mean"": 0.042020283337196505, ""measured_model_count"": 56, ""median"": 0.027297324657613566, 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""first_quartile"": -0.578482228308965, ""interquartile_range"": 0.4189281838514242, ""maximum"": 0.252437482852541, ""mean"": -0.41218035078685417, ""measured_model_count"": 56, ""median"": -0.38895098205912615, ""minimum"": -1.3657303916368035, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.1595540444575408, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.08598020716229524, ""interquartile_range"": 0.5882115796602083, ""maximum"": 0.9908781940957316, ""mean"": 0.42114568711213035, ""measured_model_count"": 56, ""median"": 0.38746891216194834, ""minimum"": 0.002703798825683424, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.6741917868225036, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.39285714285714285, ""numerator"": 22, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.23214285714285715, ""numerator"": 13, ""threshold"": 0.8}], 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symbol:MAPK1|entrez:5594 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -1.2761774074770886, ""interquartile_range"": 0.7786423452235494, ""maximum"": 0.18419597775603253, ""mean"": -0.8981201774701383, ""measured_model_count"": 56, ""median"": -0.8129894142767058, ""minimum"": -2.2162133589722837, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.4975350622535393, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.5766186743058375, ""interquartile_range"": 0.41754805922924465, ""maximum"": 1.0, ""mean"": 0.7418741798461861, ""measured_model_count"": 56, ""median"": 0.8931882816760448, ""minimum"": 0.0015643431120909866, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.9941667335350821, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.7857142857142857, ""numerator"": 44, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 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valid candidate_overlay.tsv;selected_target_profiles.tsv +MAX symbol:MAX|entrez:4149 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.8226826734631729, ""interquartile_range"": 0.23233480918405225, ""maximum"": -0.2112248166458427, ""mean"": -0.710188390541159, ""measured_model_count"": 56, ""median"": -0.688268648265024, ""minimum"": -1.2966052450452203, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.5903478642791207, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.703880450962148, ""interquartile_range"": 0.24126058863373134, ""maximum"": 0.9931135114720926, ""mean"": 0.7818475651475402, ""measured_model_count"": 56, ""median"": 0.8762894271334364, ""minimum"": 0.11802670198216508, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.9451410395958794, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.875, ""numerator"": 49, 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than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 29.62962962962963}" valid candidate_overlay.tsv;selected_target_profiles.tsv +MC1R symbol:MC1R|entrez:4157 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.13574258291049882, ""interquartile_range"": 0.2294889026785944, ""maximum"": 0.3088799835855469, ""mean"": -0.07405014885167535, ""measured_model_count"": 56, ""median"": -0.014394286830063385, ""minimum"": -1.4266168769158605, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.0937463197680956, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.00957570675501504, ""interquartile_range"": 0.06469958618077154, ""maximum"": 0.9986640403125104, ""mean"": 0.093014007762533, ""measured_model_count"": 56, ""median"": 0.024505635992432086, ""minimum"": 0.002172093001064544, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 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candidate_overlay.tsv;selected_target_profiles.tsv +MECOM symbol:MECOM|entrez:2122 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.03318121755950547, ""interquartile_range"": 0.14709745093791188, ""maximum"": 1.1159229428618254, ""mean"": 0.04519617222218534, ""measured_model_count"": 56, ""median"": 0.06243448810213843, ""minimum"": -0.4043002287802036, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.1139162333784064, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.007059075844818929, ""interquartile_range"": 0.0174121661972337, ""maximum"": 0.3482881257463481, ""mean"": 0.03171024366566652, ""measured_model_count"": 56, ""median"": 0.01239713433525657, ""minimum"": 0.0, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.02447124204205263, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 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""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 70.37037037037037}" valid candidate_overlay.tsv;selected_target_profiles.tsv +MERTK symbol:MERTK|entrez:10461 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.18881505762195927, ""interquartile_range"": 0.16208785261332045, ""maximum"": 0.3193293249145177, ""mean"": -0.10122912464953086, ""measured_model_count"": 56, ""median"": -0.10690991997138019, ""minimum"": -0.37059543781934634, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.02672720500863881, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.024416867332033472, ""interquartile_range"": 0.08662821894971165, ""maximum"": 0.2986950469092032, ""mean"": 0.07873373296246423, ""measured_model_count"": 56, ""median"": 0.05270852886247373, ""minimum"": 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+MN1 symbol:MN1|entrez:4330 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.01062534893898931, ""interquartile_range"": 0.20506169154087153, ""maximum"": 0.4941061788942517, ""mean"": 0.10398082189212046, ""measured_model_count"": 56, ""median"": 0.1147031423956377, ""minimum"": -0.2283786381698714, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.19443634260188222, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.002738853757670439, ""interquartile_range"": 0.018564266438373188, ""maximum"": 0.11449885931721446, ""mean"": 0.018046659942068676, ""measured_model_count"": 56, ""median"": 0.0071448822915313025, ""minimum"": 5.345680221332841e-05, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.021303120196043628, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, 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symbol:MSH2|entrez:4436 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.26003559151177824, ""interquartile_range"": 0.13672139042893577, ""maximum"": 0.021496894857538112, ""mean"": -0.20764010596590654, ""measured_model_count"": 56, ""median"": -0.19916068457846808, ""minimum"": -0.5451116448448519, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.12331420108284245, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.06592450097849478, ""interquartile_range"": 0.13342337190007386, ""maximum"": 0.5982055659846949, ""mean"": 0.15553859836993347, ""measured_model_count"": 56, ""median"": 0.12392476588127996, ""minimum"": 0.009111683646020614, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.19934787287856864, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.03571428571428571, ""numerator"": 2, ""threshold"": 0.5}, 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symbol:NF2|entrez:4771 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.0033319999520227406, ""interquartile_range"": 0.4985835437227313, ""maximum"": 1.4967874348475283, ""mean"": 0.257261458735955, ""measured_model_count"": 56, ""median"": 0.24139439051277362, ""minimum"": -0.9790795352267114, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.49525154377070857, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.00017270873873151513, ""interquartile_range"": 0.019002620285019006, ""maximum"": 0.9430258163992079, ""mean"": 0.07984631308479892, ""measured_model_count"": 56, ""median"": 0.0025437083249686757, ""minimum"": 0.0, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.01917532902375052, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.07142857142857142, ""numerator"": 4, ""threshold"": 0.5}, {""denominator"": 56, 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negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 48.148148148148145}" valid candidate_overlay.tsv;selected_target_profiles.tsv +NKX2-1 symbol:NKX2-1|entrez:7080 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.12276799614693762, ""interquartile_range"": 0.18307558688335396, ""maximum"": 0.27550802661951984, ""mean"": -0.043376474182780414, ""measured_model_count"": 56, ""median"": -0.03133446214879327, ""minimum"": -0.4273642289892, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.060307590736416325, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.010194888921109245, ""interquartile_range"": 0.04847112414292441, ""maximum"": 0.3976824988928863, ""mean"": 0.060590058138209654, ""measured_model_count"": 56, ""median"": 0.02987755063188091, ""minimum"": 0.0012628047782111012, ""missing_fraction"": 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symbol:NRAS|entrez:4893 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.3305911123197959, ""interquartile_range"": 0.20369185017668184, ""maximum"": 0.09354479287791917, ""mean"": -0.44904229263305867, ""measured_model_count"": 56, ""median"": -0.19958349119150692, ""minimum"": -2.9561530105181015, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.12689926214311403, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.05768686105568797, ""interquartile_range"": 0.22765180742178384, ""maximum"": 1.0, ""mean"": 0.27492022095168256, ""measured_model_count"": 56, ""median"": 0.11160490099703885, ""minimum"": 0.004688799268174339, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.2853386684774718, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.19642857142857142, ""numerator"": 11, ""threshold"": 0.5}, {""denominator"": 56, 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negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 51.851851851851855}" valid candidate_overlay.tsv;selected_target_profiles.tsv +NUTM1 symbol:NUTM1|entrez:256646 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.06766413170933441, ""interquartile_range"": 0.12230469464003679, ""maximum"": 0.23858120904323193, ""mean"": -0.013250682999457888, ""measured_model_count"": 56, ""median"": -0.01540965770348755, ""minimum"": -0.33765216343614773, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.05464056293070238, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.012373005021698226, ""interquartile_range"": 0.026164771633834467, ""maximum"": 0.22158294522974528, ""mean"": 0.03317301826003201, ""measured_model_count"": 56, ""median"": 0.023444423153857114, ""minimum"": 0.0015163016029478907, 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[{""context_fraction"": 0.0, ""difference"": -0.0026041666666666665, ""non_context_fraction"": 0.0026041666666666665, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0026041666666666665, ""non_context_fraction"": 0.0026041666666666665, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.0006934300990349106, ""gene_effect_context_minus_non_context_median"": -0.005295065741185927}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 51.851851851851855}" valid candidate_overlay.tsv;selected_target_profiles.tsv +OCA2 symbol:OCA2|entrez:4948 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.11003886894933272, ""interquartile_range"": 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true, ""first_quartile"": -0.21337700367028087, ""interquartile_range"": 0.13030410006901616, ""maximum"": 0.1548473717667494, ""mean"": -0.15100029050775082, ""measured_model_count"": 56, ""median"": -0.1391172000683189, ""minimum"": -0.4179920396603739, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.08307290360126471, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.04269880256237364, ""interquartile_range"": 0.1065916921003043, ""maximum"": 0.39286694038493386, ""mean"": 0.1137033476788312, ""measured_model_count"": 56, ""median"": 0.0798356188482517, ""minimum"": 0.005100727127091044, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.14929049466267794, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" 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candidate_overlay.tsv;selected_target_profiles.tsv +PBRM1 symbol:PBRM1|entrez:55193 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.16479697620735534, ""interquartile_range"": 0.3034207952026297, ""maximum"": 0.4448525230836686, ""mean"": -0.022173015534992117, ""measured_model_count"": 56, ""median"": -0.04422832147235136, ""minimum"": -0.6075030044826925, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.13862381899527437, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.005101405183288445, ""interquartile_range"": 0.08901199505560088, ""maximum"": 0.6419488286639063, ""mean"": 0.07271163892119407, ""measured_model_count"": 56, ""median"": 0.025873981311805343, ""minimum"": 0.00026959172539142045, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.09411340023888932, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 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""eligible_lineage_count"": 28, ""value"": 100.0}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PDCD1LG2 symbol:PDCD1LG2|entrez:80380 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.05816013705757744, ""interquartile_range"": 0.11189371167739326, ""maximum"": 0.3771133025892327, ""mean"": 0.1072155941052707, ""measured_model_count"": 56, ""median"": 0.09145888055795778, ""minimum"": -0.11873669255379785, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.1700538487349707, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0037372367702815036, ""interquartile_range"": 0.010498710407831242, ""maximum"": 0.04984001631579498, ""mean"": 0.01034691838648634, ""measured_model_count"": 56, ""median"": 0.007611086135415668, ""minimum"": 0.0007532072106878847, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.014235947178112746, 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-0.12763669044546008, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.05686242904454657, ""interquartile_range"": 0.10437702981984269, ""maximum"": 0.8490391727005575, ""mean"": 0.15035186602067654, ""measured_model_count"": 56, ""median"": 0.10237428471529833, ""minimum"": 0.004926867884639238, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.16123945886438926, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.05357142857142857, ""numerator"": 3, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.017857142857142856, ""numerator"": 1, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.005719797835777085, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.05357142857142857, ""difference"": -0.016792809839167457, ""pan_cancer_fraction"": 0.07036423841059603, ""threshold"": 0.5}, 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"{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 62.96296296296296}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PDGFRB symbol:PDGFRB|entrez:5159 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.1533298824968127, ""interquartile_range"": 0.19320922610917157, ""maximum"": 0.28340888139004716, ""mean"": -0.060062062579911354, ""measured_model_count"": 56, ""median"": -0.07629056372993706, ""minimum"": -0.39446206414889434, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.03987934361235887, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.015103099225042448, ""interquartile_range"": 0.0632267186652943, ""maximum"": 0.3425415988456145, ""mean"": 0.06299017017119603, ""measured_model_count"": 56, ""median"": 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""first_quartile"": 0.03086128251576374, ""interquartile_range"": 0.1190081708614905, ""maximum"": 0.28867284705445984, ""mean"": 0.08991771449382154, ""measured_model_count"": 56, ""median"": 0.09976442986895973, ""minimum"": -0.14227097328950417, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.14986945337725424, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.004534189618738785, ""interquartile_range"": 0.010004848593089312, ""maximum"": 0.058565348415219765, ""mean"": 0.01211886409344396, ""measured_model_count"": 56, ""median"": 0.00844002980337798, ""minimum"": 0.0010624023055272463, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.014539038211828097, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.0019063463449663235, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.8}], ""gene_effect_mean"": -0.04444946194894421, ""gene_effect_median"": -0.03379244700598999}, ""dependency_probability_context_minus_non_context_median"": 0.0019906329524445677, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.04661019968257342, 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0.002024788990909656, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.008680555555555556, ""non_context_fraction"": 0.008680555555555556, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.003472222222222222, ""non_context_fraction"": 0.003472222222222222, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.011374235325742013, ""gene_effect_context_minus_non_context_median"": -0.02260278248246078}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 81.48148148148148}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PIK3CA symbol:PIK3CA|entrez:5290 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.3926242184937075, ""interquartile_range"": 0.2029757534853182, ""maximum"": 0.11683662531876016, ""mean"": -0.2863294055143963, ""measured_model_count"": 56, ""median"": -0.2939677758894327, ""minimum"": -0.6891435375577224, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.18964846500838928, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.10419575803316142, ""interquartile_range"": 0.2948881615068477, ""maximum"": 0.8761345885208559, ""mean"": 0.2630345989934602, ""measured_model_count"": 56, ""median"": 0.20917938968000044, ""minimum"": 0.005989732137504378, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.39908391954000916, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.14285714285714285, ""numerator"": 8, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.03571428571428571, ""numerator"": 2, 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median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 85.18518518518519}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PIK3R1 symbol:PIK3R1|entrez:5295 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.03837001138190876, ""interquartile_range"": 0.2663987206667829, ""maximum"": 0.6800493745081021, ""mean"": 0.08456744924235596, ""measured_model_count"": 56, ""median"": 0.07693671363161786, ""minimum"": -0.35984488150574573, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.22802870928487412, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.002696889421791202, ""interquartile_range"": 0.02538843082361781, ""maximum"": 0.3583474394213573, ""mean"": 0.029228288317221747, ""measured_model_count"": 56, ""median"": 0.009912816186445288, ""minimum"": 2.073664012003869e-05, ""missing_fraction"": 0.0, 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"{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 51.851851851851855}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PLXNB2 symbol:PLXNB2|entrez:23654 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.016739809784034065, ""interquartile_range"": 0.13622487385793947, ""maximum"": 0.39172179779208477, ""mean"": 0.09250986907465496, ""measured_model_count"": 56, ""median"": 0.07287237929257996, ""minimum"": -0.17175670111727442, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.15296468364197352, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.004153007557135326, ""interquartile_range"": 0.013950921193240031, ""maximum"": 0.06888512238549067, ""mean"": 0.014042510139181064, ""measured_model_count"": 56, ""median"": 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+POU2AF1 symbol:POU2AF1|entrez:5450 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.06144299452441082, ""interquartile_range"": 0.16721482908748944, ""maximum"": 0.25598488770962047, ""mean"": 0.012489908148375358, ""measured_model_count"": 56, ""median"": 0.010038770990871998, ""minimum"": -0.29326722424317075, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.10577183456307862, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0067145750699271175, ""interquartile_range"": 0.03315913931173384, ""maximum"": 0.24566225721850554, ""mean"": 0.033463484590643744, ""measured_model_count"": 56, ""median"": 0.02258460016959892, ""minimum"": 0.0018220453406680766, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.03987371438166096, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.0009895798520293334, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.04304635761589404, ""pan_cancer_fraction"": 0.04304635761589404, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.03228476821192053, ""pan_cancer_fraction"": 0.03228476821192053, ""threshold"": 0.8}], ""gene_effect_mean"": 0.05904330364299119, ""gene_effect_median"": 0.017333354677480317}, ""dependency_probability_context_minus_non_context_median"": -0.0009895798520293334, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.04513888888888889, ""non_context_fraction"": 0.04513888888888889, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.033854166666666664, ""non_context_fraction"": 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stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 88.88888888888889}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PPP6C symbol:PPP6C|entrez:5537 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -1.0180315911310092, ""interquartile_range"": 0.5621537586484284, ""maximum"": 0.11025640550708837, ""mean"": -0.7830457115397375, ""measured_model_count"": 56, ""median"": -0.781903782242473, ""minimum"": -2.174202672852065, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.4558778324825807, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.5280855865269243, ""interquartile_range"": 0.4428703885392822, ""maximum"": 1.0, ""mean"": 0.7228752811217215, ""measured_model_count"": 56, ""median"": 0.8982627669210668, ""minimum"": 0.012641297187679104, ""missing_fraction"": 0.0, 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symbol:PREX2|entrez:80243 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.06544856986628139, ""interquartile_range"": 0.12703400620022845, ""maximum"": 0.49542242427329963, ""mean"": 0.13323863617645906, ""measured_model_count"": 56, ""median"": 0.11155773430019963, ""minimum"": -0.09874246278849794, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.19248257606650984, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0025839773065120717, ""interquartile_range"": 0.009416781894391853, ""maximum"": 0.03580333716191526, ""mean"": 0.008801885456245927, ""measured_model_count"": 56, ""median"": 0.007049386132260232, ""minimum"": 0.00015597332978287568, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.012000759200903925, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, 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the context group."", ""gene_effect_context_minus_non_context_mean"": 0.0037787176182225712, ""gene_effect_context_minus_non_context_median"": -0.013121553883521181}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 62.96296296296296}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PRF1 symbol:PRF1|entrez:5551 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.05478050797948658, ""interquartile_range"": 0.09711305586290947, ""maximum"": 0.4078675016027466, ""mean"": -0.0015226298621399592, ""measured_model_count"": 56, ""median"": 0.0047451788481697, ""minimum"": -0.22679163161826915, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.042332547883422895, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.011764494825794149, ""interquartile_range"": 0.03005355888286111, ""maximum"": 0.23055611608468068, ""mean"": 0.030715219026443995, ""measured_model_count"": 56, ""median"": 0.02139926937725605, ""minimum"": 0.0005486674577255344, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.04181805370865526, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.0025959982232196567, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.8}], ""gene_effect_mean"": 0.006103480234065759, ""gene_effect_median"": 0.014688023320211133}, ""dependency_probability_context_minus_non_context_median"": -0.0026635317946805265, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.006400177189888426, ""gene_effect_context_minus_non_context_median"": 0.015379095495603068}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 22.22222222222222}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PTCH1 symbol:PTCH1|entrez:5727 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.09588063885275669, ""interquartile_range"": 0.21009150163000154, ""maximum"": 0.3324175140971824, ""mean"": 0.011094539588050975, ""measured_model_count"": 56, ""median"": 0.018151218696463505, ""minimum"": -0.46600755029575164, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.11421086277724485, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.005977946450391312, ""interquartile_range"": 0.03975630865182156, ""maximum"": 0.37309691491643426, ""mean"": 0.036336117075092225, ""measured_model_count"": 56, ""median"": 0.020825055662632826, ""minimum"": 0.0010684762208753433, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.04573425510221287, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.0037906453790609515, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.0016556291390728477, ""pan_cancer_fraction"": 0.0016556291390728477, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.8}], ""gene_effect_mean"": -0.00793799435793612, ""gene_effect_median"": -0.006583365323387894}, ""dependency_probability_context_minus_non_context_median"": 0.004053431081731743, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.001736111111111111, ""non_context_fraction"": 0.001736111111111111, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.00832386908366914, ""gene_effect_context_minus_non_context_median"": -0.006583365323387894}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 25.925925925925927}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PTEN symbol:PTEN|entrez:5728 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.1774273786697296, ""interquartile_range"": 0.3538259685928198, ""maximum"": 1.736156453910227, ""mean"": 0.35005025729220074, ""measured_model_count"": 56, ""median"": 0.3093834287818784, ""minimum"": -0.5425024630491011, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.5312533472625494, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.00014782039573808722, ""interquartile_range"": 0.003600925362963198, ""maximum"": 0.5552301573186749, ""mean"": 0.029092579805179958, ""measured_model_count"": 56, ""median"": 0.0016319869133616688, ""minimum"": 0.0, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.0037487457587012853, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.017857142857142856, ""numerator"": 1, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.0006340736706280773, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.017857142857142856, ""difference"": 0.00378429517502365, ""pan_cancer_fraction"": 0.014072847682119206, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.008278145695364239, ""pan_cancer_fraction"": 0.008278145695364239, ""threshold"": 0.8}], ""gene_effect_mean"": -0.04551705089091174, ""gene_effect_median"": -0.03148194444479169}, ""dependency_probability_context_minus_non_context_median"": 0.0006571060699895603, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.017857142857142856, ""difference"": 0.003968253968253968, ""non_context_fraction"": 0.013888888888888888, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.008680555555555556, ""non_context_fraction"": 0.008680555555555556, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.047729685309219894, ""gene_effect_context_minus_non_context_median"": -0.03305045121014427}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 55.55555555555556}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PTK6 symbol:PTK6|entrez:5753 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.1840162742298729, ""interquartile_range"": 0.1997483929044233, ""maximum"": 0.3222356768075394, ""mean"": -0.09758380127941914, ""measured_model_count"": 56, ""median"": -0.12026321213311797, ""minimum"": -0.5349203287149611, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.015732118674550405, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.018529924530914635, ""interquartile_range"": 0.09544668456352441, ""maximum"": 0.7582481910067956, ""mean"": 0.09733291620033664, ""measured_model_count"": 56, ""median"": 0.05169764005554711, ""minimum"": 0.0011785351628772456, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.11397660909443905, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.017857142857142856, ""numerator"": 1, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.018319115017753004, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.017857142857142856, ""difference"": -0.002010406811731317, ""pan_cancer_fraction"": 0.019867549668874173, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0016556291390728477, ""pan_cancer_fraction"": 0.0016556291390728477, ""threshold"": 0.8}], ""gene_effect_mean"": 0.04000233454004308, ""gene_effect_median"": 0.011755430048686955}, ""dependency_probability_context_minus_non_context_median"": -0.01906178797118574, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.017857142857142856, ""difference"": -0.00210813492063492, ""non_context_fraction"": 0.019965277777777776, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.001736111111111111, ""non_context_fraction"": 0.001736111111111111, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.041946892469073, ""gene_effect_context_minus_non_context_median"": 0.013003588814756994}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 33.333333333333336}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PTPN11 symbol:PTPN11|entrez:5781 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.3533909262374086, ""interquartile_range"": 0.29119952608175426, ""maximum"": 0.17635991627900627, ""mean"": -0.2706024316129988, ""measured_model_count"": 56, ""median"": -0.22336959724687172, ""minimum"": -1.2437665525555057, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.06219140015565436, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.03844928397309019, ""interquartile_range"": 0.284016781985858, ""maximum"": 0.9954390112631097, ""mean"": 0.24807679949177336, ""measured_model_count"": 56, ""median"": 0.15755716577163256, ""minimum"": 0.004383763089454739, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.3224660659589482, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.14285714285714285, ""numerator"": 8, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.10714285714285714, ""numerator"": 6, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.7093328754750823, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.14285714285714285, ""difference"": -0.5616130558183539, ""pan_cancer_fraction"": 0.7044701986754967, ""threshold"": 0.5}, {""context_fraction"": 0.10714285714285714, ""difference"": -0.45245979186376534, ""pan_cancer_fraction"": 0.5596026490066225, ""threshold"": 0.8}], ""gene_effect_mean"": 0.45975065413160154, ""gene_effect_median"": 0.5201246616645117}, ""dependency_probability_context_minus_non_context_median"": -0.7213579715718752, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.14285714285714285, ""difference"": -0.5889136904761905, ""non_context_fraction"": 0.7317708333333334, ""threshold"": 0.5}, {""context_fraction"": 0.10714285714285714, ""difference"": -0.47445436507936506, ""non_context_fraction"": 0.5815972222222222, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.4820996442629989, ""gene_effect_context_minus_non_context_median"": 0.5437117352527387}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 3.7037037037037037}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PTPN13 symbol:PTPN13|entrez:5783 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.040896381394369005, ""interquartile_range"": 0.14700691920925746, ""maximum"": 0.31995876843033, ""mean"": 0.028346182847745472, ""measured_model_count"": 56, ""median"": 0.0242865690164243, ""minimum"": -0.24895582715208994, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.10611053781488845, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.007373541485068309, ""interquartile_range"": 0.022925124109128, ""maximum"": 0.1390811639666005, ""mean"": 0.02462924447522302, ""measured_model_count"": 56, ""median"": 0.015851864845906453, ""minimum"": 0.0018513373217926266, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.03029866559419631, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.0012871058769384144, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.0016556291390728477, ""pan_cancer_fraction"": 0.0016556291390728477, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.8}], ""gene_effect_mean"": -0.016492866144982073, ""gene_effect_median"": -0.01797633936413052}, ""dependency_probability_context_minus_non_context_median"": 0.0013234472008851663, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.001736111111111111, ""non_context_fraction"": 0.001736111111111111, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.017294602693696478, ""gene_effect_context_minus_non_context_median"": -0.01815635480726488}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 59.25925925925926}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PTPRB symbol:PTPRB|entrez:5787 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.08660322861860656, ""interquartile_range"": 0.15326593446016268, ""maximum"": 0.26799591456187166, ""mean"": -0.008701379226628104, ""measured_model_count"": 56, ""median"": -0.005419265839015835, ""minimum"": -0.2918999102986819, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.06666270584155613, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.010197627844800234, ""interquartile_range"": 0.033392511824931415, ""maximum"": 0.20757819748639839, ""mean"": 0.036540181284022935, ""measured_model_count"": 56, ""median"": 0.022612690169484462, ""minimum"": 0.0021535234777501173, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.043590139669731645, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.00014758817878838745, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.8}], ""gene_effect_mean"": -0.001705276232285671, ""gene_effect_median"": -0.0021003650003931736}, ""dependency_probability_context_minus_non_context_median"": -0.00014758817878838745, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.0017881716046884528, ""gene_effect_context_minus_non_context_median"": -0.0023863247963391166}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 44.44444444444444}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PTPRC symbol:PTPRC|entrez:5788 true insufficient_measured_context_models 56 2098 "{""available"": true, ""first_quartile"": -0.2540968232068008, ""interquartile_range"": 0.27269155062254513, ""maximum"": 0.2667060877154521, ""mean"": -0.10718411476264175, ""measured_model_count"": 7, ""median"": -0.1839674851282336, ""minimum"": -0.3620232143435977, ""missing_fraction"": 0.875, ""missing_model_count"": 49, ""third_quartile"": 0.018594727415744333, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.03535790079068784, ""interquartile_range"": 0.11700097399538673, ""maximum"": 0.3130619067559611, ""mean"": 0.11336025072294678, ""measured_model_count"": 7, ""median"": 0.10142439265024349, ""minimum"": 0.0036019045008981055, ""missing_fraction"": 0.875, ""missing_model_count"": 49, ""third_quartile"": 0.15235887478607457, ""threshold_fractions"": [{""denominator"": 7, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 7, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": null, ""dependency_probability_threshold_fractions"": [], ""gene_effect_mean"": null, ""gene_effect_median"": null}, ""dependency_probability_context_minus_non_context_median"": null, ""dependency_probability_context_minus_non_context_threshold_fractions"": [], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": null, ""gene_effect_context_minus_non_context_median"": null}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 21, ""value"": 65.0}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PTPRK symbol:PTPRK|entrez:5796 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.04914152862613752, ""interquartile_range"": 0.12518664825956582, ""maximum"": 0.2998279934328426, ""mean"": 0.1114437103978233, ""measured_model_count"": 56, ""median"": 0.11574090709819299, ""minimum"": -0.0681971223240274, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.17432817688570335, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0035664525085002926, ""interquartile_range"": 0.00992274915531969, ""maximum"": 0.03943903737818359, ""mean"": 0.010132813629039368, ""measured_model_count"": 56, ""median"": 0.007097817765832145, 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""non_context_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.01300006485195189, ""gene_effect_context_minus_non_context_median"": -0.004484083873970465}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 81.48148148148148}" valid candidate_overlay.tsv;selected_target_profiles.tsv +PTPRT symbol:PTPRT|entrez:11122 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.12557464182869493, ""interquartile_range"": 0.1670050372331764, ""maximum"": 0.35192836037169745, ""mean"": -0.04846570793613747, ""measured_model_count"": 56, ""median"": 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-1.132219886481244, ""interquartile_range"": 0.3450850855482519, ""maximum"": -0.23357021391240496, ""mean"": -0.9872570564091132, ""measured_model_count"": 56, ""median"": -0.9644656313374076, ""minimum"": -1.9398398272208595, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.7871348009329922, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.8903158974511705, ""interquartile_range"": 0.0970528051333146, ""maximum"": 1.0, ""mean"": 0.9143828073836274, ""measured_model_count"": 56, ""median"": 0.9718981505657296, ""minimum"": 0.12114557537340254, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.9873687025844851, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.9821428571428571, ""numerator"": 55, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.875, ""numerator"": 49, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": 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""eligible_lineage_count"": 28, ""value"": 88.88888888888889}" valid candidate_overlay.tsv;selected_target_profiles.tsv +RAF1 symbol:RAF1|entrez:5894 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.1256271216117195, ""interquartile_range"": 0.1888216209784189, ""maximum"": 0.20431855926131795, ""mean"": -0.15615906924769854, ""measured_model_count"": 56, ""median"": -0.02220851631360249, ""minimum"": -1.736546085109907, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.06319449936669941, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.012033750897031764, ""interquartile_range"": 0.04288567210061994, ""maximum"": 1.0, ""mean"": 0.17290387330361726, ""measured_model_count"": 56, ""median"": 0.02468474918939307, ""minimum"": 0.0024816460659539356, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.05491942299765171, ""threshold_fractions"": 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sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.14612119713856755, ""interquartile_range"": 0.14575295943199149, ""maximum"": 0.17499522346494442, ""mean"": -0.06749277025807235, ""measured_model_count"": 56, ""median"": -0.07167217571962779, ""minimum"": -0.24627934225885015, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.000368237706576062, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.018037570779840997, ""interquartile_range"": 0.06104268632906562, ""maximum"": 0.17637743727038194, ""mean"": 0.056573689560530285, ""measured_model_count"": 56, ""median"": 0.04047103264540877, ""minimum"": 0.004538060086491297, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.07908025710890662, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 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lineages."", ""eligible_lineage_count"": 28, ""value"": 33.333333333333336}" valid candidate_overlay.tsv;selected_target_profiles.tsv +ROS1 symbol:ROS1|entrez:6098 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.08392049067782814, ""interquartile_range"": 0.12341727033690336, ""maximum"": 0.3254661141771581, ""mean"": 0.126330303900205, ""measured_model_count"": 56, ""median"": 0.12383389748495374, ""minimum"": -0.20924597391267008, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.2073377610147315, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0027627089855649873, ""interquartile_range"": 0.007337207312868303, ""maximum"": 0.10622139999463978, ""mean"": 0.012021715750322627, ""measured_model_count"": 56, ""median"": 0.005657972826808763, ""minimum"": 0.0007528764526069915, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 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+RRM1 symbol:RRM1|entrez:6240 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -3.7866713498714786, ""interquartile_range"": 0.7142138038474664, ""maximum"": -2.0291077684100465, ""mean"": -3.4304476414103555, ""measured_model_count"": 56, ""median"": -3.527279701684648, ""minimum"": -4.272254363112374, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -3.072457546024012, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 1.0, ""interquartile_range"": 0.0, ""maximum"": 1.0, ""mean"": 1.0, ""measured_model_count"": 56, ""median"": 1.0, ""minimum"": 1.0, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 1.0, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 1.0, ""numerator"": 56, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 1.0, ""numerator"": 56, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": 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-0.2582819782444661}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 100.0}" valid candidate_overlay.tsv;selected_target_profiles.tsv +RRM2 symbol:RRM2|entrez:6241 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -3.0848036344428675, ""interquartile_range"": 0.517328228067063, ""maximum"": -1.1915182107798357, ""mean"": -2.782417065774602, ""measured_model_count"": 56, ""median"": -2.8483434965014958, ""minimum"": -3.607628637950257, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -2.5674754063758045, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 1.0, ""interquartile_range"": 0.0, ""maximum"": 1.0, ""mean"": 0.9999699992385163, ""measured_model_count"": 56, ""median"": 1.0, ""minimum"": 0.9983332637171632, ""missing_fraction"": 0.0, 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"{""available"": true, ""first_quartile"": -0.13566465830643035, ""interquartile_range"": 0.13712660498832815, ""maximum"": 0.3325082771559966, ""mean"": -0.061407429436107094, ""measured_model_count"": 56, ""median"": -0.05751971111293863, ""minimum"": -0.37072006405562824, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.0014619466818978008, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.02069457658383381, ""interquartile_range"": 0.03437754339962874, ""maximum"": 0.3217848067260631, ""mean"": 0.051741718849113674, ""measured_model_count"": 56, ""median"": 0.036589651850089416, ""minimum"": 0.001902674157795965, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.05507211998346255, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], 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0.052908110898977054}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 11.11111111111111}" valid candidate_overlay.tsv;selected_target_profiles.tsv +SMAD2 symbol:SMAD2|entrez:4087 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.04437470527249164, ""interquartile_range"": 0.10986926077333312, ""maximum"": 0.1719519122172183, ""mean"": 0.0053355756530233155, ""measured_model_count"": 56, ""median"": 0.020857726704379374, ""minimum"": -0.24627069147106154, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.06549455550084148, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.010600862933249054, ""interquartile_range"": 0.016872658456282188, ""maximum"": 0.15468658704651223, ""mean"": 0.02527240623956528, ""measured_model_count"": 56, 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70.37037037037037}" valid candidate_overlay.tsv;selected_target_profiles.tsv +SMO symbol:SMO|entrez:6608 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.09197586746769547, ""interquartile_range"": 0.12796016494418277, ""maximum"": 0.37503303447012404, ""mean"": -0.014626427931529379, ""measured_model_count"": 56, ""median"": -0.016674116349569723, ""minimum"": -0.21920401677704732, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.03598429747648731, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.01294561446721113, ""interquartile_range"": 0.03573012833095012, ""maximum"": 0.18896716316175619, ""mean"": 0.03749273032273328, ""measured_model_count"": 56, ""median"": 0.025248343352956944, ""minimum"": 0.0009806870821544142, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.04867574279816125, ""threshold_fractions"": [{""denominator"": 56, 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negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 96.29629629629629}" valid candidate_overlay.tsv;selected_target_profiles.tsv +SPOP symbol:SPOP|entrez:8405 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.10868585464553142, ""interquartile_range"": 0.1953317650864464, ""maximum"": 0.31868793248113303, ""mean"": -0.02062799177610516, ""measured_model_count"": 56, ""median"": -0.0011139874447977718, ""minimum"": -0.5162901003081669, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.08664591044091499, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.008332047232900763, ""interquartile_range"": 0.04870586649525993, ""maximum"": 0.5876800902917391, ""mean"": 0.058468297685737296, ""measured_model_count"": 56, ""median"": 0.021659335715944927, ""minimum"": 0.0014736174637020138, ""missing_fraction"": 0.0, 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"{""available"": true, ""first_quartile"": -0.23573951656616127, ""interquartile_range"": 0.20424707807953718, ""maximum"": 0.34140535907966685, ""mean"": -0.13581506022797174, ""measured_model_count"": 56, ""median"": -0.144887275560554, ""minimum"": -0.5553790334161137, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.031492438486624086, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.025720312146242173, ""interquartile_range"": 0.11840113413674436, ""maximum"": 0.6616848325855214, ""mean"": 0.12232477255665541, ""measured_model_count"": 56, ""median"": 0.07955915571703014, ""minimum"": 0.0008777444154026813, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.14412144628298654, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.07142857142857142, ""numerator"": 4, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], 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candidate_overlay.tsv;selected_target_profiles.tsv +TENT5C symbol:TENT5C|entrez:54855 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.03864097744616059, ""interquartile_range"": 0.11511279099291087, ""maximum"": 0.2541597207495479, ""mean"": 0.022881062803934028, ""measured_model_count"": 56, ""median"": 0.021952823430253073, ""minimum"": -0.23474050442874117, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.07647181354675028, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.008053275498989303, ""interquartile_range"": 0.021966046073802734, ""maximum"": 0.13889360325225697, ""mean"": 0.0244585667177243, ""measured_model_count"": 56, ""median"": 0.018800263137722335, ""minimum"": 0.00141942221638269, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.030019321572792038, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, 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valid candidate_overlay.tsv;selected_target_profiles.tsv +TNFRSF18 symbol:TNFRSF18|entrez:8784 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.07992287378746069, ""interquartile_range"": 0.16347160736788924, ""maximum"": 0.32511428764823874, ""mean"": 0.005618184042927659, ""measured_model_count"": 56, ""median"": 0.0031678861143592326, ""minimum"": -0.21018912008582508, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.08354873358042854, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0081397024736693, ""interquartile_range"": 0.031395612021018315, ""maximum"": 0.15023873693250508, ""mean"": 0.03150136361917189, ""measured_model_count"": 56, ""median"": 0.020690473212946793, ""minimum"": 0.0011876348486895474, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.03953531449468761, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.0005077224690275967, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.8}], ""gene_effect_mean"": 0.0011663910963865837, ""gene_effect_median"": 0.0003505570529605071}, ""dependency_probability_context_minus_non_context_median"": 0.0005077224690275967, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.0012230906635720294, ""gene_effect_context_minus_non_context_median"": 0.00040631170298858175}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 51.851851851851855}" valid candidate_overlay.tsv;selected_target_profiles.tsv +TP53 symbol:TP53|entrez:7157 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.2682694657614673, ""interquartile_range"": 0.9489021294915423, ""maximum"": 2.138262318199002, ""mean"": 0.8412020305059892, ""measured_model_count"": 56, ""median"": 0.8202592324433257, ""minimum"": -0.056749573342901705, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 1.2171715952530096, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0, ""interquartile_range"": 0.0022901272198506146, ""maximum"": 0.0445887680510194, ""mean"": 0.0038902041225716394, ""measured_model_count"": 56, ""median"": 2.371112152923413e-07, ""minimum"": 0.0, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.0022901272198506146, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.002697179320060296, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.0041390728476821195, ""pan_cancer_fraction"": 0.0041390728476821195, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0024834437086092716, ""pan_cancer_fraction"": 0.0024834437086092716, ""threshold"": 0.8}], ""gene_effect_mean"": 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candidate_overlay.tsv;selected_target_profiles.tsv +TP63 symbol:TP63|entrez:8626 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.03646717175085289, ""interquartile_range"": 0.15602502361875212, ""maximum"": 0.26270167319502213, ""mean"": 0.02883004458571577, ""measured_model_count"": 56, ""median"": 0.06069628975320457, ""minimum"": -1.13379244109757, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.11955785186789922, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0056286828889941356, ""interquartile_range"": 0.02006209381979438, ""maximum"": 0.996906606222216, ""mean"": 0.043125430114191884, ""measured_model_count"": 56, ""median"": 0.012420727182457592, ""minimum"": 0.0009590426965118661, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.025690776708788516, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 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0.0954861111111111, ""threshold"": 0.5}, {""context_fraction"": 0.017857142857142856, ""difference"": -0.05592757936507937, ""non_context_fraction"": 0.07378472222222222, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.11874283587802412, ""gene_effect_context_minus_non_context_median"": 0.06721157973110539}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 7.407407407407407}" valid candidate_overlay.tsv;selected_target_profiles.tsv +TRAF7 symbol:TRAF7|entrez:84231 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.2406753121206499, ""interquartile_range"": 0.24695097977219208, ""maximum"": 0.3790647504468809, ""mean"": -0.12737792628681918, 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candidate_overlay.tsv;selected_target_profiles.tsv +TRRAP symbol:TRRAP|entrez:8295 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -1.5213804808497076, ""interquartile_range"": 0.433843564982187, ""maximum"": -0.6227212037899151, ""mean"": -1.3167452715650814, ""measured_model_count"": 56, ""median"": -1.2709263893882927, ""minimum"": -2.0119956971319883, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -1.0875369158675205, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.9777798803483504, ""interquartile_range"": 0.022107860279671154, ""maximum"": 1.0, ""mean"": 0.9787434420409532, ""measured_model_count"": 56, ""median"": 0.9937763894442102, ""minimum"": 0.7036541177148524, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.9998877406280215, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 1.0, ""numerator"": 56, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.9821428571428571, ""numerator"": 55, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.005300264985414804, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 1.0, ""difference"": 0.004966887417218513, ""pan_cancer_fraction"": 0.9950331125827815, ""threshold"": 0.5}, {""context_fraction"": 0.9821428571428571, ""difference"": 0.0003547776726584573, ""pan_cancer_fraction"": 0.9817880794701986, ""threshold"": 0.8}], ""gene_effect_mean"": 0.17644201944194293, ""gene_effect_median"": 0.2275108688164056}, ""dependency_probability_context_minus_non_context_median"": -0.005395260689111003, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 1.0, ""difference"": 0.00520833333333337, ""non_context_fraction"": 0.9947916666666666, ""threshold"": 0.5}, {""context_fraction"": 0.9821428571428571, ""difference"": 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2098 "{""available"": true, ""first_quartile"": -0.021924422131844194, ""interquartile_range"": 0.13036313008930414, ""maximum"": 0.22068382718892765, ""mean"": 0.03780463155728201, ""measured_model_count"": 56, ""median"": 0.039761465584603584, ""minimum"": -0.16487265242462967, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.10843870795745994, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.00790018032460166, ""interquartile_range"": 0.016458370447756117, ""maximum"": 0.12554764195984902, ""mean"": 0.019476503614389358, ""measured_model_count"": 56, ""median"": 0.013953535396493747, ""minimum"": 0.00202859216667188, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.024358550772357775, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], 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+U2AF1 symbol:U2AF1|entrez:7307 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -2.2850637997149565, ""interquartile_range"": 0.5402155616805826, ""maximum"": -1.3937878711893064, ""mean"": -2.003858590452997, ""measured_model_count"": 56, ""median"": -1.9445118925982248, ""minimum"": -2.7346918251771903, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -1.744848238034374, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.9999988989874314, ""interquartile_range"": 1.1010125685606553e-06, ""maximum"": 1.0, ""mean"": 0.9997710798620709, ""measured_model_count"": 56, ""median"": 1.0, ""minimum"": 0.9927101937690168, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 1.0, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 1.0, ""numerator"": 56, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 1.0, ""numerator"": 56, ""threshold"": 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55.55555555555556}" valid candidate_overlay.tsv;selected_target_profiles.tsv +USP6 symbol:USP6|entrez:9098 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.21946144443193774, ""interquartile_range"": 0.1836133575142457, ""maximum"": 0.09091474588958395, ""mean"": -0.13462308545365242, ""measured_model_count"": 56, ""median"": -0.14083080016013066, ""minimum"": -0.4133470078215248, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.035848086917692035, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.03158062220146937, ""interquartile_range"": 0.10676534490012221, ""maximum"": 0.38024577182219427, ""mean"": 0.09450311024282725, ""measured_model_count"": 56, ""median"": 0.07325111118993291, ""minimum"": 0.007333353368402815, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.13834596710159158, ""threshold_fractions"": [{""denominator"": 56, 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means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 22.22222222222222}" valid candidate_overlay.tsv;selected_target_profiles.tsv +WNT5A symbol:WNT5A|entrez:7474 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.013475623132929507, ""interquartile_range"": 0.12987435128430827, ""maximum"": 0.3150759319494393, ""mean"": 0.053669849425937624, ""measured_model_count"": 56, ""median"": 0.058772730317348545, ""minimum"": -0.24052616114158287, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.11639872815137876, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.0056110526655506286, ""interquartile_range"": 0.019919012256410858, ""maximum"": 0.11933478473212114, ""mean"": 0.01871307104063123, ""measured_model_count"": 56, ""median"": 0.01236916749744851, ""minimum"": 0.0021382880799880946, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.025530064921961488, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": -0.003466261549901078, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.8}], ""gene_effect_mean"": 0.016387858683863096, ""gene_effect_median"": 0.021945093816684393}, ""dependency_probability_context_minus_non_context_median"": -0.0035947955386887165, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.01718449070321755, ""gene_effect_context_minus_non_context_median"": 0.022721044347566006}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 22.22222222222222}" valid candidate_overlay.tsv;selected_target_profiles.tsv +WRN symbol:WRN|entrez:7486 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.22747322797558123, ""interquartile_range"": 0.18738191531852705, ""maximum"": 0.1869225639090439, ""mean"": -0.1472173168641097, ""measured_model_count"": 56, ""median"": -0.1359431135451314, ""minimum"": -0.6702924398334323, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": -0.040091312657054186, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.029615962721536174, ""interquartile_range"": 0.12028353472893429, ""maximum"": 0.7328436063532079, ""mean"": 0.1242273410614679, ""measured_model_count"": 56, ""median"": 0.06804582138278752, ""minimum"": 0.005152580595719504, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.14989949745047046, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.05357142857142857, ""numerator"": 3, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.0054367770673847265, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.05357142857142857, ""difference"": -0.022587511825922425, ""pan_cancer_fraction"": 0.076158940397351, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.041390728476821195, ""pan_cancer_fraction"": 0.041390728476821195, ""threshold"": 0.8}], ""gene_effect_mean"": 0.03292790495233883, ""gene_effect_median"": -0.014512486907057545}, ""dependency_probability_context_minus_non_context_median"": 0.005489758575097134, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.05357142857142857, ""difference"": -0.02368551587301588, ""non_context_fraction"": 0.07725694444444445, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.043402777777777776, ""non_context_fraction"": 0.043402777777777776, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": 0.034528566998633076, ""gene_effect_context_minus_non_context_median"": -0.01488164753445749}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 59.25925925925926}" valid candidate_overlay.tsv;selected_target_profiles.tsv +ZBTB16 symbol:ZBTB16|entrez:7704 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.009823719243372997, ""interquartile_range"": 0.16578865722223748, ""maximum"": 0.41204654436023724, ""mean"": 0.07249807663874529, ""measured_model_count"": 56, ""median"": 0.07415276241873536, ""minimum"": -0.30348607293974983, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.1559649379788645, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.004890986360055396, ""interquartile_range"": 0.018207855814234508, ""maximum"": 0.185233568494693, ""mean"": 0.019665096749805024, ""measured_model_count"": 56, ""median"": 0.010731332181391433, ""minimum"": 0.00039811689207587927, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.023098842174289903, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.0007056036329970497, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.0033112582781456954, ""pan_cancer_fraction"": 0.0033112582781456954, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.0016556291390728477, ""pan_cancer_fraction"": 0.0016556291390728477, ""threshold"": 0.8}], ""gene_effect_mean"": -0.010563662912873154, ""gene_effect_median"": -0.009279418078398133}, ""dependency_probability_context_minus_non_context_median"": 0.0007056036329970497, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.003472222222222222, ""non_context_fraction"": 0.003472222222222222, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": -0.001736111111111111, ""non_context_fraction"": 0.001736111111111111, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.011077174304471166, ""gene_effect_context_minus_non_context_median"": -0.009864062164104292}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 59.25925925925926}" valid candidate_overlay.tsv;selected_target_profiles.tsv +ZFHX3 symbol:ZFHX3|entrez:463 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": -0.06146208289047472, ""interquartile_range"": 0.14758793421665212, ""maximum"": 0.2881461102807952, ""mean"": 0.007927014410996538, ""measured_model_count"": 55, ""median"": 0.007593842404380845, ""minimum"": -0.33029884415193866, ""missing_fraction"": 0.017857142857142856, ""missing_model_count"": 1, ""third_quartile"": 0.08612585132617741, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.008564060822250814, ""interquartile_range"": 0.02700284675819572, ""maximum"": 0.23484293062520295, ""mean"": 0.03819658296592888, ""measured_model_count"": 55, ""median"": 0.019485636278314837, ""minimum"": 0.0010067610165416245, ""missing_fraction"": 0.017857142857142856, ""missing_model_count"": 1, ""third_quartile"": 0.03556690758044653, ""threshold_fractions"": [{""denominator"": 55, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 55, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.004526778394754729, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.0017167381974248926, ""pan_cancer_fraction"": 0.0017167381974248926, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.8}], ""gene_effect_mean"": -0.029396869620069162, ""gene_effect_median"": -0.032940962307585524}, ""dependency_probability_context_minus_non_context_median"": 0.004707711822055958, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": -0.0018018018018018018, ""non_context_fraction"": 0.0018018018018018018, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.03085347126791045, ""gene_effect_context_minus_non_context_median"": -0.03387072477789323}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 77.77777777777777}" valid candidate_overlay.tsv;selected_target_profiles.tsv +ZNF331 symbol:ZNF331|entrez:55422 true sufficient_complete_coverage 56 2098 "{""available"": true, ""first_quartile"": 0.1254636788972895, ""interquartile_range"": 0.14498040321724526, ""maximum"": 0.7050101742014865, ""mean"": 0.19150820508534952, ""measured_model_count"": 56, ""median"": 0.19280092244168862, ""minimum"": -0.15201787565274216, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.27044408211453475, ""threshold_fractions"": [], ""total_model_count"": 56}" "{""available"": true, ""first_quartile"": 0.001704372331237138, ""interquartile_range"": 0.005424707330500494, ""maximum"": 0.10954958289983124, ""mean"": 0.009442167813529304, ""measured_model_count"": 56, ""median"": 0.003587808287988493, ""minimum"": 1.0645838207346946e-05, ""missing_fraction"": 0.0, ""missing_model_count"": 0, ""third_quartile"": 0.007129079661737632, ""threshold_fractions"": [{""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.5}, {""denominator"": 56, ""fraction"": 0.0, ""numerator"": 0, ""threshold"": 0.8}], ""total_model_count"": 56}" "{""context_minus_pan_cancer"": {""dependency_probability_median"": 0.000887099880134024, ""dependency_probability_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""pan_cancer_fraction"": 0.0, ""threshold"": 0.8}], ""gene_effect_mean"": -0.04234439864678727, ""gene_effect_median"": -0.04372457184518963}, ""dependency_probability_context_minus_non_context_median"": 0.0009410321401466981, ""dependency_probability_context_minus_non_context_threshold_fractions"": [{""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.5}, {""context_fraction"": 0.0, ""difference"": 0.0, ""non_context_fraction"": 0.0, ""threshold"": 0.8}], ""direction"": ""Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group."", ""gene_effect_context_minus_non_context_mean"": -0.04440280691433923, ""gene_effect_context_minus_non_context_median"": -0.045076343973518174}" "{""available"": true, ""direction"": ""100 means a stronger (more negative median gene-effect) context signal than most eligible lineages."", ""eligible_lineage_count"": 28, ""value"": 81.48148148148148}" valid candidate_overlay.tsv;selected_target_profiles.tsv diff --git a/data/releases/depmap/DepMap_Public_26Q1/source_manifest.json b/data/releases/depmap/DepMap_Public_26Q1/source_manifest.json new file mode 100644 index 0000000..48ac188 --- /dev/null +++ b/data/releases/depmap/DepMap_Public_26Q1/source_manifest.json @@ -0,0 +1 @@ +{"configuration_id":"v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6","context_identity":"melanoma_anti_pd1:v1","derivation":"Validated aggregate functional-dependency closure; no recalculation.","official_download_url":"https://depmap.org/portal/data_page/?release=DepMap+Public+26Q1","official_release_notes_url":"https://forum.depmap.org/t/announcing-the-26q1-release/4606","redistributability_boundary":"Raw DepMap matrices are not committed.","release_identifier":"DepMap_Public_26Q1","release_manifest_id":"dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1","scientific_closure_identity":"v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4","source_files":[{"byte_size":432362817,"filename":"CRISPRGeneDependency.csv","role":"CRISPR dependency-probability matrix","sha256":"5de498b8fba15897f4f4d6a93681c25d5d41fdbc29f82a5968abb113cc553308"},{"byte_size":440646050,"filename":"CRISPRGeneEffect.csv","role":"CRISPR gene-effect matrix","sha256":"e610a4cefb13a82b5b256b47eb08b63ff14843f8dbd0fb164bc0a32688e5b89e"},{"byte_size":25021,"filename":"CRISPRInferredCommonEssentials.csv","role":"validated DepMap release input","sha256":"c21c92c52579182a7c25bcab1f7e9ec0a54cd09d10677f7e0f1e42558303e6c8"},{"byte_size":17440425,"filename":"Gene.csv","role":"validated DepMap release input","sha256":"0f668e0fb4356a82b791a4a4f037b223b266a589177f7b1c173cc241e33422ea"},{"byte_size":697455,"filename":"Model.csv","role":"model metadata","sha256":"ea4e0b2a3bc806f81df62689a5ae75f1a100135727a3d7b8a4c7ccc8815183f8"},{"byte_size":47292,"filename":"README.txt","role":"validated DepMap release input","sha256":"350161496c7bda9031fe9ebfaa5df51fede813362dcc36b287607af568fcb9b5"}],"source_project":"DepMap","source_release":"DepMap Public 26Q1"} diff --git a/docs/data/depmap_public_26q1.md b/docs/data/depmap_public_26q1.md new file mode 100644 index 0000000..3e30257 --- /dev/null +++ b/docs/data/depmap_public_26q1.md @@ -0,0 +1,43 @@ +# DepMap Public 26Q1 source and publication guide + +TargetIntel-IO v0.5.0 uses the validated `DepMap_Public_26Q1` closure for an +optional, post-ranking functional-dependency research preview. Obtain bulk +data only from the official [DepMap downloads page](https://depmap.org/portal/data_page/?release=DepMap+Public+26Q1), not by scraping interactive portal pages. The official [26Q1 release notes](https://forum.depmap.org/t/announcing-the-26q1-release/4606) provide release context. + +The published [`source_manifest.json`](../../data/releases/depmap/DepMap_Public_26Q1/source_manifest.json) +records the exact filenames, SHA-256 checksums, sizes, and roles from the +validated download ledger. The validated run used `CRISPRGeneEffect.csv` for +gene-effect aggregates, `CRISPRGeneDependency.csv` for dependency-probability +aggregates, and `Model.csv` for model-context metadata; its ledger also records +`Gene.csv`, `CRISPRInferredCommonEssentials.csv`, and `README.txt`. Raw inputs +are not redistributed. + +Place official downloads beneath a directory such as +``. Run the validated closure externally, then publish +only its already-derived aggregate output: + +```bash +python scripts/13_publish_depmap_v050.py \ + --run-dir \ + --config-dir /config \ + --manifest-dir /manifests \ + --ranked-targets /ranked_targets.tsv \ + --output-dir /data/releases/depmap/DepMap_Public_26Q1 \ + --html-output-dir /examples/html_reports/depmap_26q1 \ + --cards-output-dir /examples/target_cards/depmap_26q1 +``` + +The command performs no network access, DepMap ingestion, profile calculation, +benchmark calculation, integration calculation, or raw-matrix modification. +It validates identities, creates aggregate records for all 331 discovery +identities, and rejects unsafe paths and oversized output. After successful +publication, the normal report workflow can use the bundle without the +original matrices: + +```bash +targetintel run --depmap-snapshot data/releases/depmap/DepMap_Public_26Q1 +``` + +Raw matrices, complete model metadata, screen-level matrices, full +18,531-gene profile JSONL, archives, caches, and operational logs remain +excluded. The bundle contains only portable aggregate report evidence. diff --git a/docs/releases/v0.5.0.md b/docs/releases/v0.5.0.md index 4fd6059..e788a98 100644 --- a/docs/releases/v0.5.0.md +++ b/docs/releases/v0.5.0.md @@ -72,8 +72,22 @@ The original 300-target antibody/IO baseline remained preserved. The dependency-aware candidate is optional, production activation is disabled, and any activation requires a separate human decision. -Repository-safe evidence is available in -[`docs/releases/evidence/v0.5.0/`](evidence/v0.5.0/). +The repository-safe aggregate evidence bundle is published at +`data/releases/depmap/DepMap_Public_26Q1`; versioned HTML and Markdown examples +are under `examples/html_reports/depmap_26q1` and +`examples/target_cards/depmap_26q1`. It contains source and publication +manifests, checksums, a complete inventory, sanitized closure reports, +aggregate profiles and portable report evidence for all 331 discovery +identities. Raw matrices, complete metadata, full profile JSONL, caches, and +local run data are excluded. See the [source guide](../data/depmap_public_26q1.md) +for official downloads and reproduction. + +When the bundle is supplied, the DepMap overlay remains research-preview only: +it reports baseline rank, dependency-aware candidate rank, and their difference +without changing the authoritative baseline. Human review remains required; no +authorization or production activation is emitted. + +Single-cell and spatial evidence integration is planned for v0.6.0. ## Scientific boundary diff --git a/examples/html_reports/depmap_26q1/depmap_discovery_overlay.html b/examples/html_reports/depmap_26q1/depmap_discovery_overlay.html new file mode 100644 index 0000000..51e1eea --- /dev/null +++ b/examples/html_reports/depmap_26q1/depmap_discovery_overlay.html @@ -0,0 +1 @@ +DepMap discovery overlay

DepMap functional-dependency research preview — discovery overlay

Complete 331-identity discovery universe. The productive 300-gene baseline remains authoritative; discovery-only identities are not promoted into it.

Coverage: 331 available profiles; 0 unavailable profiles. Benchmark and holdout membership is not available in this portable overlay unless explicitly recorded.

Rank delta = dependency-aware candidate rank minus baseline rank. Negative deltas move toward a lower numerical rank and are not biological validation. DepMap cell-line dependency is not clinical anti-PD-1 response evidence; broad dependency may reflect general essentiality, and cell lines do not reproduce the complete tumor microenvironment.

Baseline and DepMap overlay views

TargetMembershipProfile availableCoverageBaseline rankResearch-preview DepMap overlay rankRank deltaBenchmarkHoldout
ABL1productive baselineTruesufficient_complete_coverage2982980nonot recorded
ACKR3productive baselineTruesufficient_complete_coverage2222220nonot recorded
ACVR1Bproductive baselineTruesufficient_complete_coverage1901900nonot recorded
AFDNproductive baselineTruesufficient_complete_coverage1471470nonot recorded
AFF4productive baselineTruesufficient_complete_coverage2032030nonot recorded
AKT1productive baselineTruesufficient_complete_coverage69690nonot recorded
AKT2productive baselineTruesufficient_complete_coverage97970nonot recorded
ALKproductive baselineTruesufficient_complete_coverage2632630nonot recorded
AMER1productive baselineTruesufficient_complete_coverage1721720nonot recorded
APCproductive baselineTruesufficient_complete_coverage2412410nonot recorded
APOBEC3Bproductive baselineTruesufficient_complete_coverage2692690nonot recorded
ARproductive baselineTruesufficient_complete_coverage1031030nonot recorded
ARG1discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesyes
ARHGAP35productive baselineTruesufficient_complete_coverage1281280nonot recorded
ARHGEF12productive baselineTruesufficient_complete_coverage2042040nonot recorded
ARID1Aproductive baselineTruesufficient_complete_coverage1791790nonot recorded
ARID1Bproductive baselineTruesufficient_complete_coverage1621620nonot recorded
ARID2productive baselineTruesufficient_complete_coverage20200nonot recorded
ARNTproductive baselineTruesufficient_complete_coverage1361360nonot recorded
ASPSCR1productive baselineTruesufficient_complete_coverage3003000nonot recorded
ATF1productive baselineTruesufficient_complete_coverage1731730nonot recorded
ATMproductive baselineTruesufficient_complete_coverage35350nonot recorded
ATP2B3productive baselineTruesufficient_complete_coverage2522520nonot recorded
ATRproductive baselineTruesufficient_complete_coverage63630nonot recorded
ATRXproductive baselineTruesufficient_complete_coverage92920nonot recorded
AXIN1productive baselineTruesufficient_complete_coverage1511510nonot recorded
AXLdiscovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
B2Mproductive baselineTruesufficient_complete_coverage95-4yesno
BACH2productive baselineTruesufficient_complete_coverage2902900nonot recorded
BAP1productive baselineTruesufficient_complete_coverage13130yesno
BCL11Aproductive baselineTruesufficient_complete_coverage1431430nonot recorded
BCL11Bproductive baselineTruesufficient_complete_coverage2302300nonot recorded
BCL2productive baselineTruesufficient_complete_coverage2702700nonot recorded
BCL9productive baselineTruesufficient_complete_coverage2342340nonot recorded
BCL9Lproductive baselineTruesufficient_complete_coverage1341340nonot recorded
BCORproductive baselineTruesufficient_complete_coverage1561560nonot recorded
BCORL1productive baselineTruesufficient_complete_coverage2182180nonot recorded
BIRC3productive baselineTruesufficient_complete_coverage2622620nonot recorded
BRAFproductive baselineTruesufficient_complete_coverage71-6yesno
BRCA1productive baselineTruesufficient_complete_coverage68680nonot recorded
BRCA2productive baselineTruesufficient_complete_coverage31310nonot recorded
BRD3productive baselineTruesufficient_complete_coverage2352350nonot recorded
BRD4productive baselineTruesufficient_complete_coverage1831830nonot recorded
BTKproductive baselineTruesufficient_complete_coverage2282280nonot recorded
BUB1Bproductive baselineTruesufficient_complete_coverage2202200nonot recorded
CACNA1Dproductive baselineTruesufficient_complete_coverage2262260nonot recorded
CARD11productive baselineTruesufficient_complete_coverage1811810nonot recorded
CARS1productive baselineTruesufficient_complete_coverage2512510nonot recorded
CASP8productive baselineTruesufficient_complete_coverage1141140nonot recorded
CBFA2T3productive baselineTruesufficient_complete_coverage2792790nonot recorded
CBLproductive baselineTruesufficient_complete_coverage99990nonot recorded
CBLBproductive baselineTruesufficient_complete_coverage1411410nonot recorded
CCND1productive baselineTruesufficient_complete_coverage46460nonot recorded
CCND2productive baselineTruesufficient_complete_coverage1371370nonot recorded
CD274productive baselineTruesufficient_complete_coverage396yesno
CD79Aproductive baselineTruesufficient_complete_coverage2752750nonot recorded
CD8Adiscovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
CDH1productive baselineTruesufficient_complete_coverage2892890nonot recorded
CDK12productive baselineTruesufficient_complete_coverage94940nonot recorded
CDK4productive baselineTruesufficient_complete_coverage1814-4yesyes
CDK6productive baselineTruesufficient_complete_coverage1101100nonot recorded
CDKN2Aproductive baselineTruesufficient_complete_coverage12186yesno
CDKN2Bproductive baselineTruesufficient_complete_coverage2592590nonot recorded
CDX2productive baselineTruesufficient_complete_coverage1891890nonot recorded
CHD4productive baselineTruesufficient_complete_coverage2122120nonot recorded
CHEK2productive baselineTruesufficient_complete_coverage62620nonot recorded
CICproductive baselineTruesufficient_complete_coverage1641640nonot recorded
CIITAproductive baselineTruesufficient_complete_coverage1331330nonot recorded
CLPTM1Lproductive baselineTruesufficient_complete_coverage2992990nonot recorded
CLTCproductive baselineTruesufficient_complete_coverage2312310nonot recorded
CNOT3productive baselineTruesufficient_complete_coverage1701700nonot recorded
CNOT9productive baselineTruesufficient_complete_coverage2842840nonot recorded
CREB1productive baselineTruesufficient_complete_coverage1951950nonot recorded
CREBBPproductive baselineTruesufficient_complete_coverage1651650nonot recorded
CRLF2productive baselineTrueinsufficient_measured_context_models1981980nonot recorded
CSF1Rdiscovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
CSF3Rproductive baselineTruesufficient_complete_coverage38380nonot recorded
CTLA4productive baselineTruesufficient_complete_coverage1109yesno
CTNNB1productive baselineTruesufficient_complete_coverage2432430nonot recorded
CUX1productive baselineTruesufficient_complete_coverage64640nonot recorded
CXCL12discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
CXCL9discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
CXCR4discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesyes
CYLDproductive baselineTruesufficient_complete_coverage1051050nonot recorded
CYP1B1productive baselineTruesufficient_complete_coverage1311310nonot recorded
DAXXproductive baselineTruesufficient_complete_coverage1591590nonot recorded
DDR2productive baselineTruesufficient_complete_coverage1211210nonot recorded
DDX3Xproductive baselineTruesufficient_complete_coverage42420nonot recorded
DICER1productive baselineTruesufficient_complete_coverage57570nonot recorded
DNMT3Aproductive baselineTruesufficient_complete_coverage1001000nonot recorded
EGFRproductive baselineTruesufficient_complete_coverage1971970nonot recorded
ENTPD1discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
EP300productive baselineTruesufficient_complete_coverage66660nonot recorded
ERBB2productive baselineTruesufficient_complete_coverage71710nonot recorded
ERBB3productive baselineTruesufficient_complete_coverage91910nonot recorded
ERBB4productive baselineTruesufficient_complete_coverage47470nonot recorded
ERCC2productive baselineTruesufficient_complete_coverage1071070nonot recorded
ERCC3productive baselineTruesufficient_complete_coverage1571570nonot recorded
ERCC4productive baselineTruesufficient_complete_coverage1751750nonot recorded
ERCC5productive baselineTruesufficient_complete_coverage1741740nonot recorded
ESR1productive baselineTruesufficient_complete_coverage67670nonot recorded
EZH2productive baselineTruesufficient_complete_coverage1851850nonot recorded
FANCAproductive baselineTruesufficient_complete_coverage1321320nonot recorded
FANCD2productive baselineTruesufficient_complete_coverage1581580nonot recorded
FANCEproductive baselineTruesufficient_complete_coverage2602600nonot recorded
FANCFproductive baselineTruesufficient_complete_coverage2392390nonot recorded
FASproductive baselineTruesufficient_complete_coverage2162160nonot recorded
FAT1productive baselineTruesufficient_complete_coverage56560nonot recorded
FAT4productive baselineTruesufficient_complete_coverage73730nonot recorded
FBXO11productive baselineTruesufficient_complete_coverage2132130nonot recorded
FBXW7productive baselineTruesufficient_complete_coverage2962960nonot recorded
FCRL4productive baselineTruesufficient_complete_coverage1681680nonot recorded
FGFR1productive baselineTruesufficient_complete_coverage84840nonot recorded
FGFR2productive baselineTruesufficient_complete_coverage76760nonot recorded
FGFR3productive baselineTruesufficient_complete_coverage2472470nonot recorded
FGFR4productive baselineTruesufficient_complete_coverage78780nonot recorded
FHproductive baselineTruesufficient_complete_coverage2482480nonot recorded
FLGproductive baselineTruesufficient_complete_coverage1711710nonot recorded
FLT3productive baselineTruesufficient_complete_coverage2272270nonot recorded
FLT4productive baselineTruesufficient_complete_coverage37370nonot recorded
FMN1productive baselineTruesufficient_complete_coverage2662660nonot recorded
FOXP1productive baselineTruesufficient_complete_coverage43430nonot recorded
FOXP3discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
FUBP1productive baselineTruesufficient_complete_coverage2642640nonot recorded
GATA2productive baselineTruesufficient_complete_coverage2682680nonot recorded
GNA11productive baselineTruesufficient_complete_coverage2423-1yesyes
GNAQproductive baselineTruesufficient_complete_coverage1915-4yesno
GNASproductive baselineTruesufficient_complete_coverage1181180nonot recorded
GRIN2Aproductive baselineTruesufficient_complete_coverage79790nonot recorded
GZMBdiscovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
H3-3Aproductive baselineTruesufficient_complete_coverage2672670nonot recorded
H3-3Bproductive baselineTruesufficient_complete_coverage52520nonot recorded
H3C2productive baselineTruesufficient_complete_coverage2932930nonot recorded
HAVCR2discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
HGFproductive baselineTruesufficient_complete_coverage1541540nonot recorded
HLA-Adiscovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
HLA-Bdiscovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesyes
HNF1Aproductive baselineTruesufficient_complete_coverage1421420nonot recorded
HRASproductive baselineTruesufficient_complete_coverage2832830nonot recorded
IDH1productive baselineTruesufficient_complete_coverage1081080nonot recorded
IDO1discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
IFNAR1productive baselineTruesufficient_complete_coverage59590nonot recorded
IFNAR2productive baselineTruesufficient_complete_coverage83830nonot recorded
IFNGR1discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
IKBKBproductive baselineTruesufficient_complete_coverage1111110nonot recorded
IKZF1productive baselineTruesufficient_complete_coverage55550nonot recorded
IKZF3productive baselineTruesufficient_complete_coverage2582580nonot recorded
IL2RAproductive baselineTruesufficient_complete_coverage561yesyes
IL2RBproductive baselineTruesufficient_complete_coverage1491490nonot recorded
IL2RGproductive baselineTruesufficient_complete_coverage1481480nonot recorded
IL7Rproductive baselineTruesufficient_complete_coverage1161160nonot recorded
IRF1discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
IRF4productive baselineTruesufficient_complete_coverage30300nonot recorded
IRS4productive baselineTruesufficient_complete_coverage1931930nonot recorded
JAK1productive baselineTruesufficient_complete_coverage11198yesno
JAK2productive baselineTruesufficient_complete_coverage108-2yesno
JUNproductive baselineTruesufficient_complete_coverage1391390nonot recorded
KAT6Aproductive baselineTruesufficient_complete_coverage1401400nonot recorded
KAT6Bproductive baselineTruesufficient_complete_coverage2362360nonot recorded
KDM5Aproductive baselineTruesufficient_complete_coverage2112110nonot recorded
KDRproductive baselineTruesufficient_complete_coverage33330nonot recorded
KEAP1productive baselineTruesufficient_complete_coverage2912910nonot recorded
KITproductive baselineTruesufficient_complete_coverage21210yesno
KLF4productive baselineTruesufficient_complete_coverage2452450nonot recorded
KLF6productive baselineTruesufficient_complete_coverage1021020nonot recorded
KMT2Aproductive baselineTruesufficient_complete_coverage1041040nonot recorded
KMT2Cproductive baselineTruesufficient_complete_coverage74740nonot recorded
KMT2Dproductive baselineTruesufficient_complete_coverage65650nonot recorded
KNL1productive baselineTruesufficient_complete_coverage2192190nonot recorded
KRASproductive baselineTruesufficient_complete_coverage2732730nonot recorded
KRT5productive baselineTruesufficient_complete_coverage2822820nonot recorded
LAG3productive baselineTruesufficient_complete_coverage473yesno
LATS2productive baselineTruesufficient_complete_coverage2552550nonot recorded
LCKproductive baselineTruesufficient_complete_coverage1871870nonot recorded
LILRB1discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
LILRB2discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesyes
LPPproductive baselineTruesufficient_complete_coverage2762760nonot recorded
LRP1Bproductive baselineTruesufficient_complete_coverage36360nonot recorded
LZTR1productive baselineTruesufficient_complete_coverage1631630nonot recorded
MAP2K1productive baselineTruesufficient_complete_coverage82-6yesno
MAP2K2productive baselineTruesufficient_complete_coverage1412-2yesno
MAP2K4productive baselineTruesufficient_complete_coverage2332330nonot recorded
MAP3K1productive baselineTruesufficient_complete_coverage2882880nonot recorded
MAP3K13productive baselineTruesufficient_complete_coverage1691690nonot recorded
MAPK1productive baselineTruesufficient_complete_coverage2812810nonot recorded
MARCOdiscovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
MAXproductive baselineTruesufficient_complete_coverage2172170nonot recorded
MBD4productive baselineTruesufficient_complete_coverage26260nonot recorded
MC1Rproductive baselineTruesufficient_complete_coverage54540nonot recorded
MDM2productive baselineTruesufficient_complete_coverage58580nonot recorded
MDM4productive baselineTruesufficient_complete_coverage88880nonot recorded
MECOMproductive baselineTruesufficient_complete_coverage60600nonot recorded
MED12productive baselineTruesufficient_complete_coverage2922920nonot recorded
MERTKdiscovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
METproductive baselineTruesufficient_complete_coverage48480nonot recorded
MITFproductive baselineTruesufficient_complete_coverage1611-5yesno
MN1productive baselineTruesufficient_complete_coverage2322320nonot recorded
MRTFAproductive baselineTruesufficient_complete_coverage2442440nonot recorded
MSH2productive baselineTruesufficient_complete_coverage2092090nonot recorded
MTAPproductive baselineTruesufficient_complete_coverage2082080nonot recorded
MTORproductive baselineTruesufficient_complete_coverage51510nonot recorded
MUTYHproductive baselineTruesufficient_complete_coverage2492490nonot recorded
MX2productive baselineTruesufficient_complete_coverage1761760nonot recorded
MYBproductive baselineTruesufficient_complete_coverage1191190nonot recorded
MYCLproductive baselineTruesufficient_complete_coverage1661660nonot recorded
MYCNproductive baselineTruesufficient_complete_coverage1451450nonot recorded
MYH9productive baselineTruesufficient_complete_coverage1611610nonot recorded
NCOR1productive baselineTruesufficient_complete_coverage2212210nonot recorded
NCOR2productive baselineTruesufficient_complete_coverage1921920nonot recorded
NF1productive baselineTruesufficient_complete_coverage17170yesno
NF2productive baselineTruesufficient_complete_coverage2802800nonot recorded
NFE2L2productive baselineTruesufficient_complete_coverage2972970nonot recorded
NFKB2productive baselineTruesufficient_complete_coverage2022020nonot recorded
NFKBIEproductive baselineTruesufficient_complete_coverage1531530nonot recorded
NGFRdiscovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesyes
NKX2-1productive baselineTruesufficient_complete_coverage2422420nonot recorded
NOTCH1productive baselineTruesufficient_complete_coverage2872870nonot recorded
NOTCH2productive baselineTruesufficient_complete_coverage1091090nonot recorded
NRASproductive baselineTruesufficient_complete_coverage63-3yesno
NT5Ediscovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
NTRK1productive baselineTruesufficient_complete_coverage70700nonot recorded
NTRK2productive baselineTruesufficient_complete_coverage1121120nonot recorded
NTRK3productive baselineTruesufficient_complete_coverage1781780nonot recorded
NUP98productive baselineTruesufficient_complete_coverage2252250nonot recorded
NUTM1productive baselineTruesufficient_complete_coverage1351350nonot recorded
OCA2productive baselineTruesufficient_complete_coverage81810nonot recorded
PARP1productive baselineTruesufficient_complete_coverage1801800nonot recorded
PATZ1productive baselineTruesufficient_complete_coverage2652650nonot recorded
PAX5productive baselineTruesufficient_complete_coverage1301300nonot recorded
PBRM1productive baselineTruesufficient_complete_coverage44440nonot recorded
PDCD1productive baselineTruesufficient_complete_coverage242yesno
PDCD1LG2productive baselineTruesufficient_complete_coverage2852850nonot recorded
PDGFRAproductive baselineTruesufficient_complete_coverage34340nonot recorded
PDGFRBproductive baselineTruesufficient_complete_coverage39390nonot recorded
PER1productive baselineTruesufficient_complete_coverage1381380nonot recorded
PHOX2Bproductive baselineTruesufficient_complete_coverage1241240nonot recorded
PIK3CAproductive baselineTruesufficient_complete_coverage2402400nonot recorded
PIK3CBproductive baselineTruesufficient_complete_coverage2952950nonot recorded
PIK3R1productive baselineTruesufficient_complete_coverage1221220nonot recorded
PLCG1productive baselineTruesufficient_complete_coverage2152150nonot recorded
PLXNB2productive baselineTruesufficient_complete_coverage2772770nonot recorded
PMELproductive baselineTruesufficient_complete_coverage2722720nonot recorded
PMS2productive baselineTruesufficient_complete_coverage2062060nonot recorded
POLD1productive baselineTruesufficient_complete_coverage1151150nonot recorded
POLEproductive baselineTruesufficient_complete_coverage41410nonot recorded
POLQproductive baselineTruesufficient_complete_coverage75750nonot recorded
POT1productive baselineTruesufficient_complete_coverage25250nonot recorded
POU2AF1productive baselineTruesufficient_complete_coverage2712710nonot recorded
PPP2R1Aproductive baselineTruesufficient_complete_coverage1551550nonot recorded
PPP6Cproductive baselineTruesufficient_complete_coverage29290nonot recorded
PRDM1productive baselineTruesufficient_complete_coverage1461460nonot recorded
PRDM16productive baselineTruesufficient_complete_coverage2532530nonot recorded
PREX2productive baselineTruesufficient_complete_coverage72720nonot recorded
PRF1productive baselineTruesufficient_complete_coverage1911910yesyes
PTCH1productive baselineTruesufficient_complete_coverage1201200nonot recorded
PTENproductive baselineTruesufficient_complete_coverage15161yesyes
PTK6productive baselineTruesufficient_complete_coverage2542540nonot recorded
PTPN11productive baselineTruesufficient_complete_coverage87870nonot recorded
PTPN13productive baselineTruesufficient_complete_coverage2142140nonot recorded
PTPRBproductive baselineTruesufficient_complete_coverage85850nonot recorded
PTPRCproductive baselineTrueinsufficient_measured_context_models1601600nonot recorded
PTPRKproductive baselineTruesufficient_complete_coverage98980nonot recorded
PTPRTproductive baselineTruesufficient_complete_coverage86860nonot recorded
QKIproductive baselineTruesufficient_complete_coverage1171170nonot recorded
RAC1productive baselineTruesufficient_complete_coverage22220nonot recorded
RAD51Cproductive baselineTruesufficient_complete_coverage2562560nonot recorded
RAF1productive baselineTruesufficient_complete_coverage32320nonot recorded
RANBP2productive baselineTruesufficient_complete_coverage2292290nonot recorded
RB1productive baselineTruesufficient_complete_coverage96960nonot recorded
RETproductive baselineTruesufficient_complete_coverage1841840nonot recorded
RICTORproductive baselineTruesufficient_complete_coverage1821820nonot recorded
ROS1productive baselineTruesufficient_complete_coverage50500nonot recorded
RPL5productive baselineTruesufficient_complete_coverage1061060nonot recorded
RRM1productive baselineTruesufficient_complete_coverage1261260nonot recorded
RRM2productive baselineTruesufficient_complete_coverage1011010nonot recorded
RRM2Bproductive baselineTruesufficient_complete_coverage1131130nonot recorded
RUNX1T1productive baselineTruesufficient_complete_coverage93930nonot recorded
SALL4productive baselineTruesufficient_complete_coverage1521520nonot recorded
SETBP1productive baselineTruesufficient_complete_coverage1251250nonot recorded
SETD2productive baselineTruesufficient_complete_coverage45450nonot recorded
SF3B1productive baselineTruesufficient_complete_coverage28280nonot recorded
SLC24A5productive baselineTruesufficient_complete_coverage2862860yesno
SLC45A2productive baselineTruesufficient_complete_coverage1671670nonot recorded
SMAD2productive baselineTruesufficient_complete_coverage1501500nonot recorded
SMAD3productive baselineTruesufficient_complete_coverage1861860nonot recorded
SMARCA4productive baselineTruesufficient_complete_coverage82820nonot recorded
SMOproductive baselineTruesufficient_complete_coverage2232230nonot recorded
SPENproductive baselineTruesufficient_complete_coverage1271270nonot recorded
SPOPproductive baselineTruesufficient_complete_coverage1941940nonot recorded
STAT1discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesyes
STAT5Bproductive baselineTruesufficient_complete_coverage2572570nonot recorded
STK11productive baselineTruesufficient_complete_coverage49490nonot recorded
STN1productive baselineTruesufficient_complete_coverage1991990nonot recorded
SUFUproductive baselineTruesufficient_complete_coverage1771770nonot recorded
SUZ12productive baselineTruesufficient_complete_coverage2782780nonot recorded
SYKproductive baselineTruesufficient_complete_coverage1291290nonot recorded
TAP1discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
TAP2discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
TBL1XR1productive baselineTruesufficient_complete_coverage2372370nonot recorded
TBX3productive baselineTruesufficient_complete_coverage90900nonot recorded
TCL1Aproductive baselineTruesufficient_complete_coverage2502500nonot recorded
TENT5Cproductive baselineTruesufficient_complete_coverage2742740nonot recorded
TERTproductive baselineTruesufficient_complete_coverage23241yesyes
TET1productive baselineTruesufficient_complete_coverage1961960nonot recorded
TET2productive baselineTruesufficient_complete_coverage40400nonot recorded
TFE3productive baselineTruesufficient_complete_coverage2002000nonot recorded
TFEBproductive baselineTruesufficient_complete_coverage1881880nonot recorded
TGFB1discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
TGFBR1discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
TIGITdiscovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
TMEM127productive baselineTruesufficient_complete_coverage2382380nonot recorded
TNFRSF17productive baselineTruesufficient_complete_coverage2942940nonot recorded
TNFRSF18discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
TP53productive baselineTruesufficient_complete_coverage27270yesno
TP63productive baselineTruesufficient_complete_coverage77770nonot recorded
TRAF7productive baselineTruesufficient_complete_coverage2012010nonot recorded
TREM2discovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
TRRAPproductive baselineTruesufficient_complete_coverage53530nonot recorded
TSC1productive baselineTruesufficient_complete_coverage89890nonot recorded
TSC2productive baselineTruesufficient_complete_coverage1231230nonot recorded
TYRproductive baselineTruesufficient_complete_coverage95950nonot recorded
TYRP1productive baselineTruesufficient_complete_coverage2612610nonot recorded
U2AF1productive baselineTruesufficient_complete_coverage2052050nonot recorded
UBR5productive baselineTruesufficient_complete_coverage80800nonot recorded
USP6productive baselineTruesufficient_complete_coverage1441440nonot recorded
WASproductive baselineTruesufficient_complete_coverage2242240nonot recorded
WNT5Adiscovery-onlyTruesufficient_complete_coveragenot availablenot availablenot availableyesno
WRNproductive baselineTruesufficient_complete_coverage61610nonot recorded
ZBTB16productive baselineTruesufficient_complete_coverage2072070nonot recorded
ZFHX3productive baselineTruesufficient_complete_coverage2102100nonot recorded
ZNF331productive baselineTruesufficient_complete_coverage2462460nonot recorded

Strongest upward rank movements

TargetMembershipProfile availableCoverageBaseline rankResearch-preview DepMap overlay rankRank deltaBenchmarkHoldout
BRAFproductive baselineTruesufficient_complete_coverage71-6yesno
MAP2K1productive baselineTruesufficient_complete_coverage82-6yesno
MITFproductive baselineTruesufficient_complete_coverage1611-5yesno
B2Mproductive baselineTruesufficient_complete_coverage95-4yesno
CDK4productive baselineTruesufficient_complete_coverage1814-4yesyes
GNAQproductive baselineTruesufficient_complete_coverage1915-4yesno
NRASproductive baselineTruesufficient_complete_coverage63-3yesno
JAK2productive baselineTruesufficient_complete_coverage108-2yesno
MAP2K2productive baselineTruesufficient_complete_coverage1412-2yesno
GNA11productive baselineTruesufficient_complete_coverage2423-1yesyes

Strongest downward rank movements

TargetMembershipProfile availableCoverageBaseline rankResearch-preview DepMap overlay rankRank deltaBenchmarkHoldout
CTLA4productive baselineTruesufficient_complete_coverage1109yesno
JAK1productive baselineTruesufficient_complete_coverage11198yesno
CD274productive baselineTruesufficient_complete_coverage396yesno
CDKN2Aproductive baselineTruesufficient_complete_coverage12186yesno
LAG3productive baselineTruesufficient_complete_coverage473yesno
PDCD1productive baselineTruesufficient_complete_coverage242yesno
IL2RAproductive baselineTruesufficient_complete_coverage561yesyes
PTENproductive baselineTruesufficient_complete_coverage15161yesyes
TERTproductive baselineTruesufficient_complete_coverage23241yesyes
ABL1productive baselineTruesufficient_complete_coverage2982980nonot recorded
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+ +
+

TargetIntel-IO reports

+

Therapeutic-intent-aware target triage for anti-PD-1-resistant melanoma

+
+ +
+

How to read these reports

+

+ TargetIntel-IO keeps the biological role of each target stable, but ranks + targets differently depending on the therapeutic intent. +

+
    +
  • High: strong candidate for that therapeutic intent.
    • +
  • Medium: plausible secondary candidate.
    • +
  • Low: weak or indirect fit.
    • +
  • Not prioritized: not a meaningful candidate for that mode under current MVP rules.
    • +
+
+ + +
+

Top antibody / IO-combination targets

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + 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+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + 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+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
RankTargetRoleBest modalityScorePriorityRank shift
1CTLA4anti-PD-1 combination targetantibody / IO-combination target0.853high14
2PDCD1anti-PD-1 combination targetantibody / IO-combination target0.827high42
3CD274anti-PD-1 combination targetantibody / IO-combination target0.825high50
4LAG3anti-PD-1 combination targetantibody / IO-combination target0.822high76
5IL2RATreg-suppression marker / possible IO-combination targetantibody / Treg-associated IO-combination candidate0.673medium43
6NRAStumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.301low-1
7BRAFtumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.269low-5
8MAP2K1tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.262low-4
9B2Mantigen-presentation resistance biomarkerresistance biomarker / patient stratification0.227low102
10JAK2IFN-gamma resistance mechanism / biomarkerresistance biomarker / patient stratification0.215low255
11JAK1IFN-gamma resistance mechanism / biomarkerresistance biomarker / patient stratification0.214low260
12CDKN2Atumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-11
13BAP1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-10
14MAP2K2tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.000not prioritized-8
15PTENtumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-8
16MITFtumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.000not prioritized-8
17NF1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-8
18CDK4tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.000not prioritized-8
19GNAQunclear / low-confidence candidateunclear0.000not prioritized-8
20ARID2unclear / low-confidence candidateunclear0.000not prioritized-8
21KITtumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.000not prioritized-8
22RAC1unclear / low-confidence candidateunclear0.000not prioritized-8
23TERTtumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.000not prioritized-7
24GNA11unclear / low-confidence candidateunclear0.000not prioritized-7
25POT1unclear / low-confidence candidateunclear0.000not prioritized-7
26MBD4unclear / low-confidence candidateunclear0.000not prioritized-7
27TP53tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-7
28SF3B1unclear / low-confidence candidateunclear0.000not prioritized-7
29PPP6Cunclear / low-confidence candidateunclear0.000not prioritized-7
30IRF4unclear / low-confidence candidateunclear0.000not prioritized-7
31BRCA2unclear / low-confidence candidateunclear0.000not prioritized-7
32RAF1unclear / low-confidence candidateunclear0.000not prioritized-7
33KDRunclear / low-confidence candidateunclear0.000not prioritized-7
34PDGFRAunclear / low-confidence candidateunclear0.000not prioritized-7
35ATMunclear / low-confidence candidateunclear0.000not prioritized-7
36LRP1Bunclear / low-confidence candidateunclear0.000not prioritized-7
37FLT4unclear / low-confidence candidateunclear0.000not prioritized-7
38CSF3Runclear / low-confidence candidateunclear0.000not prioritized-7
39PDGFRBunclear / low-confidence candidateunclear0.000not prioritized-7
40TET2unclear / low-confidence candidateunclear0.000not prioritized-7
41POLEunclear / low-confidence candidateunclear0.000not prioritized-7
42DDX3Xunclear / low-confidence candidateunclear0.000not prioritized-7
43FOXP1unclear / low-confidence candidateunclear0.000not prioritized-7
44PBRM1unclear / low-confidence candidateunclear0.000not prioritized-7
45SETD2unclear / low-confidence candidateunclear0.000not prioritized-7
46CCND1unclear / low-confidence candidateunclear0.000not prioritized-7
47ERBB4unclear / low-confidence candidateunclear0.000not prioritized-7
48METunclear / low-confidence candidateunclear0.000not prioritized-7
49STK11unclear / low-confidence candidateunclear0.000not prioritized-7
50ROS1unclear / low-confidence candidateunclear0.000not prioritized-7
51MTORunclear / low-confidence candidateunclear0.000not prioritized-6
52H3-3Bunclear / low-confidence candidateunclear0.000not prioritized-6
53TRRAPunclear / low-confidence candidateunclear0.000not prioritized-6
54MC1Runclear / low-confidence candidateunclear0.000not prioritized-5
55IKZF1unclear / low-confidence candidateunclear0.000not prioritized-5
56FAT1unclear / low-confidence candidateunclear0.000not prioritized-5
57DICER1unclear / low-confidence candidateunclear0.000not prioritized-5
58MDM2unclear / low-confidence candidateunclear0.000not prioritized-4
59IFNAR1unclear / low-confidence candidateunclear0.000not prioritized-4
60MECOMunclear / low-confidence candidateunclear0.000not prioritized-4
61WRNunclear / low-confidence candidateunclear0.000not prioritized-4
62CHEK2unclear / low-confidence candidateunclear0.000not prioritized-4
63ATRunclear / low-confidence candidateunclear0.000not prioritized-4
64CUX1unclear / low-confidence candidateunclear0.000not prioritized-4
65KMT2Dunclear / low-confidence candidateunclear0.000not prioritized-4
66EP300unclear / low-confidence candidateunclear0.000not prioritized-4
67ESR1unclear / low-confidence candidateunclear0.000not prioritized-4
68BRCA1unclear / low-confidence candidateunclear0.000not prioritized-4
69AKT1unclear / low-confidence candidateunclear0.000not prioritized-4
70NTRK1unclear / low-confidence candidateunclear0.000not prioritized-4
71ERBB2unclear / low-confidence candidateunclear0.000not prioritized-4
72PREX2unclear / low-confidence candidateunclear0.000not prioritized-4
73FAT4unclear / low-confidence candidateunclear0.000not prioritized-4
74KMT2Cunclear / low-confidence candidateunclear0.000not prioritized-4
75POLQunclear / low-confidence candidateunclear0.000not prioritized-4
76FGFR2unclear / low-confidence candidateunclear0.000not prioritized-4
77TP63unclear / low-confidence candidateunclear0.000not prioritized-4
78FGFR4unclear / low-confidence candidateunclear0.000not prioritized-4
79GRIN2Aunclear / low-confidence candidateunclear0.000not prioritized-4
80UBR5unclear / low-confidence candidateunclear0.000not prioritized-4
81OCA2unclear / low-confidence candidateunclear0.000not prioritized-4
82SMARCA4unclear / low-confidence candidateunclear0.000not prioritized-4
83IFNAR2unclear / low-confidence candidateunclear0.000not prioritized-4
84FGFR1unclear / low-confidence candidateunclear0.000not prioritized-3
85PTPRBunclear / low-confidence candidateunclear0.000not prioritized-3
86PTPRTunclear / low-confidence candidateunclear0.000not prioritized-3
87PTPN11unclear / low-confidence candidateunclear0.000not prioritized-3
88MDM4unclear / low-confidence candidateunclear0.000not prioritized-3
89TSC1unclear / low-confidence candidateunclear0.000not prioritized-3
90TBX3unclear / low-confidence candidateunclear0.000not prioritized-3
91ERBB3unclear / low-confidence candidateunclear0.000not prioritized-3
92ATRXunclear / low-confidence candidateunclear0.000not prioritized-3
93RUNX1T1unclear / low-confidence candidateunclear0.000not prioritized-3
94CDK12unclear / low-confidence candidateunclear0.000not prioritized-3
95TYRunclear / low-confidence candidateunclear0.000not prioritized-3
96RB1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-3
97AKT2unclear / low-confidence candidateunclear0.000not prioritized-3
98PTPRKunclear / low-confidence candidateunclear0.000not prioritized-3
99CBLunclear / low-confidence candidateunclear0.000not prioritized-3
100DNMT3Aunclear / low-confidence candidateunclear0.000not prioritized-3
101RRM2unclear / low-confidence candidateunclear0.000not prioritized-3
102KLF6unclear / low-confidence candidateunclear0.000not prioritized-3
103ARunclear / low-confidence candidateunclear0.000not prioritized-3
104KMT2Aunclear / low-confidence candidateunclear0.000not prioritized-3
105CYLDunclear / low-confidence candidateunclear0.000not prioritized-3
106RPL5unclear / low-confidence candidateunclear0.000not prioritized-3
107ERCC2unclear / low-confidence candidateunclear0.000not prioritized-3
108IDH1unclear / low-confidence candidateunclear0.000not prioritized-3
109NOTCH2unclear / low-confidence candidateunclear0.000not prioritized-3
110CDK6unclear / low-confidence candidateunclear0.000not prioritized-3
111IKBKBunclear / low-confidence candidateunclear0.000not prioritized-3
112NTRK2unclear / low-confidence candidateunclear0.000not prioritized-3
113RRM2Bunclear / low-confidence candidateunclear0.000not prioritized-3
114CASP8unclear / low-confidence candidateunclear0.000not prioritized-2
115POLD1unclear / low-confidence candidateunclear0.000not prioritized-2
116IL7Runclear / low-confidence candidateunclear0.000not prioritized-2
117QKIunclear / low-confidence candidateunclear0.000not prioritized-2
118GNASunclear / low-confidence candidateunclear0.000not prioritized-2
119MYBunclear / low-confidence candidateunclear0.000not prioritized-2
120PTCH1unclear / low-confidence candidateunclear0.000not prioritized-2
121DDR2unclear / low-confidence candidateunclear0.000not prioritized-2
122PIK3R1unclear / low-confidence candidateunclear0.000not prioritized-2
123TSC2unclear / low-confidence candidateunclear0.000not prioritized-2
124PHOX2Bunclear / low-confidence candidateunclear0.000not prioritized-2
125SETBP1unclear / low-confidence candidateunclear0.000not prioritized-2
126RRM1unclear / low-confidence candidateunclear0.000not prioritized-2
127SPENunclear / low-confidence candidateunclear0.000not prioritized-2
128ARHGAP35unclear / low-confidence candidateunclear0.000not prioritized-2
129SYKunclear / low-confidence candidateunclear0.000not prioritized-2
130PAX5unclear / low-confidence candidateunclear0.000not prioritized-2
131CYP1B1unclear / low-confidence candidateunclear0.000not prioritized-2
132FANCAunclear / low-confidence candidateunclear0.000not prioritized-2
133CIITAunclear / low-confidence candidateunclear0.000not prioritized-2
134BCL9Lunclear / low-confidence candidateunclear0.000not prioritized-2
135NUTM1unclear / low-confidence candidateunclear0.000not prioritized-2
136ARNTunclear / low-confidence candidateunclear0.000not prioritized-2
137CCND2unclear / low-confidence candidateunclear0.000not prioritized-2
138PER1unclear / low-confidence candidateunclear0.000not prioritized-2
139JUNunclear / low-confidence candidateunclear0.000not prioritized-2
140KAT6Aunclear / low-confidence candidateunclear0.000not prioritized-2
141CBLBunclear / low-confidence candidateunclear0.000not prioritized-2
142HNF1Aunclear / low-confidence candidateunclear0.000not prioritized-2
143BCL11Aunclear / low-confidence candidateunclear0.000not prioritized-2
144USP6unclear / low-confidence candidateunclear0.000not prioritized-2
145MYCNunclear / low-confidence candidateunclear0.000not prioritized-2
146PRDM1unclear / low-confidence candidateunclear0.000not prioritized-2
147AFDNunclear / low-confidence candidateunclear0.000not prioritized-2
148IL2RGunclear / low-confidence candidateunclear0.000not prioritized-2
149IL2RBunclear / low-confidence candidateunclear0.000not prioritized-2
150SMAD2unclear / low-confidence candidateunclear0.000not prioritized-2
151AXIN1unclear / low-confidence candidateunclear0.000not prioritized-2
152SALL4unclear / low-confidence candidateunclear0.000not prioritized-2
153NFKBIEunclear / low-confidence candidateunclear0.000not prioritized-2
154HGFunclear / low-confidence candidateunclear0.000not prioritized-2
155PPP2R1Aunclear / low-confidence candidateunclear0.000not prioritized-2
156BCORunclear / low-confidence candidateunclear0.000not prioritized-2
157ERCC3unclear / low-confidence candidateunclear0.000not prioritized-2
158FANCD2unclear / low-confidence candidateunclear0.000not prioritized-2
159DAXXunclear / low-confidence candidateunclear0.000not prioritized-2
160PTPRCunclear / low-confidence candidateunclear0.000not prioritized-2
161MYH9unclear / low-confidence candidateunclear0.000not prioritized-2
162ARID1Bunclear / low-confidence candidateunclear0.000not prioritized-2
163LZTR1unclear / low-confidence candidateunclear0.000not prioritized-2
164CICunclear / low-confidence candidateunclear0.000not prioritized-2
165CREBBPunclear / low-confidence candidateunclear0.000not prioritized-2
166MYCLunclear / low-confidence candidateunclear0.000not prioritized-2
167SLC45A2unclear / low-confidence candidateunclear0.000not prioritized-2
168FCRL4unclear / low-confidence candidateunclear0.000not prioritized-2
169MAP3K13unclear / low-confidence candidateunclear0.000not prioritized-2
170CNOT3unclear / low-confidence candidateunclear0.000not prioritized-2
171FLGunclear / low-confidence candidateunclear0.000not prioritized-2
172AMER1unclear / low-confidence candidateunclear0.000not prioritized-2
173ATF1unclear / low-confidence candidateunclear0.000not prioritized-2
174ERCC5unclear / low-confidence candidateunclear0.000not prioritized-2
175ERCC4unclear / low-confidence candidateunclear0.000not prioritized-2
176MX2unclear / low-confidence candidateunclear0.000not prioritized-2
177SUFUunclear / low-confidence candidateunclear0.000not prioritized-2
178NTRK3unclear / low-confidence candidateunclear0.000not prioritized-2
179ARID1Aunclear / low-confidence candidateunclear0.000not prioritized-2
180PARP1unclear / low-confidence candidateunclear0.000not prioritized-2
181CARD11unclear / low-confidence candidateunclear0.000not prioritized-2
182RICTORunclear / low-confidence candidateunclear0.000not prioritized-2
183BRD4unclear / low-confidence candidateunclear0.000not prioritized-2
184RETunclear / low-confidence candidateunclear0.000not prioritized-2
185EZH2unclear / low-confidence candidateunclear0.000not prioritized-2
186SMAD3unclear / low-confidence candidateunclear0.000not prioritized-2
187LCKunclear / low-confidence candidateunclear0.000not prioritized-2
188TFEBunclear / low-confidence candidateunclear0.000not prioritized-2
189CDX2unclear / low-confidence candidateunclear0.000not prioritized-2
190ACVR1Bunclear / low-confidence candidateunclear0.000not prioritized-2
191PRF1immune-context markerimmune-context biomarker0.000not prioritized-2
192NCOR2unclear / low-confidence candidateunclear0.000not prioritized-2
193IRS4unclear / low-confidence candidateunclear0.000not prioritized-2
194SPOPunclear / low-confidence candidateunclear0.000not prioritized-2
195CREB1unclear / low-confidence candidateunclear0.000not prioritized-2
196TET1unclear / low-confidence candidateunclear0.000not prioritized-2
197EGFRunclear / low-confidence candidateunclear0.000not prioritized-2
198CRLF2unclear / low-confidence candidateunclear0.000not prioritized-2
199STN1unclear / low-confidence candidateunclear0.000not prioritized-2
200TFE3unclear / low-confidence candidateunclear0.000not prioritized-2
201TRAF7unclear / low-confidence candidateunclear0.000not prioritized-2
202NFKB2unclear / low-confidence candidateunclear0.000not prioritized-2
203AFF4unclear / low-confidence candidateunclear0.000not prioritized-2
204ARHGEF12unclear / low-confidence candidateunclear0.000not prioritized-2
205U2AF1unclear / low-confidence candidateunclear0.000not prioritized-2
206PMS2unclear / low-confidence candidateunclear0.000not prioritized-2
207ZBTB16unclear / low-confidence candidateunclear0.000not prioritized-2
208MTAPunclear / low-confidence candidateunclear0.000not prioritized-2
209MSH2unclear / low-confidence candidateunclear0.000not prioritized-2
210ZFHX3unclear / low-confidence candidateunclear0.000not prioritized-2
211KDM5Aunclear / low-confidence candidateunclear0.000not prioritized-2
212CHD4unclear / low-confidence candidateunclear0.000not prioritized-2
213FBXO11unclear / low-confidence candidateunclear0.000not prioritized-2
214PTPN13unclear / low-confidence candidateunclear0.000not prioritized-2
215PLCG1unclear / low-confidence candidateunclear0.000not prioritized-2
216FASunclear / low-confidence candidateunclear0.000not prioritized-2
217MAXunclear / low-confidence candidateunclear0.000not prioritized-2
218BCORL1unclear / low-confidence candidateunclear0.000not prioritized-2
219KNL1unclear / low-confidence candidateunclear0.000not prioritized-2
220BUB1Bunclear / low-confidence candidateunclear0.000not prioritized-2
221NCOR1unclear / low-confidence candidateunclear0.000not prioritized-2
222ACKR3unclear / low-confidence candidateunclear0.000not prioritized-2
223SMOunclear / low-confidence candidateunclear0.000not prioritized-2
224WASunclear / low-confidence candidateunclear0.000not prioritized-2
225NUP98unclear / low-confidence candidateunclear0.000not prioritized-2
226CACNA1Dunclear / low-confidence candidateunclear0.000not prioritized-2
227FLT3unclear / low-confidence candidateunclear0.000not prioritized-2
228BTKunclear / low-confidence candidateunclear0.000not prioritized-2
229RANBP2unclear / low-confidence candidateunclear0.000not prioritized-2
230BCL11Bunclear / low-confidence candidateunclear0.000not prioritized-2
231CLTCunclear / low-confidence candidateunclear0.000not prioritized-2
232MN1unclear / low-confidence candidateunclear0.000not prioritized-2
233MAP2K4unclear / low-confidence candidateunclear0.000not prioritized-2
234BCL9unclear / low-confidence candidateunclear0.000not prioritized-2
235BRD3unclear / low-confidence candidateunclear0.000not prioritized-2
236KAT6Bunclear / low-confidence candidateunclear0.000not prioritized-2
237TBL1XR1unclear / low-confidence candidateunclear0.000not prioritized-2
238TMEM127unclear / low-confidence candidateunclear0.000not prioritized-2
239FANCFunclear / low-confidence candidateunclear0.000not prioritized-2
240PIK3CAunclear / low-confidence candidateunclear0.000not prioritized-2
241APCunclear / low-confidence candidateunclear0.000not prioritized-2
242NKX2-1unclear / low-confidence candidateunclear0.000not prioritized-2
243CTNNB1unclear / low-confidence candidateunclear0.000not prioritized-2
244MRTFAunclear / low-confidence candidateunclear0.000not prioritized-2
245KLF4unclear / low-confidence candidateunclear0.000not prioritized-2
246ZNF331unclear / low-confidence candidateunclear0.000not prioritized-2
247FGFR3unclear / low-confidence candidateunclear0.000not prioritized-2
248FHunclear / low-confidence candidateunclear0.000not prioritized-2
249MUTYHunclear / low-confidence candidateunclear0.000not prioritized-2
250TCL1Aunclear / low-confidence candidateunclear0.000not prioritized-2
251CARS1unclear / low-confidence candidateunclear0.000not prioritized-2
252ATP2B3unclear / low-confidence candidateunclear0.000not prioritized-2
253PRDM16unclear / low-confidence candidateunclear0.000not prioritized-2
254PTK6unclear / low-confidence candidateunclear0.000not prioritized-2
255LATS2unclear / low-confidence candidateunclear0.000not prioritized-2
256RAD51Cunclear / low-confidence candidateunclear0.000not prioritized-2
257STAT5Bunclear / low-confidence candidateunclear0.000not prioritized-2
258IKZF3unclear / low-confidence candidateunclear0.000not prioritized-2
259CDKN2Bunclear / low-confidence candidateunclear0.000not prioritized-2
260FANCEunclear / low-confidence candidateunclear0.000not prioritized-2
261TYRP1unclear / low-confidence candidateunclear0.000not prioritized-2
262BIRC3unclear / low-confidence candidateunclear0.000not prioritized-2
263ALKunclear / low-confidence candidateunclear0.000not prioritized-2
264FUBP1unclear / low-confidence candidateunclear0.000not prioritized-2
265PATZ1unclear / low-confidence candidateunclear0.000not prioritized-2
266FMN1unclear / low-confidence candidateunclear0.000not prioritized-2
267H3-3Aunclear / low-confidence candidateunclear0.000not prioritized-1
268GATA2unclear / low-confidence candidateunclear0.000not prioritized-1
269APOBEC3Bunclear / low-confidence candidateunclear0.000not prioritized-1
270BCL2unclear / low-confidence candidateunclear0.000not prioritized-1
271POU2AF1unclear / low-confidence candidateunclear0.000not prioritized-1
272PMELunclear / low-confidence candidateunclear0.000not prioritized0
273KRASunclear / low-confidence candidateunclear0.000not prioritized0
274TENT5Cunclear / low-confidence candidateunclear0.000not prioritized0
275CD79Aunclear / low-confidence candidateunclear0.000not prioritized0
276LPPunclear / low-confidence candidateunclear0.000not prioritized0
277PLXNB2unclear / low-confidence candidateunclear0.000not prioritized0
278SUZ12unclear / low-confidence candidateunclear0.000not prioritized0
279CBFA2T3unclear / low-confidence candidateunclear0.000not prioritized0
280NF2unclear / low-confidence candidateunclear0.000not prioritized0
281MAPK1unclear / low-confidence candidateunclear0.000not prioritized0
282KRT5unclear / low-confidence candidateunclear0.000not prioritized0
283HRASunclear / low-confidence candidateunclear0.000not prioritized0
284CNOT9unclear / low-confidence candidateunclear0.000not prioritized0
285PDCD1LG2unclear / low-confidence candidateunclear0.000not prioritized0
286SLC24A5unclear / low-confidence candidateunclear0.000not prioritized0
287NOTCH1unclear / low-confidence candidateunclear0.000not prioritized0
288MAP3K1unclear / low-confidence candidateunclear0.000not prioritized0
289CDH1unclear / low-confidence candidateunclear0.000not prioritized0
290BACH2unclear / low-confidence candidateunclear0.000not prioritized0
291KEAP1unclear / low-confidence candidateunclear0.000not prioritized0
292MED12unclear / low-confidence candidateunclear0.000not prioritized0
293H3C2unclear / low-confidence candidateunclear0.000not prioritized0
294TNFRSF17unclear / low-confidence candidateunclear0.000not prioritized0
295PIK3CBunclear / low-confidence candidateunclear0.000not prioritized0
296FBXW7unclear / low-confidence candidateunclear0.000not prioritized0
297NFE2L2unclear / low-confidence candidateunclear0.000not prioritized0
298ABL1unclear / low-confidence candidateunclear0.000not prioritized0
299CLPTM1Lunclear / low-confidence candidateunclear0.000not prioritized0
300ASPSCR1unclear / low-confidence candidateunclear0.000not prioritized0
+
+ + + +
+

Top resistance biomarker candidates

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + 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+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
RankTargetRoleBest modalityScorePriorityRank shift
1B2Mantigen-presentation resistance biomarkerresistance biomarker / patient stratification0.806high110
2JAK2IFN-gamma resistance mechanism / biomarkerresistance biomarker / patient stratification0.793high263
3JAK1IFN-gamma resistance mechanism / biomarkerresistance biomarker / patient stratification0.792high268
4NRAStumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.760high1
5IL2RATreg-suppression marker / possible IO-combination targetantibody / Treg-associated IO-combination candidate0.628medium43
6CTLA4anti-PD-1 combination targetantibody / IO-combination target0.524medium9
7PRF1immune-context markerimmune-context biomarker0.500medium182
8PDCD1anti-PD-1 combination targetantibody / IO-combination target0.498medium36
9CD274anti-PD-1 combination targetantibody / IO-combination target0.496medium44
10LAG3anti-PD-1 combination targetantibody / IO-combination target0.493medium70
11BRAFtumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.482medium-9
12MAP2K1tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.476medium-8
13MITFtumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.391low-5
14TERTtumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.385low2
15CDKN2Atumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.329low-14
16PTENtumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.313low-9
17NF1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.309low-8
18BAP1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.128low-15
19TP53tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.111low1
20MAP2K2tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.106low-14
21CDK4tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.101low-11
22KITtumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.098not prioritized-9
23RB1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.094not prioritized70
24GNAQunclear / low-confidence candidateunclear0.000not prioritized-13
25ARID2unclear / low-confidence candidateunclear0.000not prioritized-13
26RAC1unclear / low-confidence candidateunclear0.000not prioritized-12
27GNA11unclear / low-confidence candidateunclear0.000not prioritized-10
28POT1unclear / low-confidence candidateunclear0.000not prioritized-10
29MBD4unclear / low-confidence candidateunclear0.000not prioritized-10
30SF3B1unclear / low-confidence candidateunclear0.000not prioritized-9
31PPP6Cunclear / low-confidence candidateunclear0.000not prioritized-9
32IRF4unclear / low-confidence candidateunclear0.000not prioritized-9
33BRCA2unclear / low-confidence candidateunclear0.000not prioritized-9
34RAF1unclear / low-confidence candidateunclear0.000not prioritized-9
35KDRunclear / low-confidence candidateunclear0.000not prioritized-9
36PDGFRAunclear / low-confidence candidateunclear0.000not prioritized-9
37ATMunclear / low-confidence candidateunclear0.000not prioritized-9
38LRP1Bunclear / low-confidence candidateunclear0.000not prioritized-9
39FLT4unclear / low-confidence candidateunclear0.000not prioritized-9
40CSF3Runclear / low-confidence candidateunclear0.000not prioritized-9
41PDGFRBunclear / low-confidence candidateunclear0.000not prioritized-9
42TET2unclear / low-confidence candidateunclear0.000not prioritized-9
43POLEunclear / low-confidence candidateunclear0.000not prioritized-9
44DDX3Xunclear / low-confidence candidateunclear0.000not prioritized-9
45FOXP1unclear / low-confidence candidateunclear0.000not prioritized-9
46PBRM1unclear / low-confidence candidateunclear0.000not prioritized-9
47SETD2unclear / low-confidence candidateunclear0.000not prioritized-9
48CCND1unclear / low-confidence candidateunclear0.000not prioritized-9
49ERBB4unclear / low-confidence candidateunclear0.000not prioritized-9
50METunclear / low-confidence candidateunclear0.000not prioritized-9
51STK11unclear / low-confidence candidateunclear0.000not prioritized-9
52ROS1unclear / low-confidence candidateunclear0.000not prioritized-9
53MTORunclear / low-confidence candidateunclear0.000not prioritized-8
54H3-3Bunclear / low-confidence candidateunclear0.000not prioritized-8
55TRRAPunclear / low-confidence candidateunclear0.000not prioritized-8
56MC1Runclear / low-confidence candidateunclear0.000not prioritized-7
57IKZF1unclear / low-confidence candidateunclear0.000not prioritized-7
58FAT1unclear / low-confidence candidateunclear0.000not prioritized-7
59DICER1unclear / low-confidence candidateunclear0.000not prioritized-7
60MDM2unclear / low-confidence candidateunclear0.000not prioritized-6
61IFNAR1unclear / low-confidence candidateunclear0.000not prioritized-6
62MECOMunclear / low-confidence candidateunclear0.000not prioritized-6
63WRNunclear / low-confidence candidateunclear0.000not prioritized-6
64CHEK2unclear / low-confidence candidateunclear0.000not prioritized-6
65ATRunclear / low-confidence candidateunclear0.000not prioritized-6
66CUX1unclear / low-confidence candidateunclear0.000not prioritized-6
67KMT2Dunclear / low-confidence candidateunclear0.000not prioritized-6
68EP300unclear / low-confidence candidateunclear0.000not prioritized-6
69ESR1unclear / low-confidence candidateunclear0.000not prioritized-6
70BRCA1unclear / low-confidence candidateunclear0.000not prioritized-6
71AKT1unclear / low-confidence candidateunclear0.000not prioritized-6
72NTRK1unclear / low-confidence candidateunclear0.000not prioritized-6
73ERBB2unclear / low-confidence candidateunclear0.000not prioritized-6
74PREX2unclear / low-confidence candidateunclear0.000not prioritized-6
75FAT4unclear / low-confidence candidateunclear0.000not prioritized-6
76KMT2Cunclear / low-confidence candidateunclear0.000not prioritized-6
77POLQunclear / low-confidence candidateunclear0.000not prioritized-6
78FGFR2unclear / low-confidence candidateunclear0.000not prioritized-6
79TP63unclear / low-confidence candidateunclear0.000not prioritized-6
80FGFR4unclear / low-confidence candidateunclear0.000not prioritized-6
81GRIN2Aunclear / low-confidence candidateunclear0.000not prioritized-6
82UBR5unclear / low-confidence candidateunclear0.000not prioritized-6
83OCA2unclear / low-confidence candidateunclear0.000not prioritized-6
84SMARCA4unclear / low-confidence candidateunclear0.000not prioritized-6
85IFNAR2unclear / low-confidence candidateunclear0.000not prioritized-6
86FGFR1unclear / low-confidence candidateunclear0.000not prioritized-5
87PTPRBunclear / low-confidence candidateunclear0.000not prioritized-5
88PTPRTunclear / low-confidence candidateunclear0.000not prioritized-5
89PTPN11unclear / low-confidence candidateunclear0.000not prioritized-5
90MDM4unclear / low-confidence candidateunclear0.000not prioritized-5
91TSC1unclear / low-confidence candidateunclear0.000not prioritized-5
92TBX3unclear / low-confidence candidateunclear0.000not prioritized-5
93ERBB3unclear / low-confidence candidateunclear0.000not prioritized-5
94ATRXunclear / low-confidence candidateunclear0.000not prioritized-5
95RUNX1T1unclear / low-confidence candidateunclear0.000not prioritized-5
96CDK12unclear / low-confidence candidateunclear0.000not prioritized-5
97TYRunclear / low-confidence candidateunclear0.000not prioritized-5
98AKT2unclear / low-confidence candidateunclear0.000not prioritized-4
99PTPRKunclear / low-confidence candidateunclear0.000not prioritized-4
100CBLunclear / low-confidence candidateunclear0.000not prioritized-4
101DNMT3Aunclear / low-confidence candidateunclear0.000not prioritized-4
102RRM2unclear / low-confidence candidateunclear0.000not prioritized-4
103KLF6unclear / low-confidence candidateunclear0.000not prioritized-4
104ARunclear / low-confidence candidateunclear0.000not prioritized-4
105KMT2Aunclear / low-confidence candidateunclear0.000not prioritized-4
106CYLDunclear / low-confidence candidateunclear0.000not prioritized-4
107RPL5unclear / low-confidence candidateunclear0.000not prioritized-4
108ERCC2unclear / low-confidence candidateunclear0.000not prioritized-4
109IDH1unclear / low-confidence candidateunclear0.000not prioritized-4
110NOTCH2unclear / low-confidence candidateunclear0.000not prioritized-4
111CDK6unclear / low-confidence candidateunclear0.000not prioritized-4
112IKBKBunclear / low-confidence candidateunclear0.000not prioritized-4
113NTRK2unclear / low-confidence candidateunclear0.000not prioritized-4
114RRM2Bunclear / low-confidence candidateunclear0.000not prioritized-4
115CASP8unclear / low-confidence candidateunclear0.000not prioritized-3
116POLD1unclear / low-confidence candidateunclear0.000not prioritized-3
117IL7Runclear / low-confidence candidateunclear0.000not prioritized-3
118QKIunclear / low-confidence candidateunclear0.000not prioritized-3
119GNASunclear / low-confidence candidateunclear0.000not prioritized-3
120MYBunclear / low-confidence candidateunclear0.000not prioritized-3
121PTCH1unclear / low-confidence candidateunclear0.000not prioritized-3
122DDR2unclear / low-confidence candidateunclear0.000not prioritized-3
123PIK3R1unclear / low-confidence candidateunclear0.000not prioritized-3
124TSC2unclear / low-confidence candidateunclear0.000not prioritized-3
125PHOX2Bunclear / low-confidence candidateunclear0.000not prioritized-3
126SETBP1unclear / low-confidence candidateunclear0.000not prioritized-3
127RRM1unclear / low-confidence candidateunclear0.000not prioritized-3
128SPENunclear / low-confidence candidateunclear0.000not prioritized-3
129ARHGAP35unclear / low-confidence candidateunclear0.000not prioritized-3
130SYKunclear / low-confidence candidateunclear0.000not prioritized-3
131PAX5unclear / low-confidence candidateunclear0.000not prioritized-3
132CYP1B1unclear / low-confidence candidateunclear0.000not prioritized-3
133FANCAunclear / low-confidence candidateunclear0.000not prioritized-3
134CIITAunclear / low-confidence candidateunclear0.000not prioritized-3
135BCL9Lunclear / low-confidence candidateunclear0.000not prioritized-3
136NUTM1unclear / low-confidence candidateunclear0.000not prioritized-3
137ARNTunclear / low-confidence candidateunclear0.000not prioritized-3
138CCND2unclear / low-confidence candidateunclear0.000not prioritized-3
139PER1unclear / low-confidence candidateunclear0.000not prioritized-3
140JUNunclear / low-confidence candidateunclear0.000not prioritized-3
141KAT6Aunclear / low-confidence candidateunclear0.000not prioritized-3
142CBLBunclear / low-confidence candidateunclear0.000not prioritized-3
143HNF1Aunclear / low-confidence candidateunclear0.000not prioritized-3
144BCL11Aunclear / low-confidence candidateunclear0.000not prioritized-3
145USP6unclear / low-confidence candidateunclear0.000not prioritized-3
146MYCNunclear / low-confidence candidateunclear0.000not prioritized-3
147PRDM1unclear / low-confidence candidateunclear0.000not prioritized-3
148AFDNunclear / low-confidence candidateunclear0.000not prioritized-3
149IL2RGunclear / low-confidence candidateunclear0.000not prioritized-3
150IL2RBunclear / low-confidence candidateunclear0.000not prioritized-3
151SMAD2unclear / low-confidence candidateunclear0.000not prioritized-3
152AXIN1unclear / low-confidence candidateunclear0.000not prioritized-3
153SALL4unclear / low-confidence candidateunclear0.000not prioritized-3
154NFKBIEunclear / low-confidence candidateunclear0.000not prioritized-3
155HGFunclear / low-confidence candidateunclear0.000not prioritized-3
156PPP2R1Aunclear / low-confidence candidateunclear0.000not prioritized-3
157BCORunclear / low-confidence candidateunclear0.000not prioritized-3
158ERCC3unclear / low-confidence candidateunclear0.000not prioritized-3
159FANCD2unclear / low-confidence candidateunclear0.000not prioritized-3
160DAXXunclear / low-confidence candidateunclear0.000not prioritized-3
161PTPRCunclear / low-confidence candidateunclear0.000not prioritized-3
162MYH9unclear / low-confidence candidateunclear0.000not prioritized-3
163ARID1Bunclear / low-confidence candidateunclear0.000not prioritized-3
164LZTR1unclear / low-confidence candidateunclear0.000not prioritized-3
165CICunclear / low-confidence candidateunclear0.000not prioritized-3
166CREBBPunclear / low-confidence candidateunclear0.000not prioritized-3
167MYCLunclear / low-confidence candidateunclear0.000not prioritized-3
168SLC45A2unclear / low-confidence candidateunclear0.000not prioritized-3
169FCRL4unclear / low-confidence candidateunclear0.000not prioritized-3
170MAP3K13unclear / low-confidence candidateunclear0.000not prioritized-3
171CNOT3unclear / low-confidence candidateunclear0.000not prioritized-3
172FLGunclear / low-confidence candidateunclear0.000not prioritized-3
173AMER1unclear / low-confidence candidateunclear0.000not prioritized-3
174ATF1unclear / low-confidence candidateunclear0.000not prioritized-3
175ERCC5unclear / low-confidence candidateunclear0.000not prioritized-3
176ERCC4unclear / low-confidence candidateunclear0.000not prioritized-3
177MX2unclear / low-confidence candidateunclear0.000not prioritized-3
178SUFUunclear / low-confidence candidateunclear0.000not prioritized-3
179NTRK3unclear / low-confidence candidateunclear0.000not prioritized-3
180ARID1Aunclear / low-confidence candidateunclear0.000not prioritized-3
181PARP1unclear / low-confidence candidateunclear0.000not prioritized-3
182CARD11unclear / low-confidence candidateunclear0.000not prioritized-3
183RICTORunclear / low-confidence candidateunclear0.000not prioritized-3
184BRD4unclear / low-confidence candidateunclear0.000not prioritized-3
185RETunclear / low-confidence candidateunclear0.000not prioritized-3
186EZH2unclear / low-confidence candidateunclear0.000not prioritized-3
187SMAD3unclear / low-confidence candidateunclear0.000not prioritized-3
188LCKunclear / low-confidence candidateunclear0.000not prioritized-3
189TFEBunclear / low-confidence candidateunclear0.000not prioritized-3
190CDX2unclear / low-confidence candidateunclear0.000not prioritized-3
191ACVR1Bunclear / low-confidence candidateunclear0.000not prioritized-3
192NCOR2unclear / low-confidence candidateunclear0.000not prioritized-2
193IRS4unclear / low-confidence candidateunclear0.000not prioritized-2
194SPOPunclear / low-confidence candidateunclear0.000not prioritized-2
195CREB1unclear / low-confidence candidateunclear0.000not prioritized-2
196TET1unclear / low-confidence candidateunclear0.000not prioritized-2
197EGFRunclear / low-confidence candidateunclear0.000not prioritized-2
198CRLF2unclear / low-confidence candidateunclear0.000not prioritized-2
199STN1unclear / low-confidence candidateunclear0.000not prioritized-2
200TFE3unclear / low-confidence candidateunclear0.000not prioritized-2
201TRAF7unclear / low-confidence candidateunclear0.000not prioritized-2
202NFKB2unclear / low-confidence candidateunclear0.000not prioritized-2
203AFF4unclear / low-confidence candidateunclear0.000not prioritized-2
204ARHGEF12unclear / low-confidence candidateunclear0.000not prioritized-2
205U2AF1unclear / low-confidence candidateunclear0.000not prioritized-2
206PMS2unclear / low-confidence candidateunclear0.000not prioritized-2
207ZBTB16unclear / low-confidence candidateunclear0.000not prioritized-2
208MTAPunclear / low-confidence candidateunclear0.000not prioritized-2
209MSH2unclear / low-confidence candidateunclear0.000not prioritized-2
210ZFHX3unclear / low-confidence candidateunclear0.000not prioritized-2
211KDM5Aunclear / low-confidence candidateunclear0.000not prioritized-2
212CHD4unclear / low-confidence candidateunclear0.000not prioritized-2
213FBXO11unclear / low-confidence candidateunclear0.000not prioritized-2
214PTPN13unclear / low-confidence candidateunclear0.000not prioritized-2
215PLCG1unclear / low-confidence candidateunclear0.000not prioritized-2
216FASunclear / low-confidence candidateunclear0.000not prioritized-2
217MAXunclear / low-confidence candidateunclear0.000not prioritized-2
218BCORL1unclear / low-confidence candidateunclear0.000not prioritized-2
219KNL1unclear / low-confidence candidateunclear0.000not prioritized-2
220BUB1Bunclear / low-confidence candidateunclear0.000not prioritized-2
221NCOR1unclear / low-confidence candidateunclear0.000not prioritized-2
222ACKR3unclear / low-confidence candidateunclear0.000not prioritized-2
223SMOunclear / low-confidence candidateunclear0.000not prioritized-2
224WASunclear / low-confidence candidateunclear0.000not prioritized-2
225NUP98unclear / low-confidence candidateunclear0.000not prioritized-2
226CACNA1Dunclear / low-confidence candidateunclear0.000not prioritized-2
227FLT3unclear / low-confidence candidateunclear0.000not prioritized-2
228BTKunclear / low-confidence candidateunclear0.000not prioritized-2
229RANBP2unclear / low-confidence candidateunclear0.000not prioritized-2
230BCL11Bunclear / low-confidence candidateunclear0.000not prioritized-2
231CLTCunclear / low-confidence candidateunclear0.000not prioritized-2
232MN1unclear / low-confidence candidateunclear0.000not prioritized-2
233MAP2K4unclear / low-confidence candidateunclear0.000not prioritized-2
234BCL9unclear / low-confidence candidateunclear0.000not prioritized-2
235BRD3unclear / low-confidence candidateunclear0.000not prioritized-2
236KAT6Bunclear / low-confidence candidateunclear0.000not prioritized-2
237TBL1XR1unclear / low-confidence candidateunclear0.000not prioritized-2
238TMEM127unclear / low-confidence candidateunclear0.000not prioritized-2
239FANCFunclear / low-confidence candidateunclear0.000not prioritized-2
240PIK3CAunclear / low-confidence candidateunclear0.000not prioritized-2
241APCunclear / low-confidence candidateunclear0.000not prioritized-2
242NKX2-1unclear / low-confidence candidateunclear0.000not prioritized-2
243CTNNB1unclear / low-confidence candidateunclear0.000not prioritized-2
244MRTFAunclear / low-confidence candidateunclear0.000not prioritized-2
245KLF4unclear / low-confidence candidateunclear0.000not prioritized-2
246ZNF331unclear / low-confidence candidateunclear0.000not prioritized-2
247FGFR3unclear / low-confidence candidateunclear0.000not prioritized-2
248FHunclear / low-confidence candidateunclear0.000not prioritized-2
249MUTYHunclear / low-confidence candidateunclear0.000not prioritized-2
250TCL1Aunclear / low-confidence candidateunclear0.000not prioritized-2
251CARS1unclear / low-confidence candidateunclear0.000not prioritized-2
252ATP2B3unclear / low-confidence candidateunclear0.000not prioritized-2
253PRDM16unclear / low-confidence candidateunclear0.000not prioritized-2
254PTK6unclear / low-confidence candidateunclear0.000not prioritized-2
255LATS2unclear / low-confidence candidateunclear0.000not prioritized-2
256RAD51Cunclear / low-confidence candidateunclear0.000not prioritized-2
257STAT5Bunclear / low-confidence candidateunclear0.000not prioritized-2
258IKZF3unclear / low-confidence candidateunclear0.000not prioritized-2
259CDKN2Bunclear / low-confidence candidateunclear0.000not prioritized-2
260FANCEunclear / low-confidence candidateunclear0.000not prioritized-2
261TYRP1unclear / low-confidence candidateunclear0.000not prioritized-2
262BIRC3unclear / low-confidence candidateunclear0.000not prioritized-2
263ALKunclear / low-confidence candidateunclear0.000not prioritized-2
264FUBP1unclear / low-confidence candidateunclear0.000not prioritized-2
265PATZ1unclear / low-confidence candidateunclear0.000not prioritized-2
266FMN1unclear / low-confidence candidateunclear0.000not prioritized-2
267H3-3Aunclear / low-confidence candidateunclear0.000not prioritized-1
268GATA2unclear / low-confidence candidateunclear0.000not prioritized-1
269APOBEC3Bunclear / low-confidence candidateunclear0.000not prioritized-1
270BCL2unclear / low-confidence candidateunclear0.000not prioritized-1
271POU2AF1unclear / low-confidence candidateunclear0.000not prioritized-1
272PMELunclear / low-confidence candidateunclear0.000not prioritized0
273KRASunclear / low-confidence candidateunclear0.000not prioritized0
274TENT5Cunclear / low-confidence candidateunclear0.000not prioritized0
275CD79Aunclear / low-confidence candidateunclear0.000not prioritized0
276LPPunclear / low-confidence candidateunclear0.000not prioritized0
277PLXNB2unclear / low-confidence candidateunclear0.000not prioritized0
278SUZ12unclear / low-confidence candidateunclear0.000not prioritized0
279CBFA2T3unclear / low-confidence candidateunclear0.000not prioritized0
280NF2unclear / low-confidence candidateunclear0.000not prioritized0
281MAPK1unclear / low-confidence candidateunclear0.000not prioritized0
282KRT5unclear / low-confidence candidateunclear0.000not prioritized0
283HRASunclear / low-confidence candidateunclear0.000not prioritized0
284CNOT9unclear / low-confidence candidateunclear0.000not prioritized0
285PDCD1LG2unclear / low-confidence candidateunclear0.000not prioritized0
286SLC24A5unclear / low-confidence candidateunclear0.000not prioritized0
287NOTCH1unclear / low-confidence candidateunclear0.000not prioritized0
288MAP3K1unclear / low-confidence candidateunclear0.000not prioritized0
289CDH1unclear / low-confidence candidateunclear0.000not prioritized0
290BACH2unclear / low-confidence candidateunclear0.000not prioritized0
291KEAP1unclear / low-confidence candidateunclear0.000not prioritized0
292MED12unclear / low-confidence candidateunclear0.000not prioritized0
293H3C2unclear / low-confidence candidateunclear0.000not prioritized0
294TNFRSF17unclear / low-confidence candidateunclear0.000not prioritized0
295PIK3CBunclear / low-confidence candidateunclear0.000not prioritized0
296FBXW7unclear / low-confidence candidateunclear0.000not prioritized0
297NFE2L2unclear / low-confidence candidateunclear0.000not prioritized0
298ABL1unclear / low-confidence candidateunclear0.000not prioritized0
299CLPTM1Lunclear / low-confidence candidateunclear0.000not prioritized0
300ASPSCR1unclear / low-confidence candidateunclear0.000not prioritized0
+
+ + + +
+

Top tumor-intrinsic / small-molecule candidates

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
RankTargetRoleBest modalityScorePriorityRank shift
1BRAFtumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.845high1
2MAP2K1tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.836high2
3MAP2K2tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.689medium3
4CDK4tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.682medium6
5KITtumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.679medium8
6NRAStumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.666medium-1
7MITFtumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.521medium1
8TERTtumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.513medium8
9CTLA4anti-PD-1 combination targetantibody / IO-combination target0.159low6
10PDCD1anti-PD-1 combination targetantibody / IO-combination target0.144low34
11CD274anti-PD-1 combination targetantibody / IO-combination target0.141low42
12LAG3anti-PD-1 combination targetantibody / IO-combination target0.137low68
13B2Mantigen-presentation resistance biomarkerresistance biomarker / patient stratification0.132low98
14IL2RATreg-suppression marker / possible IO-combination targetantibody / Treg-associated IO-combination candidate0.126low34
15JAK2IFN-gamma resistance mechanism / biomarkerresistance biomarker / patient stratification0.115low250
16JAK1IFN-gamma resistance mechanism / biomarkerresistance biomarker / patient stratification0.114low255
17GNAQunclear / low-confidence candidateunclear0.015not prioritized-6
18ARID2unclear / low-confidence candidateunclear0.015not prioritized-6
19RAC1unclear / low-confidence candidateunclear0.013not prioritized-5
20GNA11unclear / low-confidence candidateunclear0.012not prioritized-3
21POT1unclear / low-confidence candidateunclear0.012not prioritized-3
22MBD4unclear / low-confidence candidateunclear0.012not prioritized-3
23SF3B1unclear / low-confidence candidateunclear0.011not prioritized-2
24PPP6Cunclear / low-confidence candidateunclear0.010not prioritized-2
25IRF4unclear / low-confidence candidateunclear0.009not prioritized-2
26BRCA2unclear / low-confidence candidateunclear0.008not prioritized-2
27RAF1unclear / low-confidence candidateunclear0.005not prioritized-2
28KDRunclear / low-confidence candidateunclear0.005not prioritized-2
29PDGFRAunclear / low-confidence candidateunclear0.004not prioritized-2
30ATMunclear / low-confidence candidateunclear0.003not prioritized-2
31LRP1Bunclear / low-confidence candidateunclear0.002not prioritized-2
32FLT4unclear / low-confidence candidateunclear0.001not prioritized-2
33CSF3Runclear / low-confidence candidateunclear0.001not prioritized-2
34PDGFRBunclear / low-confidence candidateunclear0.000not prioritized-2
35TET2unclear / low-confidence candidateunclear0.000not prioritized-2
36CDKN2Atumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-35
37BAP1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-34
38PTENtumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-31
39NF1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-30
40TP53tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-20
41POLEunclear / low-confidence candidateunclear0.000not prioritized-7
42DDX3Xunclear / low-confidence candidateunclear0.000not prioritized-7
43FOXP1unclear / low-confidence candidateunclear0.000not prioritized-7
44PBRM1unclear / low-confidence candidateunclear0.000not prioritized-7
45SETD2unclear / low-confidence candidateunclear0.000not prioritized-7
46CCND1unclear / low-confidence candidateunclear0.000not prioritized-7
47ERBB4unclear / low-confidence candidateunclear0.000not prioritized-7
48METunclear / low-confidence candidateunclear0.000not prioritized-7
49STK11unclear / low-confidence candidateunclear0.000not prioritized-7
50ROS1unclear / low-confidence candidateunclear0.000not prioritized-7
51MTORunclear / low-confidence candidateunclear0.000not prioritized-6
52H3-3Bunclear / low-confidence candidateunclear0.000not prioritized-6
53TRRAPunclear / low-confidence candidateunclear0.000not prioritized-6
54MC1Runclear / low-confidence candidateunclear0.000not prioritized-5
55IKZF1unclear / low-confidence candidateunclear0.000not prioritized-5
56FAT1unclear / low-confidence candidateunclear0.000not prioritized-5
57DICER1unclear / low-confidence candidateunclear0.000not prioritized-5
58MDM2unclear / low-confidence candidateunclear0.000not prioritized-4
59IFNAR1unclear / low-confidence candidateunclear0.000not prioritized-4
60MECOMunclear / low-confidence candidateunclear0.000not prioritized-4
61WRNunclear / low-confidence candidateunclear0.000not prioritized-4
62CHEK2unclear / low-confidence candidateunclear0.000not prioritized-4
63ATRunclear / low-confidence candidateunclear0.000not prioritized-4
64CUX1unclear / low-confidence candidateunclear0.000not prioritized-4
65KMT2Dunclear / low-confidence candidateunclear0.000not prioritized-4
66EP300unclear / low-confidence candidateunclear0.000not prioritized-4
67ESR1unclear / low-confidence candidateunclear0.000not prioritized-4
68BRCA1unclear / low-confidence candidateunclear0.000not prioritized-4
69AKT1unclear / low-confidence candidateunclear0.000not prioritized-4
70NTRK1unclear / low-confidence candidateunclear0.000not prioritized-4
71ERBB2unclear / low-confidence candidateunclear0.000not prioritized-4
72PREX2unclear / low-confidence candidateunclear0.000not prioritized-4
73FAT4unclear / low-confidence candidateunclear0.000not prioritized-4
74KMT2Cunclear / low-confidence candidateunclear0.000not prioritized-4
75POLQunclear / low-confidence candidateunclear0.000not prioritized-4
76FGFR2unclear / low-confidence candidateunclear0.000not prioritized-4
77TP63unclear / low-confidence candidateunclear0.000not prioritized-4
78FGFR4unclear / low-confidence candidateunclear0.000not prioritized-4
79GRIN2Aunclear / low-confidence candidateunclear0.000not prioritized-4
80UBR5unclear / low-confidence candidateunclear0.000not prioritized-4
81OCA2unclear / low-confidence candidateunclear0.000not prioritized-4
82SMARCA4unclear / low-confidence candidateunclear0.000not prioritized-4
83IFNAR2unclear / low-confidence candidateunclear0.000not prioritized-4
84FGFR1unclear / low-confidence candidateunclear0.000not prioritized-3
85PTPRBunclear / low-confidence candidateunclear0.000not prioritized-3
86PTPRTunclear / low-confidence candidateunclear0.000not prioritized-3
87PTPN11unclear / low-confidence candidateunclear0.000not prioritized-3
88MDM4unclear / low-confidence candidateunclear0.000not prioritized-3
89TSC1unclear / low-confidence candidateunclear0.000not prioritized-3
90TBX3unclear / low-confidence candidateunclear0.000not prioritized-3
91ERBB3unclear / low-confidence candidateunclear0.000not prioritized-3
92ATRXunclear / low-confidence candidateunclear0.000not prioritized-3
93RUNX1T1unclear / low-confidence candidateunclear0.000not prioritized-3
94CDK12unclear / low-confidence candidateunclear0.000not prioritized-3
95TYRunclear / low-confidence candidateunclear0.000not prioritized-3
96RB1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-3
97AKT2unclear / low-confidence candidateunclear0.000not prioritized-3
98PTPRKunclear / low-confidence candidateunclear0.000not prioritized-3
99CBLunclear / low-confidence candidateunclear0.000not prioritized-3
100DNMT3Aunclear / low-confidence candidateunclear0.000not prioritized-3
101RRM2unclear / low-confidence candidateunclear0.000not prioritized-3
102KLF6unclear / low-confidence candidateunclear0.000not prioritized-3
103ARunclear / low-confidence candidateunclear0.000not prioritized-3
104KMT2Aunclear / low-confidence candidateunclear0.000not prioritized-3
105CYLDunclear / low-confidence candidateunclear0.000not prioritized-3
106RPL5unclear / low-confidence candidateunclear0.000not prioritized-3
107ERCC2unclear / low-confidence candidateunclear0.000not prioritized-3
108IDH1unclear / low-confidence candidateunclear0.000not prioritized-3
109NOTCH2unclear / low-confidence candidateunclear0.000not prioritized-3
110CDK6unclear / low-confidence candidateunclear0.000not prioritized-3
111IKBKBunclear / low-confidence candidateunclear0.000not prioritized-3
112NTRK2unclear / low-confidence candidateunclear0.000not prioritized-3
113RRM2Bunclear / low-confidence candidateunclear0.000not prioritized-3
114CASP8unclear / low-confidence candidateunclear0.000not prioritized-2
115POLD1unclear / low-confidence candidateunclear0.000not prioritized-2
116IL7Runclear / low-confidence candidateunclear0.000not prioritized-2
117QKIunclear / low-confidence candidateunclear0.000not prioritized-2
118GNASunclear / low-confidence candidateunclear0.000not prioritized-2
119MYBunclear / low-confidence candidateunclear0.000not prioritized-2
120PTCH1unclear / low-confidence candidateunclear0.000not prioritized-2
121DDR2unclear / low-confidence candidateunclear0.000not prioritized-2
122PIK3R1unclear / low-confidence candidateunclear0.000not prioritized-2
123TSC2unclear / low-confidence candidateunclear0.000not prioritized-2
124PHOX2Bunclear / low-confidence candidateunclear0.000not prioritized-2
125SETBP1unclear / low-confidence candidateunclear0.000not prioritized-2
126RRM1unclear / low-confidence candidateunclear0.000not prioritized-2
127SPENunclear / low-confidence candidateunclear0.000not prioritized-2
128ARHGAP35unclear / low-confidence candidateunclear0.000not prioritized-2
129SYKunclear / low-confidence candidateunclear0.000not prioritized-2
130PAX5unclear / low-confidence candidateunclear0.000not prioritized-2
131CYP1B1unclear / low-confidence candidateunclear0.000not prioritized-2
132FANCAunclear / low-confidence candidateunclear0.000not prioritized-2
133CIITAunclear / low-confidence candidateunclear0.000not prioritized-2
134BCL9Lunclear / low-confidence candidateunclear0.000not prioritized-2
135NUTM1unclear / low-confidence candidateunclear0.000not prioritized-2
136ARNTunclear / low-confidence candidateunclear0.000not prioritized-2
137CCND2unclear / low-confidence candidateunclear0.000not prioritized-2
138PER1unclear / low-confidence candidateunclear0.000not prioritized-2
139JUNunclear / low-confidence candidateunclear0.000not prioritized-2
140KAT6Aunclear / low-confidence candidateunclear0.000not prioritized-2
141CBLBunclear / low-confidence candidateunclear0.000not prioritized-2
142HNF1Aunclear / low-confidence candidateunclear0.000not prioritized-2
143BCL11Aunclear / low-confidence candidateunclear0.000not prioritized-2
144USP6unclear / low-confidence candidateunclear0.000not prioritized-2
145MYCNunclear / low-confidence candidateunclear0.000not prioritized-2
146PRDM1unclear / low-confidence candidateunclear0.000not prioritized-2
147AFDNunclear / low-confidence candidateunclear0.000not prioritized-2
148IL2RGunclear / low-confidence candidateunclear0.000not prioritized-2
149IL2RBunclear / low-confidence candidateunclear0.000not prioritized-2
150SMAD2unclear / low-confidence candidateunclear0.000not prioritized-2
151AXIN1unclear / low-confidence candidateunclear0.000not prioritized-2
152SALL4unclear / low-confidence candidateunclear0.000not prioritized-2
153NFKBIEunclear / low-confidence candidateunclear0.000not prioritized-2
154HGFunclear / low-confidence candidateunclear0.000not prioritized-2
155PPP2R1Aunclear / low-confidence candidateunclear0.000not prioritized-2
156BCORunclear / low-confidence candidateunclear0.000not prioritized-2
157ERCC3unclear / low-confidence candidateunclear0.000not prioritized-2
158FANCD2unclear / low-confidence candidateunclear0.000not prioritized-2
159DAXXunclear / low-confidence candidateunclear0.000not prioritized-2
160PTPRCunclear / low-confidence candidateunclear0.000not prioritized-2
161MYH9unclear / low-confidence candidateunclear0.000not prioritized-2
162ARID1Bunclear / low-confidence candidateunclear0.000not prioritized-2
163LZTR1unclear / low-confidence candidateunclear0.000not prioritized-2
164CICunclear / low-confidence candidateunclear0.000not prioritized-2
165CREBBPunclear / low-confidence candidateunclear0.000not prioritized-2
166MYCLunclear / low-confidence candidateunclear0.000not prioritized-2
167SLC45A2unclear / low-confidence candidateunclear0.000not prioritized-2
168FCRL4unclear / low-confidence candidateunclear0.000not prioritized-2
169MAP3K13unclear / low-confidence candidateunclear0.000not prioritized-2
170CNOT3unclear / low-confidence candidateunclear0.000not prioritized-2
171FLGunclear / low-confidence candidateunclear0.000not prioritized-2
172AMER1unclear / low-confidence candidateunclear0.000not prioritized-2
173ATF1unclear / low-confidence candidateunclear0.000not prioritized-2
174ERCC5unclear / low-confidence candidateunclear0.000not prioritized-2
175ERCC4unclear / low-confidence candidateunclear0.000not prioritized-2
176MX2unclear / low-confidence candidateunclear0.000not prioritized-2
177SUFUunclear / low-confidence candidateunclear0.000not prioritized-2
178NTRK3unclear / low-confidence candidateunclear0.000not prioritized-2
179ARID1Aunclear / low-confidence candidateunclear0.000not prioritized-2
180PARP1unclear / low-confidence candidateunclear0.000not prioritized-2
181CARD11unclear / low-confidence candidateunclear0.000not prioritized-2
182RICTORunclear / low-confidence candidateunclear0.000not prioritized-2
183BRD4unclear / low-confidence candidateunclear0.000not prioritized-2
184RETunclear / low-confidence candidateunclear0.000not prioritized-2
185EZH2unclear / low-confidence candidateunclear0.000not prioritized-2
186SMAD3unclear / low-confidence candidateunclear0.000not prioritized-2
187LCKunclear / low-confidence candidateunclear0.000not prioritized-2
188TFEBunclear / low-confidence candidateunclear0.000not prioritized-2
189CDX2unclear / low-confidence candidateunclear0.000not prioritized-2
190ACVR1Bunclear / low-confidence candidateunclear0.000not prioritized-2
191PRF1immune-context markerimmune-context biomarker0.000not prioritized-2
192NCOR2unclear / low-confidence candidateunclear0.000not prioritized-2
193IRS4unclear / low-confidence candidateunclear0.000not prioritized-2
194SPOPunclear / low-confidence candidateunclear0.000not prioritized-2
195CREB1unclear / low-confidence candidateunclear0.000not prioritized-2
196TET1unclear / low-confidence candidateunclear0.000not prioritized-2
197EGFRunclear / low-confidence candidateunclear0.000not prioritized-2
198CRLF2unclear / low-confidence candidateunclear0.000not prioritized-2
199STN1unclear / low-confidence candidateunclear0.000not prioritized-2
200TFE3unclear / low-confidence candidateunclear0.000not prioritized-2
201TRAF7unclear / low-confidence candidateunclear0.000not prioritized-2
202NFKB2unclear / low-confidence candidateunclear0.000not prioritized-2
203AFF4unclear / low-confidence candidateunclear0.000not prioritized-2
204ARHGEF12unclear / low-confidence candidateunclear0.000not prioritized-2
205U2AF1unclear / low-confidence candidateunclear0.000not prioritized-2
206PMS2unclear / low-confidence candidateunclear0.000not prioritized-2
207ZBTB16unclear / low-confidence candidateunclear0.000not prioritized-2
208MTAPunclear / low-confidence candidateunclear0.000not prioritized-2
209MSH2unclear / low-confidence candidateunclear0.000not prioritized-2
210ZFHX3unclear / low-confidence candidateunclear0.000not prioritized-2
211KDM5Aunclear / low-confidence candidateunclear0.000not prioritized-2
212CHD4unclear / low-confidence candidateunclear0.000not prioritized-2
213FBXO11unclear / low-confidence candidateunclear0.000not prioritized-2
214PTPN13unclear / low-confidence candidateunclear0.000not prioritized-2
215PLCG1unclear / low-confidence candidateunclear0.000not prioritized-2
216FASunclear / low-confidence candidateunclear0.000not prioritized-2
217MAXunclear / low-confidence candidateunclear0.000not prioritized-2
218BCORL1unclear / low-confidence candidateunclear0.000not prioritized-2
219KNL1unclear / low-confidence candidateunclear0.000not prioritized-2
220BUB1Bunclear / low-confidence candidateunclear0.000not prioritized-2
221NCOR1unclear / low-confidence candidateunclear0.000not prioritized-2
222ACKR3unclear / low-confidence candidateunclear0.000not prioritized-2
223SMOunclear / low-confidence candidateunclear0.000not prioritized-2
224WASunclear / low-confidence candidateunclear0.000not prioritized-2
225NUP98unclear / low-confidence candidateunclear0.000not prioritized-2
226CACNA1Dunclear / low-confidence candidateunclear0.000not prioritized-2
227FLT3unclear / low-confidence candidateunclear0.000not prioritized-2
228BTKunclear / low-confidence candidateunclear0.000not prioritized-2
229RANBP2unclear / low-confidence candidateunclear0.000not prioritized-2
230BCL11Bunclear / low-confidence candidateunclear0.000not prioritized-2
231CLTCunclear / low-confidence candidateunclear0.000not prioritized-2
232MN1unclear / low-confidence candidateunclear0.000not prioritized-2
233MAP2K4unclear / low-confidence candidateunclear0.000not prioritized-2
234BCL9unclear / low-confidence candidateunclear0.000not prioritized-2
235BRD3unclear / low-confidence candidateunclear0.000not prioritized-2
236KAT6Bunclear / low-confidence candidateunclear0.000not prioritized-2
237TBL1XR1unclear / low-confidence candidateunclear0.000not prioritized-2
238TMEM127unclear / low-confidence candidateunclear0.000not prioritized-2
239FANCFunclear / low-confidence candidateunclear0.000not prioritized-2
240PIK3CAunclear / low-confidence candidateunclear0.000not prioritized-2
241APCunclear / low-confidence candidateunclear0.000not prioritized-2
242NKX2-1unclear / low-confidence candidateunclear0.000not prioritized-2
243CTNNB1unclear / low-confidence candidateunclear0.000not prioritized-2
244MRTFAunclear / low-confidence candidateunclear0.000not prioritized-2
245KLF4unclear / low-confidence candidateunclear0.000not prioritized-2
246ZNF331unclear / low-confidence candidateunclear0.000not prioritized-2
247FGFR3unclear / low-confidence candidateunclear0.000not prioritized-2
248FHunclear / low-confidence candidateunclear0.000not prioritized-2
249MUTYHunclear / low-confidence candidateunclear0.000not prioritized-2
250TCL1Aunclear / low-confidence candidateunclear0.000not prioritized-2
251CARS1unclear / low-confidence candidateunclear0.000not prioritized-2
252ATP2B3unclear / low-confidence candidateunclear0.000not prioritized-2
253PRDM16unclear / low-confidence candidateunclear0.000not prioritized-2
254PTK6unclear / low-confidence candidateunclear0.000not prioritized-2
255LATS2unclear / low-confidence candidateunclear0.000not prioritized-2
256RAD51Cunclear / low-confidence candidateunclear0.000not prioritized-2
257STAT5Bunclear / low-confidence candidateunclear0.000not prioritized-2
258IKZF3unclear / low-confidence candidateunclear0.000not prioritized-2
259CDKN2Bunclear / low-confidence candidateunclear0.000not prioritized-2
260FANCEunclear / low-confidence candidateunclear0.000not prioritized-2
261TYRP1unclear / low-confidence candidateunclear0.000not prioritized-2
262BIRC3unclear / low-confidence candidateunclear0.000not prioritized-2
263ALKunclear / low-confidence candidateunclear0.000not prioritized-2
264FUBP1unclear / low-confidence candidateunclear0.000not prioritized-2
265PATZ1unclear / low-confidence candidateunclear0.000not prioritized-2
266FMN1unclear / low-confidence candidateunclear0.000not prioritized-2
267H3-3Aunclear / low-confidence candidateunclear0.000not prioritized-1
268GATA2unclear / low-confidence candidateunclear0.000not prioritized-1
269APOBEC3Bunclear / low-confidence candidateunclear0.000not prioritized-1
270BCL2unclear / low-confidence candidateunclear0.000not prioritized-1
271POU2AF1unclear / low-confidence candidateunclear0.000not prioritized-1
272PMELunclear / low-confidence candidateunclear0.000not prioritized0
273KRASunclear / low-confidence candidateunclear0.000not prioritized0
274TENT5Cunclear / low-confidence candidateunclear0.000not prioritized0
275CD79Aunclear / low-confidence candidateunclear0.000not prioritized0
276LPPunclear / low-confidence candidateunclear0.000not prioritized0
277PLXNB2unclear / low-confidence candidateunclear0.000not prioritized0
278SUZ12unclear / low-confidence candidateunclear0.000not prioritized0
279CBFA2T3unclear / low-confidence candidateunclear0.000not prioritized0
280NF2unclear / low-confidence candidateunclear0.000not prioritized0
281MAPK1unclear / low-confidence candidateunclear0.000not prioritized0
282KRT5unclear / low-confidence candidateunclear0.000not prioritized0
283HRASunclear / low-confidence candidateunclear0.000not prioritized0
284CNOT9unclear / low-confidence candidateunclear0.000not prioritized0
285PDCD1LG2unclear / low-confidence candidateunclear0.000not prioritized0
286SLC24A5unclear / low-confidence candidateunclear0.000not prioritized0
287NOTCH1unclear / low-confidence candidateunclear0.000not prioritized0
288MAP3K1unclear / low-confidence candidateunclear0.000not prioritized0
289CDH1unclear / low-confidence candidateunclear0.000not prioritized0
290BACH2unclear / low-confidence candidateunclear0.000not prioritized0
291KEAP1unclear / low-confidence candidateunclear0.000not prioritized0
292MED12unclear / low-confidence candidateunclear0.000not prioritized0
293H3C2unclear / low-confidence candidateunclear0.000not prioritized0
294TNFRSF17unclear / low-confidence candidateunclear0.000not prioritized0
295PIK3CBunclear / low-confidence candidateunclear0.000not prioritized0
296FBXW7unclear / low-confidence candidateunclear0.000not prioritized0
297NFE2L2unclear / low-confidence candidateunclear0.000not prioritized0
298ABL1unclear / low-confidence candidateunclear0.000not prioritized0
299CLPTM1Lunclear / low-confidence candidateunclear0.000not prioritized0
300ASPSCR1unclear / low-confidence candidateunclear0.000not prioritized0
+
+ + + +
+

DepMap functional-dependency research preview

+

Research-preview DepMap overlay rank is not the productive rank. Rank delta = dependency-aware candidate rank minus baseline rank. Negative deltas indicate movement toward a lower numerical rank, not biological validation.

+

DepMap cell-line dependency is not clinical anti-PD-1 response evidence; human review remains required.

+
TargetRoleBaseline scoreProfileCoverageContext modelsReference modelsGene effectDependency probabilitySelectivityBaseline rankResearch-preview DepMap overlay rankRank deltaIntegrationHuman review
ABL1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.05206080637452079, 'interquartile_range': 0.13179040761692934, 'maximum': 0.28090126723303777, 'mean': 0.0004447170999685991, 'measured_model_count': 56, 'median': 0.016656009569385857, 'minimum': -0.39424595195096673, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07972960124240855, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008384728233917674, 'interquartile_range': 0.028339679307337506, 'maximum': 0.3238668973345923, 'mean': 0.038111215003978426, 'measured_model_count': 56, 'median': 0.018554196815730083, 'minimum': 0.0019480816982328645, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03672440754125518, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 29.62962962962963}2982980blocked_insufficient_evidencerequired
ACKR3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.04688567353100497, 'interquartile_range': 0.17672355876386034, 'maximum': 0.3406804666190274, 'mean': 0.044219612203129, 'measured_model_count': 56, 'median': 0.051971504824438984, 'minimum': -0.248858520923774, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.12983788523285536, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.00480346215672851, 'interquartile_range': 0.022247043897867892, 'maximum': 0.1649058271995307, 'mean': 0.023943900342633655, 'measured_model_count': 56, 'median': 0.012531187649904931, 'minimum': 0.0007241920367250855, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.027050506054596402, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}2222220blocked_insufficient_evidencerequired
ACVR1Bunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.14711929218671402, 'interquartile_range': 0.12432204341482385, 'maximum': 0.3375441114825275, 'mean': -0.07998009592778019, 'measured_model_count': 56, 'median': -0.08515877044475642, 'minimum': -0.3764694607361463, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.022797248771890172, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.025659946006875323, 'interquartile_range': 0.046932751916033716, 'maximum': 0.3513129074264774, 'mean': 0.06341236180240215, 'measured_model_count': 56, 'median': 0.04447697969775254, 'minimum': 0.0007005068208089658, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07259269792290904, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}1901900blocked_insufficient_evidencerequired
AFDNunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.18632748263487175, 'interquartile_range': 0.15100015383667187, 'maximum': 0.194234342399614, 'mean': -0.10401314871474741, 'measured_model_count': 56, 'median': -0.09824333463123369, 'minimum': -0.3508544694256321, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.03532732879819988, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.02930714986928311, 'interquartile_range': 0.08549755078471634, 'maximum': 0.3273106965579132, 'mean': 0.08008016796975555, 'measured_model_count': 56, 'median': 0.04490595607597833, 'minimum': 0.002530139433360224, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11480470065399945, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 66.66666666666667}1471470blocked_insufficient_evidencerequired
AFF4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.13292375310772922, 'interquartile_range': 0.18416980660063442, 'maximum': 0.38654768840037734, 'mean': -0.039908295314705654, 'measured_model_count': 56, 'median': -0.05939864471942567, 'minimum': -0.34030817268214186, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0512460534929052, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01317409187949549, 'interquartile_range': 0.05043407141525695, 'maximum': 0.3328242072309353, 'mean': 0.05984196045726369, 'measured_model_count': 56, 'median': 0.03392475612734393, 'minimum': 0.00032369241265077216, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06360816329475244, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}2032030blocked_insufficient_evidencerequired
AKT1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.0696113940207029, 'interquartile_range': 0.13322895560601336, 'maximum': 0.34970543918655067, 'mean': -0.009742474845817481, 'measured_model_count': 56, 'median': 0.0046377124629188235, 'minimum': -0.38907832484150034, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06361756158531046, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.010254024576999815, 'interquartile_range': 0.02635393549780505, 'maximum': 0.44844945288476895, 'mean': 0.04874750692925877, 'measured_model_count': 56, 'median': 0.020344346257189568, 'minimum': 0.00037661393714791936, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.036607960074804866, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 3.7037037037037037}69690blocked_insufficient_evidencerequired
AKT2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.10698692296778596, 'interquartile_range': 0.18636044860159254, 'maximum': 0.2588885738209947, 'mean': -0.017972665153818613, 'measured_model_count': 56, 'median': -0.007401318928414405, 'minimum': -0.38332530305186063, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07937352563380658, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008499792764108715, 'interquartile_range': 0.05882776154012727, 'maximum': 0.32445036409429234, 'mean': 0.043810063779630086, 'measured_model_count': 56, 'median': 0.020804451087822785, 'minimum': 0.0014235690597476042, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06732755430423598, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 14.814814814814815}97970blocked_insufficient_evidencerequired
ALKunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.1391055879500493, 'interquartile_range': 0.1173851257210915, 'maximum': 0.24723686687943555, 'mean': -0.08817782520037898, 'measured_model_count': 56, 'median': -0.09243115642296142, 'minimum': -0.414971861038247, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.0217204622289578, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.023770154172617915, 'interquartile_range': 0.06796426553020232, 'maximum': 0.3791912417275072, 'mean': 0.0725077327529867, 'measured_model_count': 56, 'median': 0.0461958733533957, 'minimum': 0.00275245343127817, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09173441970282024, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}2632630blocked_insufficient_evidencerequired
AMER1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.009345387043821714, 'interquartile_range': 0.12788514596415662, 'maximum': 0.4383787682074304, 'mean': 0.07528086605188714, 'measured_model_count': 56, 'median': 0.08276667476476582, 'minimum': -0.19040979327961766, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.13723053300797833, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005306404228444668, 'interquartile_range': 0.01706158235075618, 'maximum': 0.149077231539901, 'mean': 0.018513075756905417, 'measured_model_count': 56, 'median': 0.009990647380253341, 'minimum': 0.00021627471873552294, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.022367986579200846, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 14.814814814814815}1721720blocked_insufficient_evidencerequired
APCunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.5859774841020371, 'interquartile_range': 0.38179195205040023, 'maximum': 0.28455865946694375, 'mean': -0.35785147041774285, 'measured_model_count': 56, 'median': -0.3380178346085523, 'minimum': -1.1406373050762526, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.20418553205163686, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.11658056622142303, 'interquartile_range': 0.5927857513786858, 'maximum': 0.9936482374577086, 'mean': 0.38426650867741774, 'measured_model_count': 56, 'median': 0.27761769575678924, 'minimum': 0.0013598374302337113, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.7093663176001088, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.3392857142857143, 'numerator': 19, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.17857142857142858, 'numerator': 10, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}2412410blocked_insufficient_evidencerequired
APOBEC3Bunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.09606841814979647, 'interquartile_range': 0.23515113567892895, 'maximum': 0.4400708139139492, 'mean': 0.026699711051649557, 'measured_model_count': 56, 'median': 0.005793906262137797, 'minimum': -0.4283263401162755, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.13908271752913248, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005510925052745797, 'interquartile_range': 0.041485165212828315, 'maximum': 0.3365293082591688, 'mean': 0.0420897143545745, 'measured_model_count': 56, 'median': 0.019179227319746587, 'minimum': 0.00020440713068760097, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04699609026557411, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}2692690blocked_insufficient_evidencerequired
ARunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.041097870345206546, 'interquartile_range': 0.1546972619994098, 'maximum': 0.4537651498544541, 'mean': 0.09982159752496085, 'measured_model_count': 56, 'median': 0.09918225274948897, 'minimum': -0.28630325474580987, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.19579513234461635, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.004300171032795553, 'interquartile_range': 0.012979205717451568, 'maximum': 0.1346611349824717, 'mean': 0.01616543771498364, 'measured_model_count': 56, 'median': 0.007519158470395323, 'minimum': 0.00024636522631291607, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.01727937675024712, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 25.925925925925927}1031030blocked_insufficient_evidencerequired
ARG1research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.01952750081956353, 'interquartile_range': 0.15704048446148916, 'maximum': 0.4503933085737245, 'mean': 0.11178133015127081, 'measured_model_count': 56, 'median': 0.11451918046801807, 'minimum': -0.188393571489023, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1765679852810527, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.002940917113951669, 'interquartile_range': 0.013001543968601731, 'maximum': 0.14703040964480976, 'mean': 0.01426250886872838, 'measured_model_count': 56, 'median': 0.006837278753817717, 'minimum': 0.0007338381832860604, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0159424610825534, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}not availablenot availablenot availableblocked_insufficient_evidencerequired
ARHGAP35unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.05883410528362672, 'interquartile_range': 0.17857380242184923, 'maximum': 0.6903895828374135, 'mean': 0.16384045492536617, 'measured_model_count': 56, 'median': 0.1631803821345646, 'minimum': -0.05352249745888138, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.23740790770547593, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0024143042641998377, 'interquartile_range': 0.008129801540448407, 'maximum': 0.034355451535692104, 'mean': 0.007660889307250123, 'measured_model_count': 56, 'median': 0.004719702771807059, 'minimum': 2.496236796331053e-05, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.010544105804648245, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}1281280blocked_insufficient_evidencerequired
ARHGEF12unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06317094016798837, 'interquartile_range': 0.12563105896818386, 'maximum': 0.2270279094210083, 'mean': -0.008020450715228684, 'measured_model_count': 56, 'median': 0.034871420237681874, 'minimum': -0.41302734708348443, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06246011880019548, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008032339590528874, 'interquartile_range': 0.03030221418076693, 'maximum': 0.3240745714209432, 'mean': 0.04467501766624043, 'measured_model_count': 56, 'median': 0.015320245248807533, 'minimum': 0.003552775301786233, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.038334553771295805, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}2042040blocked_insufficient_evidencerequired
ARID1Aunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.43557053844131854, 'interquartile_range': 0.3219228042395692, 'maximum': 0.34226669290859557, 'mean': -0.32606024413870033, 'measured_model_count': 56, 'median': -0.2619302515505961, 'minimum': -1.2757799512718386, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.11364773420174931, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.05457689627272941, 'interquartile_range': 0.43366939129216586, 'maximum': 0.9991107761621311, 'mean': 0.32125495906040114, 'measured_model_count': 56, 'median': 0.1554943077693044, 'minimum': 0.0021031613531615964, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.4882462875648953, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.25, 'numerator': 14, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.16071428571428573, 'numerator': 9, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}1791790blocked_insufficient_evidencerequired
ARID1Bunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.12835629844328875, 'interquartile_range': 0.17664885205400177, 'maximum': 0.36199530982159556, 'mean': -0.044734329690283126, 'measured_model_count': 56, 'median': -0.04386019774725303, 'minimum': -0.6603854276514436, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04829255361071304, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.011252177444106795, 'interquartile_range': 0.06423641939851084, 'maximum': 0.7207650483372453, 'mean': 0.06040518347981727, 'measured_model_count': 56, 'median': 0.032552869087177506, 'minimum': 0.0008909390586229766, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07548859684261763, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}1621620blocked_insufficient_evidencerequired
ARID2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.015availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.4704228591773787, 'interquartile_range': 0.40651398153145546, 'maximum': 0.3411982550552147, 'mean': -0.26655617429891615, 'measured_model_count': 56, 'median': -0.2207698686925888, 'minimum': -0.996786364696395, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.0639088776459232, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.03116399473948154, 'interquartile_range': 0.46389475167534294, 'maximum': 0.9745826114257009, 'mean': 0.27967584939597845, 'measured_model_count': 56, 'median': 0.15054546566780236, 'minimum': 0.0022844621532051974, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.4950587464148245, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.25, 'numerator': 14, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 18.51851851851852}20200blocked_insufficient_evidencerequired
ARNTunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.3581074854447507, 'interquartile_range': 0.3039227377270318, 'maximum': 1.0399727157355843, 'mean': -0.19191197960061698, 'measured_model_count': 56, 'median': -0.20315562003917215, 'minimum': -0.8571155954005378, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.05418474771771889, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.02937998694058869, 'interquartile_range': 0.2622623014624777, 'maximum': 0.9255765328229291, 'mean': 0.2264542684912856, 'measured_model_count': 56, 'median': 0.11103222682700858, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2916422884030664, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.17857142857142858, 'numerator': 10, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}1361360blocked_insufficient_evidencerequired
ASPSCR1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.197432624657035, 'interquartile_range': 0.14713784975672511, 'maximum': 0.08866600605484734, 'mean': -0.13710999970506296, 'measured_model_count': 56, 'median': -0.1028582496030106, 'minimum': -0.4406863774006863, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.0502947749003099, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.03159872449810511, 'interquartile_range': 0.09714302943381564, 'maximum': 0.4966970706033939, 'mean': 0.10482145638843436, 'measured_model_count': 56, 'median': 0.05442591831673187, 'minimum': 0.007136843313635444, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.12874175393192075, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 7.407407407407407}3003000blocked_insufficient_evidencerequired
ATF1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.31199003147965054, 'interquartile_range': 0.19505157988805688, 'maximum': 0.20303160162622352, 'mean': -0.2070263048606922, 'measured_model_count': 56, 'median': -0.23658966248001567, 'minimum': -0.6261219152697686, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.11693845159159365, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.06743848309059797, 'interquartile_range': 0.17343780682176396, 'maximum': 0.7946224472456699, 'mean': 0.1843216141685337, 'measured_model_count': 56, 'median': 0.14648723614834475, 'minimum': 0.004121566474625243, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.24087628991236193, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 92.5925925925926}1731730blocked_insufficient_evidencerequired
ATMunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.003availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.0020259254350783124, 'interquartile_range': 0.3216274073763178, 'maximum': 0.8941780165066932, 'mean': 0.16248329861889094, 'measured_model_count': 56, 'median': 0.08719509887627361, 'minimum': -0.3490614222046967, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.3196014819412395, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.001660484890086447, 'interquartile_range': 0.020616259399120065, 'maximum': 0.40357518870553377, 'mean': 0.024982232330452915, 'measured_model_count': 56, 'median': 0.007002239522950301, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02227674428920651, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 7.407407407407407}35350blocked_insufficient_evidencerequired
ATP2B3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.12434728095818147, 'interquartile_range': 0.22825275912574455, 'maximum': 0.47230728751688694, 'mean': -0.008667745235625602, 'measured_model_count': 56, 'median': -0.036856086964585304, 'minimum': -0.34970797377659013, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10390547816756308, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.009082734404598202, 'interquartile_range': 0.05326351901840336, 'maximum': 0.3112851098819218, 'mean': 0.04792125591852207, 'measured_model_count': 56, 'median': 0.03490888626221475, 'minimum': 0.0002188965827178968, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06234625342300156, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}2522520blocked_insufficient_evidencerequired
ATRunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.3321653972992362, 'interquartile_range': 0.26959811435888104, 'maximum': -0.8369811425904811, 'mean': -1.230833734102214, 'measured_model_count': 56, 'median': -1.172755189115312, 'minimum': -1.9629129476130718, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.0625672829403552, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9788404513704841, 'interquartile_range': 0.019620482322990296, 'maximum': 1.0, 'mean': 0.9848397947268778, 'measured_model_count': 56, 'median': 0.9904158847911251, 'minimum': 0.9189537502260394, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9984609336934744, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}63630blocked_insufficient_evidencerequired
ATRXunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.4980924165161724, 'interquartile_range': 0.32325243518896685, 'maximum': 0.42042034947144924, 'mean': -0.34566514357228256, 'measured_model_count': 56, 'median': -0.3302554609174006, 'minimum': -0.8970558577974759, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.17483998132720557, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.09010910049335963, 'interquartile_range': 0.4892689464867115, 'maximum': 0.9394427095826552, 'mean': 0.3615166505326878, 'measured_model_count': 56, 'median': 0.30795028110934963, 'minimum': 0.0005373738842964715, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.5793780469800711, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.32142857142857145, 'numerator': 18, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.08928571428571429, 'numerator': 5, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}92920blocked_insufficient_evidencerequired
AXIN1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.037343116083035185, 'interquartile_range': 0.26661108518976745, 'maximum': 0.9196883699197242, 'mean': 0.08748785591226547, 'measured_model_count': 56, 'median': 0.08289157811043477, 'minimum': -0.7764618367290135, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.22926796910673228, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.001998134253073587, 'interquartile_range': 0.0260986272540997, 'maximum': 0.8778227499507888, 'mean': 0.06161891085070346, 'measured_model_count': 56, 'median': 0.009616196179705327, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.028096761507173287, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 29.62962962962963}1511510blocked_insufficient_evidencerequired
AXLresearch-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.09669271225359513, 'interquartile_range': 0.13838293442208938, 'maximum': 0.33269592966644873, 'mean': -0.05402248348828266, 'measured_model_count': 56, 'median': -0.05461535624294615, 'minimum': -0.591523976802867, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.041690222168494245, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01321277007165553, 'interquartile_range': 0.047403672929686676, 'maximum': 0.5937823231403992, 'mean': 0.06668973321292734, 'measured_model_count': 56, 'median': 0.03594859224302639, 'minimum': 0.0021112287349255585, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0606164430013422, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}not availablenot availablenot availableblocked_insufficient_evidencerequired
B2Mantigen-presentation resistance biomarkerantibody / IO: 0.227; biomarker: 0.806; small molecule: 0.132availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.03419536124041851, 'interquartile_range': 0.13539073572534133, 'maximum': 0.222441908549175, 'mean': 0.02537352064559218, 'measured_model_count': 56, 'median': 0.015821163143747298, 'minimum': -0.26075783687617665, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10119537448492283, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.006961531439831104, 'interquartile_range': 0.02038009892374358, 'maximum': 0.23444542085876965, 'mean': 0.025135791460166153, 'measured_model_count': 56, 'median': 0.0164348942055268, 'minimum': 0.001654700032914229, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.027341630363574686, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}95-4blocked_insufficient_evidencerequired
BACH2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.01884643567221031, 'interquartile_range': 0.12885452737206532, 'maximum': 0.2922363938617609, 'mean': 0.04157837025826655, 'measured_model_count': 56, 'median': 0.039909660670576906, 'minimum': -0.1728292133635718, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11000809169985502, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.007121448360295681, 'interquartile_range': 0.020012121577146845, 'maximum': 0.06841314448379879, 'mean': 0.019631283583679472, 'measured_model_count': 56, 'median': 0.013053911679737119, 'minimum': 0.0010205824014244435, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.027133569937442526, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}2902900blocked_insufficient_evidencerequired
BAP1tumor-intrinsic driver / poor direct therapeutic targetantibody / IO: 0.000; biomarker: 0.128; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.7617301000041377, 'interquartile_range': 0.39215821877949375, 'maximum': -0.027665093614035463, 'mean': -0.580660108206857, 'measured_model_count': 56, 'median': -0.5909145722746947, 'minimum': -1.1970868602866886, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.3695718812246439, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.30705277763360284, 'interquartile_range': 0.5817669754730993, 'maximum': 0.9966187017789548, 'mean': 0.6221644187853995, 'measured_model_count': 56, 'median': 0.7153010101416735, 'minimum': 0.026783164047011688, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.8888197531067021, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.6607142857142857, 'numerator': 37, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.4107142857142857, 'numerator': 23, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}13130blocked_insufficient_evidencerequired
BCL11Aunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.11420819046622246, 'interquartile_range': 0.16659082868984246, 'maximum': 0.43518189292339327, 'mean': -0.045648604296433484, 'measured_model_count': 56, 'median': -0.056271293868629293, 'minimum': -0.5045098076749046, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.052382638223619986, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.013988075492537793, 'interquartile_range': 0.044676824510456764, 'maximum': 0.6734265664462808, 'mean': 0.060102345993402966, 'measured_model_count': 56, 'median': 0.033069240860764355, 'minimum': 0.0008709175060067826, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.058664900002994555, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}1431430blocked_insufficient_evidencerequired
BCL11Bunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.04299951768347804, 'interquartile_range': 0.12128991572901711, 'maximum': 0.2227864472704803, 'mean': 0.01497917009073292, 'measured_model_count': 56, 'median': 0.019832171594732825, 'minimum': -0.30944805285306837, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07829039804553907, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.007893891610742113, 'interquartile_range': 0.023567574776098024, 'maximum': 0.2051689240725753, 'mean': 0.024793767381785202, 'measured_model_count': 56, 'median': 0.018108339873370675, 'minimum': 0.0026566262890120834, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03146146638684014, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 70.37037037037037}2302300blocked_insufficient_evidencerequired
BCL2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.08696651149816556, 'interquartile_range': 0.14561016392955564, 'maximum': 0.2680923594186532, 'mean': -0.016920171192513926, 'measured_model_count': 56, 'median': -0.025311452898357994, 'minimum': -0.25176194650284295, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05864365243139008, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.012691998621583553, 'interquartile_range': 0.03380030655700515, 'maximum': 0.161056642128686, 'mean': 0.03713254238273757, 'measured_model_count': 56, 'median': 0.02454383022252416, 'minimum': 0.0023418864731136555, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.046492305178588704, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}2702700blocked_insufficient_evidencerequired
BCL9unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.38494598357777626, 'interquartile_range': 0.3330532366091112, 'maximum': 0.4089113515279511, 'mean': -0.2320473630104575, 'measured_model_count': 56, 'median': -0.23320556013071192, 'minimum': -0.9150034496838594, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.0518927469686651, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.03469806330531005, 'interquartile_range': 0.2717156659809888, 'maximum': 0.9363484371526809, 'mean': 0.24510724830209973, 'measured_model_count': 56, 'median': 0.14987003186885173, 'minimum': 6.792628342980656e-05, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.30641372928629884, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.19642857142857142, 'numerator': 11, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.07142857142857142, 'numerator': 4, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}2342340blocked_insufficient_evidencerequired
BCL9Lunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.1688428463252949, 'interquartile_range': 0.19093666889847527, 'maximum': 0.2938285868937669, 'mean': -0.07602213222019842, 'measured_model_count': 56, 'median': -0.08759133713750625, 'minimum': -0.8127726660093453, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.022093822573180377, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01697105113102501, 'interquartile_range': 0.09072755309577211, 'maximum': 0.8980221838973915, 'mean': 0.08478326576217181, 'measured_model_count': 56, 'median': 0.03968158389728285, 'minimum': 0.0014820722411286198, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10769860422679713, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}1341340blocked_insufficient_evidencerequired
BCORunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.09843137692846265, 'interquartile_range': 0.3024111110874371, 'maximum': 0.5123476618974896, 'mean': 0.043399310001232275, 'measured_model_count': 56, 'median': 0.025163160100960116, 'minimum': -0.46608548605258826, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2039797341589745, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.004385523455098974, 'interquartile_range': 0.049122236208953576, 'maximum': 0.5695078292114721, 'mean': 0.04532958920474263, 'measured_model_count': 56, 'median': 0.01380619756232246, 'minimum': 0.00015610740691107978, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05350775966405255, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}1561560blocked_insufficient_evidencerequired
BCORL1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.040014746834881765, 'interquartile_range': 0.1883396297572965, 'maximum': 0.45603754792744744, 'mean': 0.09678094437513547, 'measured_model_count': 56, 'median': 0.10564126028540002, 'minimum': -0.6082875411667698, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.22835437659217828, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0023587471886702166, 'interquartile_range': 0.011221787353487667, 'maximum': 0.7004279011526633, 'mean': 0.04059999544600247, 'measured_model_count': 56, 'median': 0.007299775968082389, 'minimum': 0.00014814138376582694, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.013580534542157883, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}2182180blocked_insufficient_evidencerequired
BIRC3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.053832945649035846, 'interquartile_range': 0.17211190378930316, 'maximum': 0.29394174579102555, 'mean': 0.021754678809343127, 'measured_model_count': 56, 'median': 0.0066408270165531635, 'minimum': -0.27705052981998146, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11827895814026732, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.006081698993193586, 'interquartile_range': 0.0270064902459861, 'maximum': 0.2690632218111069, 'mean': 0.029979679761486938, 'measured_model_count': 56, 'median': 0.01746802168718406, 'minimum': 0.0015399221549407625, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03308818923917969, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}2622620blocked_insufficient_evidencerequired
BRAFtumor-intrinsic driver / small-molecule targetantibody / IO: 0.269; biomarker: 0.482; small molecule: 0.845availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.6227668727162368, 'interquartile_range': 0.9795415688905247, 'maximum': -0.015881149663220406, 'mean': -1.1769393408178332, 'measured_model_count': 56, 'median': -1.2347703095627218, 'minimum': -2.6355354158678552, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.6432253038257121, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.8542815144561293, 'interquartile_range': 0.14570215220149452, 'maximum': 1.0, 'mean': 0.7983333399564246, 'measured_model_count': 56, 'median': 0.9910996581121145, 'minimum': 0.018849964783263323, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9999836666576238, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.7857142857142857, 'numerator': 44, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.75, 'numerator': 42, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 100.0}71-6blocked_insufficient_evidencerequired
BRCA1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.8334513137692443, 'interquartile_range': 0.3666416803437246, 'maximum': 0.062275150039045934, 'mean': -0.6446669874885088, 'measured_model_count': 56, 'median': -0.6447037480808876, 'minimum': -1.4679161979282245, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.46680963342551973, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.5092257497253594, 'interquartile_range': 0.4183593833250353, 'maximum': 0.9994909191982082, 'mean': 0.6709476213577762, 'measured_model_count': 56, 'median': 0.7565224518784195, 'minimum': 0.009461623428259134, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9275851330503947, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.7678571428571429, 'numerator': 43, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.4642857142857143, 'numerator': 26, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 92.5925925925926}68680blocked_insufficient_evidencerequired
BRCA2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.008availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.6488829996539245, 'interquartile_range': 0.2518526421601791, 'maximum': -0.11644136524611565, 'mean': -0.5194239412699343, 'measured_model_count': 56, 'median': -0.5458386512220574, 'minimum': -0.9883316064136789, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.3970303574937454, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.3920368984175355, 'interquartile_range': 0.4198271479602616, 'maximum': 0.9795182103056468, 'mean': 0.5793265400728955, 'measured_model_count': 56, 'median': 0.6356233831085945, 'minimum': 0.047399772777465814, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.8118640463777971, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.625, 'numerator': 35, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.2857142857142857, 'numerator': 16, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}31310blocked_insufficient_evidencerequired
BRD3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.033964049706230695, 'interquartile_range': 0.09288662604572513, 'maximum': 0.3470103010805555, 'mean': 0.07953525307711658, 'measured_model_count': 56, 'median': 0.08710923930845982, 'minimum': -0.17690537289100544, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.12685067575195583, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.00500462514257108, 'interquartile_range': 0.013542976338508669, 'maximum': 0.07572924687956509, 'mean': 0.014028321936522852, 'measured_model_count': 56, 'median': 0.0076650310535126605, 'minimum': 0.0008221952078158884, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.01854760148107975, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}2352350blocked_insufficient_evidencerequired
BRD4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.248457530692548, 'interquartile_range': 0.31380168154055843, 'maximum': -0.23565820283589978, 'mean': -1.077419296229426, 'measured_model_count': 56, 'median': -1.107477935554086, 'minimum': -1.7448082336119686, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.9346558491519896, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.955950792547962, 'interquartile_range': 0.03830238730638025, 'maximum': 0.9999959988125812, 'mean': 0.9347159273213392, 'measured_model_count': 56, 'median': 0.9859241206511045, 'minimum': 0.16171450657858166, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9942531798543423, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.9642857142857143, 'numerator': 54, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.9107142857142857, 'numerator': 51, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}1831830blocked_insufficient_evidencerequired
BTKunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.035771337179793285, 'interquartile_range': 0.11021362664917433, 'maximum': 0.3015345371345652, 'mean': 0.03015665145976979, 'measured_model_count': 56, 'median': 0.021314724552192434, 'minimum': -0.21445633651626686, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07444228946938104, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.009506480463942741, 'interquartile_range': 0.01914368707509713, 'maximum': 0.17509651908925622, 'mean': 0.022697174251634644, 'measured_model_count': 56, 'median': 0.014886149558598682, 'minimum': 0.0014470532586933651, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02865016753903987, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 18.51851851851852}2282280blocked_insufficient_evidencerequired
BUB1Bunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.3026861749001495, 'interquartile_range': 0.34471355076042975, 'maximum': -0.35062174656503176, 'mean': -1.1293619487648725, 'measured_model_count': 56, 'median': -1.1239831043751725, 'minimum': -1.9513382130061605, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.9579726241397197, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9661276307634157, 'interquartile_range': 0.027854131010518257, 'maximum': 1.0, 'mean': 0.9478580814276604, 'measured_model_count': 56, 'median': 0.9837485018692456, 'minimum': 0.27364189485863244, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9939817617739339, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.9821428571428571, 'numerator': 55, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.9285714285714286, 'numerator': 52, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}2202200blocked_insufficient_evidencerequired
CACNA1Dunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06948366200968034, 'interquartile_range': 0.12410483739837593, 'maximum': 0.22152661199200682, 'mean': -0.013247144110869868, 'measured_model_count': 56, 'median': -0.019408167580945213, 'minimum': -0.3736384929932119, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.054621175388695584, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01215263379668628, 'interquartile_range': 0.02561710835008954, 'maximum': 0.3270060202736238, 'mean': 0.037954791056176954, 'measured_model_count': 56, 'median': 0.02156477750214402, 'minimum': 0.0011308355940113652, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03776974214677582, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}2262260blocked_insufficient_evidencerequired
CARD11unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.09562676156794828, 'interquartile_range': 0.19020488634525662, 'maximum': 0.404261290756003, 'mean': -0.01514292880487186, 'measured_model_count': 56, 'median': -0.00843369100614956, 'minimum': -0.54090902690978, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09457812477730834, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008250132462729496, 'interquartile_range': 0.053159633659909625, 'maximum': 0.49703376053943404, 'mean': 0.04895601126388154, 'measured_model_count': 56, 'median': 0.022444793911606052, 'minimum': 0.00045958623127264427, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06140976612263912, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 7.407407407407407}1811810blocked_insufficient_evidencerequired
CARS1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.8026753461573768, 'interquartile_range': 0.3885820681187324, 'maximum': -0.8250676982589952, 'mean': -1.6092899115753092, 'measured_model_count': 56, 'median': -1.5980364353584418, 'minimum': -2.3420142033697706, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.4140932780386444, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9965804422428789, 'interquartile_range': 0.0034195577571211055, 'maximum': 1.0, 'mean': 0.9922324381369838, 'measured_model_count': 56, 'median': 0.9999665853145443, 'minimum': 0.8994039933591144, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 1.0, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}2512510blocked_insufficient_evidencerequired
CASP8unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.011897068060551866, 'interquartile_range': 0.12536036995353528, 'maximum': 0.8713892618394627, 'mean': 0.06026911617051994, 'measured_model_count': 56, 'median': 0.04398793623669359, 'minimum': -0.3339036816398781, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11346330189298341, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005880240328625039, 'interquartile_range': 0.022025935311596547, 'maximum': 0.2593446374523578, 'mean': 0.026311317489120405, 'measured_model_count': 56, 'median': 0.010841974401337703, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.027906175640221586, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}1141140blocked_insufficient_evidencerequired
CBFA2T3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.136964140758632, 'interquartile_range': 0.16167139541119036, 'maximum': 0.21418474445863944, 'mean': -0.05229143749802029, 'measured_model_count': 56, 'median': -0.01977128242853117, 'minimum': -0.4116048408666105, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02470725465255836, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.015136985019785953, 'interquartile_range': 0.05489342649673515, 'maximum': 0.3112207868780006, 'mean': 0.05585963773120791, 'measured_model_count': 56, 'median': 0.02561603909201212, 'minimum': 0.0020054058447227492, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0700304115165211, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}2792790blocked_insufficient_evidencerequired
CBLunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.03494968754517518, 'interquartile_range': 0.12545142715306176, 'maximum': 0.38716705456969325, 'mean': 0.03013536038410847, 'measured_model_count': 56, 'median': 0.019575406859070273, 'minimum': -0.21767347114684926, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09050173960788657, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0085481911101527, 'interquartile_range': 0.01963866209088416, 'maximum': 0.10180326303471457, 'mean': 0.022745420875610177, 'measured_model_count': 56, 'median': 0.015865046905975483, 'minimum': 0.0010694223846413645, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02818685320103686, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}99990blocked_insufficient_evidencerequired
CBLBunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.05384536648266203, 'interquartile_range': 0.1050815451078648, 'maximum': 0.3454643691830615, 'mean': 0.007447681590991319, 'measured_model_count': 56, 'median': -0.0034065031597723177, 'minimum': -0.16375155174679337, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05123617862520277, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.010491807935730858, 'interquartile_range': 0.0307455167698769, 'maximum': 0.12149399207427411, 'mean': 0.026859285847007187, 'measured_model_count': 56, 'median': 0.020538144383673726, 'minimum': 0.0006857831670003677, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04123732470560776, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}1411410blocked_insufficient_evidencerequired
CCND1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -2.5159803501587126, 'interquartile_range': 1.317293670034944, 'maximum': -0.05330788682190524, 'mean': -1.8967774740528005, 'measured_model_count': 56, 'median': -1.828765775143998, 'minimum': -3.3354607159421072, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.1986866801237686, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9930169828579302, 'interquartile_range': 0.006983017142069836, 'maximum': 1.0, 'mean': 0.9517735651535275, 'measured_model_count': 56, 'median': 1.0, 'minimum': 0.045554294167438766, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 1.0, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.9642857142857143, 'numerator': 54, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.9107142857142857, 'numerator': 51, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 85.18518518518519}46460blocked_insufficient_evidencerequired
CCND2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.15579197515311352, 'interquartile_range': 0.17786015005357908, 'maximum': 0.37138012941204834, 'mean': -0.05966427508651161, 'measured_model_count': 56, 'median': -0.08633474069631311, 'minimum': -0.22837474318280288, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.022068174900465552, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.013285731471925577, 'interquartile_range': 0.06560912247822459, 'maximum': 0.1904888154369347, 'mean': 0.05466906017495544, 'measured_model_count': 56, 'median': 0.04813965995942092, 'minimum': 0.0008839430891336923, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07889485395015017, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}1371370blocked_insufficient_evidencerequired
CD274anti-PD-1 combination targetantibody / IO: 0.825; biomarker: 0.496; small molecule: 0.141availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.1219432529423023, 'interquartile_range': 0.14942892394873147, 'maximum': 0.5564732732340494, 'mean': 0.19436573097880774, 'measured_model_count': 56, 'median': 0.1863639156999815, 'minimum': -0.07863180936507297, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.27137217689103377, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.001499226517437284, 'interquartile_range': 0.0064206254383672645, 'maximum': 0.036701970754130495, 'mean': 0.006382432047991671, 'measured_model_count': 56, 'median': 0.0035318069749596765, 'minimum': 8.135797076424987e-05, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.007919851955804549, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 25.925925925925927}396blocked_insufficient_evidencerequired
CD79Aunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.059678830445944894, 'interquartile_range': 0.09997205789462581, 'maximum': 0.26466406443135215, 'mean': 0.1122462807561854, 'measured_model_count': 56, 'median': 0.1100920547426244, 'minimum': -0.02926449099631112, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1596508883405707, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.003938865463013505, 'interquartile_range': 0.009093021526598969, 'maximum': 0.02573885019852544, 'mean': 0.008905088974721555, 'measured_model_count': 56, 'median': 0.0069261069107548695, 'minimum': 0.0007298659872511824, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.013031886989612475, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}2752750blocked_insufficient_evidencerequired
CD8Aresearch-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.027430912377545535, 'interquartile_range': 0.13942569209925004, 'maximum': 0.46165860344769677, 'mean': 0.045785073452028605, 'measured_model_count': 56, 'median': 0.03928974584334112, 'minimum': -0.26540822030616257, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11199477972170452, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.007483582094896921, 'interquartile_range': 0.017911250672013962, 'maximum': 0.201806266723021, 'mean': 0.02445228992923763, 'measured_model_count': 56, 'median': 0.011938528707279468, 'minimum': 0.0002748136637528369, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02539483276691088, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 11.11111111111111}not availablenot availablenot availableblocked_insufficient_evidencerequired
CDH1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.15427271942471482, 'interquartile_range': 0.1577065173221155, 'maximum': 0.2295208783394289, 'mean': -0.10742966270794449, 'measured_model_count': 56, 'median': -0.07204685958685368, 'minimum': -0.8750426660413623, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.00343379789740067, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0180917185977245, 'interquartile_range': 0.06286002234786717, 'maximum': 0.874379672670159, 'mean': 0.10329287088429209, 'measured_model_count': 56, 'median': 0.04375955195407501, 'minimum': 0.0028271732493434652, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08095174094559167, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 25.925925925925927}2892890blocked_insufficient_evidencerequired
CDK12unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.5586337757206544, 'interquartile_range': 0.19059665446702484, 'maximum': -0.13749466210671846, 'mean': -0.47143749469136337, 'measured_model_count': 56, 'median': -0.47096900533770847, 'minimum': -1.200422877513772, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.3680371212536296, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.35421745198329635, 'interquartile_range': 0.31026076242553446, 'maximum': 0.9783518078107925, 'mean': 0.49957849685747113, 'measured_model_count': 56, 'median': 0.4693828317812654, 'minimum': 0.04818076524574193, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.6644782144088308, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.44642857142857145, 'numerator': 25, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.16071428571428573, 'numerator': 9, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 85.18518518518519}94940blocked_insufficient_evidencerequired
CDK4tumor-intrinsic driver / small-molecule targetantibody / IO: 0.000; biomarker: 0.101; small molecule: 0.682availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.1460787729249597, 'interquartile_range': 0.6487242724872709, 'maximum': 0.14819456849436097, 'mean': -0.9690295177076944, 'measured_model_count': 56, 'median': -0.7802086880629331, 'minimum': -2.6012252653565273, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.4973545004376888, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.5276778197266463, 'interquartile_range': 0.46063984426021753, 'maximum': 1.0, 'mean': 0.7625651007343259, 'measured_model_count': 56, 'median': 0.8640150958074966, 'minimum': 0.0044507692556070445, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9883176639868638, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.7857142857142857, 'numerator': 44, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.5892857142857143, 'numerator': 33, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 66.66666666666667}1814-4blocked_insufficient_evidencerequired
CDK6unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.827840200340922, 'interquartile_range': 0.5564369377066776, 'maximum': 0.053999009787811136, 'mean': -0.6040550843316354, 'measured_model_count': 56, 'median': -0.4741396489201388, 'minimum': -1.9939384470287465, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.2714032626342444, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.21797895301513842, 'interquartile_range': 0.7309485506409665, 'maximum': 1.0, 'mean': 0.5655746850424314, 'measured_model_count': 56, 'median': 0.5298570181549593, 'minimum': 0.009549200402016388, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.948927503656105, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.5178571428571429, 'numerator': 29, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.39285714285714285, 'numerator': 22, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}1101100blocked_insufficient_evidencerequired
CDKN2Atumor-intrinsic driver / poor direct therapeutic targetantibody / IO: 0.000; biomarker: 0.329; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.0614428613918262, 'interquartile_range': 0.17868173128792053, 'maximum': 0.8033652137565361, 'mean': 0.15445826248821265, 'measured_model_count': 56, 'median': 0.16082152009903888, 'minimum': -0.4366709312086744, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.24012459267974673, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0017200751468406438, 'interquartile_range': 0.014484209677434792, 'maximum': 0.35063429324839185, 'mean': 0.024559879767375458, 'measured_model_count': 56, 'median': 0.0038283808957741555, 'minimum': 1.261747964913208e-06, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.016204284824275435, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}12186blocked_insufficient_evidencerequired
CDKN2Bunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.0404825098272594, 'interquartile_range': 0.19472070385108634, 'maximum': 0.6165124700793739, 'mean': 0.1636209642579699, 'measured_model_count': 55, 'median': 0.15881718146129087, 'minimum': -0.12693022289918005, 'missing_fraction': 0.017857142857142856, 'missing_model_count': 1, 'third_quartile': 0.23520321367834574, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0013846813277508152, 'interquartile_range': 0.01286710860460067, 'maximum': 0.06171403833365283, 'mean': 0.009855320712572656, 'measured_model_count': 55, 'median': 0.005092649083602317, 'minimum': 4.676073979628638e-06, 'missing_fraction': 0.017857142857142856, 'missing_model_count': 1, 'third_quartile': 0.014251789932351485, 'threshold_fractions': (mappingproxy({'denominator': 55, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 55, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 11.11111111111111}2592590blocked_insufficient_evidencerequired
CDX2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.13942254695053768, 'interquartile_range': 0.16163068207457448, 'maximum': 0.29566206461172795, 'mean': -0.06736407857919634, 'measured_model_count': 56, 'median': -0.059264623715066425, 'minimum': -0.41280316373867654, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.022208135124036785, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.015200994236108184, 'interquartile_range': 0.06085001454530309, 'maximum': 0.43100994254852387, 'mean': 0.062366427518474085, 'measured_model_count': 56, 'median': 0.03842983462576611, 'minimum': 0.0017620750891681012, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07605100878141127, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}1891890blocked_insufficient_evidencerequired
CHD4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.4566567459085873, 'interquartile_range': 0.35622946135425004, 'maximum': -0.5235966708192303, 'mean': -1.256281075871031, 'measured_model_count': 56, 'median': -1.2512662213227028, 'minimum': -2.0043420178114166, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.1004272845543372, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9815862695547178, 'interquartile_range': 0.017558270975871704, 'maximum': 1.0, 'mean': 0.978835362557547, 'measured_model_count': 56, 'median': 0.9929567916053474, 'minimum': 0.6621869651205554, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9991445405305895, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.9821428571428571, 'numerator': 55, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 70.37037037037037}2122120blocked_insufficient_evidencerequired
CHEK2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.23674494928062137, 'interquartile_range': 0.22708131202008544, 'maximum': 0.931883971568137, 'mean': 0.3426903444379113, 'measured_model_count': 56, 'median': 0.3224042378144514, 'minimum': -0.16147390203749837, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.4638262613007068, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 9.751658835563242e-05, 'interquartile_range': 0.003480886578628852, 'maximum': 0.0694434148067228, 'mean': 0.0052062046687379885, 'measured_model_count': 56, 'median': 0.0006560276296503497, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.003578403166984485, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 7.407407407407407}62620blocked_insufficient_evidencerequired
CICunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.20969753443445882, 'interquartile_range': 0.3188863089690407, 'maximum': 0.7212674338591033, 'mean': -0.05479185248369578, 'measured_model_count': 56, 'median': -0.0724818295618623, 'minimum': -0.5922742740203383, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10918877453458187, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0060443484088349726, 'interquartile_range': 0.10425416850941045, 'maximum': 0.6755686797363436, 'mean': 0.11305469201665709, 'measured_model_count': 56, 'median': 0.041316844193587124, 'minimum': 3.871106505121315e-06, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11029851691824542, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.08928571428571429, 'numerator': 5, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}1641640blocked_insufficient_evidencerequired
CIITAunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.07481705516268009, 'interquartile_range': 0.14392723189675605, 'maximum': 0.21949437633984192, 'mean': -0.005468924475870724, 'measured_model_count': 56, 'median': 0.01143269694703151, 'minimum': -0.30489474426374596, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06911017673407598, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.009702019229598511, 'interquartile_range': 0.02840255596041054, 'maximum': 0.24617646555482525, 'mean': 0.03490953789092406, 'measured_model_count': 56, 'median': 0.016486777927961806, 'minimum': 0.001692034244815741, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03810457519000905, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}1331330blocked_insufficient_evidencerequired
CLPTM1Lunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.03365827977140918, 'interquartile_range': 0.15583008785031374, 'maximum': 0.37251074770739345, 'mean': 0.12263371690035856, 'measured_model_count': 56, 'median': 0.11157894179367531, 'minimum': -0.1922015107403494, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.18948836762172291, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0033575428305555734, 'interquartile_range': 0.009723968496991963, 'maximum': 0.07590534725685125, 'mean': 0.011504028916612676, 'measured_model_count': 56, 'median': 0.006899426529077324, 'minimum': 0.00046431606993314206, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.013081511327547536, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 11.11111111111111}2992990blocked_insufficient_evidencerequired
CLTCunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.7857849350335733, 'interquartile_range': 0.4306299282056192, 'maximum': -0.2347483018845844, 'mean': -1.549072628527409, 'measured_model_count': 56, 'median': -1.5407053756609363, 'minimum': -2.506829210747692, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.355155006827954, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9948774232974522, 'interquartile_range': 0.0051225767025477875, 'maximum': 1.0, 'mean': 0.9698856164023175, 'measured_model_count': 56, 'median': 0.999767927569396, 'minimum': 0.16076082935524, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 1.0, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.9821428571428571, 'numerator': 55, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.9464285714285714, 'numerator': 53, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}2312310blocked_insufficient_evidencerequired
CNOT3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.8102802206023003, 'interquartile_range': 0.4759133947241436, 'maximum': -0.8320933333393696, 'mean': -1.6171401145919593, 'measured_model_count': 56, 'median': -1.5936584691809363, 'minimum': -2.6290172946051253, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.3343668258781567, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9957864519235283, 'interquartile_range': 0.004213548076471674, 'maximum': 1.0, 'mean': 0.9930468015225653, 'measured_model_count': 56, 'median': 0.9998302256586487, 'minimum': 0.8246629510819868, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 1.0, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}1701700blocked_insufficient_evidencerequired
CNOT9unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.6980036127159327, 'interquartile_range': 0.4192275870718812, 'maximum': 0.0003976307814048674, 'mean': -0.49817548218173485, 'measured_model_count': 56, 'median': -0.4553898880376292, 'minimum': -1.1718258935647998, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.2787760256440515, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.19957058817837095, 'interquartile_range': 0.6479136217544184, 'maximum': 0.9908538830614388, 'mean': 0.5144858160287195, 'measured_model_count': 56, 'median': 0.5364384999804481, 'minimum': 0.021283857638038285, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.8474842099327893, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.5178571428571429, 'numerator': 29, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.30357142857142855, 'numerator': 17, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}2842840blocked_insufficient_evidencerequired
CREB1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.20042128709993842, 'interquartile_range': 0.20137238184885764, 'maximum': 0.14087319726168263, 'mean': -0.10908124010337102, 'measured_model_count': 56, 'median': -0.0970478339479603, 'minimum': -0.6695722044017831, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0009510947489192074, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01905577727158126, 'interquartile_range': 0.09002192959362232, 'maximum': 0.7720182537652055, 'mean': 0.09194841684548548, 'measured_model_count': 56, 'median': 0.04475869080138886, 'minimum': 0.004161614464259778, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10907770686520359, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 37.03703703703704}1951950blocked_insufficient_evidencerequired
CREBBPunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.12137022065317296, 'interquartile_range': 0.35378815047690215, 'maximum': 0.7647019650205802, 'mean': 0.07497423361604329, 'measured_model_count': 56, 'median': 0.12434295478017252, 'minimum': -0.6954204183084232, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.23241792982372922, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0021103076008664352, 'interquartile_range': 0.04964725377051653, 'maximum': 0.8631610740408037, 'mean': 0.06300891143216202, 'measured_model_count': 56, 'median': 0.006852358906610696, 'minimum': 2.812680241471588e-07, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05175756137138296, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 25.925925925925927}1651650blocked_insufficient_evidencerequired
CRLF2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availableinsufficient_measured_context_models562098{'available': True, 'first_quartile': 0.05632700021176619, 'interquartile_range': 0.08015585556302292, 'maximum': 0.17530677089212182, 'mean': 0.08935700887110595, 'measured_model_count': 4, 'median': 0.10345284711544935, 'minimum': -0.024784429638596728, 'missing_fraction': 0.9285714285714286, 'missing_model_count': 52, 'third_quartile': 0.1364828557747891, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005030190068819156, 'interquartile_range': 0.004354267600952262, 'maximum': 0.019128257672105322, 'mean': 0.008512832422354143, 'measured_model_count': 4, 'median': 0.005901815316236432, 'minimum': 0.0031194413848383844, 'missing_fraction': 0.9285714285714286, 'missing_model_count': 52, 'third_quartile': 0.009384457669771418, 'threshold_fractions': (mappingproxy({'denominator': 4, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 4, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 16, 'value': 26.666666666666668}1981980blocked_insufficient_evidencerequired
CSF1Rresearch-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.05283149907401659, 'interquartile_range': 0.13328060459387842, 'maximum': 0.1974333024511772, 'mean': 0.012647423121772904, 'measured_model_count': 56, 'median': 0.016248024381766507, 'minimum': -0.32563828230030123, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08044910551986181, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.011012411673845528, 'interquartile_range': 0.018320867883454574, 'maximum': 0.223657165679814, 'mean': 0.023988383212230846, 'measured_model_count': 56, 'median': 0.018261184417227513, 'minimum': 0.0026785033287129723, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.029333279557300102, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}not availablenot availablenot availableblocked_insufficient_evidencerequired
CSF3Runclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.001availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.171973299240679, 'interquartile_range': 0.12121511297415707, 'maximum': 0.18391648947435318, 'mean': -0.11817486019417255, 'measured_model_count': 56, 'median': -0.1036037219983435, 'minimum': -0.6312179909842395, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.050758186266521926, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.030544914905776988, 'interquartile_range': 0.05752607440635536, 'maximum': 0.6352167069178504, 'mean': 0.08797870213130601, 'measured_model_count': 56, 'median': 0.05600813177010951, 'minimum': 0.004903090995091903, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08807098931213235, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}38380blocked_insufficient_evidencerequired
CTLA4anti-PD-1 combination targetantibody / IO: 0.853; biomarker: 0.524; small molecule: 0.159availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06677599448402638, 'interquartile_range': 0.15253383708406643, 'maximum': 0.3177811729630463, 'mean': 0.003779328948540078, 'measured_model_count': 56, 'median': 0.005832932383737247, 'minimum': -0.3866083097477906, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08575784260004005, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.007825870156587311, 'interquartile_range': 0.027571901541887642, 'maximum': 0.3372485312184015, 'mean': 0.036804396485517345, 'measured_model_count': 56, 'median': 0.01842904351594934, 'minimum': 0.0011469855891770616, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03539777169847495, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 37.03703703703704}1109blocked_insufficient_evidencerequired
CTNNB1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.30307444434386505, 'interquartile_range': 0.2000363522550953, 'maximum': 0.05464336452334989, 'mean': -0.22538887888625375, 'measured_model_count': 56, 'median': -0.20773415732109757, 'minimum': -0.7761741014319005, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.10303809208876974, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.04604754552361335, 'interquartile_range': 0.21650665079839038, 'maximum': 0.8885074947332431, 'mean': 0.192631362342245, 'measured_model_count': 56, 'median': 0.13451455384394487, 'minimum': 0.010324586920754095, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2625541963220037, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.07142857142857142, 'numerator': 4, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}2432430blocked_insufficient_evidencerequired
CUX1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.03317565768701193, 'interquartile_range': 0.2361234109929508, 'maximum': 0.34979611804200594, 'mean': 0.05857234852190869, 'measured_model_count': 56, 'median': 0.04287214215173468, 'minimum': -0.31298842224761375, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2029477533059389, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.003610855440009605, 'interquartile_range': 0.02993966487182269, 'maximum': 0.30936718298453664, 'mean': 0.03780538778138749, 'measured_model_count': 56, 'median': 0.010248060779731664, 'minimum': 0.00015854270563116197, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.033550520311832296, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}64640blocked_insufficient_evidencerequired
CXCL12research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.07577724494448412, 'interquartile_range': 0.190110507410803, 'maximum': 0.34935751396725395, 'mean': 0.017638110056187435, 'measured_model_count': 56, 'median': -0.022205827285089998, 'minimum': -0.3095502799648677, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11433326246631886, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.006556502005797096, 'interquartile_range': 0.03252096833817649, 'maximum': 0.21923669386606784, 'mean': 0.03273003379914769, 'measured_model_count': 56, 'median': 0.020696994642275326, 'minimum': 0.00042313838806690856, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03907747034397359, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}not availablenot availablenot availableblocked_insufficient_evidencerequired
CXCL9research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.03134505628584463, 'interquartile_range': 0.14056117568087112, 'maximum': 0.24029992912418896, 'mean': 0.04110868821178555, 'measured_model_count': 56, 'median': 0.05281410370015513, 'minimum': -0.21141841880282625, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10921611939502648, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.00658768123852596, 'interquartile_range': 0.022355271394094645, 'maximum': 0.10831268763368852, 'mean': 0.0204631377324164, 'measured_model_count': 56, 'median': 0.012647935195006565, 'minimum': 0.001717118643636866, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.028942952632620606, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}not availablenot availablenot availableblocked_insufficient_evidencerequired
CXCR4research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.0002591435523185224, 'interquartile_range': 0.10501169832073538, 'maximum': 0.3673246231079541, 'mean': 0.05559721646707475, 'measured_model_count': 56, 'median': 0.05891644317724552, 'minimum': -0.20885269756363484, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10527084187305391, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.006540828823287489, 'interquartile_range': 0.015723870922962044, 'maximum': 0.08216220534230984, 'mean': 0.016496695055018395, 'measured_model_count': 56, 'median': 0.012532064623048806, 'minimum': 0.0009317497895514716, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.022264699746249533, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}not availablenot availablenot availableblocked_insufficient_evidencerequired
CYLDunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.16691152028267855, 'interquartile_range': 0.19889307085090385, 'maximum': 0.4122109349705019, 'mean': -0.06497487104668735, 'measured_model_count': 56, 'median': -0.08653479539938982, 'minimum': -0.4925174203145259, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03198155056822531, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.016821912273541333, 'interquartile_range': 0.07211093367154234, 'maximum': 0.5035553746667468, 'mean': 0.07855783986616326, 'measured_model_count': 56, 'median': 0.04655640165652187, 'minimum': 0.0004562974591991458, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08893284594508367, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}1051050blocked_insufficient_evidencerequired
CYP1B1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.03368777508498383, 'interquartile_range': 0.13687684126148855, 'maximum': 0.47048455575590914, 'mean': 0.08384933870127811, 'measured_model_count': 56, 'median': 0.09166972667834505, 'minimum': -0.37744433712582043, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.17056461634647238, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0037660000533670107, 'interquartile_range': 0.01510846197304637, 'maximum': 0.2633327191464861, 'mean': 0.022453628011962906, 'measured_model_count': 56, 'median': 0.008242491577905423, 'minimum': 0.00022499114610257485, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.01887446202641338, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}1311310blocked_insufficient_evidencerequired
DAXXunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.544977811841365, 'interquartile_range': 0.26742254574989294, 'maximum': 0.106113115533227, 'mean': -0.4087807091327999, 'measured_model_count': 56, 'median': -0.383732915488141, 'minimum': -1.3662485543529452, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.277555266091472, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.21600580895105526, 'interquartile_range': 0.40819467544094223, 'maximum': 0.9983879181677233, 'mean': 0.42374344131493585, 'measured_model_count': 56, 'median': 0.4007934163278375, 'minimum': 0.006374091952721311, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.6242004843919975, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.42857142857142855, 'numerator': 24, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.10714285714285714, 'numerator': 6, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 70.37037037037037}1591590blocked_insufficient_evidencerequired
DDR2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06972286446924252, 'interquartile_range': 0.1045132250182792, 'maximum': 0.2898346836075851, 'mean': -0.014019195812266821, 'measured_model_count': 56, 'median': -0.020729125875991173, 'minimum': -0.23140278730236627, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.034790360549036684, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.014961917782642614, 'interquartile_range': 0.02193127226654084, 'maximum': 0.19539254739293155, 'mean': 0.03367981023215328, 'measured_model_count': 56, 'median': 0.022905507258844444, 'minimum': 0.0015916488853983351, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.036893190049183455, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}1211210blocked_insufficient_evidencerequired
DDX3Xunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.9698286536882877, 'interquartile_range': 0.7569406323261909, 'maximum': 0.3339853718118322, 'mean': -0.6088234854143035, 'measured_model_count': 56, 'median': -0.6607130262900589, 'minimum': -2.0147135010407675, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.21288802136209684, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.14926781403958722, 'interquartile_range': 0.8089440313140834, 'maximum': 1.0, 'mean': 0.6154656913017502, 'measured_model_count': 56, 'median': 0.7872151954624422, 'minimum': 0.001289807589254826, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9582118453536707, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.6785714285714286, 'numerator': 38, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.5, 'numerator': 28, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 18.51851851851852}42420blocked_insufficient_evidencerequired
DICER1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.7994467283841284, 'interquartile_range': 0.30023678430572287, 'maximum': 0.13013407460107784, 'mean': -0.6305602766259601, 'measured_model_count': 56, 'median': -0.6573228251847951, 'minimum': -1.2712552972640037, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.4992099440784056, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.5721275138636308, 'interquartile_range': 0.35380378565895265, 'maximum': 0.9952544360565102, 'mean': 0.6998550174732641, 'measured_model_count': 56, 'median': 0.8229355663334141, 'minimum': 0.006706062225289876, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9259312995225835, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.7678571428571429, 'numerator': 43, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.5178571428571429, 'numerator': 29, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}57570blocked_insufficient_evidencerequired
DNMT3Aunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.1244767471160199, 'interquartile_range': 0.11774663236443546, 'maximum': 0.6310082394813034, 'mean': 0.18192937029876807, 'measured_model_count': 56, 'median': 0.18235534714872575, 'minimum': -0.18603726549592337, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.24222337948045536, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0018838619254996766, 'interquartile_range': 0.005556895059722717, 'maximum': 0.08869695724474873, 'mean': 0.007644426594225991, 'measured_model_count': 56, 'median': 0.0035343347073587836, 'minimum': 1.1862181692386457e-05, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.007440756985222394, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}1001000blocked_insufficient_evidencerequired
EGFRunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.17742898304365823, 'interquartile_range': 0.2395414323145233, 'maximum': 0.2660120139862773, 'mean': -0.0768374949690435, 'measured_model_count': 56, 'median': -0.08543314878433285, 'minimum': -0.46622495115702955, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06211244927086508, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.013536831847736476, 'interquartile_range': 0.07782264300434415, 'maximum': 0.5606370090600415, 'mean': 0.08069588416595065, 'measured_model_count': 56, 'median': 0.05061839110667351, 'minimum': 0.0011475887843435738, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09135947485208062, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}1971970blocked_insufficient_evidencerequired
ENTPD1research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.017204446642615827, 'interquartile_range': 0.10523556299931044, 'maximum': 0.32256544354857597, 'mean': 0.03613007161465716, 'measured_model_count': 56, 'median': 0.03958058875364162, 'minimum': -0.17214377639477035, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08803111635669461, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008971876754590337, 'interquartile_range': 0.015497793480308062, 'maximum': 0.08656995332646747, 'mean': 0.020822634312535802, 'measured_model_count': 56, 'median': 0.014386164975697509, 'minimum': 0.0010515004995813155, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.024469670234898398, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}not availablenot availablenot availableblocked_insufficient_evidencerequired
EP300unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.6301650470635833, 'interquartile_range': 0.4709206521961253, 'maximum': 0.44756105949178754, 'mean': -0.3907983166708622, 'measured_model_count': 56, 'median': -0.3520231118620166, 'minimum': -1.34610578400845, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.15924439486745806, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0690136792815241, 'interquartile_range': 0.6549061339214883, 'maximum': 0.994735297730019, 'mean': 0.4060882923478336, 'measured_model_count': 56, 'median': 0.30719246495550195, 'minimum': 0.00014797171299792128, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.7239198132030125, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.375, 'numerator': 21, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.23214285714285715, 'numerator': 13, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}66660blocked_insufficient_evidencerequired
ERBB2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.33467527164131333, 'interquartile_range': 0.14828615220047953, 'maximum': 0.04056593393173724, 'mean': -0.26561967130517056, 'measured_model_count': 56, 'median': -0.246206895071223, 'minimum': -0.5119897770568183, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.1863891194408338, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.10583038909718276, 'interquartile_range': 0.14106667753996144, 'maximum': 0.669070278252544, 'mean': 0.21661886597937663, 'measured_model_count': 56, 'median': 0.1734088090428273, 'minimum': 0.011341833442620627, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2468970666371442, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.10714285714285714, 'numerator': 6, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}71710blocked_insufficient_evidencerequired
ERBB3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.29677275810467674, 'interquartile_range': 0.15902387121322126, 'maximum': 0.10539895655935005, 'mean': -0.2172892726108315, 'measured_model_count': 56, 'median': -0.2064135944999752, 'minimum': -0.5667130081211204, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.13774888689145548, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0701533166345286, 'interquartile_range': 0.14491007038238968, 'maximum': 0.6026137920472711, 'mean': 0.16367057810715754, 'measured_model_count': 56, 'median': 0.13126533178718724, 'minimum': 0.01069996622191269, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2150633870169183, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.07142857142857142, 'numerator': 4, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 85.18518518518519}91910blocked_insufficient_evidencerequired
ERBB4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.14569118463855116, 'interquartile_range': 0.14276472370214452, 'maximum': 0.22026504101142866, 'mean': -0.0806414136689627, 'measured_model_count': 56, 'median': -0.08133237680604319, 'minimum': -0.5111124546060511, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.002926460936406628, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.022843399052722917, 'interquartile_range': 0.053439931630912645, 'maximum': 0.4447439005088343, 'mean': 0.06866226929506587, 'measured_model_count': 56, 'median': 0.04663575266879736, 'minimum': 0.0026245223564960677, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07628333068363556, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}47470blocked_insufficient_evidencerequired
ERCC2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.0497755608773027, 'interquartile_range': 0.3813255384814084, 'maximum': -0.16396640750377933, 'mean': -0.8559048256834219, 'measured_model_count': 56, 'median': -0.8344001265829372, 'minimum': -1.6026495241794065, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.6684500223958943, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.7685887429345672, 'interquartile_range': 0.21456944658217048, 'maximum': 0.9999142385164158, 'mean': 0.8514767156342421, 'measured_model_count': 56, 'median': 0.9417257675715691, 'minimum': 0.12430696530259147, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9831581895167377, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.9285714285714286, 'numerator': 52, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.7321428571428571, 'numerator': 41, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 3.7037037037037037}1071070blocked_insufficient_evidencerequired
ERCC3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.1181967186257906, 'interquartile_range': 0.21936811054409455, 'maximum': -0.1968165974284698, 'mean': -0.9861971850757215, 'measured_model_count': 56, 'median': -1.0257305946001085, 'minimum': -1.2003431761784857, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.8988286080816961, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9546022888982366, 'interquartile_range': 0.035122029420819545, 'maximum': 0.9976916871199579, 'mean': 0.9395766573450544, 'measured_model_count': 56, 'median': 0.9767427569343496, 'minimum': 0.15568980756884207, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9897243183190562, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.9821428571428571, 'numerator': 55, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.9642857142857143, 'numerator': 54, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}1571570blocked_insufficient_evidencerequired
ERCC4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.3854903365144424, 'interquartile_range': 0.21652135195847766, 'maximum': 0.001120471494265196, 'mean': -0.2899236303985298, 'measured_model_count': 56, 'median': -0.312962794264828, 'minimum': -0.5607238476333932, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.16896898455596476, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.09450249828397053, 'interquartile_range': 0.2539646020376588, 'maximum': 0.6497895426015371, 'mean': 0.2577241034021173, 'measured_model_count': 56, 'median': 0.25032416264247376, 'minimum': 0.020314845019689234, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.3484671003216293, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.16071428571428573, 'numerator': 9, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}1751750blocked_insufficient_evidencerequired
ERCC5unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.04519528389004527, 'interquartile_range': 0.11019899927943605, 'maximum': 0.2710955571001969, 'mean': 0.005332502631850874, 'measured_model_count': 56, 'median': 0.02281300196535606, 'minimum': -0.23518481053140836, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06500371538939079, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008780224985984577, 'interquartile_range': 0.031486563305523046, 'maximum': 0.10076459232175562, 'mean': 0.02723915059114595, 'measured_model_count': 56, 'median': 0.016749164858456053, 'minimum': 0.001704687039870745, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04026678829150762, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}1741740blocked_insufficient_evidencerequired
ESR1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.0848593775445727, 'interquartile_range': 0.13395979595344146, 'maximum': 0.23922527191565976, 'mean': -0.0185218839167705, 'measured_model_count': 56, 'median': -0.00802662620138481, 'minimum': -0.3259164362790145, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.049100418408868744, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.012130319443407039, 'interquartile_range': 0.026440137649247547, 'maximum': 0.2259091707228821, 'mean': 0.035293228110319055, 'measured_model_count': 56, 'median': 0.02133572171212511, 'minimum': 0.0024119361921403825, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03857045709265459, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 25.925925925925927}67670blocked_insufficient_evidencerequired
EZH2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.05304773802010125, 'interquartile_range': 0.19476652921775417, 'maximum': 0.4109850863433474, 'mean': 0.0257700942153801, 'measured_model_count': 56, 'median': 0.0320485927146671, 'minimum': -0.41701781626943923, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.14171879119765293, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005567747692544567, 'interquartile_range': 0.02796596898671179, 'maximum': 0.38625828574385734, 'mean': 0.04412555204592233, 'measured_model_count': 56, 'median': 0.01521772005739586, 'minimum': 0.000795920235174292, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03353371667925636, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}1851850blocked_insufficient_evidencerequired
FANCAunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.39440710682115865, 'interquartile_range': 0.2515883236857389, 'maximum': 0.12296597316977459, 'mean': -0.27177681109686624, 'measured_model_count': 56, 'median': -0.2676352166799574, 'minimum': -0.8702254040849512, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.14281878313541974, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.06949355765826927, 'interquartile_range': 0.39275603779407636, 'maximum': 0.9139864368396176, 'mean': 0.2615344748466097, 'measured_model_count': 56, 'median': 0.18706360909548436, 'minimum': 0.00882008373465794, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.4622495954523456, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.21428571428571427, 'numerator': 12, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}1321320blocked_insufficient_evidencerequired
FANCD2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.34113845335061077, 'interquartile_range': 0.21209073145092927, 'maximum': 0.30763589641378847, 'mean': -0.2358248940686561, 'measured_model_count': 56, 'median': -0.24333725518628152, 'minimum': -0.639276633988662, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.1290477218996815, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.06847084215026893, 'interquartile_range': 0.23966001971981649, 'maximum': 0.734910238754248, 'mean': 0.21108429639298154, 'measured_model_count': 56, 'median': 0.16569585838507817, 'minimum': 0.0015781144865433508, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.3081308618700854, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.08928571428571429, 'numerator': 5, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}1581580blocked_insufficient_evidencerequired
FANCEunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.30468282446630407, 'interquartile_range': 0.23709348450999423, 'maximum': 0.1449555156044862, 'mean': -0.19703014558258644, 'measured_model_count': 56, 'median': -0.19399076273649424, 'minimum': -0.6634268715160248, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.06758933995630984, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.05160543946265888, 'interquartile_range': 0.20409383149367327, 'maximum': 0.8359188291300516, 'mean': 0.17355839520632504, 'measured_model_count': 56, 'median': 0.12078053526514522, 'minimum': 0.0063814556847987345, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.25569927095633216, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}2602600blocked_insufficient_evidencerequired
FANCFunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.41615021274621306, 'interquartile_range': 0.22066287913849758, 'maximum': 0.018453039839361474, 'mean': -0.32504242532536193, 'measured_model_count': 56, 'median': -0.31555455536594124, 'minimum': -0.9314961101442203, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.19548733360771547, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.11743406537297933, 'interquartile_range': 0.35662513437807863, 'maximum': 0.9457808378607613, 'mean': 0.3108121278616506, 'measured_model_count': 56, 'median': 0.24263160040327705, 'minimum': 0.01631160733986358, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.474059199751058, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.23214285714285715, 'numerator': 13, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 70.37037037037037}2392390blocked_insufficient_evidencerequired
FASunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.16162206893853046, 'interquartile_range': 0.13172923906542297, 'maximum': 0.18036452107576528, 'mean': -0.08960286791582976, 'measured_model_count': 56, 'median': -0.11478192715046522, 'minimum': -0.31079330755796136, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.029892829873107492, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.026861749551291544, 'interquartile_range': 0.06845940434177648, 'maximum': 0.2343847619311021, 'mean': 0.06411442895668948, 'measured_model_count': 56, 'median': 0.05203040919741203, 'minimum': 0.0031442763076645645, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09532115389306803, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 37.03703703703704}2162160blocked_insufficient_evidencerequired
FAT1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.010190119994076867, 'interquartile_range': 0.1327527813060256, 'maximum': 0.3239877898348623, 'mean': 0.05787560641765308, 'measured_model_count': 56, 'median': 0.04713508116369999, 'minimum': -0.1477656314088705, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.12256266131194873, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.006042510039561404, 'interquartile_range': 0.01801475636113281, 'maximum': 0.12678724791693652, 'mean': 0.019558783916784724, 'measured_model_count': 56, 'median': 0.013016969463129585, 'minimum': 0.0013710596238751416, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.024057266400694215, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 66.66666666666667}56560blocked_insufficient_evidencerequired
FAT4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.08010063621579745, 'interquartile_range': 0.13017968110048778, 'maximum': 0.21669532988519838, 'mean': -0.025541252959918388, 'measured_model_count': 56, 'median': -0.023054746641925847, 'minimum': -0.47842898548034124, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.050079044884690324, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01326244371222652, 'interquartile_range': 0.033213141154614684, 'maximum': 0.3959491092740444, 'mean': 0.039079867410627044, 'measured_model_count': 56, 'median': 0.026496833584941027, 'minimum': 0.0022160403622951044, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0464755848668412, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 37.03703703703704}73730blocked_insufficient_evidencerequired
FBXO11unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.15074818038210167, 'interquartile_range': 0.281308577050804, 'maximum': 0.42220203584434846, 'mean': -0.04560795363310931, 'measured_model_count': 56, 'median': -0.03427403620395675, 'minimum': -0.6741261622322151, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1305603966687023, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.007285169440329596, 'interquartile_range': 0.09745011838978633, 'maximum': 0.7905134474847286, 'mean': 0.10611223844677944, 'measured_model_count': 56, 'median': 0.029319765084054497, 'minimum': 0.0004413568234268305, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10473528783011593, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.08928571428571429, 'numerator': 5, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 11.11111111111111}2132130blocked_insufficient_evidencerequired
FBXW7unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.10168761872706197, 'interquartile_range': 0.31951626522136356, 'maximum': 0.7477705375903348, 'mean': 0.07512290288357788, 'measured_model_count': 56, 'median': 0.08885012160126604, 'minimum': -0.42999840215935103, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.21782864649430156, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0023602908105894663, 'interquartile_range': 0.04698617022723407, 'maximum': 0.3990660245341544, 'mean': 0.048686281727830724, 'measured_model_count': 56, 'median': 0.00790827217292547, 'minimum': 7.339235394045013e-07, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04934646103782354, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}2962960blocked_insufficient_evidencerequired
FCRL4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.182975187793387, 'interquartile_range': 0.13243973999157846, 'maximum': 0.14030049532262745, 'mean': -0.11330662488132592, 'measured_model_count': 56, 'median': -0.10620558769013834, 'minimum': -0.451675523595505, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.05053544780180854, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.03271037791063712, 'interquartile_range': 0.057892317786895325, 'maximum': 0.4302335386003559, 'mean': 0.07745410574824914, 'measured_model_count': 56, 'median': 0.05680147102116183, 'minimum': 0.003675204351939972, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09060269569753245, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}1681680blocked_insufficient_evidencerequired
FGFR1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.10585312617805011, 'interquartile_range': 0.1474329702619552, 'maximum': 0.24676378195924795, 'mean': -0.04075960883877906, 'measured_model_count': 56, 'median': -0.04514236242722311, 'minimum': -0.45737015923785884, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04157984408390509, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.013136544667759788, 'interquartile_range': 0.042445470736148155, 'maximum': 0.5845513123281094, 'mean': 0.05509342663926976, 'measured_model_count': 56, 'median': 0.030469376280351304, 'minimum': 0.0018396455361303317, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05558201540390795, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 29.62962962962963}84840blocked_insufficient_evidencerequired
FGFR2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.12929769810455707, 'interquartile_range': 0.12395274435376992, 'maximum': 0.275230036665003, 'mean': -0.05821593340182014, 'measured_model_count': 56, 'median': -0.05163254238200452, 'minimum': -0.5200819479761457, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.005344953750787151, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.022649497580184946, 'interquartile_range': 0.038355964705018376, 'maximum': 0.7009253574543882, 'mean': 0.05743963083468188, 'measured_model_count': 56, 'median': 0.03537906820870254, 'minimum': 0.0017046287467954388, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06100546228520332, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}76760blocked_insufficient_evidencerequired
FGFR3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.05194312301230575, 'interquartile_range': 0.17413908661637087, 'maximum': 0.3363122041950665, 'mean': 0.03525864250811891, 'measured_model_count': 56, 'median': 0.04922997969645476, 'minimum': -0.46980050826203773, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.12219596360406512, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005922891813622169, 'interquartile_range': 0.023690854120683086, 'maximum': 0.37901610456587304, 'mean': 0.036640727013179324, 'measured_model_count': 56, 'median': 0.015458308668818171, 'minimum': 0.0005398320917780566, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.029613745934305255, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}2472470blocked_insufficient_evidencerequired
FGFR4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.04827777998776034, 'interquartile_range': 0.1004719025100316, 'maximum': 0.2993306227887731, 'mean': 0.0031693776232304136, 'measured_model_count': 56, 'median': -0.0050449308179600395, 'minimum': -0.19963413413040304, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05219412252227127, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.010744829149114411, 'interquartile_range': 0.023094813491983453, 'maximum': 0.10374246297872541, 'mean': 0.02619568029732398, 'measured_model_count': 56, 'median': 0.01975265020738414, 'minimum': 0.0007450975600135493, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.033839642641097865, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}78780blocked_insufficient_evidencerequired
FHunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.48235854532561034, 'interquartile_range': 0.30092341372102055, 'maximum': 0.21734868313383282, 'mean': -0.3452825522263905, 'measured_model_count': 56, 'median': -0.3487538509937572, 'minimum': -1.1620329173001207, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.1814351316045898, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.11598339367742898, 'interquartile_range': 0.4138461833340011, 'maximum': 0.9842926507309879, 'mean': 0.3562568102014801, 'measured_model_count': 56, 'median': 0.293119690869387, 'minimum': 0.002688067009743821, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.5298295770114301, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.2857142857142857, 'numerator': 16, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.10714285714285714, 'numerator': 6, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 85.18518518518519}2482480blocked_insufficient_evidencerequired
FLGunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.014090010880866456, 'interquartile_range': 0.12299878821956789, 'maximum': 0.40211935160462337, 'mean': 0.05468800059532417, 'measured_model_count': 56, 'median': 0.053553678456244605, 'minimum': -0.18698379576091817, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10890877733870144, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.007642926736823383, 'interquartile_range': 0.017284387507036578, 'maximum': 0.0830094575624924, 'mean': 0.019436951498532508, 'measured_model_count': 56, 'median': 0.012053492803449247, 'minimum': 0.0003584647512974246, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.024927314243859963, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 66.66666666666667}1711710blocked_insufficient_evidencerequired
FLT3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.22595354553005761, 'interquartile_range': 0.14998026773463285, 'maximum': 0.154995004034906, 'mean': -0.14385366187633805, 'measured_model_count': 56, 'median': -0.13862055477951635, 'minimum': -0.48307639187962104, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.07597327779542476, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.04545758737215939, 'interquartile_range': 0.09978084071418072, 'maximum': 0.5397629699994875, 'mean': 0.10755393878508068, 'measured_model_count': 56, 'median': 0.08088979303060306, 'minimum': 0.005060271666928569, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1452384280863401, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}2272270blocked_insufficient_evidencerequired
FLT4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.001availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.019570219331166372, 'interquartile_range': 0.12035885290869781, 'maximum': 0.2540552513736699, 'mean': 0.039597374010813514, 'measured_model_count': 56, 'median': 0.029329758113223747, 'minimum': -0.16137096768294212, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10078863357753144, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008675884303708739, 'interquartile_range': 0.018278780420746883, 'maximum': 0.08326337223205958, 'mean': 0.019447313633772216, 'measured_model_count': 56, 'median': 0.016517954870417618, 'minimum': 0.0012689987898533725, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.026954664724455624, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}37370blocked_insufficient_evidencerequired
FMN1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.04804373333999466, 'interquartile_range': 0.15223200943340148, 'maximum': 0.5097227332643849, 'mean': 0.11250660008204064, 'measured_model_count': 56, 'median': 0.13594679027128903, 'minimum': -0.7270702453089212, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.20027574277339613, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0025879797549131995, 'interquartile_range': 0.011864780776770868, 'maximum': 0.8049195799577559, 'mean': 0.029415923175659203, 'measured_model_count': 56, 'median': 0.005465761799348213, 'minimum': 0.00019623882159085373, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.014452760531684069, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 11.11111111111111}2662660blocked_insufficient_evidencerequired
FOXP1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.08925622719291582, 'interquartile_range': 0.15725199103704537, 'maximum': 0.3896693910511839, 'mean': -0.012717309353639877, 'measured_model_count': 56, 'median': 0.006684601879123767, 'minimum': -0.48806446905551293, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06799576384412956, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.009684733628868597, 'interquartile_range': 0.03702886243106225, 'maximum': 0.45881000128768495, 'mean': 0.05421199659843505, 'measured_model_count': 56, 'median': 0.018906366489225244, 'minimum': 0.0005847063168429513, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04671359605993085, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}43430blocked_insufficient_evidencerequired
FOXP3research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.015325840605122043, 'interquartile_range': 0.09965029971967573, 'maximum': 0.2660450679919454, 'mean': 0.06567559829110299, 'measured_model_count': 56, 'median': 0.06163214472920807, 'minimum': -0.23676786606528333, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11497614032479778, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.006236233508914037, 'interquartile_range': 0.00910131640870038, 'maximum': 0.13569945974455236, 'mean': 0.016217094032263086, 'measured_model_count': 56, 'median': 0.01160893644614088, 'minimum': 0.0011550462651738536, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.015337549917614417, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 66.66666666666667}not availablenot availablenot availableblocked_insufficient_evidencerequired
FUBP1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.2881247391090692, 'interquartile_range': 0.16340607882358316, 'maximum': 0.1842388495263189, 'mean': -0.20610670889766866, 'measured_model_count': 56, 'median': -0.19477172807427562, 'minimum': -0.6381129392361081, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.12471866028548606, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.06338988632503986, 'interquartile_range': 0.16076528927297246, 'maximum': 0.7540646184472742, 'mean': 0.1760565738449998, 'measured_model_count': 56, 'median': 0.10461075385553599, 'minimum': 0.0027667622892301744, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.22415517559801232, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}2642640blocked_insufficient_evidencerequired
GATA2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.007575429545667133, 'interquartile_range': 0.12492924525133178, 'maximum': 0.38970793669976095, 'mean': 0.0577966749928754, 'measured_model_count': 56, 'median': 0.05691850044409493, 'minimum': -0.29724211223823427, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11735381570566465, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005785166202300651, 'interquartile_range': 0.01713490940782536, 'maximum': 0.3018103137464197, 'mean': 0.022289382974630133, 'measured_model_count': 56, 'median': 0.012027009295317814, 'minimum': 0.0007343235547851637, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02292007561012601, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}2682680blocked_insufficient_evidencerequired
GNA11unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.012availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.24420661980895522, 'interquartile_range': 0.15532874743496847, 'maximum': 0.03808760466256192, 'mean': -0.1684084279156771, 'measured_model_count': 56, 'median': -0.1566551127202881, 'minimum': -0.45115937023528413, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.08887787237398675, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.03757946210475693, 'interquartile_range': 0.11724926833434487, 'maximum': 0.5638151018002555, 'mean': 0.11858227556158243, 'measured_model_count': 56, 'median': 0.09407439748766974, 'minimum': 0.010923528122944231, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1548287304391018, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}2423-1blocked_insufficient_evidencerequired
GNAQunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.015availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.45136196689657815, 'interquartile_range': 0.22233080091499816, 'maximum': -0.040557723214412034, 'mean': -0.365139823702521, 'measured_model_count': 56, 'median': -0.3311970646804885, 'minimum': -1.1688313734515619, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.22903116598158, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.16462592677727933, 'interquartile_range': 0.30738138279626565, 'maximum': 0.9920765810689797, 'mean': 0.3481970522328733, 'measured_model_count': 56, 'median': 0.27679032897507927, 'minimum': 0.02048184269862659, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.472007309573545, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.23214285714285715, 'numerator': 13, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.07142857142857142, 'numerator': 4, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}1915-4blocked_insufficient_evidencerequired
GNASunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.12914624361583124, 'interquartile_range': 0.16880844265574943, 'maximum': 0.3443254273478986, 'mean': -0.04885626544081799, 'measured_model_count': 56, 'median': -0.0395043305663757, 'minimum': -0.5772557917183418, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.039662199039918196, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.011990605387231526, 'interquartile_range': 0.056437399568218624, 'maximum': 0.6486813918352867, 'mean': 0.06710232936679815, 'measured_model_count': 56, 'median': 0.032055853208135324, 'minimum': 0.0008476741953656707, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06842800495545015, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}1181180blocked_insufficient_evidencerequired
GRIN2Aunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.14411748716861636, 'interquartile_range': 0.1211869515324273, 'maximum': 0.11187573454467088, 'mean': -0.07796016160118857, 'measured_model_count': 56, 'median': -0.08077181172218598, 'minimum': -0.27600553638489433, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.02293053563618906, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.023766660725572302, 'interquartile_range': 0.05338835758759475, 'maximum': 0.24021664161407277, 'mean': 0.056171638224705486, 'measured_model_count': 56, 'median': 0.04293536851828147, 'minimum': 0.007086734633626951, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07715501831316705, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 18.51851851851852}79790blocked_insufficient_evidencerequired
GZMBresearch-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.17244025699697157, 'interquartile_range': 0.2215586500992243, 'maximum': 0.3725292682983529, 'mean': -0.043664638800793, 'measured_model_count': 56, 'median': -0.06917978710613715, 'minimum': -0.31096479898487983, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04911839310225271, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.009710803170775517, 'interquartile_range': 0.08752127492675235, 'maximum': 0.246250297339304, 'mean': 0.05926205677955833, 'measured_model_count': 56, 'median': 0.034480980287158486, 'minimum': 0.0007627617070437107, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09723207809752787, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 14.814814814814815}not availablenot availablenot availableblocked_insufficient_evidencerequired
H3-3Aunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.6291221340498359, 'interquartile_range': 0.5747953137617774, 'maximum': -0.5969404951509958, 'mean': -1.3551787569326883, 'measured_model_count': 55, 'median': -1.346906237251263, 'minimum': -2.244889055499746, 'missing_fraction': 0.017857142857142856, 'missing_model_count': 1, 'third_quartile': -1.0543268202880585, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9837331286620297, 'interquartile_range': 0.016249656069920126, 'maximum': 1.0, 'mean': 0.9764838454893447, 'measured_model_count': 55, 'median': 0.995866238899257, 'minimum': 0.6036936797196938, 'missing_fraction': 0.017857142857142856, 'missing_model_count': 1, 'third_quartile': 0.9999827847319498, 'threshold_fractions': (mappingproxy({'denominator': 55, 'fraction': 1.0, 'numerator': 55, 'threshold': 0.5}), mappingproxy({'denominator': 55, 'fraction': 0.9818181818181818, 'numerator': 54, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}2672670blocked_insufficient_evidencerequired
H3-3Bunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.48313503447175277, 'interquartile_range': 0.21974635922869223, 'maximum': -0.012604660993106698, 'mean': -0.3755518963514822, 'measured_model_count': 56, 'median': -0.33933172423069585, 'minimum': -0.830902835454018, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.26338867524306053, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.19076786329106843, 'interquartile_range': 0.3226438251221172, 'maximum': 0.9130818463893109, 'mean': 0.36860403231261063, 'measured_model_count': 56, 'median': 0.3108532559759873, 'minimum': 0.019520162834314427, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.5134116884131856, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.2857142857142857, 'numerator': 16, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.08928571428571429, 'numerator': 5, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}52520blocked_insufficient_evidencerequired
H3C2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.3206454080265252, 'interquartile_range': 0.1975554737523422, 'maximum': 0.16775661599292177, 'mean': -0.21381437868097847, 'measured_model_count': 56, 'median': -0.20958209107011988, 'minimum': -0.5450733007125406, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.123089934274183, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.07225970162530683, 'interquartile_range': 0.1622007492055575, 'maximum': 0.6438797380322532, 'mean': 0.1724341084996443, 'measured_model_count': 56, 'median': 0.13346229752303382, 'minimum': 0.003772158858215319, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2344604508308643, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 96.29629629629629}2932930blocked_insufficient_evidencerequired
HAVCR2research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.02987708632932152, 'interquartile_range': 0.10506951338618359, 'maximum': 0.30558334855827995, 'mean': 0.028231970147176263, 'measured_model_count': 56, 'median': 0.021078887581460377, 'minimum': -0.19101340457200128, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07519242705686208, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.00789883343293582, 'interquartile_range': 0.01833445389224319, 'maximum': 0.11204404808981419, 'mean': 0.023435654418921713, 'measured_model_count': 56, 'median': 0.014689188029942131, 'minimum': 0.0016295139647264294, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02623328732517901, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}not availablenot availablenot availableblocked_insufficient_evidencerequired
HGFunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.027861706906206877, 'interquartile_range': 0.14525680904923657, 'maximum': 0.4677803805613251, 'mean': 0.09965417928922386, 'measured_model_count': 56, 'median': 0.11360474924188933, 'minimum': -0.25539137465273065, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.17311851595544345, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0037531548730815527, 'interquartile_range': 0.013962672062846015, 'maximum': 0.22696926601274922, 'mean': 0.016201461765943802, 'measured_model_count': 56, 'median': 0.007790645531783854, 'minimum': 0.0002821764476149182, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.01771582693592757, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}1541540blocked_insufficient_evidencerequired
HLA-Aresearch-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.2552972965494641, 'interquartile_range': 0.15781341479361444, 'maximum': 0.08996078518352843, 'mean': -0.18008238783186595, 'measured_model_count': 56, 'median': -0.17280744614212706, 'minimum': -0.5750630715153462, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.09748388175584964, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.049497676353652244, 'interquartile_range': 0.1167644450917843, 'maximum': 0.6029775488822585, 'mean': 0.13965062801032252, 'measured_model_count': 56, 'median': 0.09981467563830992, 'minimum': 0.007059461637493488, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.16626212144543653, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}not availablenot availablenot availableblocked_insufficient_evidencerequired
HLA-Bresearch-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.15968912982781502, 'interquartile_range': 0.18480063823124976, 'maximum': 0.27007374516910987, 'mean': -0.07374631368331996, 'measured_model_count': 56, 'median': -0.07423159504405025, 'minimum': -0.485704165710984, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02511150840343474, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01395180875400719, 'interquartile_range': 0.07055243596738246, 'maximum': 0.49127695693581824, 'mean': 0.0784175275143234, 'measured_model_count': 56, 'median': 0.04113581826807637, 'minimum': 0.0013968572167001247, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08450424472138965, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 66.66666666666667}not availablenot availablenot availableblocked_insufficient_evidencerequired
HNF1Aunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.16293366063630432, 'interquartile_range': 0.19824401087906468, 'maximum': 0.1912757751751536, 'mean': -0.07256376755814067, 'measured_model_count': 56, 'median': -0.04778355491386431, 'minimum': -0.5122705302653734, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.035310350242760344, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01457113924168986, 'interquartile_range': 0.07886206050438543, 'maximum': 0.6658078682606292, 'mean': 0.07098839603343211, 'measured_model_count': 56, 'median': 0.03521909600150257, 'minimum': 0.0039146957197934325, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0934331997460753, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}1421420blocked_insufficient_evidencerequired
HRASunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.27036777326378536, 'interquartile_range': 0.18381116909250983, 'maximum': 0.12159438311188783, 'mean': -0.2120542528403669, 'measured_model_count': 56, 'median': -0.15093706759740222, 'minimum': -1.3098886826432632, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.08655660417127553, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.03936622590302448, 'interquartile_range': 0.15378447332836542, 'maximum': 0.9996455744842113, 'mean': 0.17412857012370694, 'measured_model_count': 56, 'median': 0.09876526486851311, 'minimum': 0.004326422830182301, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.19315069923138992, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.07142857142857142, 'numerator': 4, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}2832830blocked_insufficient_evidencerequired
IDH1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.15448357052904954, 'interquartile_range': 0.1485721977747924, 'maximum': 0.20896505721913816, 'mean': -0.09337330784363378, 'measured_model_count': 56, 'median': -0.07154041810566106, 'minimum': -1.0350852467755454, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.005911372754257127, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.02007757384147797, 'interquartile_range': 0.06085228289583204, 'maximum': 0.9942833245620363, 'mean': 0.08093502900778993, 'measured_model_count': 56, 'median': 0.03720868827740238, 'minimum': 0.0038582797922045104, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08092985673731001, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}1081080blocked_insufficient_evidencerequired
IDO1research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.012105508427349601, 'interquartile_range': 0.1220095967242903, 'maximum': 0.5660480673354267, 'mean': 0.05266969293575046, 'measured_model_count': 56, 'median': 0.05843457057831062, 'minimum': -0.28197971786765974, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1099040882969407, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005713555583787177, 'interquartile_range': 0.018801276132440366, 'maximum': 0.1884526002652624, 'mean': 0.028673556894948857, 'measured_model_count': 56, 'median': 0.012181418582402407, 'minimum': 0.0001486835036999761, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.024514831716227543, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}not availablenot availablenot availableblocked_insufficient_evidencerequired
IFNAR1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.02072702775838113, 'interquartile_range': 0.15827098898244746, 'maximum': 0.6503786890171347, 'mean': 0.12145333029466691, 'measured_model_count': 56, 'median': 0.10365599503808863, 'minimum': -0.16933916992926473, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1789980167408286, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.003956222562329722, 'interquartile_range': 0.01411125018501198, 'maximum': 0.07902273935717684, 'mean': 0.013110592051675965, 'measured_model_count': 56, 'median': 0.00683742314520901, 'minimum': 9.673493890419153e-06, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.018067472747341703, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 29.62962962962963}59590blocked_insufficient_evidencerequired
IFNAR2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.01738288137045248, 'interquartile_range': 0.12488492898376848, 'maximum': 0.5714236108108321, 'mean': 0.0503920619753953, 'measured_model_count': 56, 'median': 0.04386869337198644, 'minimum': -0.45216017373590417, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.107502047613316, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0072759297821299185, 'interquartile_range': 0.016571792690970602, 'maximum': 0.5636407199137389, 'mean': 0.02954335432879648, 'measured_model_count': 56, 'median': 0.012610739619383672, 'minimum': 4.461740631815872e-05, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02384772247310052, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}83830blocked_insufficient_evidencerequired
IFNGR1research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.03662359372573171, 'interquartile_range': 0.08240767601439589, 'maximum': 0.5871211700580072, 'mean': 0.0897245542698267, 'measured_model_count': 56, 'median': 0.08379368461486343, 'minimum': -0.1744025104314158, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1190312697401276, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005404275629848286, 'interquartile_range': 0.008713219530913212, 'maximum': 0.06268986152833818, 'mean': 0.01167419637458284, 'measured_model_count': 56, 'median': 0.008325044038448394, 'minimum': 0.000290948338437609, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.014117495160761499, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}not availablenot availablenot availableblocked_insufficient_evidencerequired
IKBKBunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.16570556644074375, 'interquartile_range': 0.21406066264224513, 'maximum': 0.277540361548298, 'mean': -0.0537285075628385, 'measured_model_count': 56, 'median': -0.035178888153201554, 'minimum': -0.4502159236126616, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04835509620150139, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.012418408279742225, 'interquartile_range': 0.07750041480523112, 'maximum': 0.3740135448755501, 'mean': 0.06264769752353014, 'measured_model_count': 56, 'median': 0.032710880080595445, 'minimum': 0.001974767741085321, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08991882308497334, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}1111110blocked_insufficient_evidencerequired
IKZF1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.027512744956176855, 'interquartile_range': 0.12572245092388826, 'maximum': 0.3196388161680785, 'mean': 0.08284123758726089, 'measured_model_count': 56, 'median': 0.08862815619119767, 'minimum': -0.24711666136165655, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.15323519588006512, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.004563234822409594, 'interquartile_range': 0.01368660044820895, 'maximum': 0.10706346655544202, 'mean': 0.016026068206720766, 'measured_model_count': 56, 'median': 0.008626052643370095, 'minimum': 0.001245724641473512, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.018249835270618544, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 3.7037037037037037}55550blocked_insufficient_evidencerequired
IKZF3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.15225471866134643, 'interquartile_range': 0.1450957650450127, 'maximum': 0.5687894421280447, 'mean': -0.07457440753634013, 'measured_model_count': 56, 'median': -0.08258590755905212, 'minimum': -0.4283817472108195, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.00715895361633373, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.020035342674531775, 'interquartile_range': 0.06675520347815952, 'maximum': 0.4832088876731502, 'mean': 0.06720851685893349, 'measured_model_count': 56, 'median': 0.047431048431888424, 'minimum': 0.00014254418116806933, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0867905461526913, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}2582580blocked_insufficient_evidencerequired
IL2RATreg-suppression marker / possible IO-combination targetantibody / IO: 0.673; biomarker: 0.628; small molecule: 0.126availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.020638816605233, 'interquartile_range': 0.10185439590666129, 'maximum': 0.2707955970772144, 'mean': 0.028608067454334866, 'measured_model_count': 56, 'median': 0.02141508360816008, 'minimum': -0.28140353524938666, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08121557930142828, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.009334879488875191, 'interquartile_range': 0.017097162374383305, 'maximum': 0.21297870352246084, 'mean': 0.0225685182916743, 'measured_model_count': 56, 'median': 0.01744431698994827, 'minimum': 0.0019616077520202666, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.026432041863258496, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}561blocked_insufficient_evidencerequired
IL2RBunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06167574734909529, 'interquartile_range': 0.11419653118966835, 'maximum': 0.4361428141068317, 'mean': -0.00577974216374198, 'measured_model_count': 56, 'median': 0.0038683297949551783, 'minimum': -0.31092525578047747, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.052520783840573064, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.011368937411090727, 'interquartile_range': 0.02233347339096224, 'maximum': 0.24466414856941635, 'mean': 0.03389348922793028, 'measured_model_count': 56, 'median': 0.020888460567987405, 'minimum': 0.0003780927747437147, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03370241080205297, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}1491490blocked_insufficient_evidencerequired
IL2RGunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.0212074848635695, 'interquartile_range': 0.1010287784388279, 'maximum': 0.2924073670526511, 'mean': 0.06727286663522855, 'measured_model_count': 56, 'median': 0.0675100811958824, 'minimum': -0.18469177564542644, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1222362633023974, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.00617458498793976, 'interquartile_range': 0.010574852516974416, 'maximum': 0.07360677819534792, 'mean': 0.014465831632885265, 'measured_model_count': 56, 'median': 0.010681045947869647, 'minimum': 0.0011765421315893725, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.016749437504914175, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}1481480blocked_insufficient_evidencerequired
IL7Runclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.007574111825057125, 'interquartile_range': 0.10459650304601474, 'maximum': 0.2951420481853716, 'mean': 0.06107047570028201, 'measured_model_count': 56, 'median': 0.06426875135630919, 'minimum': -0.2820855435259647, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11217061487107187, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005832086899811304, 'interquartile_range': 0.012917677632533172, 'maximum': 0.13158609085739606, 'mean': 0.01743959809337777, 'measured_model_count': 56, 'median': 0.010212835631815064, 'minimum': 0.0016609086285636968, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.018749764532344476, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 25.925925925925927}1161160blocked_insufficient_evidencerequired
IRF1research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.09754301210474758, 'interquartile_range': 0.12296515702841573, 'maximum': 0.26037306954494316, 'mean': -0.03541258134233933, 'measured_model_count': 56, 'median': -0.021794338384010233, 'minimum': -0.4899942974308896, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.025422144923668153, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.013848609180153479, 'interquartile_range': 0.03581323489428311, 'maximum': 0.49436318873189083, 'mean': 0.04739429910381706, 'measured_model_count': 56, 'median': 0.02736019181396147, 'minimum': 0.0011200409618568816, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04966184407443659, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 18.51851851851852}not availablenot availablenot availableblocked_insufficient_evidencerequired
IRF4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.009availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.6327296669157861, 'interquartile_range': 0.5324128216394848, 'maximum': 0.6235667057736118, 'mean': -0.39855183522522275, 'measured_model_count': 56, 'median': -0.23865970092198735, 'minimum': -1.5645985791747252, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.10031684527630133, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.047184383715357534, 'interquartile_range': 0.6857642743569041, 'maximum': 1.0, 'mean': 0.35466976185022175, 'measured_model_count': 56, 'median': 0.1569832292049153, 'minimum': 2.7037314917020238e-05, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.7329486580722616, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.32142857142857145, 'numerator': 18, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.23214285714285715, 'numerator': 13, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 85.18518518518519}30300blocked_insufficient_evidencerequired
IRS4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.18839419052946696, 'interquartile_range': 0.1798390999941063, 'maximum': 0.21201552366845364, 'mean': -0.09293988067528866, 'measured_model_count': 56, 'median': -0.07806148005826202, 'minimum': -0.38768029787152425, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.00855509053536067, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.018429753510722652, 'interquartile_range': 0.07826150665683715, 'maximum': 0.4219517244413161, 'mean': 0.0786677639842874, 'measured_model_count': 56, 'median': 0.0474389800368865, 'minimum': 0.003356154467398746, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0966912601675598, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 29.62962962962963}1931930blocked_insufficient_evidencerequired
JAK1IFN-gamma resistance mechanism / biomarkerantibody / IO: 0.214; biomarker: 0.792; small molecule: 0.114availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06904007760789696, 'interquartile_range': 0.19526888874388504, 'maximum': 0.9465240508757611, 'mean': 0.04591288417512017, 'measured_model_count': 56, 'median': 0.02114251550731768, 'minimum': -0.3753752648328587, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.12622881113598808, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.006062450283729294, 'interquartile_range': 0.034487534754270424, 'maximum': 0.4388416274607162, 'mean': 0.0392200208609982, 'measured_model_count': 56, 'median': 0.020298339745821688, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04054998503799972, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 7.407407407407407}11198blocked_insufficient_evidencerequired
JAK2IFN-gamma resistance mechanism / biomarkerantibody / IO: 0.215; biomarker: 0.793; small molecule: 0.115availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.09372960195593227, 'interquartile_range': 0.09638480604756475, 'maximum': 0.4345972003497355, 'mean': 0.14725027992853618, 'measured_model_count': 56, 'median': 0.14140384507405612, 'minimum': -0.10783153860797157, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.19011440800349702, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0034333194534452273, 'interquartile_range': 0.0042969091439646915, 'maximum': 0.044572665063286214, 'mean': 0.007047471137138419, 'measured_model_count': 56, 'median': 0.005546648360096902, 'minimum': 0.0003687940884532363, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.007730228597409919, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}108-2blocked_insufficient_evidencerequired
JUNunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.311009377716012, 'interquartile_range': 0.2506178311258941, 'maximum': 0.08716511131816934, 'mean': -0.20828664428562876, 'measured_model_count': 56, 'median': -0.17296392891862877, 'minimum': -1.2725810284274188, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.06039154659011792, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.038700745106317665, 'interquartile_range': 0.16927161157534584, 'maximum': 0.9953158990721827, 'mean': 0.1765632573037201, 'measured_model_count': 56, 'median': 0.08893106341563362, 'minimum': 0.005466014892066753, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2079723566816635, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.10714285714285714, 'numerator': 6, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}1391390blocked_insufficient_evidencerequired
KAT6Aunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.1905321316921751, 'interquartile_range': 0.18847406164423797, 'maximum': 0.2913844299720876, 'mean': -0.13017761755490873, 'measured_model_count': 56, 'median': -0.10723105858661139, 'minimum': -0.7313695948349267, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.0020580700479371113, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.02057695392620386, 'interquartile_range': 0.08524065376438715, 'maximum': 0.9207122230841256, 'mean': 0.1330831920605305, 'measured_model_count': 56, 'median': 0.0533855412738906, 'minimum': 0.003751296975372678, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10581760769059101, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.10714285714285714, 'numerator': 6, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}1401400blocked_insufficient_evidencerequired
KAT6Bunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06662516590668541, 'interquartile_range': 0.11394230237326466, 'maximum': 0.31418589019523446, 'mean': -0.001255060192413378, 'measured_model_count': 56, 'median': -0.027627318543472862, 'minimum': -0.1751527942425262, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04731713646657926, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01042254558613599, 'interquartile_range': 0.03023072724184981, 'maximum': 0.0937161810188809, 'mean': 0.02994953977997856, 'measured_model_count': 56, 'median': 0.02764718556997526, 'minimum': 0.0014934966998191056, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0406532728279858, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}2362360blocked_insufficient_evidencerequired
KDM5Aunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.22202348434208968, 'interquartile_range': 0.25163186515633823, 'maximum': 0.44193079074765096, 'mean': -0.09434882159752087, 'measured_model_count': 56, 'median': -0.08145184435535191, 'minimum': -0.8218153503794106, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.029608380814248568, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.013875800874593986, 'interquartile_range': 0.11339090599007796, 'maximum': 0.9230332160863932, 'mean': 0.12447802103958014, 'measured_model_count': 56, 'median': 0.043825408803144034, 'minimum': 0.00024619135451046454, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.12726670686467195, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}2112110blocked_insufficient_evidencerequired
KDRunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.005availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.15396703246047083, 'interquartile_range': 0.18579743831009796, 'maximum': 0.35412317858308234, 'mean': -0.05750978779259812, 'measured_model_count': 56, 'median': -0.0387256781978957, 'minimum': -0.3444614053834766, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03183040584962712, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.014005661846951734, 'interquartile_range': 0.06638249016346734, 'maximum': 0.28670345020567467, 'mean': 0.05762538223094942, 'measured_model_count': 56, 'median': 0.03446964505050472, 'minimum': 0.0010452495586403565, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08038815201041907, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 25.925925925925927}33330blocked_insufficient_evidencerequired
KEAP1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.7082108266491682, 'interquartile_range': 0.5938186833592835, 'maximum': 0.7135935781879718, 'mean': -0.4100413926682732, 'measured_model_count': 56, 'median': -0.3844446143597566, 'minimum': -1.446443035340094, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.11439214328988481, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.057768436553657446, 'interquartile_range': 0.8160912945797978, 'maximum': 0.9915583744017852, 'mean': 0.450257304808193, 'measured_model_count': 56, 'median': 0.37728663389576456, 'minimum': 4.915247993642987e-06, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.8738597311334553, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.42857142857142855, 'numerator': 24, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.2857142857142857, 'numerator': 16, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 92.5925925925926}2912910blocked_insufficient_evidencerequired
KITtumor-intrinsic driver / small-molecule targetantibody / IO: 0.000; biomarker: 0.098; small molecule: 0.679availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.15047254523839437, 'interquartile_range': 0.12483170574110164, 'maximum': 0.16694100888553057, 'mean': -0.10507054540120067, 'measured_model_count': 56, 'median': -0.11187987261054008, 'minimum': -0.3611196971836982, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.025640839497292737, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.026005203789725564, 'interquartile_range': 0.057675318964253264, 'maximum': 0.24582508541769998, 'mean': 0.06628476557606086, 'measured_model_count': 56, 'median': 0.05726951313842029, 'minimum': 0.006213462729592259, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08368052275397883, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}21210blocked_insufficient_evidencerequired
KLF4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.0866160725632556, 'interquartile_range': 0.09094159645890684, 'maximum': 0.29033441321163894, 'mean': -0.036429378374868294, 'measured_model_count': 56, 'median': -0.045825769626115405, 'minimum': -0.18846226428060717, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0043255238956512385, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01830988808607737, 'interquartile_range': 0.031197954431363674, 'maximum': 0.12728694959590328, 'mean': 0.03673849894871195, 'measured_model_count': 56, 'median': 0.02931121522718555, 'minimum': 0.0015769843027852257, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.049507842517441045, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}2452450blocked_insufficient_evidencerequired
KLF6unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.1740339281446544, 'interquartile_range': 0.287121816879088, 'maximum': 0.5582898749499964, 'mean': -0.020014061949726214, 'measured_model_count': 56, 'median': -0.05126217030720511, 'minimum': -0.5678287346983116, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11308788873443362, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.004045553451322353, 'interquartile_range': 0.08106591108477244, 'maximum': 0.8387756064664146, 'mean': 0.09494424049900542, 'measured_model_count': 56, 'median': 0.03244514830539762, 'minimum': 3.5093885241607115e-06, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08511146453609479, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 70.37037037037037}1021020blocked_insufficient_evidencerequired
KMT2Aunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.247834586721482, 'interquartile_range': 0.2053139586165061, 'maximum': 0.14388081055483293, 'mean': -0.1599635043193788, 'measured_model_count': 56, 'median': -0.13474643688042431, 'minimum': -0.7962726094629715, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.042520628104975915, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.028075360066156213, 'interquartile_range': 0.12381967132087579, 'maximum': 0.890939509576807, 'mean': 0.1369329942267416, 'measured_model_count': 56, 'median': 0.0731199024889937, 'minimum': 0.0032609376499916206, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.151895031387032, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}1041040blocked_insufficient_evidencerequired
KMT2Cunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.002613878383379797, 'interquartile_range': 0.22930347633925058, 'maximum': 0.7588941965548464, 'mean': 0.08533586436646227, 'measured_model_count': 56, 'median': 0.08688860720869607, 'minimum': -0.5393806663773176, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2266895979558708, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0032623542350772366, 'interquartile_range': 0.023637002199571364, 'maximum': 0.7548851600875993, 'mean': 0.047657468264772414, 'measured_model_count': 56, 'median': 0.00790666231691314, 'minimum': 3.015181277604221e-06, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0268993564346486, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}74740blocked_insufficient_evidencerequired
KMT2Dunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.5054747400504007, 'interquartile_range': 0.43801977053473673, 'maximum': 0.4453175128783058, 'mean': -0.27953827290798855, 'measured_model_count': 56, 'median': -0.2813972812521446, 'minimum': -0.9363498739499392, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.06745496951566396, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.036792875788036104, 'interquartile_range': 0.5038830443625247, 'maximum': 0.9507611503193685, 'mean': 0.315814143315189, 'measured_model_count': 56, 'median': 0.1829714967357441, 'minimum': 0.00023457193745018845, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.5406759201505609, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.30357142857142855, 'numerator': 17, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.16071428571428573, 'numerator': 9, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}65650blocked_insufficient_evidencerequired
KNL1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.8209858622248248, 'interquartile_range': 0.26800043369654103, 'maximum': 0.4114298366282715, 'mean': -0.6723034112825079, 'measured_model_count': 56, 'median': -0.6974565079231971, 'minimum': -1.276427559759107, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.5529854285282838, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.6264804733609197, 'interquartile_range': 0.29486977080895016, 'maximum': 0.9998985731748403, 'mean': 0.743338783315388, 'measured_model_count': 56, 'median': 0.83423638852549, 'minimum': 0.0011216508970974713, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9213502441698699, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.875, 'numerator': 49, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.5357142857142857, 'numerator': 30, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}2192190blocked_insufficient_evidencerequired
KRASunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.6390363697007047, 'interquartile_range': 0.3255914225769023, 'maximum': 0.037107045533280814, 'mean': -0.4615597662300834, 'measured_model_count': 56, 'median': -0.4270863694795695, 'minimum': -0.9671398918289789, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.31344494712380233, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.2804397654477754, 'interquartile_range': 0.4166743169804551, 'maximum': 0.9882225371239182, 'mean': 0.48315218978865904, 'measured_model_count': 56, 'median': 0.4738799422322064, 'minimum': 0.012521637812168088, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.6971140824282305, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.48214285714285715, 'numerator': 27, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.17857142857142858, 'numerator': 10, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}2732730blocked_insufficient_evidencerequired
KRT5unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.1162600050798901, 'interquartile_range': 0.16026986264477588, 'maximum': 0.3326259306248558, 'mean': -0.03271996044744329, 'measured_model_count': 56, 'median': -0.03875848753631785, 'minimum': -0.4083100273302143, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04400985756488579, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.013107390885123485, 'interquartile_range': 0.04935434074536283, 'maximum': 0.34081918050850224, 'mean': 0.05037789993099017, 'measured_model_count': 56, 'median': 0.027358384042971286, 'minimum': 0.0012650511761817924, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.062461731630486315, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}2822820blocked_insufficient_evidencerequired
LAG3anti-PD-1 combination targetantibody / IO: 0.822; biomarker: 0.493; small molecule: 0.137availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.05881633966392029, 'interquartile_range': 0.12893561937780812, 'maximum': 0.37914429966497276, 'mean': 0.003600261025976661, 'measured_model_count': 56, 'median': 0.006693995382591952, 'minimum': -0.31014322945440886, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07011927971388784, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.010007862547405266, 'interquartile_range': 0.025780908070300368, 'maximum': 0.2736649589269115, 'mean': 0.03207975191250165, 'measured_model_count': 56, 'median': 0.02026514620529634, 'minimum': 0.0006578282366709314, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.035788770617705634, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 70.37037037037037}473blocked_insufficient_evidencerequired
LATS2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.1556578421689475, 'interquartile_range': 0.346068833316306, 'maximum': 0.6812382978063686, 'mean': 0.020232855958764978, 'measured_model_count': 56, 'median': 0.02532013141759792, 'minimum': -0.5883085173462187, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1904109911473585, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.004812871870791315, 'interquartile_range': 0.07385812374473756, 'maximum': 0.5717176690234534, 'mean': 0.06581858221464584, 'measured_model_count': 56, 'median': 0.023948406020125466, 'minimum': 1.5225700296503551e-06, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07867099561552887, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}2552550blocked_insufficient_evidencerequired
LCKunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.08729246564785431, 'interquartile_range': 0.1844688496759413, 'maximum': 0.2059897868514309, 'mean': -0.009407769188333403, 'measured_model_count': 56, 'median': -0.015814512461379424, 'minimum': -0.38590429969641227, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09717638402808698, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.006810646880507027, 'interquartile_range': 0.04657577854208711, 'maximum': 0.336222749595819, 'mean': 0.04188276382137456, 'measured_model_count': 56, 'median': 0.022171372889984876, 'minimum': 0.0028324291920454408, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.053386425422594135, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}1871870blocked_insufficient_evidencerequired
LILRB1research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.01109020400994214, 'interquartile_range': 0.1398087266452999, 'maximum': 0.4433027675302377, 'mean': 0.05536551565827964, 'measured_model_count': 56, 'median': 0.051821418581015924, 'minimum': -0.2138537031730067, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.12871852263535774, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.006022954802638753, 'interquartile_range': 0.017556262760780754, 'maximum': 0.11051920534037452, 'mean': 0.01924822092948011, 'measured_model_count': 56, 'median': 0.013681127550983843, 'minimum': 0.00023616078642564348, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.023579217563419505, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}not availablenot availablenot availableblocked_insufficient_evidencerequired
LILRB2research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.17339256920794643, 'interquartile_range': 0.16212378681022704, 'maximum': 0.34645335742649364, 'mean': -0.08430449460370906, 'measured_model_count': 56, 'median': -0.10414190586983159, 'minimum': -0.46500847320709315, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.01126878239771938, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.023619920694685523, 'interquartile_range': 0.06576945252265654, 'maximum': 0.5581267752985244, 'mean': 0.0736724021976837, 'measured_model_count': 56, 'median': 0.054768936757054784, 'minimum': 0.0008249314826466763, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08938937321734206, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}not availablenot availablenot availableblocked_insufficient_evidencerequired
LPPunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.008783199593916918, 'interquartile_range': 0.10063549851005911, 'maximum': 0.39512059249409137, 'mean': 0.0501342135041537, 'measured_model_count': 56, 'median': 0.052278005196747614, 'minimum': -0.28660592592022155, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09185229891614219, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.00715624060802497, 'interquartile_range': 0.014590503911784831, 'maximum': 0.14433042014147968, 'mean': 0.01906680258772825, 'measured_model_count': 56, 'median': 0.012845188877211793, 'minimum': 0.0007890807311014471, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0217467445198098, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}2762760blocked_insufficient_evidencerequired
LRP1Bunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.002availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.20938505684404493, 'interquartile_range': 0.18767779569086548, 'maximum': 0.36877867713046136, 'mean': -0.11193670595354667, 'measured_model_count': 56, 'median': -0.1145412718983222, 'minimum': -0.6285265543650834, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.021707261153179447, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.022508152373858486, 'interquartile_range': 0.12726745259309719, 'maximum': 0.7916660592206599, 'mean': 0.11003149409753983, 'measured_model_count': 56, 'median': 0.0526553283158261, 'minimum': 0.0006828725992313448, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.14977560496695566, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 14.814814814814815}36360blocked_insufficient_evidencerequired
LZTR1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.09712302034637581, 'interquartile_range': 0.12603647569734755, 'maximum': 0.39835316383447017, 'mean': -0.023218800975575663, 'measured_model_count': 56, 'median': -0.032631692394577985, 'minimum': -0.31250394234035345, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.028913455350971732, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.013866497890610329, 'interquartile_range': 0.03558430953541362, 'maximum': 0.22804494863519476, 'mean': 0.042020283337196505, 'measured_model_count': 56, 'median': 0.027297324657613566, 'minimum': 0.0005298521133612584, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.049450807426023945, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}1631630blocked_insufficient_evidencerequired
MAP2K1tumor-intrinsic driver / small-molecule targetantibody / IO: 0.262; biomarker: 0.476; small molecule: 0.836availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.578482228308965, 'interquartile_range': 0.4189281838514242, 'maximum': 0.252437482852541, 'mean': -0.41218035078685417, 'measured_model_count': 56, 'median': -0.38895098205912615, 'minimum': -1.3657303916368035, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.1595540444575408, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.08598020716229524, 'interquartile_range': 0.5882115796602083, 'maximum': 0.9908781940957316, 'mean': 0.42114568711213035, 'measured_model_count': 56, 'median': 0.38746891216194834, 'minimum': 0.002703798825683424, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.6741917868225036, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.39285714285714285, 'numerator': 22, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.23214285714285715, 'numerator': 13, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 100.0}82-6blocked_insufficient_evidencerequired
MAP2K2tumor-intrinsic driver / small-molecule targetantibody / IO: 0.000; biomarker: 0.106; small molecule: 0.689availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.4908836918532778, 'interquartile_range': 0.3416845954926677, 'maximum': 0.22807594691589114, 'mean': -0.36394880908741206, 'measured_model_count': 56, 'median': -0.27913492073021595, 'minimum': -1.780927613358056, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.14919909636061007, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0796834206563264, 'interquartile_range': 0.440321969120281, 'maximum': 1.0, 'mean': 0.33519502622684805, 'measured_model_count': 56, 'median': 0.210854567680023, 'minimum': 0.0034850765734037578, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.5200053897766074, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.26785714285714285, 'numerator': 15, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.16071428571428573, 'numerator': 9, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 85.18518518518519}1412-2blocked_insufficient_evidencerequired
MAP2K4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.08166803344011006, 'interquartile_range': 0.1667224349937138, 'maximum': 0.4663584004709461, 'mean': -0.004183185081218783, 'measured_model_count': 56, 'median': 0.007155568370856763, 'minimum': -0.5620268298394391, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08505440155360375, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.00896391572726946, 'interquartile_range': 0.03983377128048464, 'maximum': 0.5761438915269841, 'mean': 0.04888816971268661, 'measured_model_count': 56, 'median': 0.02000527970907914, 'minimum': 0.0002583679371438126, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0487976870077541, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}2332330blocked_insufficient_evidencerequired
MAP3K1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.26818881495655444, 'interquartile_range': 0.2190929173625335, 'maximum': 0.16244834816557008, 'mean': -0.1754338142643515, 'measured_model_count': 56, 'median': -0.18106151480989618, 'minimum': -1.063112411214312, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.04909589759402095, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.032390313337493024, 'interquartile_range': 0.1698410110394501, 'maximum': 0.9781983157682375, 'mean': 0.1418094395845862, 'measured_model_count': 56, 'median': 0.08325360586789075, 'minimum': 0.0031087789768363826, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2022313243769431, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 92.5925925925926}2882880blocked_insufficient_evidencerequired
MAP3K13unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.12348850976267087, 'interquartile_range': 0.10356484439638564, 'maximum': 0.10601839484476286, 'mean': -0.07735031260314525, 'measured_model_count': 56, 'median': -0.07585580490508761, 'minimum': -0.4254039496856019, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.01992366536628524, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.02579139351817865, 'interquartile_range': 0.03948663532446196, 'maximum': 0.33166860073911614, 'mean': 0.05799902513451529, 'measured_model_count': 56, 'median': 0.04505395114891765, 'minimum': 0.004144288513430752, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06527802884264061, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}1691690blocked_insufficient_evidencerequired
MAPK1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.2761774074770886, 'interquartile_range': 0.7786423452235494, 'maximum': 0.18419597775603253, 'mean': -0.8981201774701383, 'measured_model_count': 56, 'median': -0.8129894142767058, 'minimum': -2.2162133589722837, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.4975350622535393, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.5766186743058375, 'interquartile_range': 0.41754805922924465, 'maximum': 1.0, 'mean': 0.7418741798461861, 'measured_model_count': 56, 'median': 0.8931882816760448, 'minimum': 0.0015643431120909866, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9941667335350821, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.7857142857142857, 'numerator': 44, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.625, 'numerator': 35, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 100.0}2812810blocked_insufficient_evidencerequired
MARCOresearch-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.144284681805267, 'interquartile_range': 0.11320090800341288, 'maximum': 0.16141479149421714, 'mean': -0.08075810496074594, 'measured_model_count': 56, 'median': -0.07657305576587008, 'minimum': -0.28995279711229627, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.031083773801854106, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.02732096604142211, 'interquartile_range': 0.0424585894956143, 'maximum': 0.21196471052683893, 'mean': 0.05275650105094353, 'measured_model_count': 56, 'median': 0.04508515552169046, 'minimum': 0.0043349896499730416, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06977955553703641, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}not availablenot availablenot availableblocked_insufficient_evidencerequired
MAXunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.8226826734631729, 'interquartile_range': 0.23233480918405225, 'maximum': -0.2112248166458427, 'mean': -0.710188390541159, 'measured_model_count': 56, 'median': -0.688268648265024, 'minimum': -1.2966052450452203, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.5903478642791207, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.703880450962148, 'interquartile_range': 0.24126058863373134, 'maximum': 0.9931135114720926, 'mean': 0.7818475651475402, 'measured_model_count': 56, 'median': 0.8762894271334364, 'minimum': 0.11802670198216508, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9451410395958794, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.875, 'numerator': 49, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.5714285714285714, 'numerator': 32, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}2172170blocked_insufficient_evidencerequired
MBD4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.012availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.14270727803868224, 'interquartile_range': 0.1568713207830758, 'maximum': 0.30240936692161213, 'mean': -0.06259349546269093, 'measured_model_count': 56, 'median': -0.08875452151828409, 'minimum': -0.2727347834743414, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.014164042744393559, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.019228656050633033, 'interquartile_range': 0.06297025851395877, 'maximum': 0.18687151897726442, 'mean': 0.057004038075143926, 'measured_model_count': 56, 'median': 0.04888988821268317, 'minimum': 0.00155875195791616, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0821989145645918, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 29.62962962962963}26260blocked_insufficient_evidencerequired
MC1Runclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.13574258291049882, 'interquartile_range': 0.2294889026785944, 'maximum': 0.3088799835855469, 'mean': -0.07405014885167535, 'measured_model_count': 56, 'median': -0.014394286830063385, 'minimum': -1.4266168769158605, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0937463197680956, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.00957570675501504, 'interquartile_range': 0.06469958618077154, 'maximum': 0.9986640403125104, 'mean': 0.093014007762533, 'measured_model_count': 56, 'median': 0.024505635992432086, 'minimum': 0.002172093001064544, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07427529293578658, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}54540blocked_insufficient_evidencerequired
MDM2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.8624748543617278, 'interquartile_range': 1.4254157644122152, 'maximum': -0.03383445987773337, 'mean': -1.2716776001752876, 'measured_model_count': 56, 'median': -1.3485460927811548, 'minimum': -2.9407816150438637, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.4370590899495126, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.5316184247932024, 'interquartile_range': 0.46838157520672297, 'maximum': 1.0, 'mean': 0.7845953373476593, 'measured_model_count': 56, 'median': 0.9964251033261587, 'minimum': 0.0191219625657424, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9999999999999254, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.75, 'numerator': 42, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.6785714285714286, 'numerator': 38, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}58580blocked_insufficient_evidencerequired
MDM4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.24624159527720413, 'interquartile_range': 0.23359604518110183, 'maximum': 0.33598072083948805, 'mean': -0.18865409124957538, 'measured_model_count': 56, 'median': -0.1410025896159544, 'minimum': -1.2812287480482205, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.012645550096102298, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.02356303103125949, 'interquartile_range': 0.1275705121704807, 'maximum': 0.9843563515754161, 'mean': 0.18013925683555612, 'measured_model_count': 56, 'median': 0.07119109464846649, 'minimum': 0.0011906140360111628, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1511335432017402, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.125, 'numerator': 7, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.08928571428571429, 'numerator': 5, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}88880blocked_insufficient_evidencerequired
MECOMunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.03318121755950547, 'interquartile_range': 0.14709745093791188, 'maximum': 1.1159229428618254, 'mean': 0.04519617222218534, 'measured_model_count': 56, 'median': 0.06243448810213843, 'minimum': -0.4043002287802036, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1139162333784064, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.007059075844818929, 'interquartile_range': 0.0174121661972337, 'maximum': 0.3482881257463481, 'mean': 0.03171024366566652, 'measured_model_count': 56, 'median': 0.01239713433525657, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02447124204205263, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}60600blocked_insufficient_evidencerequired
MED12unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.9311970062252455, 'interquartile_range': 0.5433939524223144, 'maximum': 0.35086847212010597, 'mean': -0.6610039514993754, 'measured_model_count': 56, 'median': -0.6930691904602218, 'minimum': -1.4658720277959536, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.3878030538029311, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.29330547725917067, 'interquartile_range': 0.6792518810382737, 'maximum': 1.0, 'mean': 0.6692263099022066, 'measured_model_count': 56, 'median': 0.8357673700031603, 'minimum': 0.0011196937346188206, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9725573582974444, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.7142857142857143, 'numerator': 40, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.5178571428571429, 'numerator': 29, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 70.37037037037037}2922920blocked_insufficient_evidencerequired
MERTKresearch-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.18881505762195927, 'interquartile_range': 0.16208785261332045, 'maximum': 0.3193293249145177, 'mean': -0.10122912464953086, 'measured_model_count': 56, 'median': -0.10690991997138019, 'minimum': -0.37059543781934634, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.02672720500863881, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.024416867332033472, 'interquartile_range': 0.08662821894971165, 'maximum': 0.2986950469092032, 'mean': 0.07873373296246423, 'measured_model_count': 56, 'median': 0.05270852886247373, 'minimum': 0.0014332677546677695, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11104508628174513, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}not availablenot availablenot availableblocked_insufficient_evidencerequired
METunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06431778498910111, 'interquartile_range': 0.12819068489351648, 'maximum': 0.19924513841976238, 'mean': 0.006650333009057209, 'measured_model_count': 56, 'median': 0.010664057636821479, 'minimum': -0.15857136172097158, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06387289990441536, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.010757477645204688, 'interquartile_range': 0.027227045398293084, 'maximum': 0.09865379877043438, 'mean': 0.026561617711299477, 'measured_model_count': 56, 'median': 0.01757639754618848, 'minimum': 0.003696797201785037, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.037984523043497774, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 14.814814814814815}48480blocked_insufficient_evidencerequired
MITFtumor-intrinsic driver / biomarkerantibody / IO: 0.000; biomarker: 0.391; small molecule: 0.521availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.746365662744372, 'interquartile_range': 0.5624178320790791, 'maximum': 0.13265320362187163, 'mean': -0.49718287424489066, 'measured_model_count': 56, 'median': -0.4283536938090401, 'minimum': -1.4237880033159953, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.18394783066529286, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.13075636050247558, 'interquartile_range': 0.7860916431961333, 'maximum': 0.99792821478558, 'mean': 0.479275745655577, 'measured_model_count': 56, 'median': 0.48643645267493163, 'minimum': 0.005004197500645994, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9168480036986089, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.44642857142857145, 'numerator': 25, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.26785714285714285, 'numerator': 15, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 96.29629629629629}1611-5blocked_insufficient_evidencerequired
MN1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.01062534893898931, 'interquartile_range': 0.20506169154087153, 'maximum': 0.4941061788942517, 'mean': 0.10398082189212046, 'measured_model_count': 56, 'median': 0.1147031423956377, 'minimum': -0.2283786381698714, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.19443634260188222, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.002738853757670439, 'interquartile_range': 0.018564266438373188, 'maximum': 0.11449885931721446, 'mean': 0.018046659942068676, 'measured_model_count': 56, 'median': 0.0071448822915313025, 'minimum': 5.345680221332841e-05, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.021303120196043628, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}2322320blocked_insufficient_evidencerequired
MRTFAunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.166195671969878, 'interquartile_range': 0.12432617290852266, 'maximum': 0.15263953285940676, 'mean': -0.11254910171388513, 'measured_model_count': 56, 'median': -0.12423974962740286, 'minimum': -0.4177381788941873, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.04186949906135534, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.027229735286835803, 'interquartile_range': 0.07873531064556291, 'maximum': 0.5253690791287967, 'mean': 0.08473052596126118, 'measured_model_count': 56, 'median': 0.05987725158027763, 'minimum': 0.0077482329268426875, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10596504593239872, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 18.51851851851852}2442440blocked_insufficient_evidencerequired
MSH2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.26003559151177824, 'interquartile_range': 0.13672139042893577, 'maximum': 0.021496894857538112, 'mean': -0.20764010596590654, 'measured_model_count': 56, 'median': -0.19916068457846808, 'minimum': -0.5451116448448519, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.12331420108284245, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.06592450097849478, 'interquartile_range': 0.13342337190007386, 'maximum': 0.5982055659846949, 'mean': 0.15553859836993347, 'measured_model_count': 56, 'median': 0.12392476588127996, 'minimum': 0.009111683646020614, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.19934787287856864, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}2092090blocked_insufficient_evidencerequired
MTAPunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.05322379422075565, 'interquartile_range': 0.13163768390226643, 'maximum': 0.35647138964450364, 'mean': 0.013438769004057596, 'measured_model_count': 56, 'median': 0.001765919917108864, 'minimum': -0.2742755175918499, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07841388968151078, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008275996775491557, 'interquartile_range': 0.027631247160987107, 'maximum': 0.16335356271029838, 'mean': 0.030024490344690378, 'measured_model_count': 56, 'median': 0.01798254575130081, 'minimum': 0.0005565877691906464, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.035907243936478664, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}2082080blocked_insufficient_evidencerequired
MTORunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.4510131041083276, 'interquartile_range': 0.4066619987330087, 'maximum': -0.49744427330148155, 'mean': -1.2670230716667266, 'measured_model_count': 56, 'median': -1.2341950136618125, 'minimum': -2.149561296556447, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.044351105375319, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9789619639208639, 'interquartile_range': 0.02043554028117034, 'maximum': 1.0, 'mean': 0.9737317482994322, 'measured_model_count': 56, 'median': 0.991899482877697, 'minimum': 0.6985320335577506, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9993975042020342, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.9821428571428571, 'numerator': 55, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}51510blocked_insufficient_evidencerequired
MUTYHunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.11748028310013764, 'interquartile_range': 0.09479599365178082, 'maximum': 0.1934608651174256, 'mean': -0.06611412498298225, 'measured_model_count': 56, 'median': -0.06371844317038643, 'minimum': -0.35421944238261915, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.022684289448356824, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.02107456457132147, 'interquartile_range': 0.04260159227968066, 'maximum': 0.2790151431662099, 'mean': 0.05206646685426908, 'measured_model_count': 56, 'median': 0.0372447418479774, 'minimum': 0.004238146635538509, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06367615685100213, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 66.66666666666667}2492490blocked_insufficient_evidencerequired
MX2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.02134365997612272, 'interquartile_range': 0.07743728420864318, 'maximum': 0.28073769634204876, 'mean': 0.059560748516648006, 'measured_model_count': 56, 'median': 0.06322339592467445, 'minimum': -0.2090932215477918, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0987809441847659, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.007638541718115839, 'interquartile_range': 0.010072703648349442, 'maximum': 0.11866301644172314, 'mean': 0.01634520388322014, 'measured_model_count': 56, 'median': 0.010155243511429223, 'minimum': 0.002370897831436602, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.017711245366465282, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}1761760blocked_insufficient_evidencerequired
MYBunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.3259231883678356, 'interquartile_range': 0.21035580309281268, 'maximum': 0.2857082762935745, 'mean': -0.2178685317305252, 'measured_model_count': 56, 'median': -0.2383668513811943, 'minimum': -0.5880233849070193, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.11556738527502294, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.05526327096966057, 'interquartile_range': 0.19608087680463585, 'maximum': 0.7574785900752413, 'mean': 0.18520779917804936, 'measured_model_count': 56, 'median': 0.1759008399302746, 'minimum': 0.001253210856482248, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2513441477742964, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 7.407407407407407}1191190blocked_insufficient_evidencerequired
MYCLunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.09896427298002167, 'interquartile_range': 0.14969798704101517, 'maximum': 0.3274052023063336, 'mean': -0.0172760396628093, 'measured_model_count': 56, 'median': -0.02694371489350945, 'minimum': -0.23412237491718474, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05073371406099349, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.014034643973738554, 'interquartile_range': 0.029981870470997513, 'maximum': 0.15381720551862854, 'mean': 0.036321603814873385, 'measured_model_count': 56, 'median': 0.02648200137173792, 'minimum': 0.001437699008765543, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04401651444473607, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}1661660blocked_insufficient_evidencerequired
MYCNunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.16216867965324833, 'interquartile_range': 0.13075761344972117, 'maximum': 0.18745096512794407, 'mean': -0.09335767882402103, 'measured_model_count': 56, 'median': -0.10231313440314074, 'minimum': -0.31346284796372825, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.031411066203527155, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.021207991240808396, 'interquartile_range': 0.07056960336598046, 'maximum': 0.31588339444654384, 'mean': 0.06842223106795756, 'measured_model_count': 56, 'median': 0.04657996803044029, 'minimum': 0.004017152964376389, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09177759460678886, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}1451450blocked_insufficient_evidencerequired
MYH9unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.43531095200717707, 'interquartile_range': 0.4321296864755354, 'maximum': 0.5003544202391196, 'mean': -0.2775936121216364, 'measured_model_count': 56, 'median': -0.16774301545077763, 'minimum': -1.6066004375290057, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.0031812655316416916, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.019496240001612868, 'interquartile_range': 0.39325137250511455, 'maximum': 1.0, 'mean': 0.2679155181304677, 'measured_model_count': 56, 'median': 0.09881359449198113, 'minimum': 0.0001475945704716096, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.4127476125067274, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.21428571428571427, 'numerator': 12, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.14285714285714285, 'numerator': 8, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 0.0}1611610blocked_insufficient_evidencerequired
NCOR1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.14874722675576924, 'interquartile_range': 0.19613442982199808, 'maximum': 0.40869956664500295, 'mean': -0.050841057199357345, 'measured_model_count': 56, 'median': -0.06479063151622333, 'minimum': -0.47358794580058783, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.047387203066228845, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0142035703777452, 'interquartile_range': 0.05741298227323171, 'maximum': 0.6135325032976449, 'mean': 0.07185270495360432, 'measured_model_count': 56, 'median': 0.03644019619439713, 'minimum': 0.0004819219900222099, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07161655265097691, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 11.11111111111111}2212210blocked_insufficient_evidencerequired
NCOR2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.19677150936375593, 'interquartile_range': 0.21722888807469082, 'maximum': 0.3135537156941089, 'mean': -0.0794500067734865, 'measured_model_count': 56, 'median': -0.08617660679431993, 'minimum': -0.5326903318404643, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.020457378710934896, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.014692639727071004, 'interquartile_range': 0.08912182751889369, 'maximum': 0.7102176386085275, 'mean': 0.08821307570204999, 'measured_model_count': 56, 'median': 0.04143923631202472, 'minimum': 0.0012173477572731738, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1038144672459647, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 37.03703703703704}1921920blocked_insufficient_evidencerequired
NF1tumor-intrinsic driver / poor direct therapeutic targetantibody / IO: 0.000; biomarker: 0.309; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06668735429589426, 'interquartile_range': 0.13438545277483557, 'maximum': 1.0698235652637622, 'mean': 0.01868900574791985, 'measured_model_count': 56, 'median': 0.0019771339155402017, 'minimum': -0.2401975756059271, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06769809847894132, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.010584583348384757, 'interquartile_range': 0.02670090210183779, 'maximum': 0.16869809455036536, 'mean': 0.029899133533875046, 'measured_model_count': 56, 'median': 0.019721964712171004, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03728548545022255, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}17170blocked_insufficient_evidencerequired
NF2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.0033319999520227406, 'interquartile_range': 0.4985835437227313, 'maximum': 1.4967874348475283, 'mean': 0.257261458735955, 'measured_model_count': 56, 'median': 0.24139439051277362, 'minimum': -0.9790795352267114, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.49525154377070857, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.00017270873873151513, 'interquartile_range': 0.019002620285019006, 'maximum': 0.9430258163992079, 'mean': 0.07984631308479892, 'measured_model_count': 56, 'median': 0.0025437083249686757, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.01917532902375052, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.07142857142857142, 'numerator': 4, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}2802800blocked_insufficient_evidencerequired
NFE2L2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.2520091656406369, 'interquartile_range': 0.20548262734606618, 'maximum': 0.31448187297091834, 'mean': -0.13768003790624178, 'measured_model_count': 56, 'median': -0.14924719674865072, 'minimum': -0.4886761370341983, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.046526538294570735, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.031692531987762916, 'interquartile_range': 0.13629651356662498, 'maximum': 0.5844930902604566, 'mean': 0.1270283768174245, 'measured_model_count': 56, 'median': 0.08432932917261374, 'minimum': 0.0003081043336782536, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1679890455543879, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 7.407407407407407}2972970blocked_insufficient_evidencerequired
NFKB2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.1463779154801344, 'interquartile_range': 0.16275217738118264, 'maximum': 0.3906297033324104, 'mean': -0.06272083452331122, 'measured_model_count': 56, 'median': -0.07291431839673687, 'minimum': -0.5332535016531746, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.016374261901048223, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01669333637117928, 'interquartile_range': 0.06426057937780422, 'maximum': 0.5792888550716845, 'mean': 0.07237504948051252, 'measured_model_count': 56, 'median': 0.039965302273933655, 'minimum': 0.0005060565776778315, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0809539157489835, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 18.51851851851852}2022020blocked_insufficient_evidencerequired
NFKBIEunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.4747394844173423, 'interquartile_range': 0.2676801224614766, 'maximum': 0.41948154320340647, 'mean': -0.3416210665817968, 'measured_model_count': 56, 'median': -0.3591398799415844, 'minimum': -1.083785830359554, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.20705936195586572, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.1375067692802133, 'interquartile_range': 0.37049721185843076, 'maximum': 0.958742819767064, 'mean': 0.3531347237615799, 'measured_model_count': 56, 'median': 0.3441621104153567, 'minimum': 0.0002733574349602312, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.5080039811386441, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.26785714285714285, 'numerator': 15, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 25.925925925925927}1531530blocked_insufficient_evidencerequired
NGFRresearch-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.30792591558766197, 'interquartile_range': 0.11989661346851041, 'maximum': 0.11576261821187195, 'mean': -0.24643987201509007, 'measured_model_count': 56, 'median': -0.24041421960464082, 'minimum': -0.4807813402770903, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.18802930211915156, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.09390776865702505, 'interquartile_range': 0.16367174704167087, 'maximum': 0.5605448986371326, 'mean': 0.1942768969038153, 'measured_model_count': 56, 'median': 0.1667282415797557, 'minimum': 0.008597790397277472, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2575795156986959, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}not availablenot availablenot availableblocked_insufficient_evidencerequired
NKX2-1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.12276799614693762, 'interquartile_range': 0.18307558688335396, 'maximum': 0.27550802661951984, 'mean': -0.043376474182780414, 'measured_model_count': 56, 'median': -0.03133446214879327, 'minimum': -0.4273642289892, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.060307590736416325, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.010194888921109245, 'interquartile_range': 0.04847112414292441, 'maximum': 0.3976824988928863, 'mean': 0.060590058138209654, 'measured_model_count': 56, 'median': 0.02987755063188091, 'minimum': 0.0012628047782111012, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.058666013064033656, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 85.18518518518519}2422420blocked_insufficient_evidencerequired
NOTCH1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.04943752847392074, 'interquartile_range': 0.11481559041215458, 'maximum': 0.16997708658381597, 'mean': -0.0011867456856176305, 'measured_model_count': 56, 'median': 0.008586282728026395, 'minimum': -0.2810791148673261, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06537806193823384, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.012038295662059835, 'interquartile_range': 0.022845606718235385, 'maximum': 0.18447254484328296, 'mean': 0.030522579666454237, 'measured_model_count': 56, 'median': 0.015886080712783135, 'minimum': 0.004403982739587212, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03488390238029522, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}2872870blocked_insufficient_evidencerequired
NOTCH2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.13850163507429375, 'interquartile_range': 0.2244656275170174, 'maximum': 0.3986273246825719, 'mean': -0.030350525395588388, 'measured_model_count': 56, 'median': -0.034328145661024975, 'minimum': -0.44916442200119266, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08596399244272365, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.007945313328654979, 'interquartile_range': 0.08294853524488494, 'maximum': 0.4118005119658145, 'mean': 0.06629039133767924, 'measured_model_count': 56, 'median': 0.025783870960812194, 'minimum': 0.002243224020282026, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09089384857353991, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 37.03703703703704}1091090blocked_insufficient_evidencerequired
NRAStumor-intrinsic driver / biomarkerantibody / IO: 0.301; biomarker: 0.760; small molecule: 0.666availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.3305911123197959, 'interquartile_range': 0.20369185017668184, 'maximum': 0.09354479287791917, 'mean': -0.44904229263305867, 'measured_model_count': 56, 'median': -0.19958349119150692, 'minimum': -2.9561530105181015, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.12689926214311403, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.05768686105568797, 'interquartile_range': 0.22765180742178384, 'maximum': 1.0, 'mean': 0.27492022095168256, 'measured_model_count': 56, 'median': 0.11160490099703885, 'minimum': 0.004688799268174339, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2853386684774718, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.19642857142857142, 'numerator': 11, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.16071428571428573, 'numerator': 9, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 85.18518518518519}63-3blocked_insufficient_evidencerequired
NT5Eresearch-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.07327247215096008, 'interquartile_range': 0.1162611666370785, 'maximum': 0.2732322344641132, 'mean': -0.0047660578695370584, 'measured_model_count': 56, 'median': -0.008866378941955744, 'minimum': -0.262273581288223, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04298869448611842, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.014413470815455534, 'interquartile_range': 0.024615083725310807, 'maximum': 0.20865009438516322, 'mean': 0.03134252380078864, 'measured_model_count': 56, 'median': 0.0211052075698444, 'minimum': 0.0020125603678799444, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03902855454076634, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}not availablenot availablenot availableblocked_insufficient_evidencerequired
NTRK1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.04264846706192717, 'interquartile_range': 0.1195819914607735, 'maximum': 0.20114723020449096, 'mean': 0.015540283237262965, 'measured_model_count': 56, 'median': 0.026272854423689842, 'minimum': -0.23366332567258905, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07693352439884633, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.009811935298125282, 'interquartile_range': 0.024365972544399282, 'maximum': 0.14777656422626312, 'mean': 0.024222066161382748, 'measured_model_count': 56, 'median': 0.01863576450281533, 'minimum': 0.00207213738312382, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.034177907842524564, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}70700blocked_insufficient_evidencerequired
NTRK2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.014221021812303218, 'interquartile_range': 0.14884406245468834, 'maximum': 0.42475333414356103, 'mean': 0.09655480444725151, 'measured_model_count': 56, 'median': 0.08551856745146294, 'minimum': -0.2698832809930628, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.16306508426699157, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.003994279326308055, 'interquartile_range': 0.015022230202413047, 'maximum': 0.16008520535900733, 'mean': 0.015090863385395179, 'measured_model_count': 56, 'median': 0.007605478950701532, 'minimum': 0.00032944850035258275, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.019016509528721103, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 66.66666666666667}1121120blocked_insufficient_evidencerequired
NTRK3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.07238517527802066, 'interquartile_range': 0.13988816637951834, 'maximum': 0.27181984530850334, 'mean': -0.008595154891903269, 'measured_model_count': 56, 'median': 0.00021986816198801135, 'minimum': -0.4322775348198563, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06750299110149767, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.010213270016093746, 'interquartile_range': 0.03102434821200728, 'maximum': 0.3764846557634913, 'mean': 0.03842677280420746, 'measured_model_count': 56, 'median': 0.019114279173136295, 'minimum': 0.0013946676886993539, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04123761822810103, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 70.37037037037037}1781780blocked_insufficient_evidencerequired
NUP98unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.946727819118484, 'interquartile_range': 0.2497531610528998, 'maximum': -0.35725870489878797, 'mean': -0.8454054346865577, 'measured_model_count': 56, 'median': -0.8055598197254084, 'minimum': -1.97097650992929, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.6969746580655842, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.8242508054226083, 'interquartile_range': 0.14214214374173795, 'maximum': 0.9999613193078875, 'mean': 0.855911828309157, 'measured_model_count': 56, 'median': 0.9185618693763015, 'minimum': 0.25117687375019454, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9663929491643463, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.9464285714285714, 'numerator': 53, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.8035714285714286, 'numerator': 45, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}2252250blocked_insufficient_evidencerequired
NUTM1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06766413170933441, 'interquartile_range': 0.12230469464003679, 'maximum': 0.23858120904323193, 'mean': -0.013250682999457888, 'measured_model_count': 56, 'median': -0.01540965770348755, 'minimum': -0.33765216343614773, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05464056293070238, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.012373005021698226, 'interquartile_range': 0.026164771633834467, 'maximum': 0.22158294522974528, 'mean': 0.03317301826003201, 'measured_model_count': 56, 'median': 0.023444423153857114, 'minimum': 0.0015163016029478907, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03853777665553269, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}1351350blocked_insufficient_evidencerequired
OCA2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.11003886894933272, 'interquartile_range': 0.12428844836998826, 'maximum': 0.17215928504056552, 'mean': -0.04570717775043043, 'measured_model_count': 56, 'median': -0.024477812493177965, 'minimum': -0.2893171738503026, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.014249579420655543, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01726318105631539, 'interquartile_range': 0.03416598908030699, 'maximum': 0.2544187739476363, 'mean': 0.04408398212649205, 'measured_model_count': 56, 'median': 0.025337616392692195, 'minimum': 0.0036640872919462475, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.051429170136622376, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 18.51851851851852}81810blocked_insufficient_evidencerequired
PARP1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.3126108449025472, 'interquartile_range': 0.19294837361965708, 'maximum': 0.11033739065298756, 'mean': -0.2123893655849565, 'measured_model_count': 56, 'median': -0.20900614511179944, 'minimum': -0.5526061990232184, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.11966247128289012, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0579623906831193, 'interquartile_range': 0.22040785644401745, 'maximum': 0.6102638834732295, 'mean': 0.1765929122874719, 'measured_model_count': 56, 'median': 0.13645456881846418, 'minimum': 0.005254797527991211, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.27837024712713676, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}1801800blocked_insufficient_evidencerequired
PATZ1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.21337700367028087, 'interquartile_range': 0.13030410006901616, 'maximum': 0.1548473717667494, 'mean': -0.15100029050775082, 'measured_model_count': 56, 'median': -0.1391172000683189, 'minimum': -0.4179920396603739, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.08307290360126471, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.04269880256237364, 'interquartile_range': 0.1065916921003043, 'maximum': 0.39286694038493386, 'mean': 0.1137033476788312, 'measured_model_count': 56, 'median': 0.0798356188482517, 'minimum': 0.005100727127091044, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.14929049466267794, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}2652650blocked_insufficient_evidencerequired
PAX5unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.1088845448548971, 'interquartile_range': 0.14703441884732282, 'maximum': 0.13854687883744554, 'mean': -0.03206191587252125, 'measured_model_count': 56, 'median': -0.014464371335449124, 'minimum': -0.30679469825273975, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03814987399242574, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.011626966753839703, 'interquartile_range': 0.04602638788189701, 'maximum': 0.26838932138817734, 'mean': 0.0402637735904481, 'measured_model_count': 56, 'median': 0.023559907731496195, 'minimum': 0.004857244948173928, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05765335463573671, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 11.11111111111111}1301300blocked_insufficient_evidencerequired
PBRM1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.16479697620735534, 'interquartile_range': 0.3034207952026297, 'maximum': 0.4448525230836686, 'mean': -0.022173015534992117, 'measured_model_count': 56, 'median': -0.04422832147235136, 'minimum': -0.6075030044826925, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.13862381899527437, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005101405183288445, 'interquartile_range': 0.08901199505560088, 'maximum': 0.6419488286639063, 'mean': 0.07271163892119407, 'measured_model_count': 56, 'median': 0.025873981311805343, 'minimum': 0.00026959172539142045, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09411340023888932, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}44440blocked_insufficient_evidencerequired
PDCD1anti-PD-1 combination targetantibody / IO: 0.827; biomarker: 0.498; small molecule: 0.144availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.07586317533990133, 'interquartile_range': 0.1536254155593421, 'maximum': 0.3225183637936061, 'mean': -0.0001670624551346131, 'measured_model_count': 56, 'median': -0.01957298536283847, 'minimum': -0.3110634393914682, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07776224021944075, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008553814788841528, 'interquartile_range': 0.03284445323467796, 'maximum': 0.2333724479616654, 'mean': 0.04119029126229425, 'measured_model_count': 56, 'median': 0.02164243704516978, 'minimum': 0.0004402840326518532, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04139826802351949, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 100.0}242blocked_insufficient_evidencerequired
PDCD1LG2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.05816013705757744, 'interquartile_range': 0.11189371167739326, 'maximum': 0.3771133025892327, 'mean': 0.1072155941052707, 'measured_model_count': 56, 'median': 0.09145888055795778, 'minimum': -0.11873669255379785, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1700538487349707, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0037372367702815036, 'interquartile_range': 0.010498710407831242, 'maximum': 0.04984001631579498, 'mean': 0.01034691838648634, 'measured_model_count': 56, 'median': 0.007611086135415668, 'minimum': 0.0007532072106878847, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.014235947178112746, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}2852850blocked_insufficient_evidencerequired
PDGFRAunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.004availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.2533602866327354, 'interquartile_range': 0.12572359618727533, 'maximum': 0.09819146945773913, 'mean': -0.1964573159629175, 'measured_model_count': 56, 'median': -0.18362142417989624, 'minimum': -0.6817254249652711, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.12763669044546008, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.05686242904454657, 'interquartile_range': 0.10437702981984269, 'maximum': 0.8490391727005575, 'mean': 0.15035186602067654, 'measured_model_count': 56, 'median': 0.10237428471529833, 'minimum': 0.004926867884639238, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.16123945886438926, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}34340blocked_insufficient_evidencerequired
PDGFRBunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.1533298824968127, 'interquartile_range': 0.19320922610917157, 'maximum': 0.28340888139004716, 'mean': -0.060062062579911354, 'measured_model_count': 56, 'median': -0.07629056372993706, 'minimum': -0.39446206414889434, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03987934361235887, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.015103099225042448, 'interquartile_range': 0.0632267186652943, 'maximum': 0.3425415988456145, 'mean': 0.06299017017119603, 'measured_model_count': 56, 'median': 0.04135928988080292, 'minimum': 0.0019110310657141872, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07832981789033674, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}39390blocked_insufficient_evidencerequired
PER1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.03086128251576374, 'interquartile_range': 0.1190081708614905, 'maximum': 0.28867284705445984, 'mean': 0.08991771449382154, 'measured_model_count': 56, 'median': 0.09976442986895973, 'minimum': -0.14227097328950417, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.14986945337725424, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.004534189618738785, 'interquartile_range': 0.010004848593089312, 'maximum': 0.058565348415219765, 'mean': 0.01211886409344396, 'measured_model_count': 56, 'median': 0.00844002980337798, 'minimum': 0.0010624023055272463, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.014539038211828097, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}1381380blocked_insufficient_evidencerequired
PHOX2Bunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.03090500613816374, 'interquartile_range': 0.1454216583568894, 'maximum': 0.41213169639238095, 'mean': 0.09788717649919845, 'measured_model_count': 56, 'median': 0.09159221551687652, 'minimum': -0.36911677256516784, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.17632666449505313, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.003112541444687733, 'interquartile_range': 0.014775071158484721, 'maximum': 0.23396617386517476, 'mean': 0.01769875721200918, 'measured_model_count': 56, 'median': 0.009699743764547134, 'minimum': 0.0001502625548091212, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.017887612603172454, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}1241240blocked_insufficient_evidencerequired
PIK3CAunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.3926242184937075, 'interquartile_range': 0.2029757534853182, 'maximum': 0.11683662531876016, 'mean': -0.2863294055143963, 'measured_model_count': 56, 'median': -0.2939677758894327, 'minimum': -0.6891435375577224, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.18964846500838928, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.10419575803316142, 'interquartile_range': 0.2948881615068477, 'maximum': 0.8761345885208559, 'mean': 0.2630345989934602, 'measured_model_count': 56, 'median': 0.20917938968000044, 'minimum': 0.005989732137504378, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.39908391954000916, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.14285714285714285, 'numerator': 8, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 14.814814814814815}2402400blocked_insufficient_evidencerequired
PIK3CBunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.3628942051472416, 'interquartile_range': 0.3084161617199057, 'maximum': 0.2007035324921781, 'mean': -0.24425789928383776, 'measured_model_count': 56, 'median': -0.16430375541703418, 'minimum': -1.0565353629457381, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.05447804342733584, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0338053475717404, 'interquartile_range': 0.32662358663277163, 'maximum': 0.9951060501601744, 'mean': 0.24446303063227964, 'measured_model_count': 56, 'median': 0.08159559753139387, 'minimum': 0.003445438951288355, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.36042893420451205, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.19642857142857142, 'numerator': 11, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.125, 'numerator': 7, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 85.18518518518519}2952950blocked_insufficient_evidencerequired
PIK3R1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.03837001138190876, 'interquartile_range': 0.2663987206667829, 'maximum': 0.6800493745081021, 'mean': 0.08456744924235596, 'measured_model_count': 56, 'median': 0.07693671363161786, 'minimum': -0.35984488150574573, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.22802870928487412, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.002696889421791202, 'interquartile_range': 0.02538843082361781, 'maximum': 0.3583474394213573, 'mean': 0.029228288317221747, 'measured_model_count': 56, 'median': 0.009912816186445288, 'minimum': 2.073664012003869e-05, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02808532024540901, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 3.7037037037037037}1221220blocked_insufficient_evidencerequired
PLCG1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.056839178567636914, 'interquartile_range': 0.1366667894574548, 'maximum': 0.2632874125269735, 'mean': 0.015463572567236987, 'measured_model_count': 56, 'median': 0.02301043378246097, 'minimum': -0.31270963525517503, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07982761088981788, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008139315582853286, 'interquartile_range': 0.028860875205757974, 'maximum': 0.15688435402465603, 'mean': 0.02672685825084457, 'measured_model_count': 56, 'median': 0.01620788943023691, 'minimum': 0.001386197774518595, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03700019078861126, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}2152150blocked_insufficient_evidencerequired
PLXNB2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.016739809784034065, 'interquartile_range': 0.13622487385793947, 'maximum': 0.39172179779208477, 'mean': 0.09250986907465496, 'measured_model_count': 56, 'median': 0.07287237929257996, 'minimum': -0.17175670111727442, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.15296468364197352, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.004153007557135326, 'interquartile_range': 0.013950921193240031, 'maximum': 0.06888512238549067, 'mean': 0.014042510139181064, 'measured_model_count': 56, 'median': 0.010539954198750902, 'minimum': 0.0007187168733285372, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.018103928750375357, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 70.37037037037037}2772770blocked_insufficient_evidencerequired
PMELunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.2400016434090602, 'interquartile_range': 0.20927280835888581, 'maximum': 0.10533139840966646, 'mean': -0.1324141548909928, 'measured_model_count': 56, 'median': -0.13772450645851692, 'minimum': -0.5253708137934905, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.030728835050174378, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.026923220466624286, 'interquartile_range': 0.11529393681860517, 'maximum': 0.6538000146205327, 'mean': 0.10254274521418213, 'measured_model_count': 56, 'median': 0.07252845996137892, 'minimum': 0.0052803313388520646, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.14221715728522946, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}2722720blocked_insufficient_evidencerequired
PMS2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.055192771409656866, 'interquartile_range': 0.14739073725694488, 'maximum': 0.38523856553318947, 'mean': 0.12017485590510182, 'measured_model_count': 56, 'median': 0.11394202876623996, 'minimum': -0.18820183094115384, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.20258350866660174, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0024973371316166187, 'interquartile_range': 0.011151597509534487, 'maximum': 0.1140254341691312, 'mean': 0.013196658557872531, 'measured_model_count': 56, 'median': 0.005788126840964296, 'minimum': 0.000614212746071096, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.013648934641151106, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}2062060blocked_insufficient_evidencerequired
POLD1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -2.2555126211580916, 'interquartile_range': 0.39839849563843344, 'maximum': -1.2480701178321307, 'mean': -2.047820149678809, 'measured_model_count': 56, 'median': -2.0748283180612623, 'minimum': -2.9554520157837465, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.8571141255196582, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 1.0, 'interquartile_range': 0.0, 'maximum': 1.0, 'mean': 0.9997822098855916, 'measured_model_count': 56, 'median': 1.0, 'minimum': 0.9959820103493834, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 1.0, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}1151150blocked_insufficient_evidencerequired
POLEunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.7686221790937948, 'interquartile_range': 0.49019054275043095, 'maximum': -0.8864340679478432, 'mean': -1.5445676761570897, 'measured_model_count': 56, 'median': -1.512475654018234, 'minimum': -2.691654838050905, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.2784316363433639, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9937930644505688, 'interquartile_range': 0.006206935528471291, 'maximum': 1.0, 'mean': 0.995224255991806, 'measured_model_count': 56, 'median': 0.9994873578486327, 'minimum': 0.9596816798789393, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9999999999790401, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}41410blocked_insufficient_evidencerequired
POLQunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.39901280322112664, 'interquartile_range': 0.22486613245338025, 'maximum': 0.05185493446814471, 'mean': -0.29887660161957547, 'measured_model_count': 56, 'median': -0.2878340309311357, 'minimum': -1.0029113047323868, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.1741466707677464, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.10011844551019167, 'interquartile_range': 0.2983836803191332, 'maximum': 0.9620343470390572, 'mean': 0.2837371101307486, 'measured_model_count': 56, 'median': 0.2125326319656341, 'minimum': 0.008170163671162276, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.39850212582932487, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.17857142857142858, 'numerator': 10, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}75750blocked_insufficient_evidencerequired
POT1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.012availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.5635819718766873, 'interquartile_range': 0.26505416396453424, 'maximum': -0.06251627466615711, 'mean': -0.44935742447896204, 'measured_model_count': 56, 'median': -0.42293149499519567, 'minimum': -1.1041577617026235, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.2985278079121531, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.23950012403748594, 'interquartile_range': 0.43079365738697023, 'maximum': 0.9717428477917653, 'mean': 0.4692116059277039, 'measured_model_count': 56, 'median': 0.4805480850355817, 'minimum': 0.052371667803121746, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.6702937814244562, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.48214285714285715, 'numerator': 27, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.14285714285714285, 'numerator': 8, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 70.37037037037037}25250blocked_insufficient_evidencerequired
POU2AF1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06144299452441082, 'interquartile_range': 0.16721482908748944, 'maximum': 0.25598488770962047, 'mean': 0.012489908148375358, 'measured_model_count': 56, 'median': 0.010038770990871998, 'minimum': -0.29326722424317075, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10577183456307862, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0067145750699271175, 'interquartile_range': 0.03315913931173384, 'maximum': 0.24566225721850554, 'mean': 0.033463484590643744, 'measured_model_count': 56, 'median': 0.02258460016959892, 'minimum': 0.0018220453406680766, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03987371438166096, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}2712710blocked_insufficient_evidencerequired
PPP2R1Aunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.6847459075068567, 'interquartile_range': 0.46834225071689306, 'maximum': -0.4896122806584271, 'mean': -1.4730530296832878, 'measured_model_count': 56, 'median': -1.471863264456811, 'minimum': -2.8617405459735346, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.2164036567899636, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.991270804140258, 'interquartile_range': 0.008718189144905297, 'maximum': 1.0, 'mean': 0.9648698306535062, 'measured_model_count': 56, 'median': 0.9991692822150705, 'minimum': 0.4482521452993049, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9999889932851633, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.9821428571428571, 'numerator': 55, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.9285714285714286, 'numerator': 52, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}1551550blocked_insufficient_evidencerequired
PPP6Cunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.010availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.0180315911310092, 'interquartile_range': 0.5621537586484284, 'maximum': 0.11025640550708837, 'mean': -0.7830457115397375, 'measured_model_count': 56, 'median': -0.781903782242473, 'minimum': -2.174202672852065, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.4558778324825807, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.5280855865269243, 'interquartile_range': 0.4428703885392822, 'maximum': 1.0, 'mean': 0.7228752811217215, 'measured_model_count': 56, 'median': 0.8982627669210668, 'minimum': 0.012641297187679104, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9709559750662065, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.75, 'numerator': 42, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.6428571428571429, 'numerator': 36, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 100.0}29290blocked_insufficient_evidencerequired
PRDM1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.08291657465478372, 'interquartile_range': 0.14691125593049534, 'maximum': 0.31777949130823113, 'mean': -0.0004918904971693967, 'measured_model_count': 56, 'median': -0.008524764962677182, 'minimum': -0.234721655796034, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06399468127571162, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.009277719511873131, 'interquartile_range': 0.037261079629678555, 'maximum': 0.19958293481324751, 'mean': 0.032832412014046124, 'measured_model_count': 56, 'median': 0.02097438411360496, 'minimum': 0.0017317366625563182, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.046538799141551686, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 18.51851851851852}1461460blocked_insufficient_evidencerequired
PRDM16unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.16713623178169615, 'interquartile_range': 0.16512730681889062, 'maximum': 0.2569246975507734, 'mean': -0.08575797188179488, 'measured_model_count': 56, 'median': -0.09204657993987507, 'minimum': -0.4186847355613391, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.0020089249628055354, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.02149112015272428, 'interquartile_range': 0.07412131422340887, 'maximum': 0.3514851749930976, 'mean': 0.07152261488348251, 'measured_model_count': 56, 'median': 0.04697655942427176, 'minimum': 0.0025971801743869516, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09561243437613315, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 48.148148148148145}2532530blocked_insufficient_evidencerequired
PREX2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.06544856986628139, 'interquartile_range': 0.12703400620022845, 'maximum': 0.49542242427329963, 'mean': 0.13323863617645906, 'measured_model_count': 56, 'median': 0.11155773430019963, 'minimum': -0.09874246278849794, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.19248257606650984, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0025839773065120717, 'interquartile_range': 0.009416781894391853, 'maximum': 0.03580333716191526, 'mean': 0.008801885456245927, 'measured_model_count': 56, 'median': 0.007049386132260232, 'minimum': 0.00015597332978287568, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.012000759200903925, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}72720blocked_insufficient_evidencerequired
PRF1immune-context markerantibody / IO: 0.000; biomarker: 0.500; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.05478050797948658, 'interquartile_range': 0.09711305586290947, 'maximum': 0.4078675016027466, 'mean': -0.0015226298621399592, 'measured_model_count': 56, 'median': 0.0047451788481697, 'minimum': -0.22679163161826915, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.042332547883422895, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.011764494825794149, 'interquartile_range': 0.03005355888286111, 'maximum': 0.23055611608468068, 'mean': 0.030715219026443995, 'measured_model_count': 56, 'median': 0.02139926937725605, 'minimum': 0.0005486674577255344, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04181805370865526, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}1911910blocked_insufficient_evidencerequired
PTCH1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.09588063885275669, 'interquartile_range': 0.21009150163000154, 'maximum': 0.3324175140971824, 'mean': 0.011094539588050975, 'measured_model_count': 56, 'median': 0.018151218696463505, 'minimum': -0.46600755029575164, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11421086277724485, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005977946450391312, 'interquartile_range': 0.03975630865182156, 'maximum': 0.37309691491643426, 'mean': 0.036336117075092225, 'measured_model_count': 56, 'median': 0.020825055662632826, 'minimum': 0.0010684762208753433, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04573425510221287, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 25.925925925925927}1201200blocked_insufficient_evidencerequired
PTENtumor-intrinsic driver / poor direct therapeutic targetantibody / IO: 0.000; biomarker: 0.313; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.1774273786697296, 'interquartile_range': 0.3538259685928198, 'maximum': 1.736156453910227, 'mean': 0.35005025729220074, 'measured_model_count': 56, 'median': 0.3093834287818784, 'minimum': -0.5425024630491011, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.5312533472625494, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.00014782039573808722, 'interquartile_range': 0.003600925362963198, 'maximum': 0.5552301573186749, 'mean': 0.029092579805179958, 'measured_model_count': 56, 'median': 0.0016319869133616688, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0037487457587012853, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}15161blocked_insufficient_evidencerequired
PTK6unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.1840162742298729, 'interquartile_range': 0.1997483929044233, 'maximum': 0.3222356768075394, 'mean': -0.09758380127941914, 'measured_model_count': 56, 'median': -0.12026321213311797, 'minimum': -0.5349203287149611, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.015732118674550405, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.018529924530914635, 'interquartile_range': 0.09544668456352441, 'maximum': 0.7582481910067956, 'mean': 0.09733291620033664, 'measured_model_count': 56, 'median': 0.05169764005554711, 'minimum': 0.0011785351628772456, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11397660909443905, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}2542540blocked_insufficient_evidencerequired
PTPN11unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.3533909262374086, 'interquartile_range': 0.29119952608175426, 'maximum': 0.17635991627900627, 'mean': -0.2706024316129988, 'measured_model_count': 56, 'median': -0.22336959724687172, 'minimum': -1.2437665525555057, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.06219140015565436, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.03844928397309019, 'interquartile_range': 0.284016781985858, 'maximum': 0.9954390112631097, 'mean': 0.24807679949177336, 'measured_model_count': 56, 'median': 0.15755716577163256, 'minimum': 0.004383763089454739, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.3224660659589482, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.14285714285714285, 'numerator': 8, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.10714285714285714, 'numerator': 6, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 3.7037037037037037}87870blocked_insufficient_evidencerequired
PTPN13unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.040896381394369005, 'interquartile_range': 0.14700691920925746, 'maximum': 0.31995876843033, 'mean': 0.028346182847745472, 'measured_model_count': 56, 'median': 0.0242865690164243, 'minimum': -0.24895582715208994, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10611053781488845, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.007373541485068309, 'interquartile_range': 0.022925124109128, 'maximum': 0.1390811639666005, 'mean': 0.02462924447522302, 'measured_model_count': 56, 'median': 0.015851864845906453, 'minimum': 0.0018513373217926266, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03029866559419631, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}2142140blocked_insufficient_evidencerequired
PTPRBunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.08660322861860656, 'interquartile_range': 0.15326593446016268, 'maximum': 0.26799591456187166, 'mean': -0.008701379226628104, 'measured_model_count': 56, 'median': -0.005419265839015835, 'minimum': -0.2918999102986819, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06666270584155613, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.010197627844800234, 'interquartile_range': 0.033392511824931415, 'maximum': 0.20757819748639839, 'mean': 0.036540181284022935, 'measured_model_count': 56, 'median': 0.022612690169484462, 'minimum': 0.0021535234777501173, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.043590139669731645, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}85850blocked_insufficient_evidencerequired
PTPRCunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availableinsufficient_measured_context_models562098{'available': True, 'first_quartile': -0.2540968232068008, 'interquartile_range': 0.27269155062254513, 'maximum': 0.2667060877154521, 'mean': -0.10718411476264175, 'measured_model_count': 7, 'median': -0.1839674851282336, 'minimum': -0.3620232143435977, 'missing_fraction': 0.875, 'missing_model_count': 49, 'third_quartile': 0.018594727415744333, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.03535790079068784, 'interquartile_range': 0.11700097399538673, 'maximum': 0.3130619067559611, 'mean': 0.11336025072294678, 'measured_model_count': 7, 'median': 0.10142439265024349, 'minimum': 0.0036019045008981055, 'missing_fraction': 0.875, 'missing_model_count': 49, 'third_quartile': 0.15235887478607457, 'threshold_fractions': (mappingproxy({'denominator': 7, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 7, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 21, 'value': 65.0}1601600blocked_insufficient_evidencerequired
PTPRKunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.04914152862613752, 'interquartile_range': 0.12518664825956582, 'maximum': 0.2998279934328426, 'mean': 0.1114437103978233, 'measured_model_count': 56, 'median': 0.11574090709819299, 'minimum': -0.0681971223240274, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.17432817688570335, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0035664525085002926, 'interquartile_range': 0.00992274915531969, 'maximum': 0.03943903737818359, 'mean': 0.010132813629039368, 'measured_model_count': 56, 'median': 0.007097817765832145, 'minimum': 0.0008647637371804818, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.013489201663819983, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}98980blocked_insufficient_evidencerequired
PTPRTunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.12557464182869493, 'interquartile_range': 0.1670050372331764, 'maximum': 0.35192836037169745, 'mean': -0.04846570793613747, 'measured_model_count': 56, 'median': -0.04661431473671101, 'minimum': -0.4938301685425578, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04143039540448146, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.014120381189881645, 'interquartile_range': 0.04546098758688822, 'maximum': 0.3639539499414603, 'mean': 0.054018527133764996, 'measured_model_count': 56, 'median': 0.03077532270482216, 'minimum': 0.0012548301955076896, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.059581368776769866, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 14.814814814814815}86860blocked_insufficient_evidencerequired
QKIunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.16545727142804292, 'interquartile_range': 0.2785191649890655, 'maximum': 0.4490044663426027, 'mean': -0.030217967806080992, 'measured_model_count': 56, 'median': -0.021443690625028444, 'minimum': -0.6118606202127194, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11306189356102253, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.006750055723509366, 'interquartile_range': 0.0877187794340263, 'maximum': 0.7819981814289125, 'mean': 0.08535186107724975, 'measured_model_count': 56, 'median': 0.02434871601799806, 'minimum': 0.000661291005771635, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09446883515753567, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}1171170blocked_insufficient_evidencerequired
RAC1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.013availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.132219886481244, 'interquartile_range': 0.3450850855482519, 'maximum': -0.23357021391240496, 'mean': -0.9872570564091132, 'measured_model_count': 56, 'median': -0.9644656313374076, 'minimum': -1.9398398272208595, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.7871348009329922, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.8903158974511705, 'interquartile_range': 0.0970528051333146, 'maximum': 1.0, 'mean': 0.9143828073836274, 'measured_model_count': 56, 'median': 0.9718981505657296, 'minimum': 0.12114557537340254, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9873687025844851, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.9821428571428571, 'numerator': 55, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.875, 'numerator': 49, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 92.5925925925926}22220blocked_insufficient_evidencerequired
RAD51Cunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.932549595300154, 'interquartile_range': 0.3013109434520187, 'maximum': -0.21826138124369032, 'mean': -0.7877103314357428, 'measured_model_count': 56, 'median': -0.811587320321768, 'minimum': -1.3356950303254789, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.6312386518481353, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.7658254388663606, 'interquartile_range': 0.2058807169367769, 'maximum': 0.9999550620977978, 'mean': 0.8249481295068888, 'measured_model_count': 56, 'median': 0.8957799704120795, 'minimum': 0.10762375437683037, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9717061558031375, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.9107142857142857, 'numerator': 51, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.6964285714285714, 'numerator': 39, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 88.88888888888889}2562560blocked_insufficient_evidencerequired
RAF1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.005availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.1256271216117195, 'interquartile_range': 0.1888216209784189, 'maximum': 0.20431855926131795, 'mean': -0.15615906924769854, 'measured_model_count': 56, 'median': -0.02220851631360249, 'minimum': -1.736546085109907, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06319449936669941, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.012033750897031764, 'interquartile_range': 0.04288567210061994, 'maximum': 1.0, 'mean': 0.17290387330361726, 'measured_model_count': 56, 'median': 0.02468474918939307, 'minimum': 0.0024816460659539356, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05491942299765171, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.16071428571428573, 'numerator': 9, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.125, 'numerator': 7, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}32320blocked_insufficient_evidencerequired
RANBP2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.5908589284378346, 'interquartile_range': 0.16318241965130414, 'maximum': -0.11226020940158005, 'mean': -0.5039476915345732, 'measured_model_count': 56, 'median': -0.5210149465256304, 'minimum': -0.9624691006672143, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.42767650878653046, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.43796867139031853, 'interquartile_range': 0.26936444553060407, 'maximum': 0.961332400882081, 'mean': 0.5705831573863455, 'measured_model_count': 56, 'median': 0.6193692604611463, 'minimum': 0.046772958901499954, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.7073331169209226, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.6785714285714286, 'numerator': 38, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.17857142857142858, 'numerator': 10, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}2292290blocked_insufficient_evidencerequired
RB1tumor-intrinsic driver / poor direct therapeutic targetantibody / IO: 0.000; biomarker: 0.094; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.055364957538402405, 'interquartile_range': 0.27298439964807286, 'maximum': 0.8459136994900094, 'mean': 0.21463507902892, 'measured_model_count': 56, 'median': 0.20375104048983378, 'minimum': -0.6519186084404235, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.3283493571864753, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0005016747096900193, 'interquartile_range': 0.010403535843926915, 'maximum': 0.6691439310341896, 'mean': 0.02148722485594138, 'measured_model_count': 56, 'median': 0.003501129077626756, 'minimum': 1.653080623736478e-09, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.010905210553616934, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}96960blocked_insufficient_evidencerequired
RETunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.14612119713856755, 'interquartile_range': 0.14575295943199149, 'maximum': 0.17499522346494442, 'mean': -0.06749277025807235, 'measured_model_count': 56, 'median': -0.07167217571962779, 'minimum': -0.24627934225885015, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.000368237706576062, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.018037570779840997, 'interquartile_range': 0.06104268632906562, 'maximum': 0.17637743727038194, 'mean': 0.056573689560530285, 'measured_model_count': 56, 'median': 0.04047103264540877, 'minimum': 0.004538060086491297, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07908025710890662, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 3.7037037037037037}1841840blocked_insufficient_evidencerequired
RICTORunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.5866822345351441, 'interquartile_range': 0.34588160919168814, 'maximum': 0.16149735225992057, 'mean': -0.46055626393316357, 'measured_model_count': 56, 'median': -0.39783708129546663, 'minimum': -1.5075664457299727, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.24080062534345598, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.1350228253539574, 'interquartile_range': 0.6118989644679056, 'maximum': 0.9999801771783248, 'mean': 0.44882468393642067, 'measured_model_count': 56, 'median': 0.38868919644309075, 'minimum': 0.003186659711179904, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.746921789821863, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.35714285714285715, 'numerator': 20, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.21428571428571427, 'numerator': 12, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}1821820blocked_insufficient_evidencerequired
ROS1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.08392049067782814, 'interquartile_range': 0.12341727033690336, 'maximum': 0.3254661141771581, 'mean': 0.126330303900205, 'measured_model_count': 56, 'median': 0.12383389748495374, 'minimum': -0.20924597391267008, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2073377610147315, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0027627089855649873, 'interquartile_range': 0.007337207312868303, 'maximum': 0.10622139999463978, 'mean': 0.012021715750322627, 'measured_model_count': 56, 'median': 0.005657972826808763, 'minimum': 0.0007528764526069915, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.01009991629843329, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 11.11111111111111}50500blocked_insufficient_evidencerequired
RPL5unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -2.3140510776793413, 'interquartile_range': 0.5596836672474383, 'maximum': -1.2945186569708296, 'mean': -2.0478521024180614, 'measured_model_count': 56, 'median': -2.0634465911044617, 'minimum': -2.8814886097008965, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.754367410431903, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9999896314895338, 'interquartile_range': 1.0368510466207681e-05, 'maximum': 1.0, 'mean': 0.9995504351830853, 'measured_model_count': 56, 'median': 1.0, 'minimum': 0.9841023605416382, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 1.0, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 25.925925925925927}1061060blocked_insufficient_evidencerequired
RRM1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -3.7866713498714786, 'interquartile_range': 0.7142138038474664, 'maximum': -2.0291077684100465, 'mean': -3.4304476414103555, 'measured_model_count': 56, 'median': -3.527279701684648, 'minimum': -4.272254363112374, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -3.072457546024012, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 1.0, 'interquartile_range': 0.0, 'maximum': 1.0, 'mean': 1.0, 'measured_model_count': 56, 'median': 1.0, 'minimum': 1.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 1.0, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 100.0}1261260blocked_insufficient_evidencerequired
RRM2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -3.0848036344428675, 'interquartile_range': 0.517328228067063, 'maximum': -1.1915182107798357, 'mean': -2.782417065774602, 'measured_model_count': 56, 'median': -2.8483434965014958, 'minimum': -3.607628637950257, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -2.5674754063758045, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 1.0, 'interquartile_range': 0.0, 'maximum': 1.0, 'mean': 0.9999699992385163, 'measured_model_count': 56, 'median': 1.0, 'minimum': 0.9983332637171632, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 1.0, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}1011010blocked_insufficient_evidencerequired
RRM2Bunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.030440159428604997, 'interquartile_range': 0.09226055303100826, 'maximum': 0.23615443777033013, 'mean': 0.01593588710866817, 'measured_model_count': 56, 'median': 0.006488471619161884, 'minimum': -0.18121780207352717, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06182039360240326, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01078722232470268, 'interquartile_range': 0.01897368961587206, 'maximum': 0.07183784488213862, 'mean': 0.021949966235280397, 'measured_model_count': 56, 'median': 0.017595754218379635, 'minimum': 0.002689755558466425, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02976091194057474, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}1131130blocked_insufficient_evidencerequired
RUNX1T1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.09884952652793141, 'interquartile_range': 0.11970965709835064, 'maximum': 0.27356305825023636, 'mean': -0.04295758676242804, 'measured_model_count': 56, 'median': -0.04714232020834208, 'minimum': -0.3818943189986762, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02086013057041923, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0161003914275484, 'interquartile_range': 0.041744408958407656, 'maximum': 0.4366432533874732, 'mean': 0.04657444844566352, 'measured_model_count': 56, 'median': 0.03193243688624428, 'minimum': 0.0019998872365112946, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.057844800385956054, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 37.03703703703704}93930blocked_insufficient_evidencerequired
SALL4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.13566465830643035, 'interquartile_range': 0.13712660498832815, 'maximum': 0.3325082771559966, 'mean': -0.061407429436107094, 'measured_model_count': 56, 'median': -0.05751971111293863, 'minimum': -0.37072006405562824, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0014619466818978008, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.02069457658383381, 'interquartile_range': 0.03437754339962874, 'maximum': 0.3217848067260631, 'mean': 0.051741718849113674, 'measured_model_count': 56, 'median': 0.036589651850089416, 'minimum': 0.001902674157795965, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05507211998346255, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 14.814814814814815}1521520blocked_insufficient_evidencerequired
SETBP1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.03797804622296906, 'interquartile_range': 0.11603569982367719, 'maximum': 0.23410999453740547, 'mean': 0.026320814579516943, 'measured_model_count': 56, 'median': 0.020794089042544255, 'minimum': -0.1749570667473206, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07805765360070813, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.009273976484867677, 'interquartile_range': 0.017960499834995435, 'maximum': 0.1341463196615172, 'mean': 0.022262575208713727, 'measured_model_count': 56, 'median': 0.016776289101935012, 'minimum': 0.002760614285472168, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.027234476319863112, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 25.925925925925927}1251250blocked_insufficient_evidencerequired
SETD2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.5047376254956473, 'interquartile_range': 0.37448050917812936, 'maximum': 0.1846584412323803, 'mean': -0.3291048407412958, 'measured_model_count': 56, 'median': -0.3280383584112302, 'minimum': -1.0317415681684419, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.1302571163175179, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.08620996554393631, 'interquartile_range': 0.5051609618146871, 'maximum': 0.9761682730353267, 'mean': 0.34026916308678895, 'measured_model_count': 56, 'median': 0.26696470082025603, 'minimum': 0.0024915270161495534, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.5913709273586234, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.32142857142857145, 'numerator': 18, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.07142857142857142, 'numerator': 4, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}45450blocked_insufficient_evidencerequired
SF3B1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.011availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.6704389910023474, 'interquartile_range': 0.32745833716446127, 'maximum': -0.9508810647263816, 'mean': -1.5338619757571077, 'measured_model_count': 56, 'median': -1.4947664924641337, 'minimum': -2.378982043724258, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.3429806538378861, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9931771615712739, 'interquartile_range': 0.006820375637453746, 'maximum': 1.0, 'mean': 0.9957113192764605, 'measured_model_count': 56, 'median': 0.9993767217839019, 'minimum': 0.9673445342927015, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9999975372087276, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}28280blocked_insufficient_evidencerequired
SLC24A5unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.003025095303933984, 'interquartile_range': 0.10082197260395905, 'maximum': 0.22263284691640708, 'mean': 0.04178003697152555, 'measured_model_count': 56, 'median': 0.04566657198688534, 'minimum': -0.28433300526663596, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10384706790789303, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.007485941222069663, 'interquartile_range': 0.013936761588715495, 'maximum': 0.13392583893250115, 'mean': 0.02036981003205173, 'measured_model_count': 56, 'median': 0.012767474299341924, 'minimum': 0.0016006595218845212, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02142270281078516, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}2862860blocked_insufficient_evidencerequired
SLC45A2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.040933783966169555, 'interquartile_range': 0.14882908611197646, 'maximum': 0.3227303488010275, 'mean': 0.11567695785061881, 'measured_model_count': 56, 'median': 0.11861136448699858, 'minimum': -0.08536406441108876, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.18976287007814602, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0035499116606889656, 'interquartile_range': 0.009916857053356331, 'maximum': 0.0395367321012825, 'mean': 0.010096898602229057, 'measured_model_count': 56, 'median': 0.006829464645826495, 'minimum': 0.0006995658646645975, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.013466768714045296, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 11.11111111111111}1671670blocked_insufficient_evidencerequired
SMAD2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.04437470527249164, 'interquartile_range': 0.10986926077333312, 'maximum': 0.1719519122172183, 'mean': 0.0053355756530233155, 'measured_model_count': 56, 'median': 0.020857726704379374, 'minimum': -0.24627069147106154, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06549455550084148, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.010600862933249054, 'interquartile_range': 0.016872658456282188, 'maximum': 0.15468658704651223, 'mean': 0.02527240623956528, 'measured_model_count': 56, 'median': 0.019602222042527484, 'minimum': 0.003858964670826867, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02747352138953124, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}1501500blocked_insufficient_evidencerequired
SMAD3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.090841081469131, 'interquartile_range': 0.10274341436989691, 'maximum': 0.19788349112491374, 'mean': -0.03155614431899213, 'measured_model_count': 56, 'median': -0.019242661334844407, 'minimum': -0.20426070247573397, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.011902332900765911, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01586107320694835, 'interquartile_range': 0.026251711901153427, 'maximum': 0.14349263118807176, 'mean': 0.03783132268640034, 'measured_model_count': 56, 'median': 0.026968181859627394, 'minimum': 0.003981175606287827, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04211278510810178, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}1861860blocked_insufficient_evidencerequired
SMARCA4unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.6036613983479087, 'interquartile_range': 0.39227301538187714, 'maximum': 0.23567647510109768, 'mean': -0.4060004403164458, 'measured_model_count': 56, 'median': -0.40356272875642973, 'minimum': -0.9591300526864226, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.21138838296603152, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.11991230214906738, 'interquartile_range': 0.642015102234534, 'maximum': 0.9765745525207847, 'mean': 0.43724903443681506, 'measured_model_count': 56, 'median': 0.3939739872865238, 'minimum': 0.001644732447700285, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.7619274043836013, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.4642857142857143, 'numerator': 26, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.14285714285714285, 'numerator': 8, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 70.37037037037037}82820blocked_insufficient_evidencerequired
SMOunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.09197586746769547, 'interquartile_range': 0.12796016494418277, 'maximum': 0.37503303447012404, 'mean': -0.014626427931529379, 'measured_model_count': 56, 'median': -0.016674116349569723, 'minimum': -0.21920401677704732, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03598429747648731, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01294561446721113, 'interquartile_range': 0.03573012833095012, 'maximum': 0.18896716316175619, 'mean': 0.03749273032273328, 'measured_model_count': 56, 'median': 0.025248343352956944, 'minimum': 0.0009806870821544142, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04867574279816125, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 11.11111111111111}2232230blocked_insufficient_evidencerequired
SPENunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.20590850785643827, 'interquartile_range': 0.30629871670536163, 'maximum': 0.2961929358661407, 'mean': -0.07464402855012801, 'measured_model_count': 56, 'median': -0.1069708047403998, 'minimum': -0.5774269486938107, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10039020884892337, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008554559805812224, 'interquartile_range': 0.10390388758026911, 'maximum': 0.6483530280352656, 'mean': 0.08850620961868054, 'measured_model_count': 56, 'median': 0.051609868437919544, 'minimum': 0.001341103131926982, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11245844738608134, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 96.29629629629629}1271270blocked_insufficient_evidencerequired
SPOPunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.10868585464553142, 'interquartile_range': 0.1953317650864464, 'maximum': 0.31868793248113303, 'mean': -0.02062799177610516, 'measured_model_count': 56, 'median': -0.0011139874447977718, 'minimum': -0.5162901003081669, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08664591044091499, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008332047232900763, 'interquartile_range': 0.04870586649525993, 'maximum': 0.5876800902917391, 'mean': 0.058468297685737296, 'measured_model_count': 56, 'median': 0.021659335715944927, 'minimum': 0.0014736174637020138, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.057037913728160694, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 3.7037037037037037}1941940blocked_insufficient_evidencerequired
STAT1research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.023715990107306573, 'interquartile_range': 0.11483236587820499, 'maximum': 0.594601062886091, 'mean': 0.03826927595427404, 'measured_model_count': 56, 'median': 0.03441501730713435, 'minimum': -0.18865251629494253, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09111637577089841, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.007581757478393323, 'interquartile_range': 0.018907350585128907, 'maximum': 0.11007117420691961, 'mean': 0.021312047695286645, 'measured_model_count': 56, 'median': 0.015444040039196624, 'minimum': 0.0002561875140645888, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02648910806352223, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}not availablenot availablenot availableblocked_insufficient_evidencerequired
STAT5Bunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.21254486379258475, 'interquartile_range': 0.1507730685086402, 'maximum': 0.10221524728073916, 'mean': -0.1297580516271845, 'measured_model_count': 56, 'median': -0.11715704066883736, 'minimum': -0.45256549872929824, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.061771795283944546, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.03489943369349236, 'interquartile_range': 0.09272969085043448, 'maximum': 0.4369411155234448, 'mean': 0.09325839392333803, 'measured_model_count': 56, 'median': 0.059652060425314735, 'minimum': 0.00564129311272788, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.12762912454392683, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 3.7037037037037037}2572570blocked_insufficient_evidencerequired
STK11unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.33769402041129626, 'interquartile_range': 0.34553422259709676, 'maximum': 1.3773386060676387, 'mean': -0.1472549078841526, 'measured_model_count': 56, 'median': -0.14109773350213328, 'minimum': -0.8534586542297331, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.007840202185800504, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.01945733984178246, 'interquartile_range': 0.2964351119072127, 'maximum': 0.9205200111570674, 'mean': 0.21506176370357213, 'measured_model_count': 56, 'median': 0.07264424891737002, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.31589245174899516, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.14285714285714285, 'numerator': 8, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.08928571428571429, 'numerator': 5, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 44.44444444444444}49490blocked_insufficient_evidencerequired
STN1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.4779879422685708, 'interquartile_range': 0.29444075349956655, 'maximum': 0.16849346309225044, 'mean': -0.3457827371641288, 'measured_model_count': 56, 'median': -0.3320372797448661, 'minimum': -0.9777832742302645, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.18354718876900422, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.09289156314684381, 'interquartile_range': 0.45956568201046494, 'maximum': 0.9778197824284264, 'mean': 0.35360489820405777, 'measured_model_count': 56, 'median': 0.2679704032719562, 'minimum': 0.002797966808841758, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.5524572451573088, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.30357142857142855, 'numerator': 17, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.14285714285714285, 'numerator': 8, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 37.03703703703704}1991990blocked_insufficient_evidencerequired
SUFUunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.023938544589964868, 'interquartile_range': 0.1774876002492798, 'maximum': 0.95481212338376, 'mean': 0.06462142656096546, 'measured_model_count': 56, 'median': 0.05071099091677807, 'minimum': -0.7061946864814099, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.15354905565931493, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005377839592163817, 'interquartile_range': 0.021656509327421553, 'maximum': 0.811876611301506, 'mean': 0.03797623516616818, 'measured_model_count': 56, 'median': 0.012147568247679989, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02703434891958537, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}1771770blocked_insufficient_evidencerequired
SUZ12unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.4965029253131678, 'interquartile_range': 0.34493944854229963, 'maximum': 0.4677630930028186, 'mean': -0.34131115668653944, 'measured_model_count': 56, 'median': -0.33607475463804537, 'minimum': -1.2517467051124003, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.15156347677086815, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0804547369061895, 'interquartile_range': 0.522462756994033, 'maximum': 0.9941988949339067, 'mean': 0.35415518658327777, 'measured_model_count': 56, 'median': 0.28560992279472086, 'minimum': 0.0008325024643399397, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.6029174939002225, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.3392857142857143, 'numerator': 19, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.08928571428571429, 'numerator': 5, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}2782780blocked_insufficient_evidencerequired
SYKunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.028301337947750776, 'interquartile_range': 0.09846484453277939, 'maximum': 0.2761142482769202, 'mean': 0.024136028244293617, 'measured_model_count': 56, 'median': 0.008529689252564848, 'minimum': -0.19785112063596755, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07016350658502861, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.009531068922012565, 'interquartile_range': 0.01679429075027903, 'maximum': 0.12053995537301158, 'mean': 0.021483934728060494, 'measured_model_count': 56, 'median': 0.018472304540237433, 'minimum': 0.0016419199380332049, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.026325359672291597, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 70.37037037037037}1291290blocked_insufficient_evidencerequired
TAP1research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.16724802560020013, 'interquartile_range': 0.1985094558616541, 'maximum': 0.5470468266686689, 'mean': -0.07939806290217721, 'measured_model_count': 56, 'median': -0.07247945665159533, 'minimum': -0.5733755101579874, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03126143026145397, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.014782179225490823, 'interquartile_range': 0.08211488592426243, 'maximum': 0.6446446410081932, 'mean': 0.08772285017978665, 'measured_model_count': 56, 'median': 0.0447208452197298, 'minimum': 6.830493540377923e-05, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.09689706514975326, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}not availablenot availablenot availableblocked_insufficient_evidencerequired
TAP2research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.11718440590337778, 'interquartile_range': 0.341363350857, 'maximum': 0.48787387730742277, 'mean': 0.046799923839240254, 'measured_model_count': 56, 'median': 0.034986271431895845, 'minimum': -0.4092929272676856, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.2241789449536222, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0019427190737520005, 'interquartile_range': 0.06363806528902216, 'maximum': 0.36713822743055147, 'mean': 0.04596588318721421, 'measured_model_count': 56, 'median': 0.012748389342080056, 'minimum': 0.00018033560046999035, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06558078436277416, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 85.18518518518519}not availablenot availablenot availableblocked_insufficient_evidencerequired
TBL1XR1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.44322955679950454, 'interquartile_range': 0.2668450960778149, 'maximum': 0.9833284356887129, 'mean': -0.3174421086565639, 'measured_model_count': 56, 'median': -0.33277910671051136, 'minimum': -1.9646819675877583, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.17638446072168962, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.08652037502979554, 'interquartile_range': 0.41937699416997204, 'maximum': 1.0, 'mean': 0.3189140280518254, 'measured_model_count': 56, 'median': 0.27129473782400343, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.5058973691997676, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.26785714285714285, 'numerator': 15, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 37.03703703703704}2372370blocked_insufficient_evidencerequired
TBX3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.23573951656616127, 'interquartile_range': 0.20424707807953718, 'maximum': 0.34140535907966685, 'mean': -0.13581506022797174, 'measured_model_count': 56, 'median': -0.144887275560554, 'minimum': -0.5553790334161137, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.031492438486624086, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.025720312146242173, 'interquartile_range': 0.11840113413674436, 'maximum': 0.6616848325855214, 'mean': 0.12232477255665541, 'measured_model_count': 56, 'median': 0.07955915571703014, 'minimum': 0.0008777444154026813, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.14412144628298654, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.07142857142857142, 'numerator': 4, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}90900blocked_insufficient_evidencerequired
TCL1Aunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.11206944388589762, 'interquartile_range': 0.13506523175571503, 'maximum': 0.353208737650306, 'mean': -0.029016807448142428, 'measured_model_count': 56, 'median': -0.000812838632041863, 'minimum': -0.45051063472828873, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.022995787869817392, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.015122906774957338, 'interquartile_range': 0.04261576512491955, 'maximum': 0.40792408921870826, 'mean': 0.05089308425254634, 'measured_model_count': 56, 'median': 0.02026722678410809, 'minimum': 0.0009637063547128886, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05773867189987689, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}2502500blocked_insufficient_evidencerequired
TENT5Cunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.03864097744616059, 'interquartile_range': 0.11511279099291087, 'maximum': 0.2541597207495479, 'mean': 0.022881062803934028, 'measured_model_count': 56, 'median': 0.021952823430253073, 'minimum': -0.23474050442874117, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07647181354675028, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008053275498989303, 'interquartile_range': 0.021966046073802734, 'maximum': 0.13889360325225697, 'mean': 0.0244585667177243, 'measured_model_count': 56, 'median': 0.018800263137722335, 'minimum': 0.00141942221638269, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.030019321572792038, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}2742740blocked_insufficient_evidencerequired
TERTtumor-intrinsic driver / biomarkerantibody / IO: 0.000; biomarker: 0.385; small molecule: 0.513availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.13632697698590185, 'interquartile_range': 0.17256257719257062, 'maximum': 0.31463935418414035, 'mean': -0.053094014995252854, 'measured_model_count': 56, 'median': -0.04819403767771936, 'minimum': -0.39336959009981265, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.036235600206668786, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.013545260600762363, 'interquartile_range': 0.05502605515873926, 'maximum': 0.4509431568440402, 'mean': 0.05984677273308569, 'measured_model_count': 56, 'median': 0.03060298315596087, 'minimum': 0.0014867736856534384, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06857131575950162, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}23241blocked_insufficient_evidencerequired
TET1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06612237325348896, 'interquartile_range': 0.10021823049998557, 'maximum': 0.1271729541137778, 'mean': -0.028190732169697717, 'measured_model_count': 56, 'median': -0.01236085251979058, 'minimum': -0.2695130876604978, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.034095857246496615, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.015077381903148862, 'interquartile_range': 0.022546163524319658, 'maximum': 0.14865571836631888, 'mean': 0.03450340317400059, 'measured_model_count': 56, 'median': 0.024035437041026612, 'minimum': 0.006922954810222002, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03762354542746852, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}1961960blocked_insufficient_evidencerequired
TET2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.020242220098773266, 'interquartile_range': 0.13103610160268922, 'maximum': 0.3622793156577621, 'mean': 0.08204156574215123, 'measured_model_count': 56, 'median': 0.08659371212470038, 'minimum': -0.1670518659975791, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1512783217014625, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005266320111456892, 'interquartile_range': 0.015500246077887905, 'maximum': 0.11891323222815336, 'mean': 0.015839052780095838, 'measured_model_count': 56, 'median': 0.007554157730363114, 'minimum': 0.001314782273029547, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.020766566189344797, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}40400blocked_insufficient_evidencerequired
TFE3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.049611378294050275, 'interquartile_range': 0.12705938681379497, 'maximum': 0.3972896850342244, 'mean': 0.01444431817727483, 'measured_model_count': 56, 'median': -0.010454951169714191, 'minimum': -0.29319215632904333, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.07744800851974469, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008716575061100169, 'interquartile_range': 0.026418028876411564, 'maximum': 0.18711563988246177, 'mean': 0.032323017648411424, 'measured_model_count': 56, 'median': 0.020410044427780348, 'minimum': 0.0002168070410135217, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.035134603937511735, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}2002000blocked_insufficient_evidencerequired
TFEBunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.0555191255330701, 'interquartile_range': 0.11292522004414328, 'maximum': 0.28573843056988407, 'mean': 0.003798524527747693, 'measured_model_count': 56, 'median': 0.0019224156039644225, 'minimum': -0.22832367937072187, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.05740609451107318, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.011692148037405516, 'interquartile_range': 0.01921849388295361, 'maximum': 0.14720540313854205, 'mean': 0.026132526521341532, 'measured_model_count': 56, 'median': 0.01872188394700413, 'minimum': 0.0016405899904093201, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.030910641920359125, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}1881880blocked_insufficient_evidencerequired
TGFB1research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.1175744957723274, 'interquartile_range': 0.14613260242689258, 'maximum': 0.20122114815229164, 'mean': -0.053333625094820716, 'measured_model_count': 56, 'median': -0.0584569922925765, 'minimum': -0.33194533256770453, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02855810665456519, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.013271787489163883, 'interquartile_range': 0.05501703382036138, 'maximum': 0.29440262801615275, 'mean': 0.0509541191786031, 'measured_model_count': 56, 'median': 0.03879322257892474, 'minimum': 0.004071154988135978, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06828882130952527, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 40.74074074074074}not availablenot availablenot availableblocked_insufficient_evidencerequired
TGFBR1research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.11823496925689045, 'interquartile_range': 0.1815436279172879, 'maximum': 0.43900246007390836, 'mean': -0.06367073288882538, 'measured_model_count': 56, 'median': -0.04561856834087192, 'minimum': -1.1646984150993804, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06330865866039743, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.009869685591532288, 'interquartile_range': 0.05375446023576694, 'maximum': 0.9941992212349525, 'mean': 0.0798662849461864, 'measured_model_count': 56, 'median': 0.03221306181112013, 'minimum': 0.0002895613022257384, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06362414582729922, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.03571428571428571, 'numerator': 2, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 11.11111111111111}not availablenot availablenot availableblocked_insufficient_evidencerequired
TIGITresearch-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.09649098266140216, 'interquartile_range': 0.14024504818016426, 'maximum': 0.20955328804252174, 'mean': -0.038102640455839755, 'measured_model_count': 56, 'median': -0.026380581032389563, 'minimum': -0.31063674659862406, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.043754065518762084, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.014662390053882784, 'interquartile_range': 0.035014807249186236, 'maximum': 0.22730028300055188, 'mean': 0.04368399569486412, 'measured_model_count': 56, 'median': 0.029299535174605706, 'minimum': 0.004326948526831013, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.04967719730306902, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 7.407407407407407}not availablenot availablenot availableblocked_insufficient_evidencerequired
TMEM127unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.37160855924898195, 'interquartile_range': 0.23945586380532383, 'maximum': 0.04819261286756693, 'mean': -0.2743793036390408, 'measured_model_count': 56, 'median': -0.2801840245311775, 'minimum': -0.7302462912517111, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.13215269544365812, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.07290625944096693, 'interquartile_range': 0.35628977617921886, 'maximum': 0.8298694277716979, 'mean': 0.2563707669744083, 'measured_model_count': 56, 'median': 0.1948213468608736, 'minimum': 0.006835996438229038, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.4291960356201858, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.17857142857142858, 'numerator': 10, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}2382380blocked_insufficient_evidencerequired
TNFRSF17unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.10457536925669791, 'interquartile_range': 0.07142883580734052, 'maximum': 0.10918749680547649, 'mean': -0.06992867394566103, 'measured_model_count': 56, 'median': -0.07182926242556906, 'minimum': -0.24504065716705284, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.0331465334493574, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.023074013879230557, 'interquartile_range': 0.0433904521116308, 'maximum': 0.1443957018357807, 'mean': 0.04704715320781859, 'measured_model_count': 56, 'median': 0.04088511534774647, 'minimum': 0.0063179500583258425, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.06646446599086135, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}2942940blocked_insufficient_evidencerequired
TNFRSF18research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.07992287378746069, 'interquartile_range': 0.16347160736788924, 'maximum': 0.32511428764823874, 'mean': 0.005618184042927659, 'measured_model_count': 56, 'median': 0.0031678861143592326, 'minimum': -0.21018912008582508, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.08354873358042854, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0081397024736693, 'interquartile_range': 0.031395612021018315, 'maximum': 0.15023873693250508, 'mean': 0.03150136361917189, 'measured_model_count': 56, 'median': 0.020690473212946793, 'minimum': 0.0011876348486895474, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.03953531449468761, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 51.851851851851855}not availablenot availablenot availableblocked_insufficient_evidencerequired
TP53tumor-intrinsic driver / poor direct therapeutic targetantibody / IO: 0.000; biomarker: 0.111; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.2682694657614673, 'interquartile_range': 0.9489021294915423, 'maximum': 2.138262318199002, 'mean': 0.8412020305059892, 'measured_model_count': 56, 'median': 0.8202592324433257, 'minimum': -0.056749573342901705, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 1.2171715952530096, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0, 'interquartile_range': 0.0022901272198506146, 'maximum': 0.0445887680510194, 'mean': 0.0038902041225716394, 'measured_model_count': 56, 'median': 2.371112152923413e-07, 'minimum': 0.0, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.0022901272198506146, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 14.814814814814815}27270blocked_insufficient_evidencerequired
TP63unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.03646717175085289, 'interquartile_range': 0.15602502361875212, 'maximum': 0.26270167319502213, 'mean': 0.02883004458571577, 'measured_model_count': 56, 'median': 0.06069628975320457, 'minimum': -1.13379244109757, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11955785186789922, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0056286828889941356, 'interquartile_range': 0.02006209381979438, 'maximum': 0.996906606222216, 'mean': 0.043125430114191884, 'measured_model_count': 56, 'median': 0.012420727182457592, 'minimum': 0.0009590426965118661, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.025690776708788516, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 7.407407407407407}77770blocked_insufficient_evidencerequired
TRAF7unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.2406753121206499, 'interquartile_range': 0.24695097977219208, 'maximum': 0.3790647504468809, 'mean': -0.12737792628681918, 'measured_model_count': 56, 'median': -0.13475684387968312, 'minimum': -0.610764948450708, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.006275667651542173, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.015945069753414774, 'interquartile_range': 0.16421762374968268, 'maximum': 0.8396091166189825, 'mean': 0.14316015942576582, 'measured_model_count': 56, 'median': 0.06819388689452299, 'minimum': 0.0004979956302897705, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.18016269350309747, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.017857142857142856, 'numerator': 1, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}2012010blocked_insufficient_evidencerequired
TREM2research-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.0443206760018002, 'interquartile_range': 0.17039455367149228, 'maximum': 0.21602878466395123, 'mean': 0.03343137007746267, 'measured_model_count': 56, 'median': 0.0323268773346124, 'minimum': -0.2109254937822177, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.12607387766969208, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.006309502008753942, 'interquartile_range': 0.021860319009730143, 'maximum': 0.1244326991346321, 'mean': 0.023524014701307532, 'measured_model_count': 56, 'median': 0.014501080563188398, 'minimum': 0.0027434337345621554, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.028169821018484087, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 29.62962962962963}not availablenot availablenot availableblocked_insufficient_evidencerequired
TRRAPunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -1.5213804808497076, 'interquartile_range': 0.433843564982187, 'maximum': -0.6227212037899151, 'mean': -1.3167452715650814, 'measured_model_count': 56, 'median': -1.2709263893882927, 'minimum': -2.0119956971319883, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.0875369158675205, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9777798803483504, 'interquartile_range': 0.022107860279671154, 'maximum': 1.0, 'mean': 0.9787434420409532, 'measured_model_count': 56, 'median': 0.9937763894442102, 'minimum': 0.7036541177148524, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.9998877406280215, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.9821428571428571, 'numerator': 55, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 14.814814814814815}53530blocked_insufficient_evidencerequired
TSC1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.3016134218269153, 'interquartile_range': 0.4540279484323619, 'maximum': 0.7560681310029174, 'mean': -0.05250989686051594, 'measured_model_count': 56, 'median': -0.06139145221472085, 'minimum': -0.9355770319117922, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.15241452660544658, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005114952756170495, 'interquartile_range': 0.2066037360107815, 'maximum': 0.9475024496853242, 'mean': 0.17255563233916282, 'measured_model_count': 56, 'median': 0.036748465525459184, 'minimum': 1.463315655819427e-06, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.211718688766952, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.16071428571428573, 'numerator': 9, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.07142857142857142, 'numerator': 4, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}89890blocked_insufficient_evidencerequired
TSC2unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.48178270738847034, 'interquartile_range': 0.6094882759655369, 'maximum': 0.7960520265311837, 'mean': -0.17905815724769766, 'measured_model_count': 56, 'median': -0.19336827495763223, 'minimum': -1.1623050845253171, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.12770556857706658, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005510173816997374, 'interquartile_range': 0.529793110570655, 'maximum': 0.9825524213104214, 'mean': 0.29430495118778816, 'measured_model_count': 56, 'median': 0.11191983755845783, 'minimum': 1.2968376951898574e-06, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.5353032843876524, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.2857142857142857, 'numerator': 16, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.17857142857142858, 'numerator': 10, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 74.07407407407408}1231230blocked_insufficient_evidencerequired
TYRunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.021924422131844194, 'interquartile_range': 0.13036313008930414, 'maximum': 0.22068382718892765, 'mean': 0.03780463155728201, 'measured_model_count': 56, 'median': 0.039761465584603584, 'minimum': -0.16487265242462967, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10843870795745994, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.00790018032460166, 'interquartile_range': 0.016458370447756117, 'maximum': 0.12554764195984902, 'mean': 0.019476503614389358, 'measured_model_count': 56, 'median': 0.013953535396493747, 'minimum': 0.00202859216667188, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.024358550772357775, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}95950blocked_insufficient_evidencerequired
TYRP1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.10410635283115738, 'interquartile_range': 0.15932084168058958, 'maximum': 0.23571165368114302, 'mean': -0.014436755487099202, 'measured_model_count': 56, 'median': -0.00467660277186081, 'minimum': -0.285963111504857, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.055214488849432204, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.011364526712981583, 'interquartile_range': 0.03289509253254978, 'maximum': 0.19098949806792395, 'mean': 0.03524535298675518, 'measured_model_count': 56, 'median': 0.02110733051641108, 'minimum': 0.0022871834283302536, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.044259619245531366, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 33.333333333333336}2612610blocked_insufficient_evidencerequired
U2AF1unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -2.2850637997149565, 'interquartile_range': 0.5402155616805826, 'maximum': -1.3937878711893064, 'mean': -2.003858590452997, 'measured_model_count': 56, 'median': -1.9445118925982248, 'minimum': -2.7346918251771903, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -1.744848238034374, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.9999988989874314, 'interquartile_range': 1.1010125685606553e-06, 'maximum': 1.0, 'mean': 0.9997710798620709, 'measured_model_count': 56, 'median': 1.0, 'minimum': 0.9927101937690168, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 1.0, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 1.0, 'numerator': 56, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 62.96296296296296}2052050blocked_insufficient_evidencerequired
UBR5unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.7334089926493355, 'interquartile_range': 0.45556632888926424, 'maximum': 0.3415255034442515, 'mean': -0.4921227769355524, 'measured_model_count': 56, 'median': -0.4989999347581911, 'minimum': -1.5684017610891217, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.2778426637600712, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.1845620071921631, 'interquartile_range': 0.691845206624218, 'maximum': 0.9982874212452946, 'mean': 0.5183145222853321, 'measured_model_count': 56, 'median': 0.5029036917489552, 'minimum': 0.0005451520676103827, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.8764072138163811, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.5, 'numerator': 28, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.3392857142857143, 'numerator': 19, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 55.55555555555556}80800blocked_insufficient_evidencerequired
USP6unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.21946144443193774, 'interquartile_range': 0.1836133575142457, 'maximum': 0.09091474588958395, 'mean': -0.13462308545365242, 'measured_model_count': 56, 'median': -0.14083080016013066, 'minimum': -0.4133470078215248, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.035848086917692035, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.03158062220146937, 'interquartile_range': 0.10676534490012221, 'maximum': 0.38024577182219427, 'mean': 0.09450311024282725, 'measured_model_count': 56, 'median': 0.07325111118993291, 'minimum': 0.007333353368402815, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.13834596710159158, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 18.51851851851852}1441440blocked_insufficient_evidencerequired
WASunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.0081124743479323, 'interquartile_range': 0.11365188739509363, 'maximum': 0.3717879401122316, 'mean': 0.05648455771783551, 'measured_model_count': 56, 'median': 0.04235581384965959, 'minimum': -0.20632925372342162, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.10553941304716133, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.005830434234521276, 'interquartile_range': 0.016806642972809215, 'maximum': 0.10452119793228946, 'mean': 0.01779230363124099, 'measured_model_count': 56, 'median': 0.013549175642979312, 'minimum': 0.0005349464613209364, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.02263707720733049, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}2242240blocked_insufficient_evidencerequired
WNT5Aresearch-preview discovery identitynot in productive baselineavailablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.013475623132929507, 'interquartile_range': 0.12987435128430827, 'maximum': 0.3150759319494393, 'mean': 0.053669849425937624, 'measured_model_count': 56, 'median': 0.058772730317348545, 'minimum': -0.24052616114158287, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.11639872815137876, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.0056110526655506286, 'interquartile_range': 0.019919012256410858, 'maximum': 0.11933478473212114, 'mean': 0.01871307104063123, 'measured_model_count': 56, 'median': 0.01236916749744851, 'minimum': 0.0021382880799880946, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.025530064921961488, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 22.22222222222222}not availablenot availablenot availableblocked_insufficient_evidencerequired
WRNunclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.22747322797558123, 'interquartile_range': 0.18738191531852705, 'maximum': 0.1869225639090439, 'mean': -0.1472173168641097, 'measured_model_count': 56, 'median': -0.1359431135451314, 'minimum': -0.6702924398334323, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': -0.040091312657054186, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.029615962721536174, 'interquartile_range': 0.12028353472893429, 'maximum': 0.7328436063532079, 'mean': 0.1242273410614679, 'measured_model_count': 56, 'median': 0.06804582138278752, 'minimum': 0.005152580595719504, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.14989949745047046, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.05357142857142857, 'numerator': 3, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}61610blocked_insufficient_evidencerequired
ZBTB16unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.009823719243372997, 'interquartile_range': 0.16578865722223748, 'maximum': 0.41204654436023724, 'mean': 0.07249807663874529, 'measured_model_count': 56, 'median': 0.07415276241873536, 'minimum': -0.30348607293974983, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.1559649379788645, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.004890986360055396, 'interquartile_range': 0.018207855814234508, 'maximum': 0.185233568494693, 'mean': 0.019665096749805024, 'measured_model_count': 56, 'median': 0.010731332181391433, 'minimum': 0.00039811689207587927, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.023098842174289903, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 59.25925925925926}2072070blocked_insufficient_evidencerequired
ZFHX3unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': -0.06146208289047472, 'interquartile_range': 0.14758793421665212, 'maximum': 0.2881461102807952, 'mean': 0.007927014410996538, 'measured_model_count': 55, 'median': 0.007593842404380845, 'minimum': -0.33029884415193866, 'missing_fraction': 0.017857142857142856, 'missing_model_count': 1, 'third_quartile': 0.08612585132617741, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.008564060822250814, 'interquartile_range': 0.02700284675819572, 'maximum': 0.23484293062520295, 'mean': 0.03819658296592888, 'measured_model_count': 55, 'median': 0.019485636278314837, 'minimum': 0.0010067610165416245, 'missing_fraction': 0.017857142857142856, 'missing_model_count': 1, 'third_quartile': 0.03556690758044653, 'threshold_fractions': (mappingproxy({'denominator': 55, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 55, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 77.77777777777777}2102100blocked_insufficient_evidencerequired
ZNF331unclear / low-confidence candidateantibody / IO: 0.000; biomarker: 0.000; small molecule: 0.000availablesufficient_complete_coverage562098{'available': True, 'first_quartile': 0.1254636788972895, 'interquartile_range': 0.14498040321724526, 'maximum': 0.7050101742014865, 'mean': 0.19150820508534952, 'measured_model_count': 56, 'median': 0.19280092244168862, 'minimum': -0.15201787565274216, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.27044408211453475, 'threshold_fractions': (), 'total_model_count': 56}{'available': True, 'first_quartile': 0.001704372331237138, 'interquartile_range': 0.005424707330500494, 'maximum': 0.10954958289983124, 'mean': 0.009442167813529304, 'measured_model_count': 56, 'median': 0.003587808287988493, 'minimum': 1.0645838207346946e-05, 'missing_fraction': 0.0, 'missing_model_count': 0, 'third_quartile': 0.007129079661737632, 'threshold_fractions': (mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.5}), mappingproxy({'denominator': 56, 'fraction': 0.0, 'numerator': 0, 'threshold': 0.8})), 'total_model_count': 56}{'available': True, 'direction': '100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.', 'eligible_lineage_count': 28, 'value': 81.48148148148148}2462460blocked_insufficient_evidencerequired
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/report_manifest.json b/examples/html_reports/depmap_26q1/report_manifest.json new file mode 100644 index 0000000..2468f86 --- /dev/null +++ b/examples/html_reports/depmap_26q1/report_manifest.json @@ -0,0 +1 @@ +{"discovery_count": 331, "human_review_required": true, "productive_baseline_count": 300} diff --git a/examples/html_reports/depmap_26q1/targets/ABL1.html b/examples/html_reports/depmap_26q1/targets/ABL1.html new file mode 100644 index 0000000..c20aaf3 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ABL1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ABL1 + + + + +
+ +
+

Target hypothesis report: ABL1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ABL1
+
+
+
Target name
+
ABL proto-oncogene 1, non-receptor tyrosine kinase
+
+
+
Open Targets melanoma score
+
0.459
+
+
+
+
Open Targets baseline rank
+
298
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.05206080637452079,"interquartile_range":0.13179040761692934,"maximum":0.28090126723303777,"mean":0.0004447170999685991,"measured_model_count":56,"median":0.016656009569385857,"minimum":-0.39424595195096673,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07972960124240855,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008384728233917674,"interquartile_range":0.028339679307337506,"maximum":0.3238668973345923,"mean":0.038111215003978426,"measured_model_count":56,"median":0.018554196815730083,"minimum":0.0019480816982328645,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03672440754125518,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005268596799601434,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.011589403973509934,"pan_cancer_fraction":0.011589403973509934,"threshold":0.5},{"context_fraction":0.0,"difference":-0.009105960264900662,"pan_cancer_fraction":0.009105960264900662,"threshold":0.8}],"gene_effect_mean":0.028025674336998208,"gene_effect_median":0.029341478281553125},"dependency_probability_context_minus_non_context_median":-0.0058653162345687,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.012152777777777778,"non_context_fraction":0.012152777777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.009548611111111112,"non_context_fraction":0.009548611111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.02938803350615787,"gene_effect_context_minus_non_context_median":0.031052462802977448}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 298
+- **Dependency-aware candidate rank:** 298
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_3dfe0aaf44dae880f7a9069d3811f36a4cf75ed3c3bc338e1e85acb68fc2aa5b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ABL1|entrez:25`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
298not prioritized0
Resistance biomarker0.000
298not prioritized0
Tumor-intrinsic / small molecule0.000
298not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.459)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ABL1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ABL1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ACKR3.html b/examples/html_reports/depmap_26q1/targets/ACKR3.html new file mode 100644 index 0000000..8ab54c2 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ACKR3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ACKR3 + + + + +
+ +
+

Target hypothesis report: ACKR3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ACKR3
+
+
+
Target name
+
atypical chemokine receptor 3
+
+
+
Open Targets melanoma score
+
0.518
+
+
+
+
Open Targets baseline rank
+
220
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.04688567353100497,"interquartile_range":0.17672355876386034,"maximum":0.3406804666190274,"mean":0.044219612203129,"measured_model_count":56,"median":0.051971504824438984,"minimum":-0.248858520923774,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12983788523285536,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.00480346215672851,"interquartile_range":0.022247043897867892,"maximum":0.1649058271995307,"mean":0.023943900342633655,"measured_model_count":56,"median":0.012531187649904931,"minimum":0.0007241920367250855,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.027050506054596402,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0007630456786245857,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.009176056073463577,"gene_effect_median":0.0004076142221738424},"dependency_probability_context_minus_non_context_median":-0.0007630456786245857,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.009622114354812535,"gene_effect_context_minus_non_context_median":0.0005160131333996135}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 222
+- **Dependency-aware candidate rank:** 222
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_6da09dd6bfd55bdc7914f8c87aede8f5fd2319a5758d27ff90418fe816e4b80e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ACKR3|entrez:57007`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
222not prioritized-2
Resistance biomarker0.000
222not prioritized-2
Tumor-intrinsic / small molecule0.000
222not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.518)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ACKR3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ACKR3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ACVR1B.html b/examples/html_reports/depmap_26q1/targets/ACVR1B.html new file mode 100644 index 0000000..5adf506 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ACVR1B.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ACVR1B + + + + +
+ +
+

Target hypothesis report: ACVR1B

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ACVR1B
+
+
+
Target name
+
activin A receptor type 1B
+
+
+
Open Targets melanoma score
+
0.529
+
+
+
+
Open Targets baseline rank
+
188
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.14711929218671402,"interquartile_range":0.12432204341482385,"maximum":0.3375441114825275,"mean":-0.07998009592778019,"measured_model_count":56,"median":-0.08515877044475642,"minimum":-0.3764694607361463,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.022797248771890172,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.025659946006875323,"interquartile_range":0.046932751916033716,"maximum":0.3513129074264774,"mean":0.06341236180240215,"measured_model_count":56,"median":0.04447697969775254,"minimum":0.0007005068208089658,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07259269792290904,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003451019779143062,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.018211920529801324,"pan_cancer_fraction":0.018211920529801324,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.8}],"gene_effect_mean":0.01932084102200554,"gene_effect_median":0.007571133145735126},"dependency_probability_context_minus_non_context_median":-0.00363455842123752,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.019097222222222224,"non_context_fraction":0.019097222222222224,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.020260048571686465,"gene_effect_context_minus_non_context_median":0.008340856057287335}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 190
+- **Dependency-aware candidate rank:** 190
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_7fef00de913eb60dc7d7091f97bc92aca7cc60b24d6d5c58bbdee2f7b315d6dd`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ACVR1B|entrez:91`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
190not prioritized-2
Resistance biomarker0.000
191not prioritized-3
Tumor-intrinsic / small molecule0.000
190not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.529)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ACVR1B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ACVR1B in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/AFDN.html b/examples/html_reports/depmap_26q1/targets/AFDN.html new file mode 100644 index 0000000..b03e915 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/AFDN.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: AFDN + + + + +
+ +
+

Target hypothesis report: AFDN

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
AFDN
+
+
+
Target name
+
afadin, adherens junction formation factor
+
+
+
Open Targets melanoma score
+
0.554
+
+
+
+
Open Targets baseline rank
+
145
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.18632748263487175,"interquartile_range":0.15100015383667187,"maximum":0.194234342399614,"mean":-0.10401314871474741,"measured_model_count":56,"median":-0.09824333463123369,"minimum":-0.3508544694256321,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.03532732879819988,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.02930714986928311,"interquartile_range":0.08549755078471634,"maximum":0.3273106965579132,"mean":0.08008016796975555,"measured_model_count":56,"median":0.04490595607597833,"minimum":0.002530139433360224,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11480470065399945,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.010186756173332173,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03228476821192053,"pan_cancer_fraction":0.03228476821192053,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.8}],"gene_effect_mean":-0.028113817942100536,"gene_effect_median":-0.041421613596168916},"dependency_probability_context_minus_non_context_median":0.01161967098779828,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.033854166666666664,"non_context_fraction":0.033854166666666664,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.029480461869841587,"gene_effect_context_minus_non_context_median":-0.04789679998052801}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 147
+- **Dependency-aware candidate rank:** 147
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a77d9c1a553179212884e60516135e05fa1ea0ca72afbc38003b213684f13da6`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:AFDN|entrez:4301`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
147not prioritized-2
Resistance biomarker0.000
148not prioritized-3
Tumor-intrinsic / small molecule0.000
147not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.554)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: AFDN lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for AFDN in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/AFF4.html b/examples/html_reports/depmap_26q1/targets/AFF4.html new file mode 100644 index 0000000..d4f15e1 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/AFF4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: AFF4 + + + + +
+ +
+

Target hypothesis report: AFF4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
AFF4
+
+
+
Target name
+
ALF transcription elongation factor 4
+
+
+
Open Targets melanoma score
+
0.522
+
+
+
+
Open Targets baseline rank
+
201
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.13292375310772922,"interquartile_range":0.18416980660063442,"maximum":0.38654768840037734,"mean":-0.039908295314705654,"measured_model_count":56,"median":-0.05939864471942567,"minimum":-0.34030817268214186,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0512460534929052,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01317409187949549,"interquartile_range":0.05043407141525695,"maximum":0.3328242072309353,"mean":0.05984196045726369,"measured_model_count":56,"median":0.03392475612734393,"minimum":0.00032369241265077216,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06360816329475244,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0007668804580707456,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.016068698734252658,"gene_effect_median":-0.010437559937850657},"dependency_probability_context_minus_non_context_median":-0.0007668804580707456,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01684981603383439,"gene_effect_context_minus_non_context_median":-0.010932048141568743}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 203
+- **Dependency-aware candidate rank:** 203
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_daca383d448a59953d52c8cd6fa98117e94d36e01db9b7f640f5167cc4203d27`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:AFF4|entrez:27125`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
203not prioritized-2
Resistance biomarker0.000
203not prioritized-2
Tumor-intrinsic / small molecule0.000
203not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.522)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: AFF4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for AFF4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/AKT1.html b/examples/html_reports/depmap_26q1/targets/AKT1.html new file mode 100644 index 0000000..98042f2 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/AKT1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: AKT1 + + + + +
+ +
+

Target hypothesis report: AKT1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
AKT1
+
+
+
Target name
+
AKT serine/threonine kinase 1
+
+
+
Open Targets melanoma score
+
0.603
+
+
+
+
Open Targets baseline rank
+
65
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.0696113940207029,"interquartile_range":0.13322895560601336,"maximum":0.34970543918655067,"mean":-0.009742474845817481,"measured_model_count":56,"median":0.0046377124629188235,"minimum":-0.38907832484150034,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06361756158531046,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.010254024576999815,"interquartile_range":0.02635393549780505,"maximum":0.44844945288476895,"mean":0.04874750692925877,"measured_model_count":56,"median":0.020344346257189568,"minimum":0.00037661393714791936,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.036607960074804866,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.014890288201914133,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04304635761589404,"pan_cancer_fraction":0.04304635761589404,"threshold":0.5},{"context_fraction":0.0,"difference":-0.012417218543046357,"pan_cancer_fraction":0.012417218543046357,"threshold":0.8}],"gene_effect_mean":0.07683367026191354,"gene_effect_median":0.061701304441597535},"dependency_probability_context_minus_non_context_median":-0.016664789319484452,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04513888888888889,"non_context_fraction":0.04513888888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013020833333333334,"non_context_fraction":0.013020833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08056864034408984,"gene_effect_context_minus_non_context_median":0.06642333397803044}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 69
+- **Dependency-aware candidate rank:** 69
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_c524a3ba63651f0e15c4f8215dd50116139df5323fdc0348c5e448a92f93249e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:AKT1|entrez:207`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
69not prioritized-4
Resistance biomarker0.000
71not prioritized-6
Tumor-intrinsic / small molecule0.000
69not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.603)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: AKT1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for AKT1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/AKT2.html b/examples/html_reports/depmap_26q1/targets/AKT2.html new file mode 100644 index 0000000..8635643 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/AKT2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: AKT2 + + + + +
+ +
+

Target hypothesis report: AKT2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
AKT2
+
+
+
Target name
+
AKT serine/threonine kinase 2
+
+
+
Open Targets melanoma score
+
0.585
+
+
+
+
Open Targets baseline rank
+
94
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.10698692296778596,"interquartile_range":0.18636044860159254,"maximum":0.2588885738209947,"mean":-0.017972665153818613,"measured_model_count":56,"median":-0.007401318928414405,"minimum":-0.38332530305186063,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07937352563380658,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008499792764108715,"interquartile_range":0.05882776154012727,"maximum":0.32445036409429234,"mean":0.043810063779630086,"measured_model_count":56,"median":0.020804451087822785,"minimum":0.0014235690597476042,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06732755430423598,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01610885761667067,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03145695364238411,"pan_cancer_fraction":0.03145695364238411,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013245033112582781,"pan_cancer_fraction":0.013245033112582781,"threshold":0.8}],"gene_effect_mean":0.05533570749708823,"gene_effect_median":0.052685305081329424},"dependency_probability_context_minus_non_context_median":-0.016317549937989013,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03298611111111111,"non_context_fraction":0.03298611111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013888888888888888,"non_context_fraction":0.013888888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05802563772264094,"gene_effect_context_minus_non_context_median":0.05442605404088425}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 97
+- **Dependency-aware candidate rank:** 97
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_f1e3d17bbf7af67106ed5461365f64d2ff4f926ae9bf8f4f04336a5df09f4dd0`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:AKT2|entrez:208`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
97not prioritized-3
Resistance biomarker0.000
98not prioritized-4
Tumor-intrinsic / small molecule0.000
97not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.585)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: AKT2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for AKT2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ALK.html b/examples/html_reports/depmap_26q1/targets/ALK.html new file mode 100644 index 0000000..82afc9d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ALK.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ALK + + + + +
+ +
+

Target hypothesis report: ALK

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ALK
+
+
+
Target name
+
ALK receptor tyrosine kinase
+
+
+
Open Targets melanoma score
+
0.492
+
+
+
+
Open Targets baseline rank
+
261
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.1391055879500493,"interquartile_range":0.1173851257210915,"maximum":0.24723686687943555,"mean":-0.08817782520037898,"measured_model_count":56,"median":-0.09243115642296142,"minimum":-0.414971861038247,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0217204622289578,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.023770154172617915,"interquartile_range":0.06796426553020232,"maximum":0.3791912417275072,"mean":0.0725077327529867,"measured_model_count":56,"median":0.0461958733533957,"minimum":0.00275245343127817,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09173441970282024,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0006553669293226511,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.8}],"gene_effect_mean":-0.0003571287333825335,"gene_effect_median":-0.008402991678772107},"dependency_probability_context_minus_non_context_median":0.0006553669293226511,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0003744891579219589,"gene_effect_context_minus_non_context_median":-0.008729152984485275}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 263
+- **Dependency-aware candidate rank:** 263
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_c898e5032b38a6b5a605f5041eaa96f4cba4b017f3f221903bd4a8bfa1e0a5da`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ALK|entrez:238`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
263not prioritized-2
Resistance biomarker0.000
263not prioritized-2
Tumor-intrinsic / small molecule0.000
263not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.492)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ALK lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ALK in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/AMER1.html b/examples/html_reports/depmap_26q1/targets/AMER1.html new file mode 100644 index 0000000..87d5fb1 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/AMER1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: AMER1 + + + + +
+ +
+

Target hypothesis report: AMER1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
AMER1
+
+
+
Target name
+
APC membrane recruitment protein 1
+
+
+
Open Targets melanoma score
+
0.545
+
+
+
+
Open Targets baseline rank
+
170
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.009345387043821714,"interquartile_range":0.12788514596415662,"maximum":0.4383787682074304,"mean":0.07528086605188714,"measured_model_count":56,"median":0.08276667476476582,"minimum":-0.19040979327961766,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.13723053300797833,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005306404228444668,"interquartile_range":0.01706158235075618,"maximum":0.149077231539901,"mean":0.018513075756905417,"measured_model_count":56,"median":0.009990647380253341,"minimum":0.00021627471873552294,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.022367986579200846,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0025894206152058258,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.014413422384766096,"gene_effect_median":0.02671472109252339},"dependency_probability_context_minus_non_context_median":-0.002687022545325067,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.015114074861803335,"gene_effect_context_minus_non_context_median":0.027051252928677064}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 172
+- **Dependency-aware candidate rank:** 172
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a7f7490e823486f66688a444df162f849e16fc7bd434b0ef2d4016376f0c6cdf`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:AMER1|entrez:139285`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
172not prioritized-2
Resistance biomarker0.000
173not prioritized-3
Tumor-intrinsic / small molecule0.000
172not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.545)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: AMER1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for AMER1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/APC.html b/examples/html_reports/depmap_26q1/targets/APC.html new file mode 100644 index 0000000..52f14a1 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/APC.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: APC + + + + +
+ +
+

Target hypothesis report: APC

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
APC
+
+
+
Target name
+
APC regulator of Wnt signaling pathway
+
+
+
Open Targets melanoma score
+
0.510
+
+
+
+
Open Targets baseline rank
+
239
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.5859774841020371,"interquartile_range":0.38179195205040023,"maximum":0.28455865946694375,"mean":-0.35785147041774285,"measured_model_count":56,"median":-0.3380178346085523,"minimum":-1.1406373050762526,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.20418553205163686,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.11658056622142303,"interquartile_range":0.5927857513786858,"maximum":0.9936482374577086,"mean":0.38426650867741774,"measured_model_count":56,"median":0.27761769575678924,"minimum":0.0013598374302337113,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.7093663176001088,"threshold_fractions":[{"denominator":56,"fraction":0.3392857142857143,"numerator":19,"threshold":0.5},{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.037316397101886556,"dependency_probability_threshold_fractions":[{"context_fraction":0.3392857142857143,"difference":0.02306054872280039,"pan_cancer_fraction":0.3162251655629139,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":0.05274361400189215,"pan_cancer_fraction":0.12582781456953643,"threshold":0.8}],"gene_effect_mean":0.0028794144866692295,"gene_effect_median":0.019559681208588586},"dependency_probability_context_minus_non_context_median":-0.03998799613543175,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.3392857142857143,"difference":0.024181547619047616,"non_context_fraction":0.3151041666666667,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":0.05530753968253968,"non_context_fraction":0.1232638888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.003019386024215698,"gene_effect_context_minus_non_context_median":0.02054380019079738}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 241
+- **Dependency-aware candidate rank:** 241
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_22a18cf431d07d3aa1e8c8953221792abd3f094e82d1e0fd675602c7277a5d06`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:APC|entrez:324`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
241not prioritized-2
Resistance biomarker0.000
241not prioritized-2
Tumor-intrinsic / small molecule0.000
241not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.510)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: APC lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for APC in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/APOBEC3B.html b/examples/html_reports/depmap_26q1/targets/APOBEC3B.html new file mode 100644 index 0000000..1523743 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/APOBEC3B.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: APOBEC3B + + + + +
+ +
+

Target hypothesis report: APOBEC3B

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
APOBEC3B
+
+
+
Target name
+
apolipoprotein B mRNA editing enzyme catalytic subunit 3B
+
+
+
Open Targets melanoma score
+
0.484
+
+
+
+
Open Targets baseline rank
+
268
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.09606841814979647,"interquartile_range":0.23515113567892895,"maximum":0.4400708139139492,"mean":0.026699711051649557,"measured_model_count":56,"median":0.005793906262137797,"minimum":-0.4283263401162755,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.13908271752913248,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005510925052745797,"interquartile_range":0.041485165212828315,"maximum":0.3365293082591688,"mean":0.0420897143545745,"measured_model_count":56,"median":0.019179227319746587,"minimum":0.00020440713068760097,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04699609026557411,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0018136909695100657,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.021622478459315107,"gene_effect_median":0.0003500566170188098},"dependency_probability_context_minus_non_context_median":-0.0019574494229148386,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.022673571162198494,"gene_effect_context_minus_non_context_median":0.0003500566170188098}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 269
+- **Dependency-aware candidate rank:** 269
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ca98257f2c856960f4df260901e6f315d270b0b86f4f932559dff06ccb40ad7b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:APOBEC3B|entrez:9582`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
269not prioritized-1
Resistance biomarker0.000
269not prioritized-1
Tumor-intrinsic / small molecule0.000
269not prioritized-1
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.484)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: APOBEC3B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for APOBEC3B in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/AR.html b/examples/html_reports/depmap_26q1/targets/AR.html new file mode 100644 index 0000000..6dfd24d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/AR.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: AR + + + + +
+ +
+

Target hypothesis report: AR

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
AR
+
+
+
Target name
+
androgen receptor
+
+
+
Open Targets melanoma score
+
0.581
+
+
+
+
Open Targets baseline rank
+
100
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.041097870345206546,"interquartile_range":0.1546972619994098,"maximum":0.4537651498544541,"mean":0.09982159752496085,"measured_model_count":56,"median":0.09918225274948897,"minimum":-0.28630325474580987,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.19579513234461635,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.004300171032795553,"interquartile_range":0.012979205717451568,"maximum":0.1346611349824717,"mean":0.01616543771498364,"measured_model_count":56,"median":0.007519158470395323,"minimum":0.00024636522631291607,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.01727937675024712,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0013001356911354744,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.0044244188818144264,"gene_effect_median":-0.000327980058559052},"dependency_probability_context_minus_non_context_median":-0.0014093923703961363,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0046394947996803715,"gene_effect_context_minus_non_context_median":-0.00040665467292552715}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 103
+- **Dependency-aware candidate rank:** 103
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_63cf6c20ea0c2587b1f1cb3617869b24003624ab7142c9d915bf56baad985f33`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:AR|entrez:367`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
103not prioritized-3
Resistance biomarker0.000
104not prioritized-4
Tumor-intrinsic / small molecule0.000
103not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.581)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: AR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for AR in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ARG1.html b/examples/html_reports/depmap_26q1/targets/ARG1.html new file mode 100644 index 0000000..9e46883 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ARG1.html @@ -0,0 +1,70 @@ +ARG1 — DepMap research preview

ARG1

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.01952750081956353,"interquartile_range":0.15704048446148916,"maximum":0.4503933085737245,"mean":0.11178133015127081,"measured_model_count":56,"median":0.11451918046801807,"minimum":-0.188393571489023,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1765679852810527,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.002940917113951669,"interquartile_range":0.013001543968601731,"maximum":0.14703040964480976,"mean":0.01426250886872838,"measured_model_count":56,"median":0.006837278753817717,"minimum":0.0007338381832860604,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0159424610825534,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0018869795464472481,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.04646815350637501,"gene_effect_median":-0.04360907833315336},"dependency_probability_context_minus_non_context_median":0.0019344483310067394,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0487270220796015,"gene_effect_context_minus_non_context_median":-0.04471943426963257}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_402671f307b2534b8c3c198063ffa9f7de1c0c43a708f07a2b1036e16e824648`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ARG1|entrez:383`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/ARHGAP35.html b/examples/html_reports/depmap_26q1/targets/ARHGAP35.html new file mode 100644 index 0000000..07763b9 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ARHGAP35.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ARHGAP35 + + + + +
+ +
+

Target hypothesis report: ARHGAP35

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ARHGAP35
+
+
+
Target name
+
Rho GTPase activating protein 35
+
+
+
Open Targets melanoma score
+
0.564
+
+
+
+
Open Targets baseline rank
+
126
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.05883410528362672,"interquartile_range":0.17857380242184923,"maximum":0.6903895828374135,"mean":0.16384045492536617,"measured_model_count":56,"median":0.1631803821345646,"minimum":-0.05352249745888138,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.23740790770547593,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0024143042641998377,"interquartile_range":0.008129801540448407,"maximum":0.034355451535692104,"mean":0.007660889307250123,"measured_model_count":56,"median":0.004719702771807059,"minimum":2.496236796331053e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.010544105804648245,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0010038891695393877,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.009726160134216844,"gene_effect_median":0.012715675769759294},"dependency_probability_context_minus_non_context_median":-0.001027896030419067,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.010198959585185796,"gene_effect_context_minus_non_context_median":0.01396706078741472}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 128
+- **Dependency-aware candidate rank:** 128
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_8efa1be9f1230da1dcbcba68d23d75c37039d944c1cbd624fc7b05f1f52caf80`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ARHGAP35|entrez:2909`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
128not prioritized-2
Resistance biomarker0.000
129not prioritized-3
Tumor-intrinsic / small molecule0.000
128not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.564)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ARHGAP35 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ARHGAP35 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ARHGEF12.html b/examples/html_reports/depmap_26q1/targets/ARHGEF12.html new file mode 100644 index 0000000..8f00fa8 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ARHGEF12.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ARHGEF12 + + + + +
+ +
+

Target hypothesis report: ARHGEF12

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ARHGEF12
+
+
+
Target name
+
Rho guanine nucleotide exchange factor 12
+
+
+
Open Targets melanoma score
+
0.522
+
+
+
+
Open Targets baseline rank
+
202
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06317094016798837,"interquartile_range":0.12563105896818386,"maximum":0.2270279094210083,"mean":-0.008020450715228684,"measured_model_count":56,"median":0.034871420237681874,"minimum":-0.41302734708348443,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06246011880019548,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008032339590528874,"interquartile_range":0.03030221418076693,"maximum":0.3240745714209432,"mean":0.04467501766624043,"measured_model_count":56,"median":0.015320245248807533,"minimum":0.003552775301786233,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.038334553771295805,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0036176550486326214,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.0672116048856585,"gene_effect_median":-0.02838751380254602},"dependency_probability_context_minus_non_context_median":0.003783884628871687,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.07047883567871134,"gene_effect_context_minus_non_context_median":-0.03215817044333766}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 204
+- **Dependency-aware candidate rank:** 204
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_c48af391967e4045e4b5565d671700860d523527e92f6b2ab6e93fb7c2ae82af`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ARHGEF12|entrez:23365`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
204not prioritized-2
Resistance biomarker0.000
204not prioritized-2
Tumor-intrinsic / small molecule0.000
204not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.522)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ARHGEF12 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ARHGEF12 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ARID1A.html b/examples/html_reports/depmap_26q1/targets/ARID1A.html new file mode 100644 index 0000000..a61177a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ARID1A.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ARID1A + + + + +
+ +
+

Target hypothesis report: ARID1A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ARID1A
+
+
+
Target name
+
AT-rich interaction domain 1A
+
+
+
Open Targets melanoma score
+
0.543
+
+
+
+
Open Targets baseline rank
+
177
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.43557053844131854,"interquartile_range":0.3219228042395692,"maximum":0.34226669290859557,"mean":-0.32606024413870033,"measured_model_count":56,"median":-0.2619302515505961,"minimum":-1.2757799512718386,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.11364773420174931,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.05457689627272941,"interquartile_range":0.43366939129216586,"maximum":0.9991107761621311,"mean":0.32125495906040114,"measured_model_count":56,"median":0.1554943077693044,"minimum":0.0021031613531615964,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.4882462875648953,"threshold_fractions":[{"denominator":56,"fraction":0.25,"numerator":14,"threshold":0.5},{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03646513983227573,"dependency_probability_threshold_fractions":[{"context_fraction":0.25,"difference":0.049668874172185434,"pan_cancer_fraction":0.20033112582781457,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.06054872280037844,"pan_cancer_fraction":0.10016556291390728,"threshold":0.8}],"gene_effect_mean":-0.0924020779430966,"gene_effect_median":-0.0586934200985495},"dependency_probability_context_minus_non_context_median":0.04286844721026127,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.25,"difference":0.05208333333333334,"non_context_fraction":0.19791666666666666,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.0634920634920635,"non_context_fraction":0.09722222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.09689384562088613,"gene_effect_context_minus_non_context_median":-0.06322739542564623}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 179
+- **Dependency-aware candidate rank:** 179
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_b5c100bd1a20ee14f11c4115a568f5f78536beecd8acb7908fed5614a2e7d100`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ARID1A|entrez:8289`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
179not prioritized-2
Resistance biomarker0.000
180not prioritized-3
Tumor-intrinsic / small molecule0.000
179not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.543)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ARID1A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ARID1A in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ARID1B.html b/examples/html_reports/depmap_26q1/targets/ARID1B.html new file mode 100644 index 0000000..29792a4 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ARID1B.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ARID1B + + + + +
+ +
+

Target hypothesis report: ARID1B

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ARID1B
+
+
+
Target name
+
AT-rich interaction domain 1B
+
+
+
Open Targets melanoma score
+
0.550
+
+
+
+
Open Targets baseline rank
+
160
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.12835629844328875,"interquartile_range":0.17664885205400177,"maximum":0.36199530982159556,"mean":-0.044734329690283126,"measured_model_count":56,"median":-0.04386019774725303,"minimum":-0.6603854276514436,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04829255361071304,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.011252177444106795,"interquartile_range":0.06423641939851084,"maximum":0.7207650483372453,"mean":0.06040518347981727,"measured_model_count":56,"median":0.032552869087177506,"minimum":0.0008909390586229766,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07548859684261763,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00029433981757961275,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.02767265846736045,"pan_cancer_fraction":0.04552980132450331,"threshold":0.5},{"context_fraction":0.0,"difference":-0.023178807947019868,"pan_cancer_fraction":0.023178807947019868,"threshold":0.8}],"gene_effect_mean":0.030369032009685992,"gene_effect_median":0.0022480180521348148},"dependency_probability_context_minus_non_context_median":-0.00029433981757961275,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.029017857142857144,"non_context_fraction":0.046875,"threshold":0.5},{"context_fraction":0.0,"difference":-0.024305555555555556,"non_context_fraction":0.024305555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03184530439904584,"gene_effect_context_minus_non_context_median":0.0023570820931195086}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 162
+- **Dependency-aware candidate rank:** 162
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_4f2d8813a9b1a599910baad407eacc0577d3e77782dc8aa03f0b2715cf9967f7`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ARID1B|entrez:57492`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
162not prioritized-2
Resistance biomarker0.000
163not prioritized-3
Tumor-intrinsic / small molecule0.000
162not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.550)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ARID1B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ARID1B in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ARID2.html b/examples/html_reports/depmap_26q1/targets/ARID2.html new file mode 100644 index 0000000..fe26cdd --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ARID2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ARID2 + + + + +
+ +
+

Target hypothesis report: ARID2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ARID2
+
+
+
Target name
+
AT-rich interaction domain 2
+
+
+
Open Targets melanoma score
+
0.719
+
+
+
+
Open Targets baseline rank
+
12
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.4704228591773787,"interquartile_range":0.40651398153145546,"maximum":0.3411982550552147,"mean":-0.26655617429891615,"measured_model_count":56,"median":-0.2207698686925888,"minimum":-0.996786364696395,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0639088776459232,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.03116399473948154,"interquartile_range":0.46389475167534294,"maximum":0.9745826114257009,"mean":0.27967584939597845,"measured_model_count":56,"median":0.15054546566780236,"minimum":0.0022844621532051974,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.4950587464148245,"threshold_fractions":[{"denominator":56,"fraction":0.25,"numerator":14,"threshold":0.5},{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.21875498593775644,"dependency_probability_threshold_fractions":[{"context_fraction":0.25,"difference":-0.14072847682119205,"pan_cancer_fraction":0.39072847682119205,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.119441816461684,"pan_cancer_fraction":0.17301324503311258,"threshold":0.8}],"gene_effect_mean":0.13569919074304576,"gene_effect_median":0.1709331014111793},"dependency_probability_context_minus_non_context_median":-0.2260909259708198,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.25,"difference":-0.14756944444444442,"non_context_fraction":0.3975694444444444,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.12524801587301587,"non_context_fraction":0.17881944444444445,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.14229567918194364,"gene_effect_context_minus_non_context_median":0.17491031155534215}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 20
+- **Dependency-aware candidate rank:** 20
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_30708d70482c02d0743a5b7210b4353e2ba5a07cd9748efa83ef42a731093315`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ARID2|entrez:196528`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
20not prioritized-8
Resistance biomarker0.000
25not prioritized-13
Tumor-intrinsic / small molecule0.015
18not prioritized-6
+
+ +
+

Evidence for

+
    +
  • High Open Targets melanoma association score (0.719)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ARID2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ARID2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ARNT.html b/examples/html_reports/depmap_26q1/targets/ARNT.html new file mode 100644 index 0000000..c6131c2 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ARNT.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ARNT + + + + +
+ +
+

Target hypothesis report: ARNT

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ARNT
+
+
+
Target name
+
aryl hydrocarbon receptor nuclear translocator
+
+
+
Open Targets melanoma score
+
0.560
+
+
+
+
Open Targets baseline rank
+
134
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.3581074854447507,"interquartile_range":0.3039227377270318,"maximum":1.0399727157355843,"mean":-0.19191197960061698,"measured_model_count":56,"median":-0.20315562003917215,"minimum":-0.8571155954005378,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.05418474771771889,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.02937998694058869,"interquartile_range":0.2622623014624777,"maximum":0.9255765328229291,"mean":0.2264542684912856,"measured_model_count":56,"median":0.11103222682700858,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2916422884030664,"threshold_fractions":[{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.08288184637712813,"dependency_probability_threshold_fractions":[{"context_fraction":0.17857142857142858,"difference":0.12559129612109746,"pan_cancer_fraction":0.052980132450331126,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.020813623462630083,"pan_cancer_fraction":0.014900662251655629,"threshold":0.8}],"gene_effect_mean":-0.1667360406715155,"gene_effect_median":-0.1683438224054163},"dependency_probability_context_minus_non_context_median":0.08490840786278225,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.17857142857142858,"difference":0.13169642857142858,"non_context_fraction":0.046875,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.021825396825396824,"non_context_fraction":0.013888888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.17484126487082507,"gene_effect_context_minus_non_context_median":-0.17368853329719552}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 136
+- **Dependency-aware candidate rank:** 136
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_9951155d6dd22791d2de802a6c133a1889361b1d796714df0f5b1670205a205c`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ARNT|entrez:405`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
136not prioritized-2
Resistance biomarker0.000
137not prioritized-3
Tumor-intrinsic / small molecule0.000
136not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.560)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ARNT lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ARNT in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ASPSCR1.html b/examples/html_reports/depmap_26q1/targets/ASPSCR1.html new file mode 100644 index 0000000..65b0984 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ASPSCR1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ASPSCR1 + + + + +
+ +
+

Target hypothesis report: ASPSCR1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ASPSCR1
+
+
+
Target name
+
ASPSCR1 tether for SLC2A4, UBX domain containing
+
+
+
Open Targets melanoma score
+
0.456
+
+
+
+
Open Targets baseline rank
+
300
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.197432624657035,"interquartile_range":0.14713784975672511,"maximum":0.08866600605484734,"mean":-0.13710999970506296,"measured_model_count":56,"median":-0.1028582496030106,"minimum":-0.4406863774006863,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0502947749003099,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.03159872449810511,"interquartile_range":0.09714302943381564,"maximum":0.4966970706033939,"mean":0.10482145638843436,"measured_model_count":56,"median":0.05442591831673187,"minimum":0.007136843313635444,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12874175393192075,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.03481117021973189,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.01903973509933775,"pan_cancer_fraction":0.01903973509933775,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.031133585779895,"gene_effect_median":0.06007323046735241},"dependency_probability_context_minus_non_context_median":-0.036358897608151766,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.019965277777777776,"non_context_fraction":0.019965277777777776,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.032647023977528694,"gene_effect_context_minus_non_context_median":0.062161919009254774}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 300
+- **Dependency-aware candidate rank:** 300
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_01669b833c79ae330151d436836ad2fa6a4d2c039d2d7019547b4dd13e3cfa3b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ASPSCR1|entrez:79058`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
300not prioritized0
Resistance biomarker0.000
300not prioritized0
Tumor-intrinsic / small molecule0.000
300not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.456)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ASPSCR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ASPSCR1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ATF1.html b/examples/html_reports/depmap_26q1/targets/ATF1.html new file mode 100644 index 0000000..963dc87 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ATF1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ATF1 + + + + +
+ +
+

Target hypothesis report: ATF1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ATF1
+
+
+
Target name
+
activating transcription factor 1
+
+
+
Open Targets melanoma score
+
0.544
+
+
+
+
Open Targets baseline rank
+
171
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.31199003147965054,"interquartile_range":0.19505157988805688,"maximum":0.20303160162622352,"mean":-0.2070263048606922,"measured_model_count":56,"median":-0.23658966248001567,"minimum":-0.6261219152697686,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.11693845159159365,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.06743848309059797,"interquartile_range":0.17343780682176396,"maximum":0.7946224472456699,"mean":0.1843216141685337,"measured_model_count":56,"median":0.14648723614834475,"minimum":0.004121566474625243,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.24087628991236193,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03760624946544386,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":0.008869441816461682,"pan_cancer_fraction":0.04470198675496689,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.017478392867401077,"gene_effect_median":-0.05376381313699782},"dependency_probability_context_minus_non_context_median":0.03861838203078313,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":0.009300595238095233,"non_context_fraction":0.044270833333333336,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.018328036965122002,"gene_effect_context_minus_non_context_median":-0.05523338406781739}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":92.5925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 173
+- **Dependency-aware candidate rank:** 173
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e25281946199947768b892e74af26d515e64be3ddd2868d8a50cfeef8311d8f7`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ATF1|entrez:466`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
173not prioritized-2
Resistance biomarker0.000
174not prioritized-3
Tumor-intrinsic / small molecule0.000
173not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.544)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ATF1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ATF1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ATM.html b/examples/html_reports/depmap_26q1/targets/ATM.html new file mode 100644 index 0000000..b3a94c4 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ATM.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ATM + + + + +
+ +
+

Target hypothesis report: ATM

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ATM
+
+
+
Target name
+
ATM serine/threonine kinase
+
+
+
Open Targets melanoma score
+
0.661
+
+
+
+
Open Targets baseline rank
+
28
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.0020259254350783124,"interquartile_range":0.3216274073763178,"maximum":0.8941780165066932,"mean":0.16248329861889094,"measured_model_count":56,"median":0.08719509887627361,"minimum":-0.3490614222046967,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.3196014819412395,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.001660484890086447,"interquartile_range":0.020616259399120065,"maximum":0.40357518870553377,"mean":0.024982232330452915,"measured_model_count":56,"median":0.007002239522950301,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02227674428920651,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.02110179665390864,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.016556291390728478,"pan_cancer_fraction":0.016556291390728478,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":0.17757116970453563,"gene_effect_median":0.11577610392977825},"dependency_probability_context_minus_non_context_median":-0.022564276487489134,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.017361111111111112,"non_context_fraction":0.017361111111111112,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.18620310156517278,"gene_effect_context_minus_non_context_median":0.11990687881798565}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 35
+- **Dependency-aware candidate rank:** 35
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_f659edd937045b717d650fab018fee8c7abb0cf8dd8a54835685647c64c01557`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ATM|entrez:472`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
35not prioritized-7
Resistance biomarker0.000
37not prioritized-9
Tumor-intrinsic / small molecule0.003
30not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.661)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ATM lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ATM in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ATP2B3.html b/examples/html_reports/depmap_26q1/targets/ATP2B3.html new file mode 100644 index 0000000..0d87794 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ATP2B3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ATP2B3 + + + + +
+ +
+

Target hypothesis report: ATP2B3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ATP2B3
+
+
+
Target name
+
ATPase plasma membrane Ca2+ transporting 3
+
+
+
Open Targets melanoma score
+
0.503
+
+
+
+
Open Targets baseline rank
+
250
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.12434728095818147,"interquartile_range":0.22825275912574455,"maximum":0.47230728751688694,"mean":-0.008667745235625602,"measured_model_count":56,"median":-0.036856086964585304,"minimum":-0.34970797377659013,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10390547816756308,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.009082734404598202,"interquartile_range":0.05326351901840336,"maximum":0.3112851098819218,"mean":0.04792125591852207,"measured_model_count":56,"median":0.03490888626221475,"minimum":0.0002188965827178968,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06234625342300156,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.011465927239286071,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.00448372850637792,"gene_effect_median":-0.028392774720121416},"dependency_probability_context_minus_non_context_median":0.011733976837337394,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.004701687530993483,"gene_effect_context_minus_non_context_median":-0.03064534348728724}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 252
+- **Dependency-aware candidate rank:** 252
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_4345b9f420de21332b32038e89a18fcd9d1fe78fcabe78d9f91f8fbfa04b1fde`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ATP2B3|entrez:492`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
252not prioritized-2
Resistance biomarker0.000
252not prioritized-2
Tumor-intrinsic / small molecule0.000
252not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.503)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ATP2B3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ATP2B3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ATR.html b/examples/html_reports/depmap_26q1/targets/ATR.html new file mode 100644 index 0000000..91c9d92 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ATR.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ATR + + + + +
+ +
+

Target hypothesis report: ATR

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ATR
+
+
+
Target name
+
ATR checkpoint kinase
+
+
+
Open Targets melanoma score
+
0.607
+
+
+
+
Open Targets baseline rank
+
59
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.3321653972992362,"interquartile_range":0.26959811435888104,"maximum":-0.8369811425904811,"mean":-1.230833734102214,"measured_model_count":56,"median":-1.172755189115312,"minimum":-1.9629129476130718,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.0625672829403552,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9788404513704841,"interquartile_range":0.019620482322990296,"maximum":1.0,"mean":0.9848397947268778,"measured_model_count":56,"median":0.9904158847911251,"minimum":0.9189537502260394,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9984609336934744,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.007277304019570607,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.026490066225165587,"pan_cancer_fraction":0.9735099337748344,"threshold":0.5},{"context_fraction":1.0,"difference":0.06953642384105962,"pan_cancer_fraction":0.9304635761589404,"threshold":0.8}],"gene_effect_mean":-0.12345707377225956,"gene_effect_median":-0.07212354509362151},"dependency_probability_context_minus_non_context_median":0.007810294213553393,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.02777777777777779,"non_context_fraction":0.9722222222222222,"threshold":0.5},{"context_fraction":1.0,"difference":0.07291666666666663,"non_context_fraction":0.9270833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.12945845930285538,"gene_effect_context_minus_non_context_median":-0.07890300754043578}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 63
+- **Dependency-aware candidate rank:** 63
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e05075a57487520a3ef8c2552aa212d23654885ece8d4225110dbf0b3eef6df2`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ATR|entrez:545`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
63not prioritized-4
Resistance biomarker0.000
65not prioritized-6
Tumor-intrinsic / small molecule0.000
63not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.607)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ATR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ATR in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ATRX.html b/examples/html_reports/depmap_26q1/targets/ATRX.html new file mode 100644 index 0000000..e561a5d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ATRX.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ATRX + + + + +
+ +
+

Target hypothesis report: ATRX

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ATRX
+
+
+
Target name
+
ATRX chromatin remodeler
+
+
+
Open Targets melanoma score
+
0.587
+
+
+
+
Open Targets baseline rank
+
89
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.4980924165161724,"interquartile_range":0.32325243518896685,"maximum":0.42042034947144924,"mean":-0.34566514357228256,"measured_model_count":56,"median":-0.3302554609174006,"minimum":-0.8970558577974759,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.17483998132720557,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.09010910049335963,"interquartile_range":0.4892689464867115,"maximum":0.9394427095826552,"mean":0.3615166505326878,"measured_model_count":56,"median":0.30795028110934963,"minimum":0.0005373738842964715,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5793780469800711,"threshold_fractions":[{"denominator":56,"fraction":0.32142857142857145,"numerator":18,"threshold":0.5},{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.21746991569394805,"dependency_probability_threshold_fractions":[{"context_fraction":0.32142857142857145,"difference":0.1914616840113529,"pan_cancer_fraction":0.12996688741721854,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":0.0445837275307474,"pan_cancer_fraction":0.04470198675496689,"threshold":0.8}],"gene_effect_mean":-0.14128892377984786,"gene_effect_median":-0.1592475685537306},"dependency_probability_context_minus_non_context_median":0.21986921327752046,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.32142857142857145,"difference":0.20076884920634924,"non_context_fraction":0.12065972222222222,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":0.046750992063492064,"non_context_fraction":0.042534722222222224,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.1481571353524796,"gene_effect_context_minus_non_context_median":-0.16429773664113811}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 92
+- **Dependency-aware candidate rank:** 92
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a9a1db04e736dc8c304ac3fa6521e031189647161bbb85f740331b9c1e7fbcd3`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ATRX|entrez:546`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
92not prioritized-3
Resistance biomarker0.000
94not prioritized-5
Tumor-intrinsic / small molecule0.000
92not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.587)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ATRX lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ATRX in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/AXIN1.html b/examples/html_reports/depmap_26q1/targets/AXIN1.html new file mode 100644 index 0000000..f39cd6f --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/AXIN1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: AXIN1 + + + + +
+ +
+

Target hypothesis report: AXIN1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
AXIN1
+
+
+
Target name
+
axin 1
+
+
+
Open Targets melanoma score
+
0.552
+
+
+
+
Open Targets baseline rank
+
149
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.037343116083035185,"interquartile_range":0.26661108518976745,"maximum":0.9196883699197242,"mean":0.08748785591226547,"measured_model_count":56,"median":0.08289157811043477,"minimum":-0.7764618367290135,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.22926796910673228,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.001998134253073587,"interquartile_range":0.0260986272540997,"maximum":0.8778227499507888,"mean":0.06161891085070346,"measured_model_count":56,"median":0.009616196179705327,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.028096761507173287,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005075620768799749,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.0059129612109744545,"pan_cancer_fraction":0.029801324503311258,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.00792336802270577,"pan_cancer_fraction":0.009933774834437087,"threshold":0.8}],"gene_effect_mean":0.05980391935434875,"gene_effect_median":0.03889600853611898},"dependency_probability_context_minus_non_context_median":-0.005271964576623166,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.006200396825396824,"non_context_fraction":0.029513888888888888,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.008308531746031744,"non_context_fraction":0.009548611111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.06271105432296295,"gene_effect_context_minus_non_context_median":0.040327951312166335}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 151
+- **Dependency-aware candidate rank:** 151
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a7a17af0a257bc40977527542e34c96f843a4c6c02174c75b38457bdc95dbad4`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:AXIN1|entrez:8312`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
151not prioritized-2
Resistance biomarker0.000
152not prioritized-3
Tumor-intrinsic / small molecule0.000
151not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.552)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: AXIN1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for AXIN1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/AXL.html b/examples/html_reports/depmap_26q1/targets/AXL.html new file mode 100644 index 0000000..f9ba07e --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/AXL.html @@ -0,0 +1,70 @@ +AXL — DepMap research preview

AXL

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.09669271225359513,"interquartile_range":0.13838293442208938,"maximum":0.33269592966644873,"mean":-0.05402248348828266,"measured_model_count":56,"median":-0.05461535624294615,"minimum":-0.591523976802867,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.041690222168494245,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01321277007165553,"interquartile_range":0.047403672929686676,"maximum":0.5937823231403992,"mean":0.06668973321292734,"measured_model_count":56,"median":0.03594859224302639,"minimum":0.0021112287349255585,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0606164430013422,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00841929504751433,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.005439924314096499,"pan_cancer_fraction":0.012417218543046357,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.009449488770846413,"gene_effect_median":-0.028192670549813503},"dependency_probability_context_minus_non_context_median":0.00855861376300604,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.005704365079365078,"non_context_fraction":0.012152777777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.009908838919429161,"gene_effect_context_minus_non_context_median":-0.029581425927257432}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_4998e8d48eb17bd589670b508f8684da20ab3963cc8de33d05845accbfaee6be`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:AXL|entrez:558`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/B2M.html b/examples/html_reports/depmap_26q1/targets/B2M.html new file mode 100644 index 0000000..7eb2035 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/B2M.html @@ -0,0 +1,440 @@ + + + + +TargetIntel-IO report: B2M + + + + +
+ +
+

Target hypothesis report: B2M

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
B2M
+
+
+
Target name
+
beta-2-microglobulin
+
+
+
Open Targets melanoma score
+
0.572
+
+
+
+
Open Targets baseline rank
+
111
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.03419536124041851,"interquartile_range":0.13539073572534133,"maximum":0.222441908549175,"mean":0.02537352064559218,"measured_model_count":56,"median":0.015821163143747298,"minimum":-0.26075783687617665,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10119537448492283,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.006961531439831104,"interquartile_range":0.02038009892374358,"maximum":0.23444542085876965,"mean":0.025135791460166153,"measured_model_count":56,"median":0.0164348942055268,"minimum":0.001654700032914229,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.027341630363574686,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.000853410138454436,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.007267390625760095,"gene_effect_median":-0.01927512526788492},"dependency_probability_context_minus_non_context_median":0.0009027441678660965,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.007620666558956747,"gene_effect_context_minus_non_context_median":-0.020399321418123194}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 9
+- **Dependency-aware candidate rank:** 5
+- **Rank delta:** -4
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_1b6574683ae76a819dfc9ca0014d7c3b1867009f10cded7fc4cf73749063eb81`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:B2M|entrez:567`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
antigen-presentation resistance biomarker
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
use as biomarker / patient stratification
+
+
+
Best modality
+
resistance biomarker / patient stratification
+
+
+
Resistance axis
+
antigen_presentation_loss
+
+
+
Matched resistance programs
+
Antigen-presentation loss
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.227
9low102
Resistance biomarker0.806
1high110
Tumor-intrinsic / small molecule0.132
13low98
+
+ +
+

Evidence for

+
    +
  • Directly linked to tumor immune escape
    • +
  • Relevant to T-cell recognition
    • +
  • Useful for resistance stratification
    • +
  • Moderate Open Targets melanoma association score (0.572)
    • +
  • Maps to curated anti-PD-1 resistance program: Antigen-presentation loss
    • +
  • Stable role classifier confidence is high
    • +
  • Biomarker fit is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Loss-of-function events may be difficult to pharmacologically reverse
    • +
  • Often not a direct therapeutic target
    • +
  • Poor fit for antibody targeting
    • +
  • Most useful as biomarker or stratification marker rather than direct therapeutic target
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
high confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.320
+
+
+
+
Main limitation
+
Likely more useful for stratification than direct therapeutic targeting
+
+
+

Uncertainty reason: Main limitation: Likely more useful for stratification than direct therapeutic targeting

+

Deprioritization reason: B2M should not be deprioritized globally, but should be ranked mainly in biomarker or patient-stratification mode.

+
+ +
+

Recommended next validation experiment

+

Validation category: biomarker validation

+

Next experiment: Test whether B2M status or expression differs between anti-PD-1 responders and non-responders in an independent melanoma cohort.

+

Rationale: This would determine whether the candidate has practical value as a resistance biomarker or patient-stratification feature.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BACH2.html b/examples/html_reports/depmap_26q1/targets/BACH2.html new file mode 100644 index 0000000..0502716 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BACH2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BACH2 + + + + +
+ +
+

Target hypothesis report: BACH2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BACH2
+
+
+
Target name
+
BACH transcriptional regulator 2
+
+
+
Open Targets melanoma score
+
0.465
+
+
+
+
Open Targets baseline rank
+
290
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.01884643567221031,"interquartile_range":0.12885452737206532,"maximum":0.2922363938617609,"mean":0.04157837025826655,"measured_model_count":56,"median":0.039909660670576906,"minimum":-0.1728292133635718,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11000809169985502,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.007121448360295681,"interquartile_range":0.020012121577146845,"maximum":0.06841314448379879,"mean":0.019631283583679472,"measured_model_count":56,"median":0.013053911679737119,"minimum":0.0010205824014244435,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.027133569937442526,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0015546041641899405,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.005821714463687698,"gene_effect_median":-0.0016066987038449096},"dependency_probability_context_minus_non_context_median":-0.0016402089908457793,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006104714472339179,"gene_effect_context_minus_non_context_median":-0.0016066987038449096}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 290
+- **Dependency-aware candidate rank:** 290
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_cd083763ccfa62bdd53cc6d82e9663ea2c57a38514c3d7b809e4541fa851f9fc`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BACH2|entrez:60468`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
290not prioritized0
Resistance biomarker0.000
290not prioritized0
Tumor-intrinsic / small molecule0.000
290not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.465)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BACH2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BACH2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BAP1.html b/examples/html_reports/depmap_26q1/targets/BAP1.html new file mode 100644 index 0000000..86da556 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BAP1.html @@ -0,0 +1,435 @@ + + + + +TargetIntel-IO report: BAP1 + + + + +
+ +
+

Target hypothesis report: BAP1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BAP1
+
+
+
Target name
+
BRCA1 associated deubiquitinase 1
+
+
+
Open Targets melanoma score
+
0.816
+
+
+
+
Open Targets baseline rank
+
3
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.7617301000041377,"interquartile_range":0.39215821877949375,"maximum":-0.027665093614035463,"mean":-0.580660108206857,"measured_model_count":56,"median":-0.5909145722746947,"minimum":-1.1970868602866886,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.3695718812246439,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.30705277763360284,"interquartile_range":0.5817669754730993,"maximum":0.9966187017789548,"mean":0.6221644187853995,"measured_model_count":56,"median":0.7153010101416735,"minimum":0.026783164047011688,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.8888197531067021,"threshold_fractions":[{"denominator":56,"fraction":0.6607142857142857,"numerator":37,"threshold":0.5},{"denominator":56,"fraction":0.4107142857142857,"numerator":23,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.11991243702833909,"dependency_probability_threshold_fractions":[{"context_fraction":0.6607142857142857,"difference":0.09614474929044459,"pan_cancer_fraction":0.5645695364238411,"threshold":0.5},{"context_fraction":0.4107142857142857,"difference":0.11435666982024595,"pan_cancer_fraction":0.29635761589403975,"threshold":0.8}],"gene_effect_mean":-0.0702426311969423,"gene_effect_median":-0.07650321152341633},"dependency_probability_context_minus_non_context_median":0.1287251125435065,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.6607142857142857,"difference":0.10081845238095233,"non_context_fraction":0.5598958333333334,"threshold":0.5},{"context_fraction":0.4107142857142857,"difference":0.1199156746031746,"non_context_fraction":0.2907986111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0736572035467935,"gene_effect_context_minus_non_context_median":-0.08087977316397721}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 13
+- **Dependency-aware candidate rank:** 13
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ca2583b9c8b88d48220f585a16c6d2e695dff2d01157b025046c548705a99a05`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BAP1|entrez:8314`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / poor direct therapeutic target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
avoid as direct target / use as biomarker or pathway context
+
+
+
Best modality
+
biomarker / pathway context only
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
13not prioritized-10
Resistance biomarker0.128
18low-15
Tumor-intrinsic / small molecule0.000
37not prioritized-34
+
+ +
+

Evidence for

+
    +
  • High Open Targets melanoma association score (0.816)
    • +
  • Stable role classifier confidence is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Flagged as poor direct therapeutic target for this MVP
    • +
  • Role classifier indicates biological relevance but poor direct targetability
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
0.889
+
+
+
+
Contradiction score
+
0.570
+
+
+
+
Main limitation
+
Poor direct therapeutic target despite biological relevance
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Moderate contradiction score indicates caution is needed | Main limitation: Poor direct therapeutic target despite biological relevance

+

Deprioritization reason: BAP1 should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context.

+
+ +
+

Recommended next validation experiment

+

Validation category: tumor-intrinsic functional validation

+

Next experiment: Evaluate whether perturbing BAP1 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays.

+

Rationale: This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BCL11A.html b/examples/html_reports/depmap_26q1/targets/BCL11A.html new file mode 100644 index 0000000..93a141a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BCL11A.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BCL11A + + + + +
+ +
+

Target hypothesis report: BCL11A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BCL11A
+
+
+
Target name
+
BCL11 transcription factor A
+
+
+
Open Targets melanoma score
+
0.558
+
+
+
+
Open Targets baseline rank
+
141
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.11420819046622246,"interquartile_range":0.16659082868984246,"maximum":0.43518189292339327,"mean":-0.045648604296433484,"measured_model_count":56,"median":-0.056271293868629293,"minimum":-0.5045098076749046,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.052382638223619986,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.013988075492537793,"interquartile_range":0.044676824510456764,"maximum":0.6734265664462808,"mean":0.060102345993402966,"measured_model_count":56,"median":0.033069240860764355,"minimum":0.0008709175060067826,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.058664900002994555,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0013133876807193273,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.005439924314096499,"pan_cancer_fraction":0.012417218543046357,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.0032663000309570214,"gene_effect_median":-0.012237703308827015},"dependency_probability_context_minus_non_context_median":0.0013133876807193273,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.005704365079365078,"non_context_fraction":0.012152777777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.003425078504684133,"gene_effect_context_minus_non_context_median":-0.012597092084299488}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 143
+- **Dependency-aware candidate rank:** 143
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_4530b1bef3c9d166c8e11998299c11629395297b3b900a556bc5b0e5f050aded`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BCL11A|entrez:53335`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
143not prioritized-2
Resistance biomarker0.000
144not prioritized-3
Tumor-intrinsic / small molecule0.000
143not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.558)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BCL11A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BCL11A in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BCL11B.html b/examples/html_reports/depmap_26q1/targets/BCL11B.html new file mode 100644 index 0000000..3160dbf --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BCL11B.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BCL11B + + + + +
+ +
+

Target hypothesis report: BCL11B

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BCL11B
+
+
+
Target name
+
BCL11 transcription factor B
+
+
+
Open Targets melanoma score
+
0.515
+
+
+
+
Open Targets baseline rank
+
228
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.04299951768347804,"interquartile_range":0.12128991572901711,"maximum":0.2227864472704803,"mean":0.01497917009073292,"measured_model_count":56,"median":0.019832171594732825,"minimum":-0.30944805285306837,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07829039804553907,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.007893891610742113,"interquartile_range":0.023567574776098024,"maximum":0.2051689240725753,"mean":0.024793767381785202,"measured_model_count":56,"median":0.018108339873370675,"minimum":0.0026566262890120834,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03146146638684014,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0008022985700595793,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.014900662251655629,"pan_cancer_fraction":0.014900662251655629,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.8}],"gene_effect_mean":0.006140626290001,"gene_effect_median":-0.005813637403148674},"dependency_probability_context_minus_non_context_median":0.0008022985700595793,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.015625,"non_context_fraction":0.015625,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006439128956876032,"gene_effect_context_minus_non_context_median":-0.0066135845459349175}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 230
+- **Dependency-aware candidate rank:** 230
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ef2636b1f28658470b715acc8b410918b8d08e55469f189f2868b3cd7c3c745a`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BCL11B|entrez:64919`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
230not prioritized-2
Resistance biomarker0.000
230not prioritized-2
Tumor-intrinsic / small molecule0.000
230not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.515)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BCL11B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BCL11B in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BCL2.html b/examples/html_reports/depmap_26q1/targets/BCL2.html new file mode 100644 index 0000000..8d074e8 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BCL2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BCL2 + + + + +
+ +
+

Target hypothesis report: BCL2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BCL2
+
+
+
Target name
+
BCL2 apoptosis regulator
+
+
+
Open Targets melanoma score
+
0.484
+
+
+
+
Open Targets baseline rank
+
269
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.08696651149816556,"interquartile_range":0.14561016392955564,"maximum":0.2680923594186532,"mean":-0.016920171192513926,"measured_model_count":56,"median":-0.025311452898357994,"minimum":-0.25176194650284295,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05864365243139008,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.012691998621583553,"interquartile_range":0.03380030655700515,"maximum":0.161056642128686,"mean":0.03713254238273757,"measured_model_count":56,"median":0.02454383022252416,"minimum":0.0023418864731136555,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.046492305178588704,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.002009118404849311,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03642384105960265,"pan_cancer_fraction":0.03642384105960265,"threshold":0.5},{"context_fraction":0.0,"difference":-0.022350993377483443,"pan_cancer_fraction":0.022350993377483443,"threshold":0.8}],"gene_effect_mean":0.019261563818710054,"gene_effect_median":-0.022196683352156837},"dependency_probability_context_minus_non_context_median":0.002223118359550566,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03819444444444445,"non_context_fraction":0.03819444444444445,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0234375,"non_context_fraction":0.0234375,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0201978898376751,"gene_effect_context_minus_non_context_median":-0.023006579966283445}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 270
+- **Dependency-aware candidate rank:** 270
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ea3de1e2aa77018152520942e86464bdd295cf75fd360da1688e062513ad57c8`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BCL2|entrez:596`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
270not prioritized-1
Resistance biomarker0.000
270not prioritized-1
Tumor-intrinsic / small molecule0.000
270not prioritized-1
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.484)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BCL2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BCL2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BCL9.html b/examples/html_reports/depmap_26q1/targets/BCL9.html new file mode 100644 index 0000000..d0cada9 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BCL9.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BCL9 + + + + +
+ +
+

Target hypothesis report: BCL9

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BCL9
+
+
+
Target name
+
BCL9 transcription coactivator
+
+
+
Open Targets melanoma score
+
0.512
+
+
+
+
Open Targets baseline rank
+
232
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.38494598357777626,"interquartile_range":0.3330532366091112,"maximum":0.4089113515279511,"mean":-0.2320473630104575,"measured_model_count":56,"median":-0.23320556013071192,"minimum":-0.9150034496838594,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0518927469686651,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.03469806330531005,"interquartile_range":0.2717156659809888,"maximum":0.9363484371526809,"mean":0.24510724830209973,"measured_model_count":56,"median":0.14987003186885173,"minimum":6.792628342980656e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.30641372928629884,"threshold_fractions":[{"denominator":56,"fraction":0.19642857142857142,"numerator":11,"threshold":0.5},{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.04722901062703447,"dependency_probability_threshold_fractions":[{"context_fraction":0.19642857142857142,"difference":0.055700094607379375,"pan_cancer_fraction":0.14072847682119205,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":0.029210028382213808,"pan_cancer_fraction":0.042218543046357616,"threshold":0.8}],"gene_effect_mean":-0.05197525956023036,"gene_effect_median":-0.0496702568894708},"dependency_probability_context_minus_non_context_median":0.0495749823570763,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.19642857142857142,"difference":0.05840773809523808,"non_context_fraction":0.13802083333333334,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":0.030629960317460313,"non_context_fraction":0.04079861111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.054501834677741084,"gene_effect_context_minus_non_context_median":-0.05535524771486566}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 234
+- **Dependency-aware candidate rank:** 234
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ccf55366fc66b6ecabb3c3e841d40ed564813d67765ad22918c7f7b57dd90d21`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BCL9|entrez:607`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
234not prioritized-2
Resistance biomarker0.000
234not prioritized-2
Tumor-intrinsic / small molecule0.000
234not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.512)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BCL9 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BCL9 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BCL9L.html b/examples/html_reports/depmap_26q1/targets/BCL9L.html new file mode 100644 index 0000000..3dc5225 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BCL9L.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BCL9L + + + + +
+ +
+

Target hypothesis report: BCL9L

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BCL9L
+
+
+
Target name
+
BCL9 like
+
+
+
Open Targets melanoma score
+
0.562
+
+
+
+
Open Targets baseline rank
+
132
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.1688428463252949,"interquartile_range":0.19093666889847527,"maximum":0.2938285868937669,"mean":-0.07602213222019842,"measured_model_count":56,"median":-0.08759133713750625,"minimum":-0.8127726660093453,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.022093822573180377,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01697105113102501,"interquartile_range":0.09072755309577211,"maximum":0.8980221838973915,"mean":0.08478326576217181,"measured_model_count":56,"median":0.03968158389728285,"minimum":0.0014820722411286198,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10769860422679713,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01015602430234061,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.03512298959318827,"pan_cancer_fraction":0.052980132450331126,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.0004730368968779569,"pan_cancer_fraction":0.0173841059602649,"threshold":0.8}],"gene_effect_mean":0.03112072905089716,"gene_effect_median":0.0035155689233583864},"dependency_probability_context_minus_non_context_median":-0.01068925285951225,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.036830357142857144,"non_context_fraction":0.0546875,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.0004960317460317443,"non_context_fraction":0.017361111111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03263354226864924,"gene_effect_context_minus_non_context_median":0.004168050231747947}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 134
+- **Dependency-aware candidate rank:** 134
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_130620cecb7880eff894c17a3415fa9c58e6144f3d5bd568b075473b897a4877`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BCL9L|entrez:283149`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
134not prioritized-2
Resistance biomarker0.000
135not prioritized-3
Tumor-intrinsic / small molecule0.000
134not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.562)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BCL9L lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BCL9L in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BCOR.html b/examples/html_reports/depmap_26q1/targets/BCOR.html new file mode 100644 index 0000000..987b0cd --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BCOR.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BCOR + + + + +
+ +
+

Target hypothesis report: BCOR

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BCOR
+
+
+
Target name
+
BCL6 corepressor
+
+
+
Open Targets melanoma score
+
0.552
+
+
+
+
Open Targets baseline rank
+
154
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.09843137692846265,"interquartile_range":0.3024111110874371,"maximum":0.5123476618974896,"mean":0.043399310001232275,"measured_model_count":56,"median":0.025163160100960116,"minimum":-0.46608548605258826,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2039797341589745,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.004385523455098974,"interquartile_range":0.049122236208953576,"maximum":0.5695078292114721,"mean":0.04532958920474263,"measured_model_count":56,"median":0.01380619756232246,"minimum":0.00015610740691107978,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05350775966405255,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0027150348663232526,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.0069772942289498575,"pan_cancer_fraction":0.024834437086092714,"threshold":0.5},{"context_fraction":0.0,"difference":-0.01076158940397351,"pan_cancer_fraction":0.01076158940397351,"threshold":0.8}],"gene_effect_mean":0.0182954776524825,"gene_effect_median":-0.009540080025807921},"dependency_probability_context_minus_non_context_median":-0.002821261181018683,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.007316468253968256,"non_context_fraction":0.025173611111111112,"threshold":0.5},{"context_fraction":0.0,"difference":-0.011284722222222222,"non_context_fraction":0.011284722222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01918484114947815,"gene_effect_context_minus_non_context_median":-0.01101162275375667}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 156
+- **Dependency-aware candidate rank:** 156
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_b97d297300843c94981e764c1cabdaf082a810f52b0f25a54c7bba9d923cbeae`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BCOR|entrez:54880`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
156not prioritized-2
Resistance biomarker0.000
157not prioritized-3
Tumor-intrinsic / small molecule0.000
156not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.552)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BCOR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BCOR in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BCORL1.html b/examples/html_reports/depmap_26q1/targets/BCORL1.html new file mode 100644 index 0000000..512c79f --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BCORL1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BCORL1 + + + + +
+ +
+

Target hypothesis report: BCORL1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BCORL1
+
+
+
Target name
+
BCL6 corepressor like 1
+
+
+
Open Targets melanoma score
+
0.519
+
+
+
+
Open Targets baseline rank
+
216
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.040014746834881765,"interquartile_range":0.1883396297572965,"maximum":0.45603754792744744,"mean":0.09678094437513547,"measured_model_count":56,"median":0.10564126028540002,"minimum":-0.6082875411667698,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.22835437659217828,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0023587471886702166,"interquartile_range":0.011221787353487667,"maximum":0.7004279011526633,"mean":0.04059999544600247,"measured_model_count":56,"median":0.007299775968082389,"minimum":0.00014814138376582694,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.013580534542157883,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003567309948364188,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.028263954588457898,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.019726784915498313,"gene_effect_median":0.0258835663828344},"dependency_probability_context_minus_non_context_median":-0.003764269348550839,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.029637896825396824,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.020685725848890543,"gene_effect_context_minus_non_context_median":0.027067192809979018}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 218
+- **Dependency-aware candidate rank:** 218
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d15423ff4eb3865580e87cecd978a3a6783cf73e5f8593373d060031c5d6d748`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BCORL1|entrez:63035`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
218not prioritized-2
Resistance biomarker0.000
218not prioritized-2
Tumor-intrinsic / small molecule0.000
218not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.519)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BCORL1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BCORL1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BIRC3.html b/examples/html_reports/depmap_26q1/targets/BIRC3.html new file mode 100644 index 0000000..393779d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BIRC3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BIRC3 + + + + +
+ +
+

Target hypothesis report: BIRC3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BIRC3
+
+
+
Target name
+
baculoviral IAP repeat containing 3
+
+
+
Open Targets melanoma score
+
0.494
+
+
+
+
Open Targets baseline rank
+
260
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.053832945649035846,"interquartile_range":0.17211190378930316,"maximum":0.29394174579102555,"mean":0.021754678809343127,"measured_model_count":56,"median":0.0066408270165531635,"minimum":-0.27705052981998146,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11827895814026732,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.006081698993193586,"interquartile_range":0.0270064902459861,"maximum":0.2690632218111069,"mean":0.029979679761486938,"measured_model_count":56,"median":0.01746802168718406,"minimum":0.0015399221549407625,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03308818923917969,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.003910880564498082,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.025029029858429405,"gene_effect_median":-0.039950423932228474},"dependency_probability_context_minus_non_context_median":0.004155410292051574,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.02624571880988088,"gene_effect_context_minus_non_context_median":-0.0407441913722429}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 262
+- **Dependency-aware candidate rank:** 262
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d67ae8b5fbdcb102428afa986cd612ca739aeeb1d45287ac293992df25f8cadd`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BIRC3|entrez:330`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
262not prioritized-2
Resistance biomarker0.000
262not prioritized-2
Tumor-intrinsic / small molecule0.000
262not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.494)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BIRC3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BIRC3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BRAF.html b/examples/html_reports/depmap_26q1/targets/BRAF.html new file mode 100644 index 0000000..2b6c3f8 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BRAF.html @@ -0,0 +1,440 @@ + + + + +TargetIntel-IO report: BRAF + + + + +
+ +
+

Target hypothesis report: BRAF

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BRAF
+
+
+
Target name
+
B-Raf proto-oncogene, serine/threonine kinase
+
+
+
Open Targets melanoma score
+
0.853
+
+
+
+
Open Targets baseline rank
+
2
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.6227668727162368,"interquartile_range":0.9795415688905247,"maximum":-0.015881149663220406,"mean":-1.1769393408178332,"measured_model_count":56,"median":-1.2347703095627218,"minimum":-2.6355354158678552,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.6432253038257121,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.8542815144561293,"interquartile_range":0.14570215220149452,"maximum":1.0,"mean":0.7983333399564246,"measured_model_count":56,"median":0.9910996581121145,"minimum":0.018849964783263323,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9999836666576238,"threshold_fractions":[{"denominator":56,"fraction":0.7857142857142857,"numerator":44,"threshold":0.5},{"denominator":56,"fraction":0.75,"numerator":42,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.941093110695153,"dependency_probability_threshold_fractions":[{"context_fraction":0.7857142857142857,"difference":0.690515610217597,"pan_cancer_fraction":0.09519867549668874,"threshold":0.5},{"context_fraction":0.75,"difference":0.6846026490066225,"pan_cancer_fraction":0.06539735099337748,"threshold":0.8}],"gene_effect_mean":-0.9973071133238599,"gene_effect_median":-1.1421352404225718},"dependency_probability_context_minus_non_context_median":0.943697459010603,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.7857142857142857,"difference":0.7240823412698413,"non_context_fraction":0.06163194444444445,"threshold":0.5},{"context_fraction":0.75,"difference":0.7178819444444444,"non_context_fraction":0.03211805555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-1.0457873202215475,"gene_effect_context_minus_non_context_median":-1.1485856638282403}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":100.0}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 7
+- **Dependency-aware candidate rank:** 1
+- **Rank delta:** -6
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_47a7c9ba52d4567bf9a8f2d1a63c5270380178383e2ea2bdace38fadfec9aaca`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BRAF|entrez:673`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / small-molecule target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
small-molecule inhibition / pathway targeting
+
+
+
Best modality
+
small molecule / pathway targeting
+
+
+
Resistance axis
+
tumor_intrinsic_driver
+
+
+
Matched resistance programs
+
Tumor-intrinsic driver biology
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.269
7low-5
Resistance biomarker0.482
11medium-9
Tumor-intrinsic / small molecule0.845
1high1
+
+ +
+

Evidence for

+
    +
  • Relevant to melanoma tumor-cell biology
    • +
  • Some targets or pathways are clinically actionable
    • +
  • Useful for separating tumor-intrinsic drivers from immune-combination targets
    • +
  • High Open Targets melanoma association score (0.853)
    • +
  • Maps to curated anti-PD-1 resistance program: Tumor-intrinsic driver biology
    • +
  • Stable role classifier confidence is high
    • +
  • Small-molecule fit is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Many tumor-intrinsic drivers are poor antibody targets
    • +
  • Melanoma association does not automatically imply anti-PD-1 combination suitability
    • +
  • Tumor suppressors are often poor direct therapeutic targets
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
high confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.320
+
+
+
+
Main limitation
+
Poor fit for antibody / IO-combination modality
+
+
+

Uncertainty reason: Main limitation: Poor fit for antibody / IO-combination modality

+

Deprioritization reason: No strong deprioritization reason from current MVP rules

+
+ +
+

Recommended next validation experiment

+

Validation category: tumor-intrinsic functional validation

+

Next experiment: Evaluate whether perturbing BRAF alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays.

+

Rationale: This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BRCA1.html b/examples/html_reports/depmap_26q1/targets/BRCA1.html new file mode 100644 index 0000000..d7ef808 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BRCA1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BRCA1 + + + + +
+ +
+

Target hypothesis report: BRCA1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BRCA1
+
+
+
Target name
+
BRCA1 DNA repair associated
+
+
+
Open Targets melanoma score
+
0.604
+
+
+
+
Open Targets baseline rank
+
64
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.8334513137692443,"interquartile_range":0.3666416803437246,"maximum":0.062275150039045934,"mean":-0.6446669874885088,"measured_model_count":56,"median":-0.6447037480808876,"minimum":-1.4679161979282245,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.46680963342551973,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.5092257497253594,"interquartile_range":0.4183593833250353,"maximum":0.9994909191982082,"mean":0.6709476213577762,"measured_model_count":56,"median":0.7565224518784195,"minimum":0.009461623428259134,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9275851330503947,"threshold_fractions":[{"denominator":56,"fraction":0.7678571428571429,"numerator":43,"threshold":0.5},{"denominator":56,"fraction":0.4642857142857143,"numerator":26,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.25058042664477276,"dependency_probability_threshold_fractions":[{"context_fraction":0.7678571428571429,"difference":0.262062440870388,"pan_cancer_fraction":0.5057947019867549,"threshold":0.5},{"context_fraction":0.4642857142857143,"difference":0.20683538315988648,"pan_cancer_fraction":0.2574503311258278,"threshold":0.8}],"gene_effect_mean":-0.15249501305905494,"gene_effect_median":-0.18012596237736855},"dependency_probability_context_minus_non_context_median":0.2653220437390733,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.7678571428571429,"difference":0.2748015873015873,"non_context_fraction":0.4930555555555556,"threshold":0.5},{"context_fraction":0.4642857142857143,"difference":0.21688988095238096,"non_context_fraction":0.24739583333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.15990796508275879,"gene_effect_context_minus_non_context_median":-0.18493748969522855}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":92.5925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 68
+- **Dependency-aware candidate rank:** 68
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_c3abf02d3576b30a9ea568ee8d2cd2fc27df2cfd402aa7a28eccaa2022a08fda`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BRCA1|entrez:672`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
68not prioritized-4
Resistance biomarker0.000
70not prioritized-6
Tumor-intrinsic / small molecule0.000
68not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.604)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BRCA1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BRCA1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BRCA2.html b/examples/html_reports/depmap_26q1/targets/BRCA2.html new file mode 100644 index 0000000..8b5426c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BRCA2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BRCA2 + + + + +
+ +
+

Target hypothesis report: BRCA2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BRCA2
+
+
+
Target name
+
BRCA2 DNA repair associated
+
+
+
Open Targets melanoma score
+
0.687
+
+
+
+
Open Targets baseline rank
+
24
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.6488829996539245,"interquartile_range":0.2518526421601791,"maximum":-0.11644136524611565,"mean":-0.5194239412699343,"measured_model_count":56,"median":-0.5458386512220574,"minimum":-0.9883316064136789,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.3970303574937454,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.3920368984175355,"interquartile_range":0.4198271479602616,"maximum":0.9795182103056468,"mean":0.5793265400728955,"measured_model_count":56,"median":0.6356233831085945,"minimum":0.047399772777465814,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.8118640463777971,"threshold_fractions":[{"denominator":56,"fraction":0.625,"numerator":35,"threshold":0.5},{"denominator":56,"fraction":0.2857142857142857,"numerator":16,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.041063484097139114,"dependency_probability_threshold_fractions":[{"context_fraction":0.625,"difference":0.04387417218543044,"pan_cancer_fraction":0.5811258278145696,"threshold":0.5},{"context_fraction":0.2857142857142857,"difference":0.00011825922421948576,"pan_cancer_fraction":0.2855960264900662,"threshold":0.8}],"gene_effect_mean":-0.0015668993950327392,"gene_effect_median":-0.029499749646440088},"dependency_probability_context_minus_non_context_median":0.044335610678987836,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.625,"difference":0.04600694444444442,"non_context_fraction":0.5789930555555556,"threshold":0.5},{"context_fraction":0.2857142857142857,"difference":0.0001240079365079083,"non_context_fraction":0.2855902777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0016430681156246463,"gene_effect_context_minus_non_context_median":-0.031023442845045324}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 31
+- **Dependency-aware candidate rank:** 31
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_5bf109b23dc5449b6b55fa3337d49d7364cd1955795cf233da6d22d2aee4dbb8`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BRCA2|entrez:675`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
31not prioritized-7
Resistance biomarker0.000
33not prioritized-9
Tumor-intrinsic / small molecule0.008
26not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.687)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BRCA2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BRCA2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BRD3.html b/examples/html_reports/depmap_26q1/targets/BRD3.html new file mode 100644 index 0000000..882f1ee --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BRD3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BRD3 + + + + +
+ +
+

Target hypothesis report: BRD3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BRD3
+
+
+
Target name
+
bromodomain containing 3
+
+
+
Open Targets melanoma score
+
0.511
+
+
+
+
Open Targets baseline rank
+
233
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.033964049706230695,"interquartile_range":0.09288662604572513,"maximum":0.3470103010805555,"mean":0.07953525307711658,"measured_model_count":56,"median":0.08710923930845982,"minimum":-0.17690537289100544,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12685067575195583,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.00500462514257108,"interquartile_range":0.013542976338508669,"maximum":0.07572924687956509,"mean":0.014028321936522852,"measured_model_count":56,"median":0.0076650310535126605,"minimum":0.0008221952078158884,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.01854760148107975,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0017194904093865027,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.008998811123027362,"gene_effect_median":-0.005389341021779709},"dependency_probability_context_minus_non_context_median":-0.0018624797060952606,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.009436253330396771,"gene_effect_context_minus_non_context_median":-0.005524901020421788}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 235
+- **Dependency-aware candidate rank:** 235
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_84f0aee76b7517c0713b74a66cc7787f61493cf2d644a12f7c125e6a7b1ee66f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BRD3|entrez:8019`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
235not prioritized-2
Resistance biomarker0.000
235not prioritized-2
Tumor-intrinsic / small molecule0.000
235not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.511)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BRD3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BRD3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BRD4.html b/examples/html_reports/depmap_26q1/targets/BRD4.html new file mode 100644 index 0000000..7d957f0 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BRD4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BRD4 + + + + +
+ +
+

Target hypothesis report: BRD4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BRD4
+
+
+
Target name
+
bromodomain containing 4
+
+
+
Open Targets melanoma score
+
0.538
+
+
+
+
Open Targets baseline rank
+
181
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.248457530692548,"interquartile_range":0.31380168154055843,"maximum":-0.23565820283589978,"mean":-1.077419296229426,"measured_model_count":56,"median":-1.107477935554086,"minimum":-1.7448082336119686,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.9346558491519896,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.955950792547962,"interquartile_range":0.03830238730638025,"maximum":0.9999959988125812,"mean":0.9347159273213392,"measured_model_count":56,"median":0.9859241206511045,"minimum":0.16171450657858166,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9942531798543423,"threshold_fractions":[{"denominator":56,"fraction":0.9642857142857143,"numerator":54,"threshold":0.5},{"denominator":56,"fraction":0.9107142857142857,"numerator":51,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.012852118011719371,"dependency_probability_threshold_fractions":[{"context_fraction":0.9642857142857143,"difference":0.012298959318826852,"pan_cancer_fraction":0.9519867549668874,"threshold":0.5},{"context_fraction":0.9107142857142857,"difference":0.05640964995269626,"pan_cancer_fraction":0.8543046357615894,"threshold":0.8}],"gene_effect_mean":-0.06262569475045776,"gene_effect_median":-0.0852599501660074},"dependency_probability_context_minus_non_context_median":0.013431985355028209,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9642857142857143,"difference":0.012896825396825462,"non_context_fraction":0.9513888888888888,"threshold":0.5},{"context_fraction":0.9107142857142857,"difference":0.0591517857142857,"non_context_fraction":0.8515625,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0656699993563834,"gene_effect_context_minus_non_context_median":-0.08666583394816563}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 183
+- **Dependency-aware candidate rank:** 183
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_adc5929d4b75660699e849fe64220e0ada6c45e9c7fb0367b31d5dab4d09fd09`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BRD4|entrez:23476`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
183not prioritized-2
Resistance biomarker0.000
184not prioritized-3
Tumor-intrinsic / small molecule0.000
183not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.538)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BRD4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BRD4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BTK.html b/examples/html_reports/depmap_26q1/targets/BTK.html new file mode 100644 index 0000000..cdb220d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BTK.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BTK + + + + +
+ +
+

Target hypothesis report: BTK

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BTK
+
+
+
Target name
+
Bruton tyrosine kinase
+
+
+
Open Targets melanoma score
+
0.516
+
+
+
+
Open Targets baseline rank
+
226
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.035771337179793285,"interquartile_range":0.11021362664917433,"maximum":0.3015345371345652,"mean":0.03015665145976979,"measured_model_count":56,"median":0.021314724552192434,"minimum":-0.21445633651626686,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07444228946938104,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.009506480463942741,"interquartile_range":0.01914368707509713,"maximum":0.17509651908925622,"mean":0.022697174251634644,"measured_model_count":56,"median":0.014886149558598682,"minimum":0.0014470532586933651,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02865016753903987,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.007619040350417529,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0074503311258278145,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.04085015215705611,"gene_effect_median":0.02781483045251088},"dependency_probability_context_minus_non_context_median":-0.00791877146594909,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0078125,"non_context_fraction":0.0078125,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04283592344246858,"gene_effect_context_minus_non_context_median":0.028645312644089246}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 228
+- **Dependency-aware candidate rank:** 228
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_bdff26cd1390682ce0aab280e0ad3136f9ebd8df2a4e41abd2cf34287ace1a21`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BTK|entrez:695`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
228not prioritized-2
Resistance biomarker0.000
228not prioritized-2
Tumor-intrinsic / small molecule0.000
228not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.516)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BTK lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BTK in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/BUB1B.html b/examples/html_reports/depmap_26q1/targets/BUB1B.html new file mode 100644 index 0000000..e6c4fad --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/BUB1B.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: BUB1B + + + + +
+ +
+

Target hypothesis report: BUB1B

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
BUB1B
+
+
+
Target name
+
BUB1 mitotic checkpoint serine/threonine kinase B
+
+
+
Open Targets melanoma score
+
0.519
+
+
+
+
Open Targets baseline rank
+
218
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.3026861749001495,"interquartile_range":0.34471355076042975,"maximum":-0.35062174656503176,"mean":-1.1293619487648725,"measured_model_count":56,"median":-1.1239831043751725,"minimum":-1.9513382130061605,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.9579726241397197,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9661276307634157,"interquartile_range":0.027854131010518257,"maximum":1.0,"mean":0.9478580814276604,"measured_model_count":56,"median":0.9837485018692456,"minimum":0.27364189485863244,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9939817617739339,"threshold_fractions":[{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.5},{"denominator":56,"fraction":0.9285714285714286,"numerator":52,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004764787764668599,"dependency_probability_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":-0.00047303689687805406,"pan_cancer_fraction":0.9826158940397351,"threshold":0.5},{"context_fraction":0.9285714285714286,"difference":-0.02838221381267736,"pan_cancer_fraction":0.956953642384106,"threshold":0.8}],"gene_effect_mean":0.09650160394376806,"gene_effect_median":0.08149630964729271},"dependency_probability_context_minus_non_context_median":-0.0049250007582350985,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":-0.0004960317460317443,"non_context_fraction":0.9826388888888888,"threshold":0.5},{"context_fraction":0.9285714285714286,"difference":-0.029761904761904767,"non_context_fraction":0.9583333333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.10119265413547818,"gene_effect_context_minus_non_context_median":0.08446568961822298}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 220
+- **Dependency-aware candidate rank:** 220
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_52cb19a67699623cc57a20835603781eea551f4092f163861315d52368c52ee5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:BUB1B|entrez:701`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
220not prioritized-2
Resistance biomarker0.000
220not prioritized-2
Tumor-intrinsic / small molecule0.000
220not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.519)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: BUB1B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for BUB1B in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CACNA1D.html b/examples/html_reports/depmap_26q1/targets/CACNA1D.html new file mode 100644 index 0000000..16926b3 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CACNA1D.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CACNA1D + + + + +
+ +
+

Target hypothesis report: CACNA1D

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CACNA1D
+
+
+
Target name
+
calcium voltage-gated channel subunit alpha1 D
+
+
+
Open Targets melanoma score
+
0.517
+
+
+
+
Open Targets baseline rank
+
224
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06948366200968034,"interquartile_range":0.12410483739837593,"maximum":0.22152661199200682,"mean":-0.013247144110869868,"measured_model_count":56,"median":-0.019408167580945213,"minimum":-0.3736384929932119,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.054621175388695584,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01215263379668628,"interquartile_range":0.02561710835008954,"maximum":0.3270060202736238,"mean":0.037954791056176954,"measured_model_count":56,"median":0.02156477750214402,"minimum":0.0011308355940113652,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03776974214677582,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.008126721128793965,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.023986554352201293,"gene_effect_median":0.017300102971426506},"dependency_probability_context_minus_non_context_median":-0.008561961886107583,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.02515256741098892,"gene_effect_context_minus_non_context_median":0.018531630100138224}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 226
+- **Dependency-aware candidate rank:** 226
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e38bf98f2041ad8780c0febfb438a421cc87a6cd5eecd343f6b41ada521b2b62`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CACNA1D|entrez:776`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
226not prioritized-2
Resistance biomarker0.000
226not prioritized-2
Tumor-intrinsic / small molecule0.000
226not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.517)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CACNA1D lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CACNA1D in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CARD11.html b/examples/html_reports/depmap_26q1/targets/CARD11.html new file mode 100644 index 0000000..a036e8e --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CARD11.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CARD11 + + + + +
+ +
+

Target hypothesis report: CARD11

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CARD11
+
+
+
Target name
+
caspase recruitment domain family member 11
+
+
+
Open Targets melanoma score
+
0.542
+
+
+
+
Open Targets baseline rank
+
179
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.09562676156794828,"interquartile_range":0.19020488634525662,"maximum":0.404261290756003,"mean":-0.01514292880487186,"measured_model_count":56,"median":-0.00843369100614956,"minimum":-0.54090902690978,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09457812477730834,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008250132462729496,"interquartile_range":0.053159633659909625,"maximum":0.49703376053943404,"mean":0.04895601126388154,"measured_model_count":56,"median":0.022444793911606052,"minimum":0.00045958623127264427,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06140976612263912,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01098489607869009,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.040418300808156796,"gene_effect_median":0.041333582837208976},"dependency_probability_context_minus_non_context_median":-0.011567731999631077,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.042383079319664396,"gene_effect_context_minus_non_context_median":0.042901069216673346}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 181
+- **Dependency-aware candidate rank:** 181
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_1633149fe392bc6524f87b3b4533182241d32393c25a454a335fc48d3b783f12`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CARD11|entrez:84433`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
181not prioritized-2
Resistance biomarker0.000
182not prioritized-3
Tumor-intrinsic / small molecule0.000
181not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.542)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CARD11 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CARD11 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CARS1.html b/examples/html_reports/depmap_26q1/targets/CARS1.html new file mode 100644 index 0000000..2a190bf --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CARS1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CARS1 + + + + +
+ +
+

Target hypothesis report: CARS1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CARS1
+
+
+
Target name
+
cysteinyl-tRNA synthetase 1
+
+
+
Open Targets melanoma score
+
0.504
+
+
+
+
Open Targets baseline rank
+
249
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.8026753461573768,"interquartile_range":0.3885820681187324,"maximum":-0.8250676982589952,"mean":-1.6092899115753092,"measured_model_count":56,"median":-1.5980364353584418,"minimum":-2.3420142033697706,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.4140932780386444,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9965804422428789,"interquartile_range":0.0034195577571211055,"maximum":1.0,"mean":0.9922324381369838,"measured_model_count":56,"median":0.9999665853145443,"minimum":0.8994039933591144,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-1.52871546978961e-05,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0016556291390728006,"pan_cancer_fraction":0.9983443708609272,"threshold":0.5},{"context_fraction":1.0,"difference":0.004966887417218513,"pan_cancer_fraction":0.9950331125827815,"threshold":0.8}],"gene_effect_mean":0.08020409235119175,"gene_effect_median":0.08857204807747632},"dependency_probability_context_minus_non_context_median":-1.6309468427122553e-05,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0017361111111111605,"non_context_fraction":0.9982638888888888,"threshold":0.5},{"context_fraction":1.0,"difference":0.00520833333333337,"non_context_fraction":0.9947916666666666,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08410290239604046,"gene_effect_context_minus_non_context_median":0.09378399626638156}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 251
+- **Dependency-aware candidate rank:** 251
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_3cc6e86715493ffe54d22b16e5c74b51d97db2d4907b1cb92ab2daf32b222e4e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CARS1|entrez:833`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
251not prioritized-2
Resistance biomarker0.000
251not prioritized-2
Tumor-intrinsic / small molecule0.000
251not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.504)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CARS1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CARS1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CASP8.html b/examples/html_reports/depmap_26q1/targets/CASP8.html new file mode 100644 index 0000000..f317c4f --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CASP8.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CASP8 + + + + +
+ +
+

Target hypothesis report: CASP8

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CASP8
+
+
+
Target name
+
caspase 8
+
+
+
Open Targets melanoma score
+
0.572
+
+
+
+
Open Targets baseline rank
+
112
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.011897068060551866,"interquartile_range":0.12536036995353528,"maximum":0.8713892618394627,"mean":0.06026911617051994,"measured_model_count":56,"median":0.04398793623669359,"minimum":-0.3339036816398781,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11346330189298341,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005880240328625039,"interquartile_range":0.022025935311596547,"maximum":0.2593446374523578,"mean":0.026311317489120405,"measured_model_count":56,"median":0.010841974401337703,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.027906175640221586,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":9.028752303627194e-05,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.0277111166708659,"gene_effect_median":-0.03366897379591392},"dependency_probability_context_minus_non_context_median":9.028752303627194e-05,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.029058184842366372,"gene_effect_context_minus_non_context_median":-0.035154619781945506}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 114
+- **Dependency-aware candidate rank:** 114
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_53df70bb8fc55be15417576e10356b10b76a98092555cecfcd70ea00ec9847b6`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CASP8|entrez:841`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
114not prioritized-2
Resistance biomarker0.000
115not prioritized-3
Tumor-intrinsic / small molecule0.000
114not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.572)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CASP8 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CASP8 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CBFA2T3.html b/examples/html_reports/depmap_26q1/targets/CBFA2T3.html new file mode 100644 index 0000000..690267c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CBFA2T3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CBFA2T3 + + + + +
+ +
+

Target hypothesis report: CBFA2T3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CBFA2T3
+
+
+
Target name
+
CBFA2/RUNX1 partner transcriptional co-repressor 3
+
+
+
Open Targets melanoma score
+
0.475
+
+
+
+
Open Targets baseline rank
+
279
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.136964140758632,"interquartile_range":0.16167139541119036,"maximum":0.21418474445863944,"mean":-0.05229143749802029,"measured_model_count":56,"median":-0.01977128242853117,"minimum":-0.4116048408666105,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02470725465255836,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.015136985019785953,"interquartile_range":0.05489342649673515,"maximum":0.3112207868780006,"mean":0.05585963773120791,"measured_model_count":56,"median":0.02561603909201212,"minimum":0.0020054058447227492,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0700304115165211,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0045371008859744,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.05239136326576069,"gene_effect_median":-0.02362187206276809},"dependency_probability_context_minus_non_context_median":0.004677530502939297,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.05493816564673518,"gene_effect_context_minus_non_context_median":-0.026067259451230895}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 279
+- **Dependency-aware candidate rank:** 279
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e5ae10bfdb0910742e6621de3128718715c20aefe67309b801c2f01f1e9e608b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CBFA2T3|entrez:863`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
279not prioritized0
Resistance biomarker0.000
279not prioritized0
Tumor-intrinsic / small molecule0.000
279not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.475)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CBFA2T3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CBFA2T3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CBL.html b/examples/html_reports/depmap_26q1/targets/CBL.html new file mode 100644 index 0000000..6f05ef4 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CBL.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CBL + + + + +
+ +
+

Target hypothesis report: CBL

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CBL
+
+
+
Target name
+
Cbl proto-oncogene
+
+
+
Open Targets melanoma score
+
0.582
+
+
+
+
Open Targets baseline rank
+
96
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.03494968754517518,"interquartile_range":0.12545142715306176,"maximum":0.38716705456969325,"mean":0.03013536038410847,"measured_model_count":56,"median":0.019575406859070273,"minimum":-0.21767347114684926,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09050173960788657,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0085481911101527,"interquartile_range":0.01963866209088416,"maximum":0.10180326303471457,"mean":0.022745420875610177,"measured_model_count":56,"median":0.015865046905975483,"minimum":0.0010694223846413645,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02818685320103686,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0006230784257667266,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.004217348259192944,"gene_effect_median":-0.004799686634262463},"dependency_probability_context_minus_non_context_median":-0.00069776111089127,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.004422358244014844,"gene_effect_context_minus_non_context_median":-0.004873586214154284}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 99
+- **Dependency-aware candidate rank:** 99
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_4b2aac16496b16aafe4d48688b4e149959c98fe30ba2a36f2df34730aa9b9406`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CBL|entrez:867`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
99not prioritized-3
Resistance biomarker0.000
100not prioritized-4
Tumor-intrinsic / small molecule0.000
99not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.582)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CBL lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CBL in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CBLB.html b/examples/html_reports/depmap_26q1/targets/CBLB.html new file mode 100644 index 0000000..755bf36 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CBLB.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CBLB + + + + +
+ +
+

Target hypothesis report: CBLB

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CBLB
+
+
+
Target name
+
Cbl proto-oncogene B
+
+
+
Open Targets melanoma score
+
0.558
+
+
+
+
Open Targets baseline rank
+
139
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.05384536648266203,"interquartile_range":0.1050815451078648,"maximum":0.3454643691830615,"mean":0.007447681590991319,"measured_model_count":56,"median":-0.0034065031597723177,"minimum":-0.16375155174679337,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05123617862520277,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.010491807935730858,"interquartile_range":0.0307455167698769,"maximum":0.12149399207427411,"mean":0.026859285847007187,"measured_model_count":56,"median":0.020538144383673726,"minimum":0.0006857831670003677,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04123732470560776,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0032368472237769494,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.01643998313273535,"gene_effect_median":0.011004086664659123},"dependency_probability_context_minus_non_context_median":-0.0033771440743860168,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01723914897946556,"gene_effect_context_minus_non_context_median":0.011426898627511239}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 141
+- **Dependency-aware candidate rank:** 141
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_7d1e1cd259415931be46985e73b7babfbae13a0705fcdfdf58d1c28892b51406`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CBLB|entrez:868`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
141not prioritized-2
Resistance biomarker0.000
142not prioritized-3
Tumor-intrinsic / small molecule0.000
141not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.558)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CBLB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CBLB in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CCND1.html b/examples/html_reports/depmap_26q1/targets/CCND1.html new file mode 100644 index 0000000..87df601 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CCND1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CCND1 + + + + +
+ +
+

Target hypothesis report: CCND1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CCND1
+
+
+
Target name
+
cyclin D1
+
+
+
Open Targets melanoma score
+
0.635
+
+
+
+
Open Targets baseline rank
+
39
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-2.5159803501587126,"interquartile_range":1.317293670034944,"maximum":-0.05330788682190524,"mean":-1.8967774740528005,"measured_model_count":56,"median":-1.828765775143998,"minimum":-3.3354607159421072,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.1986866801237686,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9930169828579302,"interquartile_range":0.006983017142069836,"maximum":1.0,"mean":0.9517735651535275,"measured_model_count":56,"median":1.0,"minimum":0.045554294167438766,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":0.9642857142857143,"numerator":54,"threshold":0.5},{"denominator":56,"fraction":0.9107142857142857,"numerator":51,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.01699677125141008,"dependency_probability_threshold_fractions":[{"context_fraction":0.9642857142857143,"difference":0.21925260170293281,"pan_cancer_fraction":0.7450331125827815,"threshold":0.5},{"context_fraction":0.9107142857142857,"difference":0.2567407757805109,"pan_cancer_fraction":0.6539735099337748,"threshold":0.8}],"gene_effect_mean":-0.650858557444201,"gene_effect_median":-0.7516415503073022},"dependency_probability_context_minus_non_context_median":0.02102358843125729,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9642857142857143,"difference":0.2299107142857143,"non_context_fraction":0.734375,"threshold":0.5},{"context_fraction":0.9107142857142857,"difference":0.2692212301587301,"non_context_fraction":0.6414930555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.6824975150977388,"gene_effect_context_minus_non_context_median":-0.7884990157905569}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 46
+- **Dependency-aware candidate rank:** 46
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ca8fd343d55b4e0866b281cdb13f04e7eb09a3d99a6fa26dfa3a2f7efb22ddf2`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CCND1|entrez:595`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
46not prioritized-7
Resistance biomarker0.000
48not prioritized-9
Tumor-intrinsic / small molecule0.000
46not prioritized-7
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.635)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CCND1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CCND1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CCND2.html b/examples/html_reports/depmap_26q1/targets/CCND2.html new file mode 100644 index 0000000..baec19b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CCND2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CCND2 + + + + +
+ +
+

Target hypothesis report: CCND2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CCND2
+
+
+
Target name
+
cyclin D2
+
+
+
Open Targets melanoma score
+
0.560
+
+
+
+
Open Targets baseline rank
+
135
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.15579197515311352,"interquartile_range":0.17786015005357908,"maximum":0.37138012941204834,"mean":-0.05966427508651161,"measured_model_count":56,"median":-0.08633474069631311,"minimum":-0.22837474318280288,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.022068174900465552,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.013285731471925577,"interquartile_range":0.06560912247822459,"maximum":0.1904888154369347,"mean":0.05466906017495544,"measured_model_count":56,"median":0.04813965995942092,"minimum":0.0008839430891336923,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07889485395015017,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00577555222621233,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.06705298013245033,"pan_cancer_fraction":0.06705298013245033,"threshold":0.5},{"context_fraction":0.0,"difference":-0.048841059602649006,"pan_cancer_fraction":0.048841059602649006,"threshold":0.8}],"gene_effect_mean":0.10164960237461951,"gene_effect_median":0.011970886367573319},"dependency_probability_context_minus_non_context_median":-0.007143100926483945,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0703125,"non_context_fraction":0.0703125,"threshold":0.5},{"context_fraction":0.0,"difference":-0.051215277777777776,"non_context_fraction":0.051215277777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.1065909024900524,"gene_effect_context_minus_non_context_median":0.012724641971365469}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 137
+- **Dependency-aware candidate rank:** 137
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_86d669a6908841a2c507d635b235616e6726255d8546fbba0fa0fca90a3d8f86`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CCND2|entrez:894`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
137not prioritized-2
Resistance biomarker0.000
138not prioritized-3
Tumor-intrinsic / small molecule0.000
137not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.560)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CCND2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CCND2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CD274.html b/examples/html_reports/depmap_26q1/targets/CD274.html new file mode 100644 index 0000000..7cfe7ad --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CD274.html @@ -0,0 +1,441 @@ + + + + +TargetIntel-IO report: CD274 + + + + +
+ +
+

Target hypothesis report: CD274

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CD274
+
+
+
Target name
+
CD274 molecule
+
+
+
Open Targets melanoma score
+
0.612
+
+
+
+
Open Targets baseline rank
+
53
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.1219432529423023,"interquartile_range":0.14942892394873147,"maximum":0.5564732732340494,"mean":0.19436573097880774,"measured_model_count":56,"median":0.1863639156999815,"minimum":-0.07863180936507297,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.27137217689103377,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.001499226517437284,"interquartile_range":0.0064206254383672645,"maximum":0.036701970754130495,"mean":0.006382432047991671,"measured_model_count":56,"median":0.0035318069749596765,"minimum":8.135797076424987e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.007919851955804549,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0006216088255521519,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.014569741459674629,"gene_effect_median":0.0027778599042512786},"dependency_probability_context_minus_non_context_median":-0.0006866699950678077,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01527799278063105,"gene_effect_context_minus_non_context_median":0.00343451210457299}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 3
+- **Dependency-aware candidate rank:** 9
+- **Rank delta:** 6
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_c33d7ba54af47d54589acf9c900707872f41fa304ee8236c34732f1ac9546be5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CD274|entrez:29126`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
anti-PD-1 combination target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
block / inhibit
+
+
+
Best modality
+
antibody / IO-combination target
+
+
+
Resistance axis
+
checkpoint_redundancy
+
+
+
Matched resistance programs
+
Checkpoint redundancy
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.825
3high50
Resistance biomarker0.496
9medium44
Tumor-intrinsic / small molecule0.141
11low42
+
+ +
+

Evidence for

+
    +
  • Immune checkpoint biology
    • +
  • Potential compensatory inhibitory pathway after PD-1 blockade
    • +
  • Surface-accessible immune receptor or ligand
    • +
  • Moderate Open Targets melanoma association score (0.612)
    • +
  • Maps to curated anti-PD-1 resistance program: Checkpoint redundancy
    • +
  • Stable role classifier confidence is high
    • +
  • Antibody fit is high
    • +
  • IO-combination fit is high
    • +
  • Checkpoint-axis biology supports anti-PD-1 combination rationale
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Crowded IO target space
    • +
  • Expression may reflect exhausted immune-cell abundance rather than causal resistance in all tumors
    • +
  • Patient selection may be required
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
high confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.240
+
+
+
+
Main limitation
+
No major limitation flagged by current MVP rules
+
+
+

Uncertainty reason: Main limitation: No major limitation flagged by current MVP rules

+

Deprioritization reason: No strong deprioritization reason from current MVP rules

+
+ +
+

Recommended next validation experiment

+

Validation category: immune-checkpoint functional validation

+

Next experiment: Validate CD274 expression in exhausted CD8 T-cell populations from anti-PD-1-resistant melanoma samples and test blockade in a melanoma/T-cell co-culture assay.

+

Rationale: This would test whether the candidate marks a relevant checkpoint axis and whether blockade can improve anti-tumor T-cell activity.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CD79A.html b/examples/html_reports/depmap_26q1/targets/CD79A.html new file mode 100644 index 0000000..e290813 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CD79A.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CD79A + + + + +
+ +
+

Target hypothesis report: CD79A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CD79A
+
+
+
Target name
+
CD79a molecule
+
+
+
Open Targets melanoma score
+
0.478
+
+
+
+
Open Targets baseline rank
+
275
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.059678830445944894,"interquartile_range":0.09997205789462581,"maximum":0.26466406443135215,"mean":0.1122462807561854,"measured_model_count":56,"median":0.1100920547426244,"minimum":-0.02926449099631112,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1596508883405707,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.003938865463013505,"interquartile_range":0.009093021526598969,"maximum":0.02573885019852544,"mean":0.008905088974721555,"measured_model_count":56,"median":0.0069261069107548695,"minimum":0.0007298659872511824,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.013031886989612475,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0013563893853354046,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.01076158940397351,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008278145695364239,"pan_cancer_fraction":0.008278145695364239,"threshold":0.8}],"gene_effect_mean":-0.023727691561340747,"gene_effect_median":-0.039209474166331776},"dependency_probability_context_minus_non_context_median":0.0014130548944801266,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.011284722222222222,"non_context_fraction":0.011284722222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008680555555555556,"non_context_fraction":0.008680555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.024881121012239216,"gene_effect_context_minus_non_context_median":-0.04017112868584041}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 275
+- **Dependency-aware candidate rank:** 275
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d66951d288524081e861b8a63210e1cfeea6f700d99b6bb6b29b038a380c1404`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CD79A|entrez:973`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
275not prioritized0
Resistance biomarker0.000
275not prioritized0
Tumor-intrinsic / small molecule0.000
275not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.478)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CD79A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CD79A in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CD8A.html b/examples/html_reports/depmap_26q1/targets/CD8A.html new file mode 100644 index 0000000..4c23733 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CD8A.html @@ -0,0 +1,70 @@ +CD8A — DepMap research preview

CD8A

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.027430912377545535,"interquartile_range":0.13942569209925004,"maximum":0.46165860344769677,"mean":0.045785073452028605,"measured_model_count":56,"median":0.03928974584334112,"minimum":-0.26540822030616257,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11199477972170452,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.007483582094896921,"interquartile_range":0.017911250672013962,"maximum":0.201806266723021,"mean":0.02445228992923763,"measured_model_count":56,"median":0.011938528707279468,"minimum":0.0002748136637528369,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02539483276691088,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.007151854567642068,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.03066633825677472,"gene_effect_median":0.028327006093492063},"dependency_probability_context_minus_non_context_median":-0.007658030597719308,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03215706303314572,"gene_effect_context_minus_non_context_median":0.029962877737475586}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a02967e9bd1b73443ee516c0ffa8cfd4e3078490f5c32a7a829dc9b8e62d2549`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CD8A|entrez:925`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/CDH1.html b/examples/html_reports/depmap_26q1/targets/CDH1.html new file mode 100644 index 0000000..1d35062 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CDH1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CDH1 + + + + +
+ +
+

Target hypothesis report: CDH1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CDH1
+
+
+
Target name
+
cadherin 1
+
+
+
Open Targets melanoma score
+
0.466
+
+
+
+
Open Targets baseline rank
+
289
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.15427271942471482,"interquartile_range":0.1577065173221155,"maximum":0.2295208783394289,"mean":-0.10742966270794449,"measured_model_count":56,"median":-0.07204685958685368,"minimum":-0.8750426660413623,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.00343379789740067,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0180917185977245,"interquartile_range":0.06286002234786717,"maximum":0.874379672670159,"mean":0.10329287088429209,"measured_model_count":56,"median":0.04375955195407501,"minimum":0.0028271732493434652,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08095174094559167,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-6.01063460411444e-05,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.008159886471144753,"pan_cancer_fraction":0.043874172185430466,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.010879848628192999,"pan_cancer_fraction":0.024834437086092714,"threshold":0.8}],"gene_effect_mean":-0.007372814336056799,"gene_effect_median":0.005760578127514945},"dependency_probability_context_minus_non_context_median":-6.01063460411444e-05,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.008556547619047623,"non_context_fraction":0.044270833333333336,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.011408730158730156,"non_context_fraction":0.024305555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.007731215032948366,"gene_effect_context_minus_non_context_median":0.005760578127514945}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 289
+- **Dependency-aware candidate rank:** 289
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_c455a8c6e42620397cabba760e778dd7d0d54d24712c2e40cab8b7b2953492cf`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CDH1|entrez:999`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
289not prioritized0
Resistance biomarker0.000
289not prioritized0
Tumor-intrinsic / small molecule0.000
289not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.466)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CDH1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CDH1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CDK12.html b/examples/html_reports/depmap_26q1/targets/CDK12.html new file mode 100644 index 0000000..7a2cac2 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CDK12.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CDK12 + + + + +
+ +
+

Target hypothesis report: CDK12

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CDK12
+
+
+
Target name
+
cyclin dependent kinase 12
+
+
+
Open Targets melanoma score
+
0.587
+
+
+
+
Open Targets baseline rank
+
91
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.5586337757206544,"interquartile_range":0.19059665446702484,"maximum":-0.13749466210671846,"mean":-0.47143749469136337,"measured_model_count":56,"median":-0.47096900533770847,"minimum":-1.200422877513772,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.3680371212536296,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.35421745198329635,"interquartile_range":0.31026076242553446,"maximum":0.9783518078107925,"mean":0.49957849685747113,"measured_model_count":56,"median":0.4693828317812654,"minimum":0.04818076524574193,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.6644782144088308,"threshold_fractions":[{"denominator":56,"fraction":0.44642857142857145,"numerator":25,"threshold":0.5},{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.07074255210397296,"dependency_probability_threshold_fractions":[{"context_fraction":0.44642857142857145,"difference":0.07473982970671716,"pan_cancer_fraction":0.3716887417218543,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.046475875118259236,"pan_cancer_fraction":0.11423841059602649,"threshold":0.8}],"gene_effect_mean":-0.061717368517177074,"gene_effect_median":-0.06553518413091808},"dependency_probability_context_minus_non_context_median":0.07651601515871376,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.44642857142857145,"difference":0.07837301587301587,"non_context_fraction":0.3680555555555556,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.048735119047619055,"non_context_fraction":0.11197916666666667,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.06471751837565104,"gene_effect_context_minus_non_context_median":-0.06899439882165848}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 94
+- **Dependency-aware candidate rank:** 94
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d6da70bd96d09fc51c8e74fc16b62eae8b994e974460e3dcbfd6b05d6855d847`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CDK12|entrez:51755`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
94not prioritized-3
Resistance biomarker0.000
96not prioritized-5
Tumor-intrinsic / small molecule0.000
94not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.587)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CDK12 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CDK12 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CDK4.html b/examples/html_reports/depmap_26q1/targets/CDK4.html new file mode 100644 index 0000000..5d22a50 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CDK4.html @@ -0,0 +1,434 @@ + + + + +TargetIntel-IO report: CDK4 + + + + +
+ +
+

Target hypothesis report: CDK4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CDK4
+
+
+
Target name
+
cyclin dependent kinase 4
+
+
+
Open Targets melanoma score
+
0.735
+
+
+
+
Open Targets baseline rank
+
10
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.1460787729249597,"interquartile_range":0.6487242724872709,"maximum":0.14819456849436097,"mean":-0.9690295177076944,"measured_model_count":56,"median":-0.7802086880629331,"minimum":-2.6012252653565273,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.4973545004376888,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.5276778197266463,"interquartile_range":0.46063984426021753,"maximum":1.0,"mean":0.7625651007343259,"measured_model_count":56,"median":0.8640150958074966,"minimum":0.0044507692556070445,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9883176639868638,"threshold_fractions":[{"denominator":56,"fraction":0.7857142857142857,"numerator":44,"threshold":0.5},{"denominator":56,"fraction":0.5892857142857143,"numerator":33,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.19303827080821434,"dependency_probability_threshold_fractions":[{"context_fraction":0.7857142857142857,"difference":0.14167455061494794,"pan_cancer_fraction":0.6440397350993378,"threshold":0.5},{"context_fraction":0.5892857142857143,"difference":0.18200094607379375,"pan_cancer_fraction":0.40728476821192056,"threshold":0.8}],"gene_effect_mean":-0.23795306295958707,"gene_effect_median":-0.21969659440659983},"dependency_probability_context_minus_non_context_median":0.19930434880478232,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.7857142857142857,"difference":0.1485615079365079,"non_context_fraction":0.6371527777777778,"threshold":0.5},{"context_fraction":0.5892857142857143,"difference":0.1908482142857143,"non_context_fraction":0.3984375,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.24952022574234523,"gene_effect_context_minus_non_context_median":-0.22500520575267613}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 18
+- **Dependency-aware candidate rank:** 14
+- **Rank delta:** -4
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_71442941b019de45c466e32e7241f8d7bfdaa6dc865747d44e280e0a14e246ad`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CDK4|entrez:1019`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / small-molecule target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
small-molecule inhibition / pathway targeting
+
+
+
Best modality
+
small molecule / pathway targeting
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
18not prioritized-8
Resistance biomarker0.101
21low-11
Tumor-intrinsic / small molecule0.682
4medium6
+
+ +
+

Evidence for

+
    +
  • High Open Targets melanoma association score (0.735)
    • +
  • Stable role classifier confidence is high
    • +
  • Small-molecule fit is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
0.889
+
+
+
+
Contradiction score
+
0.160
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CDK4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: tumor-intrinsic functional validation

+

Next experiment: Evaluate whether perturbing CDK4 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays.

+

Rationale: This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CDK6.html b/examples/html_reports/depmap_26q1/targets/CDK6.html new file mode 100644 index 0000000..5081d23 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CDK6.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CDK6 + + + + +
+ +
+

Target hypothesis report: CDK6

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CDK6
+
+
+
Target name
+
cyclin dependent kinase 6
+
+
+
Open Targets melanoma score
+
0.575
+
+
+
+
Open Targets baseline rank
+
107
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.827840200340922,"interquartile_range":0.5564369377066776,"maximum":0.053999009787811136,"mean":-0.6040550843316354,"measured_model_count":56,"median":-0.4741396489201388,"minimum":-1.9939384470287465,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.2714032626342444,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.21797895301513842,"interquartile_range":0.7309485506409665,"maximum":1.0,"mean":0.5655746850424314,"measured_model_count":56,"median":0.5298570181549593,"minimum":0.009549200402016388,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.948927503656105,"threshold_fractions":[{"denominator":56,"fraction":0.5178571428571429,"numerator":29,"threshold":0.5},{"denominator":56,"fraction":0.39285714285714285,"numerator":22,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.09549984337280804,"dependency_probability_threshold_fractions":[{"context_fraction":0.5178571428571429,"difference":-0.024361400189214732,"pan_cancer_fraction":0.5422185430463576,"threshold":0.5},{"context_fraction":0.39285714285714285,"difference":-0.024361400189214788,"pan_cancer_fraction":0.41721854304635764,"threshold":0.8}],"gene_effect_mean":0.02827248424985951,"gene_effect_median":0.054575631840271366},"dependency_probability_context_minus_non_context_median":-0.09879939553115324,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.5178571428571429,"difference":-0.025545634920634885,"non_context_fraction":0.5434027777777778,"threshold":0.5},{"context_fraction":0.39285714285714285,"difference":-0.02554563492063494,"non_context_fraction":0.4184027777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.02964684112311744,"gene_effect_context_minus_non_context_median":0.055977625413455634}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 110
+- **Dependency-aware candidate rank:** 110
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d432699f277936d0a0710e776785be716c2382f5549aa72d6ea6cb5b97df404e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CDK6|entrez:1021`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
110not prioritized-3
Resistance biomarker0.000
111not prioritized-4
Tumor-intrinsic / small molecule0.000
110not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.575)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CDK6 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CDK6 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CDKN2A.html b/examples/html_reports/depmap_26q1/targets/CDKN2A.html new file mode 100644 index 0000000..02140d2 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CDKN2A.html @@ -0,0 +1,441 @@ + + + + +TargetIntel-IO report: CDKN2A + + + + +
+ +
+

Target hypothesis report: CDKN2A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CDKN2A
+
+
+
Target name
+
cyclin dependent kinase inhibitor 2A
+
+
+
Open Targets melanoma score
+
0.870
+
+
+
+
Open Targets baseline rank
+
1
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.0614428613918262,"interquartile_range":0.17868173128792053,"maximum":0.8033652137565361,"mean":0.15445826248821265,"measured_model_count":56,"median":0.16082152009903888,"minimum":-0.4366709312086744,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.24012459267974673,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0017200751468406438,"interquartile_range":0.014484209677434792,"maximum":0.35063429324839185,"mean":0.024559879767375458,"measured_model_count":56,"median":0.0038283808957741555,"minimum":1.261747964913208e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.016204284824275435,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0019739676633992193,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.005233775424175274,"gene_effect_median":0.007051042654115713},"dependency_probability_context_minus_non_context_median":-0.0020327056425661766,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.005488195062850421,"gene_effect_context_minus_non_context_median":0.007081072312246278}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 12
+- **Dependency-aware candidate rank:** 18
+- **Rank delta:** 6
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_af0669fbbe0ab3cee1677b9b37ac27abdf1a632e7a02f16c03de98c74dfd6de5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CDKN2A|entrez:1029`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / poor direct therapeutic target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
avoid as direct target / use as biomarker or pathway context
+
+
+
Best modality
+
biomarker / pathway context only
+
+
+
Resistance axis
+
tumor_intrinsic_driver
+
+
+
Matched resistance programs
+
Tumor-intrinsic driver biology
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
12not prioritized-11
Resistance biomarker0.329
15low-14
Tumor-intrinsic / small molecule0.000
36not prioritized-35
+
+ +
+

Evidence for

+
    +
  • Relevant to melanoma tumor-cell biology
    • +
  • Some targets or pathways are clinically actionable
    • +
  • Useful for separating tumor-intrinsic drivers from immune-combination targets
    • +
  • High Open Targets melanoma association score (0.870)
    • +
  • Maps to curated anti-PD-1 resistance program: Tumor-intrinsic driver biology
    • +
  • Stable role classifier confidence is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Many tumor-intrinsic drivers are poor antibody targets
    • +
  • Melanoma association does not automatically imply anti-PD-1 combination suitability
    • +
  • Tumor suppressors are often poor direct therapeutic targets
    • +
  • Flagged as poor direct therapeutic target for this MVP
    • +
  • Role classifier indicates biological relevance but poor direct targetability
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.650
+
+
+
+
Main limitation
+
Poor direct therapeutic target despite biological relevance
+
+
+

Uncertainty reason: High contradiction score indicates important opposing evidence | Main limitation: Poor direct therapeutic target despite biological relevance

+

Deprioritization reason: CDKN2A should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context.

+
+ +
+

Recommended next validation experiment

+

Validation category: tumor-intrinsic functional validation

+

Next experiment: Evaluate whether perturbing CDKN2A alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays.

+

Rationale: This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CDKN2B.html b/examples/html_reports/depmap_26q1/targets/CDKN2B.html new file mode 100644 index 0000000..1c06fef --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CDKN2B.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CDKN2B + + + + +
+ +
+

Target hypothesis report: CDKN2B

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CDKN2B
+
+
+
Target name
+
cyclin dependent kinase inhibitor 2B
+
+
+
Open Targets melanoma score
+
0.496
+
+
+
+
Open Targets baseline rank
+
257
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 55
+- **Available reference observations:** 1110
+- **Coverage fraction:** 0.9821428571428571
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.0404825098272594,"interquartile_range":0.19472070385108634,"maximum":0.6165124700793739,"mean":0.1636209642579699,"measured_model_count":55,"median":0.15881718146129087,"minimum":-0.12693022289918005,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":0.23520321367834574,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0013846813277508152,"interquartile_range":0.01286710860460067,"maximum":0.06171403833365283,"mean":0.009855320712572656,"measured_model_count":55,"median":0.005092649083602317,"minimum":4.676073979628638e-06,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":0.014251789932351485,"threshold_fractions":[{"denominator":55,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":55,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0035823099792716053,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008583690987124463,"pan_cancer_fraction":0.0008583690987124463,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.04530797019094235,"gene_effect_median":0.05950721862052126},"dependency_probability_context_minus_non_context_median":-0.003853541450446498,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0009009009009009009,"non_context_fraction":0.0009009009009009009,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04755295970490793,"gene_effect_context_minus_non_context_median":0.06235235195401219}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 259
+- **Dependency-aware candidate rank:** 259
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_f55e29f5bfe9f319f252aa005c39aa1bb9c3cc6b22ccb92171ede2cb04873f4b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CDKN2B|entrez:1030`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
259not prioritized-2
Resistance biomarker0.000
259not prioritized-2
Tumor-intrinsic / small molecule0.000
259not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.496)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CDKN2B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CDKN2B in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CDX2.html b/examples/html_reports/depmap_26q1/targets/CDX2.html new file mode 100644 index 0000000..b9758c0 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CDX2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CDX2 + + + + +
+ +
+

Target hypothesis report: CDX2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CDX2
+
+
+
Target name
+
caudal type homeobox 2
+
+
+
Open Targets melanoma score
+
0.530
+
+
+
+
Open Targets baseline rank
+
187
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.13942254695053768,"interquartile_range":0.16163068207457448,"maximum":0.29566206461172795,"mean":-0.06736407857919634,"measured_model_count":56,"median":-0.059264623715066425,"minimum":-0.41280316373867654,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.022208135124036785,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.015200994236108184,"interquartile_range":0.06085001454530309,"maximum":0.43100994254852387,"mean":0.062366427518474085,"measured_model_count":56,"median":0.03842983462576611,"minimum":0.0017620750891681012,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07605100878141127,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.010355728954199207,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.02566225165562914,"pan_cancer_fraction":0.02566225165562914,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014072847682119206,"pan_cancer_fraction":0.014072847682119206,"threshold":0.8}],"gene_effect_mean":0.03963938525951244,"gene_effect_median":0.030046028123697097},"dependency_probability_context_minus_non_context_median":-0.010947717597245561,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.026909722222222224,"non_context_fraction":0.026909722222222224,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014756944444444444,"non_context_fraction":0.014756944444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04156629982073877,"gene_effect_context_minus_non_context_median":0.030874335457464375}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 189
+- **Dependency-aware candidate rank:** 189
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_f532f7772ff1101af041bee1f2781fa30b78e5aa23bbe47309c33b4908ee29de`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CDX2|entrez:1045`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
189not prioritized-2
Resistance biomarker0.000
190not prioritized-3
Tumor-intrinsic / small molecule0.000
189not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.530)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CDX2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CDX2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CHD4.html b/examples/html_reports/depmap_26q1/targets/CHD4.html new file mode 100644 index 0000000..8c5ccf4 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CHD4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CHD4 + + + + +
+ +
+

Target hypothesis report: CHD4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CHD4
+
+
+
Target name
+
chromodomain helicase DNA binding protein 4
+
+
+
Open Targets melanoma score
+
0.520
+
+
+
+
Open Targets baseline rank
+
210
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.4566567459085873,"interquartile_range":0.35622946135425004,"maximum":-0.5235966708192303,"mean":-1.256281075871031,"measured_model_count":56,"median":-1.2512662213227028,"minimum":-2.0043420178114166,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.1004272845543372,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9815862695547178,"interquartile_range":0.017558270975871704,"maximum":1.0,"mean":0.978835362557547,"measured_model_count":56,"median":0.9929567916053474,"minimum":0.6621869651205554,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9991445405305895,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.010208504155061693,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0314569536423841,"pan_cancer_fraction":0.9685430463576159,"threshold":0.5},{"context_fraction":0.9821428571428571,"difference":0.08148060548722791,"pan_cancer_fraction":0.9006622516556292,"threshold":0.8}],"gene_effect_mean":-0.1396756467244169,"gene_effect_median":-0.14570596698181015},"dependency_probability_context_minus_non_context_median":0.010845726535144928,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.03298611111111116,"non_context_fraction":0.9670138888888888,"threshold":0.5},{"context_fraction":0.9821428571428571,"difference":0.08544146825396826,"non_context_fraction":0.8967013888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.14646543510685328,"gene_effect_context_minus_non_context_median":-0.1557376988814274}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 212
+- **Dependency-aware candidate rank:** 212
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ff6f93762cf60634a0c2870dd7eedf4d385ff4a98109a2db6f6b4e8729158796`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CHD4|entrez:1108`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
212not prioritized-2
Resistance biomarker0.000
212not prioritized-2
Tumor-intrinsic / small molecule0.000
212not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.520)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CHD4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CHD4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CHEK2.html b/examples/html_reports/depmap_26q1/targets/CHEK2.html new file mode 100644 index 0000000..541bb64 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CHEK2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CHEK2 + + + + +
+ +
+

Target hypothesis report: CHEK2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CHEK2
+
+
+
Target name
+
checkpoint kinase 2
+
+
+
Open Targets melanoma score
+
0.609
+
+
+
+
Open Targets baseline rank
+
58
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.23674494928062137,"interquartile_range":0.22708131202008544,"maximum":0.931883971568137,"mean":0.3426903444379113,"measured_model_count":56,"median":0.3224042378144514,"minimum":-0.16147390203749837,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.4638262613007068,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":9.751658835563242e-05,"interquartile_range":0.003480886578628852,"maximum":0.0694434148067228,"mean":0.0052062046687379885,"measured_model_count":56,"median":0.0006560276296503497,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.003578403166984485,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0028864308678459333,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.12317797889945803,"gene_effect_median":0.12028586236296915},"dependency_probability_context_minus_non_context_median":-0.003037398527081421,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.12916579731818173,"gene_effect_context_minus_non_context_median":0.12552324945476412}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 62
+- **Dependency-aware candidate rank:** 62
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_09f9262c521cf121a5d9e852ab259938008d088fd5a38e1310de927d0bd04837`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CHEK2|entrez:11200`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
62not prioritized-4
Resistance biomarker0.000
64not prioritized-6
Tumor-intrinsic / small molecule0.000
62not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.609)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CHEK2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CHEK2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CIC.html b/examples/html_reports/depmap_26q1/targets/CIC.html new file mode 100644 index 0000000..d3967c2 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CIC.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CIC + + + + +
+ +
+

Target hypothesis report: CIC

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CIC
+
+
+
Target name
+
capicua transcriptional repressor
+
+
+
Open Targets melanoma score
+
0.548
+
+
+
+
Open Targets baseline rank
+
162
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.20969753443445882,"interquartile_range":0.3188863089690407,"maximum":0.7212674338591033,"mean":-0.05479185248369578,"measured_model_count":56,"median":-0.0724818295618623,"minimum":-0.5922742740203383,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10918877453458187,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0060443484088349726,"interquartile_range":0.10425416850941045,"maximum":0.6755686797363436,"mean":0.11305469201665709,"measured_model_count":56,"median":0.041316844193587124,"minimum":3.871106505121315e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11029851691824542,"threshold_fractions":[{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.008067677213065963,"dependency_probability_threshold_fractions":[{"context_fraction":0.08928571428571429,"difference":0.06279564806054873,"pan_cancer_fraction":0.026490066225165563,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.004468862662839836,"gene_effect_median":-0.02461731785542992},"dependency_probability_context_minus_non_context_median":0.008224799734887003,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.08928571428571429,"difference":0.06584821428571429,"non_context_fraction":0.0234375,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0046860990422833634,"gene_effect_context_minus_non_context_median":-0.02528609467709926}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 164
+- **Dependency-aware candidate rank:** 164
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_bf7e717c579a7d7a14cf42c0df9464f601e211197d021369f7e618579d91330e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CIC|entrez:23152`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
164not prioritized-2
Resistance biomarker0.000
165not prioritized-3
Tumor-intrinsic / small molecule0.000
164not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.548)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CIC lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CIC in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CIITA.html b/examples/html_reports/depmap_26q1/targets/CIITA.html new file mode 100644 index 0000000..21b6874 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CIITA.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CIITA + + + + +
+ +
+

Target hypothesis report: CIITA

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CIITA
+
+
+
Target name
+
class II major histocompatibility complex transactivator
+
+
+
Open Targets melanoma score
+
0.562
+
+
+
+
Open Targets baseline rank
+
131
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.07481705516268009,"interquartile_range":0.14392723189675605,"maximum":0.21949437633984192,"mean":-0.005468924475870724,"measured_model_count":56,"median":0.01143269694703151,"minimum":-0.30489474426374596,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06911017673407598,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.009702019229598511,"interquartile_range":0.02840255596041054,"maximum":0.24617646555482525,"mean":0.03490953789092406,"measured_model_count":56,"median":0.016486777927961806,"minimum":0.001692034244815741,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03810457519000905,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00250613097564693,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.04724097755465141,"gene_effect_median":-0.03827391409799615},"dependency_probability_context_minus_non_context_median":0.0025912562613762628,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.049537413963558055,"gene_effect_context_minus_non_context_median":-0.040293550612653085}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 133
+- **Dependency-aware candidate rank:** 133
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_8bc1c2d3f4d300f45d815f33d7bae0eddb7438eb8acbbe6165053511428be195`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CIITA|entrez:4261`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
133not prioritized-2
Resistance biomarker0.000
134not prioritized-3
Tumor-intrinsic / small molecule0.000
133not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.562)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CIITA lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CIITA in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CLPTM1L.html b/examples/html_reports/depmap_26q1/targets/CLPTM1L.html new file mode 100644 index 0000000..be70f1b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CLPTM1L.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CLPTM1L + + + + +
+ +
+

Target hypothesis report: CLPTM1L

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CLPTM1L
+
+
+
Target name
+
CLPTM1 like
+
+
+
Open Targets melanoma score
+
0.456
+
+
+
+
Open Targets baseline rank
+
299
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.03365827977140918,"interquartile_range":0.15583008785031374,"maximum":0.37251074770739345,"mean":0.12263371690035856,"measured_model_count":56,"median":0.11157894179367531,"minimum":-0.1922015107403494,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.18948836762172291,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0033575428305555734,"interquartile_range":0.009723968496991963,"maximum":0.07590534725685125,"mean":0.011504028916612676,"measured_model_count":56,"median":0.006899426529077324,"minimum":0.00046431606993314206,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.013081511327547536,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0022339082976504682,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.028843209870716507,"gene_effect_median":0.01954405845942203},"dependency_probability_context_minus_non_context_median":-0.0022567855655024355,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03024531035054301,"gene_effect_context_minus_non_context_median":0.020226207783525463}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 299
+- **Dependency-aware candidate rank:** 299
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e3507298a18eda64715615f3e322d67277805cadadaca2c9f73698595a9fecde`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CLPTM1L|entrez:81037`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
299not prioritized0
Resistance biomarker0.000
299not prioritized0
Tumor-intrinsic / small molecule0.000
299not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.456)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CLPTM1L lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CLPTM1L in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CLTC.html b/examples/html_reports/depmap_26q1/targets/CLTC.html new file mode 100644 index 0000000..31fe58b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CLTC.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CLTC + + + + +
+ +
+

Target hypothesis report: CLTC

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CLTC
+
+
+
Target name
+
clathrin heavy chain
+
+
+
Open Targets melanoma score
+
0.514
+
+
+
+
Open Targets baseline rank
+
229
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.7857849350335733,"interquartile_range":0.4306299282056192,"maximum":-0.2347483018845844,"mean":-1.549072628527409,"measured_model_count":56,"median":-1.5407053756609363,"minimum":-2.506829210747692,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.355155006827954,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9948774232974522,"interquartile_range":0.0051225767025477875,"maximum":1.0,"mean":0.9698856164023175,"measured_model_count":56,"median":0.999767927569396,"minimum":0.16076082935524,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.5},{"denominator":56,"fraction":0.9464285714285714,"numerator":53,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-1.795863215137139e-05,"dependency_probability_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":-0.005439924314096567,"pan_cancer_fraction":0.9875827814569537,"threshold":0.5},{"context_fraction":0.9464285714285714,"difference":-0.021286660359508103,"pan_cancer_fraction":0.9677152317880795,"threshold":0.8}],"gene_effect_mean":0.0327071509863226,"gene_effect_median":0.04624486316265575},"dependency_probability_context_minus_non_context_median":-2.9353196633219447e-05,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":-0.005704365079365115,"non_context_fraction":0.9878472222222222,"threshold":0.5},{"context_fraction":0.9464285714285714,"difference":-0.022321428571428603,"non_context_fraction":0.96875,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03429708193704584,"gene_effect_context_minus_non_context_median":0.04997579342742209}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 231
+- **Dependency-aware candidate rank:** 231
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_7033e45925283774f8ad12f2cf22ae8953bfaf570022fc4559990370faf98b2c`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CLTC|entrez:1213`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
231not prioritized-2
Resistance biomarker0.000
231not prioritized-2
Tumor-intrinsic / small molecule0.000
231not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.514)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CLTC lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CLTC in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CNOT3.html b/examples/html_reports/depmap_26q1/targets/CNOT3.html new file mode 100644 index 0000000..36134e5 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CNOT3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CNOT3 + + + + +
+ +
+

Target hypothesis report: CNOT3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CNOT3
+
+
+
Target name
+
CCR4-NOT transcription complex subunit 3
+
+
+
Open Targets melanoma score
+
0.546
+
+
+
+
Open Targets baseline rank
+
168
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.8102802206023003,"interquartile_range":0.4759133947241436,"maximum":-0.8320933333393696,"mean":-1.6171401145919593,"measured_model_count":56,"median":-1.5936584691809363,"minimum":-2.6290172946051253,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.3343668258781567,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9957864519235283,"interquartile_range":0.004213548076471674,"maximum":1.0,"mean":0.9930468015225653,"measured_model_count":56,"median":0.9998302256586487,"minimum":0.8246629510819868,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00016741878021642176,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.008278145695364225,"pan_cancer_fraction":0.9917218543046358,"threshold":0.5},{"context_fraction":1.0,"difference":0.01407284768211925,"pan_cancer_fraction":0.9859271523178808,"threshold":0.8}],"gene_effect_mean":-0.04720372317674393,"gene_effect_median":-0.044002518378368105},"dependency_probability_context_minus_non_context_median":0.00018512556946592706,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.00868055555555558,"non_context_fraction":0.9913194444444444,"threshold":0.5},{"context_fraction":1.0,"difference":0.01475694444444442,"non_context_fraction":0.9852430555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.04949834860894686,"gene_effect_context_minus_non_context_median":-0.04539883321473104}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 170
+- **Dependency-aware candidate rank:** 170
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e98afc18cc10dc80ef4b4c4311d9b732c3ca08ac4cb21c1dfc1556054ea2ab8f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CNOT3|entrez:4849`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
170not prioritized-2
Resistance biomarker0.000
171not prioritized-3
Tumor-intrinsic / small molecule0.000
170not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.546)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CNOT3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CNOT3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CNOT9.html b/examples/html_reports/depmap_26q1/targets/CNOT9.html new file mode 100644 index 0000000..d3f4e61 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CNOT9.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CNOT9 + + + + +
+ +
+

Target hypothesis report: CNOT9

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CNOT9
+
+
+
Target name
+
CCR4-NOT transcription complex subunit 9
+
+
+
Open Targets melanoma score
+
0.470
+
+
+
+
Open Targets baseline rank
+
284
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.6980036127159327,"interquartile_range":0.4192275870718812,"maximum":0.0003976307814048674,"mean":-0.49817548218173485,"measured_model_count":56,"median":-0.4553898880376292,"minimum":-1.1718258935647998,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.2787760256440515,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.19957058817837095,"interquartile_range":0.6479136217544184,"maximum":0.9908538830614388,"mean":0.5144858160287195,"measured_model_count":56,"median":0.5364384999804481,"minimum":0.021283857638038285,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.8474842099327893,"threshold_fractions":[{"denominator":56,"fraction":0.5178571428571429,"numerator":29,"threshold":0.5},{"denominator":56,"fraction":0.30357142857142855,"numerator":17,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0546445171227149,"dependency_probability_threshold_fractions":[{"context_fraction":0.5178571428571429,"difference":-0.059957426679280945,"pan_cancer_fraction":0.5778145695364238,"threshold":0.5},{"context_fraction":0.30357142857142855,"difference":-0.007686849574266796,"pan_cancer_fraction":0.31125827814569534,"threshold":0.8}],"gene_effect_mean":0.029476910923491306,"gene_effect_median":0.05949085474867183},"dependency_probability_context_minus_non_context_median":-0.056290615104885644,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.5178571428571429,"difference":-0.06287202380952372,"non_context_fraction":0.5807291666666666,"threshold":0.5},{"context_fraction":0.30357142857142855,"difference":-0.008060515873015872,"non_context_fraction":0.3116319444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.030909816315605354,"gene_effect_context_minus_non_context_median":0.05978971492624369}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 284
+- **Dependency-aware candidate rank:** 284
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d631e042e6716d0a9f0925ecaf1901409ec38bc825ea7d82af93c7cbf2572762`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CNOT9|entrez:9125`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
284not prioritized0
Resistance biomarker0.000
284not prioritized0
Tumor-intrinsic / small molecule0.000
284not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.470)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CNOT9 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CNOT9 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CREB1.html b/examples/html_reports/depmap_26q1/targets/CREB1.html new file mode 100644 index 0000000..182e9a0 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CREB1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CREB1 + + + + +
+ +
+

Target hypothesis report: CREB1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CREB1
+
+
+
Target name
+
cAMP responsive element binding protein 1
+
+
+
Open Targets melanoma score
+
0.525
+
+
+
+
Open Targets baseline rank
+
193
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.20042128709993842,"interquartile_range":0.20137238184885764,"maximum":0.14087319726168263,"mean":-0.10908124010337102,"measured_model_count":56,"median":-0.0970478339479603,"minimum":-0.6695722044017831,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0009510947489192074,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01905577727158126,"interquartile_range":0.09002192959362232,"maximum":0.7720182537652055,"mean":0.09194841684548548,"measured_model_count":56,"median":0.04475869080138886,"minimum":0.004161614464259778,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10907770686520359,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005796561793895302,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.01773888363292337,"pan_cancer_fraction":0.03559602649006623,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.8}],"gene_effect_mean":0.002202922419011835,"gene_effect_median":0.0008634284276914928},"dependency_probability_context_minus_non_context_median":-0.0061364271717659485,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.01860119047619048,"non_context_fraction":0.036458333333333336,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0023100089254915884,"gene_effect_context_minus_non_context_median":0.0010568504270360157}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 195
+- **Dependency-aware candidate rank:** 195
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_8080a075f5bb2d1a2544822688fc9af57849ed9288d6451bd00ab4fc5e45e00d`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CREB1|entrez:1385`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
195not prioritized-2
Resistance biomarker0.000
195not prioritized-2
Tumor-intrinsic / small molecule0.000
195not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.525)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CREB1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CREB1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CREBBP.html b/examples/html_reports/depmap_26q1/targets/CREBBP.html new file mode 100644 index 0000000..3857482 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CREBBP.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CREBBP + + + + +
+ +
+

Target hypothesis report: CREBBP

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CREBBP
+
+
+
Target name
+
CREB binding lysine acetyltransferase
+
+
+
Open Targets melanoma score
+
0.548
+
+
+
+
Open Targets baseline rank
+
163
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.12137022065317296,"interquartile_range":0.35378815047690215,"maximum":0.7647019650205802,"mean":0.07497423361604329,"measured_model_count":56,"median":0.12434295478017252,"minimum":-0.6954204183084232,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.23241792982372922,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0021103076008664352,"interquartile_range":0.04964725377051653,"maximum":0.8631610740408037,"mean":0.06300891143216202,"measured_model_count":56,"median":0.006852358906610696,"minimum":2.812680241471588e-07,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05175756137138296,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.026165016201327825,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.10300378429517504,"pan_cancer_fraction":0.12086092715231789,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.0500236518448439,"pan_cancer_fraction":0.06788079470198675,"threshold":0.8}],"gene_effect_mean":0.16572833559020977,"gene_effect_median":0.17318758736483686},"dependency_probability_context_minus_non_context_median":-0.027795804532297918,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.1080109126984127,"non_context_fraction":0.12586805555555555,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.052455357142857144,"non_context_fraction":0.0703125,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.17378457412584483,"gene_effect_context_minus_non_context_median":0.1796950424085603}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 165
+- **Dependency-aware candidate rank:** 165
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_493d659d4010adb81dc703190a85a90e88f05aaa7ba55c687d36265b8e22fe55`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CREBBP|entrez:1387`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
165not prioritized-2
Resistance biomarker0.000
166not prioritized-3
Tumor-intrinsic / small molecule0.000
165not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.548)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CREBBP lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CREBBP in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CRLF2.html b/examples/html_reports/depmap_26q1/targets/CRLF2.html new file mode 100644 index 0000000..b3cc4af --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CRLF2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CRLF2 + + + + +
+ +
+

Target hypothesis report: CRLF2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CRLF2
+
+
+
Target name
+
cytokine receptor like factor 2
+
+
+
Open Targets melanoma score
+
0.524
+
+
+
+
Open Targets baseline rank
+
196
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** insufficient_measured_context_models
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 4
+- **Available reference observations:** 70
+- **Coverage fraction:** 0.07142857142857142
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.05632700021176619,"interquartile_range":0.08015585556302292,"maximum":0.17530677089212182,"mean":0.08935700887110595,"measured_model_count":4,"median":0.10345284711544935,"minimum":-0.024784429638596728,"missing_fraction":0.9285714285714286,"missing_model_count":52,"third_quartile":0.1364828557747891,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005030190068819156,"interquartile_range":0.004354267600952262,"maximum":0.019128257672105322,"mean":0.008512832422354143,"measured_model_count":4,"median":0.005901815316236432,"minimum":0.0031194413848383844,"missing_fraction":0.9285714285714286,"missing_model_count":52,"third_quartile":0.009384457669771418,"threshold_fractions":[{"denominator":4,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":4,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":null,"dependency_probability_threshold_fractions":[],"gene_effect_mean":null,"gene_effect_median":null},"dependency_probability_context_minus_non_context_median":null,"dependency_probability_context_minus_non_context_threshold_fractions":[],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":null,"gene_effect_context_minus_non_context_median":null}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":16,"value":26.666666666666668}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 198
+- **Dependency-aware candidate rank:** 198
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_4b22d8602f73d5a1791649888a35d40e8d5297b0bf040d2fe94dcd66ba394024`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CRLF2|entrez:64109`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
198not prioritized-2
Resistance biomarker0.000
198not prioritized-2
Tumor-intrinsic / small molecule0.000
198not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.524)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CRLF2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CRLF2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CSF1R.html b/examples/html_reports/depmap_26q1/targets/CSF1R.html new file mode 100644 index 0000000..4fc7d30 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CSF1R.html @@ -0,0 +1,70 @@ +CSF1R — DepMap research preview

CSF1R

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.05283149907401659,"interquartile_range":0.13328060459387842,"maximum":0.1974333024511772,"mean":0.012647423121772904,"measured_model_count":56,"median":0.016248024381766507,"minimum":-0.32563828230030123,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08044910551986181,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.011012411673845528,"interquartile_range":0.018320867883454574,"maximum":0.223657165679814,"mean":0.023988383212230846,"measured_model_count":56,"median":0.018261184417227513,"minimum":0.0026785033287129723,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.029333279557300102,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00521709253462831,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.02693273342487096,"gene_effect_median":0.027742050845867068},"dependency_probability_context_minus_non_context_median":-0.005580588241829228,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.028241963521913268,"gene_effect_context_minus_non_context_median":0.02888135390516621}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_5317881082554f3d278499aca75ba805691f06daca02ef9f17a801f642503e45`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CSF1R|entrez:1436`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/CSF3R.html b/examples/html_reports/depmap_26q1/targets/CSF3R.html new file mode 100644 index 0000000..1d8c98f --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CSF3R.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CSF3R + + + + +
+ +
+

Target hypothesis report: CSF3R

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CSF3R
+
+
+
Target name
+
colony stimulating factor 3 receptor
+
+
+
Open Targets melanoma score
+
0.651
+
+
+
+
Open Targets baseline rank
+
31
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.171973299240679,"interquartile_range":0.12121511297415707,"maximum":0.18391648947435318,"mean":-0.11817486019417255,"measured_model_count":56,"median":-0.1036037219983435,"minimum":-0.6312179909842395,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.050758186266521926,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.030544914905776988,"interquartile_range":0.05752607440635536,"maximum":0.6352167069178504,"mean":0.08797870213130601,"measured_model_count":56,"median":0.05600813177010951,"minimum":0.004903090995091903,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08807098931213235,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00020504580053250232,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.007095553453169347,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.005250566274807966,"gene_effect_median":0.00193246870381511},"dependency_probability_context_minus_non_context_median":-0.00020504580053250232,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.00744047619047619,"non_context_fraction":0.010416666666666666,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0055058021353889125,"gene_effect_context_minus_non_context_median":0.0021304083713885313}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 38
+- **Dependency-aware candidate rank:** 38
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_606c31d0132f1c9a0651de8053093bad951a1a810a259da1898e1f695ffcba3e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CSF3R|entrez:1441`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
38not prioritized-7
Resistance biomarker0.000
40not prioritized-9
Tumor-intrinsic / small molecule0.001
33not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.651)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CSF3R lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CSF3R in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CTLA4.html b/examples/html_reports/depmap_26q1/targets/CTLA4.html new file mode 100644 index 0000000..6f7da14 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CTLA4.html @@ -0,0 +1,447 @@ + + + + +TargetIntel-IO report: CTLA4 + + + + +
+ +
+

Target hypothesis report: CTLA4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CTLA4
+
+
+
Target name
+
cytotoxic T-lymphocyte associated protein 4
+
+
+
Open Targets melanoma score
+
0.709
+
+
+
+
Open Targets baseline rank
+
15
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06677599448402638,"interquartile_range":0.15253383708406643,"maximum":0.3177811729630463,"mean":0.003779328948540078,"measured_model_count":56,"median":0.005832932383737247,"minimum":-0.3866083097477906,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08575784260004005,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.007825870156587311,"interquartile_range":0.027571901541887642,"maximum":0.3372485312184015,"mean":0.036804396485517345,"measured_model_count":56,"median":0.01842904351594934,"minimum":0.0011469855891770616,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03539777169847495,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003898367006285295,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.013253178477796149,"gene_effect_median":0.01208800428615434},"dependency_probability_context_minus_non_context_median":-0.004206617757383093,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.013897430209355667,"gene_effect_context_minus_non_context_median":0.012635598331851272}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 1
+- **Dependency-aware candidate rank:** 10
+- **Rank delta:** 9
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_b9abdd2055e5117fd2a7ad81e2fb4f17c2e329c8398a2378182f948a74f80daa`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CTLA4|entrez:1493`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
anti-PD-1 combination target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
block / inhibit
+
+
+
Best modality
+
antibody / IO-combination target
+
+
+
Resistance axis
+
checkpoint_redundancy; treg_suppression
+
+
+
Matched resistance programs
+
Checkpoint redundancy; Treg-mediated suppression
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.853
1high14
Resistance biomarker0.524
6medium9
Tumor-intrinsic / small molecule0.159
9low6
+
+ +
+

Evidence for

+
    +
  • Immune checkpoint biology
    • +
  • May support patient stratification or Treg-targeting hypotheses
    • +
  • Potential compensatory inhibitory pathway after PD-1 blockade
    • +
  • Relevant to immune suppression in the tumor microenvironment
    • +
  • Some targets are surface-accessible
    • +
  • Surface-accessible immune receptor or ligand
    • +
  • High Open Targets melanoma association score (0.709)
    • +
  • Maps to curated anti-PD-1 resistance program: Checkpoint redundancy; Treg-mediated suppression
    • +
  • Stable role classifier confidence is high
    • +
  • Antibody fit is high
    • +
  • IO-combination fit is high
    • +
  • Checkpoint-axis biology supports anti-PD-1 combination rationale
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Crowded IO target space
    • +
  • Expression may reflect exhausted immune-cell abundance rather than causal resistance in all tumors
    • +
  • Patient selection may be required
    • +
  • Requires careful distinction between biomarker and causal target
    • +
  • Some markers are lineage markers rather than safe therapeutic targets
    • +
  • Treg targeting can affect normal immune tolerance
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
high confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.400
+
+
+
+
Main limitation
+
No major limitation flagged by current MVP rules
+
+
+

Uncertainty reason: Moderate contradiction score indicates caution is needed | Main limitation: No major limitation flagged by current MVP rules

+

Deprioritization reason: No strong deprioritization reason from current MVP rules

+
+ +
+

Recommended next validation experiment

+

Validation category: immune-checkpoint functional validation

+

Next experiment: Validate CTLA4 expression in exhausted CD8 T-cell populations from anti-PD-1-resistant melanoma samples and test blockade in a melanoma/T-cell co-culture assay.

+

Rationale: This would test whether the candidate marks a relevant checkpoint axis and whether blockade can improve anti-tumor T-cell activity.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CTNNB1.html b/examples/html_reports/depmap_26q1/targets/CTNNB1.html new file mode 100644 index 0000000..29f15e3 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CTNNB1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CTNNB1 + + + + +
+ +
+

Target hypothesis report: CTNNB1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CTNNB1
+
+
+
Target name
+
catenin beta 1
+
+
+
Open Targets melanoma score
+
0.509
+
+
+
+
Open Targets baseline rank
+
241
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.30307444434386505,"interquartile_range":0.2000363522550953,"maximum":0.05464336452334989,"mean":-0.22538887888625375,"measured_model_count":56,"median":-0.20773415732109757,"minimum":-0.7761741014319005,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.10303809208876974,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.04604754552361335,"interquartile_range":0.21650665079839038,"maximum":0.8885074947332431,"mean":0.192631362342245,"measured_model_count":56,"median":0.13451455384394487,"minimum":0.010324586920754095,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2625541963220037,"threshold_fractions":[{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.05950575769005392,"dependency_probability_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":-0.059366130558183544,"pan_cancer_fraction":0.13079470198675497,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.07071901608325448,"pan_cancer_fraction":0.08857615894039735,"threshold":0.8}],"gene_effect_mean":0.021879911950915515,"gene_effect_median":-0.06766368045703583},"dependency_probability_context_minus_non_context_median":0.06114873919813857,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":-0.06225198412698413,"non_context_fraction":0.13368055555555555,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.07415674603174605,"non_context_fraction":0.0920138888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.022943518781862793,"gene_effect_context_minus_non_context_median":-0.07173187988508836}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 243
+- **Dependency-aware candidate rank:** 243
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_cbe302602f1052761e7a090a9bec399ddec4b76049ac5315c17786ec269d72e3`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CTNNB1|entrez:1499`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
243not prioritized-2
Resistance biomarker0.000
243not prioritized-2
Tumor-intrinsic / small molecule0.000
243not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.509)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CTNNB1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CTNNB1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CUX1.html b/examples/html_reports/depmap_26q1/targets/CUX1.html new file mode 100644 index 0000000..9e92948 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CUX1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CUX1 + + + + +
+ +
+

Target hypothesis report: CUX1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CUX1
+
+
+
Target name
+
cut like homeobox 1
+
+
+
Open Targets melanoma score
+
0.607
+
+
+
+
Open Targets baseline rank
+
60
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.03317565768701193,"interquartile_range":0.2361234109929508,"maximum":0.34979611804200594,"mean":0.05857234852190869,"measured_model_count":56,"median":0.04287214215173468,"minimum":-0.31298842224761375,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2029477533059389,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.003610855440009605,"interquartile_range":0.02993966487182269,"maximum":0.30936718298453664,"mean":0.03780538778138749,"measured_model_count":56,"median":0.010248060779731664,"minimum":0.00015854270563116197,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.033550520311832296,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0003123410595084891,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.8}],"gene_effect_mean":-0.023283646818891016,"gene_effect_median":-0.04264979885974313},"dependency_probability_context_minus_non_context_median":0.0003123410595084891,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.02441549076147595,"gene_effect_context_minus_non_context_median":-0.04411035860106202}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 64
+- **Dependency-aware candidate rank:** 64
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_076b62fe23db165037ade89a32df7bfdb37c19494ed249330b338d0b24a16b55`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CUX1|entrez:1523`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
64not prioritized-4
Resistance biomarker0.000
66not prioritized-6
Tumor-intrinsic / small molecule0.000
64not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.607)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CUX1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CUX1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CXCL12.html b/examples/html_reports/depmap_26q1/targets/CXCL12.html new file mode 100644 index 0000000..c6b5a5e --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CXCL12.html @@ -0,0 +1,70 @@ +CXCL12 — DepMap research preview

CXCL12

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.07577724494448412,"interquartile_range":0.190110507410803,"maximum":0.34935751396725395,"mean":0.017638110056187435,"measured_model_count":56,"median":-0.022205827285089998,"minimum":-0.3095502799648677,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11433326246631886,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.006556502005797096,"interquartile_range":0.03252096833817649,"maximum":0.21923669386606784,"mean":0.03273003379914769,"measured_model_count":56,"median":0.020696994642275326,"minimum":0.00042313838806690856,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03907747034397359,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00550717310759696,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.045236190025914044,"gene_effect_median":-0.00010726319640060392},"dependency_probability_context_minus_non_context_median":-0.005690951872236477,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04743517148550706,"gene_effect_context_minus_non_context_median":-0.00019117609302459967}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_5f75942ca13b5b7cc81ccc05fbdf4fc8532ad5012a3ab697f6d0e86a9640a499`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CXCL12|entrez:6387`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/CXCL9.html b/examples/html_reports/depmap_26q1/targets/CXCL9.html new file mode 100644 index 0000000..0f23cb1 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CXCL9.html @@ -0,0 +1,70 @@ +CXCL9 — DepMap research preview

CXCL9

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.03134505628584463,"interquartile_range":0.14056117568087112,"maximum":0.24029992912418896,"mean":0.04110868821178555,"measured_model_count":56,"median":0.05281410370015513,"minimum":-0.21141841880282625,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10921611939502648,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.00658768123852596,"interquartile_range":0.022355271394094645,"maximum":0.10831268763368852,"mean":0.0204631377324164,"measured_model_count":56,"median":0.012647935195006565,"minimum":0.001717118643636866,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.028942952632620606,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-9.538839180254707e-05,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.013954215585890863,"gene_effect_median":-0.0025869928644431245},"dependency_probability_context_minus_non_context_median":-9.538839180254707e-05,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.014632545510205,"gene_effect_context_minus_non_context_median":-0.0028313770175858455}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_753bc049b92ea8d1d3491362437565283681da2bf359811b7a35d70d20308ed0`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CXCL9|entrez:4283`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/CXCR4.html b/examples/html_reports/depmap_26q1/targets/CXCR4.html new file mode 100644 index 0000000..1bcc8cb --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CXCR4.html @@ -0,0 +1,70 @@ +CXCR4 — DepMap research preview

CXCR4

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.0002591435523185224,"interquartile_range":0.10501169832073538,"maximum":0.3673246231079541,"mean":0.05559721646707475,"measured_model_count":56,"median":0.05891644317724552,"minimum":-0.20885269756363484,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10527084187305391,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.006540828823287489,"interquartile_range":0.015723870922962044,"maximum":0.08216220534230984,"mean":0.016496695055018395,"measured_model_count":56,"median":0.012532064623048806,"minimum":0.0009317497895514716,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.022264699746249533,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002805419479474677,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.015668202208521706,"gene_effect_median":0.022358444411732868},"dependency_probability_context_minus_non_context_median":-0.00296975485108379,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.016429850926991514,"gene_effect_context_minus_non_context_median":0.02340116280440281}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_27167cd30fdf604ddec8ac3ca343fd18cbcf0ad4da47feb76041b7c691590b39`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CXCR4|entrez:7852`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/CYLD.html b/examples/html_reports/depmap_26q1/targets/CYLD.html new file mode 100644 index 0000000..8e22c19 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CYLD.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CYLD + + + + +
+ +
+

Target hypothesis report: CYLD

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CYLD
+
+
+
Target name
+
CYLD lysine 63 deubiquitinase
+
+
+
Open Targets melanoma score
+
0.580
+
+
+
+
Open Targets baseline rank
+
102
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.16691152028267855,"interquartile_range":0.19889307085090385,"maximum":0.4122109349705019,"mean":-0.06497487104668735,"measured_model_count":56,"median":-0.08653479539938982,"minimum":-0.4925174203145259,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03198155056822531,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.016821912273541333,"interquartile_range":0.07211093367154234,"maximum":0.5035553746667468,"mean":0.07855783986616326,"measured_model_count":56,"median":0.04655640165652187,"minimum":0.0004562974591991458,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08893284594508367,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004043674105023709,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.010288552507095556,"pan_cancer_fraction":0.028145695364238412,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":0.043755948689382956,"gene_effect_median":0.008757544410644177},"dependency_probability_context_minus_non_context_median":-0.004206455521640895,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.010788690476190476,"non_context_fraction":0.028645833333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04588297397289473,"gene_effect_context_minus_non_context_median":0.009368028928493657}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 105
+- **Dependency-aware candidate rank:** 105
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_8af65338931f6fdd6b4ac209b6cf1b5ed61453c68b152a6d1f252e5336eedd12`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CYLD|entrez:1540`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
105not prioritized-3
Resistance biomarker0.000
106not prioritized-4
Tumor-intrinsic / small molecule0.000
105not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.580)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CYLD lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CYLD in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/CYP1B1.html b/examples/html_reports/depmap_26q1/targets/CYP1B1.html new file mode 100644 index 0000000..131560e --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/CYP1B1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: CYP1B1 + + + + +
+ +
+

Target hypothesis report: CYP1B1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
CYP1B1
+
+
+
Target name
+
cytochrome P450 family 1 subfamily B member 1
+
+
+
Open Targets melanoma score
+
0.563
+
+
+
+
Open Targets baseline rank
+
129
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.03368777508498383,"interquartile_range":0.13687684126148855,"maximum":0.47048455575590914,"mean":0.08384933870127811,"measured_model_count":56,"median":0.09166972667834505,"minimum":-0.37744433712582043,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.17056461634647238,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0037660000533670107,"interquartile_range":0.01510846197304637,"maximum":0.2633327191464861,"mean":0.022453628011962906,"measured_model_count":56,"median":0.008242491577905423,"minimum":0.00022499114610257485,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.01887446202641338,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002526088889266493,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.009384434653959994,"gene_effect_median":0.01423679476823242},"dependency_probability_context_minus_non_context_median":-0.0027784546294805316,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.009840622449638611,"gene_effect_context_minus_non_context_median":0.014620556398485474}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 131
+- **Dependency-aware candidate rank:** 131
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_6b6dc01d1037ab7588d7507b59b5873c424dd60af50ef2b9f1b9cccf7f170b36`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:CYP1B1|entrez:1545`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
131not prioritized-2
Resistance biomarker0.000
132not prioritized-3
Tumor-intrinsic / small molecule0.000
131not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.563)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: CYP1B1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for CYP1B1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/DAXX.html b/examples/html_reports/depmap_26q1/targets/DAXX.html new file mode 100644 index 0000000..9fd465f --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/DAXX.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: DAXX + + + + +
+ +
+

Target hypothesis report: DAXX

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
DAXX
+
+
+
Target name
+
death domain associated protein
+
+
+
Open Targets melanoma score
+
0.550
+
+
+
+
Open Targets baseline rank
+
157
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.544977811841365,"interquartile_range":0.26742254574989294,"maximum":0.106113115533227,"mean":-0.4087807091327999,"measured_model_count":56,"median":-0.383732915488141,"minimum":-1.3662485543529452,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.277555266091472,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.21600580895105526,"interquartile_range":0.40819467544094223,"maximum":0.9983879181677233,"mean":0.42374344131493585,"measured_model_count":56,"median":0.4007934163278375,"minimum":0.006374091952721311,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.6242004843919975,"threshold_fractions":[{"denominator":56,"fraction":0.42857142857142855,"numerator":24,"threshold":0.5},{"denominator":56,"fraction":0.10714285714285714,"numerator":6,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.11380922710420216,"dependency_probability_threshold_fractions":[{"context_fraction":0.42857142857142855,"difference":0.12310785241248817,"pan_cancer_fraction":0.3054635761589404,"threshold":0.5},{"context_fraction":0.10714285714285714,"difference":-0.023651844843897832,"pan_cancer_fraction":0.13079470198675497,"threshold":0.8}],"gene_effect_mean":-0.03430155764609022,"gene_effect_median":-0.053760835452685674},"dependency_probability_context_minus_non_context_median":0.12201466100433733,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.42857142857142855,"difference":0.12909226190476186,"non_context_fraction":0.2994791666666667,"threshold":0.5},{"context_fraction":0.10714285714285714,"difference":-0.02480158730158731,"non_context_fraction":0.13194444444444445,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03596899447610846,"gene_effect_context_minus_non_context_median":-0.05591574640915642}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 159
+- **Dependency-aware candidate rank:** 159
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_afbc3bdc67a8e0dc3c3f194456eb04569c7ead987c1059a681ade7cf4eb260f3`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:DAXX|entrez:1616`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
159not prioritized-2
Resistance biomarker0.000
160not prioritized-3
Tumor-intrinsic / small molecule0.000
159not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.550)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: DAXX lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for DAXX in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/DDR2.html b/examples/html_reports/depmap_26q1/targets/DDR2.html new file mode 100644 index 0000000..031439d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/DDR2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: DDR2 + + + + +
+ +
+

Target hypothesis report: DDR2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
DDR2
+
+
+
Target name
+
discoidin domain receptor tyrosine kinase 2
+
+
+
Open Targets melanoma score
+
0.569
+
+
+
+
Open Targets baseline rank
+
119
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06972286446924252,"interquartile_range":0.1045132250182792,"maximum":0.2898346836075851,"mean":-0.014019195812266821,"measured_model_count":56,"median":-0.020729125875991173,"minimum":-0.23140278730236627,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.034790360549036684,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.014961917782642614,"interquartile_range":0.02193127226654084,"maximum":0.19539254739293155,"mean":0.03367981023215328,"measured_model_count":56,"median":0.022905507258844444,"minimum":0.0015916488853983351,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.036893190049183455,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004563261403949671,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.012800079573396912,"gene_effect_median":0.0036931926323622195},"dependency_probability_context_minus_non_context_median":-0.004778792064880334,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.013422305663770409,"gene_effect_context_minus_non_context_median":0.004263007062741037}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 121
+- **Dependency-aware candidate rank:** 121
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ef9206a1ce724e78d8c1aa27d8eb08bca4a2756bcf0378d4bba36777bcb8c874`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:DDR2|entrez:4921`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
121not prioritized-2
Resistance biomarker0.000
122not prioritized-3
Tumor-intrinsic / small molecule0.000
121not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.569)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: DDR2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for DDR2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/DDX3X.html b/examples/html_reports/depmap_26q1/targets/DDX3X.html new file mode 100644 index 0000000..9dbc966 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/DDX3X.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: DDX3X + + + + +
+ +
+

Target hypothesis report: DDX3X

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
DDX3X
+
+
+
Target name
+
DEAD-box helicase 3 X-linked
+
+
+
Open Targets melanoma score
+
0.641
+
+
+
+
Open Targets baseline rank
+
35
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.9698286536882877,"interquartile_range":0.7569406323261909,"maximum":0.3339853718118322,"mean":-0.6088234854143035,"measured_model_count":56,"median":-0.6607130262900589,"minimum":-2.0147135010407675,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.21288802136209684,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.14926781403958722,"interquartile_range":0.8089440313140834,"maximum":1.0,"mean":0.6154656913017502,"measured_model_count":56,"median":0.7872151954624422,"minimum":0.001289807589254826,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9582118453536707,"threshold_fractions":[{"denominator":56,"fraction":0.6785714285714286,"numerator":38,"threshold":0.5},{"denominator":56,"fraction":0.5,"numerator":28,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.16685803865653503,"dependency_probability_threshold_fractions":[{"context_fraction":0.6785714285714286,"difference":-0.10040208136234618,"pan_cancer_fraction":0.7789735099337748,"threshold":0.5},{"context_fraction":0.5,"difference":-0.20281456953642385,"pan_cancer_fraction":0.7028145695364238,"threshold":0.8}],"gene_effect_mean":0.2318562995522585,"gene_effect_median":0.24842949495470001},"dependency_probability_context_minus_non_context_median":-0.1700928838399589,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.6785714285714286,"difference":-0.10528273809523803,"non_context_fraction":0.7838541666666666,"threshold":0.5},{"context_fraction":0.5,"difference":-0.21267361111111116,"non_context_fraction":0.7126736111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.24312709189160442,"gene_effect_context_minus_non_context_median":0.2597624582856295}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 42
+- **Dependency-aware candidate rank:** 42
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_58b097ef5c176fce070a148275373b6687240d855387f464238a649fbf198364`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:DDX3X|entrez:1654`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
42not prioritized-7
Resistance biomarker0.000
44not prioritized-9
Tumor-intrinsic / small molecule0.000
42not prioritized-7
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.641)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: DDX3X lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for DDX3X in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/DICER1.html b/examples/html_reports/depmap_26q1/targets/DICER1.html new file mode 100644 index 0000000..94c899b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/DICER1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: DICER1 + + + + +
+ +
+

Target hypothesis report: DICER1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
DICER1
+
+
+
Target name
+
dicer 1, ribonuclease III
+
+
+
Open Targets melanoma score
+
0.616
+
+
+
+
Open Targets baseline rank
+
52
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.7994467283841284,"interquartile_range":0.30023678430572287,"maximum":0.13013407460107784,"mean":-0.6305602766259601,"measured_model_count":56,"median":-0.6573228251847951,"minimum":-1.2712552972640037,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.4992099440784056,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.5721275138636308,"interquartile_range":0.35380378565895265,"maximum":0.9952544360565102,"mean":0.6998550174732641,"measured_model_count":56,"median":0.8229355663334141,"minimum":0.006706062225289876,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9259312995225835,"threshold_fractions":[{"denominator":56,"fraction":0.7678571428571429,"numerator":43,"threshold":0.5},{"denominator":56,"fraction":0.5178571428571429,"numerator":29,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.17199606447334514,"dependency_probability_threshold_fractions":[{"context_fraction":0.7678571428571429,"difference":0.15610217596972564,"pan_cancer_fraction":0.6117549668874173,"threshold":0.5},{"context_fraction":0.5178571428571429,"difference":0.16189687795648067,"pan_cancer_fraction":0.35596026490066224,"threshold":0.8}],"gene_effect_mean":-0.08784562065277612,"gene_effect_median":-0.11679075840874076},"dependency_probability_context_minus_non_context_median":0.17636754028478918,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.7678571428571429,"difference":0.16369047619047628,"non_context_fraction":0.6041666666666666,"threshold":0.5},{"context_fraction":0.5178571428571429,"difference":0.16976686507936511,"non_context_fraction":0.3480902777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.09211589387895269,"gene_effect_context_minus_non_context_median":-0.12397328735897672}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 57
+- **Dependency-aware candidate rank:** 57
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_484de98defbe0cf173c2e8ba861a01993a059d3ccc346631c08ef0a1fd43c647`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:DICER1|entrez:23405`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
57not prioritized-5
Resistance biomarker0.000
59not prioritized-7
Tumor-intrinsic / small molecule0.000
57not prioritized-5
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.616)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: DICER1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for DICER1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/DNMT3A.html b/examples/html_reports/depmap_26q1/targets/DNMT3A.html new file mode 100644 index 0000000..9e198ab --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/DNMT3A.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: DNMT3A + + + + +
+ +
+

Target hypothesis report: DNMT3A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
DNMT3A
+
+
+
Target name
+
DNA methyltransferase 3 alpha
+
+
+
Open Targets melanoma score
+
0.581
+
+
+
+
Open Targets baseline rank
+
97
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.1244767471160199,"interquartile_range":0.11774663236443546,"maximum":0.6310082394813034,"mean":0.18192937029876807,"measured_model_count":56,"median":0.18235534714872575,"minimum":-0.18603726549592337,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.24222337948045536,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0018838619254996766,"interquartile_range":0.005556895059722717,"maximum":0.08869695724474873,"mean":0.007644426594225991,"measured_model_count":56,"median":0.0035343347073587836,"minimum":1.1862181692386457e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.007440756985222394,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0011400640495491015,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.010599921784739702,"gene_effect_median":0.012843073103306124},"dependency_probability_context_minus_non_context_median":-0.0011569302952267454,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01111519576038672,"gene_effect_context_minus_non_context_median":0.01322258993081063}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 100
+- **Dependency-aware candidate rank:** 100
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_be96e5150bdb496a7a39bcddbb88ac108797d06217f8197f24f78df1d9a2da48`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:DNMT3A|entrez:1788`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
100not prioritized-3
Resistance biomarker0.000
101not prioritized-4
Tumor-intrinsic / small molecule0.000
100not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.581)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: DNMT3A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for DNMT3A in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/EGFR.html b/examples/html_reports/depmap_26q1/targets/EGFR.html new file mode 100644 index 0000000..4d06759 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/EGFR.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: EGFR + + + + +
+ +
+

Target hypothesis report: EGFR

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
EGFR
+
+
+
Target name
+
epidermal growth factor receptor
+
+
+
Open Targets melanoma score
+
0.524
+
+
+
+
Open Targets baseline rank
+
195
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.17742898304365823,"interquartile_range":0.2395414323145233,"maximum":0.2660120139862773,"mean":-0.0768374949690435,"measured_model_count":56,"median":-0.08543314878433285,"minimum":-0.46622495115702955,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06211244927086508,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.013536831847736476,"interquartile_range":0.07782264300434415,"maximum":0.5606370090600415,"mean":0.08069588416595065,"measured_model_count":56,"median":0.05061839110667351,"minimum":0.0011475887843435738,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09135947485208062,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.012226944748200914,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.1717123935666982,"pan_cancer_fraction":0.18956953642384106,"threshold":0.5},{"context_fraction":0.0,"difference":-0.1183774834437086,"pan_cancer_fraction":0.1183774834437086,"threshold":0.8}],"gene_effect_mean":0.16048959750885244,"gene_effect_median":0.044865508404849666},"dependency_probability_context_minus_non_context_median":-0.01360040995761299,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.1800595238095238,"non_context_fraction":0.19791666666666666,"threshold":0.5},{"context_fraction":0.0,"difference":-0.12413194444444445,"non_context_fraction":0.12413194444444445,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.1682911751655326,"gene_effect_context_minus_non_context_median":0.047549781624125445}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 197
+- **Dependency-aware candidate rank:** 197
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2a70c9fd5fa9ed272df4bd2dc91722b65ce1a817cbd085b025dddcb62acc94ad`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:EGFR|entrez:1956`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
197not prioritized-2
Resistance biomarker0.000
197not prioritized-2
Tumor-intrinsic / small molecule0.000
197not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.524)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: EGFR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for EGFR in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ENTPD1.html b/examples/html_reports/depmap_26q1/targets/ENTPD1.html new file mode 100644 index 0000000..9b39334 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ENTPD1.html @@ -0,0 +1,70 @@ +ENTPD1 — DepMap research preview

ENTPD1

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.017204446642615827,"interquartile_range":0.10523556299931044,"maximum":0.32256544354857597,"mean":0.03613007161465716,"measured_model_count":56,"median":0.03958058875364162,"minimum":-0.17214377639477035,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08803111635669461,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008971876754590337,"interquartile_range":0.015497793480308062,"maximum":0.08656995332646747,"mean":0.020822634312535802,"measured_model_count":56,"median":0.014386164975697509,"minimum":0.0010515004995813155,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.024469670234898398,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00036529600012544065,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.005500676522773799,"gene_effect_median":-0.0019880259017703017},"dependency_probability_context_minus_non_context_median":-0.00046668099051278347,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.005768070520408633,"gene_effect_context_minus_non_context_median":-0.002175443103434427}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_88a4ac5fab879425f2d36cb78f6cca0d2a9303f47e26440d3fbf5d29ffdb0c4c`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ENTPD1|entrez:953`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/EP300.html b/examples/html_reports/depmap_26q1/targets/EP300.html new file mode 100644 index 0000000..f2a5eaa --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/EP300.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: EP300 + + + + +
+ +
+

Target hypothesis report: EP300

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
EP300
+
+
+
Target name
+
EP300 lysine acetyltransferase
+
+
+
Open Targets melanoma score
+
0.605
+
+
+
+
Open Targets baseline rank
+
62
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.6301650470635833,"interquartile_range":0.4709206521961253,"maximum":0.44756105949178754,"mean":-0.3907983166708622,"measured_model_count":56,"median":-0.3520231118620166,"minimum":-1.34610578400845,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.15924439486745806,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0690136792815241,"interquartile_range":0.6549061339214883,"maximum":0.994735297730019,"mean":0.4060882923478336,"measured_model_count":56,"median":0.30719246495550195,"minimum":0.00014797171299792128,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.7239198132030125,"threshold_fractions":[{"denominator":56,"fraction":0.375,"numerator":21,"threshold":0.5},{"denominator":56,"fraction":0.23214285714285715,"numerator":13,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.04992797303338542,"dependency_probability_threshold_fractions":[{"context_fraction":0.375,"difference":0.01572847682119205,"pan_cancer_fraction":0.35927152317880795,"threshold":0.5},{"context_fraction":0.23214285714285715,"difference":0.009460737937559138,"pan_cancer_fraction":0.222682119205298,"threshold":0.8}],"gene_effect_mean":-0.03225721062927511,"gene_effect_median":-0.03480287000380533},"dependency_probability_context_minus_non_context_median":0.05588253082748845,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.375,"difference":0.01649305555555558,"non_context_fraction":0.3585069444444444,"threshold":0.5},{"context_fraction":0.23214285714285715,"difference":0.009920634920634941,"non_context_fraction":0.2222222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03382526947930953,"gene_effect_context_minus_non_context_median":-0.03827708333683888}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 66
+- **Dependency-aware candidate rank:** 66
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_c8bf2b0a53226f54571eef5bd76eb44fbcf366497efff6c0d571a380adae1a6e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:EP300|entrez:2033`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
66not prioritized-4
Resistance biomarker0.000
68not prioritized-6
Tumor-intrinsic / small molecule0.000
66not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.605)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: EP300 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for EP300 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ERBB2.html b/examples/html_reports/depmap_26q1/targets/ERBB2.html new file mode 100644 index 0000000..8b8509b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ERBB2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ERBB2 + + + + +
+ +
+

Target hypothesis report: ERBB2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ERBB2
+
+
+
Target name
+
erb-b2 receptor tyrosine kinase 2
+
+
+
Open Targets melanoma score
+
0.603
+
+
+
+
Open Targets baseline rank
+
67
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.33467527164131333,"interquartile_range":0.14828615220047953,"maximum":0.04056593393173724,"mean":-0.26561967130517056,"measured_model_count":56,"median":-0.246206895071223,"minimum":-0.5119897770568183,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.1863891194408338,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.10583038909718276,"interquartile_range":0.14106667753996144,"maximum":0.669070278252544,"mean":0.21661886597937663,"measured_model_count":56,"median":0.1734088090428273,"minimum":0.011341833442620627,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2468970666371442,"threshold_fractions":[{"denominator":56,"fraction":0.10714285714285714,"numerator":6,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.02793739386262034,"dependency_probability_threshold_fractions":[{"context_fraction":0.10714285714285714,"difference":-0.09401608325449386,"pan_cancer_fraction":0.201158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.09850993377483444,"pan_cancer_fraction":0.09850993377483444,"threshold":0.8}],"gene_effect_mean":0.08925720783764057,"gene_effect_median":0.029340983554862532},"dependency_probability_context_minus_non_context_median":-0.03211618750590295,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.10714285714285714,"difference":-0.09858630952380952,"non_context_fraction":0.20572916666666666,"threshold":0.5},{"context_fraction":0.0,"difference":-0.1032986111111111,"non_context_fraction":0.1032986111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.09359609988530393,"gene_effect_context_minus_non_context_median":0.03032500080514161}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 71
+- **Dependency-aware candidate rank:** 71
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_85651a2e1e5fccdaa36943dabfc67d700562e875d4bb8301e0ebc7d1a2db6f88`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ERBB2|entrez:2064`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
71not prioritized-4
Resistance biomarker0.000
73not prioritized-6
Tumor-intrinsic / small molecule0.000
71not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.603)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ERBB2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ERBB2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ERBB3.html b/examples/html_reports/depmap_26q1/targets/ERBB3.html new file mode 100644 index 0000000..4759752 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ERBB3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ERBB3 + + + + +
+ +
+

Target hypothesis report: ERBB3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ERBB3
+
+
+
Target name
+
erb-b2 receptor tyrosine kinase 3
+
+
+
Open Targets melanoma score
+
0.587
+
+
+
+
Open Targets baseline rank
+
88
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.29677275810467674,"interquartile_range":0.15902387121322126,"maximum":0.10539895655935005,"mean":-0.2172892726108315,"measured_model_count":56,"median":-0.2064135944999752,"minimum":-0.5667130081211204,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.13774888689145548,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0701533166345286,"interquartile_range":0.14491007038238968,"maximum":0.6026137920472711,"mean":0.16367057810715754,"measured_model_count":56,"median":0.13126533178718724,"minimum":0.01069996622191269,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2150633870169183,"threshold_fractions":[{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.04329157941874143,"dependency_probability_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":-0.01963103122043519,"pan_cancer_fraction":0.09105960264900662,"threshold":0.5},{"context_fraction":0.0,"difference":-0.046357615894039736,"pan_cancer_fraction":0.046357615894039736,"threshold":0.8}],"gene_effect_mean":-0.010919738131060064,"gene_effect_median":-0.0461099890637964},"dependency_probability_context_minus_non_context_median":0.045517050458931174,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":-0.02058531746031747,"non_context_fraction":0.0920138888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.04861111111111111,"non_context_fraction":0.04861111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.011450558734653199,"gene_effect_context_minus_non_context_median":-0.047486382929025794}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 91
+- **Dependency-aware candidate rank:** 91
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_509bf22e2f5a6168ef36638c1f2838b26bc131fd72532af852051a66541ee1a9`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ERBB3|entrez:2065`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
91not prioritized-3
Resistance biomarker0.000
93not prioritized-5
Tumor-intrinsic / small molecule0.000
91not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.587)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ERBB3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ERBB3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ERBB4.html b/examples/html_reports/depmap_26q1/targets/ERBB4.html new file mode 100644 index 0000000..e266393 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ERBB4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ERBB4 + + + + +
+ +
+

Target hypothesis report: ERBB4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ERBB4
+
+
+
Target name
+
erb-b2 receptor tyrosine kinase 4
+
+
+
Open Targets melanoma score
+
0.634
+
+
+
+
Open Targets baseline rank
+
40
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.14569118463855116,"interquartile_range":0.14276472370214452,"maximum":0.22026504101142866,"mean":-0.0806414136689627,"measured_model_count":56,"median":-0.08133237680604319,"minimum":-0.5111124546060511,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.002926460936406628,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.022843399052722917,"interquartile_range":0.053439931630912645,"maximum":0.4447439005088343,"mean":0.06866226929506587,"measured_model_count":56,"median":0.04663575266879736,"minimum":0.0026245223564960677,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07628333068363556,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0028838586732600827,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.003982051068016801,"gene_effect_median":-0.0012821078178077983},"dependency_probability_context_minus_non_context_median":0.0029295309373640263,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.004175622994934278,"gene_effect_context_minus_non_context_median":-0.0016777736254505182}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 47
+- **Dependency-aware candidate rank:** 47
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_dbbab5a67067b1bda4c70eb8973b159c25141dc1be365953b465c06acb38ae9f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ERBB4|entrez:2066`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
47not prioritized-7
Resistance biomarker0.000
49not prioritized-9
Tumor-intrinsic / small molecule0.000
47not prioritized-7
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.634)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ERBB4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ERBB4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ERCC2.html b/examples/html_reports/depmap_26q1/targets/ERCC2.html new file mode 100644 index 0000000..731e3cc --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ERCC2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ERCC2 + + + + +
+ +
+

Target hypothesis report: ERCC2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ERCC2
+
+
+
Target name
+
ERCC excision repair 2, TFIIH core complex helicase subunit
+
+
+
Open Targets melanoma score
+
0.579
+
+
+
+
Open Targets baseline rank
+
104
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.0497755608773027,"interquartile_range":0.3813255384814084,"maximum":-0.16396640750377933,"mean":-0.8559048256834219,"measured_model_count":56,"median":-0.8344001265829372,"minimum":-1.6026495241794065,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.6684500223958943,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.7685887429345672,"interquartile_range":0.21456944658217048,"maximum":0.9999142385164158,"mean":0.8514767156342421,"measured_model_count":56,"median":0.9417257675715691,"minimum":0.12430696530259147,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9831581895167377,"threshold_fractions":[{"denominator":56,"fraction":0.9285714285714286,"numerator":52,"threshold":0.5},{"denominator":56,"fraction":0.7321428571428571,"numerator":41,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.031116564543193448,"dependency_probability_threshold_fractions":[{"context_fraction":0.9285714285714286,"difference":-0.019276253547776734,"pan_cancer_fraction":0.9478476821192053,"threshold":0.5},{"context_fraction":0.7321428571428571,"difference":-0.11967833491012303,"pan_cancer_fraction":0.8518211920529801,"threshold":0.8}],"gene_effect_mean":0.15736689035266194,"gene_effect_median":0.17219872117991863},"dependency_probability_context_minus_non_context_median":-0.032439978921928736,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9285714285714286,"difference":-0.020213293650793607,"non_context_fraction":0.9487847222222222,"threshold":0.5},{"context_fraction":0.7321428571428571,"difference":-0.12549603174603174,"non_context_fraction":0.8576388888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.1650166697448061,"gene_effect_context_minus_non_context_median":0.18209450243057768}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 107
+- **Dependency-aware candidate rank:** 107
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d2cc074964cf9c696a455e5924e2651a866708047ef2f12e243dd4c04fa06084`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ERCC2|entrez:2068`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
107not prioritized-3
Resistance biomarker0.000
108not prioritized-4
Tumor-intrinsic / small molecule0.000
107not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.579)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ERCC2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ERCC2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ERCC3.html b/examples/html_reports/depmap_26q1/targets/ERCC3.html new file mode 100644 index 0000000..68cdc4e --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ERCC3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ERCC3 + + + + +
+ +
+

Target hypothesis report: ERCC3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ERCC3
+
+
+
Target name
+
ERCC excision repair 3, TFIIH core complex helicase subunit
+
+
+
Open Targets melanoma score
+
0.551
+
+
+
+
Open Targets baseline rank
+
155
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.1181967186257906,"interquartile_range":0.21936811054409455,"maximum":-0.1968165974284698,"mean":-0.9861971850757215,"measured_model_count":56,"median":-1.0257305946001085,"minimum":-1.2003431761784857,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.8988286080816961,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9546022888982366,"interquartile_range":0.035122029420819545,"maximum":0.9976916871199579,"mean":0.9395766573450544,"measured_model_count":56,"median":0.9767427569343496,"minimum":0.15568980756884207,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9897243183190562,"threshold_fractions":[{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.5},{"denominator":56,"fraction":0.9642857142857143,"numerator":54,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.002812007009274531,"dependency_probability_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":0.002838221381267658,"pan_cancer_fraction":0.9793046357615894,"threshold":0.5},{"context_fraction":0.9642857142857143,"difference":0.033822138126773926,"pan_cancer_fraction":0.9304635761589404,"threshold":0.8}],"gene_effect_mean":0.03186839973649114,"gene_effect_median":-0.01496544170922709},"dependency_probability_context_minus_non_context_median":0.002916995705352421,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":0.0029761904761904656,"non_context_fraction":0.9791666666666666,"threshold":0.5},{"context_fraction":0.9642857142857143,"difference":0.03546626984126988,"non_context_fraction":0.9288194444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03341755805701585,"gene_effect_context_minus_non_context_median":-0.01579770104131084}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 157
+- **Dependency-aware candidate rank:** 157
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_151ac710b13364d64e7de307056de35149a8a93d487fef97333dfa698f138881`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ERCC3|entrez:2071`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
157not prioritized-2
Resistance biomarker0.000
158not prioritized-3
Tumor-intrinsic / small molecule0.000
157not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.551)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ERCC3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ERCC3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ERCC4.html b/examples/html_reports/depmap_26q1/targets/ERCC4.html new file mode 100644 index 0000000..2177f81 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ERCC4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ERCC4 + + + + +
+ +
+

Target hypothesis report: ERCC4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ERCC4
+
+
+
Target name
+
ERCC excision repair 4, endonuclease catalytic subunit
+
+
+
Open Targets melanoma score
+
0.543
+
+
+
+
Open Targets baseline rank
+
173
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.3854903365144424,"interquartile_range":0.21652135195847766,"maximum":0.001120471494265196,"mean":-0.2899236303985298,"measured_model_count":56,"median":-0.312962794264828,"minimum":-0.5607238476333932,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.16896898455596476,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.09450249828397053,"interquartile_range":0.2539646020376588,"maximum":0.6497895426015371,"mean":0.2577241034021173,"measured_model_count":56,"median":0.25032416264247376,"minimum":0.020314845019689234,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.3484671003216293,"threshold_fractions":[{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03807707323341175,"dependency_probability_threshold_fractions":[{"context_fraction":0.16071428571428573,"difference":-0.042100283822138124,"pan_cancer_fraction":0.20281456953642385,"threshold":0.5},{"context_fraction":0.0,"difference":-0.054635761589403975,"pan_cancer_fraction":0.054635761589403975,"threshold":0.8}],"gene_effect_mean":0.018671101005857837,"gene_effect_median":-0.029595103502446873},"dependency_probability_context_minus_non_context_median":0.03978289177958286,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.16071428571428573,"difference":-0.04414682539682538,"non_context_fraction":0.2048611111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.057291666666666664,"non_context_fraction":0.057291666666666664,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01957872397142002,"gene_effect_context_minus_non_context_median":-0.03036033876069405}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 175
+- **Dependency-aware candidate rank:** 175
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_57fa3f79c563d7d8a27b411a7849e95077a7642f56919c9aede4ab6df25e0823`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ERCC4|entrez:2072`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
175not prioritized-2
Resistance biomarker0.000
176not prioritized-3
Tumor-intrinsic / small molecule0.000
175not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.543)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ERCC4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ERCC4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ERCC5.html b/examples/html_reports/depmap_26q1/targets/ERCC5.html new file mode 100644 index 0000000..997bdd2 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ERCC5.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ERCC5 + + + + +
+ +
+

Target hypothesis report: ERCC5

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ERCC5
+
+
+
Target name
+
ERCC excision repair 5, endonuclease
+
+
+
Open Targets melanoma score
+
0.544
+
+
+
+
Open Targets baseline rank
+
172
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.04519528389004527,"interquartile_range":0.11019899927943605,"maximum":0.2710955571001969,"mean":0.005332502631850874,"measured_model_count":56,"median":0.02281300196535606,"minimum":-0.23518481053140836,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06500371538939079,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008780224985984577,"interquartile_range":0.031486563305523046,"maximum":0.10076459232175562,"mean":0.02723915059114595,"measured_model_count":56,"median":0.016749164858456053,"minimum":0.001704687039870745,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04026678829150762,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003982939681521677,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.0066125493202115315,"gene_effect_median":0.017344755611254512},"dependency_probability_context_minus_non_context_median":-0.004170855462812619,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006933992689944074,"gene_effect_context_minus_non_context_median":0.018058575388758574}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 174
+- **Dependency-aware candidate rank:** 174
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_cd975ed15f92798c752dcfdd13992481eab535c9fb742417e8abfc29c552e0f5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ERCC5|entrez:2073`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
174not prioritized-2
Resistance biomarker0.000
175not prioritized-3
Tumor-intrinsic / small molecule0.000
174not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.544)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ERCC5 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ERCC5 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ESR1.html b/examples/html_reports/depmap_26q1/targets/ESR1.html new file mode 100644 index 0000000..4c1e0ee --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ESR1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ESR1 + + + + +
+ +
+

Target hypothesis report: ESR1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ESR1
+
+
+
Target name
+
estrogen receptor 1
+
+
+
Open Targets melanoma score
+
0.604
+
+
+
+
Open Targets baseline rank
+
63
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.0848593775445727,"interquartile_range":0.13395979595344146,"maximum":0.23922527191565976,"mean":-0.0185218839167705,"measured_model_count":56,"median":-0.00802662620138481,"minimum":-0.3259164362790145,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.049100418408868744,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.012130319443407039,"interquartile_range":0.026440137649247547,"maximum":0.2259091707228821,"mean":0.035293228110319055,"measured_model_count":56,"median":0.02133572171212511,"minimum":0.0024119361921403825,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03857045709265459,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.008278000718975553,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.014072847682119206,"pan_cancer_fraction":0.014072847682119206,"threshold":0.5},{"context_fraction":0.0,"difference":-0.009933774834437087,"pan_cancer_fraction":0.009933774834437087,"threshold":0.8}],"gene_effect_mean":0.03441010632648146,"gene_effect_median":0.02581490859934631},"dependency_probability_context_minus_non_context_median":-0.00880314421140762,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.014756944444444444,"non_context_fraction":0.014756944444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.010416666666666666,"non_context_fraction":0.010416666666666666,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.036082819828463245,"gene_effect_context_minus_non_context_median":0.027045767506139604}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 67
+- **Dependency-aware candidate rank:** 67
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_943c2846124ca99709520b41b23aeb5ee539b8889a9bb74af925a517bb5ae317`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ESR1|entrez:2099`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
67not prioritized-4
Resistance biomarker0.000
69not prioritized-6
Tumor-intrinsic / small molecule0.000
67not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.604)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ESR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ESR1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/EZH2.html b/examples/html_reports/depmap_26q1/targets/EZH2.html new file mode 100644 index 0000000..1f62fba --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/EZH2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: EZH2 + + + + +
+ +
+

Target hypothesis report: EZH2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
EZH2
+
+
+
Target name
+
enhancer of zeste 2 polycomb repressive complex 2 subunit
+
+
+
Open Targets melanoma score
+
0.533
+
+
+
+
Open Targets baseline rank
+
183
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.05304773802010125,"interquartile_range":0.19476652921775417,"maximum":0.4109850863433474,"mean":0.0257700942153801,"measured_model_count":56,"median":0.0320485927146671,"minimum":-0.41701781626943923,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14171879119765293,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005567747692544567,"interquartile_range":0.02796596898671179,"maximum":0.38625828574385734,"mean":0.04412555204592233,"measured_model_count":56,"median":0.01521772005739586,"minimum":0.000795920235174292,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03353371667925636,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.009458068922002603,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0802980132450331,"pan_cancer_fraction":0.0802980132450331,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0347682119205298,"pan_cancer_fraction":0.0347682119205298,"threshold":0.8}],"gene_effect_mean":0.07476884614085007,"gene_effect_median":0.04611516268565478},"dependency_probability_context_minus_non_context_median":-0.009962040930500026,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0842013888888889,"non_context_fraction":0.0842013888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.036458333333333336,"non_context_fraction":0.036458333333333336,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.07840344282825268,"gene_effect_context_minus_non_context_median":0.04820298946438911}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 185
+- **Dependency-aware candidate rank:** 185
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_89fc6cbae49797355a70fb88c5eb89bea1500b53bf61770ee522b8d4175b525c`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:EZH2|entrez:2146`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
185not prioritized-2
Resistance biomarker0.000
186not prioritized-3
Tumor-intrinsic / small molecule0.000
185not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.533)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: EZH2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for EZH2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FANCA.html b/examples/html_reports/depmap_26q1/targets/FANCA.html new file mode 100644 index 0000000..97939a7 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FANCA.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FANCA + + + + +
+ +
+

Target hypothesis report: FANCA

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FANCA
+
+
+
Target name
+
FA complementation group A
+
+
+
Open Targets melanoma score
+
0.563
+
+
+
+
Open Targets baseline rank
+
130
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.39440710682115865,"interquartile_range":0.2515883236857389,"maximum":0.12296597316977459,"mean":-0.27177681109686624,"measured_model_count":56,"median":-0.2676352166799574,"minimum":-0.8702254040849512,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.14281878313541974,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.06949355765826927,"interquartile_range":0.39275603779407636,"maximum":0.9139864368396176,"mean":0.2615344748466097,"measured_model_count":56,"median":0.18706360909548436,"minimum":0.00882008373465794,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.4622495954523456,"threshold_fractions":[{"denominator":56,"fraction":0.21428571428571427,"numerator":12,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03743288547584378,"dependency_probability_threshold_fractions":[{"context_fraction":0.21428571428571427,"difference":0.047067171239356664,"pan_cancer_fraction":0.1672185430463576,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.03595080416272469,"pan_cancer_fraction":0.05380794701986755,"threshold":0.8}],"gene_effect_mean":-0.012940611265707225,"gene_effect_median":-0.03731075409812393},"dependency_probability_context_minus_non_context_median":0.0382085681160369,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.21428571428571427,"difference":0.04935515873015872,"non_context_fraction":0.16493055555555555,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.037698412698412696,"non_context_fraction":0.05555555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.013569668757790032,"gene_effect_context_minus_non_context_median":-0.040755914352917866}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 132
+- **Dependency-aware candidate rank:** 132
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_9d612855c15e78dd7b3fd730052e093248a8cf43206ecf80de6d56c1e71879f0`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FANCA|entrez:2175`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
132not prioritized-2
Resistance biomarker0.000
133not prioritized-3
Tumor-intrinsic / small molecule0.000
132not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.563)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FANCA lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FANCA in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FANCD2.html b/examples/html_reports/depmap_26q1/targets/FANCD2.html new file mode 100644 index 0000000..cecddaf --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FANCD2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FANCD2 + + + + +
+ +
+

Target hypothesis report: FANCD2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FANCD2
+
+
+
Target name
+
FA complementation group D2
+
+
+
Open Targets melanoma score
+
0.551
+
+
+
+
Open Targets baseline rank
+
156
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.34113845335061077,"interquartile_range":0.21209073145092927,"maximum":0.30763589641378847,"mean":-0.2358248940686561,"measured_model_count":56,"median":-0.24333725518628152,"minimum":-0.639276633988662,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.1290477218996815,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.06847084215026893,"interquartile_range":0.23966001971981649,"maximum":0.734910238754248,"mean":0.21108429639298154,"measured_model_count":56,"median":0.16569585838507817,"minimum":0.0015781144865433508,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.3081308618700854,"threshold_fractions":[{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0025366642184283805,"dependency_probability_threshold_fractions":[{"context_fraction":0.08928571428571429,"difference":-0.07958845789971618,"pan_cancer_fraction":0.16887417218543047,"threshold":0.5},{"context_fraction":0.0,"difference":-0.059602649006622516,"pan_cancer_fraction":0.059602649006622516,"threshold":0.8}],"gene_effect_mean":0.04550799068532252,"gene_effect_median":0.007226063520758941},"dependency_probability_context_minus_non_context_median":-0.003003162126274078,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.08928571428571429,"difference":-0.08345734126984126,"non_context_fraction":0.17274305555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0625,"non_context_fraction":0.0625,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04772018467697031,"gene_effect_context_minus_non_context_median":0.009441874759868407}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 158
+- **Dependency-aware candidate rank:** 158
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_38747c75a45551df32701b90edeb5b912c93eecb55956a769ccf297c959c6499`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FANCD2|entrez:2177`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
158not prioritized-2
Resistance biomarker0.000
159not prioritized-3
Tumor-intrinsic / small molecule0.000
158not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.551)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FANCD2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FANCD2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FANCE.html b/examples/html_reports/depmap_26q1/targets/FANCE.html new file mode 100644 index 0000000..6ca275c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FANCE.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FANCE + + + + +
+ +
+

Target hypothesis report: FANCE

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FANCE
+
+
+
Target name
+
FA complementation group E
+
+
+
Open Targets melanoma score
+
0.495
+
+
+
+
Open Targets baseline rank
+
258
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.30468282446630407,"interquartile_range":0.23709348450999423,"maximum":0.1449555156044862,"mean":-0.19703014558258644,"measured_model_count":56,"median":-0.19399076273649424,"minimum":-0.6634268715160248,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.06758933995630984,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.05160543946265888,"interquartile_range":0.20409383149367327,"maximum":0.8359188291300516,"mean":0.17355839520632504,"measured_model_count":56,"median":0.12078053526514522,"minimum":0.0063814556847987345,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.25569927095633216,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.010507597535913196,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.024243140964995268,"pan_cancer_fraction":0.07781456953642384,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.004493850520340587,"pan_cancer_fraction":0.022350993377483443,"threshold":0.8}],"gene_effect_mean":0.0048485338361873576,"gene_effect_median":-0.010002252875917883},"dependency_probability_context_minus_non_context_median":0.011688697304552895,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.025421626984126984,"non_context_fraction":0.07899305555555555,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.004712301587301588,"non_context_fraction":0.022569444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.005084226453224372,"gene_effect_context_minus_non_context_median":-0.010590003539978826}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 260
+- **Dependency-aware candidate rank:** 260
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_af2ef9ce5f4fd758b457c8e17953dbe83cdfdf20b1372dd55948c65268248353`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FANCE|entrez:2178`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
260not prioritized-2
Resistance biomarker0.000
260not prioritized-2
Tumor-intrinsic / small molecule0.000
260not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.495)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FANCE lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FANCE in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FANCF.html b/examples/html_reports/depmap_26q1/targets/FANCF.html new file mode 100644 index 0000000..19925ca --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FANCF.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FANCF + + + + +
+ +
+

Target hypothesis report: FANCF

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FANCF
+
+
+
Target name
+
FA complementation group F
+
+
+
Open Targets melanoma score
+
0.511
+
+
+
+
Open Targets baseline rank
+
237
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.41615021274621306,"interquartile_range":0.22066287913849758,"maximum":0.018453039839361474,"mean":-0.32504242532536193,"measured_model_count":56,"median":-0.31555455536594124,"minimum":-0.9314961101442203,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.19548733360771547,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.11743406537297933,"interquartile_range":0.35662513437807863,"maximum":0.9457808378607613,"mean":0.3108121278616506,"measured_model_count":56,"median":0.24263160040327705,"minimum":0.01631160733986358,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.474059199751058,"threshold_fractions":[{"denominator":56,"fraction":0.23214285714285715,"numerator":13,"threshold":0.5},{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03892104933244922,"dependency_probability_threshold_fractions":[{"context_fraction":0.23214285714285715,"difference":0.05085146641438032,"pan_cancer_fraction":0.18129139072847683,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.011825922421948916,"pan_cancer_fraction":0.06539735099337748,"threshold":0.8}],"gene_effect_mean":-0.027520060395061552,"gene_effect_median":-0.04656469941415908},"dependency_probability_context_minus_non_context_median":0.04155124666083371,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.23214285714285715,"difference":0.0533234126984127,"non_context_fraction":0.17881944444444445,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.012400793650793655,"non_context_fraction":0.06597222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.028857841108710203,"gene_effect_context_minus_non_context_median":-0.04936482998290259}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 239
+- **Dependency-aware candidate rank:** 239
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a25481f9b7fb6aeae93c442afd3af2320fa466eaf6af98abfe161e70ee99dba8`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FANCF|entrez:2188`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
239not prioritized-2
Resistance biomarker0.000
239not prioritized-2
Tumor-intrinsic / small molecule0.000
239not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.511)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FANCF lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FANCF in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FAS.html b/examples/html_reports/depmap_26q1/targets/FAS.html new file mode 100644 index 0000000..a709f32 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FAS.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FAS + + + + +
+ +
+

Target hypothesis report: FAS

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FAS
+
+
+
Target name
+
Fas cell surface death receptor
+
+
+
Open Targets melanoma score
+
0.520
+
+
+
+
Open Targets baseline rank
+
214
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.16162206893853046,"interquartile_range":0.13172923906542297,"maximum":0.18036452107576528,"mean":-0.08960286791582976,"measured_model_count":56,"median":-0.11478192715046522,"minimum":-0.31079330755796136,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.029892829873107492,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.026861749551291544,"interquartile_range":0.06845940434177648,"maximum":0.2343847619311021,"mean":0.06411442895668948,"measured_model_count":56,"median":0.05203040919741203,"minimum":0.0031442763076645645,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09532115389306803,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.013770595535781915,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.03749563999309223,"gene_effect_median":0.008775714037758828},"dependency_probability_context_minus_non_context_median":-0.014767391644715883,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03931834471497868,"gene_effect_context_minus_non_context_median":0.009573133482113347}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 216
+- **Dependency-aware candidate rank:** 216
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_435dbd512d7e3db5bb499780b478a732de5d1d5f6c8f09df160c88a5d8e23421`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FAS|entrez:355`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
216not prioritized-2
Resistance biomarker0.000
216not prioritized-2
Tumor-intrinsic / small molecule0.000
216not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.520)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FAS lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FAS in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FAT1.html b/examples/html_reports/depmap_26q1/targets/FAT1.html new file mode 100644 index 0000000..01f8d4a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FAT1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FAT1 + + + + +
+ +
+

Target hypothesis report: FAT1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FAT1
+
+
+
Target name
+
FAT atypical cadherin 1
+
+
+
Open Targets melanoma score
+
0.616
+
+
+
+
Open Targets baseline rank
+
51
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.010190119994076867,"interquartile_range":0.1327527813060256,"maximum":0.3239877898348623,"mean":0.05787560641765308,"measured_model_count":56,"median":0.04713508116369999,"minimum":-0.1477656314088705,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12256266131194873,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.006042510039561404,"interquartile_range":0.01801475636113281,"maximum":0.12678724791693652,"mean":0.019558783916784724,"measured_model_count":56,"median":0.013016969463129585,"minimum":0.0013710596238751416,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.024057266400694215,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0013614167784833913,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.01248027188150281,"gene_effect_median":-0.020780697114013286},"dependency_probability_context_minus_non_context_median":0.0013991729157834913,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.01308695176463142,"gene_effect_context_minus_non_context_median":-0.021291486324947137}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 56
+- **Dependency-aware candidate rank:** 56
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_6f6e747f3722d5fc2be9e32d44c9d89b9858271ca298a917a9b9c5308679b7dd`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FAT1|entrez:2195`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
56not prioritized-5
Resistance biomarker0.000
58not prioritized-7
Tumor-intrinsic / small molecule0.000
56not prioritized-5
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.616)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FAT1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FAT1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FAT4.html b/examples/html_reports/depmap_26q1/targets/FAT4.html new file mode 100644 index 0000000..4b2581f --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FAT4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FAT4 + + + + +
+ +
+

Target hypothesis report: FAT4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FAT4
+
+
+
Target name
+
FAT atypical cadherin 4
+
+
+
Open Targets melanoma score
+
0.601
+
+
+
+
Open Targets baseline rank
+
69
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.08010063621579745,"interquartile_range":0.13017968110048778,"maximum":0.21669532988519838,"mean":-0.025541252959918388,"measured_model_count":56,"median":-0.023054746641925847,"minimum":-0.47842898548034124,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.050079044884690324,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01326244371222652,"interquartile_range":0.033213141154614684,"maximum":0.3959491092740444,"mean":0.039079867410627044,"measured_model_count":56,"median":0.026496833584941027,"minimum":0.0022160403622951044,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0464755848668412,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0035919121449942,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.011374350608281528,"gene_effect_median":0.010377897671845472},"dependency_probability_context_minus_non_context_median":-0.0039031432466969836,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.011927270429517495,"gene_effect_context_minus_non_context_median":0.01086542962612444}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 73
+- **Dependency-aware candidate rank:** 73
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_fb3832e78ce8821d085e9f9e58324d7617a45c5703e4e3e6b9dd7d4f1e99e62f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FAT4|entrez:79633`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
73not prioritized-4
Resistance biomarker0.000
75not prioritized-6
Tumor-intrinsic / small molecule0.000
73not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.601)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FAT4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FAT4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FBXO11.html b/examples/html_reports/depmap_26q1/targets/FBXO11.html new file mode 100644 index 0000000..64093d7 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FBXO11.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FBXO11 + + + + +
+ +
+

Target hypothesis report: FBXO11

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FBXO11
+
+
+
Target name
+
F-box protein 11
+
+
+
Open Targets melanoma score
+
0.520
+
+
+
+
Open Targets baseline rank
+
211
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.15074818038210167,"interquartile_range":0.281308577050804,"maximum":0.42220203584434846,"mean":-0.04560795363310931,"measured_model_count":56,"median":-0.03427403620395675,"minimum":-0.6741261622322151,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1305603966687023,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.007285169440329596,"interquartile_range":0.09745011838978633,"maximum":0.7905134474847286,"mean":0.10611223844677944,"measured_model_count":56,"median":0.029319765084054497,"minimum":0.0004413568234268305,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10473528783011593,"threshold_fractions":[{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.05470028325649019,"dependency_probability_threshold_fractions":[{"context_fraction":0.08928571428571429,"difference":-0.09780037842951751,"pan_cancer_fraction":0.1870860927152318,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0869205298013245,"pan_cancer_fraction":0.0869205298013245,"threshold":0.8}],"gene_effect_mean":0.15028418975283891,"gene_effect_median":0.12440411985501812},"dependency_probability_context_minus_non_context_median":-0.06235086518264875,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.08928571428571429,"difference":-0.1025545634920635,"non_context_fraction":0.1918402777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.09114583333333333,"non_context_fraction":0.09114583333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.15758967119915746,"gene_effect_context_minus_non_context_median":0.13709329218559274}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 213
+- **Dependency-aware candidate rank:** 213
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2a9dbb49310a86c32be14cbc59e80d4d2c2add0340022fbd2770296eee5d6ab5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FBXO11|entrez:80204`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
213not prioritized-2
Resistance biomarker0.000
213not prioritized-2
Tumor-intrinsic / small molecule0.000
213not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.520)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FBXO11 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FBXO11 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FBXW7.html b/examples/html_reports/depmap_26q1/targets/FBXW7.html new file mode 100644 index 0000000..1f3f133 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FBXW7.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FBXW7 + + + + +
+ +
+

Target hypothesis report: FBXW7

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FBXW7
+
+
+
Target name
+
F-box and WD repeat domain containing 7
+
+
+
Open Targets melanoma score
+
0.459
+
+
+
+
Open Targets baseline rank
+
296
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.10168761872706197,"interquartile_range":0.31951626522136356,"maximum":0.7477705375903348,"mean":0.07512290288357788,"measured_model_count":56,"median":0.08885012160126604,"minimum":-0.42999840215935103,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.21782864649430156,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0023602908105894663,"interquartile_range":0.04698617022723407,"maximum":0.3990660245341544,"mean":0.048686281727830724,"measured_model_count":56,"median":0.00790827217292547,"minimum":7.339235394045013e-07,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04934646103782354,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.010836419724310722,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.052980132450331126,"pan_cancer_fraction":0.052980132450331126,"threshold":0.5},{"context_fraction":0.0,"difference":-0.01903973509933775,"pan_cancer_fraction":0.01903973509933775,"threshold":0.8}],"gene_effect_mean":0.08060711847084692,"gene_effect_median":0.07781843422240313},"dependency_probability_context_minus_non_context_median":-0.011215200532051196,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.05555555555555555,"non_context_fraction":0.05555555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.019965277777777776,"non_context_fraction":0.019965277777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08452552006317991,"gene_effect_context_minus_non_context_median":0.0786441323859088}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 296
+- **Dependency-aware candidate rank:** 296
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_b02eb196c82838328cafb71a23b2642af9fedccfd9c22696f2b332ac3c26fe8b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FBXW7|entrez:55294`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
296not prioritized0
Resistance biomarker0.000
296not prioritized0
Tumor-intrinsic / small molecule0.000
296not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.459)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FBXW7 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FBXW7 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FCRL4.html b/examples/html_reports/depmap_26q1/targets/FCRL4.html new file mode 100644 index 0000000..610686a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FCRL4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FCRL4 + + + + +
+ +
+

Target hypothesis report: FCRL4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FCRL4
+
+
+
Target name
+
Fc receptor like 4
+
+
+
Open Targets melanoma score
+
0.547
+
+
+
+
Open Targets baseline rank
+
166
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.182975187793387,"interquartile_range":0.13243973999157846,"maximum":0.14030049532262745,"mean":-0.11330662488132592,"measured_model_count":56,"median":-0.10620558769013834,"minimum":-0.451675523595505,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.05053544780180854,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.03271037791063712,"interquartile_range":0.057892317786895325,"maximum":0.4302335386003559,"mean":0.07745410574824914,"measured_model_count":56,"median":0.05680147102116183,"minimum":0.003675204351939972,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09060269569753245,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.008796200508185144,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.019686981945813434,"gene_effect_median":-0.017844667161811156},"dependency_probability_context_minus_non_context_median":0.009037454034450887,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.020643988012623682,"gene_effect_context_minus_non_context_median":-0.01890243276653479}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 168
+- **Dependency-aware candidate rank:** 168
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_993b3f04ca04a2b878e09007c16e57fbedf7753e2078c6925a2ff9c73d71d284`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FCRL4|entrez:83417`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
168not prioritized-2
Resistance biomarker0.000
169not prioritized-3
Tumor-intrinsic / small molecule0.000
168not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.547)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FCRL4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FCRL4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FGFR1.html b/examples/html_reports/depmap_26q1/targets/FGFR1.html new file mode 100644 index 0000000..1a6bb3f --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FGFR1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FGFR1 + + + + +
+ +
+

Target hypothesis report: FGFR1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FGFR1
+
+
+
Target name
+
fibroblast growth factor receptor 1
+
+
+
Open Targets melanoma score
+
0.592
+
+
+
+
Open Targets baseline rank
+
81
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.10585312617805011,"interquartile_range":0.1474329702619552,"maximum":0.24676378195924795,"mean":-0.04075960883877906,"measured_model_count":56,"median":-0.04514236242722311,"minimum":-0.45737015923785884,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04157984408390509,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.013136544667759788,"interquartile_range":0.042445470736148155,"maximum":0.5845513123281094,"mean":0.05509342663926976,"measured_model_count":56,"median":0.030469376280351304,"minimum":0.0018396455361303317,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05558201540390795,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01369994659970368,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.10631504257332072,"pan_cancer_fraction":0.12417218543046357,"threshold":0.5},{"context_fraction":0.0,"difference":-0.076158940397351,"pan_cancer_fraction":0.076158940397351,"threshold":0.8}],"gene_effect_mean":0.1434789721272285,"gene_effect_median":0.03823400415708511},"dependency_probability_context_minus_non_context_median":-0.014786145536563725,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.11148313492063494,"non_context_fraction":0.1293402777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0798611111111111,"non_context_fraction":0.0798611111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.1504536443834132,"gene_effect_context_minus_non_context_median":0.04293224672576107}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 84
+- **Dependency-aware candidate rank:** 84
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_0c4c822c779a509dd8f0818fdf2712c56fe01b6e397d995d2d24c31f73a62c13`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FGFR1|entrez:2260`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
84not prioritized-3
Resistance biomarker0.000
86not prioritized-5
Tumor-intrinsic / small molecule0.000
84not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.592)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FGFR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FGFR1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FGFR2.html b/examples/html_reports/depmap_26q1/targets/FGFR2.html new file mode 100644 index 0000000..98b06f1 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FGFR2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FGFR2 + + + + +
+ +
+

Target hypothesis report: FGFR2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FGFR2
+
+
+
Target name
+
fibroblast growth factor receptor 2
+
+
+
Open Targets melanoma score
+
0.597
+
+
+
+
Open Targets baseline rank
+
72
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.12929769810455707,"interquartile_range":0.12395274435376992,"maximum":0.275230036665003,"mean":-0.05821593340182014,"measured_model_count":56,"median":-0.05163254238200452,"minimum":-0.5200819479761457,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.005344953750787151,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.022649497580184946,"interquartile_range":0.038355964705018376,"maximum":0.7009253574543882,"mean":0.05743963083468188,"measured_model_count":56,"median":0.03537906820870254,"minimum":0.0017046287467954388,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06100546228520332,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0009883025349953362,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.0028382213812677415,"pan_cancer_fraction":0.020695364238410598,"threshold":0.5},{"context_fraction":0.0,"difference":-0.011589403973509934,"pan_cancer_fraction":0.011589403973509934,"threshold":0.8}],"gene_effect_mean":0.009920320730496084,"gene_effect_median":-0.0012327620399221126},"dependency_probability_context_minus_non_context_median":0.0010248143999687029,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.002976190476190476,"non_context_fraction":0.020833333333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.012152777777777778,"non_context_fraction":0.012152777777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.010402558543784114,"gene_effect_context_minus_non_context_median":-0.0012327620399221126}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 76
+- **Dependency-aware candidate rank:** 76
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_dfa107591a1ac03b755e3ff7c7cbf34b941cb9295ecfe59850965185086aaf5f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FGFR2|entrez:2263`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
76not prioritized-4
Resistance biomarker0.000
78not prioritized-6
Tumor-intrinsic / small molecule0.000
76not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.597)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FGFR2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FGFR2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FGFR3.html b/examples/html_reports/depmap_26q1/targets/FGFR3.html new file mode 100644 index 0000000..5c40647 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FGFR3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FGFR3 + + + + +
+ +
+

Target hypothesis report: FGFR3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FGFR3
+
+
+
Target name
+
fibroblast growth factor receptor 3
+
+
+
Open Targets melanoma score
+
0.508
+
+
+
+
Open Targets baseline rank
+
245
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.05194312301230575,"interquartile_range":0.17413908661637087,"maximum":0.3363122041950665,"mean":0.03525864250811891,"measured_model_count":56,"median":0.04922997969645476,"minimum":-0.46980050826203773,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12219596360406512,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005922891813622169,"interquartile_range":0.023690854120683086,"maximum":0.37901610456587304,"mean":0.036640727013179324,"measured_model_count":56,"median":0.015458308668818171,"minimum":0.0005398320917780566,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.029613745934305255,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0019648983478077423,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":-0.010620082025073661,"gene_effect_median":-0.0025159097270620323},"dependency_probability_context_minus_non_context_median":0.002078622591012949,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.011136336012403637,"gene_effect_context_minus_non_context_median":-0.0025159097270620323}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 247
+- **Dependency-aware candidate rank:** 247
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_35b283f0a5f1c62f4b53730a369193f82d2197826a40e0c00115df009af6f895`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FGFR3|entrez:2261`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
247not prioritized-2
Resistance biomarker0.000
247not prioritized-2
Tumor-intrinsic / small molecule0.000
247not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.508)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FGFR3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FGFR3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FGFR4.html b/examples/html_reports/depmap_26q1/targets/FGFR4.html new file mode 100644 index 0000000..5c82120 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FGFR4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FGFR4 + + + + +
+ +
+

Target hypothesis report: FGFR4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FGFR4
+
+
+
Target name
+
fibroblast growth factor receptor 4
+
+
+
Open Targets melanoma score
+
0.596
+
+
+
+
Open Targets baseline rank
+
74
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.04827777998776034,"interquartile_range":0.1004719025100316,"maximum":0.2993306227887731,"mean":0.0031693776232304136,"measured_model_count":56,"median":-0.0050449308179600395,"minimum":-0.19963413413040304,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05219412252227127,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.010744829149114411,"interquartile_range":0.023094813491983453,"maximum":0.10374246297872541,"mean":0.02619568029732398,"measured_model_count":56,"median":0.01975265020738414,"minimum":0.0007450975600135493,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.033839642641097865,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0009313245577814086,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":0.0066095514812883945,"gene_effect_median":-0.006960965645284039},"dependency_probability_context_minus_non_context_median":-0.0009313245577814086,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006930849122739929,"gene_effect_context_minus_non_context_median":-0.007745231305098141}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 78
+- **Dependency-aware candidate rank:** 78
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_004c3e04c159ccaa691e52e99fbfb4144510f7d9bdc39f80ac4517d3fe1423ff`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FGFR4|entrez:2264`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
78not prioritized-4
Resistance biomarker0.000
80not prioritized-6
Tumor-intrinsic / small molecule0.000
78not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.596)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FGFR4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FGFR4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FH.html b/examples/html_reports/depmap_26q1/targets/FH.html new file mode 100644 index 0000000..cb5ff02 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FH.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FH + + + + +
+ +
+

Target hypothesis report: FH

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FH
+
+
+
Target name
+
fumarate hydratase
+
+
+
Open Targets melanoma score
+
0.507
+
+
+
+
Open Targets baseline rank
+
246
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.48235854532561034,"interquartile_range":0.30092341372102055,"maximum":0.21734868313383282,"mean":-0.3452825522263905,"measured_model_count":56,"median":-0.3487538509937572,"minimum":-1.1620329173001207,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.1814351316045898,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.11598339367742898,"interquartile_range":0.4138461833340011,"maximum":0.9842926507309879,"mean":0.3562568102014801,"measured_model_count":56,"median":0.293119690869387,"minimum":0.002688067009743821,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5298295770114301,"threshold_fractions":[{"denominator":56,"fraction":0.2857142857142857,"numerator":16,"threshold":0.5},{"denominator":56,"fraction":0.10714285714285714,"numerator":6,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.10011148122363533,"dependency_probability_threshold_fractions":[{"context_fraction":0.2857142857142857,"difference":0.08289971617786185,"pan_cancer_fraction":0.20281456953642385,"threshold":0.5},{"context_fraction":0.10714285714285714,"difference":0.04008987701040681,"pan_cancer_fraction":0.06705298013245033,"threshold":0.8}],"gene_effect_mean":-0.056762207296732925,"gene_effect_median":-0.07985514795528226},"dependency_probability_context_minus_non_context_median":0.10531261956391319,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.2857142857142857,"difference":0.08692956349206349,"non_context_fraction":0.1987847222222222,"threshold":0.5},{"context_fraction":0.10714285714285714,"difference":0.042038690476190466,"non_context_fraction":0.06510416666666667,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.05952148126254625,"gene_effect_context_minus_non_context_median":-0.08371105618329383}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 248
+- **Dependency-aware candidate rank:** 248
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_4c3d50fd928c20519680c63006ca3576503bad1ed551fa5b1d6ebf7febc1fe01`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FH|entrez:2271`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
248not prioritized-2
Resistance biomarker0.000
248not prioritized-2
Tumor-intrinsic / small molecule0.000
248not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.507)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FH lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FH in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FLG.html b/examples/html_reports/depmap_26q1/targets/FLG.html new file mode 100644 index 0000000..3830b6b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FLG.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FLG + + + + +
+ +
+

Target hypothesis report: FLG

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FLG
+
+
+
Target name
+
filaggrin
+
+
+
Open Targets melanoma score
+
0.546
+
+
+
+
Open Targets baseline rank
+
169
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.014090010880866456,"interquartile_range":0.12299878821956789,"maximum":0.40211935160462337,"mean":0.05468800059532417,"measured_model_count":56,"median":0.053553678456244605,"minimum":-0.18698379576091817,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10890877733870144,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.007642926736823383,"interquartile_range":0.017284387507036578,"maximum":0.0830094575624924,"mean":0.019436951498532508,"measured_model_count":56,"median":0.012053492803449247,"minimum":0.0003584647512974246,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.024927314243859963,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.000785988056441209,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.020258498555916597,"gene_effect_median":-0.022962257860729376},"dependency_probability_context_minus_non_context_median":0.0009945662930979093,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.02124328668016256,"gene_effect_context_minus_non_context_median":-0.023969425069776965}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 171
+- **Dependency-aware candidate rank:** 171
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_8c9614fa2ecdbeeb83fe4e7758ee1d749ace6c9bfcacad385863c66e87259123`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FLG|entrez:2312`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
171not prioritized-2
Resistance biomarker0.000
172not prioritized-3
Tumor-intrinsic / small molecule0.000
171not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.546)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FLG lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FLG in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FLT3.html b/examples/html_reports/depmap_26q1/targets/FLT3.html new file mode 100644 index 0000000..3725f5e --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FLT3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FLT3 + + + + +
+ +
+

Target hypothesis report: FLT3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FLT3
+
+
+
Target name
+
fms related receptor tyrosine kinase 3
+
+
+
Open Targets melanoma score
+
0.516
+
+
+
+
Open Targets baseline rank
+
225
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.22595354553005761,"interquartile_range":0.14998026773463285,"maximum":0.154995004034906,"mean":-0.14385366187633805,"measured_model_count":56,"median":-0.13862055477951635,"minimum":-0.48307639187962104,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.07597327779542476,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.04545758737215939,"interquartile_range":0.09978084071418072,"maximum":0.5397629699994875,"mean":0.10755393878508068,"measured_model_count":56,"median":0.08088979303060306,"minimum":0.005060271666928569,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1452384280863401,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.004678428087829312,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.007095553453169347,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.8}],"gene_effect_mean":0.002763227151568154,"gene_effect_median":0.00511073170445725},"dependency_probability_context_minus_non_context_median":0.0049809751847571665,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.00744047619047619,"non_context_fraction":0.010416666666666666,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0028975506936582685,"gene_effect_context_minus_non_context_median":0.005710907745139798}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 227
+- **Dependency-aware candidate rank:** 227
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_19f78659b5c5a1a4d11d0d7a3da8405949336d2087578f076ffcebf1fd6c4549`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FLT3|entrez:2322`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
227not prioritized-2
Resistance biomarker0.000
227not prioritized-2
Tumor-intrinsic / small molecule0.000
227not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.516)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FLT3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FLT3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FLT4.html b/examples/html_reports/depmap_26q1/targets/FLT4.html new file mode 100644 index 0000000..adba853 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FLT4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FLT4 + + + + +
+ +
+

Target hypothesis report: FLT4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FLT4
+
+
+
Target name
+
fms related receptor tyrosine kinase 4
+
+
+
Open Targets melanoma score
+
0.651
+
+
+
+
Open Targets baseline rank
+
30
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.019570219331166372,"interquartile_range":0.12035885290869781,"maximum":0.2540552513736699,"mean":0.039597374010813514,"measured_model_count":56,"median":0.029329758113223747,"minimum":-0.16137096768294212,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10078863357753144,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008675884303708739,"interquartile_range":0.018278780420746883,"maximum":0.08326337223205958,"mean":0.019447313633772216,"measured_model_count":56,"median":0.016517954870417618,"minimum":0.0012689987898533725,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.026954664724455624,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0006489096814118467,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.01595184925542367,"gene_effect_median":0.006058142124424029},"dependency_probability_context_minus_non_context_median":-0.0006844353504273058,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.016727286372006774,"gene_effect_context_minus_non_context_median":0.006718596257992385}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 37
+- **Dependency-aware candidate rank:** 37
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_44c57ba5c52a55c98a9505d58528634b542af6211b3ff63f1344e345487b5d61`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FLT4|entrez:2324`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
37not prioritized-7
Resistance biomarker0.000
39not prioritized-9
Tumor-intrinsic / small molecule0.001
32not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.651)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FLT4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FLT4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FMN1.html b/examples/html_reports/depmap_26q1/targets/FMN1.html new file mode 100644 index 0000000..8b18231 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FMN1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FMN1 + + + + +
+ +
+

Target hypothesis report: FMN1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FMN1
+
+
+
Target name
+
formin 1
+
+
+
Open Targets melanoma score
+
0.489
+
+
+
+
Open Targets baseline rank
+
264
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.04804373333999466,"interquartile_range":0.15223200943340148,"maximum":0.5097227332643849,"mean":0.11250660008204064,"measured_model_count":56,"median":0.13594679027128903,"minimum":-0.7270702453089212,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.20027574277339613,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0025879797549131995,"interquartile_range":0.011864780776770868,"maximum":0.8049195799577559,"mean":0.029415923175659203,"measured_model_count":56,"median":0.005465761799348213,"minimum":0.00019623882159085373,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.014452760531684069,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0046174476303679135,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.015373699148533584,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.01702932828760643,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.03478949815416854,"gene_effect_median":0.054479413326805184},"dependency_probability_context_minus_non_context_median":-0.004784356776145761,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.016121031746031744,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.017857142857142856,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0364806543144406,"gene_effect_context_minus_non_context_median":0.05660838796219783}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 266
+- **Dependency-aware candidate rank:** 266
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_69e5314be2fbeceef14006c5abadfdb7977478310ef3e7a3a5f227fd0e52d327`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FMN1|entrez:342184`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
266not prioritized-2
Resistance biomarker0.000
266not prioritized-2
Tumor-intrinsic / small molecule0.000
266not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.489)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FMN1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FMN1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FOXP1.html b/examples/html_reports/depmap_26q1/targets/FOXP1.html new file mode 100644 index 0000000..a96a1dd --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FOXP1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FOXP1 + + + + +
+ +
+

Target hypothesis report: FOXP1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FOXP1
+
+
+
Target name
+
forkhead box P1
+
+
+
Open Targets melanoma score
+
0.636
+
+
+
+
Open Targets baseline rank
+
36
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.08925622719291582,"interquartile_range":0.15725199103704537,"maximum":0.3896693910511839,"mean":-0.012717309353639877,"measured_model_count":56,"median":0.006684601879123767,"minimum":-0.48806446905551293,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06799576384412956,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.009684733628868597,"interquartile_range":0.03702886243106225,"maximum":0.45881000128768495,"mean":0.05421199659843505,"measured_model_count":56,"median":0.018906366489225244,"minimum":0.0005847063168429513,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04671359605993085,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0033351835499027954,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.039143380154957934,"gene_effect_median":-0.024316461656596587},"dependency_probability_context_minus_non_context_median":0.003675399300320372,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.041046183356935065,"gene_effect_context_minus_non_context_median":-0.025993480373904948}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 43
+- **Dependency-aware candidate rank:** 43
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a1e2720e1e989d0d788b4b8760f1078648865d2fe750dc670b9d9ad1f8aa0d2e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FOXP1|entrez:27086`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
43not prioritized-7
Resistance biomarker0.000
45not prioritized-9
Tumor-intrinsic / small molecule0.000
43not prioritized-7
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.636)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FOXP1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FOXP1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/FOXP3.html b/examples/html_reports/depmap_26q1/targets/FOXP3.html new file mode 100644 index 0000000..35fbdb5 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FOXP3.html @@ -0,0 +1,70 @@ +FOXP3 — DepMap research preview

FOXP3

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.015325840605122043,"interquartile_range":0.09965029971967573,"maximum":0.2660450679919454,"mean":0.06567559829110299,"measured_model_count":56,"median":0.06163214472920807,"minimum":-0.23676786606528333,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11497614032479778,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.006236233508914037,"interquartile_range":0.00910131640870038,"maximum":0.13569945974455236,"mean":0.016217094032263086,"measured_model_count":56,"median":0.01160893644614088,"minimum":0.0011550462651738536,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.015337549917614417,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0014470923302244126,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.021158287619726213,"gene_effect_median":-0.021145144317778697},"dependency_probability_context_minus_non_context_median":0.0015407235934845175,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.022186815490129574,"gene_effect_context_minus_non_context_median":-0.02276042607062291}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_bf04bf99f93c0cb1a92980fe824b4f059cb02d5a8ea61bae4be73224ef941405`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FOXP3|entrez:50943`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/FUBP1.html b/examples/html_reports/depmap_26q1/targets/FUBP1.html new file mode 100644 index 0000000..6b78bd9 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/FUBP1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: FUBP1 + + + + +
+ +
+

Target hypothesis report: FUBP1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
FUBP1
+
+
+
Target name
+
far upstream element binding protein 1
+
+
+
Open Targets melanoma score
+
0.491
+
+
+
+
Open Targets baseline rank
+
262
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.2881247391090692,"interquartile_range":0.16340607882358316,"maximum":0.1842388495263189,"mean":-0.20610670889766866,"measured_model_count":56,"median":-0.19477172807427562,"minimum":-0.6381129392361081,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.12471866028548606,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.06338988632503986,"interquartile_range":0.16076528927297246,"maximum":0.7540646184472742,"mean":0.1760565738449998,"measured_model_count":56,"median":0.10461075385553599,"minimum":0.0027667622892301744,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.22415517559801232,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0019598383822274773,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.04742194891201514,"pan_cancer_fraction":0.10099337748344371,"threshold":0.5},{"context_fraction":0.0,"difference":-0.024006622516556293,"pan_cancer_fraction":0.024006622516556293,"threshold":0.8}],"gene_effect_mean":-0.01405759351501737,"gene_effect_median":-0.008173948816249},"dependency_probability_context_minus_non_context_median":0.0030925657815894375,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.049727182539682536,"non_context_fraction":0.1032986111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.025173611111111112,"non_context_fraction":0.025173611111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.014740948755330802,"gene_effect_context_minus_non_context_median":-0.009100495671172604}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 264
+- **Dependency-aware candidate rank:** 264
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_6e58d1225d1ff58877163c0cbff4987d160c4bd85f4c6abefe8fb554070ec846`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:FUBP1|entrez:8880`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
264not prioritized-2
Resistance biomarker0.000
264not prioritized-2
Tumor-intrinsic / small molecule0.000
264not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.491)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: FUBP1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for FUBP1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/GATA2.html b/examples/html_reports/depmap_26q1/targets/GATA2.html new file mode 100644 index 0000000..1abdbae --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/GATA2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: GATA2 + + + + +
+ +
+

Target hypothesis report: GATA2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
GATA2
+
+
+
Target name
+
GATA binding protein 2
+
+
+
Open Targets melanoma score
+
0.486
+
+
+
+
Open Targets baseline rank
+
267
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.007575429545667133,"interquartile_range":0.12492924525133178,"maximum":0.38970793669976095,"mean":0.0577966749928754,"measured_model_count":56,"median":0.05691850044409493,"minimum":-0.29724211223823427,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11735381570566465,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005785166202300651,"interquartile_range":0.01713490940782536,"maximum":0.3018103137464197,"mean":0.022289382974630133,"measured_model_count":56,"median":0.012027009295317814,"minimum":0.0007343235547851637,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02292007561012601,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0020969851635946023,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.022350993377483443,"pan_cancer_fraction":0.022350993377483443,"threshold":0.5},{"context_fraction":0.0,"difference":-0.011589403973509934,"pan_cancer_fraction":0.011589403973509934,"threshold":0.8}],"gene_effect_mean":0.027134737241848835,"gene_effect_median":0.005962492496855362},"dependency_probability_context_minus_non_context_median":-0.002243803387106131,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0234375,"non_context_fraction":0.0234375,"threshold":0.5},{"context_fraction":0.0,"difference":-0.012152777777777778,"non_context_fraction":0.012152777777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.028453786968883153,"gene_effect_context_minus_non_context_median":0.006359299502022693}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 268
+- **Dependency-aware candidate rank:** 268
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d9b94b7c7104e5636cbe3f4f57178a06a55a1c08c478cacb063d5011123fbd17`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:GATA2|entrez:2624`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
268not prioritized-1
Resistance biomarker0.000
268not prioritized-1
Tumor-intrinsic / small molecule0.000
268not prioritized-1
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.486)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: GATA2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for GATA2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/GNA11.html b/examples/html_reports/depmap_26q1/targets/GNA11.html new file mode 100644 index 0000000..5f314b9 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/GNA11.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: GNA11 + + + + +
+ +
+

Target hypothesis report: GNA11

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
GNA11
+
+
+
Target name
+
G protein subunit alpha 11
+
+
+
Open Targets melanoma score
+
0.708
+
+
+
+
Open Targets baseline rank
+
17
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.24420661980895522,"interquartile_range":0.15532874743496847,"maximum":0.03808760466256192,"mean":-0.1684084279156771,"measured_model_count":56,"median":-0.1566551127202881,"minimum":-0.45115937023528413,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.08887787237398675,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.03757946210475693,"interquartile_range":0.11724926833434487,"maximum":0.5638151018002555,"mean":0.11858227556158243,"measured_model_count":56,"median":0.09407439748766974,"minimum":0.010923528122944231,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1548287304391018,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.02310997207226037,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.009578997161778617,"pan_cancer_fraction":0.008278145695364239,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.026795039061602494,"gene_effect_median":-0.02109071818710906},"dependency_probability_context_minus_non_context_median":0.02350983668023343,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.010044642857142856,"non_context_fraction":0.0078125,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.028097575682652587,"gene_effect_context_minus_non_context_median":-0.02238896547077862}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 24
+- **Dependency-aware candidate rank:** 23
+- **Rank delta:** -1
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a7d87a9ec0d84e741c1cc77753996d174f0f3d0258d04962a8bf22f4fc0aa442`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:GNA11|entrez:2767`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
24not prioritized-7
Resistance biomarker0.000
27not prioritized-10
Tumor-intrinsic / small molecule0.012
20not prioritized-3
+
+ +
+

Evidence for

+
    +
  • High Open Targets melanoma association score (0.708)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: GNA11 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for GNA11 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/GNAQ.html b/examples/html_reports/depmap_26q1/targets/GNAQ.html new file mode 100644 index 0000000..e403115 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/GNAQ.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: GNAQ + + + + +
+ +
+

Target hypothesis report: GNAQ

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
GNAQ
+
+
+
Target name
+
G protein subunit alpha q
+
+
+
Open Targets melanoma score
+
0.720
+
+
+
+
Open Targets baseline rank
+
11
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.45136196689657815,"interquartile_range":0.22233080091499816,"maximum":-0.040557723214412034,"mean":-0.365139823702521,"measured_model_count":56,"median":-0.3311970646804885,"minimum":-1.1688313734515619,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.22903116598158,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.16462592677727933,"interquartile_range":0.30738138279626565,"maximum":0.9920765810689797,"mean":0.3481970522328733,"measured_model_count":56,"median":0.27679032897507927,"minimum":0.02048184269862659,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.472007309573545,"threshold_fractions":[{"denominator":56,"fraction":0.23214285714285715,"numerator":13,"threshold":0.5},{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.02775485358607166,"dependency_probability_threshold_fractions":[{"context_fraction":0.23214285714285715,"difference":0.07154683065279094,"pan_cancer_fraction":0.1605960264900662,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":0.03997161778618732,"pan_cancer_fraction":0.03145695364238411,"threshold":0.8}],"gene_effect_mean":-0.05124936895378335,"gene_effect_median":-0.026313059636482228},"dependency_probability_context_minus_non_context_median":0.028648254521146055,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.23214285714285715,"difference":0.0750248015873016,"non_context_fraction":0.15711805555555555,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":0.041914682539682536,"non_context_fraction":0.029513888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.05374065772237008,"gene_effect_context_minus_non_context_median":-0.027474495765544504}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 19
+- **Dependency-aware candidate rank:** 15
+- **Rank delta:** -4
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ae901de999d2ee02d100019c4dd3e89979c37d98c65aae0363152f56d8a418b8`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:GNAQ|entrez:2776`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
19not prioritized-8
Resistance biomarker0.000
24not prioritized-13
Tumor-intrinsic / small molecule0.015
17not prioritized-6
+
+ +
+

Evidence for

+
    +
  • High Open Targets melanoma association score (0.720)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: GNAQ lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for GNAQ in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/GNAS.html b/examples/html_reports/depmap_26q1/targets/GNAS.html new file mode 100644 index 0000000..edcdf7b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/GNAS.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: GNAS + + + + +
+ +
+

Target hypothesis report: GNAS

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
GNAS
+
+
+
Target name
+
GNAS complex locus
+
+
+
Open Targets melanoma score
+
0.569
+
+
+
+
Open Targets baseline rank
+
116
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.12914624361583124,"interquartile_range":0.16880844265574943,"maximum":0.3443254273478986,"mean":-0.04885626544081799,"measured_model_count":56,"median":-0.0395043305663757,"minimum":-0.5772557917183418,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.039662199039918196,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.011990605387231526,"interquartile_range":0.056437399568218624,"maximum":0.6486813918352867,"mean":0.06710232936679815,"measured_model_count":56,"median":0.032055853208135324,"minimum":0.0008476741953656707,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06842800495545015,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0032107523718056252,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.01206244087038789,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.011480693649686298,"gene_effect_median":-0.00926598963642166},"dependency_probability_context_minus_non_context_median":0.003590262256471081,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.012648809523809524,"non_context_fraction":0.005208333333333333,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.012038782924323865,"gene_effect_context_minus_non_context_median":-0.010368538176564888}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 118
+- **Dependency-aware candidate rank:** 118
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2121ce6ab7561f4f13a9e8a767a37ea64cba39801adb9ccd02f8d1fba46ce84c`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:GNAS|entrez:2778`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
118not prioritized-2
Resistance biomarker0.000
119not prioritized-3
Tumor-intrinsic / small molecule0.000
118not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.569)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: GNAS lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for GNAS in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/GRIN2A.html b/examples/html_reports/depmap_26q1/targets/GRIN2A.html new file mode 100644 index 0000000..2773b5b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/GRIN2A.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: GRIN2A + + + + +
+ +
+

Target hypothesis report: GRIN2A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
GRIN2A
+
+
+
Target name
+
glutamate ionotropic receptor NMDA type subunit 2A
+
+
+
Open Targets melanoma score
+
0.594
+
+
+
+
Open Targets baseline rank
+
75
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.14411748716861636,"interquartile_range":0.1211869515324273,"maximum":0.11187573454467088,"mean":-0.07796016160118857,"measured_model_count":56,"median":-0.08077181172218598,"minimum":-0.27600553638489433,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.02293053563618906,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.023766660725572302,"interquartile_range":0.05338835758759475,"maximum":0.24021664161407277,"mean":0.056171638224705486,"measured_model_count":56,"median":0.04293536851828147,"minimum":0.007086734633626951,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07715501831316705,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.011198747176608272,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.029617941574408405,"gene_effect_median":0.021573085866140762},"dependency_probability_context_minus_non_context_median":-0.01178456213463986,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.031057702623164263,"gene_effect_context_minus_non_context_median":0.022850946800319766}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 79
+- **Dependency-aware candidate rank:** 79
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_1131048334e27b8c53c9180ef40f28486cfa48c15a0b199462fde73591da1e1f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:GRIN2A|entrez:2903`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
79not prioritized-4
Resistance biomarker0.000
81not prioritized-6
Tumor-intrinsic / small molecule0.000
79not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.594)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: GRIN2A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for GRIN2A in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/GZMB.html b/examples/html_reports/depmap_26q1/targets/GZMB.html new file mode 100644 index 0000000..4a8840a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/GZMB.html @@ -0,0 +1,70 @@ +GZMB — DepMap research preview

GZMB

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.17244025699697157,"interquartile_range":0.2215586500992243,"maximum":0.3725292682983529,"mean":-0.043664638800793,"measured_model_count":56,"median":-0.06917978710613715,"minimum":-0.31096479898487983,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04911839310225271,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.009710803170775517,"interquartile_range":0.08752127492675235,"maximum":0.246250297339304,"mean":0.05926205677955833,"measured_model_count":56,"median":0.034480980287158486,"minimum":0.0007627617070437107,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09723207809752787,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01345836150324789,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03145695364238411,"pan_cancer_fraction":0.03145695364238411,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.05748615344446486,"gene_effect_median":0.02104996878975203},"dependency_probability_context_minus_non_context_median":-0.01427025841020696,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03298611111111111,"non_context_fraction":0.03298611111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.06028061923690404,"gene_effect_context_minus_non_context_median":0.021472073888966117}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_151ecdb83f44b504f40cc23529671c3a71580ccd555c775989d15d4c13db48d7`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:GZMB|entrez:3002`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/H3-3A.html b/examples/html_reports/depmap_26q1/targets/H3-3A.html new file mode 100644 index 0000000..ac2aa0c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/H3-3A.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: H3-3A + + + + +
+ +
+

Target hypothesis report: H3-3A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
H3-3A
+
+
+
Target name
+
H3.3 histone A
+
+
+
Open Targets melanoma score
+
0.489
+
+
+
+
Open Targets baseline rank
+
266
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 55
+- **Available reference observations:** 1034
+- **Coverage fraction:** 0.9821428571428571
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.6291221340498359,"interquartile_range":0.5747953137617774,"maximum":-0.5969404951509958,"mean":-1.3551787569326883,"measured_model_count":55,"median":-1.346906237251263,"minimum":-2.244889055499746,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":-1.0543268202880585,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9837331286620297,"interquartile_range":0.016249656069920126,"maximum":1.0,"mean":0.9764838454893447,"measured_model_count":55,"median":0.995866238899257,"minimum":0.6036936797196938,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":0.9999827847319498,"threshold_fractions":[{"denominator":55,"fraction":1.0,"numerator":55,"threshold":0.5},{"denominator":55,"fraction":0.9818181818181818,"numerator":54,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0013855542350874606,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0009182736455464191,"pan_cancer_fraction":0.9990817263544536,"threshold":0.5},{"context_fraction":0.9818181818181818,"difference":-0.006244260789715295,"pan_cancer_fraction":0.9880624426078971,"threshold":0.8}],"gene_effect_mean":0.09920988909591233,"gene_effect_median":0.07560014079777178},"dependency_probability_context_minus_non_context_median":-0.0015030020911090958,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0009671179883945502,"non_context_fraction":0.9990328820116054,"threshold":0.5},{"context_fraction":0.9818181818181818,"difference":-0.006576402321083141,"non_context_fraction":0.988394584139265,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.10448701085633383,"gene_effect_context_minus_non_context_median":0.08053511551815729}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 267
+- **Dependency-aware candidate rank:** 267
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_060195d120dedafc704c04a7b6ed5b376da212ca75ead35bb668ebd57a5579ce`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:H3-3A|entrez:3020`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
267not prioritized-1
Resistance biomarker0.000
267not prioritized-1
Tumor-intrinsic / small molecule0.000
267not prioritized-1
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.489)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: H3-3A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for H3-3A in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/H3-3B.html b/examples/html_reports/depmap_26q1/targets/H3-3B.html new file mode 100644 index 0000000..8de6b2c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/H3-3B.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: H3-3B + + + + +
+ +
+

Target hypothesis report: H3-3B

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
H3-3B
+
+
+
Target name
+
H3.3 histone B
+
+
+
Open Targets melanoma score
+
0.629
+
+
+
+
Open Targets baseline rank
+
46
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.48313503447175277,"interquartile_range":0.21974635922869223,"maximum":-0.012604660993106698,"mean":-0.3755518963514822,"measured_model_count":56,"median":-0.33933172423069585,"minimum":-0.830902835454018,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.26338867524306053,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.19076786329106843,"interquartile_range":0.3226438251221172,"maximum":0.9130818463893109,"mean":0.36860403231261063,"measured_model_count":56,"median":0.3108532559759873,"minimum":0.019520162834314427,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5134116884131856,"threshold_fractions":[{"denominator":56,"fraction":0.2857142857142857,"numerator":16,"threshold":0.5},{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.029032926573638707,"dependency_probability_threshold_fractions":[{"context_fraction":0.2857142857142857,"difference":0.07627719962157048,"pan_cancer_fraction":0.20943708609271522,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":0.05120624408703879,"pan_cancer_fraction":0.0380794701986755,"threshold":0.8}],"gene_effect_mean":-0.02872055273816415,"gene_effect_median":-0.006189626891782374},"dependency_probability_context_minus_non_context_median":0.03019649567191035,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.2857142857142857,"difference":0.07998511904761904,"non_context_fraction":0.20572916666666666,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":0.05369543650793651,"non_context_fraction":0.035590277777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.030116690718491712,"gene_effect_context_minus_non_context_median":-0.006385863796944391}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 52
+- **Dependency-aware candidate rank:** 52
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d9bebcb5fee3a38ce961cdd95ec7b569cf554436e7f73ccabb2d92f6959dbba9`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:H3-3B|entrez:3021`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
52not prioritized-6
Resistance biomarker0.000
54not prioritized-8
Tumor-intrinsic / small molecule0.000
52not prioritized-6
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.629)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: H3-3B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for H3-3B in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/H3C2.html b/examples/html_reports/depmap_26q1/targets/H3C2.html new file mode 100644 index 0000000..e631488 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/H3C2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: H3C2 + + + + +
+ +
+

Target hypothesis report: H3C2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
H3C2
+
+
+
Target name
+
H3 clustered histone 2
+
+
+
Open Targets melanoma score
+
0.461
+
+
+
+
Open Targets baseline rank
+
293
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.3206454080265252,"interquartile_range":0.1975554737523422,"maximum":0.16775661599292177,"mean":-0.21381437868097847,"measured_model_count":56,"median":-0.20958209107011988,"minimum":-0.5450733007125406,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.123089934274183,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.07225970162530683,"interquartile_range":0.1622007492055575,"maximum":0.6438797380322532,"mean":0.1724341084996443,"measured_model_count":56,"median":0.13346229752303382,"minimum":0.003772158858215319,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2344604508308643,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.05283129681457631,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.0031929990539262057,"pan_cancer_fraction":0.03890728476821192,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008278145695364239,"pan_cancer_fraction":0.008278145695364239,"threshold":0.8}],"gene_effect_mean":-0.0563058122332889,"gene_effect_median":-0.05730285933166218},"dependency_probability_context_minus_non_context_median":0.05647874440182907,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.0033482142857142877,"non_context_fraction":0.0390625,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008680555555555556,"non_context_fraction":0.008680555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.05904290032796286,"gene_effect_context_minus_non_context_median":-0.05928166598260526}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":96.29629629629629}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 293
+- **Dependency-aware candidate rank:** 293
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_f5072b3b792894be7d133d95de092d076e750269299cb8a4d1479670b625cc22`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:H3C2|entrez:8358`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
293not prioritized0
Resistance biomarker0.000
293not prioritized0
Tumor-intrinsic / small molecule0.000
293not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.461)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: H3C2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for H3C2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/HAVCR2.html b/examples/html_reports/depmap_26q1/targets/HAVCR2.html new file mode 100644 index 0000000..2918f0b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/HAVCR2.html @@ -0,0 +1,70 @@ +HAVCR2 — DepMap research preview

HAVCR2

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.02987708632932152,"interquartile_range":0.10506951338618359,"maximum":0.30558334855827995,"mean":0.028231970147176263,"measured_model_count":56,"median":0.021078887581460377,"minimum":-0.19101340457200128,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07519242705686208,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.00789883343293582,"interquartile_range":0.01833445389224319,"maximum":0.11204404808981419,"mean":0.023435654418921713,"measured_model_count":56,"median":0.014689188029942131,"minimum":0.0016295139647264294,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02623328732517901,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003337664315021603,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.009017409880538656,"gene_effect_median":0.0003966547468448878},"dependency_probability_context_minus_non_context_median":-0.003616138300594568,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0094557561941759,"gene_effect_context_minus_non_context_median":0.0003966547468448878}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_c248336f2529cedafa19f7abd4b8014abd56c13a26f40fcdd4e68a0f90d7196d`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:HAVCR2|entrez:84868`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/HGF.html b/examples/html_reports/depmap_26q1/targets/HGF.html new file mode 100644 index 0000000..e4ce579 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/HGF.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: HGF + + + + +
+ +
+

Target hypothesis report: HGF

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
HGF
+
+
+
Target name
+
hepatocyte growth factor
+
+
+
Open Targets melanoma score
+
0.552
+
+
+
+
Open Targets baseline rank
+
152
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.027861706906206877,"interquartile_range":0.14525680904923657,"maximum":0.4677803805613251,"mean":0.09965417928922386,"measured_model_count":56,"median":0.11360474924188933,"minimum":-0.25539137465273065,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.17311851595544345,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0037531548730815527,"interquartile_range":0.013962672062846015,"maximum":0.22696926601274922,"mean":0.016201461765943802,"measured_model_count":56,"median":0.007790645531783854,"minimum":0.0002821764476149182,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.01771582693592757,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0006945584392857775,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.0015775449469577485,"gene_effect_median":0.006504541187336843},"dependency_probability_context_minus_non_context_median":-0.0007014155545820213,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0016542311596570852,"gene_effect_context_minus_non_context_median":0.006670081421324067}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 154
+- **Dependency-aware candidate rank:** 154
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2d3d71d7bf71d9d7df55c2f5b5d686b039eed8feee14a9af9b12e41dce5e2202`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:HGF|entrez:3082`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
154not prioritized-2
Resistance biomarker0.000
155not prioritized-3
Tumor-intrinsic / small molecule0.000
154not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.552)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: HGF lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for HGF in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/HLA-A.html b/examples/html_reports/depmap_26q1/targets/HLA-A.html new file mode 100644 index 0000000..09fb4f7 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/HLA-A.html @@ -0,0 +1,70 @@ +HLA-A — DepMap research preview

HLA-A

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.2552972965494641,"interquartile_range":0.15781341479361444,"maximum":0.08996078518352843,"mean":-0.18008238783186595,"measured_model_count":56,"median":-0.17280744614212706,"minimum":-0.5750630715153462,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.09748388175584964,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.049497676353652244,"interquartile_range":0.1167644450917843,"maximum":0.6029775488822585,"mean":0.13965062801032252,"measured_model_count":56,"median":0.09981467563830992,"minimum":0.007059461637493488,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.16626212144543653,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0028874450778858807,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.014191106906338694,"pan_cancer_fraction":0.02152317880794702,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.0076694632735165025,"gene_effect_median":-0.0014223753886474788},"dependency_probability_context_minus_non_context_median":0.0028874450778858807,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.01488095238095238,"non_context_fraction":0.020833333333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.008042284404867955,"gene_effect_context_minus_non_context_median":-0.0014984427927402233}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_43d9bc0efe8d920b0cfc428175995672933871455796868dd67399d4c95a5e14`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:HLA-A|entrez:3105`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/HLA-B.html b/examples/html_reports/depmap_26q1/targets/HLA-B.html new file mode 100644 index 0000000..1fccfc2 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/HLA-B.html @@ -0,0 +1,70 @@ +HLA-B — DepMap research preview

HLA-B

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.15968912982781502,"interquartile_range":0.18480063823124976,"maximum":0.27007374516910987,"mean":-0.07374631368331996,"measured_model_count":56,"median":-0.07423159504405025,"minimum":-0.485704165710984,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02511150840343474,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01395180875400719,"interquartile_range":0.07055243596738246,"maximum":0.49127695693581824,"mean":0.0784175275143234,"measured_model_count":56,"median":0.04113581826807637,"minimum":0.0013968572167001247,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08450424472138965,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.003823438453709818,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.012417218543046357,"pan_cancer_fraction":0.012417218543046357,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.013620445179712164,"gene_effect_median":-0.013905226303427526},"dependency_probability_context_minus_non_context_median":0.00396711267390569,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.013020833333333334,"non_context_fraction":0.013020833333333334,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.014282550153725954,"gene_effect_context_minus_non_context_median":-0.014197361569255919}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_201b7f8924c1431035c311800124e678903aef894ffd7cd56ab618fdc727c07e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:HLA-B|entrez:3106`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/HNF1A.html b/examples/html_reports/depmap_26q1/targets/HNF1A.html new file mode 100644 index 0000000..a2f3b46 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/HNF1A.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: HNF1A + + + + +
+ +
+

Target hypothesis report: HNF1A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
HNF1A
+
+
+
Target name
+
HNF1 homeobox A
+
+
+
Open Targets melanoma score
+
0.558
+
+
+
+
Open Targets baseline rank
+
140
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.16293366063630432,"interquartile_range":0.19824401087906468,"maximum":0.1912757751751536,"mean":-0.07256376755814067,"measured_model_count":56,"median":-0.04778355491386431,"minimum":-0.5122705302653734,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.035310350242760344,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01457113924168986,"interquartile_range":0.07886206050438543,"maximum":0.6658078682606292,"mean":0.07098839603343211,"measured_model_count":56,"median":0.03521909600150257,"minimum":0.0039146957197934325,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0934331997460753,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.012960500764139918,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.01939451277199622,"pan_cancer_fraction":0.037251655629139076,"threshold":0.5},{"context_fraction":0.0,"difference":-0.027317880794701987,"pan_cancer_fraction":0.027317880794701987,"threshold":0.8}],"gene_effect_mean":0.042514986696841256,"gene_effect_median":0.03906099413564805},"dependency_probability_context_minus_non_context_median":-0.01386410286868471,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.02033730158730159,"non_context_fraction":0.03819444444444445,"threshold":0.5},{"context_fraction":0.0,"difference":-0.028645833333333332,"non_context_fraction":0.028645833333333332,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.044581687439048806,"gene_effect_context_minus_non_context_median":0.04095335611525912}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 142
+- **Dependency-aware candidate rank:** 142
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e95a9ab63f4796506f26238946f4a129076f4f73ff476961a82f915c9eaa7d44`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:HNF1A|entrez:6927`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
142not prioritized-2
Resistance biomarker0.000
143not prioritized-3
Tumor-intrinsic / small molecule0.000
142not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.558)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: HNF1A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for HNF1A in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/HRAS.html b/examples/html_reports/depmap_26q1/targets/HRAS.html new file mode 100644 index 0000000..77038b9 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/HRAS.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: HRAS + + + + +
+ +
+

Target hypothesis report: HRAS

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
HRAS
+
+
+
Target name
+
HRas proto-oncogene, GTPase
+
+
+
Open Targets melanoma score
+
0.470
+
+
+
+
Open Targets baseline rank
+
283
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.27036777326378536,"interquartile_range":0.18381116909250983,"maximum":0.12159438311188783,"mean":-0.2120542528403669,"measured_model_count":56,"median":-0.15093706759740222,"minimum":-1.3098886826432632,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.08655660417127553,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.03936622590302448,"interquartile_range":0.15378447332836542,"maximum":0.9996455744842113,"mean":0.17412857012370694,"measured_model_count":56,"median":0.09876526486851311,"minimum":0.004326422830182301,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.19315069923138992,"threshold_fractions":[{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0012393581733524672,"dependency_probability_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":0.03831598864711447,"pan_cancer_fraction":0.033112582781456956,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.022469252601702933,"pan_cancer_fraction":0.013245033112582781,"threshold":0.8}],"gene_effect_mean":-0.02652314465051092,"gene_effect_median":0.020462495254849472},"dependency_probability_context_minus_non_context_median":0.0012393581733524672,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":0.040178571428571425,"non_context_fraction":0.03125,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.023561507936507936,"non_context_fraction":0.012152777777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.027812464182132873,"gene_effect_context_minus_non_context_median":0.021395327108499673}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 283
+- **Dependency-aware candidate rank:** 283
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_00b8562ea04bcc22eab699d158b353dc85657751afc3bbd71beef92ccea4b0ec`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:HRAS|entrez:3265`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
283not prioritized0
Resistance biomarker0.000
283not prioritized0
Tumor-intrinsic / small molecule0.000
283not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.470)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: HRAS lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for HRAS in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/IDH1.html b/examples/html_reports/depmap_26q1/targets/IDH1.html new file mode 100644 index 0000000..fae0142 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IDH1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: IDH1 + + + + +
+ +
+

Target hypothesis report: IDH1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
IDH1
+
+
+
Target name
+
isocitrate dehydrogenase (NADP(+)) 1
+
+
+
Open Targets melanoma score
+
0.578
+
+
+
+
Open Targets baseline rank
+
105
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.15448357052904954,"interquartile_range":0.1485721977747924,"maximum":0.20896505721913816,"mean":-0.09337330784363378,"measured_model_count":56,"median":-0.07154041810566106,"minimum":-1.0350852467755454,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.005911372754257127,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.02007757384147797,"interquartile_range":0.06085228289583204,"maximum":0.9942833245620363,"mean":0.08093502900778993,"measured_model_count":56,"median":0.03720868827740238,"minimum":0.0038582797922045104,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08092985673731001,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.011733095136837665,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.028263954588457898,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.01702932828760643,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.002041933966753659,"gene_effect_median":0.017447678140363243},"dependency_probability_context_minus_non_context_median":-0.012445510404531221,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.029637896825396824,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.017857142857142856,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0021411946456930675,"gene_effect_context_minus_non_context_median":0.01793534566771285}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 108
+- **Dependency-aware candidate rank:** 108
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e331ec4f05a441ffe543c5ccc7a2c5cff7f322cc1692428e9e61601f98726a15`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IDH1|entrez:3417`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
108not prioritized-3
Resistance biomarker0.000
109not prioritized-4
Tumor-intrinsic / small molecule0.000
108not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.578)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: IDH1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for IDH1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/IDO1.html b/examples/html_reports/depmap_26q1/targets/IDO1.html new file mode 100644 index 0000000..1caeb04 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IDO1.html @@ -0,0 +1,70 @@ +IDO1 — DepMap research preview

IDO1

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.012105508427349601,"interquartile_range":0.1220095967242903,"maximum":0.5660480673354267,"mean":0.05266969293575046,"measured_model_count":56,"median":0.05843457057831062,"minimum":-0.28197971786765974,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1099040882969407,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005713555583787177,"interquartile_range":0.018801276132440366,"maximum":0.1884526002652624,"mean":0.028673556894948857,"measured_model_count":56,"median":0.012181418582402407,"minimum":0.0001486835036999761,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.024514831716227543,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0017848407840746726,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.031560927535275805,"gene_effect_median":-0.019909371893919524},"dependency_probability_context_minus_non_context_median":0.0018090039940647454,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03309513929046282,"gene_effect_context_minus_non_context_median":-0.02147555857723673}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a1cd3c9169e009a6d3cdd3adf811fb3369c178cb298a23fb81d9c8eb67be160a`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IDO1|entrez:3620`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/IFNAR1.html b/examples/html_reports/depmap_26q1/targets/IFNAR1.html new file mode 100644 index 0000000..f8740a8 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IFNAR1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: IFNAR1 + + + + +
+ +
+

Target hypothesis report: IFNAR1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
IFNAR1
+
+
+
Target name
+
interferon alpha and beta receptor subunit 1
+
+
+
Open Targets melanoma score
+
0.611
+
+
+
+
Open Targets baseline rank
+
55
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.02072702775838113,"interquartile_range":0.15827098898244746,"maximum":0.6503786890171347,"mean":0.12145333029466691,"measured_model_count":56,"median":0.10365599503808863,"minimum":-0.16933916992926473,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1789980167408286,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.003956222562329722,"interquartile_range":0.01411125018501198,"maximum":0.07902273935717684,"mean":0.013110592051675965,"measured_model_count":56,"median":0.00683742314520901,"minimum":9.673493890419153e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.018067472747341703,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0022345454968270284,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.0137521212968921,"gene_effect_median":0.01271549373961664},"dependency_probability_context_minus_non_context_median":-0.002283469781756406,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.014420627193268795,"gene_effect_context_minus_non_context_median":0.013105917150467536}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 59
+- **Dependency-aware candidate rank:** 59
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_474cbee8dab89106167f0cb772598a59caf817095f2fc1f1b144e10d26fdcf7d`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IFNAR1|entrez:3454`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
59not prioritized-4
Resistance biomarker0.000
61not prioritized-6
Tumor-intrinsic / small molecule0.000
59not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.611)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: IFNAR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for IFNAR1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/IFNAR2.html b/examples/html_reports/depmap_26q1/targets/IFNAR2.html new file mode 100644 index 0000000..3108e61 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IFNAR2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: IFNAR2 + + + + +
+ +
+

Target hypothesis report: IFNAR2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
IFNAR2
+
+
+
Target name
+
interferon alpha and beta receptor subunit 2
+
+
+
Open Targets melanoma score
+
0.592
+
+
+
+
Open Targets baseline rank
+
79
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.01738288137045248,"interquartile_range":0.12488492898376848,"maximum":0.5714236108108321,"mean":0.0503920619753953,"measured_model_count":56,"median":0.04386869337198644,"minimum":-0.45216017373590417,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.107502047613316,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0072759297821299185,"interquartile_range":0.016571792690970602,"maximum":0.5636407199137389,"mean":0.02954335432879648,"measured_model_count":56,"median":0.012610739619383672,"minimum":4.461740631815872e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02384772247310052,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.000658658850054377,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.016201513718070007,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.019012962091614093,"gene_effect_median":-0.009370796305043658},"dependency_probability_context_minus_non_context_median":-0.0007099957223426507,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.0169890873015873,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0199372033044009,"gene_effect_context_minus_non_context_median":-0.009585235386186088}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 83
+- **Dependency-aware candidate rank:** 83
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_637ea16bfbc50e923cf4d4f3355b47fb08051992ee1c7fc2e81c98159732d28f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IFNAR2|entrez:3455`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
83not prioritized-4
Resistance biomarker0.000
85not prioritized-6
Tumor-intrinsic / small molecule0.000
83not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.592)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: IFNAR2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for IFNAR2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/IFNGR1.html b/examples/html_reports/depmap_26q1/targets/IFNGR1.html new file mode 100644 index 0000000..34d26f3 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IFNGR1.html @@ -0,0 +1,70 @@ +IFNGR1 — DepMap research preview

IFNGR1

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.03662359372573171,"interquartile_range":0.08240767601439589,"maximum":0.5871211700580072,"mean":0.0897245542698267,"measured_model_count":56,"median":0.08379368461486343,"minimum":-0.1744025104314158,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1190312697401276,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005404275629848286,"interquartile_range":0.008713219530913212,"maximum":0.06268986152833818,"mean":0.01167419637458284,"measured_model_count":56,"median":0.008325044038448394,"minimum":0.000290948338437609,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.014117495160761499,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00018228979421905725,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.004881835737120865,"gene_effect_median":-0.015810743032892788},"dependency_probability_context_minus_non_context_median":-0.00021181986832344984,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.005119147196564172,"gene_effect_context_minus_non_context_median":-0.01620129900277649}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_00833cde4b1bc1e68e5a57bcb01fd89aac37a482209d44bc9c1fc0f755d665f2`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IFNGR1|entrez:3459`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/IKBKB.html b/examples/html_reports/depmap_26q1/targets/IKBKB.html new file mode 100644 index 0000000..b4a7a8c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IKBKB.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: IKBKB + + + + +
+ +
+

Target hypothesis report: IKBKB

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
IKBKB
+
+
+
Target name
+
inhibitor of nuclear factor kappa B kinase subunit beta
+
+
+
Open Targets melanoma score
+
0.575
+
+
+
+
Open Targets baseline rank
+
108
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.16570556644074375,"interquartile_range":0.21406066264224513,"maximum":0.277540361548298,"mean":-0.0537285075628385,"measured_model_count":56,"median":-0.035178888153201554,"minimum":-0.4502159236126616,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04835509620150139,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.012418408279742225,"interquartile_range":0.07750041480523112,"maximum":0.3740135448755501,"mean":0.06264769752353014,"measured_model_count":56,"median":0.032710880080595445,"minimum":0.001974767741085321,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08991882308497334,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0014713304205474648,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04304635761589404,"pan_cancer_fraction":0.04304635761589404,"threshold":0.5},{"context_fraction":0.0,"difference":-0.018211920529801324,"pan_cancer_fraction":0.018211920529801324,"threshold":0.8}],"gene_effect_mean":0.022294775116363207,"gene_effect_median":0.015432259763544134},"dependency_probability_context_minus_non_context_median":-0.0019590452564146876,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04513888888888889,"non_context_fraction":0.04513888888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.019097222222222224,"non_context_fraction":0.019097222222222224,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.023378548906742076,"gene_effect_context_minus_non_context_median":0.01584270996744524}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 111
+- **Dependency-aware candidate rank:** 111
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_af84bacaebe1a9a8604d13e8fa6610e0392d6d1d554ab54eef621eeb5636a62f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IKBKB|entrez:3551`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
111not prioritized-3
Resistance biomarker0.000
112not prioritized-4
Tumor-intrinsic / small molecule0.000
111not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.575)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: IKBKB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for IKBKB in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/IKZF1.html b/examples/html_reports/depmap_26q1/targets/IKZF1.html new file mode 100644 index 0000000..7f4962f --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IKZF1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: IKZF1 + + + + +
+ +
+

Target hypothesis report: IKZF1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
IKZF1
+
+
+
Target name
+
IKAROS family zinc finger 1
+
+
+
Open Targets melanoma score
+
0.617
+
+
+
+
Open Targets baseline rank
+
50
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.027512744956176855,"interquartile_range":0.12572245092388826,"maximum":0.3196388161680785,"mean":0.08284123758726089,"measured_model_count":56,"median":0.08862815619119767,"minimum":-0.24711666136165655,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.15323519588006512,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.004563234822409594,"interquartile_range":0.01368660044820895,"maximum":0.10706346655544202,"mean":0.016026068206720766,"measured_model_count":56,"median":0.008626052643370095,"minimum":0.001245724641473512,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.018249835270618544,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004837720636222887,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.028973509933774833,"pan_cancer_fraction":0.028973509933774833,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013245033112582781,"pan_cancer_fraction":0.013245033112582781,"threshold":0.8}],"gene_effect_mean":0.054398881930841705,"gene_effect_median":0.03638743497379943},"dependency_probability_context_minus_non_context_median":-0.005203896204431409,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.030381944444444444,"non_context_fraction":0.030381944444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013888888888888888,"non_context_fraction":0.013888888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05704327202470209,"gene_effect_context_minus_non_context_median":0.03910950912065414}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 55
+- **Dependency-aware candidate rank:** 55
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ee71f1a8c1836ce7942b2b4f6df5f928442cac42430f4395bf80b44919ee0366`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IKZF1|entrez:10320`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
55not prioritized-5
Resistance biomarker0.000
57not prioritized-7
Tumor-intrinsic / small molecule0.000
55not prioritized-5
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.617)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: IKZF1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for IKZF1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/IKZF3.html b/examples/html_reports/depmap_26q1/targets/IKZF3.html new file mode 100644 index 0000000..60b9134 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IKZF3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: IKZF3 + + + + +
+ +
+

Target hypothesis report: IKZF3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
IKZF3
+
+
+
Target name
+
IKAROS family zinc finger 3
+
+
+
Open Targets melanoma score
+
0.496
+
+
+
+
Open Targets baseline rank
+
256
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.15225471866134643,"interquartile_range":0.1450957650450127,"maximum":0.5687894421280447,"mean":-0.07457440753634013,"measured_model_count":56,"median":-0.08258590755905212,"minimum":-0.4283817472108195,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.00715895361633373,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.020035342674531775,"interquartile_range":0.06675520347815952,"maximum":0.4832088876731502,"mean":0.06720851685893349,"measured_model_count":56,"median":0.047431048431888424,"minimum":0.00014254418116806933,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0867905461526913,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00012296220340794056,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03228476821192053,"pan_cancer_fraction":0.03228476821192053,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0173841059602649,"pan_cancer_fraction":0.0173841059602649,"threshold":0.8}],"gene_effect_mean":0.02904462386694076,"gene_effect_median":0.0028492014703619395},"dependency_probability_context_minus_non_context_median":-0.00012296220340794056,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.033854166666666664,"non_context_fraction":0.033854166666666664,"threshold":0.5},{"context_fraction":0.0,"difference":-0.018229166666666668,"non_context_fraction":0.018229166666666668,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.030456515304917095,"gene_effect_context_minus_non_context_median":0.0028492014703619395}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 258
+- **Dependency-aware candidate rank:** 258
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_7d1b7610d0d4f2fd2e9bc93af5df48ea4ee9cf9f7a911b461b1a5fe6b531136d`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IKZF3|entrez:22806`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
258not prioritized-2
Resistance biomarker0.000
258not prioritized-2
Tumor-intrinsic / small molecule0.000
258not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.496)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: IKZF3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for IKZF3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/IL2RA.html b/examples/html_reports/depmap_26q1/targets/IL2RA.html new file mode 100644 index 0000000..6a48828 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IL2RA.html @@ -0,0 +1,438 @@ + + + + +TargetIntel-IO report: IL2RA + + + + +
+ +
+

Target hypothesis report: IL2RA

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
IL2RA
+
+
+
Target name
+
interleukin 2 receptor subunit alpha
+
+
+
Open Targets melanoma score
+
0.624
+
+
+
+
Open Targets baseline rank
+
48
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.020638816605233,"interquartile_range":0.10185439590666129,"maximum":0.2707955970772144,"mean":0.028608067454334866,"measured_model_count":56,"median":0.02141508360816008,"minimum":-0.28140353524938666,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08121557930142828,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.009334879488875191,"interquartile_range":0.017097162374383305,"maximum":0.21297870352246084,"mean":0.0225685182916743,"measured_model_count":56,"median":0.01744431698994827,"minimum":0.0019616077520202666,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.026432041863258496,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0018854255800013313,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.009489097668670381,"gene_effect_median":-0.012483582075400942},"dependency_probability_context_minus_non_context_median":0.0019468436361349435,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.009950373249786312,"gene_effect_context_minus_non_context_median":-0.013652839911629001}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 5
+- **Dependency-aware candidate rank:** 6
+- **Rank delta:** 1
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_b31bc15820b545d199af7c982fb3cb1fca81d05d4ef557424ef473951cdce430`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IL2RA|entrez:3559`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
Treg-suppression marker / possible IO-combination target
+
+
+
Role confidence
+
medium
+
+
+
Therapeutic direction
+
deplete / block / use as biomarker
+
+
+
Best modality
+
antibody / Treg-associated IO-combination candidate
+
+
+
Resistance axis
+
treg_suppression
+
+
+
Matched resistance programs
+
Treg-mediated suppression
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.673
5medium43
Resistance biomarker0.628
5medium43
Tumor-intrinsic / small molecule0.126
14low34
+
+ +
+

Evidence for

+
    +
  • May support patient stratification or Treg-targeting hypotheses
    • +
  • Relevant to immune suppression in the tumor microenvironment
    • +
  • Some targets are surface-accessible
    • +
  • Moderate Open Targets melanoma association score (0.624)
    • +
  • Maps to curated anti-PD-1 resistance program: Treg-mediated suppression
    • +
  • Antibody fit is medium-high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Requires careful distinction between biomarker and causal target
    • +
  • Some markers are lineage markers rather than safe therapeutic targets
    • +
  • Treg targeting can affect normal immune tolerance
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.240
+
+
+
+
Main limitation
+
No major limitation flagged by current MVP rules
+
+
+

Uncertainty reason: Main limitation: No major limitation flagged by current MVP rules

+

Deprioritization reason: No strong deprioritization reason from current MVP rules

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for IL2RA in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/IL2RB.html b/examples/html_reports/depmap_26q1/targets/IL2RB.html new file mode 100644 index 0000000..a1e8f2c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IL2RB.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: IL2RB + + + + +
+ +
+

Target hypothesis report: IL2RB

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
IL2RB
+
+
+
Target name
+
interleukin 2 receptor subunit beta
+
+
+
Open Targets melanoma score
+
0.552
+
+
+
+
Open Targets baseline rank
+
147
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06167574734909529,"interquartile_range":0.11419653118966835,"maximum":0.4361428141068317,"mean":-0.00577974216374198,"measured_model_count":56,"median":0.0038683297949551783,"minimum":-0.31092525578047747,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.052520783840573064,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.011368937411090727,"interquartile_range":0.02233347339096224,"maximum":0.24466414856941635,"mean":0.03389348922793028,"measured_model_count":56,"median":0.020888460567987405,"minimum":0.0003780927747437147,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03370241080205297,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0035625711408692542,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.03015194114942479,"gene_effect_median":-0.01896943972780838},"dependency_probability_context_minus_non_context_median":0.0035879511611938766,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03161766051085518,"gene_effect_context_minus_non_context_median":-0.02052787748195724}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 149
+- **Dependency-aware candidate rank:** 149
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_88ca4f06a51f01c16c1fb63e93cafbb314fc7796e9bbf4d5a21c67bc19e52223`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IL2RB|entrez:3560`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
149not prioritized-2
Resistance biomarker0.000
150not prioritized-3
Tumor-intrinsic / small molecule0.000
149not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.552)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: IL2RB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for IL2RB in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/IL2RG.html b/examples/html_reports/depmap_26q1/targets/IL2RG.html new file mode 100644 index 0000000..4a49b89 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IL2RG.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: IL2RG + + + + +
+ +
+

Target hypothesis report: IL2RG

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
IL2RG
+
+
+
Target name
+
interleukin 2 receptor subunit gamma
+
+
+
Open Targets melanoma score
+
0.553
+
+
+
+
Open Targets baseline rank
+
146
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.0212074848635695,"interquartile_range":0.1010287784388279,"maximum":0.2924073670526511,"mean":0.06727286663522855,"measured_model_count":56,"median":0.0675100811958824,"minimum":-0.18469177564542644,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1222362633023974,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.00617458498793976,"interquartile_range":0.010574852516974416,"maximum":0.07360677819534792,"mean":0.014465831632885265,"measured_model_count":56,"median":0.010681045947869647,"minimum":0.0011765421315893725,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.016749437504914175,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.000809560946739736,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":3.077497282899522e-05,"gene_effect_median":-0.004176339451322203},"dependency_probability_context_minus_non_context_median":-0.0009039873661311846,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":3.227097845262539e-05,"gene_effect_context_minus_non_context_median":-0.004276167374979975}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 148
+- **Dependency-aware candidate rank:** 148
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_f001ed049e478e354cb98bf6f4b4ae9778043805613e42cda9f9f2933dd65cb4`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IL2RG|entrez:3561`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
148not prioritized-2
Resistance biomarker0.000
149not prioritized-3
Tumor-intrinsic / small molecule0.000
148not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.553)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: IL2RG lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for IL2RG in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/IL7R.html b/examples/html_reports/depmap_26q1/targets/IL7R.html new file mode 100644 index 0000000..50e887c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IL7R.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: IL7R + + + + +
+ +
+

Target hypothesis report: IL7R

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
IL7R
+
+
+
Target name
+
interleukin 7 receptor
+
+
+
Open Targets melanoma score
+
0.570
+
+
+
+
Open Targets baseline rank
+
114
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.007574111825057125,"interquartile_range":0.10459650304601474,"maximum":0.2951420481853716,"mean":0.06107047570028201,"measured_model_count":56,"median":0.06426875135630919,"minimum":-0.2820855435259647,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11217061487107187,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005832086899811304,"interquartile_range":0.012917677632533172,"maximum":0.13158609085739606,"mean":0.01743959809337777,"measured_model_count":56,"median":0.010212835631815064,"minimum":0.0016609086285636968,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.018749764532344476,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002909761879021573,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.005681804761027649,"gene_effect_median":0.009355084110728065},"dependency_probability_context_minus_non_context_median":-0.0031124595115192572,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.005958003603577594,"gene_effect_context_minus_non_context_median":0.01024282360728069}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 116
+- **Dependency-aware candidate rank:** 116
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_7269dad5115f5d36f6b0dbdcc3f7e7eb7d633a0d105197d35af3ac12a02df613`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IL7R|entrez:3575`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
116not prioritized-2
Resistance biomarker0.000
117not prioritized-3
Tumor-intrinsic / small molecule0.000
116not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.570)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: IL7R lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for IL7R in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/IRF1.html b/examples/html_reports/depmap_26q1/targets/IRF1.html new file mode 100644 index 0000000..5defa1b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IRF1.html @@ -0,0 +1,70 @@ +IRF1 — DepMap research preview

IRF1

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.09754301210474758,"interquartile_range":0.12296515702841573,"maximum":0.26037306954494316,"mean":-0.03541258134233933,"measured_model_count":56,"median":-0.021794338384010233,"minimum":-0.4899942974308896,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.025422144923668153,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.013848609180153479,"interquartile_range":0.03581323489428311,"maximum":0.49436318873189083,"mean":0.04739429910381706,"measured_model_count":56,"median":0.02736019181396147,"minimum":0.0011200409618568816,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04966184407443659,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005307021890764426,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.014909579247357252,"gene_effect_median":0.02854707621615703},"dependency_probability_context_minus_non_context_median":-0.006068298031833317,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.015634350460770413,"gene_effect_context_minus_non_context_median":0.029700220772131348}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_5587d9d52511ee49fff4064d020c2c608d726eb33666de09b08d9bba455f18ee`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IRF1|entrez:3659`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/IRF4.html b/examples/html_reports/depmap_26q1/targets/IRF4.html new file mode 100644 index 0000000..91f04e5 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IRF4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: IRF4 + + + + +
+ +
+

Target hypothesis report: IRF4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
IRF4
+
+
+
Target name
+
interferon regulatory factor 4
+
+
+
Open Targets melanoma score
+
0.693
+
+
+
+
Open Targets baseline rank
+
23
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.6327296669157861,"interquartile_range":0.5324128216394848,"maximum":0.6235667057736118,"mean":-0.39855183522522275,"measured_model_count":56,"median":-0.23865970092198735,"minimum":-1.5645985791747252,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.10031684527630133,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.047184383715357534,"interquartile_range":0.6857642743569041,"maximum":1.0,"mean":0.35466976185022175,"measured_model_count":56,"median":0.1569832292049153,"minimum":2.7037314917020238e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.7329486580722616,"threshold_fractions":[{"denominator":56,"fraction":0.32142857142857145,"numerator":18,"threshold":0.5},{"denominator":56,"fraction":0.23214285714285715,"numerator":13,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.10225635227015582,"dependency_probability_threshold_fractions":[{"context_fraction":0.32142857142857145,"difference":0.24940870387890257,"pan_cancer_fraction":0.07201986754966887,"threshold":0.5},{"context_fraction":0.23214285714285715,"difference":0.17254020813623464,"pan_cancer_fraction":0.059602649006622516,"threshold":0.8}],"gene_effect_mean":-0.21403777183379744,"gene_effect_median":-0.13333449997103344},"dependency_probability_context_minus_non_context_median":0.10371211068611616,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.32142857142857145,"difference":0.26153273809523814,"non_context_fraction":0.059895833333333336,"threshold":0.5},{"context_fraction":0.23214285714285715,"difference":0.18092757936507936,"non_context_fraction":0.051215277777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.22444238574238473,"gene_effect_context_minus_non_context_median":-0.1359491297562201}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 30
+- **Dependency-aware candidate rank:** 30
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_bd0f27b20205aefe67ca908c9390ba7067e99dca131248aefebb5a532f4fc3ae`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IRF4|entrez:3662`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
30not prioritized-7
Resistance biomarker0.000
32not prioritized-9
Tumor-intrinsic / small molecule0.009
25not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.693)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: IRF4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for IRF4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/IRS4.html b/examples/html_reports/depmap_26q1/targets/IRS4.html new file mode 100644 index 0000000..128edd8 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/IRS4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: IRS4 + + + + +
+ +
+

Target hypothesis report: IRS4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
IRS4
+
+
+
Target name
+
insulin receptor substrate 4
+
+
+
Open Targets melanoma score
+
0.525
+
+
+
+
Open Targets baseline rank
+
191
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.18839419052946696,"interquartile_range":0.1798390999941063,"maximum":0.21201552366845364,"mean":-0.09293988067528866,"measured_model_count":56,"median":-0.07806148005826202,"minimum":-0.38768029787152425,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.00855509053536067,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.018429753510722652,"interquartile_range":0.07826150665683715,"maximum":0.4219517244413161,"mean":0.0786677639842874,"measured_model_count":56,"median":0.0474389800368865,"minimum":0.003356154467398746,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0966912601675598,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.008685965826528003,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.011589403973509934,"pan_cancer_fraction":0.011589403973509934,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.8}],"gene_effect_mean":0.023509037116381748,"gene_effect_median":0.02792301116680959},"dependency_probability_context_minus_non_context_median":-0.00931148966276258,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.012152777777777778,"non_context_fraction":0.012152777777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.024651837531761395,"gene_effect_context_minus_non_context_median":0.029325363379890765}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 193
+- **Dependency-aware candidate rank:** 193
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_afae59de99b761f9b7a90a373df1341d383aa0f80ba0a64a6755125681cd2271`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:IRS4|entrez:8471`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
193not prioritized-2
Resistance biomarker0.000
193not prioritized-2
Tumor-intrinsic / small molecule0.000
193not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.525)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: IRS4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for IRS4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/JAK1.html b/examples/html_reports/depmap_26q1/targets/JAK1.html new file mode 100644 index 0000000..74a1cbc --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/JAK1.html @@ -0,0 +1,440 @@ + + + + +TargetIntel-IO report: JAK1 + + + + +
+ +
+

Target hypothesis report: JAK1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
JAK1
+
+
+
Target name
+
Janus kinase 1
+
+
+
Open Targets melanoma score
+
0.482
+
+
+
+
Open Targets baseline rank
+
271
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06904007760789696,"interquartile_range":0.19526888874388504,"maximum":0.9465240508757611,"mean":0.04591288417512017,"measured_model_count":56,"median":0.02114251550731768,"minimum":-0.3753752648328587,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12622881113598808,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.006062450283729294,"interquartile_range":0.034487534754270424,"maximum":0.4388416274607162,"mean":0.0392200208609982,"measured_model_count":56,"median":0.020298339745821688,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04054998503799972,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01630133583031499,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04056291390728477,"pan_cancer_fraction":0.04056291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":-0.012417218543046357,"pan_cancer_fraction":0.012417218543046357,"threshold":0.8}],"gene_effect_mean":0.1143914024787971,"gene_effect_median":0.07852203097934171},"dependency_probability_context_minus_non_context_median":-0.017842739234583828,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.042534722222222224,"non_context_fraction":0.042534722222222224,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013020833333333334,"non_context_fraction":0.013020833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.1199520956548499,"gene_effect_context_minus_non_context_median":0.08286038187670032}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 11
+- **Dependency-aware candidate rank:** 19
+- **Rank delta:** 8
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_38d521b13eaca50b1777062b74ee94be66e56a9306d92f6dd881361e2007b804`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:JAK1|entrez:3716`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
IFN-gamma resistance mechanism / biomarker
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
use as biomarker / patient stratification
+
+
+
Best modality
+
resistance biomarker / patient stratification
+
+
+
Resistance axis
+
ifng_resistance
+
+
+
Matched resistance programs
+
IFN-gamma pathway resistance
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.214
11low260
Resistance biomarker0.792
3high268
Tumor-intrinsic / small molecule0.114
16low255
+
+ +
+

Evidence for

+
    +
  • Mechanistically linked to immune resistance
    • +
  • Relevant to interferon-response competence
    • +
  • Useful for identifying tumors with impaired immune responsiveness
    • +
  • Moderate Open Targets melanoma association score (0.482)
    • +
  • Maps to curated anti-PD-1 resistance program: IFN-gamma pathway resistance
    • +
  • Stable role classifier confidence is high
    • +
  • Biomarker fit is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Loss-of-function resistance mechanisms may be hard to target directly
    • +
  • May indicate resistance rather than therapeutic vulnerability
    • +
  • Not usually a direct IO-combination antibody target
    • +
  • Most useful as biomarker or stratification marker rather than direct therapeutic target
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
high confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.320
+
+
+
+
Main limitation
+
Likely more useful for stratification than direct therapeutic targeting
+
+
+

Uncertainty reason: Main limitation: Likely more useful for stratification than direct therapeutic targeting

+

Deprioritization reason: JAK1 should not be deprioritized globally, but should be ranked mainly in biomarker or patient-stratification mode.

+
+ +
+

Recommended next validation experiment

+

Validation category: biomarker validation

+

Next experiment: Test whether JAK1 status or expression differs between anti-PD-1 responders and non-responders in an independent melanoma cohort.

+

Rationale: This would determine whether the candidate has practical value as a resistance biomarker or patient-stratification feature.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/JAK2.html b/examples/html_reports/depmap_26q1/targets/JAK2.html new file mode 100644 index 0000000..3f02fb8 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/JAK2.html @@ -0,0 +1,440 @@ + + + + +TargetIntel-IO report: JAK2 + + + + +
+ +
+

Target hypothesis report: JAK2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
JAK2
+
+
+
Target name
+
Janus kinase 2
+
+
+
Open Targets melanoma score
+
0.489
+
+
+
+
Open Targets baseline rank
+
265
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.09372960195593227,"interquartile_range":0.09638480604756475,"maximum":0.4345972003497355,"mean":0.14725027992853618,"measured_model_count":56,"median":0.14140384507405612,"minimum":-0.10783153860797157,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.19011440800349702,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0034333194534452273,"interquartile_range":0.0042969091439646915,"maximum":0.044572665063286214,"mean":0.007047471137138419,"measured_model_count":56,"median":0.005546648360096902,"minimum":0.0003687940884532363,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.007730228597409919,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0010101027573501528,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":0.021403211381747195,"gene_effect_median":0.005774598696880573},"dependency_probability_context_minus_non_context_median":-0.0010757473599788264,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.022443645268359957,"gene_effect_context_minus_non_context_median":0.005859738498348671}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 10
+- **Dependency-aware candidate rank:** 8
+- **Rank delta:** -2
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_dcadae74d4b1f7e8d150f46e15232c9ebea66968f0ab733d2b90319fda5128f8`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:JAK2|entrez:3717`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
IFN-gamma resistance mechanism / biomarker
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
use as biomarker / patient stratification
+
+
+
Best modality
+
resistance biomarker / patient stratification
+
+
+
Resistance axis
+
ifng_resistance
+
+
+
Matched resistance programs
+
IFN-gamma pathway resistance
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.215
10low255
Resistance biomarker0.793
2high263
Tumor-intrinsic / small molecule0.115
15low250
+
+ +
+

Evidence for

+
    +
  • Mechanistically linked to immune resistance
    • +
  • Relevant to interferon-response competence
    • +
  • Useful for identifying tumors with impaired immune responsiveness
    • +
  • Moderate Open Targets melanoma association score (0.489)
    • +
  • Maps to curated anti-PD-1 resistance program: IFN-gamma pathway resistance
    • +
  • Stable role classifier confidence is high
    • +
  • Biomarker fit is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Loss-of-function resistance mechanisms may be hard to target directly
    • +
  • May indicate resistance rather than therapeutic vulnerability
    • +
  • Not usually a direct IO-combination antibody target
    • +
  • Most useful as biomarker or stratification marker rather than direct therapeutic target
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
high confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.320
+
+
+
+
Main limitation
+
Likely more useful for stratification than direct therapeutic targeting
+
+
+

Uncertainty reason: Main limitation: Likely more useful for stratification than direct therapeutic targeting

+

Deprioritization reason: JAK2 should not be deprioritized globally, but should be ranked mainly in biomarker or patient-stratification mode.

+
+ +
+

Recommended next validation experiment

+

Validation category: biomarker validation

+

Next experiment: Test whether JAK2 status or expression differs between anti-PD-1 responders and non-responders in an independent melanoma cohort.

+

Rationale: This would determine whether the candidate has practical value as a resistance biomarker or patient-stratification feature.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/JUN.html b/examples/html_reports/depmap_26q1/targets/JUN.html new file mode 100644 index 0000000..eaca650 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/JUN.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: JUN + + + + +
+ +
+

Target hypothesis report: JUN

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
JUN
+
+
+
Target name
+
Jun proto-oncogene, AP-1 transcription factor subunit
+
+
+
Open Targets melanoma score
+
0.558
+
+
+
+
Open Targets baseline rank
+
137
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.311009377716012,"interquartile_range":0.2506178311258941,"maximum":0.08716511131816934,"mean":-0.20828664428562876,"measured_model_count":56,"median":-0.17296392891862877,"minimum":-1.2725810284274188,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.06039154659011792,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.038700745106317665,"interquartile_range":0.16927161157534584,"maximum":0.9953158990721827,"mean":0.1765632573037201,"measured_model_count":56,"median":0.08893106341563362,"minimum":0.005466014892066753,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2079723566816635,"threshold_fractions":[{"denominator":56,"fraction":0.10714285714285714,"numerator":6,"threshold":0.5},{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.04028546373813935,"dependency_probability_threshold_fractions":[{"context_fraction":0.10714285714285714,"difference":-0.09732734153263954,"pan_cancer_fraction":0.20447019867549668,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.06066698202459792,"pan_cancer_fraction":0.11423841059602649,"threshold":0.8}],"gene_effect_mean":0.07566779254446426,"gene_effect_median":0.045561312447407354},"dependency_probability_context_minus_non_context_median":-0.04477764253805114,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.10714285714285714,"difference":-0.10205853174603176,"non_context_fraction":0.2092013888888889,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.06361607142857142,"non_context_fraction":0.1171875,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.07934608801537568,"gene_effect_context_minus_non_context_median":0.04855652372490543}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 139
+- **Dependency-aware candidate rank:** 139
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_037ccfa9f527c9e4580f363513b870b691086520ca44d989716d2dba9c97befe`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:JUN|entrez:3725`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
139not prioritized-2
Resistance biomarker0.000
140not prioritized-3
Tumor-intrinsic / small molecule0.000
139not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.558)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: JUN lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for JUN in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KAT6A.html b/examples/html_reports/depmap_26q1/targets/KAT6A.html new file mode 100644 index 0000000..e5b83c3 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KAT6A.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KAT6A + + + + +
+ +
+

Target hypothesis report: KAT6A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KAT6A
+
+
+
Target name
+
lysine acetyltransferase 6A
+
+
+
Open Targets melanoma score
+
0.558
+
+
+
+
Open Targets baseline rank
+
138
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.1905321316921751,"interquartile_range":0.18847406164423797,"maximum":0.2913844299720876,"mean":-0.13017761755490873,"measured_model_count":56,"median":-0.10723105858661139,"minimum":-0.7313695948349267,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0020580700479371113,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.02057695392620386,"interquartile_range":0.08524065376438715,"maximum":0.9207122230841256,"mean":0.1330831920605305,"measured_model_count":56,"median":0.0533855412738906,"minimum":0.003751296975372678,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10581760769059101,"threshold_fractions":[{"denominator":56,"fraction":0.10714285714285714,"numerator":6,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.013093793336214715,"dependency_probability_threshold_fractions":[{"context_fraction":0.10714285714285714,"difference":0.05747398297067171,"pan_cancer_fraction":0.04966887417218543,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.0036660359508041626,"pan_cancer_fraction":0.02152317880794702,"threshold":0.8}],"gene_effect_mean":-0.035265813371509025,"gene_effect_median":-0.035437214931657426},"dependency_probability_context_minus_non_context_median":0.013622219272891888,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.10714285714285714,"difference":0.06026785714285714,"non_context_fraction":0.046875,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.003844246031746032,"non_context_fraction":0.021701388888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03698012374373508,"gene_effect_context_minus_non_context_median":-0.03881376916812894}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 140
+- **Dependency-aware candidate rank:** 140
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_9ebc57a4eff144bb2aaab9763de8d0f8742e938d93ab191e8b80df98b9457057`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KAT6A|entrez:7994`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
140not prioritized-2
Resistance biomarker0.000
141not prioritized-3
Tumor-intrinsic / small molecule0.000
140not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.558)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KAT6A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KAT6A in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KAT6B.html b/examples/html_reports/depmap_26q1/targets/KAT6B.html new file mode 100644 index 0000000..df8f0a4 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KAT6B.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KAT6B + + + + +
+ +
+

Target hypothesis report: KAT6B

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KAT6B
+
+
+
Target name
+
lysine acetyltransferase 6B
+
+
+
Open Targets melanoma score
+
0.511
+
+
+
+
Open Targets baseline rank
+
234
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06662516590668541,"interquartile_range":0.11394230237326466,"maximum":0.31418589019523446,"mean":-0.001255060192413378,"measured_model_count":56,"median":-0.027627318543472862,"minimum":-0.1751527942425262,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04731713646657926,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01042254558613599,"interquartile_range":0.03023072724184981,"maximum":0.0937161810188809,"mean":0.02994953977997856,"measured_model_count":56,"median":0.02764718556997526,"minimum":0.0014934966998191056,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0406532728279858,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0026773266664892395,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.8}],"gene_effect_mean":0.021002704184916707,"gene_effect_median":-0.0100310731015332},"dependency_probability_context_minus_non_context_median":0.0026933312131079863,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.022023668971683445,"gene_effect_context_minus_non_context_median":-0.010138472012778607}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 236
+- **Dependency-aware candidate rank:** 236
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_0fd0fa194eab1745843369ba93f662d9bb1b349614f841b8a601fd61d3359eea`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KAT6B|entrez:23522`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
236not prioritized-2
Resistance biomarker0.000
236not prioritized-2
Tumor-intrinsic / small molecule0.000
236not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.511)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KAT6B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KAT6B in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KDM5A.html b/examples/html_reports/depmap_26q1/targets/KDM5A.html new file mode 100644 index 0000000..2816841 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KDM5A.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KDM5A + + + + +
+ +
+

Target hypothesis report: KDM5A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KDM5A
+
+
+
Target name
+
lysine demethylase 5A
+
+
+
Open Targets melanoma score
+
0.521
+
+
+
+
Open Targets baseline rank
+
209
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.22202348434208968,"interquartile_range":0.25163186515633823,"maximum":0.44193079074765096,"mean":-0.09434882159752087,"measured_model_count":56,"median":-0.08145184435535191,"minimum":-0.8218153503794106,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.029608380814248568,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.013875800874593986,"interquartile_range":0.11339090599007796,"maximum":0.9230332160863932,"mean":0.12447802103958014,"measured_model_count":56,"median":0.043825408803144034,"minimum":0.00024619135451046454,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12726670686467195,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.02036209927833478,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.01596499526963103,"pan_cancer_fraction":0.0695364238410596,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.01750236518448439,"pan_cancer_fraction":0.018211920529801324,"threshold":0.8}],"gene_effect_mean":0.027382521382587927,"gene_effect_median":0.04072711474304436},"dependency_probability_context_minus_non_context_median":-0.0205009517912558,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.01674107142857143,"non_context_fraction":0.0703125,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.0183531746031746,"non_context_fraction":0.017361111111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.02871361617201916,"gene_effect_context_minus_non_context_median":0.04194594711379909}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 211
+- **Dependency-aware candidate rank:** 211
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_62eda7faa4daf238a28f53278df1e400a269e104861d7c07fb2e30f15b010ec7`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KDM5A|entrez:5927`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
211not prioritized-2
Resistance biomarker0.000
211not prioritized-2
Tumor-intrinsic / small molecule0.000
211not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.521)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KDM5A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KDM5A in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KDR.html b/examples/html_reports/depmap_26q1/targets/KDR.html new file mode 100644 index 0000000..1544606 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KDR.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KDR + + + + +
+ +
+

Target hypothesis report: KDR

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KDR
+
+
+
Target name
+
kinase insert domain receptor
+
+
+
Open Targets melanoma score
+
0.669
+
+
+
+
Open Targets baseline rank
+
26
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.15396703246047083,"interquartile_range":0.18579743831009796,"maximum":0.35412317858308234,"mean":-0.05750978779259812,"measured_model_count":56,"median":-0.0387256781978957,"minimum":-0.3444614053834766,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03183040584962712,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.014005661846951734,"interquartile_range":0.06638249016346734,"maximum":0.28670345020567467,"mean":0.05762538223094942,"measured_model_count":56,"median":0.03446964505050472,"minimum":0.0010452495586403565,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08038815201041907,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.018665865810338793,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0074503311258278145,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.052792893277689865,"gene_effect_median":0.06605930169914},"dependency_probability_context_minus_non_context_median":-0.019212846437965572,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0078125,"non_context_fraction":0.0078125,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.055359214478688704,"gene_effect_context_minus_non_context_median":0.06756047105449794}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 33
+- **Dependency-aware candidate rank:** 33
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_7188d564b28cb2df9750a78deb062a7facf73318ad82c053152b331ed15e4d9f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KDR|entrez:3791`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
33not prioritized-7
Resistance biomarker0.000
35not prioritized-9
Tumor-intrinsic / small molecule0.005
28not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.669)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KDR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KDR in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KEAP1.html b/examples/html_reports/depmap_26q1/targets/KEAP1.html new file mode 100644 index 0000000..9275b43 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KEAP1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KEAP1 + + + + +
+ +
+

Target hypothesis report: KEAP1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KEAP1
+
+
+
Target name
+
kelch like ECH associated protein 1
+
+
+
Open Targets melanoma score
+
0.465
+
+
+
+
Open Targets baseline rank
+
291
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.7082108266491682,"interquartile_range":0.5938186833592835,"maximum":0.7135935781879718,"mean":-0.4100413926682732,"measured_model_count":56,"median":-0.3844446143597566,"minimum":-1.446443035340094,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.11439214328988481,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.057768436553657446,"interquartile_range":0.8160912945797978,"maximum":0.9915583744017852,"mean":0.450257304808193,"measured_model_count":56,"median":0.37728663389576456,"minimum":4.915247993642987e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.8738597311334553,"threshold_fractions":[{"denominator":56,"fraction":0.42857142857142855,"numerator":24,"threshold":0.5},{"denominator":56,"fraction":0.2857142857142857,"numerator":16,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.31071286266727666,"dependency_probability_threshold_fractions":[{"context_fraction":0.42857142857142855,"difference":0.21582308420056762,"pan_cancer_fraction":0.21274834437086093,"threshold":0.5},{"context_fraction":0.2857142857142857,"difference":0.15657521286660359,"pan_cancer_fraction":0.1291390728476821,"threshold":0.8}],"gene_effect_mean":-0.24845515864725742,"gene_effect_median":-0.2466112559431453},"dependency_probability_context_minus_non_context_median":0.31619030392886477,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.42857142857142855,"difference":0.2263144841269841,"non_context_fraction":0.20225694444444445,"threshold":0.5},{"context_fraction":0.2857142857142857,"difference":0.1641865079365079,"non_context_fraction":0.12152777777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.2605328399703881,"gene_effect_context_minus_non_context_median":-0.25568042144857883}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":92.5925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 291
+- **Dependency-aware candidate rank:** 291
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_18670903b2c5a4ae65294304c59c6d8863904e118ab3a9abd592281dbc3d67f3`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KEAP1|entrez:9817`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
291not prioritized0
Resistance biomarker0.000
291not prioritized0
Tumor-intrinsic / small molecule0.000
291not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.465)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KEAP1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KEAP1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KIT.html b/examples/html_reports/depmap_26q1/targets/KIT.html new file mode 100644 index 0000000..810d2fa --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KIT.html @@ -0,0 +1,434 @@ + + + + +TargetIntel-IO report: KIT + + + + +
+ +
+

Target hypothesis report: KIT

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KIT
+
+
+
Target name
+
KIT proto-oncogene, receptor tyrosine kinase
+
+
+
Open Targets melanoma score
+
0.718
+
+
+
+
Open Targets baseline rank
+
13
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.15047254523839437,"interquartile_range":0.12483170574110164,"maximum":0.16694100888553057,"mean":-0.10507054540120067,"measured_model_count":56,"median":-0.11187987261054008,"minimum":-0.3611196971836982,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.025640839497292737,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.026005203789725564,"interquartile_range":0.057675318964253264,"maximum":0.24582508541769998,"mean":0.06628476557606086,"measured_model_count":56,"median":0.05726951313842029,"minimum":0.006213462729592259,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08368052275397883,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.022794176676194843,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.05068503375570338,"gene_effect_median":-0.05884822613831423},"dependency_probability_context_minus_non_context_median":0.023172068420461857,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.05314888956327223,"gene_effect_context_minus_non_context_median":-0.06235982604084975}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 21
+- **Dependency-aware candidate rank:** 21
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2720bbf5793b4600ea51971093e4c95473a8226c4dbc0f9f2a9303cf41648754`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KIT|entrez:3815`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / small-molecule target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
small-molecule inhibition / pathway targeting
+
+
+
Best modality
+
small molecule / pathway targeting
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
21not prioritized-8
Resistance biomarker0.098
22not prioritized-9
Tumor-intrinsic / small molecule0.679
5medium8
+
+ +
+

Evidence for

+
    +
  • High Open Targets melanoma association score (0.718)
    • +
  • Stable role classifier confidence is high
    • +
  • Small-molecule fit is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
0.889
+
+
+
+
Contradiction score
+
0.160
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KIT lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: tumor-intrinsic functional validation

+

Next experiment: Evaluate whether perturbing KIT alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays.

+

Rationale: This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KLF4.html b/examples/html_reports/depmap_26q1/targets/KLF4.html new file mode 100644 index 0000000..d0aa697 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KLF4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KLF4 + + + + +
+ +
+

Target hypothesis report: KLF4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KLF4
+
+
+
Target name
+
KLF transcription factor 4
+
+
+
Open Targets melanoma score
+
0.508
+
+
+
+
Open Targets baseline rank
+
243
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.0866160725632556,"interquartile_range":0.09094159645890684,"maximum":0.29033441321163894,"mean":-0.036429378374868294,"measured_model_count":56,"median":-0.045825769626115405,"minimum":-0.18846226428060717,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0043255238956512385,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01830988808607737,"interquartile_range":0.031197954431363674,"maximum":0.12728694959590328,"mean":0.03673849894871195,"measured_model_count":56,"median":0.02931121522718555,"minimum":0.0015769843027852257,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.049507842517441045,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00027614128553087036,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.01076158940397351,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":0.010892401367839824,"gene_effect_median":-0.009569965295020279},"dependency_probability_context_minus_non_context_median":0.00027614128553087036,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.011284722222222222,"non_context_fraction":0.011284722222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.011421893100998753,"gene_effect_context_minus_non_context_median":-0.010052677582369572}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 245
+- **Dependency-aware candidate rank:** 245
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ca94fac79b9d2871cf2dd70632376361a49d8a3afa84250a1002eb5e15b2526b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KLF4|entrez:9314`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
245not prioritized-2
Resistance biomarker0.000
245not prioritized-2
Tumor-intrinsic / small molecule0.000
245not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.508)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KLF4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KLF4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KLF6.html b/examples/html_reports/depmap_26q1/targets/KLF6.html new file mode 100644 index 0000000..474d616 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KLF6.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KLF6 + + + + +
+ +
+

Target hypothesis report: KLF6

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KLF6
+
+
+
Target name
+
KLF transcription factor 6
+
+
+
Open Targets melanoma score
+
0.581
+
+
+
+
Open Targets baseline rank
+
99
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.1740339281446544,"interquartile_range":0.287121816879088,"maximum":0.5582898749499964,"mean":-0.020014061949726214,"measured_model_count":56,"median":-0.05126217030720511,"minimum":-0.5678287346983116,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11308788873443362,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.004045553451322353,"interquartile_range":0.08106591108477244,"maximum":0.8387756064664146,"mean":0.09494424049900542,"measured_model_count":56,"median":0.03244514830539762,"minimum":3.5093885241607115e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08511146453609479,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.018934247933076763,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.012535477767265844,"pan_cancer_fraction":0.023178807947019868,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.010406811731315042,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.8}],"gene_effect_mean":-0.04910407777982369,"gene_effect_median":-0.10661125299604379},"dependency_probability_context_minus_non_context_median":0.01914453044385907,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.013144841269841268,"non_context_fraction":0.022569444444444444,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.010912698412698412,"non_context_fraction":0.006944444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.05149108156078732,"gene_effect_context_minus_non_context_median":-0.107981493548363}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 102
+- **Dependency-aware candidate rank:** 102
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_10da6f5b842aec03914d79436d05f2b5d13c4451d6fc835af124e56317f6d235`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KLF6|entrez:1316`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
102not prioritized-3
Resistance biomarker0.000
103not prioritized-4
Tumor-intrinsic / small molecule0.000
102not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.581)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KLF6 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KLF6 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KMT2A.html b/examples/html_reports/depmap_26q1/targets/KMT2A.html new file mode 100644 index 0000000..29815be --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KMT2A.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KMT2A + + + + +
+ +
+

Target hypothesis report: KMT2A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KMT2A
+
+
+
Target name
+
lysine methyltransferase 2A
+
+
+
Open Targets melanoma score
+
0.580
+
+
+
+
Open Targets baseline rank
+
101
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.247834586721482,"interquartile_range":0.2053139586165061,"maximum":0.14388081055483293,"mean":-0.1599635043193788,"measured_model_count":56,"median":-0.13474643688042431,"minimum":-0.7962726094629715,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.042520628104975915,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.028075360066156213,"interquartile_range":0.12381967132087579,"maximum":0.890939509576807,"mean":0.1369329942267416,"measured_model_count":56,"median":0.0731199024889937,"minimum":0.0032609376499916206,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.151895031387032,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.022529632958707357,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.10501419110690634,"pan_cancer_fraction":0.14072847682119205,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.013954588457899715,"pan_cancer_fraction":0.04966887417218543,"threshold":0.8}],"gene_effect_mean":0.04620430632163236,"gene_effect_median":0.04073661712261353},"dependency_probability_context_minus_non_context_median":-0.024362426630622852,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.11011904761904763,"non_context_fraction":0.14583333333333334,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.014632936507936511,"non_context_fraction":0.050347222222222224,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04845034899004538,"gene_effect_context_minus_non_context_median":0.04274723665726088}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 104
+- **Dependency-aware candidate rank:** 104
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_8436dbeba9b280b6ec14d9da09e082858c496e644deaf920d8877f659b3d861a`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KMT2A|entrez:4297`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
104not prioritized-3
Resistance biomarker0.000
105not prioritized-4
Tumor-intrinsic / small molecule0.000
104not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.580)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KMT2A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KMT2A in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KMT2C.html b/examples/html_reports/depmap_26q1/targets/KMT2C.html new file mode 100644 index 0000000..1fbaae4 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KMT2C.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KMT2C + + + + +
+ +
+

Target hypothesis report: KMT2C

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KMT2C
+
+
+
Target name
+
lysine methyltransferase 2C
+
+
+
Open Targets melanoma score
+
0.598
+
+
+
+
Open Targets baseline rank
+
70
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.002613878383379797,"interquartile_range":0.22930347633925058,"maximum":0.7588941965548464,"mean":0.08533586436646227,"measured_model_count":56,"median":0.08688860720869607,"minimum":-0.5393806663773176,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2266895979558708,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0032623542350772366,"interquartile_range":0.023637002199571364,"maximum":0.7548851600875993,"mean":0.047657468264772414,"measured_model_count":56,"median":0.00790666231691314,"minimum":3.015181277604221e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0268993564346486,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.008378037643394922,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.005321665089877012,"pan_cancer_fraction":0.023178807947019868,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":0.07308581728239892,"gene_effect_median":0.056357339633505504},"dependency_probability_context_minus_non_context_median":-0.00913467488608257,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.005580357142857144,"non_context_fraction":0.0234375,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.07663860006696002,"gene_effect_context_minus_non_context_median":0.059724463300712356}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 74
+- **Dependency-aware candidate rank:** 74
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d369b29a656346078e2f9ac3565002afaeb50e0db72fcd474bf060dd7e6d66f5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KMT2C|entrez:58508`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
74not prioritized-4
Resistance biomarker0.000
76not prioritized-6
Tumor-intrinsic / small molecule0.000
74not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.598)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KMT2C lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KMT2C in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KMT2D.html b/examples/html_reports/depmap_26q1/targets/KMT2D.html new file mode 100644 index 0000000..ccf4b03 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KMT2D.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KMT2D + + + + +
+ +
+

Target hypothesis report: KMT2D

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KMT2D
+
+
+
Target name
+
lysine methyltransferase 2D
+
+
+
Open Targets melanoma score
+
0.606
+
+
+
+
Open Targets baseline rank
+
61
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.5054747400504007,"interquartile_range":0.43801977053473673,"maximum":0.4453175128783058,"mean":-0.27953827290798855,"measured_model_count":56,"median":-0.2813972812521446,"minimum":-0.9363498739499392,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.06745496951566396,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.036792875788036104,"interquartile_range":0.5038830443625247,"maximum":0.9507611503193685,"mean":0.315814143315189,"measured_model_count":56,"median":0.1829714967357441,"minimum":0.00023457193745018845,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5406759201505609,"threshold_fractions":[{"denominator":56,"fraction":0.30357142857142855,"numerator":17,"threshold":0.5},{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.12194237947038289,"dependency_probability_threshold_fractions":[{"context_fraction":0.30357142857142855,"difference":-0.05818353831598866,"pan_cancer_fraction":0.3617549668874172,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":-0.021404919583727505,"pan_cancer_fraction":0.18211920529801323,"threshold":0.8}],"gene_effect_mean":0.11216053843555868,"gene_effect_median":0.07237576799848949},"dependency_probability_context_minus_non_context_median":-0.13011903737267616,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.30357142857142855,"difference":-0.06101190476190477,"non_context_fraction":0.3645833333333333,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":-0.022445436507936484,"non_context_fraction":0.1831597222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.11761278683173171,"gene_effect_context_minus_non_context_median":0.07649088974832446}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 65
+- **Dependency-aware candidate rank:** 65
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ba82733dc35e0dd2a1a3e56ad370a99476c5e79c7bc647f881fe9c41c76bfdac`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KMT2D|entrez:8085`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
65not prioritized-4
Resistance biomarker0.000
67not prioritized-6
Tumor-intrinsic / small molecule0.000
65not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.606)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KMT2D lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KMT2D in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KNL1.html b/examples/html_reports/depmap_26q1/targets/KNL1.html new file mode 100644 index 0000000..b1bf79d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KNL1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KNL1 + + + + +
+ +
+

Target hypothesis report: KNL1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KNL1
+
+
+
Target name
+
kinetochore scaffold 1
+
+
+
Open Targets melanoma score
+
0.519
+
+
+
+
Open Targets baseline rank
+
217
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.8209858622248248,"interquartile_range":0.26800043369654103,"maximum":0.4114298366282715,"mean":-0.6723034112825079,"measured_model_count":56,"median":-0.6974565079231971,"minimum":-1.276427559759107,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.5529854285282838,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.6264804733609197,"interquartile_range":0.29486977080895016,"maximum":0.9998985731748403,"mean":0.743338783315388,"measured_model_count":56,"median":0.83423638852549,"minimum":0.0011216508970974713,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9213502441698699,"threshold_fractions":[{"denominator":56,"fraction":0.875,"numerator":49,"threshold":0.5},{"denominator":56,"fraction":0.5357142857142857,"numerator":30,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0408741270024463,"dependency_probability_threshold_fractions":[{"context_fraction":0.875,"difference":0.05794701986754969,"pan_cancer_fraction":0.8170529801324503,"threshold":0.5},{"context_fraction":0.5357142857142857,"difference":0.05061494796594135,"pan_cancer_fraction":0.48509933774834435,"threshold":0.8}],"gene_effect_mean":-0.008917433590880264,"gene_effect_median":-0.05584297946607175},"dependency_probability_context_minus_non_context_median":0.04473365357168113,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.875,"difference":0.06076388888888884,"non_context_fraction":0.8142361111111112,"threshold":0.5},{"context_fraction":0.5357142857142857,"difference":0.0530753968253968,"non_context_fraction":0.4826388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.009350919945992131,"gene_effect_context_minus_non_context_median":-0.05706975577620854}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 219
+- **Dependency-aware candidate rank:** 219
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_42afc55e8df2c56e9de2c6d8093aec35b6bbaf8d02786599579a25e599effa59`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KNL1|entrez:57082`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
219not prioritized-2
Resistance biomarker0.000
219not prioritized-2
Tumor-intrinsic / small molecule0.000
219not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.519)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KNL1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KNL1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KRAS.html b/examples/html_reports/depmap_26q1/targets/KRAS.html new file mode 100644 index 0000000..3eefcf3 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KRAS.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KRAS + + + + +
+ +
+

Target hypothesis report: KRAS

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KRAS
+
+
+
Target name
+
KRas proto-oncogene, GTPase
+
+
+
Open Targets melanoma score
+
0.480
+
+
+
+
Open Targets baseline rank
+
273
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.6390363697007047,"interquartile_range":0.3255914225769023,"maximum":0.037107045533280814,"mean":-0.4615597662300834,"measured_model_count":56,"median":-0.4270863694795695,"minimum":-0.9671398918289789,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.31344494712380233,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.2804397654477754,"interquartile_range":0.4166743169804551,"maximum":0.9882225371239182,"mean":0.48315218978865904,"measured_model_count":56,"median":0.4738799422322064,"minimum":0.012521637812168088,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.6971140824282305,"threshold_fractions":[{"denominator":56,"fraction":0.48214285714285715,"numerator":27,"threshold":0.5},{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.11562974175001095,"dependency_probability_threshold_fractions":[{"context_fraction":0.48214285714285715,"difference":-0.09401608325449379,"pan_cancer_fraction":0.5761589403973509,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":-0.16248817407757807,"pan_cancer_fraction":0.34105960264900664,"threshold":0.8}],"gene_effect_mean":0.2633418509692072,"gene_effect_median":0.08983073184763496},"dependency_probability_context_minus_non_context_median":-0.1300421110614044,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.48214285714285715,"difference":-0.09858630952380948,"non_context_fraction":0.5807291666666666,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":-0.17038690476190474,"non_context_fraction":0.3489583333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.2761431909468766,"gene_effect_context_minus_non_context_median":0.10109950535962081}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 273
+- **Dependency-aware candidate rank:** 273
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_cf088782b794ba81973df7072f9b9c92d402cd3cddbb610dda021707b8b66cbf`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KRAS|entrez:3845`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
273not prioritized0
Resistance biomarker0.000
273not prioritized0
Tumor-intrinsic / small molecule0.000
273not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.480)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KRAS lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KRAS in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/KRT5.html b/examples/html_reports/depmap_26q1/targets/KRT5.html new file mode 100644 index 0000000..6964ef6 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/KRT5.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: KRT5 + + + + +
+ +
+

Target hypothesis report: KRT5

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
KRT5
+
+
+
Target name
+
keratin 5
+
+
+
Open Targets melanoma score
+
0.471
+
+
+
+
Open Targets baseline rank
+
282
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.1162600050798901,"interquartile_range":0.16026986264477588,"maximum":0.3326259306248558,"mean":-0.03271996044744329,"measured_model_count":56,"median":-0.03875848753631785,"minimum":-0.4083100273302143,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04400985756488579,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.013107390885123485,"interquartile_range":0.04935434074536283,"maximum":0.34081918050850224,"mean":0.05037789993099017,"measured_model_count":56,"median":0.027358384042971286,"minimum":0.0012650511761817924,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.062461731630486315,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005669141450315225,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.018647943378540567,"gene_effect_median":0.008795443937758655},"dependency_probability_context_minus_non_context_median":-0.0059289590279801505,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.019554440626108442,"gene_effect_context_minus_non_context_median":0.008975446451295908}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 282
+- **Dependency-aware candidate rank:** 282
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_064edcceeec27225416d8f3dfdfe36d40162fcbfadc1b53d55162123b6ddd806`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:KRT5|entrez:3852`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
282not prioritized0
Resistance biomarker0.000
282not prioritized0
Tumor-intrinsic / small molecule0.000
282not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.471)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: KRT5 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for KRT5 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/LAG3.html b/examples/html_reports/depmap_26q1/targets/LAG3.html new file mode 100644 index 0000000..2dafd71 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/LAG3.html @@ -0,0 +1,441 @@ + + + + +TargetIntel-IO report: LAG3 + + + + +
+ +
+

Target hypothesis report: LAG3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
LAG3
+
+
+
Target name
+
lymphocyte activating 3
+
+
+
Open Targets melanoma score
+
0.592
+
+
+
+
Open Targets baseline rank
+
80
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.05881633966392029,"interquartile_range":0.12893561937780812,"maximum":0.37914429966497276,"mean":0.003600261025976661,"measured_model_count":56,"median":0.006693995382591952,"minimum":-0.31014322945440886,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07011927971388784,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.010007862547405266,"interquartile_range":0.025780908070300368,"maximum":0.2736649589269115,"mean":0.03207975191250165,"measured_model_count":56,"median":0.02026514620529634,"minimum":0.0006578282366709314,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.035788770617705634,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0018901915706334774,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.011693795017936399,"gene_effect_median":0.010169669641757669},"dependency_probability_context_minus_non_context_median":-0.001965981755923319,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01226224338686388,"gene_effect_context_minus_non_context_median":0.01031202269999554}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 4
+- **Dependency-aware candidate rank:** 7
+- **Rank delta:** 3
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_0f145797159a290f7ec8bfc040c8f479017766ab656ef31fa4f80f000ae67a65`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:LAG3|entrez:3902`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
anti-PD-1 combination target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
block / inhibit
+
+
+
Best modality
+
antibody / IO-combination target
+
+
+
Resistance axis
+
checkpoint_redundancy
+
+
+
Matched resistance programs
+
Checkpoint redundancy
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.822
4high76
Resistance biomarker0.493
10medium70
Tumor-intrinsic / small molecule0.137
12low68
+
+ +
+

Evidence for

+
    +
  • Immune checkpoint biology
    • +
  • Potential compensatory inhibitory pathway after PD-1 blockade
    • +
  • Surface-accessible immune receptor or ligand
    • +
  • Moderate Open Targets melanoma association score (0.592)
    • +
  • Maps to curated anti-PD-1 resistance program: Checkpoint redundancy
    • +
  • Stable role classifier confidence is high
    • +
  • Antibody fit is high
    • +
  • IO-combination fit is high
    • +
  • Checkpoint-axis biology supports anti-PD-1 combination rationale
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Crowded IO target space
    • +
  • Expression may reflect exhausted immune-cell abundance rather than causal resistance in all tumors
    • +
  • Patient selection may be required
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
high confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.240
+
+
+
+
Main limitation
+
No major limitation flagged by current MVP rules
+
+
+

Uncertainty reason: Main limitation: No major limitation flagged by current MVP rules

+

Deprioritization reason: No strong deprioritization reason from current MVP rules

+
+ +
+

Recommended next validation experiment

+

Validation category: immune-checkpoint functional validation

+

Next experiment: Validate LAG3 expression in exhausted CD8 T-cell populations from anti-PD-1-resistant melanoma samples and test blockade in a melanoma/T-cell co-culture assay.

+

Rationale: This would test whether the candidate marks a relevant checkpoint axis and whether blockade can improve anti-tumor T-cell activity.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/LATS2.html b/examples/html_reports/depmap_26q1/targets/LATS2.html new file mode 100644 index 0000000..5be1e89 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/LATS2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: LATS2 + + + + +
+ +
+

Target hypothesis report: LATS2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
LATS2
+
+
+
Target name
+
large tumor suppressor kinase 2
+
+
+
Open Targets melanoma score
+
0.501
+
+
+
+
Open Targets baseline rank
+
253
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.1556578421689475,"interquartile_range":0.346068833316306,"maximum":0.6812382978063686,"mean":0.020232855958764978,"measured_model_count":56,"median":0.02532013141759792,"minimum":-0.5883085173462187,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1904109911473585,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.004812871870791315,"interquartile_range":0.07385812374473756,"maximum":0.5717176690234534,"mean":0.06581858221464584,"measured_model_count":56,"median":0.023948406020125466,"minimum":1.5225700296503551e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07867099561552887,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.007094941296658438,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.007095553453169347,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.04324556828627929,"gene_effect_median":0.06935077629481798},"dependency_probability_context_minus_non_context_median":-0.007375489439448841,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.00744047619047619,"non_context_fraction":0.010416666666666666,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04534778341130678,"gene_effect_context_minus_non_context_median":0.07086233124569989}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 255
+- **Dependency-aware candidate rank:** 255
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e53da3b2eb0faa199f618e2cfe62d4f48847b820fd8d00281249004ac5c8597f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:LATS2|entrez:26524`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
255not prioritized-2
Resistance biomarker0.000
255not prioritized-2
Tumor-intrinsic / small molecule0.000
255not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.501)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: LATS2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for LATS2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/LCK.html b/examples/html_reports/depmap_26q1/targets/LCK.html new file mode 100644 index 0000000..c315305 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/LCK.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: LCK + + + + +
+ +
+

Target hypothesis report: LCK

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
LCK
+
+
+
Target name
+
LCK proto-oncogene, Src family tyrosine kinase
+
+
+
Open Targets melanoma score
+
0.532
+
+
+
+
Open Targets baseline rank
+
185
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.08729246564785431,"interquartile_range":0.1844688496759413,"maximum":0.2059897868514309,"mean":-0.009407769188333403,"measured_model_count":56,"median":-0.015814512461379424,"minimum":-0.38590429969641227,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09717638402808698,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.006810646880507027,"interquartile_range":0.04657577854208711,"maximum":0.336222749595819,"mean":0.04188276382137456,"measured_model_count":56,"median":0.022171372889984876,"minimum":0.0028324291920454408,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.053386425422594135,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-6.781987367632594e-05,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.009722048599233306,"gene_effect_median":-0.011438666328224274},"dependency_probability_context_minus_non_context_median":-7.216257711747248e-05,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.010194648183918242,"gene_effect_context_minus_non_context_median":-0.011644779982110654}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 187
+- **Dependency-aware candidate rank:** 187
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2875136be9b593d0d2c16ed94c6f477189a2ed21146b5ecafa6630302f57e0da`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:LCK|entrez:3932`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
187not prioritized-2
Resistance biomarker0.000
188not prioritized-3
Tumor-intrinsic / small molecule0.000
187not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.532)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: LCK lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for LCK in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/LILRB1.html b/examples/html_reports/depmap_26q1/targets/LILRB1.html new file mode 100644 index 0000000..b6a1e16 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/LILRB1.html @@ -0,0 +1,70 @@ +LILRB1 — DepMap research preview

LILRB1

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.01109020400994214,"interquartile_range":0.1398087266452999,"maximum":0.4433027675302377,"mean":0.05536551565827964,"measured_model_count":56,"median":0.051821418581015924,"minimum":-0.2138537031730067,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12871852263535774,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.006022954802638753,"interquartile_range":0.017556262760780754,"maximum":0.11051920534037452,"mean":0.01924822092948011,"measured_model_count":56,"median":0.013681127550983843,"minimum":0.00023616078642564348,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.023579217563419505,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0023882042686036477,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.018479761103356432,"gene_effect_median":-0.02006817567605361},"dependency_probability_context_minus_non_context_median":0.0024795342371092023,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.019378082823658466,"gene_effect_context_minus_non_context_median":-0.020608548639528948}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_297dbadda58e632878208cfea8f7dbf9674be3b2cbe98cc3e4b7c3ad66a29cdf`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:LILRB1|entrez:10859`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/LILRB2.html b/examples/html_reports/depmap_26q1/targets/LILRB2.html new file mode 100644 index 0000000..63be996 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/LILRB2.html @@ -0,0 +1,70 @@ +LILRB2 — DepMap research preview

LILRB2

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.17339256920794643,"interquartile_range":0.16212378681022704,"maximum":0.34645335742649364,"mean":-0.08430449460370906,"measured_model_count":56,"median":-0.10414190586983159,"minimum":-0.46500847320709315,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.01126878239771938,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.023619920694685523,"interquartile_range":0.06576945252265654,"maximum":0.5581267752985244,"mean":0.0736724021976837,"measured_model_count":56,"median":0.054768936757054784,"minimum":0.0008249314826466763,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08938937321734206,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.008650022490033216,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.0003547776726584677,"pan_cancer_fraction":0.018211920529801324,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.006249131641514638,"gene_effect_median":-0.02012539418414107},"dependency_probability_context_minus_non_context_median":0.009154837808549234,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.00037202380952381167,"non_context_fraction":0.018229166666666668,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006552908874088131,"gene_effect_context_minus_non_context_median":-0.021010398615674636}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_9f5b156b8ca8296e2660e2c1c6ff44617563f1355b6bedee7dc7ac3db453a680`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:LILRB2|entrez:10288`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/LPP.html b/examples/html_reports/depmap_26q1/targets/LPP.html new file mode 100644 index 0000000..2a71b96 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/LPP.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: LPP + + + + +
+ +
+

Target hypothesis report: LPP

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
LPP
+
+
+
Target name
+
LIM domain containing preferred translocation partner in lipoma
+
+
+
Open Targets melanoma score
+
0.478
+
+
+
+
Open Targets baseline rank
+
276
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.008783199593916918,"interquartile_range":0.10063549851005911,"maximum":0.39512059249409137,"mean":0.0501342135041537,"measured_model_count":56,"median":0.052278005196747614,"minimum":-0.28660592592022155,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09185229891614219,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.00715624060802497,"interquartile_range":0.014590503911784831,"maximum":0.14433042014147968,"mean":0.01906680258772825,"measured_model_count":56,"median":0.012845188877211793,"minimum":0.0007890807311014471,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0217467445198098,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00035221455346442707,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.009982655850077647,"gene_effect_median":-0.007920830474404186},"dependency_probability_context_minus_non_context_median":0.00036946973229592603,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.010467923842789745,"gene_effect_context_minus_non_context_median":-0.008244035266807816}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 276
+- **Dependency-aware candidate rank:** 276
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_c1157616598db6523351ef7f64b9b59d25bdb05e49835820ea1a27f220822615`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:LPP|entrez:4026`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
276not prioritized0
Resistance biomarker0.000
276not prioritized0
Tumor-intrinsic / small molecule0.000
276not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.478)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: LPP lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for LPP in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/LRP1B.html b/examples/html_reports/depmap_26q1/targets/LRP1B.html new file mode 100644 index 0000000..a308728 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/LRP1B.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: LRP1B + + + + +
+ +
+

Target hypothesis report: LRP1B

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
LRP1B
+
+
+
Target name
+
LDL receptor related protein 1B
+
+
+
Open Targets melanoma score
+
0.658
+
+
+
+
Open Targets baseline rank
+
29
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.20938505684404493,"interquartile_range":0.18767779569086548,"maximum":0.36877867713046136,"mean":-0.11193670595354667,"measured_model_count":56,"median":-0.1145412718983222,"minimum":-0.6285265543650834,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.021707261153179447,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.022508152373858486,"interquartile_range":0.12726745259309719,"maximum":0.7916660592206599,"mean":0.11003149409753983,"measured_model_count":56,"median":0.0526553283158261,"minimum":0.0006828725992313448,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14977560496695566,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.02437487176960501,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.004257332071901605,"pan_cancer_fraction":0.03145695364238411,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":0.04106198802050763,"gene_effect_median":0.029746098922292713},"dependency_probability_context_minus_non_context_median":-0.025565720848670967,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.004464285714285712,"non_context_fraction":0.03125,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.043058056882615534,"gene_effect_context_minus_non_context_median":0.03159413837855338}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 36
+- **Dependency-aware candidate rank:** 36
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_fc8697ab41635af1e865ae379c122664e10f6757572457039f83e8333f82e203`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:LRP1B|entrez:53353`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
36not prioritized-7
Resistance biomarker0.000
38not prioritized-9
Tumor-intrinsic / small molecule0.002
31not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.658)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: LRP1B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for LRP1B in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/LZTR1.html b/examples/html_reports/depmap_26q1/targets/LZTR1.html new file mode 100644 index 0000000..679222d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/LZTR1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: LZTR1 + + + + +
+ +
+

Target hypothesis report: LZTR1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
LZTR1
+
+
+
Target name
+
leucine zipper like post translational regulator 1
+
+
+
Open Targets melanoma score
+
0.550
+
+
+
+
Open Targets baseline rank
+
161
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.09712302034637581,"interquartile_range":0.12603647569734755,"maximum":0.39835316383447017,"mean":-0.023218800975575663,"measured_model_count":56,"median":-0.032631692394577985,"minimum":-0.31250394234035345,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.028913455350971732,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.013866497890610329,"interquartile_range":0.03558430953541362,"maximum":0.22804494863519476,"mean":0.042020283337196505,"measured_model_count":56,"median":0.027297324657613566,"minimum":0.0005298521133612584,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.049450807426023945,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.004856881233996087,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.008278145695364239,"pan_cancer_fraction":0.008278145695364239,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.02513772052294517,"gene_effect_median":-0.025816726004031957},"dependency_probability_context_minus_non_context_median":0.005100042611575185,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.008680555555555556,"non_context_fraction":0.008680555555555556,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.02635969304836607,"gene_effect_context_minus_non_context_median":-0.02853208828617576}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 163
+- **Dependency-aware candidate rank:** 163
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_87f8d0fec9a6ce256574b4e21801a8ddfcb76cf0fad45745b3d2ed84878f0329`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:LZTR1|entrez:8216`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
163not prioritized-2
Resistance biomarker0.000
164not prioritized-3
Tumor-intrinsic / small molecule0.000
163not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.550)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: LZTR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for LZTR1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MAP2K1.html b/examples/html_reports/depmap_26q1/targets/MAP2K1.html new file mode 100644 index 0000000..ac0412c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MAP2K1.html @@ -0,0 +1,440 @@ + + + + +TargetIntel-IO report: MAP2K1 + + + + +
+ +
+

Target hypothesis report: MAP2K1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MAP2K1
+
+
+
Target name
+
mitogen-activated protein kinase kinase 1
+
+
+
Open Targets melanoma score
+
0.807
+
+
+
+
Open Targets baseline rank
+
4
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.578482228308965,"interquartile_range":0.4189281838514242,"maximum":0.252437482852541,"mean":-0.41218035078685417,"measured_model_count":56,"median":-0.38895098205912615,"minimum":-1.3657303916368035,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.1595540444575408,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.08598020716229524,"interquartile_range":0.5882115796602083,"maximum":0.9908781940957316,"mean":0.42114568711213035,"measured_model_count":56,"median":0.38746891216194834,"minimum":0.002703798825683424,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.6741917868225036,"threshold_fractions":[{"denominator":56,"fraction":0.39285714285714285,"numerator":22,"threshold":0.5},{"denominator":56,"fraction":0.23214285714285715,"numerator":13,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.3150396652239056,"dependency_probability_threshold_fractions":[{"context_fraction":0.39285714285714285,"difference":0.33904919583727533,"pan_cancer_fraction":0.05380794701986755,"threshold":0.5},{"context_fraction":0.23214285714285715,"difference":0.20482497634815516,"pan_cancer_fraction":0.027317880794701987,"threshold":0.8}],"gene_effect_mean":-0.248319609934331,"gene_effect_median":-0.24836184470154712},"dependency_probability_context_minus_non_context_median":0.3176976923105364,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.39285714285714285,"difference":0.35553075396825395,"non_context_fraction":0.03732638888888889,"threshold":0.5},{"context_fraction":0.23214285714285715,"difference":0.21478174603174605,"non_context_fraction":0.017361111111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.2603907020839166,"gene_effect_context_minus_non_context_median":-0.2535817455567181}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":100.0}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 8
+- **Dependency-aware candidate rank:** 2
+- **Rank delta:** -6
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2adc2fdd57e57d2cb39182fa984d99b6744fb8c281824b652417022c29ead2ed`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MAP2K1|entrez:5604`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / small-molecule target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
small-molecule inhibition / pathway targeting
+
+
+
Best modality
+
small molecule / pathway targeting
+
+
+
Resistance axis
+
tumor_intrinsic_driver
+
+
+
Matched resistance programs
+
Tumor-intrinsic driver biology
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.262
8low-4
Resistance biomarker0.476
12medium-8
Tumor-intrinsic / small molecule0.836
2high2
+
+ +
+

Evidence for

+
    +
  • Relevant to melanoma tumor-cell biology
    • +
  • Some targets or pathways are clinically actionable
    • +
  • Useful for separating tumor-intrinsic drivers from immune-combination targets
    • +
  • High Open Targets melanoma association score (0.807)
    • +
  • Maps to curated anti-PD-1 resistance program: Tumor-intrinsic driver biology
    • +
  • Stable role classifier confidence is high
    • +
  • Small-molecule fit is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Many tumor-intrinsic drivers are poor antibody targets
    • +
  • Melanoma association does not automatically imply anti-PD-1 combination suitability
    • +
  • Tumor suppressors are often poor direct therapeutic targets
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
high confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.320
+
+
+
+
Main limitation
+
Poor fit for antibody / IO-combination modality
+
+
+

Uncertainty reason: Main limitation: Poor fit for antibody / IO-combination modality

+

Deprioritization reason: No strong deprioritization reason from current MVP rules

+
+ +
+

Recommended next validation experiment

+

Validation category: tumor-intrinsic functional validation

+

Next experiment: Evaluate whether perturbing MAP2K1 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays.

+

Rationale: This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MAP2K2.html b/examples/html_reports/depmap_26q1/targets/MAP2K2.html new file mode 100644 index 0000000..660d9a1 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MAP2K2.html @@ -0,0 +1,434 @@ + + + + +TargetIntel-IO report: MAP2K2 + + + + +
+ +
+

Target hypothesis report: MAP2K2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MAP2K2
+
+
+
Target name
+
mitogen-activated protein kinase kinase 2
+
+
+
Open Targets melanoma score
+
0.769
+
+
+
+
Open Targets baseline rank
+
6
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.4908836918532778,"interquartile_range":0.3416845954926677,"maximum":0.22807594691589114,"mean":-0.36394880908741206,"measured_model_count":56,"median":-0.27913492073021595,"minimum":-1.780927613358056,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.14919909636061007,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0796834206563264,"interquartile_range":0.440321969120281,"maximum":1.0,"mean":0.33519502622684805,"measured_model_count":56,"median":0.210854567680023,"minimum":0.0034850765734037578,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5200053897766074,"threshold_fractions":[{"denominator":56,"fraction":0.26785714285714285,"numerator":15,"threshold":0.5},{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.1138375819439125,"dependency_probability_threshold_fractions":[{"context_fraction":0.26785714285714285,"difference":0.2281220435193945,"pan_cancer_fraction":0.039735099337748346,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.14746925260170293,"pan_cancer_fraction":0.013245033112582781,"threshold":0.8}],"gene_effect_mean":-0.17677737897716392,"gene_effect_median":-0.10871776689925783},"dependency_probability_context_minus_non_context_median":0.11672469895653054,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.26785714285714285,"difference":0.2392113095238095,"non_context_fraction":0.028645833333333332,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.15463789682539683,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.1853707237885538,"gene_effect_context_minus_non_context_median":-0.11069460399729478}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 14
+- **Dependency-aware candidate rank:** 12
+- **Rank delta:** -2
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ff1752f6f093d35ab80a1dc5742a4c196be05cb6f535109d4d887901709b6b00`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MAP2K2|entrez:5605`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / small-molecule target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
small-molecule inhibition / pathway targeting
+
+
+
Best modality
+
small molecule / pathway targeting
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
14not prioritized-8
Resistance biomarker0.106
20low-14
Tumor-intrinsic / small molecule0.689
3medium3
+
+ +
+

Evidence for

+
    +
  • High Open Targets melanoma association score (0.769)
    • +
  • Stable role classifier confidence is high
    • +
  • Small-molecule fit is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
0.889
+
+
+
+
Contradiction score
+
0.160
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MAP2K2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: tumor-intrinsic functional validation

+

Next experiment: Evaluate whether perturbing MAP2K2 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays.

+

Rationale: This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MAP2K4.html b/examples/html_reports/depmap_26q1/targets/MAP2K4.html new file mode 100644 index 0000000..51d4112 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MAP2K4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MAP2K4 + + + + +
+ +
+

Target hypothesis report: MAP2K4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MAP2K4
+
+
+
Target name
+
mitogen-activated protein kinase kinase 4
+
+
+
Open Targets melanoma score
+
0.513
+
+
+
+
Open Targets baseline rank
+
231
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.08166803344011006,"interquartile_range":0.1667224349937138,"maximum":0.4663584004709461,"mean":-0.004183185081218783,"measured_model_count":56,"median":0.007155568370856763,"minimum":-0.5620268298394391,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08505440155360375,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.00896391572726946,"interquartile_range":0.03983377128048464,"maximum":0.5761438915269841,"mean":0.04888816971268661,"measured_model_count":56,"median":0.02000527970907914,"minimum":0.0002583679371438126,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0487976870077541,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.010008220510560543,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.004612109744560075,"pan_cancer_fraction":0.013245033112582781,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.08467368581701021,"gene_effect_median":-0.07899657992657283},"dependency_probability_context_minus_non_context_median":0.010477315489236343,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.004836309523809522,"non_context_fraction":0.013020833333333334,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0887897677664482,"gene_effect_context_minus_non_context_median":-0.08435345703588204}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 233
+- **Dependency-aware candidate rank:** 233
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_afc0aea71e3da6ba41b95c62c14a329fbab39ebf8e502e8f20de70e562815bea`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MAP2K4|entrez:6416`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
233not prioritized-2
Resistance biomarker0.000
233not prioritized-2
Tumor-intrinsic / small molecule0.000
233not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.513)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MAP2K4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MAP2K4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MAP3K1.html b/examples/html_reports/depmap_26q1/targets/MAP3K1.html new file mode 100644 index 0000000..f6e0c91 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MAP3K1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MAP3K1 + + + + +
+ +
+

Target hypothesis report: MAP3K1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MAP3K1
+
+
+
Target name
+
mitogen-activated protein kinase kinase kinase 1
+
+
+
Open Targets melanoma score
+
0.466
+
+
+
+
Open Targets baseline rank
+
288
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.26818881495655444,"interquartile_range":0.2190929173625335,"maximum":0.16244834816557008,"mean":-0.1754338142643515,"measured_model_count":56,"median":-0.18106151480989618,"minimum":-1.063112411214312,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.04909589759402095,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.032390313337493024,"interquartile_range":0.1698410110394501,"maximum":0.9781983157682375,"mean":0.1418094395845862,"measured_model_count":56,"median":0.08325360586789075,"minimum":0.0031087789768363826,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2022313243769431,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.030618882721477725,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.004612109744560075,"pan_cancer_fraction":0.013245033112582781,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.015373699148533584,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.07259773849015544,"gene_effect_median":-0.07872399920058051},"dependency_probability_context_minus_non_context_median":0.031198178018647063,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.004836309523809522,"non_context_fraction":0.013020833333333334,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.016121031746031744,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0761267952223159,"gene_effect_context_minus_non_context_median":-0.08035780971994266}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":92.5925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 288
+- **Dependency-aware candidate rank:** 288
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_cf756e479e88717eef86a602dafabe0e751c785b349ef9f4818088cb9cc18d94`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MAP3K1|entrez:4214`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
288not prioritized0
Resistance biomarker0.000
288not prioritized0
Tumor-intrinsic / small molecule0.000
288not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.466)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MAP3K1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MAP3K1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MAP3K13.html b/examples/html_reports/depmap_26q1/targets/MAP3K13.html new file mode 100644 index 0000000..d8620e6 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MAP3K13.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MAP3K13 + + + + +
+ +
+

Target hypothesis report: MAP3K13

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MAP3K13
+
+
+
Target name
+
mitogen-activated protein kinase kinase kinase 13
+
+
+
Open Targets melanoma score
+
0.546
+
+
+
+
Open Targets baseline rank
+
167
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.12348850976267087,"interquartile_range":0.10356484439638564,"maximum":0.10601839484476286,"mean":-0.07735031260314525,"measured_model_count":56,"median":-0.07585580490508761,"minimum":-0.4254039496856019,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.01992366536628524,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.02579139351817865,"interquartile_range":0.03948663532446196,"maximum":0.33166860073911614,"mean":0.05799902513451529,"measured_model_count":56,"median":0.04505395114891765,"minimum":0.004144288513430752,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06527802884264061,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.009695406371026893,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.017009365555747898,"gene_effect_median":-0.01812639278195812},"dependency_probability_context_minus_non_context_median":0.009797872690404191,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.017836209714707826,"gene_effect_context_minus_non_context_median":-0.019202972460153143}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 169
+- **Dependency-aware candidate rank:** 169
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_4c5e6e27cf8ad909398012feeb14dc4fac40b65dc835a80193725b642260beaa`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MAP3K13|entrez:9175`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
169not prioritized-2
Resistance biomarker0.000
170not prioritized-3
Tumor-intrinsic / small molecule0.000
169not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.546)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MAP3K13 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MAP3K13 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MAPK1.html b/examples/html_reports/depmap_26q1/targets/MAPK1.html new file mode 100644 index 0000000..058e8d3 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MAPK1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MAPK1 + + + + +
+ +
+

Target hypothesis report: MAPK1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MAPK1
+
+
+
Target name
+
mitogen-activated protein kinase 1
+
+
+
Open Targets melanoma score
+
0.472
+
+
+
+
Open Targets baseline rank
+
281
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.2761774074770886,"interquartile_range":0.7786423452235494,"maximum":0.18419597775603253,"mean":-0.8981201774701383,"measured_model_count":56,"median":-0.8129894142767058,"minimum":-2.2162133589722837,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.4975350622535393,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.5766186743058375,"interquartile_range":0.41754805922924465,"maximum":1.0,"mean":0.7418741798461861,"measured_model_count":56,"median":0.8931882816760448,"minimum":0.0015643431120909866,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9941667335350821,"threshold_fractions":[{"denominator":56,"fraction":0.7857142857142857,"numerator":44,"threshold":0.5},{"denominator":56,"fraction":0.625,"numerator":35,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.8193481073490543,"dependency_probability_threshold_fractions":[{"context_fraction":0.7857142857142857,"difference":0.6433301797540207,"pan_cancer_fraction":0.1423841059602649,"threshold":0.5},{"context_fraction":0.625,"difference":0.554635761589404,"pan_cancer_fraction":0.07036423841059603,"threshold":0.8}],"gene_effect_mean":-0.6959215725352872,"gene_effect_median":-0.668531079535996},"dependency_probability_context_minus_non_context_median":0.8263496162531797,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.7857142857142857,"difference":0.6746031746031746,"non_context_fraction":0.1111111111111111,"threshold":0.5},{"context_fraction":0.625,"difference":0.5815972222222222,"non_context_fraction":0.043402777777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.7297510934224184,"gene_effect_context_minus_non_context_median":-0.6776694707116295}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":100.0}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 281
+- **Dependency-aware candidate rank:** 281
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_13a046ae6acb61e39222890294953e6597010cc823eca9a788473d8b39647ca5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MAPK1|entrez:5594`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
281not prioritized0
Resistance biomarker0.000
281not prioritized0
Tumor-intrinsic / small molecule0.000
281not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.472)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MAPK1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MAPK1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MARCO.html b/examples/html_reports/depmap_26q1/targets/MARCO.html new file mode 100644 index 0000000..3ce9f92 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MARCO.html @@ -0,0 +1,70 @@ +MARCO — DepMap research preview

MARCO

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.144284681805267,"interquartile_range":0.11320090800341288,"maximum":0.16141479149421714,"mean":-0.08075810496074594,"measured_model_count":56,"median":-0.07657305576587008,"minimum":-0.28995279711229627,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.031083773801854106,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.02732096604142211,"interquartile_range":0.0424585894956143,"maximum":0.21196471052683893,"mean":0.05275650105094353,"measured_model_count":56,"median":0.04508515552169046,"minimum":0.0043349896499730416,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06977955553703641,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.013009959661225763,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.03107970228961196,"gene_effect_median":-0.029934995161084763},"dependency_probability_context_minus_non_context_median":0.01325816819398256,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.032590521150912544,"gene_effect_context_minus_non_context_median":-0.031918688171550635}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_5434253dea93a61134ae09bfa7579a9b778992e03b22ebb1463b8a488900ba7d`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MARCO|entrez:8685`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/MAX.html b/examples/html_reports/depmap_26q1/targets/MAX.html new file mode 100644 index 0000000..883c37b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MAX.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MAX + + + + +
+ +
+

Target hypothesis report: MAX

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MAX
+
+
+
Target name
+
MYC associated transcriptional regulator X
+
+
+
Open Targets melanoma score
+
0.519
+
+
+
+
Open Targets baseline rank
+
215
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.8226826734631729,"interquartile_range":0.23233480918405225,"maximum":-0.2112248166458427,"mean":-0.710188390541159,"measured_model_count":56,"median":-0.688268648265024,"minimum":-1.2966052450452203,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.5903478642791207,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.703880450962148,"interquartile_range":0.24126058863373134,"maximum":0.9931135114720926,"mean":0.7818475651475402,"measured_model_count":56,"median":0.8762894271334364,"minimum":0.11802670198216508,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9451410395958794,"threshold_fractions":[{"denominator":56,"fraction":0.875,"numerator":49,"threshold":0.5},{"denominator":56,"fraction":0.5714285714285714,"numerator":32,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.03808533788005786,"dependency_probability_threshold_fractions":[{"context_fraction":0.875,"difference":-0.019039735099337762,"pan_cancer_fraction":0.8940397350993378,"threshold":0.5},{"context_fraction":0.5714285714285714,"difference":-0.1438032166508988,"pan_cancer_fraction":0.7152317880794702,"threshold":0.8}],"gene_effect_mean":0.09858119787523068,"gene_effect_median":0.10484178465136451},"dependency_probability_context_minus_non_context_median":-0.04166605320801209,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.875,"difference":-0.01996527777777779,"non_context_fraction":0.8949652777777778,"threshold":0.5},{"context_fraction":0.5714285714285714,"difference":-0.1507936507936508,"non_context_fraction":0.7222222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.10337333943860993,"gene_effect_context_minus_non_context_median":0.11415946668113963}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 217
+- **Dependency-aware candidate rank:** 217
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_641d4a223df2992246b524bc55714e0cdb392ead46f6403678cb167632070672`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MAX|entrez:4149`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
217not prioritized-2
Resistance biomarker0.000
217not prioritized-2
Tumor-intrinsic / small molecule0.000
217not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.519)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MAX lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MAX in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MBD4.html b/examples/html_reports/depmap_26q1/targets/MBD4.html new file mode 100644 index 0000000..aae09d3 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MBD4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MBD4 + + + + +
+ +
+

Target hypothesis report: MBD4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MBD4
+
+
+
Target name
+
methyl-CpG binding domain 4, DNA glycosylase
+
+
+
Open Targets melanoma score
+
0.706
+
+
+
+
Open Targets baseline rank
+
19
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.14270727803868224,"interquartile_range":0.1568713207830758,"maximum":0.30240936692161213,"mean":-0.06259349546269093,"measured_model_count":56,"median":-0.08875452151828409,"minimum":-0.2727347834743414,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.014164042744393559,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.019228656050633033,"interquartile_range":0.06297025851395877,"maximum":0.18687151897726442,"mean":0.057004038075143926,"measured_model_count":56,"median":0.04888988821268317,"minimum":0.00155875195791616,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0821989145645918,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0030046031138560095,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.042133056139012845,"gene_effect_median":0.010588283750192731},"dependency_probability_context_minus_non_context_median":-0.0030046031138560095,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.044181190812437335,"gene_effect_context_minus_non_context_median":0.011006948674245717}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 26
+- **Dependency-aware candidate rank:** 26
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_7dc2c3aa2235e2919a098358a150f2ae924092bb451d788463c09b7057dbe8ff`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MBD4|entrez:8930`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
26not prioritized-7
Resistance biomarker0.000
29not prioritized-10
Tumor-intrinsic / small molecule0.012
22not prioritized-3
+
+ +
+

Evidence for

+
    +
  • High Open Targets melanoma association score (0.706)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MBD4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MBD4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MC1R.html b/examples/html_reports/depmap_26q1/targets/MC1R.html new file mode 100644 index 0000000..1bdd127 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MC1R.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MC1R + + + + +
+ +
+

Target hypothesis report: MC1R

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MC1R
+
+
+
Target name
+
melanocortin 1 receptor
+
+
+
Open Targets melanoma score
+
0.621
+
+
+
+
Open Targets baseline rank
+
49
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.13574258291049882,"interquartile_range":0.2294889026785944,"maximum":0.3088799835855469,"mean":-0.07405014885167535,"measured_model_count":56,"median":-0.014394286830063385,"minimum":-1.4266168769158605,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0937463197680956,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.00957570675501504,"interquartile_range":0.06469958618077154,"maximum":0.9986640403125104,"mean":0.093014007762533,"measured_model_count":56,"median":0.024505635992432086,"minimum":0.002172093001064544,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07427529293578658,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0007702689419332685,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.026608325449385052,"pan_cancer_fraction":0.009105960264900662,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.03323084200567644,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.05521604278224079,"gene_effect_median":-0.0006908143769098138},"dependency_probability_context_minus_non_context_median":-0.0008110824397527007,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.027901785714285712,"non_context_fraction":0.0078125,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.03484623015873016,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.057900155973044154,"gene_effect_context_minus_non_context_median":-0.0006908143769098138}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 54
+- **Dependency-aware candidate rank:** 54
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_add7084b48ba681f9c3c43ad3406300c681284745c7914a5347a8eb34a0e3bfe`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MC1R|entrez:4157`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
54not prioritized-5
Resistance biomarker0.000
56not prioritized-7
Tumor-intrinsic / small molecule0.000
54not prioritized-5
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.621)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MC1R lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MC1R in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MDM2.html b/examples/html_reports/depmap_26q1/targets/MDM2.html new file mode 100644 index 0000000..a884bb2 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MDM2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MDM2 + + + + +
+ +
+

Target hypothesis report: MDM2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MDM2
+
+
+
Target name
+
MDM2 proto-oncogene
+
+
+
Open Targets melanoma score
+
0.612
+
+
+
+
Open Targets baseline rank
+
54
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.8624748543617278,"interquartile_range":1.4254157644122152,"maximum":-0.03383445987773337,"mean":-1.2716776001752876,"measured_model_count":56,"median":-1.3485460927811548,"minimum":-2.9407816150438637,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.4370590899495126,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.5316184247932024,"interquartile_range":0.46838157520672297,"maximum":1.0,"mean":0.7845953373476593,"measured_model_count":56,"median":0.9964251033261587,"minimum":0.0191219625657424,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9999999999999254,"threshold_fractions":[{"denominator":56,"fraction":0.75,"numerator":42,"threshold":0.5},{"denominator":56,"fraction":0.6785714285714286,"numerator":38,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.5433058761368279,"dependency_probability_threshold_fractions":[{"context_fraction":0.75,"difference":0.2955298013245033,"pan_cancer_fraction":0.4544701986754967,"threshold":0.5},{"context_fraction":0.6785714285714286,"difference":0.3979422894985809,"pan_cancer_fraction":0.2806291390728477,"threshold":0.8}],"gene_effect_mean":-0.6248918769217581,"gene_effect_median":-0.9221060164000108},"dependency_probability_context_minus_non_context_median":0.5560757861291269,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.75,"difference":0.3098958333333333,"non_context_fraction":0.4401041666666667,"threshold":0.5},{"context_fraction":0.6785714285714286,"difference":0.4172867063492064,"non_context_fraction":0.2612847222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.6552685653832329,"gene_effect_context_minus_non_context_median":-0.9313150551905067}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 58
+- **Dependency-aware candidate rank:** 58
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e09c30cbdcf926c360d142cc79ceb8c2ea3b01d759c047f4db377618133cfc1b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MDM2|entrez:4193`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
58not prioritized-4
Resistance biomarker0.000
60not prioritized-6
Tumor-intrinsic / small molecule0.000
58not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.612)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MDM2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MDM2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MDM4.html b/examples/html_reports/depmap_26q1/targets/MDM4.html new file mode 100644 index 0000000..6964438 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MDM4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MDM4 + + + + +
+ +
+

Target hypothesis report: MDM4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MDM4
+
+
+
Target name
+
MDM4 regulator of p53
+
+
+
Open Targets melanoma score
+
0.588
+
+
+
+
Open Targets baseline rank
+
85
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.24624159527720413,"interquartile_range":0.23359604518110183,"maximum":0.33598072083948805,"mean":-0.18865409124957538,"measured_model_count":56,"median":-0.1410025896159544,"minimum":-1.2812287480482205,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.012645550096102298,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.02356303103125949,"interquartile_range":0.1275705121704807,"maximum":0.9843563515754161,"mean":0.18013925683555612,"measured_model_count":56,"median":0.07119109464846649,"minimum":0.0011906140360111628,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1511335432017402,"threshold_fractions":[{"denominator":56,"fraction":0.125,"numerator":7,"threshold":0.5},{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03168778141474956,"dependency_probability_threshold_fractions":[{"context_fraction":0.125,"difference":0.0033112582781456984,"pan_cancer_fraction":0.1216887417218543,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":0.0023651844843897846,"pan_cancer_fraction":0.0869205298013245,"threshold":0.8}],"gene_effect_mean":-0.031354144465446654,"gene_effect_median":-0.07842570599532141},"dependency_probability_context_minus_non_context_median":0.03217559712298432,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.125,"difference":0.0034722222222222238,"non_context_fraction":0.12152777777777778,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":0.0024801587301587352,"non_context_fraction":0.08680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.032878304265850256,"gene_effect_context_minus_non_context_median":-0.08145299746058135}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 88
+- **Dependency-aware candidate rank:** 88
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e5dd23533b8b3973fc6a616ca8c1b9dc27a975778e4c4b05db1eaf2fbdadf5de`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MDM4|entrez:4194`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
88not prioritized-3
Resistance biomarker0.000
90not prioritized-5
Tumor-intrinsic / small molecule0.000
88not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.588)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MDM4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MDM4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MECOM.html b/examples/html_reports/depmap_26q1/targets/MECOM.html new file mode 100644 index 0000000..e3ad583 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MECOM.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MECOM + + + + +
+ +
+

Target hypothesis report: MECOM

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MECOM
+
+
+
Target name
+
MDS1 and EVI1 complex locus
+
+
+
Open Targets melanoma score
+
0.611
+
+
+
+
Open Targets baseline rank
+
56
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.03318121755950547,"interquartile_range":0.14709745093791188,"maximum":1.1159229428618254,"mean":0.04519617222218534,"measured_model_count":56,"median":0.06243448810213843,"minimum":-0.4043002287802036,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1139162333784064,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.007059075844818929,"interquartile_range":0.0174121661972337,"maximum":0.3482881257463481,"mean":0.03171024366566652,"measured_model_count":56,"median":0.01239713433525657,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02447124204205263,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0021296773257739286,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.023178807947019868,"pan_cancer_fraction":0.023178807947019868,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014072847682119206,"pan_cancer_fraction":0.014072847682119206,"threshold":0.8}],"gene_effect_mean":0.025965655811218857,"gene_effect_median":0.021937058319371316},"dependency_probability_context_minus_non_context_median":-0.0022692047268848513,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.024305555555555556,"non_context_fraction":0.024305555555555556,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014756944444444444,"non_context_fraction":0.014756944444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.02722787519093091,"gene_effect_context_minus_non_context_median":0.02275885204514158}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 60
+- **Dependency-aware candidate rank:** 60
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_b6f1f671850c3b480918c17280b141df71e490b462aff992fbbcaa882a243ac9`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MECOM|entrez:2122`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
60not prioritized-4
Resistance biomarker0.000
62not prioritized-6
Tumor-intrinsic / small molecule0.000
60not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.611)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MECOM lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MECOM in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MED12.html b/examples/html_reports/depmap_26q1/targets/MED12.html new file mode 100644 index 0000000..c131814 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MED12.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MED12 + + + + +
+ +
+

Target hypothesis report: MED12

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MED12
+
+
+
Target name
+
mediator complex subunit 12
+
+
+
Open Targets melanoma score
+
0.464
+
+
+
+
Open Targets baseline rank
+
292
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.9311970062252455,"interquartile_range":0.5433939524223144,"maximum":0.35086847212010597,"mean":-0.6610039514993754,"measured_model_count":56,"median":-0.6930691904602218,"minimum":-1.4658720277959536,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.3878030538029311,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.29330547725917067,"interquartile_range":0.6792518810382737,"maximum":1.0,"mean":0.6692263099022066,"measured_model_count":56,"median":0.8357673700031603,"minimum":0.0011196937346188206,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9725573582974444,"threshold_fractions":[{"denominator":56,"fraction":0.7142857142857143,"numerator":40,"threshold":0.5},{"denominator":56,"fraction":0.5178571428571429,"numerator":29,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.15037299236736146,"dependency_probability_threshold_fractions":[{"context_fraction":0.7142857142857143,"difference":0.11825922421948909,"pan_cancer_fraction":0.5960264900662252,"threshold":0.5},{"context_fraction":0.5178571428571429,"difference":0.0940160832544939,"pan_cancer_fraction":0.423841059602649,"threshold":0.8}],"gene_effect_mean":-0.10478938114699055,"gene_effect_median":-0.12192678639433197},"dependency_probability_context_minus_non_context_median":0.1640140677254437,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.7142857142857143,"difference":0.12400793650793651,"non_context_fraction":0.5902777777777778,"threshold":0.5},{"context_fraction":0.5178571428571429,"difference":0.09858630952380959,"non_context_fraction":0.4192708333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.1098833093971916,"gene_effect_context_minus_non_context_median":-0.1290268263356823}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 292
+- **Dependency-aware candidate rank:** 292
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_8bf6e9b1a0bba3c2a4234d4fff5fb8795f78dc6189a0e4ac0f726c986cdd741d`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MED12|entrez:9968`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
292not prioritized0
Resistance biomarker0.000
292not prioritized0
Tumor-intrinsic / small molecule0.000
292not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.464)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MED12 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MED12 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MERTK.html b/examples/html_reports/depmap_26q1/targets/MERTK.html new file mode 100644 index 0000000..fa84989 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MERTK.html @@ -0,0 +1,70 @@ +MERTK — DepMap research preview

MERTK

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.18881505762195927,"interquartile_range":0.16208785261332045,"maximum":0.3193293249145177,"mean":-0.10122912464953086,"measured_model_count":56,"median":-0.10690991997138019,"minimum":-0.37059543781934634,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.02672720500863881,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.024416867332033472,"interquartile_range":0.08662821894971165,"maximum":0.2986950469092032,"mean":0.07873373296246423,"measured_model_count":56,"median":0.05270852886247373,"minimum":0.0014332677546677695,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11104508628174513,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.010399266300551047,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.022814040606935662,"gene_effect_median":-0.031910909320972014},"dependency_probability_context_minus_non_context_median":0.010756021506766654,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.02392305646977287,"gene_effect_context_minus_non_context_median":-0.03325595444556945}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e7dcf175a6aaabbf2699fa0a66746cf326ea684280ea261a3bdc4530ddcb8799`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MERTK|entrez:10461`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/MET.html b/examples/html_reports/depmap_26q1/targets/MET.html new file mode 100644 index 0000000..fdce42d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MET.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MET + + + + +
+ +
+

Target hypothesis report: MET

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MET
+
+
+
Target name
+
MET proto-oncogene, receptor tyrosine kinase
+
+
+
Open Targets melanoma score
+
0.633
+
+
+
+
Open Targets baseline rank
+
41
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06431778498910111,"interquartile_range":0.12819068489351648,"maximum":0.19924513841976238,"mean":0.006650333009057209,"measured_model_count":56,"median":0.010664057636821479,"minimum":-0.15857136172097158,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06387289990441536,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.010757477645204688,"interquartile_range":0.027227045398293084,"maximum":0.09865379877043438,"mean":0.026561617711299477,"measured_model_count":56,"median":0.01757639754618848,"minimum":0.003696797201785037,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.037984523043497774,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.006124645788141078,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.027317880794701987,"pan_cancer_fraction":0.027317880794701987,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014900662251655629,"pan_cancer_fraction":0.014900662251655629,"threshold":0.8}],"gene_effect_mean":0.04397450202284898,"gene_effect_median":0.02311840445736779},"dependency_probability_context_minus_non_context_median":-0.006467760987337593,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.028645833333333332,"non_context_fraction":0.028645833333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.015625,"non_context_fraction":0.015625,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04611215142673745,"gene_effect_context_minus_non_context_median":0.024839366368137623}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 48
+- **Dependency-aware candidate rank:** 48
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_346cf45e9e08768179c2ff8a443efc9872e87dd2398d8b81a08f8455e2525b97`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MET|entrez:4233`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
48not prioritized-7
Resistance biomarker0.000
50not prioritized-9
Tumor-intrinsic / small molecule0.000
48not prioritized-7
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.633)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MET lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MET in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MITF.html b/examples/html_reports/depmap_26q1/targets/MITF.html new file mode 100644 index 0000000..d774650 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MITF.html @@ -0,0 +1,435 @@ + + + + +TargetIntel-IO report: MITF + + + + +
+ +
+

Target hypothesis report: MITF

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MITF
+
+
+
Target name
+
melanocyte inducing transcription factor
+
+
+
Open Targets melanoma score
+
0.747
+
+
+
+
Open Targets baseline rank
+
8
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.746365662744372,"interquartile_range":0.5624178320790791,"maximum":0.13265320362187163,"mean":-0.49718287424489066,"measured_model_count":56,"median":-0.4283536938090401,"minimum":-1.4237880033159953,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.18394783066529286,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.13075636050247558,"interquartile_range":0.7860916431961333,"maximum":0.99792821478558,"mean":0.479275745655577,"measured_model_count":56,"median":0.48643645267493163,"minimum":0.005004197500645994,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9168480036986089,"threshold_fractions":[{"denominator":56,"fraction":0.44642857142857145,"numerator":25,"threshold":0.5},{"denominator":56,"fraction":0.26785714285714285,"numerator":15,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.4526589328486887,"dependency_probability_threshold_fractions":[{"context_fraction":0.44642857142857145,"difference":0.4166272469252602,"pan_cancer_fraction":0.029801324503311258,"threshold":0.5},{"context_fraction":0.26785714285714285,"difference":0.2488174077578051,"pan_cancer_fraction":0.01903973509933775,"threshold":0.8}],"gene_effect_mean":-0.42578503903945053,"gene_effect_median":-0.3769637760275986},"dependency_probability_context_minus_non_context_median":0.45443980360081326,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.44642857142857145,"difference":0.43687996031746035,"non_context_fraction":0.009548611111111112,"threshold":0.5},{"context_fraction":0.26785714285714285,"difference":0.26091269841269843,"non_context_fraction":0.006944444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.44648292288164615,"gene_effect_context_minus_non_context_median":-0.3798754716345232}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":96.29629629629629}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 16
+- **Dependency-aware candidate rank:** 11
+- **Rank delta:** -5
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_3583e52fbd3a99eddcd14bbd58a55479403c429f643a952616d15dd72d84c0cb`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MITF|entrez:4286`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / biomarker
+
+
+
Role confidence
+
medium-high
+
+
+
Therapeutic direction
+
use as biomarker / pathway targeting if appropriate
+
+
+
Best modality
+
tumor-intrinsic biomarker / pathway context
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
16not prioritized-8
Resistance biomarker0.391
13low-5
Tumor-intrinsic / small molecule0.521
7medium1
+
+ +
+

Evidence for

+
    +
  • High Open Targets melanoma association score (0.747)
    • +
  • Stable role classifier confidence is medium-high
    • +
  • Biomarker fit is medium-high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Most useful as biomarker or stratification marker rather than direct therapeutic target
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
0.889
+
+
+
+
Contradiction score
+
0.240
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MITF lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: biomarker validation

+

Next experiment: Test whether MITF status or expression differs between anti-PD-1 responders and non-responders in an independent melanoma cohort.

+

Rationale: This would determine whether the candidate has practical value as a resistance biomarker or patient-stratification feature.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MN1.html b/examples/html_reports/depmap_26q1/targets/MN1.html new file mode 100644 index 0000000..83b052b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MN1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MN1 + + + + +
+ +
+

Target hypothesis report: MN1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MN1
+
+
+
Target name
+
MN1 proto-oncogene, transcriptional regulator
+
+
+
Open Targets melanoma score
+
0.513
+
+
+
+
Open Targets baseline rank
+
230
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.01062534893898931,"interquartile_range":0.20506169154087153,"maximum":0.4941061788942517,"mean":0.10398082189212046,"measured_model_count":56,"median":0.1147031423956377,"minimum":-0.2283786381698714,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.19443634260188222,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.002738853757670439,"interquartile_range":0.018564266438373188,"maximum":0.11449885931721446,"mean":0.018046659942068676,"measured_model_count":56,"median":0.0071448822915313025,"minimum":5.345680221332841e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.021303120196043628,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0015149813892774682,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.0009876008661242885,"gene_effect_median":0.01054620202494945},"dependency_probability_context_minus_non_context_median":-0.0015307667801673294,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0010356092415608753,"gene_effect_context_minus_non_context_median":0.011556046281122473}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 232
+- **Dependency-aware candidate rank:** 232
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_8016e193e3e5b91402ab503122579da9c48e7103385c1be1859a544c5ac7c130`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MN1|entrez:4330`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
232not prioritized-2
Resistance biomarker0.000
232not prioritized-2
Tumor-intrinsic / small molecule0.000
232not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.513)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MN1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MN1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MRTFA.html b/examples/html_reports/depmap_26q1/targets/MRTFA.html new file mode 100644 index 0000000..0a516ff --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MRTFA.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MRTFA + + + + +
+ +
+

Target hypothesis report: MRTFA

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MRTFA
+
+
+
Target name
+
myocardin related transcription factor A
+
+
+
Open Targets melanoma score
+
0.509
+
+
+
+
Open Targets baseline rank
+
242
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.166195671969878,"interquartile_range":0.12432617290852266,"maximum":0.15263953285940676,"mean":-0.11254910171388513,"measured_model_count":56,"median":-0.12423974962740286,"minimum":-0.4177381788941873,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.04186949906135534,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.027229735286835803,"interquartile_range":0.07873531064556291,"maximum":0.5253690791287967,"mean":0.08473052596126118,"measured_model_count":56,"median":0.05987725158027763,"minimum":0.0077482329268426875,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10596504593239872,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01280692034900676,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.0003547776726584677,"pan_cancer_fraction":0.018211920529801324,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.03301940166574069,"gene_effect_median":0.011134527709864062},"dependency_probability_context_minus_non_context_median":-0.013394416437087324,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.00037202380952381167,"non_context_fraction":0.018229166666666668,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.034624511468936386,"gene_effect_context_minus_non_context_median":0.012017949940479278}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 244
+- **Dependency-aware candidate rank:** 244
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d2d5471e7ab8e527c116994e65686fefc9d6151bb378ce10089a6f98cde1cef3`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MRTFA|entrez:57591`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
244not prioritized-2
Resistance biomarker0.000
244not prioritized-2
Tumor-intrinsic / small molecule0.000
244not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.509)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MRTFA lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MRTFA in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MSH2.html b/examples/html_reports/depmap_26q1/targets/MSH2.html new file mode 100644 index 0000000..efa879e --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MSH2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MSH2 + + + + +
+ +
+

Target hypothesis report: MSH2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MSH2
+
+
+
Target name
+
mutS homolog 2
+
+
+
Open Targets melanoma score
+
0.521
+
+
+
+
Open Targets baseline rank
+
207
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.26003559151177824,"interquartile_range":0.13672139042893577,"maximum":0.021496894857538112,"mean":-0.20764010596590654,"measured_model_count":56,"median":-0.19916068457846808,"minimum":-0.5451116448448519,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.12331420108284245,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.06592450097849478,"interquartile_range":0.13342337190007386,"maximum":0.5982055659846949,"mean":0.15553859836993347,"measured_model_count":56,"median":0.12392476588127996,"minimum":0.009111683646020614,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.19934787287856864,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005144771662147579,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.016674550614947964,"pan_cancer_fraction":0.01903973509933775,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.004853918329945944,"gene_effect_median":0.004878184038607014},"dependency_probability_context_minus_non_context_median":-0.005144771662147579,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.017485119047619044,"non_context_fraction":0.018229166666666668,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.005089872693207098,"gene_effect_context_minus_non_context_median":0.005598657965552867}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 209
+- **Dependency-aware candidate rank:** 209
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ac594daaf6cd0c8ac4bca7a58e29e5f647b3e259783512c43f03887172d16793`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MSH2|entrez:4436`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
209not prioritized-2
Resistance biomarker0.000
209not prioritized-2
Tumor-intrinsic / small molecule0.000
209not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.521)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MSH2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MSH2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MTAP.html b/examples/html_reports/depmap_26q1/targets/MTAP.html new file mode 100644 index 0000000..4224120 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MTAP.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MTAP + + + + +
+ +
+

Target hypothesis report: MTAP

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MTAP
+
+
+
Target name
+
methylthioadenosine phosphorylase
+
+
+
Open Targets melanoma score
+
0.522
+
+
+
+
Open Targets baseline rank
+
206
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.05322379422075565,"interquartile_range":0.13163768390226643,"maximum":0.35647138964450364,"mean":0.013438769004057596,"measured_model_count":56,"median":0.001765919917108864,"minimum":-0.2742755175918499,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07841388968151078,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008275996775491557,"interquartile_range":0.027631247160987107,"maximum":0.16335356271029838,"mean":0.030024490344690378,"measured_model_count":56,"median":0.01798254575130081,"minimum":0.0005565877691906464,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.035907243936478664,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0007450668116554017,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.017195420764497427,"gene_effect_median":-0.01690621483409817},"dependency_probability_context_minus_non_context_median":0.0007682046941628225,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.01803130927388271,"gene_effect_context_minus_non_context_median":-0.018115597396768914}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 208
+- **Dependency-aware candidate rank:** 208
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_9f88d63f48dc41907cb4d4ea70333550bb7c86a3093506fbe4852e4adb704cca`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MTAP|entrez:4507`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
208not prioritized-2
Resistance biomarker0.000
208not prioritized-2
Tumor-intrinsic / small molecule0.000
208not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.522)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MTAP lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MTAP in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MTOR.html b/examples/html_reports/depmap_26q1/targets/MTOR.html new file mode 100644 index 0000000..f1943f5 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MTOR.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MTOR + + + + +
+ +
+

Target hypothesis report: MTOR

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MTOR
+
+
+
Target name
+
mechanistic target of rapamycin kinase
+
+
+
Open Targets melanoma score
+
0.629
+
+
+
+
Open Targets baseline rank
+
45
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.4510131041083276,"interquartile_range":0.4066619987330087,"maximum":-0.49744427330148155,"mean":-1.2670230716667266,"measured_model_count":56,"median":-1.2341950136618125,"minimum":-2.149561296556447,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.044351105375319,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9789619639208639,"interquartile_range":0.02043554028117034,"maximum":1.0,"mean":0.9737317482994322,"measured_model_count":56,"median":0.991899482877697,"minimum":0.6985320335577506,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9993975042020342,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0008071331386185765,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.018211920529801362,"pan_cancer_fraction":0.9817880794701986,"threshold":0.5},{"context_fraction":0.9821428571428571,"difference":0.03263954588457896,"pan_cancer_fraction":0.9495033112582781,"threshold":0.8}],"gene_effect_mean":-0.008290257341191598,"gene_effect_median":0.01857181633024152},"dependency_probability_context_minus_non_context_median":0.0008411508339194462,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.01909722222222221,"non_context_fraction":0.9809027777777778,"threshold":0.5},{"context_fraction":0.9821428571428571,"difference":0.034226190476190466,"non_context_fraction":0.9479166666666666,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.00869325596194459,"gene_effect_context_minus_non_context_median":0.01888929833241426}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 51
+- **Dependency-aware candidate rank:** 51
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_599702a80c74d830dd3c4d56abadd1ae6910cfd8107a0bc443464fcdb67a13ba`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MTOR|entrez:2475`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
51not prioritized-6
Resistance biomarker0.000
53not prioritized-8
Tumor-intrinsic / small molecule0.000
51not prioritized-6
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.629)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MTOR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MTOR in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MUTYH.html b/examples/html_reports/depmap_26q1/targets/MUTYH.html new file mode 100644 index 0000000..9b2878c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MUTYH.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MUTYH + + + + +
+ +
+

Target hypothesis report: MUTYH

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MUTYH
+
+
+
Target name
+
mutY DNA glycosylase
+
+
+
Open Targets melanoma score
+
0.507
+
+
+
+
Open Targets baseline rank
+
247
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.11748028310013764,"interquartile_range":0.09479599365178082,"maximum":0.1934608651174256,"mean":-0.06611412498298225,"measured_model_count":56,"median":-0.06371844317038643,"minimum":-0.35421944238261915,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.022684289448356824,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.02107456457132147,"interquartile_range":0.04260159227968066,"maximum":0.2790151431662099,"mean":0.05206646685426908,"measured_model_count":56,"median":0.0372447418479774,"minimum":0.004238146635538509,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06367615685100213,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.000837254833749676,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.0038797027680364735,"gene_effect_median":-0.0020307322415865497},"dependency_probability_context_minus_non_context_median":-0.0008509863480279933,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.004068299430371659,"gene_effect_context_minus_non_context_median":-0.002148372875229676}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 249
+- **Dependency-aware candidate rank:** 249
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d09dd40597c32b28e6b5604a20cd1f9eb76b3d6bfe25cd41d9447aa59ef49736`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MUTYH|entrez:4595`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
249not prioritized-2
Resistance biomarker0.000
249not prioritized-2
Tumor-intrinsic / small molecule0.000
249not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.507)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MUTYH lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MUTYH in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MX2.html b/examples/html_reports/depmap_26q1/targets/MX2.html new file mode 100644 index 0000000..8f8b4cd --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MX2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MX2 + + + + +
+ +
+

Target hypothesis report: MX2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MX2
+
+
+
Target name
+
MX dynamin like GTPase 2
+
+
+
Open Targets melanoma score
+
0.543
+
+
+
+
Open Targets baseline rank
+
174
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.02134365997612272,"interquartile_range":0.07743728420864318,"maximum":0.28073769634204876,"mean":0.059560748516648006,"measured_model_count":56,"median":0.06322339592467445,"minimum":-0.2090932215477918,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0987809441847659,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.007638541718115839,"interquartile_range":0.010072703648349442,"maximum":0.11866301644172314,"mean":0.01634520388322014,"measured_model_count":56,"median":0.010155243511429223,"minimum":0.002370897831436602,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.017711245366465282,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0016150605350365964,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.006023191938568213,"gene_effect_median":-0.0010398506799526724},"dependency_probability_context_minus_non_context_median":-0.0017265595309920688,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.006315985991137536,"gene_effect_context_minus_non_context_median":-0.0010398506799526724}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 176
+- **Dependency-aware candidate rank:** 176
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_943fa2bc183388a34a0a6a43a013f63b3a0122b085517c6ff7b59349c8f27f67`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MX2|entrez:4600`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
176not prioritized-2
Resistance biomarker0.000
177not prioritized-3
Tumor-intrinsic / small molecule0.000
176not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.543)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MX2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MX2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MYB.html b/examples/html_reports/depmap_26q1/targets/MYB.html new file mode 100644 index 0000000..db3ec3e --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MYB.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MYB + + + + +
+ +
+

Target hypothesis report: MYB

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MYB
+
+
+
Target name
+
MYB proto-oncogene, transcription factor
+
+
+
Open Targets melanoma score
+
0.569
+
+
+
+
Open Targets baseline rank
+
117
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.3259231883678356,"interquartile_range":0.21035580309281268,"maximum":0.2857082762935745,"mean":-0.2178685317305252,"measured_model_count":56,"median":-0.2383668513811943,"minimum":-0.5880233849070193,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.11556738527502294,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.05526327096966057,"interquartile_range":0.19608087680463585,"maximum":0.7574785900752413,"mean":0.18520779917804936,"measured_model_count":56,"median":0.1759008399302746,"minimum":0.001253210856482248,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2513441477742964,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.05759172837452056,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.1530274361400189,"pan_cancer_fraction":0.18874172185430463,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0935430463576159,"pan_cancer_fraction":0.0935430463576159,"threshold":0.8}],"gene_effect_mean":0.1661141346455027,"gene_effect_median":0.05943151457646956},"dependency_probability_context_minus_non_context_median":-0.061943117671945436,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.16046626984126983,"non_context_fraction":0.19618055555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.09809027777777778,"non_context_fraction":0.09809027777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.17418912730188116,"gene_effect_context_minus_non_context_median":0.06108140737397355}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 119
+- **Dependency-aware candidate rank:** 119
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_9026276f063d0feb2ceb0352f57ee7a799499b51d2b998029c871936d5caa795`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MYB|entrez:4602`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
119not prioritized-2
Resistance biomarker0.000
120not prioritized-3
Tumor-intrinsic / small molecule0.000
119not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.569)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MYB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MYB in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MYCL.html b/examples/html_reports/depmap_26q1/targets/MYCL.html new file mode 100644 index 0000000..4cf66a8 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MYCL.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MYCL + + + + +
+ +
+

Target hypothesis report: MYCL

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MYCL
+
+
+
Target name
+
MYCL proto-oncogene, bHLH transcription factor
+
+
+
Open Targets melanoma score
+
0.548
+
+
+
+
Open Targets baseline rank
+
164
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.09896427298002167,"interquartile_range":0.14969798704101517,"maximum":0.3274052023063336,"mean":-0.0172760396628093,"measured_model_count":56,"median":-0.02694371489350945,"minimum":-0.23412237491718474,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05073371406099349,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.014034643973738554,"interquartile_range":0.029981870470997513,"maximum":0.15381720551862854,"mean":0.036321603814873385,"measured_model_count":56,"median":0.02648200137173792,"minimum":0.001437699008765543,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04401651444473607,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0010191664628673401,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.005045333807037918,"gene_effect_median":-0.006651287945659612},"dependency_probability_context_minus_non_context_median":0.0010854405403200908,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.005290593089324502,"gene_effect_context_minus_non_context_median":-0.00712736439954614}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 166
+- **Dependency-aware candidate rank:** 166
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ac62729becffa3b25c6f7c2c0f938f1681488b0bd85cd283ac4e40fada25d280`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MYCL|entrez:4610`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
166not prioritized-2
Resistance biomarker0.000
167not prioritized-3
Tumor-intrinsic / small molecule0.000
166not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.548)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MYCL lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MYCL in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MYCN.html b/examples/html_reports/depmap_26q1/targets/MYCN.html new file mode 100644 index 0000000..06c9822 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MYCN.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MYCN + + + + +
+ +
+

Target hypothesis report: MYCN

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MYCN
+
+
+
Target name
+
MYCN proto-oncogene, bHLH transcription factor
+
+
+
Open Targets melanoma score
+
0.556
+
+
+
+
Open Targets baseline rank
+
143
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.16216867965324833,"interquartile_range":0.13075761344972117,"maximum":0.18745096512794407,"mean":-0.09335767882402103,"measured_model_count":56,"median":-0.10231313440314074,"minimum":-0.31346284796372825,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.031411066203527155,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.021207991240808396,"interquartile_range":0.07056960336598046,"maximum":0.31588339444654384,"mean":0.06842223106795756,"measured_model_count":56,"median":0.04657996803044029,"minimum":0.004017152964376389,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09177759460678886,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003399988493472228,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03642384105960265,"pan_cancer_fraction":0.03642384105960265,"threshold":0.5},{"context_fraction":0.0,"difference":-0.028145695364238412,"pan_cancer_fraction":0.028145695364238412,"threshold":0.8}],"gene_effect_mean":0.03544620019184806,"gene_effect_median":-0.0049602520276727236},"dependency_probability_context_minus_non_context_median":-0.0035089035421211334,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03819444444444445,"non_context_fraction":0.03819444444444445,"threshold":0.5},{"context_fraction":0.0,"difference":-0.029513888888888888,"non_context_fraction":0.029513888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03716927936784069,"gene_effect_context_minus_non_context_median":-0.005334098446723098}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 145
+- **Dependency-aware candidate rank:** 145
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2f46cade691d2c3f9825ef65e74a45c7bfea8cec9850ac3720d76c25e8ee1de7`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MYCN|entrez:4613`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
145not prioritized-2
Resistance biomarker0.000
146not prioritized-3
Tumor-intrinsic / small molecule0.000
145not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.556)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MYCN lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MYCN in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/MYH9.html b/examples/html_reports/depmap_26q1/targets/MYH9.html new file mode 100644 index 0000000..f14cba4 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/MYH9.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: MYH9 + + + + +
+ +
+

Target hypothesis report: MYH9

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
MYH9
+
+
+
Target name
+
myosin heavy chain 9
+
+
+
Open Targets melanoma score
+
0.550
+
+
+
+
Open Targets baseline rank
+
159
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.43531095200717707,"interquartile_range":0.4321296864755354,"maximum":0.5003544202391196,"mean":-0.2775936121216364,"measured_model_count":56,"median":-0.16774301545077763,"minimum":-1.6066004375290057,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0031812655316416916,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.019496240001612868,"interquartile_range":0.39325137250511455,"maximum":1.0,"mean":0.2679155181304677,"measured_model_count":56,"median":0.09881359449198113,"minimum":0.0001475945704716096,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.4127476125067274,"threshold_fractions":[{"denominator":56,"fraction":0.21428571428571427,"numerator":12,"threshold":0.5},{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.48228792904388695,"dependency_probability_threshold_fractions":[{"context_fraction":0.21428571428571427,"difference":-0.33041627246925254,"pan_cancer_fraction":0.5447019867549668,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.23628192999053926,"pan_cancer_fraction":0.3791390728476821,"threshold":0.8}],"gene_effect_mean":0.2748718719037844,"gene_effect_median":0.3555839647078126},"dependency_probability_context_minus_non_context_median":-0.5048948507760035,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.21428571428571427,"difference":-0.34647817460317454,"non_context_fraction":0.5607638888888888,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.24776785714285715,"non_context_fraction":0.390625,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.28823369901021817,"gene_effect_context_minus_non_context_median":0.3752604249442647}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":0.0}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 161
+- **Dependency-aware candidate rank:** 161
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_cb8ae5586c3af65df3acb8ba8be807f38c0cc4e1d7a13a46c6d1df06c55c58ba`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:MYH9|entrez:4627`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
161not prioritized-2
Resistance biomarker0.000
162not prioritized-3
Tumor-intrinsic / small molecule0.000
161not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.550)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: MYH9 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for MYH9 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NCOR1.html b/examples/html_reports/depmap_26q1/targets/NCOR1.html new file mode 100644 index 0000000..6094292 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NCOR1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NCOR1 + + + + +
+ +
+

Target hypothesis report: NCOR1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NCOR1
+
+
+
Target name
+
nuclear receptor corepressor 1
+
+
+
Open Targets melanoma score
+
0.518
+
+
+
+
Open Targets baseline rank
+
219
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.14874722675576924,"interquartile_range":0.19613442982199808,"maximum":0.40869956664500295,"mean":-0.050841057199357345,"measured_model_count":56,"median":-0.06479063151622333,"minimum":-0.47358794580058783,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.047387203066228845,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0142035703777452,"interquartile_range":0.05741298227323171,"maximum":0.6135325032976449,"mean":0.07185270495360432,"measured_model_count":56,"median":0.03644019619439713,"minimum":0.0004819219900222099,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07161655265097691,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.024293759484647612,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.05085146641438033,"pan_cancer_fraction":0.06870860927152318,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014072847682119206,"pan_cancer_fraction":0.014072847682119206,"threshold":0.8}],"gene_effect_mean":0.08418536973784153,"gene_effect_median":0.05289848641887364},"dependency_probability_context_minus_non_context_median":-0.02542508073445545,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.053323412698412696,"non_context_fraction":0.07118055555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014756944444444444,"non_context_fraction":0.014756944444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08827771410009778,"gene_effect_context_minus_non_context_median":0.05470171183833597}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 221
+- **Dependency-aware candidate rank:** 221
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_76108c2331f584c31fb789defb5aed0b5f9708c16ea62ba60995534ac5a5b24f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NCOR1|entrez:9611`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
221not prioritized-2
Resistance biomarker0.000
221not prioritized-2
Tumor-intrinsic / small molecule0.000
221not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.518)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NCOR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NCOR1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NCOR2.html b/examples/html_reports/depmap_26q1/targets/NCOR2.html new file mode 100644 index 0000000..497d29d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NCOR2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NCOR2 + + + + +
+ +
+

Target hypothesis report: NCOR2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NCOR2
+
+
+
Target name
+
nuclear receptor corepressor 2
+
+
+
Open Targets melanoma score
+
0.527
+
+
+
+
Open Targets baseline rank
+
190
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.19677150936375593,"interquartile_range":0.21722888807469082,"maximum":0.3135537156941089,"mean":-0.0794500067734865,"measured_model_count":56,"median":-0.08617660679431993,"minimum":-0.5326903318404643,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.020457378710934896,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.014692639727071004,"interquartile_range":0.08912182751889369,"maximum":0.7102176386085275,"mean":0.08821307570204999,"measured_model_count":56,"median":0.04143923631202472,"minimum":0.0012173477572731738,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1038144672459647,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004159406552384996,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.01939451277199622,"pan_cancer_fraction":0.037251655629139076,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008278145695364239,"pan_cancer_fraction":0.008278145695364239,"threshold":0.8}],"gene_effect_mean":0.012787652786656029,"gene_effect_median":-0.005097725762859856},"dependency_probability_context_minus_non_context_median":-0.004497928115167298,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.02033730158730159,"non_context_fraction":0.03819444444444445,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008680555555555556,"non_context_fraction":0.008680555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01340927479711855,"gene_effect_context_minus_non_context_median":-0.0057190728377012195}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 192
+- **Dependency-aware candidate rank:** 192
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_9e228d6145f0b25d4922e5d1e12d7f06f9e52bd69d80434cd4d56a11bfc8dba7`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NCOR2|entrez:9612`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
192not prioritized-2
Resistance biomarker0.000
192not prioritized-2
Tumor-intrinsic / small molecule0.000
192not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.527)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NCOR2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NCOR2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NF1.html b/examples/html_reports/depmap_26q1/targets/NF1.html new file mode 100644 index 0000000..47e722c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NF1.html @@ -0,0 +1,441 @@ + + + + +TargetIntel-IO report: NF1 + + + + +
+ +
+

Target hypothesis report: NF1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NF1
+
+
+
Target name
+
neurofibromin 1
+
+
+
Open Targets melanoma score
+
0.743
+
+
+
+
Open Targets baseline rank
+
9
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06668735429589426,"interquartile_range":0.13438545277483557,"maximum":1.0698235652637622,"mean":0.01868900574791985,"measured_model_count":56,"median":0.0019771339155402017,"minimum":-0.2401975756059271,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06769809847894132,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.010584583348384757,"interquartile_range":0.02670090210183779,"maximum":0.16869809455036536,"mean":0.029899133533875046,"measured_model_count":56,"median":0.019721964712171004,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03728548545022255,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00022845419237565306,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.016556291390728478,"pan_cancer_fraction":0.016556291390728478,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.8}],"gene_effect_mean":-0.01293955913841129,"gene_effect_median":-0.006051806545345912},"dependency_probability_context_minus_non_context_median":-0.0003253137843298587,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.017361111111111112,"non_context_fraction":0.017361111111111112,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.013568565485417353,"gene_effect_context_minus_non_context_median":-0.007529220651397316}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 17
+- **Dependency-aware candidate rank:** 17
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_306bbea8c737551aa85a77a9b3c60121159faebc65dd2accf74166da5df903a2`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NF1|entrez:4763`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / poor direct therapeutic target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
avoid as direct target / use as biomarker or pathway context
+
+
+
Best modality
+
biomarker / pathway context only
+
+
+
Resistance axis
+
tumor_intrinsic_driver
+
+
+
Matched resistance programs
+
Tumor-intrinsic driver biology
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
17not prioritized-8
Resistance biomarker0.309
17low-8
Tumor-intrinsic / small molecule0.000
39not prioritized-30
+
+ +
+

Evidence for

+
    +
  • Relevant to melanoma tumor-cell biology
    • +
  • Some targets or pathways are clinically actionable
    • +
  • Useful for separating tumor-intrinsic drivers from immune-combination targets
    • +
  • High Open Targets melanoma association score (0.743)
    • +
  • Maps to curated anti-PD-1 resistance program: Tumor-intrinsic driver biology
    • +
  • Stable role classifier confidence is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Many tumor-intrinsic drivers are poor antibody targets
    • +
  • Melanoma association does not automatically imply anti-PD-1 combination suitability
    • +
  • Tumor suppressors are often poor direct therapeutic targets
    • +
  • Flagged as poor direct therapeutic target for this MVP
    • +
  • Role classifier indicates biological relevance but poor direct targetability
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.650
+
+
+
+
Main limitation
+
Poor direct therapeutic target despite biological relevance
+
+
+

Uncertainty reason: High contradiction score indicates important opposing evidence | Main limitation: Poor direct therapeutic target despite biological relevance

+

Deprioritization reason: NF1 should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context.

+
+ +
+

Recommended next validation experiment

+

Validation category: tumor-intrinsic functional validation

+

Next experiment: Evaluate whether perturbing NF1 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays.

+

Rationale: This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NF2.html b/examples/html_reports/depmap_26q1/targets/NF2.html new file mode 100644 index 0000000..f432ad5 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NF2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NF2 + + + + +
+ +
+

Target hypothesis report: NF2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NF2
+
+
+
Target name
+
NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor
+
+
+
Open Targets melanoma score
+
0.474
+
+
+
+
Open Targets baseline rank
+
280
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.0033319999520227406,"interquartile_range":0.4985835437227313,"maximum":1.4967874348475283,"mean":0.257261458735955,"measured_model_count":56,"median":0.24139439051277362,"minimum":-0.9790795352267114,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.49525154377070857,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.00017270873873151513,"interquartile_range":0.019002620285019006,"maximum":0.9430258163992079,"mean":0.07984631308479892,"measured_model_count":56,"median":0.0025437083249686757,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.01917532902375052,"threshold_fractions":[{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.001039973676862268,"dependency_probability_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":0.03334910122989593,"pan_cancer_fraction":0.0380794701986755,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.0036660359508041626,"pan_cancer_fraction":0.02152317880794702,"threshold":0.8}],"gene_effect_mean":-0.0014079923395545757,"gene_effect_median":0.028469770273931827},"dependency_probability_context_minus_non_context_median":-0.0010699086747809035,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":0.03497023809523809,"non_context_fraction":0.036458333333333336,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.003844246031746032,"non_context_fraction":0.021701388888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0014764364116162665,"gene_effect_context_minus_non_context_median":0.03120785575397461}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 280
+- **Dependency-aware candidate rank:** 280
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_05a8add15cd2bcacbd3adbfd8a68652f1c66ad80e6c3d105077d3272199c0a2b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NF2|entrez:4771`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
280not prioritized0
Resistance biomarker0.000
280not prioritized0
Tumor-intrinsic / small molecule0.000
280not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.474)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NF2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NF2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NFE2L2.html b/examples/html_reports/depmap_26q1/targets/NFE2L2.html new file mode 100644 index 0000000..fabf7ce --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NFE2L2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NFE2L2 + + + + +
+ +
+

Target hypothesis report: NFE2L2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NFE2L2
+
+
+
Target name
+
NFE2 like bZIP transcription factor 2
+
+
+
Open Targets melanoma score
+
0.459
+
+
+
+
Open Targets baseline rank
+
297
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.2520091656406369,"interquartile_range":0.20548262734606618,"maximum":0.31448187297091834,"mean":-0.13768003790624178,"measured_model_count":56,"median":-0.14924719674865072,"minimum":-0.4886761370341983,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.046526538294570735,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.031692531987762916,"interquartile_range":0.13629651356662498,"maximum":0.5844930902604566,"mean":0.1270283768174245,"measured_model_count":56,"median":0.08432932917261374,"minimum":0.0003081043336782536,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1679890455543879,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.041173957256818466,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.08384578997161779,"pan_cancer_fraction":0.13741721854304637,"threshold":0.5},{"context_fraction":0.0,"difference":-0.062086092715231786,"pan_cancer_fraction":0.062086092715231786,"threshold":0.8}],"gene_effect_mean":0.12219017207461635,"gene_effect_median":0.05562504107043592},"dependency_probability_context_minus_non_context_median":-0.04412269038471142,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.08792162698412698,"non_context_fraction":0.14149305555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.06510416666666667,"non_context_fraction":0.06510416666666667,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.12812997210602156,"gene_effect_context_minus_non_context_median":0.05789486954820591}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 297
+- **Dependency-aware candidate rank:** 297
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a434db41122df3a7efb43447fadf1f1b96b72ad8ba24f7a5f8e37dfa5f390cd7`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NFE2L2|entrez:4780`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
297not prioritized0
Resistance biomarker0.000
297not prioritized0
Tumor-intrinsic / small molecule0.000
297not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.459)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NFE2L2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NFE2L2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NFKB2.html b/examples/html_reports/depmap_26q1/targets/NFKB2.html new file mode 100644 index 0000000..c889c2a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NFKB2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NFKB2 + + + + +
+ +
+

Target hypothesis report: NFKB2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NFKB2
+
+
+
Target name
+
nuclear factor kappa B subunit 2
+
+
+
Open Targets melanoma score
+
0.522
+
+
+
+
Open Targets baseline rank
+
200
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.1463779154801344,"interquartile_range":0.16275217738118264,"maximum":0.3906297033324104,"mean":-0.06272083452331122,"measured_model_count":56,"median":-0.07291431839673687,"minimum":-0.5332535016531746,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.016374261901048223,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01669333637117928,"interquartile_range":0.06426057937780422,"maximum":0.5792888550716845,"mean":0.07237504948051252,"measured_model_count":56,"median":0.039965302273933655,"minimum":0.0005060565776778315,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0809539157489835,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.03721333081785242,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.03760643330179754,"pan_cancer_fraction":0.055463576158940396,"threshold":0.5},{"context_fraction":0.0,"difference":-0.024006622516556293,"pan_cancer_fraction":0.024006622516556293,"threshold":0.8}],"gene_effect_mean":0.09950651123097475,"gene_effect_median":0.0713352316781887},"dependency_probability_context_minus_non_context_median":-0.040284300088949794,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.03943452380952381,"non_context_fraction":0.057291666666666664,"threshold":0.5},{"context_fraction":0.0,"difference":-0.025173611111111112,"non_context_fraction":0.025173611111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.10434363330470263,"gene_effect_context_minus_non_context_median":0.076204722483839}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 202
+- **Dependency-aware candidate rank:** 202
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_5163e4a1e8bbb0722f492708f61f90aae1e907db8822be71fbe6351225a471a5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NFKB2|entrez:4791`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
202not prioritized-2
Resistance biomarker0.000
202not prioritized-2
Tumor-intrinsic / small molecule0.000
202not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.522)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NFKB2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NFKB2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NFKBIE.html b/examples/html_reports/depmap_26q1/targets/NFKBIE.html new file mode 100644 index 0000000..e70755d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NFKBIE.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NFKBIE + + + + +
+ +
+

Target hypothesis report: NFKBIE

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NFKBIE
+
+
+
Target name
+
NFKB inhibitor epsilon
+
+
+
Open Targets melanoma score
+
0.552
+
+
+
+
Open Targets baseline rank
+
151
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.4747394844173423,"interquartile_range":0.2676801224614766,"maximum":0.41948154320340647,"mean":-0.3416210665817968,"measured_model_count":56,"median":-0.3591398799415844,"minimum":-1.083785830359554,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.20705936195586572,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.1375067692802133,"interquartile_range":0.37049721185843076,"maximum":0.958742819767064,"mean":0.3531347237615799,"measured_model_count":56,"median":0.3441621104153567,"minimum":0.0002733574349602312,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5080039811386441,"threshold_fractions":[{"denominator":56,"fraction":0.26785714285714285,"numerator":15,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.057732492905683164,"dependency_probability_threshold_fractions":[{"context_fraction":0.26785714285714285,"difference":-0.12949385052034057,"pan_cancer_fraction":0.3973509933774834,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.07272942289498581,"pan_cancer_fraction":0.10844370860927152,"threshold":0.8}],"gene_effect_mean":0.07758626106936861,"gene_effect_median":0.040194233698520765},"dependency_probability_context_minus_non_context_median":-0.05994962551203031,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.26785714285714285,"difference":-0.13578869047619047,"non_context_fraction":0.4036458333333333,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.07626488095238096,"non_context_fraction":0.11197916666666667,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08135781542690734,"gene_effect_context_minus_non_context_median":0.0427321013429815}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 153
+- **Dependency-aware candidate rank:** 153
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_cb8e4c718580d371942873febe1a8c25a6c9b88dc35ffb4e96c1a0f8926a9277`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NFKBIE|entrez:4794`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
153not prioritized-2
Resistance biomarker0.000
154not prioritized-3
Tumor-intrinsic / small molecule0.000
153not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.552)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NFKBIE lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NFKBIE in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NGFR.html b/examples/html_reports/depmap_26q1/targets/NGFR.html new file mode 100644 index 0000000..4568490 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NGFR.html @@ -0,0 +1,70 @@ +NGFR — DepMap research preview

NGFR

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.30792591558766197,"interquartile_range":0.11989661346851041,"maximum":0.11576261821187195,"mean":-0.24643987201509007,"measured_model_count":56,"median":-0.24041421960464082,"minimum":-0.4807813402770903,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.18802930211915156,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.09390776865702505,"interquartile_range":0.16367174704167087,"maximum":0.5605448986371326,"mean":0.1942768969038153,"measured_model_count":56,"median":0.1667282415797557,"minimum":0.008597790397277472,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2575795156986959,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.017541887806746148,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.004020813623462634,"pan_cancer_fraction":0.039735099337748346,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.011086422347907576,"gene_effect_median":-0.012159150132109414},"dependency_probability_context_minus_non_context_median":0.017987696781701923,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.00421626984126984,"non_context_fraction":0.03993055555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.011625345656486624,"gene_effect_context_minus_non_context_median":-0.012913856993605505}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d88a4a6e8d58eb9d9be4cfa5fefe136c56be9a1fe67fea5f0472889cf6fad807`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NGFR|entrez:4804`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/NKX2-1.html b/examples/html_reports/depmap_26q1/targets/NKX2-1.html new file mode 100644 index 0000000..146a210 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NKX2-1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NKX2-1 + + + + +
+ +
+

Target hypothesis report: NKX2-1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NKX2-1
+
+
+
Target name
+
NK2 homeobox 1
+
+
+
Open Targets melanoma score
+
0.509
+
+
+
+
Open Targets baseline rank
+
240
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.12276799614693762,"interquartile_range":0.18307558688335396,"maximum":0.27550802661951984,"mean":-0.043376474182780414,"measured_model_count":56,"median":-0.03133446214879327,"minimum":-0.4273642289892,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.060307590736416325,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.010194888921109245,"interquartile_range":0.04847112414292441,"maximum":0.3976824988928863,"mean":0.060590058138209654,"measured_model_count":56,"median":0.02987755063188091,"minimum":0.0012628047782111012,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.058666013064033656,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.006920390134227572,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0173841059602649,"pan_cancer_fraction":0.0173841059602649,"threshold":0.5},{"context_fraction":0.0,"difference":-0.011589403973509934,"pan_cancer_fraction":0.011589403973509934,"threshold":0.8}],"gene_effect_mean":-0.02431278240743919,"gene_effect_median":-0.023869701579934878},"dependency_probability_context_minus_non_context_median":0.007261515319367598,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.018229166666666668,"non_context_fraction":0.018229166666666668,"threshold":0.5},{"context_fraction":0.0,"difference":-0.012152777777777778,"non_context_fraction":0.012152777777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.025494653774467475,"gene_effect_context_minus_non_context_median":-0.02458657597811076}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 242
+- **Dependency-aware candidate rank:** 242
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_5fc4628007da194a0f864fc55f87c4defaaae339f5ff022dbdcdfd337537981e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NKX2-1|entrez:7080`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
242not prioritized-2
Resistance biomarker0.000
242not prioritized-2
Tumor-intrinsic / small molecule0.000
242not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.509)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NKX2-1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NKX2-1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NOTCH1.html b/examples/html_reports/depmap_26q1/targets/NOTCH1.html new file mode 100644 index 0000000..6036d84 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NOTCH1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NOTCH1 + + + + +
+ +
+

Target hypothesis report: NOTCH1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NOTCH1
+
+
+
Target name
+
notch receptor 1
+
+
+
Open Targets melanoma score
+
0.466
+
+
+
+
Open Targets baseline rank
+
287
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.04943752847392074,"interquartile_range":0.11481559041215458,"maximum":0.16997708658381597,"mean":-0.0011867456856176305,"measured_model_count":56,"median":0.008586282728026395,"minimum":-0.2810791148673261,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06537806193823384,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.012038295662059835,"interquartile_range":0.022845606718235385,"maximum":0.18447254484328296,"mean":0.030522579666454237,"measured_model_count":56,"median":0.015886080712783135,"minimum":0.004403982739587212,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03488390238029522,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004511437646536366,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.002881876199835815,"gene_effect_median":0.0019853222554847925},"dependency_probability_context_minus_non_context_median":-0.004730151946607315,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.003021967403994499,"gene_effect_context_minus_non_context_median":0.002190064586723877}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 287
+- **Dependency-aware candidate rank:** 287
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_12522c3c7b551212b5b12d87edb900063144f2a9309c36eef95e8213577c8f8f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NOTCH1|entrez:4851`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
287not prioritized0
Resistance biomarker0.000
287not prioritized0
Tumor-intrinsic / small molecule0.000
287not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.466)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NOTCH1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NOTCH1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NOTCH2.html b/examples/html_reports/depmap_26q1/targets/NOTCH2.html new file mode 100644 index 0000000..bacdefb --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NOTCH2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NOTCH2 + + + + +
+ +
+

Target hypothesis report: NOTCH2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NOTCH2
+
+
+
Target name
+
notch receptor 2
+
+
+
Open Targets melanoma score
+
0.575
+
+
+
+
Open Targets baseline rank
+
106
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.13850163507429375,"interquartile_range":0.2244656275170174,"maximum":0.3986273246825719,"mean":-0.030350525395588388,"measured_model_count":56,"median":-0.034328145661024975,"minimum":-0.44916442200119266,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08596399244272365,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.007945313328654979,"interquartile_range":0.08294853524488494,"maximum":0.4118005119658145,"mean":0.06629039133767924,"measured_model_count":56,"median":0.025783870960812194,"minimum":0.002243224020282026,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09089384857353991,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.008359685791117233,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.01076158940397351,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.8}],"gene_effect_mean":0.018910825757955958,"gene_effect_median":0.021337019372317377},"dependency_probability_context_minus_non_context_median":-0.00914746633812634,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.011284722222222222,"non_context_fraction":0.011284722222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.019830102010078756,"gene_effect_context_minus_non_context_median":0.021599372856303388}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 109
+- **Dependency-aware candidate rank:** 109
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_fa23bea35f8129e15b88020fb8777a77b7aa952868e1fe0c1ab1eef3bdc8451b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NOTCH2|entrez:4853`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
109not prioritized-3
Resistance biomarker0.000
110not prioritized-4
Tumor-intrinsic / small molecule0.000
109not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.575)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NOTCH2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NOTCH2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NRAS.html b/examples/html_reports/depmap_26q1/targets/NRAS.html new file mode 100644 index 0000000..cc7445b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NRAS.html @@ -0,0 +1,441 @@ + + + + +TargetIntel-IO report: NRAS + + + + +
+ +
+

Target hypothesis report: NRAS

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NRAS
+
+
+
Target name
+
NRAS proto-oncogene, GTPase
+
+
+
Open Targets melanoma score
+
0.779
+
+
+
+
Open Targets baseline rank
+
5
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.3305911123197959,"interquartile_range":0.20369185017668184,"maximum":0.09354479287791917,"mean":-0.44904229263305867,"measured_model_count":56,"median":-0.19958349119150692,"minimum":-2.9561530105181015,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.12689926214311403,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.05768686105568797,"interquartile_range":0.22765180742178384,"maximum":1.0,"mean":0.27492022095168256,"measured_model_count":56,"median":0.11160490099703885,"minimum":0.004688799268174339,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2853386684774718,"threshold_fractions":[{"denominator":56,"fraction":0.19642857142857142,"numerator":11,"threshold":0.5},{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03043227636868405,"dependency_probability_threshold_fractions":[{"context_fraction":0.19642857142857142,"difference":0.11116367076631976,"pan_cancer_fraction":0.08526490066225166,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.10773415326395461,"pan_cancer_fraction":0.052980132450331126,"threshold":0.8}],"gene_effect_mean":-0.2283655354809437,"gene_effect_median":-0.05177886304443688},"dependency_probability_context_minus_non_context_median":0.03204527595438135,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.19642857142857142,"difference":0.11656746031746032,"non_context_fraction":0.0798611111111111,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.11297123015873017,"non_context_fraction":0.04774305555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.23946663790015615,"gene_effect_context_minus_non_context_median":-0.053778538177950364}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 6
+- **Dependency-aware candidate rank:** 3
+- **Rank delta:** -3
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_1006bb8f646ab657109ccdcd33c00d15c235fa96e722c0ba89e9fc9798d3ccef`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NRAS|entrez:4893`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / biomarker
+
+
+
Role confidence
+
medium-high
+
+
+
Therapeutic direction
+
use as biomarker / pathway targeting if appropriate
+
+
+
Best modality
+
tumor-intrinsic biomarker / pathway context
+
+
+
Resistance axis
+
tumor_intrinsic_driver
+
+
+
Matched resistance programs
+
Tumor-intrinsic driver biology
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.301
6low-1
Resistance biomarker0.760
4high1
Tumor-intrinsic / small molecule0.666
6medium-1
+
+ +
+

Evidence for

+
    +
  • Relevant to melanoma tumor-cell biology
    • +
  • Some targets or pathways are clinically actionable
    • +
  • Useful for separating tumor-intrinsic drivers from immune-combination targets
    • +
  • High Open Targets melanoma association score (0.779)
    • +
  • Maps to curated anti-PD-1 resistance program: Tumor-intrinsic driver biology
    • +
  • Stable role classifier confidence is medium-high
    • +
  • Biomarker fit is medium-high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Many tumor-intrinsic drivers are poor antibody targets
    • +
  • Melanoma association does not automatically imply anti-PD-1 combination suitability
    • +
  • Tumor suppressors are often poor direct therapeutic targets
    • +
  • Most useful as biomarker or stratification marker rather than direct therapeutic target
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
high confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.400
+
+
+
+
Main limitation
+
Likely more useful for stratification than direct therapeutic targeting
+
+
+

Uncertainty reason: Moderate contradiction score indicates caution is needed | Main limitation: Likely more useful for stratification than direct therapeutic targeting

+

Deprioritization reason: NRAS should not be deprioritized globally, but should be ranked mainly in biomarker or patient-stratification mode.

+
+ +
+

Recommended next validation experiment

+

Validation category: biomarker validation

+

Next experiment: Test whether NRAS status or expression differs between anti-PD-1 responders and non-responders in an independent melanoma cohort.

+

Rationale: This would determine whether the candidate has practical value as a resistance biomarker or patient-stratification feature.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NT5E.html b/examples/html_reports/depmap_26q1/targets/NT5E.html new file mode 100644 index 0000000..590b48e --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NT5E.html @@ -0,0 +1,70 @@ +NT5E — DepMap research preview

NT5E

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.07327247215096008,"interquartile_range":0.1162611666370785,"maximum":0.2732322344641132,"mean":-0.0047660578695370584,"measured_model_count":56,"median":-0.008866378941955744,"minimum":-0.262273581288223,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04298869448611842,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.014413470815455534,"interquartile_range":0.024615083725310807,"maximum":0.20865009438516322,"mean":0.03134252380078864,"measured_model_count":56,"median":0.0211052075698444,"minimum":0.0020125603678799444,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03902855454076634,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002293839989739456,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.005378338834790834,"gene_effect_median":0.0017674569453955888},"dependency_probability_context_minus_non_context_median":-0.0024087456741203536,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.00563978586148206,"gene_effect_context_minus_non_context_median":0.0017674569453955888}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_8ae6481aedc84705f6325d21e4410cf48e8b9b8631209ae795b0dcbfb9ecbecf`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NT5E|entrez:4907`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/NTRK1.html b/examples/html_reports/depmap_26q1/targets/NTRK1.html new file mode 100644 index 0000000..d6e8d24 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NTRK1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NTRK1 + + + + +
+ +
+

Target hypothesis report: NTRK1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NTRK1
+
+
+
Target name
+
neurotrophic receptor tyrosine kinase 1
+
+
+
Open Targets melanoma score
+
0.603
+
+
+
+
Open Targets baseline rank
+
66
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.04264846706192717,"interquartile_range":0.1195819914607735,"maximum":0.20114723020449096,"mean":0.015540283237262965,"measured_model_count":56,"median":0.026272854423689842,"minimum":-0.23366332567258905,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07693352439884633,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.009811935298125282,"interquartile_range":0.024365972544399282,"maximum":0.14777656422626312,"mean":0.024222066161382748,"measured_model_count":56,"median":0.01863576450281533,"minimum":0.00207213738312382,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.034177907842524564,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0026097343765249664,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.01653609182805236,"gene_effect_median":0.023617564189398383},"dependency_probability_context_minus_non_context_median":-0.0026693963472452023,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01733992962524936,"gene_effect_context_minus_non_context_median":0.024330047611103866}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 70
+- **Dependency-aware candidate rank:** 70
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2850f3a7f8e52fc114a0216526457d3eecd24446606aee50be84b2e59a719198`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NTRK1|entrez:4914`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
70not prioritized-4
Resistance biomarker0.000
72not prioritized-6
Tumor-intrinsic / small molecule0.000
70not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.603)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NTRK1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NTRK1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NTRK2.html b/examples/html_reports/depmap_26q1/targets/NTRK2.html new file mode 100644 index 0000000..7cf52ea --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NTRK2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NTRK2 + + + + +
+ +
+

Target hypothesis report: NTRK2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NTRK2
+
+
+
Target name
+
neurotrophic receptor tyrosine kinase 2
+
+
+
Open Targets melanoma score
+
0.574
+
+
+
+
Open Targets baseline rank
+
109
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.014221021812303218,"interquartile_range":0.14884406245468834,"maximum":0.42475333414356103,"mean":0.09655480444725151,"measured_model_count":56,"median":0.08551856745146294,"minimum":-0.2698832809930628,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.16306508426699157,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.003994279326308055,"interquartile_range":0.015022230202413047,"maximum":0.16008520535900733,"mean":0.015090863385395179,"measured_model_count":56,"median":0.007605478950701532,"minimum":0.00032944850035258275,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.019016509528721103,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0005276351297663958,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.013549136427241329,"gene_effect_median":-0.024133503389609345},"dependency_probability_context_minus_non_context_median":-0.0005624714137863925,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.014207775003565543,"gene_effect_context_minus_non_context_median":-0.02460948284873654}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 112
+- **Dependency-aware candidate rank:** 112
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_f1b3909e0c13b02736454cfc41d932f82b1a6941ac58b134800c06c58f0ac9e0`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NTRK2|entrez:4915`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
112not prioritized-3
Resistance biomarker0.000
113not prioritized-4
Tumor-intrinsic / small molecule0.000
112not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.574)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NTRK2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NTRK2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NTRK3.html b/examples/html_reports/depmap_26q1/targets/NTRK3.html new file mode 100644 index 0000000..026b8d2 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NTRK3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NTRK3 + + + + +
+ +
+

Target hypothesis report: NTRK3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NTRK3
+
+
+
Target name
+
neurotrophic receptor tyrosine kinase 3
+
+
+
Open Targets melanoma score
+
0.543
+
+
+
+
Open Targets baseline rank
+
176
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.07238517527802066,"interquartile_range":0.13988816637951834,"maximum":0.27181984530850334,"mean":-0.008595154891903269,"measured_model_count":56,"median":0.00021986816198801135,"minimum":-0.4322775348198563,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06750299110149767,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.010213270016093746,"interquartile_range":0.03102434821200728,"maximum":0.3764846557634913,"mean":0.03842677280420746,"measured_model_count":56,"median":0.019114279173136295,"minimum":0.0013946676886993539,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04123761822810103,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0029891060828684396,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.036162069681453,"gene_effect_median":-0.027547539772977414},"dependency_probability_context_minus_non_context_median":0.003129747662845954,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.037919948068745865,"gene_effect_context_minus_non_context_median":-0.029605263286164356}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 178
+- **Dependency-aware candidate rank:** 178
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_498ab797376e748417d1d149204710e6ff7beaf50b220e284db9d59f4bdda6f5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NTRK3|entrez:4916`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
178not prioritized-2
Resistance biomarker0.000
179not prioritized-3
Tumor-intrinsic / small molecule0.000
178not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.543)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NTRK3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NTRK3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NUP98.html b/examples/html_reports/depmap_26q1/targets/NUP98.html new file mode 100644 index 0000000..d1c5750 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NUP98.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NUP98 + + + + +
+ +
+

Target hypothesis report: NUP98

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NUP98
+
+
+
Target name
+
nucleoporin 98 and 96 precursor
+
+
+
Open Targets melanoma score
+
0.517
+
+
+
+
Open Targets baseline rank
+
223
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.946727819118484,"interquartile_range":0.2497531610528998,"maximum":-0.35725870489878797,"mean":-0.8454054346865577,"measured_model_count":56,"median":-0.8055598197254084,"minimum":-1.97097650992929,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.6969746580655842,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.8242508054226083,"interquartile_range":0.14214214374173795,"maximum":0.9999613193078875,"mean":0.855911828309157,"measured_model_count":56,"median":0.9185618693763015,"minimum":0.25117687375019454,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9663929491643463,"threshold_fractions":[{"denominator":56,"fraction":0.9464285714285714,"numerator":53,"threshold":0.5},{"denominator":56,"fraction":0.8035714285714286,"numerator":45,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.013608595849936012,"dependency_probability_threshold_fractions":[{"context_fraction":0.9464285714285714,"difference":0.020931882686849534,"pan_cancer_fraction":0.9254966887417219,"threshold":0.5},{"context_fraction":0.8035714285714286,"difference":0.08171712393566699,"pan_cancer_fraction":0.7218543046357616,"threshold":0.8}],"gene_effect_mean":-0.03771092138285437,"gene_effect_median":-0.01749412142517137},"dependency_probability_context_minus_non_context_median":0.01587729335632837,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9464285714285714,"difference":0.021949404761904767,"non_context_fraction":0.9244791666666666,"threshold":0.5},{"context_fraction":0.8035714285714286,"difference":0.08568948412698418,"non_context_fraction":0.7178819444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03954409117229907,"gene_effect_context_minus_non_context_median":-0.01970122639959393}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 225
+- **Dependency-aware candidate rank:** 225
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_1ba578635cb5aef41676cb0043c4781a1ce8bac50ca758d201877e4ced8cb0b7`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NUP98|entrez:4928`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
225not prioritized-2
Resistance biomarker0.000
225not prioritized-2
Tumor-intrinsic / small molecule0.000
225not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.517)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NUP98 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NUP98 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/NUTM1.html b/examples/html_reports/depmap_26q1/targets/NUTM1.html new file mode 100644 index 0000000..51637eb --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/NUTM1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: NUTM1 + + + + +
+ +
+

Target hypothesis report: NUTM1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
NUTM1
+
+
+
Target name
+
NUT midline carcinoma family member 1
+
+
+
Open Targets melanoma score
+
0.561
+
+
+
+
Open Targets baseline rank
+
133
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06766413170933441,"interquartile_range":0.12230469464003679,"maximum":0.23858120904323193,"mean":-0.013250682999457888,"measured_model_count":56,"median":-0.01540965770348755,"minimum":-0.33765216343614773,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05464056293070238,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.012373005021698226,"interquartile_range":0.026164771633834467,"maximum":0.22158294522974528,"mean":0.03317301826003201,"measured_model_count":56,"median":0.023444423153857114,"minimum":0.0015163016029478907,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03853777665553269,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0001316682205584757,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.000661284332854499,"gene_effect_median":-0.005158631169675826},"dependency_probability_context_minus_non_context_median":0.00014568546017170586,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0006934300990349106,"gene_effect_context_minus_non_context_median":-0.005295065741185927}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 135
+- **Dependency-aware candidate rank:** 135
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a7580b2432b014db80d8227696d1df4599afb6ffea0b59a0f07c2e74ffbd01f2`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:NUTM1|entrez:256646`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
135not prioritized-2
Resistance biomarker0.000
136not prioritized-3
Tumor-intrinsic / small molecule0.000
135not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.561)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: NUTM1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for NUTM1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/OCA2.html b/examples/html_reports/depmap_26q1/targets/OCA2.html new file mode 100644 index 0000000..074646b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/OCA2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: OCA2 + + + + +
+ +
+

Target hypothesis report: OCA2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
OCA2
+
+
+
Target name
+
OCA2 melanosomal transmembrane protein
+
+
+
Open Targets melanoma score
+
0.594
+
+
+
+
Open Targets baseline rank
+
77
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.11003886894933272,"interquartile_range":0.12428844836998826,"maximum":0.17215928504056552,"mean":-0.04570717775043043,"measured_model_count":56,"median":-0.024477812493177965,"minimum":-0.2893171738503026,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.014249579420655543,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01726318105631539,"interquartile_range":0.03416598908030699,"maximum":0.2544187739476363,"mean":0.04408398212649205,"measured_model_count":56,"median":0.025337616392692195,"minimum":0.0036640872919462475,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.051429170136622376,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.007786010091894207,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.006999676819245647,"gene_effect_median":0.023317806384539723},"dependency_probability_context_minus_non_context_median":-0.008143804426631634,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.007339938886847905,"gene_effect_context_minus_non_context_median":0.023893361550354493}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 81
+- **Dependency-aware candidate rank:** 81
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_815423402101e51b7deb2d11c38997994f088fde620e66d3bd82415408b7b1ae`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:OCA2|entrez:4948`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
81not prioritized-4
Resistance biomarker0.000
83not prioritized-6
Tumor-intrinsic / small molecule0.000
81not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.594)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: OCA2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for OCA2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PARP1.html b/examples/html_reports/depmap_26q1/targets/PARP1.html new file mode 100644 index 0000000..03f94ff --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PARP1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PARP1 + + + + +
+ +
+

Target hypothesis report: PARP1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PARP1
+
+
+
Target name
+
poly(ADP-ribose) polymerase 1
+
+
+
Open Targets melanoma score
+
0.542
+
+
+
+
Open Targets baseline rank
+
178
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.3126108449025472,"interquartile_range":0.19294837361965708,"maximum":0.11033739065298756,"mean":-0.2123893655849565,"measured_model_count":56,"median":-0.20900614511179944,"minimum":-0.5526061990232184,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.11966247128289012,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0579623906831193,"interquartile_range":0.22040785644401745,"maximum":0.6102638834732295,"mean":0.1765929122874719,"measured_model_count":56,"median":0.13645456881846418,"minimum":0.005254797527991211,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.27837024712713676,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.022842800470256275,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.0027199621570482557,"pan_cancer_fraction":0.056291390728476824,"threshold":0.5},{"context_fraction":0.0,"difference":-0.01076158940397351,"pan_cancer_fraction":0.01076158940397351,"threshold":0.8}],"gene_effect_mean":-0.003104326665073792,"gene_effect_median":-0.011763437800700827},"dependency_probability_context_minus_non_context_median":0.022954289988049728,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.0028521825396825434,"non_context_fraction":0.05642361111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.011284722222222222,"non_context_fraction":0.011284722222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.003255231433514666,"gene_effect_context_minus_non_context_median":-0.012316196722426925}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 180
+- **Dependency-aware candidate rank:** 180
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_6a05d4f572df2935e2aa57c8c0be391ab627b597e3b8d4ad8df2850c5769dd08`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PARP1|entrez:142`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
180not prioritized-2
Resistance biomarker0.000
181not prioritized-3
Tumor-intrinsic / small molecule0.000
180not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.542)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PARP1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PARP1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PATZ1.html b/examples/html_reports/depmap_26q1/targets/PATZ1.html new file mode 100644 index 0000000..7001ea2 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PATZ1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PATZ1 + + + + +
+ +
+

Target hypothesis report: PATZ1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PATZ1
+
+
+
Target name
+
POZ/BTB and AT hook containing zinc finger 1
+
+
+
Open Targets melanoma score
+
0.490
+
+
+
+
Open Targets baseline rank
+
263
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.21337700367028087,"interquartile_range":0.13030410006901616,"maximum":0.1548473717667494,"mean":-0.15100029050775082,"measured_model_count":56,"median":-0.1391172000683189,"minimum":-0.4179920396603739,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.08307290360126471,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.04269880256237364,"interquartile_range":0.1065916921003043,"maximum":0.39286694038493386,"mean":0.1137033476788312,"measured_model_count":56,"median":0.0798356188482517,"minimum":0.005100727127091044,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14929049466267794,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0165327815011949,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.018211920529801324,"pan_cancer_fraction":0.018211920529801324,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.018082096825231653,"gene_effect_median":-0.01592223397123585},"dependency_probability_context_minus_non_context_median":0.016974812374555837,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.019097222222222224,"non_context_fraction":0.019097222222222224,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.018961087643124847,"gene_effect_context_minus_non_context_median":-0.017953281291869364}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 265
+- **Dependency-aware candidate rank:** 265
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_52a78bebffa1d89f48c59775393aabee731c6dc5fc9b401178979e6d7be3839a`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PATZ1|entrez:23598`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
265not prioritized-2
Resistance biomarker0.000
265not prioritized-2
Tumor-intrinsic / small molecule0.000
265not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.490)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PATZ1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PATZ1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PAX5.html b/examples/html_reports/depmap_26q1/targets/PAX5.html new file mode 100644 index 0000000..abc2890 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PAX5.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PAX5 + + + + +
+ +
+

Target hypothesis report: PAX5

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PAX5
+
+
+
Target name
+
paired box 5
+
+
+
Open Targets melanoma score
+
0.563
+
+
+
+
Open Targets baseline rank
+
128
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.1088845448548971,"interquartile_range":0.14703441884732282,"maximum":0.13854687883744554,"mean":-0.03206191587252125,"measured_model_count":56,"median":-0.014464371335449124,"minimum":-0.30679469825273975,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03814987399242574,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.011626966753839703,"interquartile_range":0.04602638788189701,"maximum":0.26838932138817734,"mean":0.0402637735904481,"measured_model_count":56,"median":0.023559907731496195,"minimum":0.004857244948173928,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05765335463573671,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.011722016265201161,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03890728476821192,"pan_cancer_fraction":0.03890728476821192,"threshold":0.5},{"context_fraction":0.0,"difference":-0.03394039735099338,"pan_cancer_fraction":0.03394039735099338,"threshold":0.8}],"gene_effect_mean":0.055946069728392576,"gene_effect_median":0.039854709962933575},"dependency_probability_context_minus_non_context_median":-0.012750077624742832,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04079861111111111,"non_context_fraction":0.04079861111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.035590277777777776,"non_context_fraction":0.035590277777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05866567034018951,"gene_effect_context_minus_non_context_median":0.04088643415318896}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 130
+- **Dependency-aware candidate rank:** 130
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_adfc0d524f5bc6d987c20c279ea8a07cdc714fab64857b668ef270209b743fef`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PAX5|entrez:5079`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
130not prioritized-2
Resistance biomarker0.000
131not prioritized-3
Tumor-intrinsic / small molecule0.000
130not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.563)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PAX5 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PAX5 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PBRM1.html b/examples/html_reports/depmap_26q1/targets/PBRM1.html new file mode 100644 index 0000000..029eec9 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PBRM1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PBRM1 + + + + +
+ +
+

Target hypothesis report: PBRM1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PBRM1
+
+
+
Target name
+
polybromo 1
+
+
+
Open Targets melanoma score
+
0.636
+
+
+
+
Open Targets baseline rank
+
37
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.16479697620735534,"interquartile_range":0.3034207952026297,"maximum":0.4448525230836686,"mean":-0.022173015534992117,"measured_model_count":56,"median":-0.04422832147235136,"minimum":-0.6075030044826925,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.13862381899527437,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005101405183288445,"interquartile_range":0.08901199505560088,"maximum":0.6419488286639063,"mean":0.07271163892119407,"measured_model_count":56,"median":0.025873981311805343,"minimum":0.00026959172539142045,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09411340023888932,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.039527938309002454,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.07816934720908231,"pan_cancer_fraction":0.09602649006622517,"threshold":0.5},{"context_fraction":0.0,"difference":-0.026490066225165563,"pan_cancer_fraction":0.026490066225165563,"threshold":0.8}],"gene_effect_mean":0.1175627255548197,"gene_effect_median":0.0838554947391201},"dependency_probability_context_minus_non_context_median":-0.042001975597918496,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.08196924603174605,"non_context_fraction":0.0998263888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.027777777777777776,"non_context_fraction":0.027777777777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.12327758026929003,"gene_effect_context_minus_non_context_median":0.08746995500031005}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 44
+- **Dependency-aware candidate rank:** 44
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_42b9a8e63a0488f33b8490d1f61763014ede5eb8c77c504ee0c1575f9bb8103a`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PBRM1|entrez:55193`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
44not prioritized-7
Resistance biomarker0.000
46not prioritized-9
Tumor-intrinsic / small molecule0.000
44not prioritized-7
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.636)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PBRM1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PBRM1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PDCD1.html b/examples/html_reports/depmap_26q1/targets/PDCD1.html new file mode 100644 index 0000000..1964236 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PDCD1.html @@ -0,0 +1,441 @@ + + + + +TargetIntel-IO report: PDCD1 + + + + +
+ +
+

Target hypothesis report: PDCD1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PDCD1
+
+
+
Target name
+
programmed cell death 1
+
+
+
Open Targets melanoma score
+
0.630
+
+
+
+
Open Targets baseline rank
+
44
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.07586317533990133,"interquartile_range":0.1536254155593421,"maximum":0.3225183637936061,"mean":-0.0001670624551346131,"measured_model_count":56,"median":-0.01957298536283847,"minimum":-0.3110634393914682,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07776224021944075,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008553814788841528,"interquartile_range":0.03284445323467796,"maximum":0.2333724479616654,"mean":0.04119029126229425,"measured_model_count":56,"median":0.02164243704516978,"minimum":0.0004402840326518532,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04139826802351949,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00541766690770247,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.0328050342124573,"gene_effect_median":-0.05178660616511987},"dependency_probability_context_minus_non_context_median":0.005614043375074734,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03439972337556283,"gene_effect_context_minus_non_context_median":-0.05289749726051174}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":100.0}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 2
+- **Dependency-aware candidate rank:** 4
+- **Rank delta:** 2
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_9818f6abb8a6b180f62f5aa111d227fb8de1d192e5557d65ab9e3e5887da73a9`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PDCD1|entrez:5133`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
anti-PD-1 combination target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
block / inhibit
+
+
+
Best modality
+
antibody / IO-combination target
+
+
+
Resistance axis
+
checkpoint_redundancy
+
+
+
Matched resistance programs
+
Checkpoint redundancy
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.827
2high42
Resistance biomarker0.498
8medium36
Tumor-intrinsic / small molecule0.144
10low34
+
+ +
+

Evidence for

+
    +
  • Immune checkpoint biology
    • +
  • Potential compensatory inhibitory pathway after PD-1 blockade
    • +
  • Surface-accessible immune receptor or ligand
    • +
  • Moderate Open Targets melanoma association score (0.630)
    • +
  • Maps to curated anti-PD-1 resistance program: Checkpoint redundancy
    • +
  • Stable role classifier confidence is high
    • +
  • Antibody fit is high
    • +
  • IO-combination fit is high
    • +
  • Checkpoint-axis biology supports anti-PD-1 combination rationale
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Crowded IO target space
    • +
  • Expression may reflect exhausted immune-cell abundance rather than causal resistance in all tumors
    • +
  • Patient selection may be required
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
high confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.240
+
+
+
+
Main limitation
+
No major limitation flagged by current MVP rules
+
+
+

Uncertainty reason: Main limitation: No major limitation flagged by current MVP rules

+

Deprioritization reason: No strong deprioritization reason from current MVP rules

+
+ +
+

Recommended next validation experiment

+

Validation category: immune-checkpoint functional validation

+

Next experiment: Validate PDCD1 expression in exhausted CD8 T-cell populations from anti-PD-1-resistant melanoma samples and test blockade in a melanoma/T-cell co-culture assay.

+

Rationale: This would test whether the candidate marks a relevant checkpoint axis and whether blockade can improve anti-tumor T-cell activity.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PDCD1LG2.html b/examples/html_reports/depmap_26q1/targets/PDCD1LG2.html new file mode 100644 index 0000000..7ef172f --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PDCD1LG2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PDCD1LG2 + + + + +
+ +
+

Target hypothesis report: PDCD1LG2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PDCD1LG2
+
+
+
Target name
+
programmed cell death 1 ligand 2
+
+
+
Open Targets melanoma score
+
0.467
+
+
+
+
Open Targets baseline rank
+
285
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.05816013705757744,"interquartile_range":0.11189371167739326,"maximum":0.3771133025892327,"mean":0.1072155941052707,"measured_model_count":56,"median":0.09145888055795778,"minimum":-0.11873669255379785,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1700538487349707,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0037372367702815036,"interquartile_range":0.010498710407831242,"maximum":0.04984001631579498,"mean":0.01034691838648634,"measured_model_count":56,"median":0.007611086135415668,"minimum":0.0007532072106878847,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.014235947178112746,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0007237109323909741,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.003496438269033439,"gene_effect_median":-0.01053245350068871},"dependency_probability_context_minus_non_context_median":-0.0008202855656675306,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0036664040182225466,"gene_effect_context_minus_non_context_median":-0.011543940179797221}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 285
+- **Dependency-aware candidate rank:** 285
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_7a088b831eece2f58f819654d1362e7bdf2ef4a776cf8e18f8aebffc15ca7533`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PDCD1LG2|entrez:80380`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
285not prioritized0
Resistance biomarker0.000
285not prioritized0
Tumor-intrinsic / small molecule0.000
285not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.467)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PDCD1LG2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PDCD1LG2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PDGFRA.html b/examples/html_reports/depmap_26q1/targets/PDGFRA.html new file mode 100644 index 0000000..1188e22 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PDGFRA.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PDGFRA + + + + +
+ +
+

Target hypothesis report: PDGFRA

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PDGFRA
+
+
+
Target name
+
platelet derived growth factor receptor alpha
+
+
+
Open Targets melanoma score
+
0.666
+
+
+
+
Open Targets baseline rank
+
27
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.2533602866327354,"interquartile_range":0.12572359618727533,"maximum":0.09819146945773913,"mean":-0.1964573159629175,"measured_model_count":56,"median":-0.18362142417989624,"minimum":-0.6817254249652711,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.12763669044546008,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.05686242904454657,"interquartile_range":0.10437702981984269,"maximum":0.8490391727005575,"mean":0.15035186602067654,"measured_model_count":56,"median":0.10237428471529833,"minimum":0.004926867884639238,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.16123945886438926,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.005719797835777085,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.016792809839167457,"pan_cancer_fraction":0.07036423841059603,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.0069772942289498575,"pan_cancer_fraction":0.024834437086092714,"threshold":0.8}],"gene_effect_mean":0.0009692030684934905,"gene_effect_median":-0.012922540720722964},"dependency_probability_context_minus_non_context_median":0.006398554638674142,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.017609126984126984,"non_context_fraction":0.07118055555555555,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.007316468253968256,"non_context_fraction":0.025173611111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0010163171065452614,"gene_effect_context_minus_non_context_median":-0.014001735734635062}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 34
+- **Dependency-aware candidate rank:** 34
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_06444ce3e66588c496d27ac638be6bb38eeb12041940c1a78bef8333b5c6fc4a`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PDGFRA|entrez:5156`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
34not prioritized-7
Resistance biomarker0.000
36not prioritized-9
Tumor-intrinsic / small molecule0.004
29not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.666)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PDGFRA lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PDGFRA in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PDGFRB.html b/examples/html_reports/depmap_26q1/targets/PDGFRB.html new file mode 100644 index 0000000..aa2abff --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PDGFRB.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PDGFRB + + + + +
+ +
+

Target hypothesis report: PDGFRB

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PDGFRB
+
+
+
Target name
+
platelet derived growth factor receptor beta
+
+
+
Open Targets melanoma score
+
0.647
+
+
+
+
Open Targets baseline rank
+
32
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.1533298824968127,"interquartile_range":0.19320922610917157,"maximum":0.28340888139004716,"mean":-0.060062062579911354,"measured_model_count":56,"median":-0.07629056372993706,"minimum":-0.39446206414889434,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03987934361235887,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.015103099225042448,"interquartile_range":0.0632267186652943,"maximum":0.3425415988456145,"mean":0.06299017017119603,"measured_model_count":56,"median":0.04135928988080292,"minimum":0.0019110310657141872,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07832981789033674,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0003210148213632427,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.027317880794701987,"pan_cancer_fraction":0.027317880794701987,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.8}],"gene_effect_mean":0.02697270760391063,"gene_effect_median":-0.004247497673512929},"dependency_probability_context_minus_non_context_median":-0.0003210148213632427,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.028645833333333332,"non_context_fraction":0.028645833333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.028283880890211624,"gene_effect_context_minus_non_context_median":-0.004668926549293628}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 39
+- **Dependency-aware candidate rank:** 39
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_5ed44e334e2ef15392edfd4102041f8826e32da84e5286cbc3a6327b87e4aba5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PDGFRB|entrez:5159`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
39not prioritized-7
Resistance biomarker0.000
41not prioritized-9
Tumor-intrinsic / small molecule0.000
34not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.647)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PDGFRB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PDGFRB in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PER1.html b/examples/html_reports/depmap_26q1/targets/PER1.html new file mode 100644 index 0000000..d69e6dd --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PER1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PER1 + + + + +
+ +
+

Target hypothesis report: PER1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PER1
+
+
+
Target name
+
period circadian regulator 1
+
+
+
Open Targets melanoma score
+
0.559
+
+
+
+
Open Targets baseline rank
+
136
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.03086128251576374,"interquartile_range":0.1190081708614905,"maximum":0.28867284705445984,"mean":0.08991771449382154,"measured_model_count":56,"median":0.09976442986895973,"minimum":-0.14227097328950417,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14986945337725424,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.004534189618738785,"interquartile_range":0.010004848593089312,"maximum":0.058565348415219765,"mean":0.01211886409344396,"measured_model_count":56,"median":0.00844002980337798,"minimum":0.0010624023055272463,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.014539038211828097,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0019063463449663235,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.04444946194894421,"gene_effect_median":-0.03379244700598999},"dependency_probability_context_minus_non_context_median":0.0019906329524445677,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.04661019968257342,"gene_effect_context_minus_non_context_median":-0.03581383836467189}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 138
+- **Dependency-aware candidate rank:** 138
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e45fc2c45aeb6d7ca3a19443b9023d03f7256f880720c11bc9fe3f99b0654932`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PER1|entrez:5187`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
138not prioritized-2
Resistance biomarker0.000
139not prioritized-3
Tumor-intrinsic / small molecule0.000
138not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.559)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PER1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PER1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PHOX2B.html b/examples/html_reports/depmap_26q1/targets/PHOX2B.html new file mode 100644 index 0000000..2444f96 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PHOX2B.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PHOX2B + + + + +
+ +
+

Target hypothesis report: PHOX2B

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PHOX2B
+
+
+
Target name
+
paired like homeobox 2B
+
+
+
Open Targets melanoma score
+
0.568
+
+
+
+
Open Targets baseline rank
+
122
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.03090500613816374,"interquartile_range":0.1454216583568894,"maximum":0.41213169639238095,"mean":0.09788717649919845,"measured_model_count":56,"median":0.09159221551687652,"minimum":-0.36911677256516784,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.17632666449505313,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.003112541444687733,"interquartile_range":0.014775071158484721,"maximum":0.23396617386517476,"mean":0.01769875721200918,"measured_model_count":56,"median":0.009699743764547134,"minimum":0.0001502625548091212,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.017887612603172454,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0018507177720212351,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.008278145695364239,"pan_cancer_fraction":0.008278145695364239,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.01084695289342287,"gene_effect_median":-0.02208734598313361},"dependency_probability_context_minus_non_context_median":0.002024788990909656,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.008680555555555556,"non_context_fraction":0.008680555555555556,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.011374235325742013,"gene_effect_context_minus_non_context_median":-0.02260278248246078}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 124
+- **Dependency-aware candidate rank:** 124
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_228d291ac2f6a23ffec499075c1b68b8ecc23d71697eb81d38a9d369ef3f5433`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PHOX2B|entrez:8929`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
124not prioritized-2
Resistance biomarker0.000
125not prioritized-3
Tumor-intrinsic / small molecule0.000
124not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.568)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PHOX2B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PHOX2B in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PIK3CA.html b/examples/html_reports/depmap_26q1/targets/PIK3CA.html new file mode 100644 index 0000000..11bef9b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PIK3CA.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PIK3CA + + + + +
+ +
+

Target hypothesis report: PIK3CA

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PIK3CA
+
+
+
Target name
+
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
+
+
+
Open Targets melanoma score
+
0.510
+
+
+
+
Open Targets baseline rank
+
238
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.3926242184937075,"interquartile_range":0.2029757534853182,"maximum":0.11683662531876016,"mean":-0.2863294055143963,"measured_model_count":56,"median":-0.2939677758894327,"minimum":-0.6891435375577224,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.18964846500838928,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.10419575803316142,"interquartile_range":0.2948881615068477,"maximum":0.8761345885208559,"mean":0.2630345989934602,"measured_model_count":56,"median":0.20917938968000044,"minimum":0.005989732137504378,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.39908391954000916,"threshold_fractions":[{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.2509124426941805,"dependency_probability_threshold_fractions":[{"context_fraction":0.14285714285714285,"difference":-0.32568590350047305,"pan_cancer_fraction":0.4685430463576159,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.22339167455061498,"pan_cancer_fraction":0.2591059602649007,"threshold":0.8}],"gene_effect_mean":0.21877902229053886,"gene_effect_median":0.147776932467173},"dependency_probability_context_minus_non_context_median":-0.27244642186733176,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.14285714285714285,"difference":-0.34151785714285715,"non_context_fraction":0.484375,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.2342509920634921,"non_context_fraction":0.2699652777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.2294141136518844,"gene_effect_context_minus_non_context_median":0.1621624007565165}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 240
+- **Dependency-aware candidate rank:** 240
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_4df18a962ebbf65e99c3409d7123502f53b0043b2756159fb600b19536fbd4e7`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PIK3CA|entrez:5290`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
240not prioritized-2
Resistance biomarker0.000
240not prioritized-2
Tumor-intrinsic / small molecule0.000
240not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.510)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PIK3CA lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PIK3CA in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PIK3CB.html b/examples/html_reports/depmap_26q1/targets/PIK3CB.html new file mode 100644 index 0000000..ecd601a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PIK3CB.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PIK3CB + + + + +
+ +
+

Target hypothesis report: PIK3CB

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PIK3CB
+
+
+
Target name
+
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta
+
+
+
Open Targets melanoma score
+
0.461
+
+
+
+
Open Targets baseline rank
+
295
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.3628942051472416,"interquartile_range":0.3084161617199057,"maximum":0.2007035324921781,"mean":-0.24425789928383776,"measured_model_count":56,"median":-0.16430375541703418,"minimum":-1.0565353629457381,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.05447804342733584,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0338053475717404,"interquartile_range":0.32662358663277163,"maximum":0.9951060501601744,"mean":0.24446303063227964,"measured_model_count":56,"median":0.08159559753139387,"minimum":0.003445438951288355,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.36042893420451205,"threshold_fractions":[{"denominator":56,"fraction":0.19642857142857142,"numerator":11,"threshold":0.5},{"denominator":56,"fraction":0.125,"numerator":7,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03392674840806498,"dependency_probability_threshold_fractions":[{"context_fraction":0.19642857142857142,"difference":0.14427625354777673,"pan_cancer_fraction":0.052152317880794705,"threshold":0.5},{"context_fraction":0.125,"difference":0.10182119205298013,"pan_cancer_fraction":0.023178807947019868,"threshold":0.8}],"gene_effect_mean":-0.12110798632711998,"gene_effect_median":-0.07767750940672569},"dependency_probability_context_minus_non_context_median":0.036085834076885696,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.19642857142857142,"difference":0.15128968253968253,"non_context_fraction":0.04513888888888889,"threshold":0.5},{"context_fraction":0.125,"difference":0.10677083333333333,"non_context_fraction":0.018229166666666668,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.12699518010691052,"gene_effect_context_minus_non_context_median":-0.08100154515365403}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 295
+- **Dependency-aware candidate rank:** 295
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_68a06d35621318866e9ee23cbdabe5f902054c1bc59017ea3399e07b35fe2263`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PIK3CB|entrez:5291`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
295not prioritized0
Resistance biomarker0.000
295not prioritized0
Tumor-intrinsic / small molecule0.000
295not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.461)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PIK3CB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PIK3CB in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PIK3R1.html b/examples/html_reports/depmap_26q1/targets/PIK3R1.html new file mode 100644 index 0000000..1fa43d9 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PIK3R1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PIK3R1 + + + + +
+ +
+

Target hypothesis report: PIK3R1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PIK3R1
+
+
+
Target name
+
phosphoinositide-3-kinase regulatory subunit 1
+
+
+
Open Targets melanoma score
+
0.568
+
+
+
+
Open Targets baseline rank
+
120
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.03837001138190876,"interquartile_range":0.2663987206667829,"maximum":0.6800493745081021,"mean":0.08456744924235596,"measured_model_count":56,"median":0.07693671363161786,"minimum":-0.35984488150574573,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.22802870928487412,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.002696889421791202,"interquartile_range":0.02538843082361781,"maximum":0.3583474394213573,"mean":0.029228288317221747,"measured_model_count":56,"median":0.009912816186445288,"minimum":2.073664012003869e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02808532024540901,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.014832118256498852,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.037251655629139076,"pan_cancer_fraction":0.037251655629139076,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014900662251655629,"pan_cancer_fraction":0.014900662251655629,"threshold":0.8}],"gene_effect_mean":0.10651670027471553,"gene_effect_median":0.08919807712937035},"dependency_probability_context_minus_non_context_median":-0.015442377728272505,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0390625,"non_context_fraction":0.0390625,"threshold":0.5},{"context_fraction":0.0,"difference":-0.015625,"non_context_fraction":0.015625,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.11169459542695864,"gene_effect_context_minus_non_context_median":0.09247730567501805}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 122
+- **Dependency-aware candidate rank:** 122
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_1393cb6757d8dc0f45b47039e36ffd70ee45fae07bf726e9baf4c8a3f6e2103e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PIK3R1|entrez:5295`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
122not prioritized-2
Resistance biomarker0.000
123not prioritized-3
Tumor-intrinsic / small molecule0.000
122not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.568)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PIK3R1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PIK3R1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PLCG1.html b/examples/html_reports/depmap_26q1/targets/PLCG1.html new file mode 100644 index 0000000..98ce699 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PLCG1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PLCG1 + + + + +
+ +
+

Target hypothesis report: PLCG1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PLCG1
+
+
+
Target name
+
phospholipase C gamma 1
+
+
+
Open Targets melanoma score
+
0.520
+
+
+
+
Open Targets baseline rank
+
213
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.056839178567636914,"interquartile_range":0.1366667894574548,"maximum":0.2632874125269735,"mean":0.015463572567236987,"measured_model_count":56,"median":0.02301043378246097,"minimum":-0.31270963525517503,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07982761088981788,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008139315582853286,"interquartile_range":0.028860875205757974,"maximum":0.15688435402465603,"mean":0.02672685825084457,"measured_model_count":56,"median":0.01620788943023691,"minimum":0.001386197774518595,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03700019078861126,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0019000417051095453,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.014900662251655629,"pan_cancer_fraction":0.014900662251655629,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0074503311258278145,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.8}],"gene_effect_mean":0.00612146641388798,"gene_effect_median":-0.001184567417808969},"dependency_probability_context_minus_non_context_median":-0.0019422027936741026,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.015625,"non_context_fraction":0.015625,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0078125,"non_context_fraction":0.0078125,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006419037697896417,"gene_effect_context_minus_non_context_median":-0.001184567417808969}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 215
+- **Dependency-aware candidate rank:** 215
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_482771f988f3f29e984d70cf85da59bb1aa6e17e1531c8adae1cc9c51f9c8760`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PLCG1|entrez:5335`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
215not prioritized-2
Resistance biomarker0.000
215not prioritized-2
Tumor-intrinsic / small molecule0.000
215not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.520)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PLCG1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PLCG1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PLXNB2.html b/examples/html_reports/depmap_26q1/targets/PLXNB2.html new file mode 100644 index 0000000..74c74b9 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PLXNB2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PLXNB2 + + + + +
+ +
+

Target hypothesis report: PLXNB2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PLXNB2
+
+
+
Target name
+
plexin B2
+
+
+
Open Targets melanoma score
+
0.476
+
+
+
+
Open Targets baseline rank
+
277
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.016739809784034065,"interquartile_range":0.13622487385793947,"maximum":0.39172179779208477,"mean":0.09250986907465496,"measured_model_count":56,"median":0.07287237929257996,"minimum":-0.17175670111727442,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.15296468364197352,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.004153007557135326,"interquartile_range":0.013950921193240031,"maximum":0.06888512238549067,"mean":0.014042510139181064,"measured_model_count":56,"median":0.010539954198750902,"minimum":0.0007187168733285372,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.018103928750375357,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.001844309460650593,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.00753321497055269,"gene_effect_median":-0.02554119096021508},"dependency_probability_context_minus_non_context_median":0.0019365850333818296,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.007899412920510093,"gene_effect_context_minus_non_context_median":-0.027712555322041824}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 277
+- **Dependency-aware candidate rank:** 277
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_3f46e48ad4756d530369ffcfe581396565c8d099bd09b22a76ef1acee8174cf3`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PLXNB2|entrez:23654`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
277not prioritized0
Resistance biomarker0.000
277not prioritized0
Tumor-intrinsic / small molecule0.000
277not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.476)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PLXNB2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PLXNB2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PMEL.html b/examples/html_reports/depmap_26q1/targets/PMEL.html new file mode 100644 index 0000000..4c05a6d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PMEL.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PMEL + + + + +
+ +
+

Target hypothesis report: PMEL

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PMEL
+
+
+
Target name
+
premelanosome protein
+
+
+
Open Targets melanoma score
+
0.482
+
+
+
+
Open Targets baseline rank
+
272
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.2400016434090602,"interquartile_range":0.20927280835888581,"maximum":0.10533139840966646,"mean":-0.1324141548909928,"measured_model_count":56,"median":-0.13772450645851692,"minimum":-0.5253708137934905,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.030728835050174378,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.026923220466624286,"interquartile_range":0.11529393681860517,"maximum":0.6538000146205327,"mean":0.10254274521418213,"measured_model_count":56,"median":0.07252845996137892,"minimum":0.0052803313388520646,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14221715728522946,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.025257741705418175,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.015373699148533584,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.04555846417682345,"gene_effect_median":-0.05009722593245222},"dependency_probability_context_minus_non_context_median":0.02557812719302823,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.016121031746031744,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.04777311174097448,"gene_effect_context_minus_non_context_median":-0.050757805677101794}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 272
+- **Dependency-aware candidate rank:** 272
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_3e1ddb6994d9b01df9aaf937b63d46b899afd5271a876063545dcd59eb416b77`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PMEL|entrez:6490`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
272not prioritized0
Resistance biomarker0.000
272not prioritized0
Tumor-intrinsic / small molecule0.000
272not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.482)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PMEL lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PMEL in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PMS2.html b/examples/html_reports/depmap_26q1/targets/PMS2.html new file mode 100644 index 0000000..bd11f69 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PMS2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PMS2 + + + + +
+ +
+

Target hypothesis report: PMS2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PMS2
+
+
+
Target name
+
PMS1 homolog 2, mismatch repair system component
+
+
+
Open Targets melanoma score
+
0.522
+
+
+
+
Open Targets baseline rank
+
204
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.055192771409656866,"interquartile_range":0.14739073725694488,"maximum":0.38523856553318947,"mean":0.12017485590510182,"measured_model_count":56,"median":0.11394202876623996,"minimum":-0.18820183094115384,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.20258350866660174,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0024973371316166187,"interquartile_range":0.011151597509534487,"maximum":0.1140254341691312,"mean":0.013196658557872531,"measured_model_count":56,"median":0.005788126840964296,"minimum":0.000614212746071096,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.013648934641151106,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0013209939148119887,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.002652219854245824,"gene_effect_median":-0.003071921834496366},"dependency_probability_context_minus_non_context_median":-0.0013835349040086445,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.002781147208271606,"gene_effect_context_minus_non_context_median":-0.0034778106978098494}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 206
+- **Dependency-aware candidate rank:** 206
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_4c92dca4778a7b62d4c7fa8dcc8bbfa1cd7a41f47d547524cbf282cd897c1a44`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PMS2|entrez:5395`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
206not prioritized-2
Resistance biomarker0.000
206not prioritized-2
Tumor-intrinsic / small molecule0.000
206not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.522)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PMS2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PMS2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/POLD1.html b/examples/html_reports/depmap_26q1/targets/POLD1.html new file mode 100644 index 0000000..8525593 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/POLD1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: POLD1 + + + + +
+ +
+

Target hypothesis report: POLD1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
POLD1
+
+
+
Target name
+
DNA polymerase delta 1, catalytic subunit
+
+
+
Open Targets melanoma score
+
0.571
+
+
+
+
Open Targets baseline rank
+
113
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-2.2555126211580916,"interquartile_range":0.39839849563843344,"maximum":-1.2480701178321307,"mean":-2.047820149678809,"measured_model_count":56,"median":-2.0748283180612623,"minimum":-2.9554520157837465,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.8571141255196582,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":1.0,"interquartile_range":0.0,"maximum":1.0,"mean":0.9997822098855916,"measured_model_count":56,"median":1.0,"minimum":0.9959820103493834,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0,"pan_cancer_fraction":1.0,"threshold":0.5},{"context_fraction":1.0,"difference":0.0016556291390728006,"pan_cancer_fraction":0.9983443708609272,"threshold":0.8}],"gene_effect_mean":0.1497703485222317,"gene_effect_median":0.11850612430526519},"dependency_probability_context_minus_non_context_median":0.0,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0,"non_context_fraction":1.0,"threshold":0.5},{"context_fraction":1.0,"difference":0.0017361111111111605,"non_context_fraction":0.9982638888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.15705085157539633,"gene_effect_context_minus_non_context_median":0.1260869679559562}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 115
+- **Dependency-aware candidate rank:** 115
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_5159ae65cf07b2879523733bae0a6ffe7f9fc31ddffcec704c8a72a381f0435e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:POLD1|entrez:5424`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
115not prioritized-2
Resistance biomarker0.000
116not prioritized-3
Tumor-intrinsic / small molecule0.000
115not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.571)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: POLD1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for POLD1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/POLE.html b/examples/html_reports/depmap_26q1/targets/POLE.html new file mode 100644 index 0000000..2112977 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/POLE.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: POLE + + + + +
+ +
+

Target hypothesis report: POLE

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
POLE
+
+
+
Target name
+
DNA polymerase epsilon, catalytic subunit
+
+
+
Open Targets melanoma score
+
0.645
+
+
+
+
Open Targets baseline rank
+
34
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.7686221790937948,"interquartile_range":0.49019054275043095,"maximum":-0.8864340679478432,"mean":-1.5445676761570897,"measured_model_count":56,"median":-1.512475654018234,"minimum":-2.691654838050905,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.2784316363433639,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9937930644505688,"interquartile_range":0.006206935528471291,"maximum":1.0,"mean":0.995224255991806,"measured_model_count":56,"median":0.9994873578486327,"minimum":0.9596816798789393,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9999999999790401,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0003169851513706856,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0033112582781457123,"pan_cancer_fraction":0.9966887417218543,"threshold":0.5},{"context_fraction":1.0,"difference":0.0066225165562914245,"pan_cancer_fraction":0.9933774834437086,"threshold":0.8}],"gene_effect_mean":0.048138593469633006,"gene_effect_median":0.06269718431369808},"dependency_probability_context_minus_non_context_median":-0.0003307136808244904,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.00347222222222221,"non_context_fraction":0.9965277777777778,"threshold":0.5},{"context_fraction":1.0,"difference":0.00694444444444442,"non_context_fraction":0.9930555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0504786639855177,"gene_effect_context_minus_non_context_median":0.06884103214607751}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 41
+- **Dependency-aware candidate rank:** 41
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ac55f483b1302b3f00e48106eb5cfa1a9b90fc645561cccda6bae70e9c563754`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:POLE|entrez:5426`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
41not prioritized-7
Resistance biomarker0.000
43not prioritized-9
Tumor-intrinsic / small molecule0.000
41not prioritized-7
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.645)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: POLE lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for POLE in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/POLQ.html b/examples/html_reports/depmap_26q1/targets/POLQ.html new file mode 100644 index 0000000..eb88e57 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/POLQ.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: POLQ + + + + +
+ +
+

Target hypothesis report: POLQ

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
POLQ
+
+
+
Target name
+
DNA polymerase theta
+
+
+
Open Targets melanoma score
+
0.598
+
+
+
+
Open Targets baseline rank
+
71
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.39901280322112664,"interquartile_range":0.22486613245338025,"maximum":0.05185493446814471,"mean":-0.29887660161957547,"measured_model_count":56,"median":-0.2878340309311357,"minimum":-1.0029113047323868,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.1741466707677464,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.10011844551019167,"interquartile_range":0.2983836803191332,"maximum":0.9620343470390572,"mean":0.2837371101307486,"measured_model_count":56,"median":0.2125326319656341,"minimum":0.008170163671162276,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.39850212582932487,"threshold_fractions":[{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0669935904527213,"dependency_probability_threshold_fractions":[{"context_fraction":0.17857142857142858,"difference":-0.09295175023651844,"pan_cancer_fraction":0.271523178807947,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.020577105014191112,"pan_cancer_fraction":0.056291390728476824,"threshold":0.8}],"gene_effect_mean":0.05139503211426255,"gene_effect_median":0.04601330147269167},"dependency_probability_context_minus_non_context_median":-0.07063337771572298,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.17857142857142858,"difference":-0.09747023809523811,"non_context_fraction":0.2760416666666667,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.021577380952380952,"non_context_fraction":0.057291666666666664,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05389340173092816,"gene_effect_context_minus_non_context_median":0.04761758869659821}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 75
+- **Dependency-aware candidate rank:** 75
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_7e15da50fa60be32c1cd38f67f5879e2675d40bbd14334ab0cea898a93f414d0`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:POLQ|entrez:10721`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
75not prioritized-4
Resistance biomarker0.000
77not prioritized-6
Tumor-intrinsic / small molecule0.000
75not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.598)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: POLQ lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for POLQ in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/POT1.html b/examples/html_reports/depmap_26q1/targets/POT1.html new file mode 100644 index 0000000..62a5b5d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/POT1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: POT1 + + + + +
+ +
+

Target hypothesis report: POT1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
POT1
+
+
+
Target name
+
protection of telomeres 1
+
+
+
Open Targets melanoma score
+
0.707
+
+
+
+
Open Targets baseline rank
+
18
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.5635819718766873,"interquartile_range":0.26505416396453424,"maximum":-0.06251627466615711,"mean":-0.44935742447896204,"measured_model_count":56,"median":-0.42293149499519567,"minimum":-1.1041577617026235,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.2985278079121531,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.23950012403748594,"interquartile_range":0.43079365738697023,"maximum":0.9717428477917653,"mean":0.4692116059277039,"measured_model_count":56,"median":0.4805480850355817,"minimum":0.052371667803121746,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.6702937814244562,"threshold_fractions":[{"denominator":56,"fraction":0.48214285714285715,"numerator":27,"threshold":0.5},{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.06372445254465897,"dependency_probability_threshold_fractions":[{"context_fraction":0.48214285714285715,"difference":0.037606433301797526,"pan_cancer_fraction":0.4445364238410596,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.0740302743614002,"pan_cancer_fraction":0.21688741721854304,"threshold":0.8}],"gene_effect_mean":-0.009134301384618015,"gene_effect_median":-0.006132470396260303},"dependency_probability_context_minus_non_context_median":0.0659224405327859,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.48214285714285715,"difference":0.039434523809523836,"non_context_fraction":0.4427083333333333,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.07762896825396826,"non_context_fraction":0.2204861111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.009578329924148365,"gene_effect_context_minus_non_context_median":-0.0066925601843810245}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 25
+- **Dependency-aware candidate rank:** 25
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2f1a268f12b0088d5c4803f296352ff0f6de2420d06ccc515894446a27792f67`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:POT1|entrez:25913`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
25not prioritized-7
Resistance biomarker0.000
28not prioritized-10
Tumor-intrinsic / small molecule0.012
21not prioritized-3
+
+ +
+

Evidence for

+
    +
  • High Open Targets melanoma association score (0.707)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: POT1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for POT1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/POU2AF1.html b/examples/html_reports/depmap_26q1/targets/POU2AF1.html new file mode 100644 index 0000000..e9525c7 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/POU2AF1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: POU2AF1 + + + + +
+ +
+

Target hypothesis report: POU2AF1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
POU2AF1
+
+
+
Target name
+
POU class 2 homeobox associating factor 1
+
+
+
Open Targets melanoma score
+
0.483
+
+
+
+
Open Targets baseline rank
+
270
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06144299452441082,"interquartile_range":0.16721482908748944,"maximum":0.25598488770962047,"mean":0.012489908148375358,"measured_model_count":56,"median":0.010038770990871998,"minimum":-0.29326722424317075,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10577183456307862,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0067145750699271175,"interquartile_range":0.03315913931173384,"maximum":0.24566225721850554,"mean":0.033463484590643744,"measured_model_count":56,"median":0.02258460016959892,"minimum":0.0018220453406680766,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03987371438166096,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0009895798520293334,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04304635761589404,"pan_cancer_fraction":0.04304635761589404,"threshold":0.5},{"context_fraction":0.0,"difference":-0.03228476821192053,"pan_cancer_fraction":0.03228476821192053,"threshold":0.8}],"gene_effect_mean":0.05904330364299119,"gene_effect_median":0.017333354677480317},"dependency_probability_context_minus_non_context_median":-0.0009895798520293334,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04513888888888889,"non_context_fraction":0.04513888888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.033854166666666664,"non_context_fraction":0.033854166666666664,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.06191346423674769,"gene_effect_context_minus_non_context_median":0.017843546337038}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 271
+- **Dependency-aware candidate rank:** 271
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_c5e1ddb917a46809f6510c9d7f77229a549d080031e1d2daab49de3dd332fcc5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:POU2AF1|entrez:5450`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
271not prioritized-1
Resistance biomarker0.000
271not prioritized-1
Tumor-intrinsic / small molecule0.000
271not prioritized-1
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.483)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: POU2AF1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for POU2AF1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PPP2R1A.html b/examples/html_reports/depmap_26q1/targets/PPP2R1A.html new file mode 100644 index 0000000..bc9f7aa --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PPP2R1A.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PPP2R1A + + + + +
+ +
+

Target hypothesis report: PPP2R1A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PPP2R1A
+
+
+
Target name
+
protein phosphatase 2 scaffold subunit Aalpha
+
+
+
Open Targets melanoma score
+
0.552
+
+
+
+
Open Targets baseline rank
+
153
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.6847459075068567,"interquartile_range":0.46834225071689306,"maximum":-0.4896122806584271,"mean":-1.4730530296832878,"measured_model_count":56,"median":-1.471863264456811,"minimum":-2.8617405459735346,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.2164036567899636,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.991270804140258,"interquartile_range":0.008718189144905297,"maximum":1.0,"mean":0.9648698306535062,"measured_model_count":56,"median":0.9991692822150705,"minimum":0.4482521452993049,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9999889932851633,"threshold_fractions":[{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.5},{"denominator":56,"fraction":0.9285714285714286,"numerator":52,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.01656030182956203,"dependency_probability_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":0.12204351939451275,"pan_cancer_fraction":0.8600993377483444,"threshold":0.5},{"context_fraction":0.9285714285714286,"difference":0.15456480605487233,"pan_cancer_fraction":0.7740066225165563,"threshold":0.8}],"gene_effect_mean":-0.3861167984464926,"gene_effect_median":-0.3418188697362825},"dependency_probability_context_minus_non_context_median":0.01846219532556903,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":0.12797619047619047,"non_context_fraction":0.8541666666666666,"threshold":0.5},{"context_fraction":0.9285714285714286,"difference":0.16207837301587302,"non_context_fraction":0.7664930555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.4048863650376413,"gene_effect_context_minus_non_context_median":-0.3596159217731978}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 155
+- **Dependency-aware candidate rank:** 155
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_74a0b3242fc0b704162d1eda858578c031f68476245584d07d91428b05e8a3ec`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PPP2R1A|entrez:5518`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
155not prioritized-2
Resistance biomarker0.000
156not prioritized-3
Tumor-intrinsic / small molecule0.000
155not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.552)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PPP2R1A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PPP2R1A in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PPP6C.html b/examples/html_reports/depmap_26q1/targets/PPP6C.html new file mode 100644 index 0000000..f9ab5fa --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PPP6C.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PPP6C + + + + +
+ +
+

Target hypothesis report: PPP6C

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PPP6C
+
+
+
Target name
+
protein phosphatase 6 catalytic subunit
+
+
+
Open Targets melanoma score
+
0.696
+
+
+
+
Open Targets baseline rank
+
22
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.0180315911310092,"interquartile_range":0.5621537586484284,"maximum":0.11025640550708837,"mean":-0.7830457115397375,"measured_model_count":56,"median":-0.781903782242473,"minimum":-2.174202672852065,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.4558778324825807,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.5280855865269243,"interquartile_range":0.4428703885392822,"maximum":1.0,"mean":0.7228752811217215,"measured_model_count":56,"median":0.8982627669210668,"minimum":0.012641297187679104,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9709559750662065,"threshold_fractions":[{"denominator":56,"fraction":0.75,"numerator":42,"threshold":0.5},{"denominator":56,"fraction":0.6428571428571429,"numerator":36,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.3472877202917415,"dependency_probability_threshold_fractions":[{"context_fraction":0.75,"difference":0.20281456953642385,"pan_cancer_fraction":0.5471854304635762,"threshold":0.5},{"context_fraction":0.6428571428571429,"difference":0.34236045411542104,"pan_cancer_fraction":0.30049668874172186,"threshold":0.8}],"gene_effect_mean":-0.2727741134536048,"gene_effect_median":-0.2858027333400428},"dependency_probability_context_minus_non_context_median":0.36076391864076207,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.75,"difference":0.21267361111111116,"non_context_fraction":0.5373263888888888,"threshold":0.5},{"context_fraction":0.6428571428571429,"difference":0.3590029761904762,"non_context_fraction":0.2838541666666667,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.28603396619093313,"gene_effect_context_minus_non_context_median":-0.29247517365734954}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":100.0}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 29
+- **Dependency-aware candidate rank:** 29
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e813ac41ad9a377599b11ff70abe02e35879024028640b8247086bcc703ff14f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PPP6C|entrez:5537`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
29not prioritized-7
Resistance biomarker0.000
31not prioritized-9
Tumor-intrinsic / small molecule0.010
24not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.696)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PPP6C lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PPP6C in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PRDM1.html b/examples/html_reports/depmap_26q1/targets/PRDM1.html new file mode 100644 index 0000000..fc24a04 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PRDM1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PRDM1 + + + + +
+ +
+

Target hypothesis report: PRDM1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PRDM1
+
+
+
Target name
+
PR/SET domain 1
+
+
+
Open Targets melanoma score
+
0.554
+
+
+
+
Open Targets baseline rank
+
144
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.08291657465478372,"interquartile_range":0.14691125593049534,"maximum":0.31777949130823113,"mean":-0.0004918904971693967,"measured_model_count":56,"median":-0.008524764962677182,"minimum":-0.234721655796034,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06399468127571162,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.009277719511873131,"interquartile_range":0.037261079629678555,"maximum":0.19958293481324751,"mean":0.032832412014046124,"measured_model_count":56,"median":0.02097438411360496,"minimum":0.0017317366625563182,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.046538799141551686,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.008056719260326754,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.019867549668874173,"pan_cancer_fraction":0.019867549668874173,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013245033112582781,"pan_cancer_fraction":0.013245033112582781,"threshold":0.8}],"gene_effect_mean":0.048284324139614594,"gene_effect_median":0.021390234673775096},"dependency_probability_context_minus_non_context_median":-0.008296152087344494,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.020833333333333332,"non_context_fraction":0.020833333333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013888888888888888,"non_context_fraction":0.013888888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05063147878529028,"gene_effect_context_minus_non_context_median":0.022262698849266106}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 146
+- **Dependency-aware candidate rank:** 146
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_cd16d753cd3ddef3c76740851b8199ffa2f6ebce99e63fda0453ed4c9b475c2f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PRDM1|entrez:639`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
146not prioritized-2
Resistance biomarker0.000
147not prioritized-3
Tumor-intrinsic / small molecule0.000
146not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.554)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PRDM1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PRDM1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PRDM16.html b/examples/html_reports/depmap_26q1/targets/PRDM16.html new file mode 100644 index 0000000..87d9432 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PRDM16.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PRDM16 + + + + +
+ +
+

Target hypothesis report: PRDM16

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PRDM16
+
+
+
Target name
+
PR/SET domain 16
+
+
+
Open Targets melanoma score
+
0.503
+
+
+
+
Open Targets baseline rank
+
251
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.16713623178169615,"interquartile_range":0.16512730681889062,"maximum":0.2569246975507734,"mean":-0.08575797188179488,"measured_model_count":56,"median":-0.09204657993987507,"minimum":-0.4186847355613391,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0020089249628055354,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.02149112015272428,"interquartile_range":0.07412131422340887,"maximum":0.3514851749930976,"mean":0.07152261488348251,"measured_model_count":56,"median":0.04697655942427176,"minimum":0.0025971801743869516,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09561243437613315,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0005969383106331147,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.01076158940397351,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.8}],"gene_effect_mean":0.004667942636622957,"gene_effect_median":-0.007271623979965711},"dependency_probability_context_minus_non_context_median":0.0006646952881589341,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.011284722222222222,"non_context_fraction":0.011284722222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.004894856514792073,"gene_effect_context_minus_non_context_median":-0.00783918239264203}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 253
+- **Dependency-aware candidate rank:** 253
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_79a992ecc90e7d1793f3cc18415bc66ff52616ac334bd55b657f71a8ad052dd1`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PRDM16|entrez:63976`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
253not prioritized-2
Resistance biomarker0.000
253not prioritized-2
Tumor-intrinsic / small molecule0.000
253not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.503)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PRDM16 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PRDM16 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PREX2.html b/examples/html_reports/depmap_26q1/targets/PREX2.html new file mode 100644 index 0000000..e8adcae --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PREX2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PREX2 + + + + +
+ +
+

Target hypothesis report: PREX2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PREX2
+
+
+
Target name
+
phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2
+
+
+
Open Targets melanoma score
+
0.602
+
+
+
+
Open Targets baseline rank
+
68
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.06544856986628139,"interquartile_range":0.12703400620022845,"maximum":0.49542242427329963,"mean":0.13323863617645906,"measured_model_count":56,"median":0.11155773430019963,"minimum":-0.09874246278849794,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.19248257606650984,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0025839773065120717,"interquartile_range":0.009416781894391853,"maximum":0.03580333716191526,"mean":0.008801885456245927,"measured_model_count":56,"median":0.007049386132260232,"minimum":0.00015597332978287568,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.012000759200903925,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00017952494098199406,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.003603545278304976,"gene_effect_median":-0.011993756937299399},"dependency_probability_context_minus_non_context_median":-0.00018375163158879278,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0037787176182225712,"gene_effect_context_minus_non_context_median":-0.013121553883521181}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 72
+- **Dependency-aware candidate rank:** 72
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d9b385fe8911d2d959d2ecb2e0c27fe68cc63d48096199f1b99e995881308763`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PREX2|entrez:80243`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
72not prioritized-4
Resistance biomarker0.000
74not prioritized-6
Tumor-intrinsic / small molecule0.000
72not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.602)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PREX2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PREX2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PRF1.html b/examples/html_reports/depmap_26q1/targets/PRF1.html new file mode 100644 index 0000000..8f6298d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PRF1.html @@ -0,0 +1,440 @@ + + + + +TargetIntel-IO report: PRF1 + + + + +
+ +
+

Target hypothesis report: PRF1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PRF1
+
+
+
Target name
+
perforin 1
+
+
+
Open Targets melanoma score
+
0.529
+
+
+
+
Open Targets baseline rank
+
189
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.05478050797948658,"interquartile_range":0.09711305586290947,"maximum":0.4078675016027466,"mean":-0.0015226298621399592,"measured_model_count":56,"median":0.0047451788481697,"minimum":-0.22679163161826915,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.042332547883422895,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.011764494825794149,"interquartile_range":0.03005355888286111,"maximum":0.23055611608468068,"mean":0.030715219026443995,"measured_model_count":56,"median":0.02139926937725605,"minimum":0.0005486674577255344,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04181805370865526,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0025959982232196567,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.006103480234065759,"gene_effect_median":0.014688023320211133},"dependency_probability_context_minus_non_context_median":-0.0026635317946805265,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006400177189888426,"gene_effect_context_minus_non_context_median":0.015379095495603068}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 191
+- **Dependency-aware candidate rank:** 191
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e6109da95b764fd7187975a931a48f28b43162312870aec3d24838aed1e67329`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PRF1|entrez:5551`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
immune-context marker
+
+
+
Role confidence
+
medium
+
+
+
Therapeutic direction
+
use as biomarker / patient stratification
+
+
+
Best modality
+
immune-context biomarker
+
+
+
Resistance axis
+
immune_cold_state
+
+
+
Matched resistance programs
+
Immune-cold tumor state
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
191not prioritized-2
Resistance biomarker0.500
7medium182
Tumor-intrinsic / small molecule0.000
191not prioritized-2
+
+ +
+

Evidence for

+
    +
  • May help distinguish inflamed from immune-cold tumors
    • +
  • Relevant to anti-PD-1 response probability
    • +
  • Useful for interpreting tumor immune context
    • +
  • Moderate Open Targets melanoma association score (0.529)
    • +
  • Maps to curated anti-PD-1 resistance program: Immune-cold tumor state
    • +
  • Biomarker fit is medium-high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • May need cohort-level expression context
    • +
  • Often reflects immune-cell abundance rather than a direct target
    • +
  • Poor direct therapeutic target class
    • +
  • Flagged as poor direct therapeutic target for this MVP
    • +
  • May reflect immune-cell abundance rather than causal target biology
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.650
+
+
+
+
Main limitation
+
Poor direct therapeutic target despite biological relevance
+
+
+

Uncertainty reason: High contradiction score indicates important opposing evidence | Main limitation: Poor direct therapeutic target despite biological relevance

+

Deprioritization reason: PRF1 should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PRF1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PTCH1.html b/examples/html_reports/depmap_26q1/targets/PTCH1.html new file mode 100644 index 0000000..3c3ab4d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PTCH1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PTCH1 + + + + +
+ +
+

Target hypothesis report: PTCH1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PTCH1
+
+
+
Target name
+
patched 1
+
+
+
Open Targets melanoma score
+
0.569
+
+
+
+
Open Targets baseline rank
+
118
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.09588063885275669,"interquartile_range":0.21009150163000154,"maximum":0.3324175140971824,"mean":0.011094539588050975,"measured_model_count":56,"median":0.018151218696463505,"minimum":-0.46600755029575164,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11421086277724485,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005977946450391312,"interquartile_range":0.03975630865182156,"maximum":0.37309691491643426,"mean":0.036336117075092225,"measured_model_count":56,"median":0.020825055662632826,"minimum":0.0010684762208753433,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04573425510221287,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0037906453790609515,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.00793799435793612,"gene_effect_median":-0.006583365323387894},"dependency_probability_context_minus_non_context_median":0.004053431081731743,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.00832386908366914,"gene_effect_context_minus_non_context_median":-0.006583365323387894}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 120
+- **Dependency-aware candidate rank:** 120
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_838413cbd4627228445817b972d7e23a9eacf6ed123c0edadf7240e3b2bd9b23`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PTCH1|entrez:5727`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
120not prioritized-2
Resistance biomarker0.000
121not prioritized-3
Tumor-intrinsic / small molecule0.000
120not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.569)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PTCH1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PTCH1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PTEN.html b/examples/html_reports/depmap_26q1/targets/PTEN.html new file mode 100644 index 0000000..e394635 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PTEN.html @@ -0,0 +1,441 @@ + + + + +TargetIntel-IO report: PTEN + + + + +
+ +
+

Target hypothesis report: PTEN

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PTEN
+
+
+
Target name
+
phosphatase and tensin homolog
+
+
+
Open Targets melanoma score
+
0.765
+
+
+
+
Open Targets baseline rank
+
7
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.1774273786697296,"interquartile_range":0.3538259685928198,"maximum":1.736156453910227,"mean":0.35005025729220074,"measured_model_count":56,"median":0.3093834287818784,"minimum":-0.5425024630491011,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5312533472625494,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.00014782039573808722,"interquartile_range":0.003600925362963198,"maximum":0.5552301573186749,"mean":0.029092579805179958,"measured_model_count":56,"median":0.0016319869133616688,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0037487457587012853,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0006340736706280773,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.00378429517502365,"pan_cancer_fraction":0.014072847682119206,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008278145695364239,"pan_cancer_fraction":0.008278145695364239,"threshold":0.8}],"gene_effect_mean":-0.04551705089091174,"gene_effect_median":-0.03148194444479169},"dependency_probability_context_minus_non_context_median":0.0006571060699895603,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.003968253968253968,"non_context_fraction":0.013888888888888888,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008680555555555556,"non_context_fraction":0.008680555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.047729685309219894,"gene_effect_context_minus_non_context_median":-0.03305045121014427}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 15
+- **Dependency-aware candidate rank:** 16
+- **Rank delta:** 1
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2cb1b0caa8f0077667dddc663b12a765d9166a7b146b4808af84830d4603f213`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PTEN|entrez:5728`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / poor direct therapeutic target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
avoid as direct target / use as biomarker or pathway context
+
+
+
Best modality
+
biomarker / pathway context only
+
+
+
Resistance axis
+
tumor_intrinsic_driver
+
+
+
Matched resistance programs
+
Tumor-intrinsic driver biology
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
15not prioritized-8
Resistance biomarker0.313
16low-9
Tumor-intrinsic / small molecule0.000
38not prioritized-31
+
+ +
+

Evidence for

+
    +
  • Relevant to melanoma tumor-cell biology
    • +
  • Some targets or pathways are clinically actionable
    • +
  • Useful for separating tumor-intrinsic drivers from immune-combination targets
    • +
  • High Open Targets melanoma association score (0.765)
    • +
  • Maps to curated anti-PD-1 resistance program: Tumor-intrinsic driver biology
    • +
  • Stable role classifier confidence is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Many tumor-intrinsic drivers are poor antibody targets
    • +
  • Melanoma association does not automatically imply anti-PD-1 combination suitability
    • +
  • Tumor suppressors are often poor direct therapeutic targets
    • +
  • Flagged as poor direct therapeutic target for this MVP
    • +
  • Role classifier indicates biological relevance but poor direct targetability
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
1.000
+
+
+
+
Contradiction score
+
0.650
+
+
+
+
Main limitation
+
Poor direct therapeutic target despite biological relevance
+
+
+

Uncertainty reason: High contradiction score indicates important opposing evidence | Main limitation: Poor direct therapeutic target despite biological relevance

+

Deprioritization reason: PTEN should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context.

+
+ +
+

Recommended next validation experiment

+

Validation category: tumor-intrinsic functional validation

+

Next experiment: Evaluate whether perturbing PTEN alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays.

+

Rationale: This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PTK6.html b/examples/html_reports/depmap_26q1/targets/PTK6.html new file mode 100644 index 0000000..01517a7 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PTK6.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PTK6 + + + + +
+ +
+

Target hypothesis report: PTK6

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PTK6
+
+
+
Target name
+
protein tyrosine kinase 6
+
+
+
Open Targets melanoma score
+
0.502
+
+
+
+
Open Targets baseline rank
+
252
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.1840162742298729,"interquartile_range":0.1997483929044233,"maximum":0.3222356768075394,"mean":-0.09758380127941914,"measured_model_count":56,"median":-0.12026321213311797,"minimum":-0.5349203287149611,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.015732118674550405,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.018529924530914635,"interquartile_range":0.09544668456352441,"maximum":0.7582481910067956,"mean":0.09733291620033664,"measured_model_count":56,"median":0.05169764005554711,"minimum":0.0011785351628772456,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11397660909443905,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.018319115017753004,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.002010406811731317,"pan_cancer_fraction":0.019867549668874173,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.04000233454004308,"gene_effect_median":0.011755430048686955},"dependency_probability_context_minus_non_context_median":-0.01906178797118574,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.00210813492063492,"non_context_fraction":0.019965277777777776,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.041946892469073,"gene_effect_context_minus_non_context_median":0.013003588814756994}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 254
+- **Dependency-aware candidate rank:** 254
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e55b812b05bef97f2a1a1caf4d24b84726fd99b4871ad83c42298a88da0946c2`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PTK6|entrez:5753`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
254not prioritized-2
Resistance biomarker0.000
254not prioritized-2
Tumor-intrinsic / small molecule0.000
254not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.502)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PTK6 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PTK6 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PTPN11.html b/examples/html_reports/depmap_26q1/targets/PTPN11.html new file mode 100644 index 0000000..217f14e --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PTPN11.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PTPN11 + + + + +
+ +
+

Target hypothesis report: PTPN11

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PTPN11
+
+
+
Target name
+
protein tyrosine phosphatase non-receptor type 11
+
+
+
Open Targets melanoma score
+
0.589
+
+
+
+
Open Targets baseline rank
+
84
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.3533909262374086,"interquartile_range":0.29119952608175426,"maximum":0.17635991627900627,"mean":-0.2706024316129988,"measured_model_count":56,"median":-0.22336959724687172,"minimum":-1.2437665525555057,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.06219140015565436,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.03844928397309019,"interquartile_range":0.284016781985858,"maximum":0.9954390112631097,"mean":0.24807679949177336,"measured_model_count":56,"median":0.15755716577163256,"minimum":0.004383763089454739,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.3224660659589482,"threshold_fractions":[{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.5},{"denominator":56,"fraction":0.10714285714285714,"numerator":6,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.7093328754750823,"dependency_probability_threshold_fractions":[{"context_fraction":0.14285714285714285,"difference":-0.5616130558183539,"pan_cancer_fraction":0.7044701986754967,"threshold":0.5},{"context_fraction":0.10714285714285714,"difference":-0.45245979186376534,"pan_cancer_fraction":0.5596026490066225,"threshold":0.8}],"gene_effect_mean":0.45975065413160154,"gene_effect_median":0.5201246616645117},"dependency_probability_context_minus_non_context_median":-0.7213579715718752,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.14285714285714285,"difference":-0.5889136904761905,"non_context_fraction":0.7317708333333334,"threshold":0.5},{"context_fraction":0.10714285714285714,"difference":-0.47445436507936506,"non_context_fraction":0.5815972222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.4820996442629989,"gene_effect_context_minus_non_context_median":0.5437117352527387}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 87
+- **Dependency-aware candidate rank:** 87
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_7f81b4ddd9276b0f28fd1944fbc7693dc9b9e72386c10391bedf12326fc30484`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PTPN11|entrez:5781`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
87not prioritized-3
Resistance biomarker0.000
89not prioritized-5
Tumor-intrinsic / small molecule0.000
87not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.589)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PTPN11 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PTPN11 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PTPN13.html b/examples/html_reports/depmap_26q1/targets/PTPN13.html new file mode 100644 index 0000000..cf22346 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PTPN13.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PTPN13 + + + + +
+ +
+

Target hypothesis report: PTPN13

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PTPN13
+
+
+
Target name
+
protein tyrosine phosphatase non-receptor type 13
+
+
+
Open Targets melanoma score
+
0.520
+
+
+
+
Open Targets baseline rank
+
212
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.040896381394369005,"interquartile_range":0.14700691920925746,"maximum":0.31995876843033,"mean":0.028346182847745472,"measured_model_count":56,"median":0.0242865690164243,"minimum":-0.24895582715208994,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10611053781488845,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.007373541485068309,"interquartile_range":0.022925124109128,"maximum":0.1390811639666005,"mean":0.02462924447522302,"measured_model_count":56,"median":0.015851864845906453,"minimum":0.0018513373217926266,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03029866559419631,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0012871058769384144,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.016492866144982073,"gene_effect_median":-0.01797633936413052},"dependency_probability_context_minus_non_context_median":0.0013234472008851663,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.017294602693696478,"gene_effect_context_minus_non_context_median":-0.01815635480726488}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 214
+- **Dependency-aware candidate rank:** 214
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_5d6f41b1786a0605ff1edadeca73ee52e0c53f21342740525ac6a63994799ed8`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PTPN13|entrez:5783`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
214not prioritized-2
Resistance biomarker0.000
214not prioritized-2
Tumor-intrinsic / small molecule0.000
214not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.520)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PTPN13 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PTPN13 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PTPRB.html b/examples/html_reports/depmap_26q1/targets/PTPRB.html new file mode 100644 index 0000000..7216833 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PTPRB.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PTPRB + + + + +
+ +
+

Target hypothesis report: PTPRB

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PTPRB
+
+
+
Target name
+
protein tyrosine phosphatase receptor type B
+
+
+
Open Targets melanoma score
+
0.592
+
+
+
+
Open Targets baseline rank
+
82
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.08660322861860656,"interquartile_range":0.15326593446016268,"maximum":0.26799591456187166,"mean":-0.008701379226628104,"measured_model_count":56,"median":-0.005419265839015835,"minimum":-0.2918999102986819,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06666270584155613,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.010197627844800234,"interquartile_range":0.033392511824931415,"maximum":0.20757819748639839,"mean":0.036540181284022935,"measured_model_count":56,"median":0.022612690169484462,"minimum":0.0021535234777501173,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.043590139669731645,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00014758817878838745,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.001705276232285671,"gene_effect_median":-0.0021003650003931736},"dependency_probability_context_minus_non_context_median":-0.00014758817878838745,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0017881716046884528,"gene_effect_context_minus_non_context_median":-0.0023863247963391166}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 85
+- **Dependency-aware candidate rank:** 85
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_444f56d5d7e1650e15dd09061a20a065ffb7fc77e546647504ead1dffb791cc7`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PTPRB|entrez:5787`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
85not prioritized-3
Resistance biomarker0.000
87not prioritized-5
Tumor-intrinsic / small molecule0.000
85not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.592)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PTPRB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PTPRB in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PTPRC.html b/examples/html_reports/depmap_26q1/targets/PTPRC.html new file mode 100644 index 0000000..9bd4584 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PTPRC.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PTPRC + + + + +
+ +
+

Target hypothesis report: PTPRC

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PTPRC
+
+
+
Target name
+
protein tyrosine phosphatase receptor type C
+
+
+
Open Targets melanoma score
+
0.550
+
+
+
+
Open Targets baseline rank
+
158
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** insufficient_measured_context_models
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 7
+- **Available reference observations:** 376
+- **Coverage fraction:** 0.125
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.2540968232068008,"interquartile_range":0.27269155062254513,"maximum":0.2667060877154521,"mean":-0.10718411476264175,"measured_model_count":7,"median":-0.1839674851282336,"minimum":-0.3620232143435977,"missing_fraction":0.875,"missing_model_count":49,"third_quartile":0.018594727415744333,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.03535790079068784,"interquartile_range":0.11700097399538673,"maximum":0.3130619067559611,"mean":0.11336025072294678,"measured_model_count":7,"median":0.10142439265024349,"minimum":0.0036019045008981055,"missing_fraction":0.875,"missing_model_count":49,"third_quartile":0.15235887478607457,"threshold_fractions":[{"denominator":7,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":7,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":null,"dependency_probability_threshold_fractions":[],"gene_effect_mean":null,"gene_effect_median":null},"dependency_probability_context_minus_non_context_median":null,"dependency_probability_context_minus_non_context_threshold_fractions":[],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":null,"gene_effect_context_minus_non_context_median":null}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":21,"value":65.0}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 160
+- **Dependency-aware candidate rank:** 160
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_83f222e4b026a60cc5e1c64b47b83d66b884c184cf2119e84f002d03e41659d9`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PTPRC|entrez:5788`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
160not prioritized-2
Resistance biomarker0.000
161not prioritized-3
Tumor-intrinsic / small molecule0.000
160not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.550)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PTPRC lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PTPRC in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PTPRK.html b/examples/html_reports/depmap_26q1/targets/PTPRK.html new file mode 100644 index 0000000..b40b569 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PTPRK.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PTPRK + + + + +
+ +
+

Target hypothesis report: PTPRK

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PTPRK
+
+
+
Target name
+
protein tyrosine phosphatase receptor type K
+
+
+
Open Targets melanoma score
+
0.582
+
+
+
+
Open Targets baseline rank
+
95
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.04914152862613752,"interquartile_range":0.12518664825956582,"maximum":0.2998279934328426,"mean":0.1114437103978233,"measured_model_count":56,"median":0.11574090709819299,"minimum":-0.0681971223240274,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.17432817688570335,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0035664525085002926,"interquartile_range":0.00992274915531969,"maximum":0.03943903737818359,"mean":0.010132813629039368,"measured_model_count":56,"median":0.007097817765832145,"minimum":0.0008647637371804818,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.013489201663819983,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0002263335995250828,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.012397412838947602,"gene_effect_median":-0.004419920066998789},"dependency_probability_context_minus_non_context_median":-0.00025654626823008383,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.01300006485195189,"gene_effect_context_minus_non_context_median":-0.004484083873970465}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 98
+- **Dependency-aware candidate rank:** 98
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_06175a71ff989b9f9b64f8c8d7ab7ecb8d9020e7edda420fd1ee8a7cd5700cc5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PTPRK|entrez:5796`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
98not prioritized-3
Resistance biomarker0.000
99not prioritized-4
Tumor-intrinsic / small molecule0.000
98not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.582)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PTPRK lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PTPRK in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/PTPRT.html b/examples/html_reports/depmap_26q1/targets/PTPRT.html new file mode 100644 index 0000000..a585c81 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/PTPRT.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: PTPRT + + + + +
+ +
+

Target hypothesis report: PTPRT

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
PTPRT
+
+
+
Target name
+
protein tyrosine phosphatase receptor type T
+
+
+
Open Targets melanoma score
+
0.591
+
+
+
+
Open Targets baseline rank
+
83
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.12557464182869493,"interquartile_range":0.1670050372331764,"maximum":0.35192836037169745,"mean":-0.04846570793613747,"measured_model_count":56,"median":-0.04661431473671101,"minimum":-0.4938301685425578,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04143039540448146,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.014120381189881645,"interquartile_range":0.04546098758688822,"maximum":0.3639539499414603,"mean":0.054018527133764996,"measured_model_count":56,"median":0.03077532270482216,"minimum":0.0012548301955076896,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.059581368776769866,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0056562130050500994,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.013856123608917748,"gene_effect_median":0.01587665848552721},"dependency_probability_context_minus_non_context_median":-0.0059721993356829026,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.014529685173240173,"gene_effect_context_minus_non_context_median":0.01653520210707666}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 86
+- **Dependency-aware candidate rank:** 86
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_da7c9029d34c85d1d5d73dec2f7c3e91af3dfee9900781623d66099408d0dad5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:PTPRT|entrez:11122`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
86not prioritized-3
Resistance biomarker0.000
88not prioritized-5
Tumor-intrinsic / small molecule0.000
86not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.591)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: PTPRT lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for PTPRT in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/QKI.html b/examples/html_reports/depmap_26q1/targets/QKI.html new file mode 100644 index 0000000..c59d92e --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/QKI.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: QKI + + + + +
+ +
+

Target hypothesis report: QKI

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
QKI
+
+
+
Target name
+
QKI, KH domain containing RNA binding
+
+
+
Open Targets melanoma score
+
0.570
+
+
+
+
Open Targets baseline rank
+
115
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.16545727142804292,"interquartile_range":0.2785191649890655,"maximum":0.4490044663426027,"mean":-0.030217967806080992,"measured_model_count":56,"median":-0.021443690625028444,"minimum":-0.6118606202127194,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11306189356102253,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.006750055723509366,"interquartile_range":0.0877187794340263,"maximum":0.7819981814289125,"mean":0.08535186107724975,"measured_model_count":56,"median":0.02434871601799806,"minimum":0.000661291005771635,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09446883515753567,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00020522040079048315,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.00922421948912015,"pan_cancer_fraction":0.026490066225165563,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0074503311258278145,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.8}],"gene_effect_mean":0.0011621618166117106,"gene_effect_median":-0.009181211737889345},"dependency_probability_context_minus_non_context_median":0.0002645484582731103,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.009672619047619044,"non_context_fraction":0.026041666666666668,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0078125,"non_context_fraction":0.0078125,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0012186557938081224,"gene_effect_context_minus_non_context_median":-0.009181211737889345}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 117
+- **Dependency-aware candidate rank:** 117
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ab32ccafb5e2a7bc73483e0c6be8088f957ab86e3c7ef1918da5c95110b996a4`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:QKI|entrez:9444`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
117not prioritized-2
Resistance biomarker0.000
118not prioritized-3
Tumor-intrinsic / small molecule0.000
117not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.570)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: QKI lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for QKI in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/RAC1.html b/examples/html_reports/depmap_26q1/targets/RAC1.html new file mode 100644 index 0000000..ee71f59 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/RAC1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: RAC1 + + + + +
+ +
+

Target hypothesis report: RAC1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
RAC1
+
+
+
Target name
+
Rac family small GTPase 1
+
+
+
Open Targets melanoma score
+
0.710
+
+
+
+
Open Targets baseline rank
+
14
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.132219886481244,"interquartile_range":0.3450850855482519,"maximum":-0.23357021391240496,"mean":-0.9872570564091132,"measured_model_count":56,"median":-0.9644656313374076,"minimum":-1.9398398272208595,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.7871348009329922,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.8903158974511705,"interquartile_range":0.0970528051333146,"maximum":1.0,"mean":0.9143828073836274,"measured_model_count":56,"median":0.9718981505657296,"minimum":0.12114557537340254,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9873687025844851,"threshold_fractions":[{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.5},{"denominator":56,"fraction":0.875,"numerator":49,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.09055764727113302,"dependency_probability_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":0.18661305581835375,"pan_cancer_fraction":0.7955298013245033,"threshold":0.5},{"context_fraction":0.875,"difference":0.26738410596026485,"pan_cancer_fraction":0.6076158940397351,"threshold":0.8}],"gene_effect_mean":-0.21449442054624301,"gene_effect_median":-0.20886143997455098},"dependency_probability_context_minus_non_context_median":0.09815552693367069,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":0.19568452380952372,"non_context_fraction":0.7864583333333334,"threshold":0.5},{"context_fraction":0.875,"difference":0.2803819444444444,"non_context_fraction":0.5946180555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.22492123265612995,"gene_effect_context_minus_non_context_median":-0.21930036283608545}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":92.5925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 22
+- **Dependency-aware candidate rank:** 22
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_bca65944daea22928e55f8da147a53d8c0994ae1fc80f09aa88644dc892ce9f3`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:RAC1|entrez:5879`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
22not prioritized-8
Resistance biomarker0.000
26not prioritized-12
Tumor-intrinsic / small molecule0.013
19not prioritized-5
+
+ +
+

Evidence for

+
    +
  • High Open Targets melanoma association score (0.710)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: RAC1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for RAC1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/RAD51C.html b/examples/html_reports/depmap_26q1/targets/RAD51C.html new file mode 100644 index 0000000..33999a8 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/RAD51C.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: RAD51C + + + + +
+ +
+

Target hypothesis report: RAD51C

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
RAD51C
+
+
+
Target name
+
RAD51 paralog C
+
+
+
Open Targets melanoma score
+
0.501
+
+
+
+
Open Targets baseline rank
+
254
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.932549595300154,"interquartile_range":0.3013109434520187,"maximum":-0.21826138124369032,"mean":-0.7877103314357428,"measured_model_count":56,"median":-0.811587320321768,"minimum":-1.3356950303254789,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.6312386518481353,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.7658254388663606,"interquartile_range":0.2058807169367769,"maximum":0.9999550620977978,"mean":0.8249481295068888,"measured_model_count":56,"median":0.8957799704120795,"minimum":0.10762375437683037,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9717061558031375,"threshold_fractions":[{"denominator":56,"fraction":0.9107142857142857,"numerator":51,"threshold":0.5},{"denominator":56,"fraction":0.6964285714285714,"numerator":39,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.01340556825025796,"dependency_probability_threshold_fractions":[{"context_fraction":0.9107142857142857,"difference":0.07296594134342482,"pan_cancer_fraction":0.8377483443708609,"threshold":0.5},{"context_fraction":0.6964285714285714,"difference":0.0697729422894986,"pan_cancer_fraction":0.6266556291390728,"threshold":0.8}],"gene_effect_mean":-0.0397879941310455,"gene_effect_median":-0.06156875609122936},"dependency_probability_context_minus_non_context_median":0.013567144515045482,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9107142857142857,"difference":0.07651289682539686,"non_context_fraction":0.8342013888888888,"threshold":0.5},{"context_fraction":0.6964285714285714,"difference":0.07316468253968256,"non_context_fraction":0.6232638888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.041722132734637984,"gene_effect_context_minus_non_context_median":-0.06400491452732326}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 256
+- **Dependency-aware candidate rank:** 256
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_9dee9ef6b7c02c5c7795b332a5274f544bbd39343738dbb793a149ce4969d71a`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:RAD51C|entrez:5889`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
256not prioritized-2
Resistance biomarker0.000
256not prioritized-2
Tumor-intrinsic / small molecule0.000
256not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.501)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: RAD51C lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for RAD51C in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/RAF1.html b/examples/html_reports/depmap_26q1/targets/RAF1.html new file mode 100644 index 0000000..c220e38 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/RAF1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: RAF1 + + + + +
+ +
+

Target hypothesis report: RAF1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
RAF1
+
+
+
Target name
+
Raf-1 proto-oncogene, serine/threonine kinase
+
+
+
Open Targets melanoma score
+
0.673
+
+
+
+
Open Targets baseline rank
+
25
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.1256271216117195,"interquartile_range":0.1888216209784189,"maximum":0.20431855926131795,"mean":-0.15615906924769854,"measured_model_count":56,"median":-0.02220851631360249,"minimum":-1.736546085109907,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06319449936669941,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.012033750897031764,"interquartile_range":0.04288567210061994,"maximum":1.0,"mean":0.17290387330361726,"measured_model_count":56,"median":0.02468474918939307,"minimum":0.0024816460659539356,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05491942299765171,"threshold_fractions":[{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.5},{"denominator":56,"fraction":0.125,"numerator":7,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.017432078846795436,"dependency_probability_threshold_fractions":[{"context_fraction":0.16071428571428573,"difference":0.052270577105014204,"pan_cancer_fraction":0.10844370860927152,"threshold":0.5},{"context_fraction":0.125,"difference":0.06622516556291391,"pan_cancer_fraction":0.058774834437086095,"threshold":0.8}],"gene_effect_mean":-0.01317995531935906,"gene_effect_median":0.054554837151042174},"dependency_probability_context_minus_non_context_median":-0.018701876642998466,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.16071428571428573,"difference":0.05481150793650795,"non_context_fraction":0.10590277777777778,"threshold":0.5},{"context_fraction":0.125,"difference":0.06944444444444445,"non_context_fraction":0.05555555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.013820647591827911,"gene_effect_context_minus_non_context_median":0.057177451218782024}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 32
+- **Dependency-aware candidate rank:** 32
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_3cadbda89e04b64c2b0f97130adfb76a89396b2abab616171877ebdccab32161`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:RAF1|entrez:5894`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
32not prioritized-7
Resistance biomarker0.000
34not prioritized-9
Tumor-intrinsic / small molecule0.005
27not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.673)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: RAF1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for RAF1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/RANBP2.html b/examples/html_reports/depmap_26q1/targets/RANBP2.html new file mode 100644 index 0000000..114bf87 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/RANBP2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: RANBP2 + + + + +
+ +
+

Target hypothesis report: RANBP2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
RANBP2
+
+
+
Target name
+
RAN binding protein 2
+
+
+
Open Targets melanoma score
+
0.515
+
+
+
+
Open Targets baseline rank
+
227
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.5908589284378346,"interquartile_range":0.16318241965130414,"maximum":-0.11226020940158005,"mean":-0.5039476915345732,"measured_model_count":56,"median":-0.5210149465256304,"minimum":-0.9624691006672143,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.42767650878653046,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.43796867139031853,"interquartile_range":0.26936444553060407,"maximum":0.961332400882081,"mean":0.5705831573863455,"measured_model_count":56,"median":0.6193692604611463,"minimum":0.046772958901499954,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.7073331169209226,"threshold_fractions":[{"denominator":56,"fraction":0.6785714285714286,"numerator":38,"threshold":0.5},{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.039967325459354,"dependency_probability_threshold_fractions":[{"context_fraction":0.6785714285714286,"difference":0.0850283822138127,"pan_cancer_fraction":0.5935430463576159,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":-0.04576631977294229,"pan_cancer_fraction":0.22433774834437087,"threshold":0.8}],"gene_effect_mean":0.009087634242605835,"gene_effect_median":-0.0153649055422318},"dependency_probability_context_minus_non_context_median":0.04531352622720208,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.6785714285714286,"difference":0.0891617063492064,"non_context_fraction":0.5894097222222222,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":-0.047991071428571425,"non_context_fraction":0.2265625,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.009529394240510136,"gene_effect_context_minus_non_context_median":-0.01618650390554499}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 229
+- **Dependency-aware candidate rank:** 229
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_c7e2695228cf1dd5e4f4054f355d2d78a178e5f21d661c29cc532bd946304524`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:RANBP2|entrez:5903`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
229not prioritized-2
Resistance biomarker0.000
229not prioritized-2
Tumor-intrinsic / small molecule0.000
229not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.515)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: RANBP2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for RANBP2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/RB1.html b/examples/html_reports/depmap_26q1/targets/RB1.html new file mode 100644 index 0000000..796922b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/RB1.html @@ -0,0 +1,435 @@ + + + + +TargetIntel-IO report: RB1 + + + + +
+ +
+

Target hypothesis report: RB1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
RB1
+
+
+
Target name
+
RB transcriptional corepressor 1
+
+
+
Open Targets melanoma score
+
0.585
+
+
+
+
Open Targets baseline rank
+
93
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.055364957538402405,"interquartile_range":0.27298439964807286,"maximum":0.8459136994900094,"mean":0.21463507902892,"measured_model_count":56,"median":0.20375104048983378,"minimum":-0.6519186084404235,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.3283493571864753,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0005016747096900193,"interquartile_range":0.010403535843926915,"maximum":0.6691439310341896,"mean":0.02148722485594138,"measured_model_count":56,"median":0.003501129077626756,"minimum":1.653080623736478e-09,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.010905210553616934,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.001734839886762509,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.016201513718070007,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.032673938556125576,"gene_effect_median":0.03869966817842668},"dependency_probability_context_minus_non_context_median":-0.0017748365583874917,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.0169890873015873,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03426225501371505,"gene_effect_context_minus_non_context_median":0.03921263260283264}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 96
+- **Dependency-aware candidate rank:** 96
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_375480e9f01e05c6eff7db357f186a598ae8a786413287ff997662540752136b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:RB1|entrez:5925`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / poor direct therapeutic target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
avoid as direct target / use as biomarker or pathway context
+
+
+
Best modality
+
biomarker / pathway context only
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
96not prioritized-3
Resistance biomarker0.094
23not prioritized70
Tumor-intrinsic / small molecule0.000
96not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.585)
    • +
  • Stable role classifier confidence is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Flagged as poor direct therapeutic target for this MVP
    • +
  • Role classifier indicates biological relevance but poor direct targetability
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
0.889
+
+
+
+
Contradiction score
+
0.570
+
+
+
+
Main limitation
+
Poor direct therapeutic target despite biological relevance
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Moderate contradiction score indicates caution is needed | Main limitation: Poor direct therapeutic target despite biological relevance

+

Deprioritization reason: RB1 should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context.

+
+ +
+

Recommended next validation experiment

+

Validation category: tumor-intrinsic functional validation

+

Next experiment: Evaluate whether perturbing RB1 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays.

+

Rationale: This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/RET.html b/examples/html_reports/depmap_26q1/targets/RET.html new file mode 100644 index 0000000..5ab58d0 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/RET.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: RET + + + + +
+ +
+

Target hypothesis report: RET

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
RET
+
+
+
Target name
+
ret proto-oncogene
+
+
+
Open Targets melanoma score
+
0.537
+
+
+
+
Open Targets baseline rank
+
182
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.14612119713856755,"interquartile_range":0.14575295943199149,"maximum":0.17499522346494442,"mean":-0.06749277025807235,"measured_model_count":56,"median":-0.07167217571962779,"minimum":-0.24627934225885015,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.000368237706576062,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.018037570779840997,"interquartile_range":0.06104268632906562,"maximum":0.17637743727038194,"mean":0.056573689560530285,"measured_model_count":56,"median":0.04047103264540877,"minimum":0.004538060086491297,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07908025710890662,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01834135332334009,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.04710982937589703,"gene_effect_median":0.03669751432842279},"dependency_probability_context_minus_non_context_median":-0.018603384608284174,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04939989052611425,"gene_effect_context_minus_non_context_median":0.038167003183957396}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 184
+- **Dependency-aware candidate rank:** 184
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_089ceaad55ef601d97aa548f69a6d4cda7591eedff2f6dec05e079c5caa2a46f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:RET|entrez:5979`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
184not prioritized-2
Resistance biomarker0.000
185not prioritized-3
Tumor-intrinsic / small molecule0.000
184not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.537)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: RET lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for RET in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/RICTOR.html b/examples/html_reports/depmap_26q1/targets/RICTOR.html new file mode 100644 index 0000000..5a4f0e3 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/RICTOR.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: RICTOR + + + + +
+ +
+

Target hypothesis report: RICTOR

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
RICTOR
+
+
+
Target name
+
RPTOR independent companion of MTOR complex 2
+
+
+
Open Targets melanoma score
+
0.539
+
+
+
+
Open Targets baseline rank
+
180
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.5866822345351441,"interquartile_range":0.34588160919168814,"maximum":0.16149735225992057,"mean":-0.46055626393316357,"measured_model_count":56,"median":-0.39783708129546663,"minimum":-1.5075664457299727,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.24080062534345598,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.1350228253539574,"interquartile_range":0.6118989644679056,"maximum":0.9999801771783248,"mean":0.44882468393642067,"measured_model_count":56,"median":0.38868919644309075,"minimum":0.003186659711179904,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.746921789821863,"threshold_fractions":[{"denominator":56,"fraction":0.35714285714285715,"numerator":20,"threshold":0.5},{"denominator":56,"fraction":0.21428571428571427,"numerator":12,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.04347991018502684,"dependency_probability_threshold_fractions":[{"context_fraction":0.35714285714285715,"difference":-0.07663197729422894,"pan_cancer_fraction":0.4337748344370861,"threshold":0.5},{"context_fraction":0.21428571428571427,"difference":-0.009224219489120167,"pan_cancer_fraction":0.22350993377483444,"threshold":0.8}],"gene_effect_mean":-0.010627998452724718,"gene_effect_median":0.02905615681435275},"dependency_probability_context_minus_non_context_median":-0.04678837140427938,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.35714285714285715,"difference":-0.08035714285714285,"non_context_fraction":0.4375,"threshold":0.5},{"context_fraction":0.21428571428571427,"difference":-0.009672619047619069,"non_context_fraction":0.22395833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.011144637266399304,"gene_effect_context_minus_non_context_median":0.03076523229366962}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 182
+- **Dependency-aware candidate rank:** 182
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2fb8124a5270f956aeb713373d82ddda01a75f6ad42e5efd31836186f8b0930c`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:RICTOR|entrez:253260`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
182not prioritized-2
Resistance biomarker0.000
183not prioritized-3
Tumor-intrinsic / small molecule0.000
182not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.539)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: RICTOR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for RICTOR in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ROS1.html b/examples/html_reports/depmap_26q1/targets/ROS1.html new file mode 100644 index 0000000..1b66866 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ROS1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ROS1 + + + + +
+ +
+

Target hypothesis report: ROS1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ROS1
+
+
+
Target name
+
ROS proto-oncogene 1, receptor tyrosine kinase
+
+
+
Open Targets melanoma score
+
0.630
+
+
+
+
Open Targets baseline rank
+
43
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.08392049067782814,"interquartile_range":0.12341727033690336,"maximum":0.3254661141771581,"mean":0.126330303900205,"measured_model_count":56,"median":0.12383389748495374,"minimum":-0.20924597391267008,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2073377610147315,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0027627089855649873,"interquartile_range":0.007337207312868303,"maximum":0.10622139999463978,"mean":0.012021715750322627,"measured_model_count":56,"median":0.005657972826808763,"minimum":0.0007528764526069915,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.01009991629843329,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0023130285792771696,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.01804290864727738,"gene_effect_median":0.016779053562060234},"dependency_probability_context_minus_non_context_median":-0.002389986475450254,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01891999448429782,"gene_effect_context_minus_non_context_median":0.017923946646624583}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 50
+- **Dependency-aware candidate rank:** 50
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_fcd33cce653a26ca6a4f20a2bdf8396a860cdd1591e3ad7d590b9985734b9f4b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ROS1|entrez:6098`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
50not prioritized-7
Resistance biomarker0.000
52not prioritized-9
Tumor-intrinsic / small molecule0.000
50not prioritized-7
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.630)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ROS1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ROS1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/RPL5.html b/examples/html_reports/depmap_26q1/targets/RPL5.html new file mode 100644 index 0000000..c65da0c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/RPL5.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: RPL5 + + + + +
+ +
+

Target hypothesis report: RPL5

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
RPL5
+
+
+
Target name
+
ribosomal protein L5
+
+
+
Open Targets melanoma score
+
0.579
+
+
+
+
Open Targets baseline rank
+
103
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-2.3140510776793413,"interquartile_range":0.5596836672474383,"maximum":-1.2945186569708296,"mean":-2.0478521024180614,"measured_model_count":56,"median":-2.0634465911044617,"minimum":-2.8814886097008965,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.754367410431903,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9999896314895338,"interquartile_range":1.0368510466207681e-05,"maximum":1.0,"mean":0.9995504351830853,"measured_model_count":56,"median":1.0,"minimum":0.9841023605416382,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0,"pan_cancer_fraction":1.0,"threshold":0.5},{"context_fraction":1.0,"difference":0.0,"pan_cancer_fraction":1.0,"threshold":0.8}],"gene_effect_mean":0.24988290222750908,"gene_effect_median":0.22211344414513423},"dependency_probability_context_minus_non_context_median":0.0,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0,"non_context_fraction":1.0,"threshold":0.5},{"context_fraction":1.0,"difference":0.0,"non_context_fraction":1.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.26202998775245856,"gene_effect_context_minus_non_context_median":0.23992133455099696}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 106
+- **Dependency-aware candidate rank:** 106
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_0b5794933620d1e2e5002d30da99c667cd6dfb3950eec37405a93a1aef637a1b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:RPL5|entrez:6125`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
106not prioritized-3
Resistance biomarker0.000
107not prioritized-4
Tumor-intrinsic / small molecule0.000
106not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.579)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: RPL5 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for RPL5 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/RRM1.html b/examples/html_reports/depmap_26q1/targets/RRM1.html new file mode 100644 index 0000000..e993581 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/RRM1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: RRM1 + + + + +
+ +
+

Target hypothesis report: RRM1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
RRM1
+
+
+
Target name
+
ribonucleotide reductase catalytic subunit M1
+
+
+
Open Targets melanoma score
+
0.565
+
+
+
+
Open Targets baseline rank
+
124
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-3.7866713498714786,"interquartile_range":0.7142138038474664,"maximum":-2.0291077684100465,"mean":-3.4304476414103555,"measured_model_count":56,"median":-3.527279701684648,"minimum":-4.272254363112374,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-3.072457546024012,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":1.0,"interquartile_range":0.0,"maximum":1.0,"mean":1.0,"measured_model_count":56,"median":1.0,"minimum":1.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0,"pan_cancer_fraction":1.0,"threshold":0.5},{"context_fraction":1.0,"difference":0.0,"pan_cancer_fraction":1.0,"threshold":0.8}],"gene_effect_mean":-0.24463607830242262,"gene_effect_median":-0.24896007414394905},"dependency_probability_context_minus_non_context_median":0.0,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0,"non_context_fraction":1.0,"threshold":0.5},{"context_fraction":1.0,"difference":0.0,"non_context_fraction":1.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.2565281098865677,"gene_effect_context_minus_non_context_median":-0.2582819782444661}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":100.0}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 126
+- **Dependency-aware candidate rank:** 126
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_7f83daeead72cedf8e1fb1a673305a40a131a738823561b96ac404a3eb72e27d`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:RRM1|entrez:6240`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
126not prioritized-2
Resistance biomarker0.000
127not prioritized-3
Tumor-intrinsic / small molecule0.000
126not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.565)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: RRM1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for RRM1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/RRM2.html b/examples/html_reports/depmap_26q1/targets/RRM2.html new file mode 100644 index 0000000..904fe8f --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/RRM2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: RRM2 + + + + +
+ +
+

Target hypothesis report: RRM2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
RRM2
+
+
+
Target name
+
ribonucleotide reductase regulatory subunit M2
+
+
+
Open Targets melanoma score
+
0.581
+
+
+
+
Open Targets baseline rank
+
98
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-3.0848036344428675,"interquartile_range":0.517328228067063,"maximum":-1.1915182107798357,"mean":-2.782417065774602,"measured_model_count":56,"median":-2.8483434965014958,"minimum":-3.607628637950257,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-2.5674754063758045,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":1.0,"interquartile_range":0.0,"maximum":1.0,"mean":0.9999699992385163,"measured_model_count":56,"median":1.0,"minimum":0.9983332637171632,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0016556291390728006,"pan_cancer_fraction":0.9983443708609272,"threshold":0.5},{"context_fraction":1.0,"difference":0.004139072847682113,"pan_cancer_fraction":0.9958609271523179,"threshold":0.8}],"gene_effect_mean":-0.17628457515973928,"gene_effect_median":-0.19028151675910987},"dependency_probability_context_minus_non_context_median":0.0,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0017361111111111605,"non_context_fraction":0.9982638888888888,"threshold":0.5},{"context_fraction":1.0,"difference":0.00434027777777779,"non_context_fraction":0.9956597222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.1848539642300029,"gene_effect_context_minus_non_context_median":-0.2016175361265704}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 101
+- **Dependency-aware candidate rank:** 101
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e0972d40a6b06a1c3ca73330907decd6609ccfeecef8be13d0e7d9d15d818e37`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:RRM2|entrez:6241`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
101not prioritized-3
Resistance biomarker0.000
102not prioritized-4
Tumor-intrinsic / small molecule0.000
101not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.581)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: RRM2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for RRM2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/RRM2B.html b/examples/html_reports/depmap_26q1/targets/RRM2B.html new file mode 100644 index 0000000..9ba46e6 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/RRM2B.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: RRM2B + + + + +
+ +
+

Target hypothesis report: RRM2B

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
RRM2B
+
+
+
Target name
+
ribonucleotide reductase regulatory TP53 inducible subunit M2B
+
+
+
Open Targets melanoma score
+
0.574
+
+
+
+
Open Targets baseline rank
+
110
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.030440159428604997,"interquartile_range":0.09226055303100826,"maximum":0.23615443777033013,"mean":0.01593588710866817,"measured_model_count":56,"median":0.006488471619161884,"minimum":-0.18121780207352717,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06182039360240326,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01078722232470268,"interquartile_range":0.01897368961587206,"maximum":0.07183784488213862,"mean":0.021949966235280397,"measured_model_count":56,"median":0.017595754218379635,"minimum":0.002689755558466425,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02976091194057474,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0031722420216032214,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.014677445462933801,"gene_effect_median":0.002554336410770526},"dependency_probability_context_minus_non_context_median":-0.003237733648874218,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.015390932395159736,"gene_effect_context_minus_non_context_median":0.0028943402896217073}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 113
+- **Dependency-aware candidate rank:** 113
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_442ec2f66d546765d9c306fdf50a355b289e7e37bd66a4824aae4fad8a1afb36`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:RRM2B|entrez:50484`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
113not prioritized-3
Resistance biomarker0.000
114not prioritized-4
Tumor-intrinsic / small molecule0.000
113not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.574)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: RRM2B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for RRM2B in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/RUNX1T1.html b/examples/html_reports/depmap_26q1/targets/RUNX1T1.html new file mode 100644 index 0000000..a60a27f --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/RUNX1T1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: RUNX1T1 + + + + +
+ +
+

Target hypothesis report: RUNX1T1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
RUNX1T1
+
+
+
Target name
+
RUNX1 partner transcriptional co-repressor 1
+
+
+
Open Targets melanoma score
+
0.587
+
+
+
+
Open Targets baseline rank
+
90
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.09884952652793141,"interquartile_range":0.11970965709835064,"maximum":0.27356305825023636,"mean":-0.04295758676242804,"measured_model_count":56,"median":-0.04714232020834208,"minimum":-0.3818943189986762,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02086013057041923,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0161003914275484,"interquartile_range":0.041744408958407656,"maximum":0.4366432533874732,"mean":0.04657444844566352,"measured_model_count":56,"median":0.03193243688624428,"minimum":0.0019998872365112946,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.057844800385956054,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0021578335492734822,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.004599600939368738,"gene_effect_median":-0.013994556049691326},"dependency_probability_context_minus_non_context_median":0.002261819284604047,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.004823192651699136,"gene_effect_context_minus_non_context_median":-0.014553293597612586}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 93
+- **Dependency-aware candidate rank:** 93
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e1c6b1a71fac0ef5330ef6d9ff0e2369355518d5687079fd508ee933a4a10132`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:RUNX1T1|entrez:862`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
93not prioritized-3
Resistance biomarker0.000
95not prioritized-5
Tumor-intrinsic / small molecule0.000
93not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.587)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: RUNX1T1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for RUNX1T1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SALL4.html b/examples/html_reports/depmap_26q1/targets/SALL4.html new file mode 100644 index 0000000..5dce999 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SALL4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SALL4 + + + + +
+ +
+

Target hypothesis report: SALL4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SALL4
+
+
+
Target name
+
spalt like transcription factor 4
+
+
+
Open Targets melanoma score
+
0.552
+
+
+
+
Open Targets baseline rank
+
150
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.13566465830643035,"interquartile_range":0.13712660498832815,"maximum":0.3325082771559966,"mean":-0.061407429436107094,"measured_model_count":56,"median":-0.05751971111293863,"minimum":-0.37072006405562824,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0014619466818978008,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.02069457658383381,"interquartile_range":0.03437754339962874,"maximum":0.3217848067260631,"mean":0.051741718849113674,"measured_model_count":56,"median":0.036589651850089416,"minimum":0.001902674157795965,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05507211998346255,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0055148678277405425,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0074503311258278145,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":0.02093560923724755,"gene_effect_median":0.017304265304520644},"dependency_probability_context_minus_non_context_median":-0.0062088255037458726,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0078125,"non_context_fraction":0.0078125,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.021953312464058142,"gene_effect_context_minus_non_context_median":0.018288384479971276}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 152
+- **Dependency-aware candidate rank:** 152
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_12f96f46af2d44484ca3a02ae488a1a66d0579041c610fa412a0748177e63950`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SALL4|entrez:57167`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
152not prioritized-2
Resistance biomarker0.000
153not prioritized-3
Tumor-intrinsic / small molecule0.000
152not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.552)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SALL4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SALL4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SETBP1.html b/examples/html_reports/depmap_26q1/targets/SETBP1.html new file mode 100644 index 0000000..83e844d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SETBP1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SETBP1 + + + + +
+ +
+

Target hypothesis report: SETBP1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SETBP1
+
+
+
Target name
+
SET binding protein 1
+
+
+
Open Targets melanoma score
+
0.568
+
+
+
+
Open Targets baseline rank
+
123
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.03797804622296906,"interquartile_range":0.11603569982367719,"maximum":0.23410999453740547,"mean":0.026320814579516943,"measured_model_count":56,"median":0.020794089042544255,"minimum":-0.1749570667473206,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07805765360070813,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.009273976484867677,"interquartile_range":0.017960499834995435,"maximum":0.1341463196615172,"mean":0.022262575208713727,"measured_model_count":56,"median":0.016776289101935012,"minimum":0.002760614285472168,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.027234476319863112,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0023143291226201367,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.01899299886253225,"gene_effect_median":0.008924208414270409},"dependency_probability_context_minus_non_context_median":-0.0024077840403488524,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01991626964057201,"gene_effect_context_minus_non_context_median":0.009956691149827442}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 125
+- **Dependency-aware candidate rank:** 125
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a377675f87c49f849e31a9b7afa4a250636177c81b5395bb18daa5011eb4b49d`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SETBP1|entrez:26040`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
125not prioritized-2
Resistance biomarker0.000
126not prioritized-3
Tumor-intrinsic / small molecule0.000
125not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.568)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SETBP1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SETBP1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SETD2.html b/examples/html_reports/depmap_26q1/targets/SETD2.html new file mode 100644 index 0000000..a22a018 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SETD2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SETD2 + + + + +
+ +
+

Target hypothesis report: SETD2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SETD2
+
+
+
Target name
+
SET domain containing 2, histone lysine methyltransferase
+
+
+
Open Targets melanoma score
+
0.635
+
+
+
+
Open Targets baseline rank
+
38
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.5047376254956473,"interquartile_range":0.37448050917812936,"maximum":0.1846584412323803,"mean":-0.3291048407412958,"measured_model_count":56,"median":-0.3280383584112302,"minimum":-1.0317415681684419,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.1302571163175179,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.08620996554393631,"interquartile_range":0.5051609618146871,"maximum":0.9761682730353267,"mean":0.34026916308678895,"measured_model_count":56,"median":0.26696470082025603,"minimum":0.0024915270161495534,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5913709273586234,"threshold_fractions":[{"denominator":56,"fraction":0.32142857142857145,"numerator":18,"threshold":0.5},{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.13397532216480423,"dependency_probability_threshold_fractions":[{"context_fraction":0.32142857142857145,"difference":-0.08171712393566694,"pan_cancer_fraction":0.4031456953642384,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":-0.0750946073793756,"pan_cancer_fraction":0.14652317880794702,"threshold":0.8}],"gene_effect_mean":0.08091953973590466,"gene_effect_median":0.07569703841773578},"dependency_probability_context_minus_non_context_median":-0.1411708969140013,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.32142857142857145,"difference":-0.08568948412698413,"non_context_fraction":0.4071180555555556,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":-0.07874503968253968,"non_context_fraction":0.1501736111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08485312847306681,"gene_effect_context_minus_non_context_median":0.0804583063181547}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 45
+- **Dependency-aware candidate rank:** 45
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_38d8acd6a14528ecff8c44461c927e87f811f304368f049bb16c6bc389a79cb3`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SETD2|entrez:29072`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
45not prioritized-7
Resistance biomarker0.000
47not prioritized-9
Tumor-intrinsic / small molecule0.000
45not prioritized-7
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.635)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SETD2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SETD2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SF3B1.html b/examples/html_reports/depmap_26q1/targets/SF3B1.html new file mode 100644 index 0000000..e303b0a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SF3B1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SF3B1 + + + + +
+ +
+

Target hypothesis report: SF3B1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SF3B1
+
+
+
Target name
+
splicing factor 3b subunit 1
+
+
+
Open Targets melanoma score
+
0.698
+
+
+
+
Open Targets baseline rank
+
21
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.6704389910023474,"interquartile_range":0.32745833716446127,"maximum":-0.9508810647263816,"mean":-1.5338619757571077,"measured_model_count":56,"median":-1.4947664924641337,"minimum":-2.378982043724258,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.3429806538378861,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9931771615712739,"interquartile_range":0.006820375637453746,"maximum":1.0,"mean":0.9957113192764605,"measured_model_count":56,"median":0.9993767217839019,"minimum":0.9673445342927015,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9999975372087276,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.000989966944183851,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0033112582781457123,"pan_cancer_fraction":0.9966887417218543,"threshold":0.5},{"context_fraction":1.0,"difference":0.01572847682119205,"pan_cancer_fraction":0.984271523178808,"threshold":0.8}],"gene_effect_mean":-0.07114636073200131,"gene_effect_median":-0.054832562133903195},"dependency_probability_context_minus_non_context_median":0.0010980663549413627,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.00347222222222221,"non_context_fraction":0.9965277777777778,"threshold":0.5},{"context_fraction":1.0,"difference":0.01649305555555558,"non_context_fraction":0.9835069444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.07460486437869474,"gene_effect_context_minus_non_context_median":-0.057426582483840916}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 28
+- **Dependency-aware candidate rank:** 28
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e09f8006beaf7360efbadeaba7ac7d0b5b2eaef0ec77e024d789a51109f10b61`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SF3B1|entrez:23451`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
28not prioritized-7
Resistance biomarker0.000
30not prioritized-9
Tumor-intrinsic / small molecule0.011
23not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.698)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SF3B1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SF3B1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SLC24A5.html b/examples/html_reports/depmap_26q1/targets/SLC24A5.html new file mode 100644 index 0000000..4d9df88 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SLC24A5.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SLC24A5 + + + + +
+ +
+

Target hypothesis report: SLC24A5

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SLC24A5
+
+
+
Target name
+
solute carrier family 24 member 5
+
+
+
Open Targets melanoma score
+
0.467
+
+
+
+
Open Targets baseline rank
+
286
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.003025095303933984,"interquartile_range":0.10082197260395905,"maximum":0.22263284691640708,"mean":0.04178003697152555,"measured_model_count":56,"median":0.04566657198688534,"minimum":-0.28433300526663596,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10384706790789303,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.007485941222069663,"interquartile_range":0.013936761588715495,"maximum":0.13392583893250115,"mean":0.02036981003205173,"measured_model_count":56,"median":0.012767474299341924,"minimum":0.0016006595218845212,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02142270281078516,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.001589657135267545,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.004963217362922899,"gene_effect_median":0.0015223561321224821},"dependency_probability_context_minus_non_context_median":-0.0016580749335111389,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.005204484873620567,"gene_effect_context_minus_non_context_median":0.0016214445087715107}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 286
+- **Dependency-aware candidate rank:** 286
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_1fc92daef66184e66d1e38ac2403101a0d5b21bc4d321f3c70d9e8379ce9bf6b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SLC24A5|entrez:283652`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
286not prioritized0
Resistance biomarker0.000
286not prioritized0
Tumor-intrinsic / small molecule0.000
286not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.467)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SLC24A5 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SLC24A5 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SLC45A2.html b/examples/html_reports/depmap_26q1/targets/SLC45A2.html new file mode 100644 index 0000000..55d05d5 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SLC45A2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SLC45A2 + + + + +
+ +
+

Target hypothesis report: SLC45A2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SLC45A2
+
+
+
Target name
+
solute carrier family 45 member 2
+
+
+
Open Targets melanoma score
+
0.547
+
+
+
+
Open Targets baseline rank
+
165
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.040933783966169555,"interquartile_range":0.14882908611197646,"maximum":0.3227303488010275,"mean":0.11567695785061881,"measured_model_count":56,"median":0.11861136448699858,"minimum":-0.08536406441108876,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.18976287007814602,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0035499116606889656,"interquartile_range":0.009916857053356331,"maximum":0.0395367321012825,"mean":0.010096898602229057,"measured_model_count":56,"median":0.006829464645826495,"minimum":0.0006995658646645975,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.013466768714045296,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0051761173448216374,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.05149240361433348,"gene_effect_median":0.05169404192771569},"dependency_probability_context_minus_non_context_median":-0.005411094838348408,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05399550656780805,"gene_effect_context_minus_non_context_median":0.052908110898977054}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 167
+- **Dependency-aware candidate rank:** 167
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_b3b0a6db95bbdbe363ed523b282b1ade2229ceeb85817ae5117b3c7af7058f2b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SLC45A2|entrez:51151`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
167not prioritized-2
Resistance biomarker0.000
168not prioritized-3
Tumor-intrinsic / small molecule0.000
167not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.547)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SLC45A2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SLC45A2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SMAD2.html b/examples/html_reports/depmap_26q1/targets/SMAD2.html new file mode 100644 index 0000000..caca2f0 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SMAD2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SMAD2 + + + + +
+ +
+

Target hypothesis report: SMAD2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SMAD2
+
+
+
Target name
+
SMAD family member 2
+
+
+
Open Targets melanoma score
+
0.552
+
+
+
+
Open Targets baseline rank
+
148
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.04437470527249164,"interquartile_range":0.10986926077333312,"maximum":0.1719519122172183,"mean":0.0053355756530233155,"measured_model_count":56,"median":0.020857726704379374,"minimum":-0.24627069147106154,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06549455550084148,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.010600862933249054,"interquartile_range":0.016872658456282188,"maximum":0.15468658704651223,"mean":0.02527240623956528,"measured_model_count":56,"median":0.019602222042527484,"minimum":0.003858964670826867,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02747352138953124,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.002283767924237845,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.01982315171908842,"gene_effect_median":-0.003612039323109724},"dependency_probability_context_minus_non_context_median":0.0023783003555883017,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.020786777149877433,"gene_effect_context_minus_non_context_median":-0.003776990002354444}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 150
+- **Dependency-aware candidate rank:** 150
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_fd3d4f728ada5f93577448ef7a9942a1c824add7aed8dd643e69147d76496b12`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SMAD2|entrez:4087`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
150not prioritized-2
Resistance biomarker0.000
151not prioritized-3
Tumor-intrinsic / small molecule0.000
150not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.552)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SMAD2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SMAD2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SMAD3.html b/examples/html_reports/depmap_26q1/targets/SMAD3.html new file mode 100644 index 0000000..44577b4 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SMAD3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SMAD3 + + + + +
+ +
+

Target hypothesis report: SMAD3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SMAD3
+
+
+
Target name
+
SMAD family member 3
+
+
+
Open Targets melanoma score
+
0.533
+
+
+
+
Open Targets baseline rank
+
184
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.090841081469131,"interquartile_range":0.10274341436989691,"maximum":0.19788349112491374,"mean":-0.03155614431899213,"measured_model_count":56,"median":-0.019242661334844407,"minimum":-0.20426070247573397,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.011902332900765911,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01586107320694835,"interquartile_range":0.026251711901153427,"maximum":0.14349263118807176,"mean":0.03783132268640034,"measured_model_count":56,"median":0.026968181859627394,"minimum":0.003981175606287827,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04211278510810178,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0012994329059359162,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.01436144254973943,"gene_effect_median":-0.0013439907680628665},"dependency_probability_context_minus_non_context_median":0.0013071120339713076,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.015059568229240775,"gene_effect_context_minus_non_context_median":-0.0013439907680628665}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 186
+- **Dependency-aware candidate rank:** 186
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_2110cd3452f34385fb6da1b287ee162c151d853acfc7ff64f2420bf885e2f347`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SMAD3|entrez:4088`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
186not prioritized-2
Resistance biomarker0.000
187not prioritized-3
Tumor-intrinsic / small molecule0.000
186not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.533)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SMAD3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SMAD3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SMARCA4.html b/examples/html_reports/depmap_26q1/targets/SMARCA4.html new file mode 100644 index 0000000..d1c7beb --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SMARCA4.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SMARCA4 + + + + +
+ +
+

Target hypothesis report: SMARCA4

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SMARCA4
+
+
+
Target name
+
SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4
+
+
+
Open Targets melanoma score
+
0.593
+
+
+
+
Open Targets baseline rank
+
78
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.6036613983479087,"interquartile_range":0.39227301538187714,"maximum":0.23567647510109768,"mean":-0.4060004403164458,"measured_model_count":56,"median":-0.40356272875642973,"minimum":-0.9591300526864226,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.21138838296603152,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.11991230214906738,"interquartile_range":0.642015102234534,"maximum":0.9765745525207847,"mean":0.43724903443681506,"measured_model_count":56,"median":0.3939739872865238,"minimum":0.001644732447700285,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.7619274043836013,"threshold_fractions":[{"denominator":56,"fraction":0.4642857142857143,"numerator":26,"threshold":0.5},{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.14332511418302418,"dependency_probability_threshold_fractions":[{"context_fraction":0.4642857142857143,"difference":0.11494796594134343,"pan_cancer_fraction":0.34933774834437087,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.047540208136234635,"pan_cancer_fraction":0.19039735099337748,"threshold":0.8}],"gene_effect_mean":-0.04237234158819192,"gene_effect_median":-0.08439069793628401},"dependency_probability_context_minus_non_context_median":0.14846696083007876,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.4642857142857143,"difference":0.1205357142857143,"non_context_fraction":0.34375,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.04985119047619049,"non_context_fraction":0.19270833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.04443210819317345,"gene_effect_context_minus_non_context_median":-0.08588989300867489}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 82
+- **Dependency-aware candidate rank:** 82
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_82bc4ef92f13b26691517fef72e6b12a768aea581a2202f644ea9788e975a62a`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SMARCA4|entrez:6597`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
82not prioritized-4
Resistance biomarker0.000
84not prioritized-6
Tumor-intrinsic / small molecule0.000
82not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.593)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SMARCA4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SMARCA4 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SMO.html b/examples/html_reports/depmap_26q1/targets/SMO.html new file mode 100644 index 0000000..133a548 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SMO.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SMO + + + + +
+ +
+

Target hypothesis report: SMO

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SMO
+
+
+
Target name
+
smoothened, frizzled class receptor
+
+
+
Open Targets melanoma score
+
0.518
+
+
+
+
Open Targets baseline rank
+
221
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.09197586746769547,"interquartile_range":0.12796016494418277,"maximum":0.37503303447012404,"mean":-0.014626427931529379,"measured_model_count":56,"median":-0.016674116349569723,"minimum":-0.21920401677704732,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03598429747648731,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01294561446721113,"interquartile_range":0.03573012833095012,"maximum":0.18896716316175619,"mean":0.03749273032273328,"measured_model_count":56,"median":0.025248343352956944,"minimum":0.0009806870821544142,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04867574279816125,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01987730449887414,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.07071470153846002,"gene_effect_median":0.065890735062588},"dependency_probability_context_minus_non_context_median":-0.020655150638843465,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.07415222175213514,"gene_effect_context_minus_non_context_median":0.0708283264465055}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 223
+- **Dependency-aware candidate rank:** 223
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_f31ee34751adbb3856a08c7eb961e5fe78b16f032a6a16b30c0db8fc2c14428a`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SMO|entrez:6608`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
223not prioritized-2
Resistance biomarker0.000
223not prioritized-2
Tumor-intrinsic / small molecule0.000
223not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.518)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SMO lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SMO in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SPEN.html b/examples/html_reports/depmap_26q1/targets/SPEN.html new file mode 100644 index 0000000..e05393b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SPEN.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SPEN + + + + +
+ +
+

Target hypothesis report: SPEN

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SPEN
+
+
+
Target name
+
spen family transcriptional repressor
+
+
+
Open Targets melanoma score
+
0.564
+
+
+
+
Open Targets baseline rank
+
125
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.20590850785643827,"interquartile_range":0.30629871670536163,"maximum":0.2961929358661407,"mean":-0.07464402855012801,"measured_model_count":56,"median":-0.1069708047403998,"minimum":-0.5774269486938107,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10039020884892337,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008554559805812224,"interquartile_range":0.10390388758026911,"maximum":0.6483530280352656,"mean":0.08850620961868054,"measured_model_count":56,"median":0.051609868437919544,"minimum":0.001341103131926982,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11245844738608134,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0345593764842699,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.00792336802270577,"pan_cancer_fraction":0.009933774834437087,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.09781353764463253,"gene_effect_median":-0.13542096809724719},"dependency_probability_context_minus_non_context_median":0.03496627856968703,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.008308531746031744,"non_context_fraction":0.009548611111111112,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.10256836239124664,"gene_effect_context_minus_non_context_median":-0.13752570185605562}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":96.29629629629629}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 127
+- **Dependency-aware candidate rank:** 127
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_b4e96c941ea4794bcaaa4f748347841026344125925996732e2ffecbee9dae29`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SPEN|entrez:23013`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
127not prioritized-2
Resistance biomarker0.000
128not prioritized-3
Tumor-intrinsic / small molecule0.000
127not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.564)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SPEN lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SPEN in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SPOP.html b/examples/html_reports/depmap_26q1/targets/SPOP.html new file mode 100644 index 0000000..83128cd --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SPOP.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SPOP + + + + +
+ +
+

Target hypothesis report: SPOP

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SPOP
+
+
+
Target name
+
speckle type BTB/POZ protein
+
+
+
Open Targets melanoma score
+
0.525
+
+
+
+
Open Targets baseline rank
+
192
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.10868585464553142,"interquartile_range":0.1953317650864464,"maximum":0.31868793248113303,"mean":-0.02062799177610516,"measured_model_count":56,"median":-0.0011139874447977718,"minimum":-0.5162901003081669,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08664591044091499,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008332047232900763,"interquartile_range":0.04870586649525993,"maximum":0.5876800902917391,"mean":0.058468297685737296,"measured_model_count":56,"median":0.021659335715944927,"minimum":0.0014736174637020138,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.057037913728160694,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.017893750255209537,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.01750236518448439,"pan_cancer_fraction":0.018211920529801324,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.8}],"gene_effect_mean":0.056645665315990565,"gene_effect_median":0.06330739048528305},"dependency_probability_context_minus_non_context_median":-0.01910772245672603,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.0183531746031746,"non_context_fraction":0.017361111111111112,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05939927404662884,"gene_effect_context_minus_non_context_median":0.06665402546532606}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 194
+- **Dependency-aware candidate rank:** 194
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_3317e48ae19c5ffa71f2d6b4c4dbe9bfcc245c28860f06c0ebb59d9006d3a71a`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SPOP|entrez:8405`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
194not prioritized-2
Resistance biomarker0.000
194not prioritized-2
Tumor-intrinsic / small molecule0.000
194not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.525)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SPOP lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SPOP in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/STAT1.html b/examples/html_reports/depmap_26q1/targets/STAT1.html new file mode 100644 index 0000000..c1a4225 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/STAT1.html @@ -0,0 +1,70 @@ +STAT1 — DepMap research preview

STAT1

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.023715990107306573,"interquartile_range":0.11483236587820499,"maximum":0.594601062886091,"mean":0.03826927595427404,"measured_model_count":56,"median":0.03441501730713435,"minimum":-0.18865251629494253,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09111637577089841,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.007581757478393323,"interquartile_range":0.018907350585128907,"maximum":0.11007117420691961,"mean":0.021312047695286645,"measured_model_count":56,"median":0.015444040039196624,"minimum":0.0002561875140645888,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02648910806352223,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00015958606018570166,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.0008335993956761281,"gene_effect_median":0.00026024357751956717},"dependency_probability_context_minus_non_context_median":-0.00021562568964750978,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.000874121588521487,"gene_effect_context_minus_non_context_median":0.00026024357751956717}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e45cf228ca8662a13ae3dec9838c879a4728d7d310e457a2e4e6708d614e3ca5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:STAT1|entrez:6772`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/STAT5B.html b/examples/html_reports/depmap_26q1/targets/STAT5B.html new file mode 100644 index 0000000..d3b4f05 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/STAT5B.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: STAT5B + + + + +
+ +
+

Target hypothesis report: STAT5B

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
STAT5B
+
+
+
Target name
+
signal transducer and activator of transcription 5B
+
+
+
Open Targets melanoma score
+
0.496
+
+
+
+
Open Targets baseline rank
+
255
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.21254486379258475,"interquartile_range":0.1507730685086402,"maximum":0.10221524728073916,"mean":-0.1297580516271845,"measured_model_count":56,"median":-0.11715704066883736,"minimum":-0.45256549872929824,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.061771795283944546,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.03489943369349236,"interquartile_range":0.09272969085043448,"maximum":0.4369411155234448,"mean":0.09325839392333803,"measured_model_count":56,"median":0.059652060425314735,"minimum":0.00564129311272788,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12762912454392683,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.029365833992934826,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.028145695364238412,"pan_cancer_fraction":0.028145695364238412,"threshold":0.5},{"context_fraction":0.0,"difference":-0.012417218543046357,"pan_cancer_fraction":0.012417218543046357,"threshold":0.8}],"gene_effect_mean":0.04488537049905639,"gene_effect_median":0.04071306645896228},"dependency_probability_context_minus_non_context_median":-0.0303876275142239,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.029513888888888888,"non_context_fraction":0.029513888888888888,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013020833333333334,"non_context_fraction":0.013020833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04706729823164932,"gene_effect_context_minus_non_context_median":0.04224545430101631}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 257
+- **Dependency-aware candidate rank:** 257
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_e21f5e617c739dca9fdc377a6421745cd78adfe0644ff739be3f201c394456e1`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:STAT5B|entrez:6777`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
257not prioritized-2
Resistance biomarker0.000
257not prioritized-2
Tumor-intrinsic / small molecule0.000
257not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.496)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: STAT5B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for STAT5B in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/STK11.html b/examples/html_reports/depmap_26q1/targets/STK11.html new file mode 100644 index 0000000..4b02f84 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/STK11.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: STK11 + + + + +
+ +
+

Target hypothesis report: STK11

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
STK11
+
+
+
Target name
+
serine/threonine kinase 11
+
+
+
Open Targets melanoma score
+
0.631
+
+
+
+
Open Targets baseline rank
+
42
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.33769402041129626,"interquartile_range":0.34553422259709676,"maximum":1.3773386060676387,"mean":-0.1472549078841526,"measured_model_count":56,"median":-0.14109773350213328,"minimum":-0.8534586542297331,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.007840202185800504,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.01945733984178246,"interquartile_range":0.2964351119072127,"maximum":0.9205200111570674,"mean":0.21506176370357213,"measured_model_count":56,"median":0.07264424891737002,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.31589245174899516,"threshold_fractions":[{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.5},{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01879693497834929,"dependency_probability_threshold_fractions":[{"context_fraction":0.14285714285714285,"difference":-0.07734153263954588,"pan_cancer_fraction":0.22019867549668873,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":-0.026608325449385045,"pan_cancer_fraction":0.11589403973509933,"threshold":0.8}],"gene_effect_mean":0.041811237349291486,"gene_effect_median":0.03470423374620135},"dependency_probability_context_minus_non_context_median":-0.020380121457312758,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.14285714285714285,"difference":-0.0811011904761905,"non_context_fraction":0.22395833333333334,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":-0.027901785714285712,"non_context_fraction":0.1171875,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04384372805377118,"gene_effect_context_minus_non_context_median":0.036281749337344266}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 49
+- **Dependency-aware candidate rank:** 49
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_f573ffdfa89f249ac5ced93e70646fc1641eb27f5beb01507a378563c58d1304`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:STK11|entrez:6794`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
49not prioritized-7
Resistance biomarker0.000
51not prioritized-9
Tumor-intrinsic / small molecule0.000
49not prioritized-7
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.631)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: STK11 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for STK11 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/STN1.html b/examples/html_reports/depmap_26q1/targets/STN1.html new file mode 100644 index 0000000..c8fca1b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/STN1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: STN1 + + + + +
+ +
+

Target hypothesis report: STN1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
STN1
+
+
+
Target name
+
STN1 subunit of CST complex
+
+
+
Open Targets melanoma score
+
0.523
+
+
+
+
Open Targets baseline rank
+
197
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.4779879422685708,"interquartile_range":0.29444075349956655,"maximum":0.16849346309225044,"mean":-0.3457827371641288,"measured_model_count":56,"median":-0.3320372797448661,"minimum":-0.9777832742302645,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.18354718876900422,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.09289156314684381,"interquartile_range":0.45956568201046494,"maximum":0.9778197824284264,"mean":0.35360489820405777,"measured_model_count":56,"median":0.2679704032719562,"minimum":0.002797966808841758,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5524572451573088,"threshold_fractions":[{"denominator":56,"fraction":0.30357142857142855,"numerator":17,"threshold":0.5},{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.1587208773509043,"dependency_probability_threshold_fractions":[{"context_fraction":0.30357142857142855,"difference":-0.14841532639545885,"pan_cancer_fraction":0.4519867549668874,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.10631504257332072,"pan_cancer_fraction":0.24917218543046357,"threshold":0.8}],"gene_effect_mean":0.12108837825884422,"gene_effect_median":0.08607346039156422},"dependency_probability_context_minus_non_context_median":-0.16553983909783232,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.30357142857142855,"difference":-0.15562996031746035,"non_context_fraction":0.4592013888888889,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.11148313492063494,"non_context_fraction":0.2543402777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.12697461886864864,"gene_effect_context_minus_non_context_median":0.09113019244100451}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 199
+- **Dependency-aware candidate rank:** 199
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_325900cec01f74632d5a8963560fd9eb0404d8bf243d051cb31d1424720729eb`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:STN1|entrez:79991`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
199not prioritized-2
Resistance biomarker0.000
199not prioritized-2
Tumor-intrinsic / small molecule0.000
199not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.523)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: STN1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for STN1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SUFU.html b/examples/html_reports/depmap_26q1/targets/SUFU.html new file mode 100644 index 0000000..c7936d4 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SUFU.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SUFU + + + + +
+ +
+

Target hypothesis report: SUFU

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SUFU
+
+
+
Target name
+
SUFU negative regulator of hedgehog signaling
+
+
+
Open Targets melanoma score
+
0.543
+
+
+
+
Open Targets baseline rank
+
175
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.023938544589964868,"interquartile_range":0.1774876002492798,"maximum":0.95481212338376,"mean":0.06462142656096546,"measured_model_count":56,"median":0.05071099091677807,"minimum":-0.7061946864814099,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.15354905565931493,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005377839592163817,"interquartile_range":0.021656509327421553,"maximum":0.811876611301506,"mean":0.03797623516616818,"measured_model_count":56,"median":0.012147568247679989,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02703434891958537,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002946423118163285,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.012890255439924312,"pan_cancer_fraction":0.004966887417218543,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.015373699148533584,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.01616561260624235,"gene_effect_median":0.010250265714132317},"dependency_probability_context_minus_non_context_median":-0.0031789831274965513,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.013516865079365078,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.016121031746031744,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01695144099682358,"gene_effect_context_minus_non_context_median":0.01124857366622331}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 177
+- **Dependency-aware candidate rank:** 177
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_942290a38450ab42ef87a67113bbfe0c6f1cc6aaabf3a1464f5ad179648e09d4`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SUFU|entrez:51684`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
177not prioritized-2
Resistance biomarker0.000
178not prioritized-3
Tumor-intrinsic / small molecule0.000
177not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.543)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SUFU lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SUFU in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SUZ12.html b/examples/html_reports/depmap_26q1/targets/SUZ12.html new file mode 100644 index 0000000..b00f26e --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SUZ12.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SUZ12 + + + + +
+ +
+

Target hypothesis report: SUZ12

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SUZ12
+
+
+
Target name
+
SUZ12 polycomb repressive complex 2 subunit
+
+
+
Open Targets melanoma score
+
0.475
+
+
+
+
Open Targets baseline rank
+
278
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.4965029253131678,"interquartile_range":0.34493944854229963,"maximum":0.4677630930028186,"mean":-0.34131115668653944,"measured_model_count":56,"median":-0.33607475463804537,"minimum":-1.2517467051124003,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.15156347677086815,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0804547369061895,"interquartile_range":0.522462756994033,"maximum":0.9941988949339067,"mean":0.35415518658327777,"measured_model_count":56,"median":0.28560992279472086,"minimum":0.0008325024643399397,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.6029174939002225,"threshold_fractions":[{"denominator":56,"fraction":0.3392857142857143,"numerator":19,"threshold":0.5},{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.09645538695062106,"dependency_probability_threshold_fractions":[{"context_fraction":0.3392857142857143,"difference":-0.07710501419110688,"pan_cancer_fraction":0.4163907284768212,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":-0.08952223273415326,"pan_cancer_fraction":0.17880794701986755,"threshold":0.8}],"gene_effect_mean":0.06396868090500646,"gene_effect_median":0.05833410563250985},"dependency_probability_context_minus_non_context_median":-0.10570987062618109,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.3392857142857143,"difference":-0.0808531746031746,"non_context_fraction":0.4201388888888889,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":-0.09387400793650792,"non_context_fraction":0.1831597222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.06707826956011098,"gene_effect_context_minus_non_context_median":0.061797847408295026}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 278
+- **Dependency-aware candidate rank:** 278
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_c6f7218c8cb45190bd221c4b32334939c435eba72386d9e50bc127e15bafcb96`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SUZ12|entrez:23512`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
278not prioritized0
Resistance biomarker0.000
278not prioritized0
Tumor-intrinsic / small molecule0.000
278not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.475)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SUZ12 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SUZ12 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/SYK.html b/examples/html_reports/depmap_26q1/targets/SYK.html new file mode 100644 index 0000000..972f25b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/SYK.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: SYK + + + + +
+ +
+

Target hypothesis report: SYK

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
SYK
+
+
+
Target name
+
spleen associated tyrosine kinase
+
+
+
Open Targets melanoma score
+
0.564
+
+
+
+
Open Targets baseline rank
+
127
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.028301337947750776,"interquartile_range":0.09846484453277939,"maximum":0.2761142482769202,"mean":0.024136028244293617,"measured_model_count":56,"median":0.008529689252564848,"minimum":-0.19785112063596755,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07016350658502861,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.009531068922012565,"interquartile_range":0.01679429075027903,"maximum":0.12053995537301158,"mean":0.021483934728060494,"measured_model_count":56,"median":0.018472304540237433,"minimum":0.0016419199380332049,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.026325359672291597,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0018682134466057876,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.019867549668874173,"pan_cancer_fraction":0.019867549668874173,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013245033112582781,"pan_cancer_fraction":0.013245033112582781,"threshold":0.8}],"gene_effect_mean":0.0126587746279189,"gene_effect_median":-0.018126393479598164},"dependency_probability_context_minus_non_context_median":0.0018882076919032077,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.020833333333333332,"non_context_fraction":0.020833333333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013888888888888888,"non_context_fraction":0.013888888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.013274131727887184,"gene_effect_context_minus_non_context_median":-0.01861567772250128}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 129
+- **Dependency-aware candidate rank:** 129
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_282298b8300d668c37fd425237e864ee18a1f85d6e44f8f47fdb715b1e30f9de`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:SYK|entrez:6850`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
129not prioritized-2
Resistance biomarker0.000
130not prioritized-3
Tumor-intrinsic / small molecule0.000
129not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.564)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: SYK lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for SYK in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TAP1.html b/examples/html_reports/depmap_26q1/targets/TAP1.html new file mode 100644 index 0000000..781ea37 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TAP1.html @@ -0,0 +1,70 @@ +TAP1 — DepMap research preview

TAP1

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.16724802560020013,"interquartile_range":0.1985094558616541,"maximum":0.5470468266686689,"mean":-0.07939806290217721,"measured_model_count":56,"median":-0.07247945665159533,"minimum":-0.5733755101579874,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03126143026145397,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.014782179225490823,"interquartile_range":0.08211488592426243,"maximum":0.6446446410081932,"mean":0.08772285017978665,"measured_model_count":56,"median":0.0447208452197298,"minimum":6.830493540377923e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09689706514975326,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.02277193409938026,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.025780510879848624,"pan_cancer_fraction":0.009933774834437087,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.04472110971213279,"gene_effect_median":0.05355281064177525},"dependency_probability_context_minus_non_context_median":-0.023657032478633322,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.027033730158730156,"non_context_fraction":0.008680555555555556,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.046895052545361415,"gene_effect_context_minus_non_context_median":0.055247717762366116}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_639b86f57c7bd2c847c9f32433cbc12a5867a71e5e95f5fe1cd7fec54f2a3cbc`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TAP1|entrez:6890`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/TAP2.html b/examples/html_reports/depmap_26q1/targets/TAP2.html new file mode 100644 index 0000000..dc68f48 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TAP2.html @@ -0,0 +1,70 @@ +TAP2 — DepMap research preview

TAP2

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.11718440590337778,"interquartile_range":0.341363350857,"maximum":0.48787387730742277,"mean":0.046799923839240254,"measured_model_count":56,"median":0.034986271431895845,"minimum":-0.4092929272676856,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2241789449536222,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0019427190737520005,"interquartile_range":0.06363806528902216,"maximum":0.36713822743055147,"mean":0.04596588318721421,"measured_model_count":56,"median":0.012748389342080056,"minimum":0.00018033560046999035,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06558078436277416,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00025281361128764654,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.015393517900672851,"gene_effect_median":-0.023019405772148102},"dependency_probability_context_minus_non_context_median":-0.00025281361128764654,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.016141813909733335,"gene_effect_context_minus_non_context_median":-0.02350817947630058}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_bc1603d100048f5a1ad3689524e11bbf7adf28285af48a5c17316f3aa27cf70e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TAP2|entrez:6891`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/TBL1XR1.html b/examples/html_reports/depmap_26q1/targets/TBL1XR1.html new file mode 100644 index 0000000..85e4dfe --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TBL1XR1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TBL1XR1 + + + + +
+ +
+

Target hypothesis report: TBL1XR1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TBL1XR1
+
+
+
Target name
+
TBL1X/Y related 1
+
+
+
Open Targets melanoma score
+
0.511
+
+
+
+
Open Targets baseline rank
+
235
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.44322955679950454,"interquartile_range":0.2668450960778149,"maximum":0.9833284356887129,"mean":-0.3174421086565639,"measured_model_count":56,"median":-0.33277910671051136,"minimum":-1.9646819675877583,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.17638446072168962,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.08652037502979554,"interquartile_range":0.41937699416997204,"maximum":1.0,"mean":0.3189140280518254,"measured_model_count":56,"median":0.27129473782400343,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5058973691997676,"threshold_fractions":[{"denominator":56,"fraction":0.26785714285714285,"numerator":15,"threshold":0.5},{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.005472140106186962,"dependency_probability_threshold_fractions":[{"context_fraction":0.26785714285714285,"difference":-0.08230842005676442,"pan_cancer_fraction":0.35016556291390727,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.1326868495742668,"pan_cancer_fraction":0.18625827814569537,"threshold":0.8}],"gene_effect_mean":0.053718896805078076,"gene_effect_median":-0.003826731972826569},"dependency_probability_context_minus_non_context_median":0.005993485466598336,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.26785714285714285,"difference":-0.08630952380952384,"non_context_fraction":0.3541666666666667,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.13913690476190477,"non_context_fraction":0.19270833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.056330232066436,"gene_effect_context_minus_non_context_median":-0.005183196194501027}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 237
+- **Dependency-aware candidate rank:** 237
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_cdac3dbccce2709d79074d20902a8768c584ebab5c7bc2f3f810c3d6694f9553`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TBL1XR1|entrez:79718`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
237not prioritized-2
Resistance biomarker0.000
237not prioritized-2
Tumor-intrinsic / small molecule0.000
237not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.511)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TBL1XR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TBL1XR1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TBX3.html b/examples/html_reports/depmap_26q1/targets/TBX3.html new file mode 100644 index 0000000..91f4d67 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TBX3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TBX3 + + + + +
+ +
+

Target hypothesis report: TBX3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TBX3
+
+
+
Target name
+
T-box transcription factor 3
+
+
+
Open Targets melanoma score
+
0.588
+
+
+
+
Open Targets baseline rank
+
87
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.23573951656616127,"interquartile_range":0.20424707807953718,"maximum":0.34140535907966685,"mean":-0.13581506022797174,"measured_model_count":56,"median":-0.144887275560554,"minimum":-0.5553790334161137,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.031492438486624086,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.025720312146242173,"interquartile_range":0.11840113413674436,"maximum":0.6616848325855214,"mean":0.12232477255665541,"measured_model_count":56,"median":0.07955915571703014,"minimum":0.0008777444154026813,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14412144628298654,"threshold_fractions":[{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0313984644600503,"dependency_probability_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":0.028382213812677387,"pan_cancer_fraction":0.04304635761589404,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014072847682119206,"pan_cancer_fraction":0.014072847682119206,"threshold":0.8}],"gene_effect_mean":-0.025790819731207726,"gene_effect_median":-0.05426358637532251},"dependency_probability_context_minus_non_context_median":0.03214660788018489,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":0.02976190476190476,"non_context_fraction":0.041666666666666664,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014756944444444444,"non_context_fraction":0.014756944444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.027044540134808087,"gene_effect_context_minus_non_context_median":-0.05659689322368143}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 90
+- **Dependency-aware candidate rank:** 90
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_20e736c6d97c92d571e7d401407894dab365db65714a9998606d9f76a28e7e6a`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TBX3|entrez:6926`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
90not prioritized-3
Resistance biomarker0.000
92not prioritized-5
Tumor-intrinsic / small molecule0.000
90not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.588)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TBX3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TBX3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TCL1A.html b/examples/html_reports/depmap_26q1/targets/TCL1A.html new file mode 100644 index 0000000..da28177 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TCL1A.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TCL1A + + + + +
+ +
+

Target hypothesis report: TCL1A

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TCL1A
+
+
+
Target name
+
TCL1 family AKT coactivator A
+
+
+
Open Targets melanoma score
+
0.506
+
+
+
+
Open Targets baseline rank
+
248
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.11206944388589762,"interquartile_range":0.13506523175571503,"maximum":0.353208737650306,"mean":-0.029016807448142428,"measured_model_count":56,"median":-0.000812838632041863,"minimum":-0.45051063472828873,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.022995787869817392,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.015122906774957338,"interquartile_range":0.04261576512491955,"maximum":0.40792408921870826,"mean":0.05089308425254634,"measured_model_count":56,"median":0.02026722678410809,"minimum":0.0009637063547128886,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05773867189987689,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0010357334647972845,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.025453933451171612,"gene_effect_median":-0.003189848265832563},"dependency_probability_context_minus_non_context_median":-0.0010798945527638222,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.026691277438381313,"gene_effect_context_minus_non_context_median":-0.00359331667726691}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 250
+- **Dependency-aware candidate rank:** 250
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_48c7ea73dcd2da21f1516254c03e3d36f9df985a59d63e0e2b8e1ce0d0c458df`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TCL1A|entrez:8115`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
250not prioritized-2
Resistance biomarker0.000
250not prioritized-2
Tumor-intrinsic / small molecule0.000
250not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.506)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TCL1A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TCL1A in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TENT5C.html b/examples/html_reports/depmap_26q1/targets/TENT5C.html new file mode 100644 index 0000000..e083f74 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TENT5C.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TENT5C + + + + +
+ +
+

Target hypothesis report: TENT5C

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TENT5C
+
+
+
Target name
+
terminal nucleotidyltransferase 5C
+
+
+
Open Targets melanoma score
+
0.479
+
+
+
+
Open Targets baseline rank
+
274
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.03864097744616059,"interquartile_range":0.11511279099291087,"maximum":0.2541597207495479,"mean":0.022881062803934028,"measured_model_count":56,"median":0.021952823430253073,"minimum":-0.23474050442874117,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07647181354675028,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008053275498989303,"interquartile_range":0.021966046073802734,"maximum":0.13889360325225697,"mean":0.0244585667177243,"measured_model_count":56,"median":0.018800263137722335,"minimum":0.00141942221638269,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.030019321572792038,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.002498147846532319,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.011498624623446477,"gene_effect_median":-0.008879290858561668},"dependency_probability_context_minus_non_context_median":0.0025907753334622093,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.012057585542641792,"gene_effect_context_minus_non_context_median":-0.009323741953518788}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 274
+- **Dependency-aware candidate rank:** 274
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_55351733ddfc8f1e09e5df5d6993253a07d9eb597f6f618c64e854fc8374f765`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TENT5C|entrez:54855`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
274not prioritized0
Resistance biomarker0.000
274not prioritized0
Tumor-intrinsic / small molecule0.000
274not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.479)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TENT5C lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TENT5C in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TERT.html b/examples/html_reports/depmap_26q1/targets/TERT.html new file mode 100644 index 0000000..95d6888 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TERT.html @@ -0,0 +1,435 @@ + + + + +TargetIntel-IO report: TERT + + + + +
+ +
+

Target hypothesis report: TERT

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TERT
+
+
+
Target name
+
telomerase reverse transcriptase
+
+
+
Open Targets melanoma score
+
0.709
+
+
+
+
Open Targets baseline rank
+
16
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.13632697698590185,"interquartile_range":0.17256257719257062,"maximum":0.31463935418414035,"mean":-0.053094014995252854,"measured_model_count":56,"median":-0.04819403767771936,"minimum":-0.39336959009981265,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.036235600206668786,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.013545260600762363,"interquartile_range":0.05502605515873926,"maximum":0.4509431568440402,"mean":0.05984677273308569,"measured_model_count":56,"median":0.03060298315596087,"minimum":0.0014867736856534384,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06857131575950162,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002953237501739467,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0173841059602649,"pan_cancer_fraction":0.0173841059602649,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.8}],"gene_effect_mean":0.00929622077226909,"gene_effect_median":-0.001507960338499259},"dependency_probability_context_minus_non_context_median":-0.002997141357305111,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.018229166666666668,"non_context_fraction":0.018229166666666668,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.009748120393143302,"gene_effect_context_minus_non_context_median":-0.0015774451250942373}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 23
+- **Dependency-aware candidate rank:** 24
+- **Rank delta:** 1
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_3aa6751335d21b56b138308a5905ac03f3165d6ce2b7ae7e136e724f715ae929`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TERT|entrez:7015`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / biomarker
+
+
+
Role confidence
+
medium-high
+
+
+
Therapeutic direction
+
use as biomarker / pathway targeting if appropriate
+
+
+
Best modality
+
tumor-intrinsic biomarker / pathway context
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
23not prioritized-7
Resistance biomarker0.385
14low2
Tumor-intrinsic / small molecule0.513
8medium8
+
+ +
+

Evidence for

+
    +
  • High Open Targets melanoma association score (0.709)
    • +
  • Stable role classifier confidence is medium-high
    • +
  • Biomarker fit is medium-high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Most useful as biomarker or stratification marker rather than direct therapeutic target
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
0.889
+
+
+
+
Contradiction score
+
0.240
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TERT lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: biomarker validation

+

Next experiment: Test whether TERT status or expression differs between anti-PD-1 responders and non-responders in an independent melanoma cohort.

+

Rationale: This would determine whether the candidate has practical value as a resistance biomarker or patient-stratification feature.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TET1.html b/examples/html_reports/depmap_26q1/targets/TET1.html new file mode 100644 index 0000000..36d3ac6 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TET1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TET1 + + + + +
+ +
+

Target hypothesis report: TET1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TET1
+
+
+
Target name
+
tet methylcytosine dioxygenase 1
+
+
+
Open Targets melanoma score
+
0.525
+
+
+
+
Open Targets baseline rank
+
194
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06612237325348896,"interquartile_range":0.10021823049998557,"maximum":0.1271729541137778,"mean":-0.028190732169697717,"measured_model_count":56,"median":-0.01236085251979058,"minimum":-0.2695130876604978,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.034095857246496615,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.015077381903148862,"interquartile_range":0.022546163524319658,"maximum":0.14865571836631888,"mean":0.03450340317400059,"measured_model_count":56,"median":0.024035437041026612,"minimum":0.006922954810222002,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03762354542746852,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0007531276788584583,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.012800927998634417,"gene_effect_median":0.001906037661590601},"dependency_probability_context_minus_non_context_median":-0.000861527866092001,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.013423195331901396,"gene_effect_context_minus_non_context_median":0.001906037661590601}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 196
+- **Dependency-aware candidate rank:** 196
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_b839bce56c8f1593e320c4d61e7f42609798cff76a042f0f9ef6d3a6793420fa`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TET1|entrez:80312`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
196not prioritized-2
Resistance biomarker0.000
196not prioritized-2
Tumor-intrinsic / small molecule0.000
196not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.525)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TET1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TET1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TET2.html b/examples/html_reports/depmap_26q1/targets/TET2.html new file mode 100644 index 0000000..f31782d --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TET2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TET2 + + + + +
+ +
+

Target hypothesis report: TET2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TET2
+
+
+
Target name
+
tet methylcytosine dioxygenase 2
+
+
+
Open Targets melanoma score
+
0.646
+
+
+
+
Open Targets baseline rank
+
33
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.020242220098773266,"interquartile_range":0.13103610160268922,"maximum":0.3622793156577621,"mean":0.08204156574215123,"measured_model_count":56,"median":0.08659371212470038,"minimum":-0.1670518659975791,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1512783217014625,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005266320111456892,"interquartile_range":0.015500246077887905,"maximum":0.11891323222815336,"mean":0.015839052780095838,"measured_model_count":56,"median":0.007554157730363114,"minimum":0.001314782273029547,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.020766566189344797,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0004343403727579114,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.029308441537724106,"gene_effect_median":-0.025866293969080884},"dependency_probability_context_minus_non_context_median":-0.0004403789008672228,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0307331574458079,"gene_effect_context_minus_non_context_median":-0.02655563898434228}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 40
+- **Dependency-aware candidate rank:** 40
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_eda1d97542f3455aedc7d5de5e9ae3b276141439c8e6539ccf897be73a44dfe4`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TET2|entrez:54790`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
40not prioritized-7
Resistance biomarker0.000
42not prioritized-9
Tumor-intrinsic / small molecule0.000
35not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.646)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TET2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TET2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TFE3.html b/examples/html_reports/depmap_26q1/targets/TFE3.html new file mode 100644 index 0000000..338553b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TFE3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TFE3 + + + + +
+ +
+

Target hypothesis report: TFE3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TFE3
+
+
+
Target name
+
transcription factor binding to IGHM enhancer 3
+
+
+
Open Targets melanoma score
+
0.523
+
+
+
+
Open Targets baseline rank
+
198
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.049611378294050275,"interquartile_range":0.12705938681379497,"maximum":0.3972896850342244,"mean":0.01444431817727483,"measured_model_count":56,"median":-0.010454951169714191,"minimum":-0.29319215632904333,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07744800851974469,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008716575061100169,"interquartile_range":0.026418028876411564,"maximum":0.18711563988246177,"mean":0.032323017648411424,"measured_model_count":56,"median":0.020410044427780348,"minimum":0.0002168070410135217,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.035134603937511735,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0042392718543003485,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.022922720848554935,"gene_effect_median":-0.042734776296091556},"dependency_probability_context_minus_non_context_median":0.004332365482609325,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.024037019778693013,"gene_effect_context_minus_non_context_median":-0.04341747415317606}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 200
+- **Dependency-aware candidate rank:** 200
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_43d8509a90cd46513ae1ff1da427d3b3d581de5e607771511933d66256fcd4f3`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TFE3|entrez:7030`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
200not prioritized-2
Resistance biomarker0.000
200not prioritized-2
Tumor-intrinsic / small molecule0.000
200not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.523)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TFE3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TFE3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TFEB.html b/examples/html_reports/depmap_26q1/targets/TFEB.html new file mode 100644 index 0000000..d1db82f --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TFEB.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TFEB + + + + +
+ +
+

Target hypothesis report: TFEB

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TFEB
+
+
+
Target name
+
transcription factor EB
+
+
+
Open Targets melanoma score
+
0.531
+
+
+
+
Open Targets baseline rank
+
186
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.0555191255330701,"interquartile_range":0.11292522004414328,"maximum":0.28573843056988407,"mean":0.003798524527747693,"measured_model_count":56,"median":0.0019224156039644225,"minimum":-0.22832367937072187,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05740609451107318,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.011692148037405516,"interquartile_range":0.01921849388295361,"maximum":0.14720540313854205,"mean":0.026132526521341532,"measured_model_count":56,"median":0.01872188394700413,"minimum":0.0016405899904093201,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.030910641920359125,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002390505293227832,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.0015270513008616253,"gene_effect_median":0.0004748142292487288},"dependency_probability_context_minus_non_context_median":-0.0025091977326434783,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.001601282961320164,"gene_effect_context_minus_non_context_median":0.0004748142292487288}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 188
+- **Dependency-aware candidate rank:** 188
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_302cc54066a963b906ae4297371c1db7ef85e9fbfa9583dbe0ae8f67ec97ef77`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TFEB|entrez:7942`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
188not prioritized-2
Resistance biomarker0.000
189not prioritized-3
Tumor-intrinsic / small molecule0.000
188not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.531)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TFEB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TFEB in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TGFB1.html b/examples/html_reports/depmap_26q1/targets/TGFB1.html new file mode 100644 index 0000000..446b82a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TGFB1.html @@ -0,0 +1,70 @@ +TGFB1 — DepMap research preview

TGFB1

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.1175744957723274,"interquartile_range":0.14613260242689258,"maximum":0.20122114815229164,"mean":-0.053333625094820716,"measured_model_count":56,"median":-0.0584569922925765,"minimum":-0.33194533256770453,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02855810665456519,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.013271787489163883,"interquartile_range":0.05501703382036138,"maximum":0.29440262801615275,"mean":0.0509541191786031,"measured_model_count":56,"median":0.03879322257892474,"minimum":0.004071154988135978,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06828882130952527,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.002229677539982232,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.0062627310967641875,"gene_effect_median":0.0028936828192190275},"dependency_probability_context_minus_non_context_median":0.002268981663492299,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0065671694139679965,"gene_effect_context_minus_non_context_median":0.0032393776818710265}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_06ec3bccac84ba7114eb5d4bf7c85ada91f20a7d62f3b59bbbff7cf322523168`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TGFB1|entrez:7040`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/TGFBR1.html b/examples/html_reports/depmap_26q1/targets/TGFBR1.html new file mode 100644 index 0000000..93b813b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TGFBR1.html @@ -0,0 +1,70 @@ +TGFBR1 — DepMap research preview

TGFBR1

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.11823496925689045,"interquartile_range":0.1815436279172879,"maximum":0.43900246007390836,"mean":-0.06367073288882538,"measured_model_count":56,"median":-0.04561856834087192,"minimum":-1.1646984150993804,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06330865866039743,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.009869685591532288,"interquartile_range":0.05375446023576694,"maximum":0.9941992212349525,"mean":0.0798662849461864,"measured_model_count":56,"median":0.03221306181112013,"minimum":0.0002895613022257384,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06362414582729922,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.027031213832151124,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.04623935666982025,"pan_cancer_fraction":0.08195364238410596,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.0152554399243141,"pan_cancer_fraction":0.033112582781456956,"threshold":0.8}],"gene_effect_mean":0.07847455721250848,"gene_effect_median":0.07036460916164552},"dependency_probability_context_minus_non_context_median":-0.029586105478545344,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.04848710317460318,"non_context_fraction":0.0842013888888889,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.015997023809523808,"non_context_fraction":0.033854166666666664,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08228929263256096,"gene_effect_context_minus_non_context_median":0.07618939226126986}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_8024c3f1a166237bfd323397a878e35e9a91c24effde75af6a2a2b954766b2da`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TGFBR1|entrez:7046`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/TIGIT.html b/examples/html_reports/depmap_26q1/targets/TIGIT.html new file mode 100644 index 0000000..04c746a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TIGIT.html @@ -0,0 +1,70 @@ +TIGIT — DepMap research preview

TIGIT

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.09649098266140216,"interquartile_range":0.14024504818016426,"maximum":0.20955328804252174,"mean":-0.038102640455839755,"measured_model_count":56,"median":-0.026380581032389563,"minimum":-0.31063674659862406,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.043754065518762084,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.014662390053882784,"interquartile_range":0.035014807249186236,"maximum":0.22730028300055188,"mean":0.04368399569486412,"measured_model_count":56,"median":0.029299535174605706,"minimum":0.004326948526831013,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04967719730306902,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.010697027991600258,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.030104735789959987,"gene_effect_median":0.042814784000523104},"dependency_probability_context_minus_non_context_median":-0.011414511459108365,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03156816044641642,"gene_effect_context_minus_non_context_median":0.04473808091663155}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ec597885a6d540cbe296f1d7dcd3082bca9b8b936454f6f0597a4c21bbd573f2`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TIGIT|entrez:201633`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/TMEM127.html b/examples/html_reports/depmap_26q1/targets/TMEM127.html new file mode 100644 index 0000000..077043c --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TMEM127.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TMEM127 + + + + +
+ +
+

Target hypothesis report: TMEM127

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TMEM127
+
+
+
Target name
+
transmembrane protein 127
+
+
+
Open Targets melanoma score
+
0.511
+
+
+
+
Open Targets baseline rank
+
236
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.37160855924898195,"interquartile_range":0.23945586380532383,"maximum":0.04819261286756693,"mean":-0.2743793036390408,"measured_model_count":56,"median":-0.2801840245311775,"minimum":-0.7302462912517111,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.13215269544365812,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.07290625944096693,"interquartile_range":0.35628977617921886,"maximum":0.8298694277716979,"mean":0.2563707669744083,"measured_model_count":56,"median":0.1948213468608736,"minimum":0.006835996438229038,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.4291960356201858,"threshold_fractions":[{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.007863065272489977,"dependency_probability_threshold_fractions":[{"context_fraction":0.17857142857142858,"difference":0.02045884578997162,"pan_cancer_fraction":0.15811258278145696,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.014427625354777672,"pan_cancer_fraction":0.03228476821192053,"threshold":0.8}],"gene_effect_mean":0.011635002407191897,"gene_effect_median":-0.0037427060854459127},"dependency_probability_context_minus_non_context_median":-0.009398192269829686,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.17857142857142858,"difference":0.021453373015873023,"non_context_fraction":0.15711805555555555,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.015128968253968256,"non_context_fraction":0.03298611111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01220059280198632,"gene_effect_context_minus_non_context_median":-0.004013585868380187}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 238
+- **Dependency-aware candidate rank:** 238
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_891aad5d1c4c9796b1c683e9cdc71c0c62a01f01c5069234267d3cea760bd5bf`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TMEM127|entrez:55654`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
238not prioritized-2
Resistance biomarker0.000
238not prioritized-2
Tumor-intrinsic / small molecule0.000
238not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.511)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TMEM127 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TMEM127 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TNFRSF17.html b/examples/html_reports/depmap_26q1/targets/TNFRSF17.html new file mode 100644 index 0000000..fb4136a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TNFRSF17.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TNFRSF17 + + + + +
+ +
+

Target hypothesis report: TNFRSF17

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TNFRSF17
+
+
+
Target name
+
TNF receptor superfamily member 17
+
+
+
Open Targets melanoma score
+
0.461
+
+
+
+
Open Targets baseline rank
+
294
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.10457536925669791,"interquartile_range":0.07142883580734052,"maximum":0.10918749680547649,"mean":-0.06992867394566103,"measured_model_count":56,"median":-0.07182926242556906,"minimum":-0.24504065716705284,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0331465334493574,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.023074013879230557,"interquartile_range":0.0433904521116308,"maximum":0.1443957018357807,"mean":0.04704715320781859,"measured_model_count":56,"median":0.04088511534774647,"minimum":0.0063179500583258425,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06646446599086135,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0049121025417101435,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.011945886868925046,"gene_effect_median":0.011137176340701466},"dependency_probability_context_minus_non_context_median":-0.0054131304480627696,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.012526589702831076,"gene_effect_context_minus_non_context_median":0.01164453388063047}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 294
+- **Dependency-aware candidate rank:** 294
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_72a0b0fce8512a7e516b1d482dcfb7f4d06530bf9564bca9ec3a211a0dd21759`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TNFRSF17|entrez:608`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
294not prioritized0
Resistance biomarker0.000
294not prioritized0
Tumor-intrinsic / small molecule0.000
294not prioritized0
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.461)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TNFRSF17 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TNFRSF17 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TNFRSF18.html b/examples/html_reports/depmap_26q1/targets/TNFRSF18.html new file mode 100644 index 0000000..eed1d54 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TNFRSF18.html @@ -0,0 +1,70 @@ +TNFRSF18 — DepMap research preview

TNFRSF18

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.07992287378746069,"interquartile_range":0.16347160736788924,"maximum":0.32511428764823874,"mean":0.005618184042927659,"measured_model_count":56,"median":0.0031678861143592326,"minimum":-0.21018912008582508,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08354873358042854,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0081397024736693,"interquartile_range":0.031395612021018315,"maximum":0.15023873693250508,"mean":0.03150136361917189,"measured_model_count":56,"median":0.020690473212946793,"minimum":0.0011876348486895474,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03953531449468761,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0005077224690275967,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.0011663910963865837,"gene_effect_median":0.0003505570529605071},"dependency_probability_context_minus_non_context_median":0.0005077224690275967,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0012230906635720294,"gene_effect_context_minus_non_context_median":0.00040631170298858175}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_a1f21dfb69f2e55b310fe38e88f66b09c1adcbd74d74b7f83987f4e78ead1d09`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TNFRSF18|entrez:8784`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/TP53.html b/examples/html_reports/depmap_26q1/targets/TP53.html new file mode 100644 index 0000000..67ccdee --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TP53.html @@ -0,0 +1,435 @@ + + + + +TargetIntel-IO report: TP53 + + + + +
+ +
+

Target hypothesis report: TP53

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TP53
+
+
+
Target name
+
tumor protein p53
+
+
+
Open Targets melanoma score
+
0.699
+
+
+
+
Open Targets baseline rank
+
20
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.2682694657614673,"interquartile_range":0.9489021294915423,"maximum":2.138262318199002,"mean":0.8412020305059892,"measured_model_count":56,"median":0.8202592324433257,"minimum":-0.056749573342901705,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.2171715952530096,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0,"interquartile_range":0.0022901272198506146,"maximum":0.0445887680510194,"mean":0.0038902041225716394,"measured_model_count":56,"median":2.371112152923413e-07,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0022901272198506146,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002697179320060296,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.41701743563053467,"gene_effect_median":0.5818272714545053},"dependency_probability_context_minus_non_context_median":-0.002942185984413948,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.43728911652924124,"gene_effect_context_minus_non_context_median":0.592868277866274}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 27
+- **Dependency-aware candidate rank:** 27
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_ce64666108a5b359fbafb7a0ba19d80daa01b7fdb39a82f26790a367a87770c6`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TP53|entrez:7157`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
tumor-intrinsic driver / poor direct therapeutic target
+
+
+
Role confidence
+
high
+
+
+
Therapeutic direction
+
avoid as direct target / use as biomarker or pathway context
+
+
+
Best modality
+
biomarker / pathway context only
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
27not prioritized-7
Resistance biomarker0.111
19low1
Tumor-intrinsic / small molecule0.000
40not prioritized-20
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.699)
    • +
  • Stable role classifier confidence is high
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Flagged as poor direct therapeutic target for this MVP
    • +
  • Role classifier indicates biological relevance but poor direct targetability
    • +
  • Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
medium confidence
+
+
+
Data completeness score
+
0.889
+
+
+
+
Contradiction score
+
0.570
+
+
+
+
Main limitation
+
Poor direct therapeutic target despite biological relevance
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Moderate contradiction score indicates caution is needed | Main limitation: Poor direct therapeutic target despite biological relevance

+

Deprioritization reason: TP53 should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context.

+
+ +
+

Recommended next validation experiment

+

Validation category: tumor-intrinsic functional validation

+

Next experiment: Evaluate whether perturbing TP53 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays.

+

Rationale: This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TP63.html b/examples/html_reports/depmap_26q1/targets/TP63.html new file mode 100644 index 0000000..9d2034b --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TP63.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TP63 + + + + +
+ +
+

Target hypothesis report: TP63

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TP63
+
+
+
Target name
+
tumor protein p63
+
+
+
Open Targets melanoma score
+
0.596
+
+
+
+
Open Targets baseline rank
+
73
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.03646717175085289,"interquartile_range":0.15602502361875212,"maximum":0.26270167319502213,"mean":0.02883004458571577,"measured_model_count":56,"median":0.06069628975320457,"minimum":-1.13379244109757,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11955785186789922,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0056286828889941356,"interquartile_range":0.02006209381979438,"maximum":0.996906606222216,"mean":0.043125430114191884,"measured_model_count":56,"median":0.012420727182457592,"minimum":0.0009590426965118661,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.025690776708788516,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.011161042797875489,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.0740302743614002,"pan_cancer_fraction":0.09188741721854304,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.0533349101229896,"pan_cancer_fraction":0.07119205298013245,"threshold":0.8}],"gene_effect_mean":0.11323820110222163,"gene_effect_median":0.06431602331215681},"dependency_probability_context_minus_non_context_median":-0.011539366478665646,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.07762896825396826,"non_context_fraction":0.0954861111111111,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.05592757936507937,"non_context_fraction":0.07378472222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.11874283587802412,"gene_effect_context_minus_non_context_median":0.06721157973110539}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 77
+- **Dependency-aware candidate rank:** 77
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_47aea6ee2f36661129a2dcd3767534849b7aafa25845e17a1f7eb00d41fd01d1`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TP63|entrez:8626`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
77not prioritized-4
Resistance biomarker0.000
79not prioritized-6
Tumor-intrinsic / small molecule0.000
77not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.596)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TP63 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TP63 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TRAF7.html b/examples/html_reports/depmap_26q1/targets/TRAF7.html new file mode 100644 index 0000000..53ebe48 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TRAF7.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TRAF7 + + + + +
+ +
+

Target hypothesis report: TRAF7

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TRAF7
+
+
+
Target name
+
TNF receptor associated factor 7
+
+
+
Open Targets melanoma score
+
0.523
+
+
+
+
Open Targets baseline rank
+
199
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.2406753121206499,"interquartile_range":0.24695097977219208,"maximum":0.3790647504468809,"mean":-0.12737792628681918,"measured_model_count":56,"median":-0.13475684387968312,"minimum":-0.610764948450708,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.006275667651542173,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.015945069753414774,"interquartile_range":0.16421762374968268,"maximum":0.8396091166189825,"mean":0.14316015942576582,"measured_model_count":56,"median":0.06819388689452299,"minimum":0.0004979956302897705,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.18016269350309747,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0009438003718074128,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.004375591296121098,"pan_cancer_fraction":0.057947019867549666,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.00378429517502365,"pan_cancer_fraction":0.014072847682119206,"threshold":0.8}],"gene_effect_mean":0.004084917885226469,"gene_effect_median":-0.0051896892898691815},"dependency_probability_context_minus_non_context_median":-0.0009438003718074128,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.004588293650793655,"non_context_fraction":0.058159722222222224,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.003968253968253968,"non_context_fraction":0.013888888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.004283490282425029,"gene_effect_context_minus_non_context_median":-0.005303738769082134}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 201
+- **Dependency-aware candidate rank:** 201
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_39469d5c3ff744db75b7677036b82a2b6052906d5713381b97c29825518058ec`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TRAF7|entrez:84231`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
201not prioritized-2
Resistance biomarker0.000
201not prioritized-2
Tumor-intrinsic / small molecule0.000
201not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.523)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TRAF7 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TRAF7 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TREM2.html b/examples/html_reports/depmap_26q1/targets/TREM2.html new file mode 100644 index 0000000..e18deb9 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TREM2.html @@ -0,0 +1,70 @@ +TREM2 — DepMap research preview

TREM2

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.0443206760018002,"interquartile_range":0.17039455367149228,"maximum":0.21602878466395123,"mean":0.03343137007746267,"measured_model_count":56,"median":0.0323268773346124,"minimum":-0.2109254937822177,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12607387766969208,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.006309502008753942,"interquartile_range":0.021860319009730143,"maximum":0.1244326991346321,"mean":0.023524014701307532,"measured_model_count":56,"median":0.014501080563188398,"minimum":0.0027434337345621554,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.028169821018484087,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0037581817852199995,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.01495476439173983,"gene_effect_median":0.015141526883319961},"dependency_probability_context_minus_non_context_median":-0.0037943511007953457,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.015681732105227185,"gene_effect_context_minus_non_context_median":0.01669816595616809}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_37329707c51acc74ca2cb22d449272702bc6744a5d56447d033a49e625ef62e1`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TREM2|entrez:54209`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/TRRAP.html b/examples/html_reports/depmap_26q1/targets/TRRAP.html new file mode 100644 index 0000000..4c3a568 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TRRAP.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TRRAP + + + + +
+ +
+

Target hypothesis report: TRRAP

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TRRAP
+
+
+
Target name
+
transformation/transcription domain associated protein
+
+
+
Open Targets melanoma score
+
0.626
+
+
+
+
Open Targets baseline rank
+
47
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-1.5213804808497076,"interquartile_range":0.433843564982187,"maximum":-0.6227212037899151,"mean":-1.3167452715650814,"measured_model_count":56,"median":-1.2709263893882927,"minimum":-2.0119956971319883,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.0875369158675205,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9777798803483504,"interquartile_range":0.022107860279671154,"maximum":1.0,"mean":0.9787434420409532,"measured_model_count":56,"median":0.9937763894442102,"minimum":0.7036541177148524,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9998877406280215,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005300264985414804,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.004966887417218513,"pan_cancer_fraction":0.9950331125827815,"threshold":0.5},{"context_fraction":0.9821428571428571,"difference":0.0003547776726584573,"pan_cancer_fraction":0.9817880794701986,"threshold":0.8}],"gene_effect_mean":0.17644201944194293,"gene_effect_median":0.2275108688164056},"dependency_probability_context_minus_non_context_median":-0.005395260689111003,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.00520833333333337,"non_context_fraction":0.9947916666666666,"threshold":0.5},{"context_fraction":0.9821428571428571,"difference":0.00037202380952372494,"non_context_fraction":0.9817708333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.18501906205370444,"gene_effect_context_minus_non_context_median":0.23667928859180454}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 53
+- **Dependency-aware candidate rank:** 53
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_6fe462e663a1c97bc5ad3f62e38d00121118446b91f3aaf2ff8a0727e32a4cc7`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TRRAP|entrez:8295`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
53not prioritized-6
Resistance biomarker0.000
55not prioritized-8
Tumor-intrinsic / small molecule0.000
53not prioritized-6
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.626)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TRRAP lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TRRAP in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TSC1.html b/examples/html_reports/depmap_26q1/targets/TSC1.html new file mode 100644 index 0000000..25a16d6 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TSC1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TSC1 + + + + +
+ +
+

Target hypothesis report: TSC1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TSC1
+
+
+
Target name
+
TSC complex subunit 1
+
+
+
Open Targets melanoma score
+
0.588
+
+
+
+
Open Targets baseline rank
+
86
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.3016134218269153,"interquartile_range":0.4540279484323619,"maximum":0.7560681310029174,"mean":-0.05250989686051594,"measured_model_count":56,"median":-0.06139145221472085,"minimum":-0.9355770319117922,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.15241452660544658,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005114952756170495,"interquartile_range":0.2066037360107815,"maximum":0.9475024496853242,"mean":0.17255563233916282,"measured_model_count":56,"median":0.036748465525459184,"minimum":1.463315655819427e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.211718688766952,"threshold_fractions":[{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.5},{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.020753081774940913,"dependency_probability_threshold_fractions":[{"context_fraction":0.16071428571428573,"difference":0.05392620624408705,"pan_cancer_fraction":0.10678807947019868,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":0.024243140964995268,"pan_cancer_fraction":0.04718543046357616,"threshold":0.8}],"gene_effect_mean":-0.08049961561053362,"gene_effect_median":-0.09133038858322812},"dependency_probability_context_minus_non_context_median":0.02101526595606716,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.16071428571428573,"difference":0.056547619047619055,"non_context_fraction":0.10416666666666667,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":0.025421626984126977,"non_context_fraction":0.04600694444444445,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.08441279136937907,"gene_effect_context_minus_non_context_median":-0.09589486022254615}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 89
+- **Dependency-aware candidate rank:** 89
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_8186ba8145eaae00bb79f7de7834c7e52f0018cae0aa360cd10997f663600067`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TSC1|entrez:7248`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
89not prioritized-3
Resistance biomarker0.000
91not prioritized-5
Tumor-intrinsic / small molecule0.000
89not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.588)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TSC1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TSC1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TSC2.html b/examples/html_reports/depmap_26q1/targets/TSC2.html new file mode 100644 index 0000000..c6ae0fc --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TSC2.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TSC2 + + + + +
+ +
+

Target hypothesis report: TSC2

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TSC2
+
+
+
Target name
+
TSC complex subunit 2
+
+
+
Open Targets melanoma score
+
0.568
+
+
+
+
Open Targets baseline rank
+
121
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.48178270738847034,"interquartile_range":0.6094882759655369,"maximum":0.7960520265311837,"mean":-0.17905815724769766,"measured_model_count":56,"median":-0.19336827495763223,"minimum":-1.1623050845253171,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12770556857706658,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005510173816997374,"interquartile_range":0.529793110570655,"maximum":0.9825524213104214,"mean":0.29430495118778816,"measured_model_count":56,"median":0.11191983755845783,"minimum":1.2968376951898574e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5353032843876524,"threshold_fractions":[{"denominator":56,"fraction":0.2857142857142857,"numerator":16,"threshold":0.5},{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.07296393578600509,"dependency_probability_threshold_fractions":[{"context_fraction":0.2857142857142857,"difference":0.08289971617786185,"pan_cancer_fraction":0.20281456953642385,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":0.06681646168401136,"pan_cancer_fraction":0.11175496688741722,"threshold":0.8}],"gene_effect_mean":-0.08411866484026737,"gene_effect_median":-0.13205223150234915},"dependency_probability_context_minus_non_context_median":0.07391335133157799,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.2857142857142857,"difference":0.08692956349206349,"non_context_fraction":0.1987847222222222,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":0.07006448412698413,"non_context_fraction":0.10850694444444445,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.08820776660333601,"gene_effect_context_minus_non_context_median":-0.13273442546728376}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 123
+- **Dependency-aware candidate rank:** 123
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_02597d1fe00363ec395bba1396c2b693627894b85a2735f9a9b0320f57a1d507`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TSC2|entrez:7249`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
123not prioritized-2
Resistance biomarker0.000
124not prioritized-3
Tumor-intrinsic / small molecule0.000
123not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.568)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TSC2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TSC2 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TYR.html b/examples/html_reports/depmap_26q1/targets/TYR.html new file mode 100644 index 0000000..0cdbe2a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TYR.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TYR + + + + +
+ +
+

Target hypothesis report: TYR

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TYR
+
+
+
Target name
+
tyrosinase
+
+
+
Open Targets melanoma score
+
0.585
+
+
+
+
Open Targets baseline rank
+
92
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.021924422131844194,"interquartile_range":0.13036313008930414,"maximum":0.22068382718892765,"mean":0.03780463155728201,"measured_model_count":56,"median":0.039761465584603584,"minimum":-0.16487265242462967,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10843870795745994,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.00790018032460166,"interquartile_range":0.016458370447756117,"maximum":0.12554764195984902,"mean":0.019476503614389358,"measured_model_count":56,"median":0.013953535396493747,"minimum":0.00202859216667188,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.024358550772357775,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.001972344387758205,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.006265099876650047,"gene_effect_median":0.005927198513196147},"dependency_probability_context_minus_non_context_median":-0.002016909180990324,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006569653342876118,"gene_effect_context_minus_non_context_median":0.00633350963583576}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 95
+- **Dependency-aware candidate rank:** 95
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_b6011643cf8b212a56809e5e47933e153af759822d9c476843e6d11de86f8f64`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TYR|entrez:7299`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
95not prioritized-3
Resistance biomarker0.000
97not prioritized-5
Tumor-intrinsic / small molecule0.000
95not prioritized-3
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.585)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TYR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TYR in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/TYRP1.html b/examples/html_reports/depmap_26q1/targets/TYRP1.html new file mode 100644 index 0000000..2c8f167 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/TYRP1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: TYRP1 + + + + +
+ +
+

Target hypothesis report: TYRP1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
TYRP1
+
+
+
Target name
+
tyrosinase related protein 1
+
+
+
Open Targets melanoma score
+
0.495
+
+
+
+
Open Targets baseline rank
+
259
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.10410635283115738,"interquartile_range":0.15932084168058958,"maximum":0.23571165368114302,"mean":-0.014436755487099202,"measured_model_count":56,"median":-0.00467660277186081,"minimum":-0.285963111504857,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.055214488849432204,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.011364526712981583,"interquartile_range":0.03289509253254978,"maximum":0.19098949806792395,"mean":0.03524535298675518,"measured_model_count":56,"median":0.02110733051641108,"minimum":0.0022871834283302536,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.044259619245531366,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004120654826854978,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":0.011142687770745322,"gene_effect_median":0.012642765427333967},"dependency_probability_context_minus_non_context_median":-0.00438180888119355,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.011684346204045388,"gene_effect_context_minus_non_context_median":0.013066480871946558}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 261
+- **Dependency-aware candidate rank:** 261
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_d4210a94654b7c77222a0cb56c441b7ed31ec0ce03ed3ccea0f732ae45bf3867`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:TYRP1|entrez:7306`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
261not prioritized-2
Resistance biomarker0.000
261not prioritized-2
Tumor-intrinsic / small molecule0.000
261not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.495)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: TYRP1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for TYRP1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/U2AF1.html b/examples/html_reports/depmap_26q1/targets/U2AF1.html new file mode 100644 index 0000000..b9f15b6 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/U2AF1.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: U2AF1 + + + + +
+ +
+

Target hypothesis report: U2AF1

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
U2AF1
+
+
+
Target name
+
U2 small nuclear RNA auxiliary factor 1
+
+
+
Open Targets melanoma score
+
0.522
+
+
+
+
Open Targets baseline rank
+
203
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-2.2850637997149565,"interquartile_range":0.5402155616805826,"maximum":-1.3937878711893064,"mean":-2.003858590452997,"measured_model_count":56,"median":-1.9445118925982248,"minimum":-2.7346918251771903,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.744848238034374,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.9999988989874314,"interquartile_range":1.1010125685606553e-06,"maximum":1.0,"mean":0.9997710798620709,"measured_model_count":56,"median":1.0,"minimum":0.9927101937690168,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0016556291390728006,"pan_cancer_fraction":0.9983443708609272,"threshold":0.5},{"context_fraction":1.0,"difference":0.002483443708609312,"pan_cancer_fraction":0.9975165562913907,"threshold":0.8}],"gene_effect_mean":-0.13232901178484746,"gene_effect_median":-0.07668830762275491},"dependency_probability_context_minus_non_context_median":0.0,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0017361111111111605,"non_context_fraction":0.9982638888888888,"threshold":0.5},{"context_fraction":1.0,"difference":0.0026041666666666297,"non_context_fraction":0.9973958333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.13876167207994716,"gene_effect_context_minus_non_context_median":-0.08078838931494281}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 205
+- **Dependency-aware candidate rank:** 205
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_f65219e78ccc3654795107e05e95ed5ef5276d5266ff9e7c0166a8cddd27272f`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:U2AF1|entrez:7307`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
205not prioritized-2
Resistance biomarker0.000
205not prioritized-2
Tumor-intrinsic / small molecule0.000
205not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.522)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: U2AF1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for U2AF1 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/UBR5.html b/examples/html_reports/depmap_26q1/targets/UBR5.html new file mode 100644 index 0000000..19e6c08 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/UBR5.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: UBR5 + + + + +
+ +
+

Target hypothesis report: UBR5

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
UBR5
+
+
+
Target name
+
ubiquitin protein ligase E3 component n-recognin 5
+
+
+
Open Targets melanoma score
+
0.594
+
+
+
+
Open Targets baseline rank
+
76
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.7334089926493355,"interquartile_range":0.45556632888926424,"maximum":0.3415255034442515,"mean":-0.4921227769355524,"measured_model_count":56,"median":-0.4989999347581911,"minimum":-1.5684017610891217,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.2778426637600712,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.1845620071921631,"interquartile_range":0.691845206624218,"maximum":0.9982874212452946,"mean":0.5183145222853321,"measured_model_count":56,"median":0.5029036917489552,"minimum":0.0005451520676103827,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.8764072138163811,"threshold_fractions":[{"denominator":56,"fraction":0.5,"numerator":28,"threshold":0.5},{"denominator":56,"fraction":0.3392857142857143,"numerator":19,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.11857267313761588,"dependency_probability_threshold_fractions":[{"context_fraction":0.5,"difference":-0.09105960264900659,"pan_cancer_fraction":0.5910596026490066,"threshold":0.5},{"context_fraction":0.3392857142857143,"difference":-0.018330179754020792,"pan_cancer_fraction":0.3576158940397351,"threshold":0.8}],"gene_effect_mean":0.06401024520393717,"gene_effect_median":0.04146862784647792},"dependency_probability_context_minus_non_context_median":-0.12431858237874993,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.5,"difference":-0.09548611111111116,"non_context_fraction":0.5954861111111112,"threshold":0.5},{"context_fraction":0.3392857142857143,"difference":-0.019221230158730118,"non_context_fraction":0.3585069444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.06712185434579554,"gene_effect_context_minus_non_context_median":0.04706650397650519}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 80
+- **Dependency-aware candidate rank:** 80
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_608621e071a11b8810b4c0207cdc91ea7b76383f87b39ced69c1be2f0556bed4`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:UBR5|entrez:51366`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
80not prioritized-4
Resistance biomarker0.000
82not prioritized-6
Tumor-intrinsic / small molecule0.000
80not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.594)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: UBR5 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for UBR5 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/USP6.html b/examples/html_reports/depmap_26q1/targets/USP6.html new file mode 100644 index 0000000..9fbab82 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/USP6.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: USP6 + + + + +
+ +
+

Target hypothesis report: USP6

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
USP6
+
+
+
Target name
+
ubiquitin specific peptidase 6
+
+
+
Open Targets melanoma score
+
0.556
+
+
+
+
Open Targets baseline rank
+
142
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.21946144443193774,"interquartile_range":0.1836133575142457,"maximum":0.09091474588958395,"mean":-0.13462308545365242,"measured_model_count":56,"median":-0.14083080016013066,"minimum":-0.4133470078215248,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.035848086917692035,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.03158062220146937,"interquartile_range":0.10676534490012221,"maximum":0.38024577182219427,"mean":0.09450311024282725,"measured_model_count":56,"median":0.07325111118993291,"minimum":0.007333353368402815,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.13834596710159158,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.029375594631216945,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.015728476821192054,"pan_cancer_fraction":0.015728476821192054,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.04882779069934445,"gene_effect_median":0.036166204101795135},"dependency_probability_context_minus_non_context_median":-0.03129187482786387,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.016493055555555556,"non_context_fraction":0.016493055555555556,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0512013638583404,"gene_effect_context_minus_non_context_median":0.037751064245996974}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 144
+- **Dependency-aware candidate rank:** 144
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_6e1e2e52e7eaeae29cbc8eced7ced09a696665447972e1e42009ed141065ee37`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:USP6|entrez:9098`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
144not prioritized-2
Resistance biomarker0.000
145not prioritized-3
Tumor-intrinsic / small molecule0.000
144not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.556)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: USP6 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for USP6 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/WAS.html b/examples/html_reports/depmap_26q1/targets/WAS.html new file mode 100644 index 0000000..0d01df6 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/WAS.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: WAS + + + + +
+ +
+

Target hypothesis report: WAS

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
WAS
+
+
+
Target name
+
WASP actin nucleation promoting factor
+
+
+
Open Targets melanoma score
+
0.517
+
+
+
+
Open Targets baseline rank
+
222
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.0081124743479323,"interquartile_range":0.11365188739509363,"maximum":0.3717879401122316,"mean":0.05648455771783551,"measured_model_count":56,"median":0.04235581384965959,"minimum":-0.20632925372342162,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10553941304716133,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.005830434234521276,"interquartile_range":0.016806642972809215,"maximum":0.10452119793228946,"mean":0.01779230363124099,"measured_model_count":56,"median":0.013549175642979312,"minimum":0.0005349464613209364,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02263707720733049,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003858876726332755,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.009933774834437087,"pan_cancer_fraction":0.009933774834437087,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.8}],"gene_effect_mean":0.04386204430490018,"gene_effect_median":0.01871539447042147},"dependency_probability_context_minus_non_context_median":-0.0042032123239720935,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.010416666666666666,"non_context_fraction":0.010416666666666666,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04599422701416618,"gene_effect_context_minus_non_context_median":0.0199203440306107}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 224
+- **Dependency-aware candidate rank:** 224
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_faa220e36cb06c9b352cfb52bb2c5ab1e401752b580e66ae940d6c5bf4d4826e`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:WAS|entrez:7454`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
224not prioritized-2
Resistance biomarker0.000
224not prioritized-2
Tumor-intrinsic / small molecule0.000
224not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.517)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: WAS lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for WAS in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/WNT5A.html b/examples/html_reports/depmap_26q1/targets/WNT5A.html new file mode 100644 index 0000000..6a958c9 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/WNT5A.html @@ -0,0 +1,70 @@ +WNT5A — DepMap research preview

WNT5A

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.013475623132929507,"interquartile_range":0.12987435128430827,"maximum":0.3150759319494393,"mean":0.053669849425937624,"measured_model_count":56,"median":0.058772730317348545,"minimum":-0.24052616114158287,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11639872815137876,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.0056110526655506286,"interquartile_range":0.019919012256410858,"maximum":0.11933478473212114,"mean":0.01871307104063123,"measured_model_count":56,"median":0.01236916749744851,"minimum":0.0021382880799880946,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.025530064921961488,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003466261549901078,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.016387858683863096,"gene_effect_median":0.021945093816684393},"dependency_probability_context_minus_non_context_median":-0.0035947955386887165,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01718449070321755,"gene_effect_context_minus_non_context_median":0.022721044347566006}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** not reported
+- **Dependency-aware candidate rank:** not reported
+- **Rank delta:** not reported
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_cc9af2f98c4153df180b2f00100fa8e0a4f8ecb1e4af8839de969f92569b35ce`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:WNT5A|entrez:7474`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
diff --git a/examples/html_reports/depmap_26q1/targets/WRN.html b/examples/html_reports/depmap_26q1/targets/WRN.html new file mode 100644 index 0000000..7dd4fb4 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/WRN.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: WRN + + + + +
+ +
+

Target hypothesis report: WRN

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
WRN
+
+
+
Target name
+
WRN RecQ like helicase
+
+
+
Open Targets melanoma score
+
0.610
+
+
+
+
Open Targets baseline rank
+
57
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.22747322797558123,"interquartile_range":0.18738191531852705,"maximum":0.1869225639090439,"mean":-0.1472173168641097,"measured_model_count":56,"median":-0.1359431135451314,"minimum":-0.6702924398334323,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.040091312657054186,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.029615962721536174,"interquartile_range":0.12028353472893429,"maximum":0.7328436063532079,"mean":0.1242273410614679,"measured_model_count":56,"median":0.06804582138278752,"minimum":0.005152580595719504,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14989949745047046,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0054367770673847265,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.022587511825922425,"pan_cancer_fraction":0.076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.041390728476821195,"pan_cancer_fraction":0.041390728476821195,"threshold":0.8}],"gene_effect_mean":0.03292790495233883,"gene_effect_median":-0.014512486907057545},"dependency_probability_context_minus_non_context_median":0.005489758575097134,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.02368551587301588,"non_context_fraction":0.07725694444444445,"threshold":0.5},{"context_fraction":0.0,"difference":-0.043402777777777776,"non_context_fraction":0.043402777777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.034528566998633076,"gene_effect_context_minus_non_context_median":-0.01488164753445749}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 61
+- **Dependency-aware candidate rank:** 61
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_8e773dfcde59398006dec33e5b5184ee4e178481e1a6bf2a2daee11deb4e83ae`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:WRN|entrez:7486`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
61not prioritized-4
Resistance biomarker0.000
63not prioritized-6
Tumor-intrinsic / small molecule0.000
61not prioritized-4
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.610)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: WRN lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for WRN in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ZBTB16.html b/examples/html_reports/depmap_26q1/targets/ZBTB16.html new file mode 100644 index 0000000..2d9a31a --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ZBTB16.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ZBTB16 + + + + +
+ +
+

Target hypothesis report: ZBTB16

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ZBTB16
+
+
+
Target name
+
zinc finger and BTB domain containing 16
+
+
+
Open Targets melanoma score
+
0.522
+
+
+
+
Open Targets baseline rank
+
205
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.009823719243372997,"interquartile_range":0.16578865722223748,"maximum":0.41204654436023724,"mean":0.07249807663874529,"measured_model_count":56,"median":0.07415276241873536,"minimum":-0.30348607293974983,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1559649379788645,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.004890986360055396,"interquartile_range":0.018207855814234508,"maximum":0.185233568494693,"mean":0.019665096749805024,"measured_model_count":56,"median":0.010731332181391433,"minimum":0.00039811689207587927,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.023098842174289903,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0007056036329970497,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.010563662912873154,"gene_effect_median":-0.009279418078398133},"dependency_probability_context_minus_non_context_median":0.0007056036329970497,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.011077174304471166,"gene_effect_context_minus_non_context_median":-0.009864062164104292}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 207
+- **Dependency-aware candidate rank:** 207
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_95f575baecdd6225abecf6aa6c5ab61b12d58645750e27090582cebbf2c64358`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ZBTB16|entrez:7704`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
207not prioritized-2
Resistance biomarker0.000
207not prioritized-2
Tumor-intrinsic / small molecule0.000
207not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.522)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ZBTB16 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ZBTB16 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ZFHX3.html b/examples/html_reports/depmap_26q1/targets/ZFHX3.html new file mode 100644 index 0000000..c68b924 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ZFHX3.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ZFHX3 + + + + +
+ +
+

Target hypothesis report: ZFHX3

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ZFHX3
+
+
+
Target name
+
zinc finger homeobox 3
+
+
+
Open Targets melanoma score
+
0.521
+
+
+
+
Open Targets baseline rank
+
208
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 55
+- **Available reference observations:** 1110
+- **Coverage fraction:** 0.9821428571428571
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":-0.06146208289047472,"interquartile_range":0.14758793421665212,"maximum":0.2881461102807952,"mean":0.007927014410996538,"measured_model_count":55,"median":0.007593842404380845,"minimum":-0.33029884415193866,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":0.08612585132617741,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.008564060822250814,"interquartile_range":0.02700284675819572,"maximum":0.23484293062520295,"mean":0.03819658296592888,"measured_model_count":55,"median":0.019485636278314837,"minimum":0.0010067610165416245,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":0.03556690758044653,"threshold_fractions":[{"denominator":55,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":55,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.004526778394754729,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0017167381974248926,"pan_cancer_fraction":0.0017167381974248926,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.029396869620069162,"gene_effect_median":-0.032940962307585524},"dependency_probability_context_minus_non_context_median":0.004707711822055958,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0018018018018018018,"non_context_fraction":0.0018018018018018018,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03085347126791045,"gene_effect_context_minus_non_context_median":-0.03387072477789323}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 210
+- **Dependency-aware candidate rank:** 210
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_93922b07a6fc0f657cd41e36eccc7c393dcf72c6e91455b1ed87ac8e4ca265a5`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ZFHX3|entrez:463`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
210not prioritized-2
Resistance biomarker0.000
210not prioritized-2
Tumor-intrinsic / small molecule0.000
210not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.521)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ZFHX3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ZFHX3 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/ZNF331.html b/examples/html_reports/depmap_26q1/targets/ZNF331.html new file mode 100644 index 0000000..bb0cda4 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/ZNF331.html @@ -0,0 +1,432 @@ + + + + +TargetIntel-IO report: ZNF331 + + + + +
+ +
+

Target hypothesis report: ZNF331

+

TargetIntel-IO therapeutic-intent-aware target triage summary

+
+ +
+

Target identity

+
+
+
Target symbol
+
ZNF331
+
+
+
Target name
+
zinc finger protein 331
+
+
+
Open Targets melanoma score
+
0.508
+
+
+
+
Open Targets baseline rank
+
244
+
+
+
+ + + +
+

Functional dependency — DepMap Public 26Q1

+

Coverage

+
+- **Profile available:** yes
+- **Coverage status:** sufficient_complete_coverage
+- **Total model count:** 2154
+- **Context model count:** 56
+- **Reference model count:** 2098
+- **Available context observations:** 56
+- **Available reference observations:** 1152
+- **Coverage fraction:** 1.0
+- **Missing-value state:** target_resolved_both_matrices
+- **Unavailable reason:** not reported
+
+

Dependency profile

+
+- **Gene-effect summary:** {"available":true,"first_quartile":0.1254636788972895,"interquartile_range":0.14498040321724526,"maximum":0.7050101742014865,"mean":0.19150820508534952,"measured_model_count":56,"median":0.19280092244168862,"minimum":-0.15201787565274216,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.27044408211453475,"threshold_fractions":[],"total_model_count":56}
+- **Dependency-probability summary:** {"available":true,"first_quartile":0.001704372331237138,"interquartile_range":0.005424707330500494,"maximum":0.10954958289983124,"mean":0.009442167813529304,"measured_model_count":56,"median":0.003587808287988493,"minimum":1.0645838207346946e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.007129079661737632,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56}
+- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.000887099880134024,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.04234439864678727,"gene_effect_median":-0.04372457184518963},"dependency_probability_context_minus_non_context_median":0.0009410321401466981,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.04440280691433923,"gene_effect_context_minus_non_context_median":-0.045076343973518174}
+- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148}
+- **Dependency interpretation state:** valid
+
+

Integration

+
+- **Baseline rank:** 246
+- **Dependency-aware candidate rank:** 246
+- **Rank delta:** 0
+- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank.
+- **Negative rank delta:** movement toward a lower numerical rank.
+- **Integration state:** blocked_insufficient_evidence
+- **Baseline preserved:** yes
+- **Production activation enabled:** disabled
+- **Approved authorization emitted:** not emitted
+- **Candidate activation readiness:** blocked
+- **Human review required:** required
+
+

Release provenance

+
+- **Evidence ID:** `drep_b5f3ff40e6903a84cec95adb93e101202320c5ee12b31a232b62549d7b70917b`
+- **Release identifier:** `DepMap_Public_26Q1`
+- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1`
+- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6`
+- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4`
+- **Context identity:** `melanoma_anti_pd1:v1`
+- **Canonical gene identity:** `symbol:ZNF331|entrez:55422`
+- **Contract format version:** `v1`
+- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv`
+
+

Limitations

+
+- Acral and drug-adapted models are excluded from the primary profile and retained separately.
+- Baseline: unchanged 300-target TargetIntel antibody-IO ranking.
+- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership.
+- DepMap Public 26Q1 cell-line dependency evidence.
+- Dependency is treated as explanatory evidence, not as clinical validation.
+- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion.
+- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values.
+- No automatic target activation or release.
+- No clinical anti-PD-1 response inference.
+- Primary context contains 56 reviewed cutaneous melanoma cell-line models.
+- Primary context: 56 reviewed cutaneous melanoma models.
+- Thresholds were fixed before inspecting benchmark outcomes.
+- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved.
+- DepMap cell-line dependency is not clinical anti-PD-1 response evidence.
+- Absence of tumor-cell dependency does not invalidate an immune target.
+- Broad dependency may reflect general essentiality.
+- Cell lines do not reproduce the complete tumor microenvironment.
+- Candidate activation requires explicit human review.
+
+ + +
+

Stable TargetIntel-IO classification

+
+
+
Role classification
+
unclear / low-confidence candidate
+
+
+
Role confidence
+
low
+
+
+
Therapeutic direction
+
unclear
+
+
+
Best modality
+
unclear
+
+
+
Resistance axis
+
unmapped
+
+
+
Matched resistance programs
+
not available
+
+
+
+ +
+

Therapeutic-intent rankings

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
Therapeutic intentScoreRankPriorityRank shift vs Open Targets
Antibody / IO-combination0.000
246not prioritized-2
Resistance biomarker0.000
246not prioritized-2
Tumor-intrinsic / small molecule0.000
246not prioritized-2
+
+ +
+

Evidence for

+
    +
  • Moderate Open Targets melanoma association score (0.508)
    • +
+
+ +
+

Evidence against / limitations

+
    +
  • Not currently mapped to a curated anti-PD-1 resistance axis
    • +
  • Stable role classifier confidence is low
    • +
+
+ +
+

Confidence and uncertainty

+
+
+
Confidence level
+
low confidence
+
+
+
Data completeness score
+
0.667
+
+
+
+
Contradiction score
+
0.360
+
+
+
+
Main limitation
+
No curated anti-PD-1 resistance-axis mapping
+
+
+

Uncertainty reason: Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping

+

Deprioritization reason: ZNF331 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO.

+
+ +
+

Recommended next validation experiment

+

Validation category: evidence-gathering

+

Next experiment: Perform literature review and cohort-level expression analysis for ZNF331 in anti-PD-1-resistant melanoma.

+

Rationale: The current evidence is insufficient for a confident therapeutic interpretation.

+
+ +
+

Interpretation note

+

+ This report is generated by TargetIntel-IO as a transparent, rule-based + target triage summary. It is intended for hypothesis generation and + portfolio demonstration only. It does not represent clinical advice or + validated therapeutic evidence. +

+
+ +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/html_reports/depmap_26q1/targets/index.html b/examples/html_reports/depmap_26q1/targets/index.html new file mode 100644 index 0000000..7bc5b58 --- /dev/null +++ b/examples/html_reports/depmap_26q1/targets/index.html @@ -0,0 +1,9291 @@ + + + + +TargetIntel-IO HTML reports + + + + +
+ +
+

TargetIntel-IO reports

+

Therapeutic-intent-aware target triage for anti-PD-1-resistant melanoma

+
+ +
+

How to read these reports

+

+ TargetIntel-IO keeps the biological role of each target stable, but ranks + targets differently depending on the therapeutic intent. +

+
    +
  • High: strong candidate for that therapeutic intent.
    • +
  • Medium: plausible secondary candidate.
    • +
  • Low: weak or indirect fit.
    • +
  • Not prioritized: not a meaningful candidate for that mode under current MVP rules.
    • +
+
+ + +
+

Top antibody / IO-combination targets

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
RankTargetRoleBest modalityScorePriorityRank shift
1CTLA4anti-PD-1 combination targetantibody / IO-combination target0.853high14
2PDCD1anti-PD-1 combination targetantibody / IO-combination target0.827high42
3CD274anti-PD-1 combination targetantibody / IO-combination target0.825high50
4LAG3anti-PD-1 combination targetantibody / IO-combination target0.822high76
5IL2RATreg-suppression marker / possible IO-combination targetantibody / Treg-associated IO-combination candidate0.673medium43
6NRAStumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.301low-1
7BRAFtumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.269low-5
8MAP2K1tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.262low-4
9B2Mantigen-presentation resistance biomarkerresistance biomarker / patient stratification0.227low102
10JAK2IFN-gamma resistance mechanism / biomarkerresistance biomarker / patient stratification0.215low255
11JAK1IFN-gamma resistance mechanism / biomarkerresistance biomarker / patient stratification0.214low260
12CDKN2Atumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-11
13BAP1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-10
14MAP2K2tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.000not prioritized-8
15PTENtumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-8
16MITFtumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.000not prioritized-8
17NF1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-8
18CDK4tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.000not prioritized-8
19GNAQunclear / low-confidence candidateunclear0.000not prioritized-8
20ARID2unclear / low-confidence candidateunclear0.000not prioritized-8
21KITtumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.000not prioritized-8
22RAC1unclear / low-confidence candidateunclear0.000not prioritized-8
23TERTtumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.000not prioritized-7
24GNA11unclear / low-confidence candidateunclear0.000not prioritized-7
25POT1unclear / low-confidence candidateunclear0.000not prioritized-7
26MBD4unclear / low-confidence candidateunclear0.000not prioritized-7
27TP53tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-7
28SF3B1unclear / low-confidence candidateunclear0.000not prioritized-7
29PPP6Cunclear / low-confidence candidateunclear0.000not prioritized-7
30IRF4unclear / low-confidence candidateunclear0.000not prioritized-7
31BRCA2unclear / low-confidence candidateunclear0.000not prioritized-7
32RAF1unclear / low-confidence candidateunclear0.000not prioritized-7
33KDRunclear / low-confidence candidateunclear0.000not prioritized-7
34PDGFRAunclear / low-confidence candidateunclear0.000not prioritized-7
35ATMunclear / low-confidence candidateunclear0.000not prioritized-7
36LRP1Bunclear / low-confidence candidateunclear0.000not prioritized-7
37FLT4unclear / low-confidence candidateunclear0.000not prioritized-7
38CSF3Runclear / low-confidence candidateunclear0.000not prioritized-7
39PDGFRBunclear / low-confidence candidateunclear0.000not prioritized-7
40TET2unclear / low-confidence candidateunclear0.000not prioritized-7
41POLEunclear / low-confidence candidateunclear0.000not prioritized-7
42DDX3Xunclear / low-confidence candidateunclear0.000not prioritized-7
43FOXP1unclear / low-confidence candidateunclear0.000not prioritized-7
44PBRM1unclear / low-confidence candidateunclear0.000not prioritized-7
45SETD2unclear / low-confidence candidateunclear0.000not prioritized-7
46CCND1unclear / low-confidence candidateunclear0.000not prioritized-7
47ERBB4unclear / low-confidence candidateunclear0.000not prioritized-7
48METunclear / low-confidence candidateunclear0.000not prioritized-7
49STK11unclear / low-confidence candidateunclear0.000not prioritized-7
50ROS1unclear / low-confidence candidateunclear0.000not prioritized-7
51MTORunclear / low-confidence candidateunclear0.000not prioritized-6
52H3-3Bunclear / low-confidence candidateunclear0.000not prioritized-6
53TRRAPunclear / low-confidence candidateunclear0.000not prioritized-6
54MC1Runclear / low-confidence candidateunclear0.000not prioritized-5
55IKZF1unclear / low-confidence candidateunclear0.000not prioritized-5
56FAT1unclear / low-confidence candidateunclear0.000not prioritized-5
57DICER1unclear / low-confidence candidateunclear0.000not prioritized-5
58MDM2unclear / low-confidence candidateunclear0.000not prioritized-4
59IFNAR1unclear / low-confidence candidateunclear0.000not prioritized-4
60MECOMunclear / low-confidence candidateunclear0.000not prioritized-4
61WRNunclear / low-confidence candidateunclear0.000not prioritized-4
62CHEK2unclear / low-confidence candidateunclear0.000not prioritized-4
63ATRunclear / low-confidence candidateunclear0.000not prioritized-4
64CUX1unclear / low-confidence candidateunclear0.000not prioritized-4
65KMT2Dunclear / low-confidence candidateunclear0.000not prioritized-4
66EP300unclear / low-confidence candidateunclear0.000not prioritized-4
67ESR1unclear / low-confidence candidateunclear0.000not prioritized-4
68BRCA1unclear / low-confidence candidateunclear0.000not prioritized-4
69AKT1unclear / low-confidence candidateunclear0.000not prioritized-4
70NTRK1unclear / low-confidence candidateunclear0.000not prioritized-4
71ERBB2unclear / low-confidence candidateunclear0.000not prioritized-4
72PREX2unclear / low-confidence candidateunclear0.000not prioritized-4
73FAT4unclear / low-confidence candidateunclear0.000not prioritized-4
74KMT2Cunclear / low-confidence candidateunclear0.000not prioritized-4
75POLQunclear / low-confidence candidateunclear0.000not prioritized-4
76FGFR2unclear / low-confidence candidateunclear0.000not prioritized-4
77TP63unclear / low-confidence candidateunclear0.000not prioritized-4
78FGFR4unclear / low-confidence candidateunclear0.000not prioritized-4
79GRIN2Aunclear / low-confidence candidateunclear0.000not prioritized-4
80UBR5unclear / low-confidence candidateunclear0.000not prioritized-4
81OCA2unclear / low-confidence candidateunclear0.000not prioritized-4
82SMARCA4unclear / low-confidence candidateunclear0.000not prioritized-4
83IFNAR2unclear / low-confidence candidateunclear0.000not prioritized-4
84FGFR1unclear / low-confidence candidateunclear0.000not prioritized-3
85PTPRBunclear / low-confidence candidateunclear0.000not prioritized-3
86PTPRTunclear / low-confidence candidateunclear0.000not prioritized-3
87PTPN11unclear / low-confidence candidateunclear0.000not prioritized-3
88MDM4unclear / low-confidence candidateunclear0.000not prioritized-3
89TSC1unclear / low-confidence candidateunclear0.000not prioritized-3
90TBX3unclear / low-confidence candidateunclear0.000not prioritized-3
91ERBB3unclear / low-confidence candidateunclear0.000not prioritized-3
92ATRXunclear / low-confidence candidateunclear0.000not prioritized-3
93RUNX1T1unclear / low-confidence candidateunclear0.000not prioritized-3
94CDK12unclear / low-confidence candidateunclear0.000not prioritized-3
95TYRunclear / low-confidence candidateunclear0.000not prioritized-3
96RB1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-3
97AKT2unclear / low-confidence candidateunclear0.000not prioritized-3
98PTPRKunclear / low-confidence candidateunclear0.000not prioritized-3
99CBLunclear / low-confidence candidateunclear0.000not prioritized-3
100DNMT3Aunclear / low-confidence candidateunclear0.000not prioritized-3
101RRM2unclear / low-confidence candidateunclear0.000not prioritized-3
102KLF6unclear / low-confidence candidateunclear0.000not prioritized-3
103ARunclear / low-confidence candidateunclear0.000not prioritized-3
104KMT2Aunclear / low-confidence candidateunclear0.000not prioritized-3
105CYLDunclear / low-confidence candidateunclear0.000not prioritized-3
106RPL5unclear / low-confidence candidateunclear0.000not prioritized-3
107ERCC2unclear / low-confidence candidateunclear0.000not prioritized-3
108IDH1unclear / low-confidence candidateunclear0.000not prioritized-3
109NOTCH2unclear / low-confidence candidateunclear0.000not prioritized-3
110CDK6unclear / low-confidence candidateunclear0.000not prioritized-3
111IKBKBunclear / low-confidence candidateunclear0.000not prioritized-3
112NTRK2unclear / low-confidence candidateunclear0.000not prioritized-3
113RRM2Bunclear / low-confidence candidateunclear0.000not prioritized-3
114CASP8unclear / low-confidence candidateunclear0.000not prioritized-2
115POLD1unclear / low-confidence candidateunclear0.000not prioritized-2
116IL7Runclear / low-confidence candidateunclear0.000not prioritized-2
117QKIunclear / low-confidence candidateunclear0.000not prioritized-2
118GNASunclear / low-confidence candidateunclear0.000not prioritized-2
119MYBunclear / low-confidence candidateunclear0.000not prioritized-2
120PTCH1unclear / low-confidence candidateunclear0.000not prioritized-2
121DDR2unclear / low-confidence candidateunclear0.000not prioritized-2
122PIK3R1unclear / low-confidence candidateunclear0.000not prioritized-2
123TSC2unclear / low-confidence candidateunclear0.000not prioritized-2
124PHOX2Bunclear / low-confidence candidateunclear0.000not prioritized-2
125SETBP1unclear / low-confidence candidateunclear0.000not prioritized-2
126RRM1unclear / low-confidence candidateunclear0.000not prioritized-2
127SPENunclear / low-confidence candidateunclear0.000not prioritized-2
128ARHGAP35unclear / low-confidence candidateunclear0.000not prioritized-2
129SYKunclear / low-confidence candidateunclear0.000not prioritized-2
130PAX5unclear / low-confidence candidateunclear0.000not prioritized-2
131CYP1B1unclear / low-confidence candidateunclear0.000not prioritized-2
132FANCAunclear / low-confidence candidateunclear0.000not prioritized-2
133CIITAunclear / low-confidence candidateunclear0.000not prioritized-2
134BCL9Lunclear / low-confidence candidateunclear0.000not prioritized-2
135NUTM1unclear / low-confidence candidateunclear0.000not prioritized-2
136ARNTunclear / low-confidence candidateunclear0.000not prioritized-2
137CCND2unclear / low-confidence candidateunclear0.000not prioritized-2
138PER1unclear / low-confidence candidateunclear0.000not prioritized-2
139JUNunclear / low-confidence candidateunclear0.000not prioritized-2
140KAT6Aunclear / low-confidence candidateunclear0.000not prioritized-2
141CBLBunclear / low-confidence candidateunclear0.000not prioritized-2
142HNF1Aunclear / low-confidence candidateunclear0.000not prioritized-2
143BCL11Aunclear / low-confidence candidateunclear0.000not prioritized-2
144USP6unclear / low-confidence candidateunclear0.000not prioritized-2
145MYCNunclear / low-confidence candidateunclear0.000not prioritized-2
146PRDM1unclear / low-confidence candidateunclear0.000not prioritized-2
147AFDNunclear / low-confidence candidateunclear0.000not prioritized-2
148IL2RGunclear / low-confidence candidateunclear0.000not prioritized-2
149IL2RBunclear / low-confidence candidateunclear0.000not prioritized-2
150SMAD2unclear / low-confidence candidateunclear0.000not prioritized-2
151AXIN1unclear / low-confidence candidateunclear0.000not prioritized-2
152SALL4unclear / low-confidence candidateunclear0.000not prioritized-2
153NFKBIEunclear / low-confidence candidateunclear0.000not prioritized-2
154HGFunclear / low-confidence candidateunclear0.000not prioritized-2
155PPP2R1Aunclear / low-confidence candidateunclear0.000not prioritized-2
156BCORunclear / low-confidence candidateunclear0.000not prioritized-2
157ERCC3unclear / low-confidence candidateunclear0.000not prioritized-2
158FANCD2unclear / low-confidence candidateunclear0.000not prioritized-2
159DAXXunclear / low-confidence candidateunclear0.000not prioritized-2
160PTPRCunclear / low-confidence candidateunclear0.000not prioritized-2
161MYH9unclear / low-confidence candidateunclear0.000not prioritized-2
162ARID1Bunclear / low-confidence candidateunclear0.000not prioritized-2
163LZTR1unclear / low-confidence candidateunclear0.000not prioritized-2
164CICunclear / low-confidence candidateunclear0.000not prioritized-2
165CREBBPunclear / low-confidence candidateunclear0.000not prioritized-2
166MYCLunclear / low-confidence candidateunclear0.000not prioritized-2
167SLC45A2unclear / low-confidence candidateunclear0.000not prioritized-2
168FCRL4unclear / low-confidence candidateunclear0.000not prioritized-2
169MAP3K13unclear / low-confidence candidateunclear0.000not prioritized-2
170CNOT3unclear / low-confidence candidateunclear0.000not prioritized-2
171FLGunclear / low-confidence candidateunclear0.000not prioritized-2
172AMER1unclear / low-confidence candidateunclear0.000not prioritized-2
173ATF1unclear / low-confidence candidateunclear0.000not prioritized-2
174ERCC5unclear / low-confidence candidateunclear0.000not prioritized-2
175ERCC4unclear / low-confidence candidateunclear0.000not prioritized-2
176MX2unclear / low-confidence candidateunclear0.000not prioritized-2
177SUFUunclear / low-confidence candidateunclear0.000not prioritized-2
178NTRK3unclear / low-confidence candidateunclear0.000not prioritized-2
179ARID1Aunclear / low-confidence candidateunclear0.000not prioritized-2
180PARP1unclear / low-confidence candidateunclear0.000not prioritized-2
181CARD11unclear / low-confidence candidateunclear0.000not prioritized-2
182RICTORunclear / low-confidence candidateunclear0.000not prioritized-2
183BRD4unclear / low-confidence candidateunclear0.000not prioritized-2
184RETunclear / low-confidence candidateunclear0.000not prioritized-2
185EZH2unclear / low-confidence candidateunclear0.000not prioritized-2
186SMAD3unclear / low-confidence candidateunclear0.000not prioritized-2
187LCKunclear / low-confidence candidateunclear0.000not prioritized-2
188TFEBunclear / low-confidence candidateunclear0.000not prioritized-2
189CDX2unclear / low-confidence candidateunclear0.000not prioritized-2
190ACVR1Bunclear / low-confidence candidateunclear0.000not prioritized-2
191PRF1immune-context markerimmune-context biomarker0.000not prioritized-2
192NCOR2unclear / low-confidence candidateunclear0.000not prioritized-2
193IRS4unclear / low-confidence candidateunclear0.000not prioritized-2
194SPOPunclear / low-confidence candidateunclear0.000not prioritized-2
195CREB1unclear / low-confidence candidateunclear0.000not prioritized-2
196TET1unclear / low-confidence candidateunclear0.000not prioritized-2
197EGFRunclear / low-confidence candidateunclear0.000not prioritized-2
198CRLF2unclear / low-confidence candidateunclear0.000not prioritized-2
199STN1unclear / low-confidence candidateunclear0.000not prioritized-2
200TFE3unclear / low-confidence candidateunclear0.000not prioritized-2
201TRAF7unclear / low-confidence candidateunclear0.000not prioritized-2
202NFKB2unclear / low-confidence candidateunclear0.000not prioritized-2
203AFF4unclear / low-confidence candidateunclear0.000not prioritized-2
204ARHGEF12unclear / low-confidence candidateunclear0.000not prioritized-2
205U2AF1unclear / low-confidence candidateunclear0.000not prioritized-2
206PMS2unclear / low-confidence candidateunclear0.000not prioritized-2
207ZBTB16unclear / low-confidence candidateunclear0.000not prioritized-2
208MTAPunclear / low-confidence candidateunclear0.000not prioritized-2
209MSH2unclear / low-confidence candidateunclear0.000not prioritized-2
210ZFHX3unclear / low-confidence candidateunclear0.000not prioritized-2
211KDM5Aunclear / low-confidence candidateunclear0.000not prioritized-2
212CHD4unclear / low-confidence candidateunclear0.000not prioritized-2
213FBXO11unclear / low-confidence candidateunclear0.000not prioritized-2
214PTPN13unclear / low-confidence candidateunclear0.000not prioritized-2
215PLCG1unclear / low-confidence candidateunclear0.000not prioritized-2
216FASunclear / low-confidence candidateunclear0.000not prioritized-2
217MAXunclear / low-confidence candidateunclear0.000not prioritized-2
218BCORL1unclear / low-confidence candidateunclear0.000not prioritized-2
219KNL1unclear / low-confidence candidateunclear0.000not prioritized-2
220BUB1Bunclear / low-confidence candidateunclear0.000not prioritized-2
221NCOR1unclear / low-confidence candidateunclear0.000not prioritized-2
222ACKR3unclear / low-confidence candidateunclear0.000not prioritized-2
223SMOunclear / low-confidence candidateunclear0.000not prioritized-2
224WASunclear / low-confidence candidateunclear0.000not prioritized-2
225NUP98unclear / low-confidence candidateunclear0.000not prioritized-2
226CACNA1Dunclear / low-confidence candidateunclear0.000not prioritized-2
227FLT3unclear / low-confidence candidateunclear0.000not prioritized-2
228BTKunclear / low-confidence candidateunclear0.000not prioritized-2
229RANBP2unclear / low-confidence candidateunclear0.000not prioritized-2
230BCL11Bunclear / low-confidence candidateunclear0.000not prioritized-2
231CLTCunclear / low-confidence candidateunclear0.000not prioritized-2
232MN1unclear / low-confidence candidateunclear0.000not prioritized-2
233MAP2K4unclear / low-confidence candidateunclear0.000not prioritized-2
234BCL9unclear / low-confidence candidateunclear0.000not prioritized-2
235BRD3unclear / low-confidence candidateunclear0.000not prioritized-2
236KAT6Bunclear / low-confidence candidateunclear0.000not prioritized-2
237TBL1XR1unclear / low-confidence candidateunclear0.000not prioritized-2
238TMEM127unclear / low-confidence candidateunclear0.000not prioritized-2
239FANCFunclear / low-confidence candidateunclear0.000not prioritized-2
240PIK3CAunclear / low-confidence candidateunclear0.000not prioritized-2
241APCunclear / low-confidence candidateunclear0.000not prioritized-2
242NKX2-1unclear / low-confidence candidateunclear0.000not prioritized-2
243CTNNB1unclear / low-confidence candidateunclear0.000not prioritized-2
244MRTFAunclear / low-confidence candidateunclear0.000not prioritized-2
245KLF4unclear / low-confidence candidateunclear0.000not prioritized-2
246ZNF331unclear / low-confidence candidateunclear0.000not prioritized-2
247FGFR3unclear / low-confidence candidateunclear0.000not prioritized-2
248FHunclear / low-confidence candidateunclear0.000not prioritized-2
249MUTYHunclear / low-confidence candidateunclear0.000not prioritized-2
250TCL1Aunclear / low-confidence candidateunclear0.000not prioritized-2
251CARS1unclear / low-confidence candidateunclear0.000not prioritized-2
252ATP2B3unclear / low-confidence candidateunclear0.000not prioritized-2
253PRDM16unclear / low-confidence candidateunclear0.000not prioritized-2
254PTK6unclear / low-confidence candidateunclear0.000not prioritized-2
255LATS2unclear / low-confidence candidateunclear0.000not prioritized-2
256RAD51Cunclear / low-confidence candidateunclear0.000not prioritized-2
257STAT5Bunclear / low-confidence candidateunclear0.000not prioritized-2
258IKZF3unclear / low-confidence candidateunclear0.000not prioritized-2
259CDKN2Bunclear / low-confidence candidateunclear0.000not prioritized-2
260FANCEunclear / low-confidence candidateunclear0.000not prioritized-2
261TYRP1unclear / low-confidence candidateunclear0.000not prioritized-2
262BIRC3unclear / low-confidence candidateunclear0.000not prioritized-2
263ALKunclear / low-confidence candidateunclear0.000not prioritized-2
264FUBP1unclear / low-confidence candidateunclear0.000not prioritized-2
265PATZ1unclear / low-confidence candidateunclear0.000not prioritized-2
266FMN1unclear / low-confidence candidateunclear0.000not prioritized-2
267H3-3Aunclear / low-confidence candidateunclear0.000not prioritized-1
268GATA2unclear / low-confidence candidateunclear0.000not prioritized-1
269APOBEC3Bunclear / low-confidence candidateunclear0.000not prioritized-1
270BCL2unclear / low-confidence candidateunclear0.000not prioritized-1
271POU2AF1unclear / low-confidence candidateunclear0.000not prioritized-1
272PMELunclear / low-confidence candidateunclear0.000not prioritized0
273KRASunclear / low-confidence candidateunclear0.000not prioritized0
274TENT5Cunclear / low-confidence candidateunclear0.000not prioritized0
275CD79Aunclear / low-confidence candidateunclear0.000not prioritized0
276LPPunclear / low-confidence candidateunclear0.000not prioritized0
277PLXNB2unclear / low-confidence candidateunclear0.000not prioritized0
278SUZ12unclear / low-confidence candidateunclear0.000not prioritized0
279CBFA2T3unclear / low-confidence candidateunclear0.000not prioritized0
280NF2unclear / low-confidence candidateunclear0.000not prioritized0
281MAPK1unclear / low-confidence candidateunclear0.000not prioritized0
282KRT5unclear / low-confidence candidateunclear0.000not prioritized0
283HRASunclear / low-confidence candidateunclear0.000not prioritized0
284CNOT9unclear / low-confidence candidateunclear0.000not prioritized0
285PDCD1LG2unclear / low-confidence candidateunclear0.000not prioritized0
286SLC24A5unclear / low-confidence candidateunclear0.000not prioritized0
287NOTCH1unclear / low-confidence candidateunclear0.000not prioritized0
288MAP3K1unclear / low-confidence candidateunclear0.000not prioritized0
289CDH1unclear / low-confidence candidateunclear0.000not prioritized0
290BACH2unclear / low-confidence candidateunclear0.000not prioritized0
291KEAP1unclear / low-confidence candidateunclear0.000not prioritized0
292MED12unclear / low-confidence candidateunclear0.000not prioritized0
293H3C2unclear / low-confidence candidateunclear0.000not prioritized0
294TNFRSF17unclear / low-confidence candidateunclear0.000not prioritized0
295PIK3CBunclear / low-confidence candidateunclear0.000not prioritized0
296FBXW7unclear / low-confidence candidateunclear0.000not prioritized0
297NFE2L2unclear / low-confidence candidateunclear0.000not prioritized0
298ABL1unclear / low-confidence candidateunclear0.000not prioritized0
299CLPTM1Lunclear / low-confidence candidateunclear0.000not prioritized0
300ASPSCR1unclear / low-confidence candidateunclear0.000not prioritized0
+
+ + + +
+

Top resistance biomarker candidates

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + 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+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
RankTargetRoleBest modalityScorePriorityRank shift
1B2Mantigen-presentation resistance biomarkerresistance biomarker / patient stratification0.806high110
2JAK2IFN-gamma resistance mechanism / biomarkerresistance biomarker / patient stratification0.793high263
3JAK1IFN-gamma resistance mechanism / biomarkerresistance biomarker / patient stratification0.792high268
4NRAStumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.760high1
5IL2RATreg-suppression marker / possible IO-combination targetantibody / Treg-associated IO-combination candidate0.628medium43
6CTLA4anti-PD-1 combination targetantibody / IO-combination target0.524medium9
7PRF1immune-context markerimmune-context biomarker0.500medium182
8PDCD1anti-PD-1 combination targetantibody / IO-combination target0.498medium36
9CD274anti-PD-1 combination targetantibody / IO-combination target0.496medium44
10LAG3anti-PD-1 combination targetantibody / IO-combination target0.493medium70
11BRAFtumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.482medium-9
12MAP2K1tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.476medium-8
13MITFtumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.391low-5
14TERTtumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.385low2
15CDKN2Atumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.329low-14
16PTENtumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.313low-9
17NF1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.309low-8
18BAP1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.128low-15
19TP53tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.111low1
20MAP2K2tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.106low-14
21CDK4tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.101low-11
22KITtumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.098not prioritized-9
23RB1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.094not prioritized70
24GNAQunclear / low-confidence candidateunclear0.000not prioritized-13
25ARID2unclear / low-confidence candidateunclear0.000not prioritized-13
26RAC1unclear / low-confidence candidateunclear0.000not prioritized-12
27GNA11unclear / low-confidence candidateunclear0.000not prioritized-10
28POT1unclear / low-confidence candidateunclear0.000not prioritized-10
29MBD4unclear / low-confidence candidateunclear0.000not prioritized-10
30SF3B1unclear / low-confidence candidateunclear0.000not prioritized-9
31PPP6Cunclear / low-confidence candidateunclear0.000not prioritized-9
32IRF4unclear / low-confidence candidateunclear0.000not prioritized-9
33BRCA2unclear / low-confidence candidateunclear0.000not prioritized-9
34RAF1unclear / low-confidence candidateunclear0.000not prioritized-9
35KDRunclear / low-confidence candidateunclear0.000not prioritized-9
36PDGFRAunclear / low-confidence candidateunclear0.000not prioritized-9
37ATMunclear / low-confidence candidateunclear0.000not prioritized-9
38LRP1Bunclear / low-confidence candidateunclear0.000not prioritized-9
39FLT4unclear / low-confidence candidateunclear0.000not prioritized-9
40CSF3Runclear / low-confidence candidateunclear0.000not prioritized-9
41PDGFRBunclear / low-confidence candidateunclear0.000not prioritized-9
42TET2unclear / low-confidence candidateunclear0.000not prioritized-9
43POLEunclear / low-confidence candidateunclear0.000not prioritized-9
44DDX3Xunclear / low-confidence candidateunclear0.000not prioritized-9
45FOXP1unclear / low-confidence candidateunclear0.000not prioritized-9
46PBRM1unclear / low-confidence candidateunclear0.000not prioritized-9
47SETD2unclear / low-confidence candidateunclear0.000not prioritized-9
48CCND1unclear / low-confidence candidateunclear0.000not prioritized-9
49ERBB4unclear / low-confidence candidateunclear0.000not prioritized-9
50METunclear / low-confidence candidateunclear0.000not prioritized-9
51STK11unclear / low-confidence candidateunclear0.000not prioritized-9
52ROS1unclear / low-confidence candidateunclear0.000not prioritized-9
53MTORunclear / low-confidence candidateunclear0.000not prioritized-8
54H3-3Bunclear / low-confidence candidateunclear0.000not prioritized-8
55TRRAPunclear / low-confidence candidateunclear0.000not prioritized-8
56MC1Runclear / low-confidence candidateunclear0.000not prioritized-7
57IKZF1unclear / low-confidence candidateunclear0.000not prioritized-7
58FAT1unclear / low-confidence candidateunclear0.000not prioritized-7
59DICER1unclear / low-confidence candidateunclear0.000not prioritized-7
60MDM2unclear / low-confidence candidateunclear0.000not prioritized-6
61IFNAR1unclear / low-confidence candidateunclear0.000not prioritized-6
62MECOMunclear / low-confidence candidateunclear0.000not prioritized-6
63WRNunclear / low-confidence candidateunclear0.000not prioritized-6
64CHEK2unclear / low-confidence candidateunclear0.000not prioritized-6
65ATRunclear / low-confidence candidateunclear0.000not prioritized-6
66CUX1unclear / low-confidence candidateunclear0.000not prioritized-6
67KMT2Dunclear / low-confidence candidateunclear0.000not prioritized-6
68EP300unclear / low-confidence candidateunclear0.000not prioritized-6
69ESR1unclear / low-confidence candidateunclear0.000not prioritized-6
70BRCA1unclear / low-confidence candidateunclear0.000not prioritized-6
71AKT1unclear / low-confidence candidateunclear0.000not prioritized-6
72NTRK1unclear / low-confidence candidateunclear0.000not prioritized-6
73ERBB2unclear / low-confidence candidateunclear0.000not prioritized-6
74PREX2unclear / low-confidence candidateunclear0.000not prioritized-6
75FAT4unclear / low-confidence candidateunclear0.000not prioritized-6
76KMT2Cunclear / low-confidence candidateunclear0.000not prioritized-6
77POLQunclear / low-confidence candidateunclear0.000not prioritized-6
78FGFR2unclear / low-confidence candidateunclear0.000not prioritized-6
79TP63unclear / low-confidence candidateunclear0.000not prioritized-6
80FGFR4unclear / low-confidence candidateunclear0.000not prioritized-6
81GRIN2Aunclear / low-confidence candidateunclear0.000not prioritized-6
82UBR5unclear / low-confidence candidateunclear0.000not prioritized-6
83OCA2unclear / low-confidence candidateunclear0.000not prioritized-6
84SMARCA4unclear / low-confidence candidateunclear0.000not prioritized-6
85IFNAR2unclear / low-confidence candidateunclear0.000not prioritized-6
86FGFR1unclear / low-confidence candidateunclear0.000not prioritized-5
87PTPRBunclear / low-confidence candidateunclear0.000not prioritized-5
88PTPRTunclear / low-confidence candidateunclear0.000not prioritized-5
89PTPN11unclear / low-confidence candidateunclear0.000not prioritized-5
90MDM4unclear / low-confidence candidateunclear0.000not prioritized-5
91TSC1unclear / low-confidence candidateunclear0.000not prioritized-5
92TBX3unclear / low-confidence candidateunclear0.000not prioritized-5
93ERBB3unclear / low-confidence candidateunclear0.000not prioritized-5
94ATRXunclear / low-confidence candidateunclear0.000not prioritized-5
95RUNX1T1unclear / low-confidence candidateunclear0.000not prioritized-5
96CDK12unclear / low-confidence candidateunclear0.000not prioritized-5
97TYRunclear / low-confidence candidateunclear0.000not prioritized-5
98AKT2unclear / low-confidence candidateunclear0.000not prioritized-4
99PTPRKunclear / low-confidence candidateunclear0.000not prioritized-4
100CBLunclear / low-confidence candidateunclear0.000not prioritized-4
101DNMT3Aunclear / low-confidence candidateunclear0.000not prioritized-4
102RRM2unclear / low-confidence candidateunclear0.000not prioritized-4
103KLF6unclear / low-confidence candidateunclear0.000not prioritized-4
104ARunclear / low-confidence candidateunclear0.000not prioritized-4
105KMT2Aunclear / low-confidence candidateunclear0.000not prioritized-4
106CYLDunclear / low-confidence candidateunclear0.000not prioritized-4
107RPL5unclear / low-confidence candidateunclear0.000not prioritized-4
108ERCC2unclear / low-confidence candidateunclear0.000not prioritized-4
109IDH1unclear / low-confidence candidateunclear0.000not prioritized-4
110NOTCH2unclear / low-confidence candidateunclear0.000not prioritized-4
111CDK6unclear / low-confidence candidateunclear0.000not prioritized-4
112IKBKBunclear / low-confidence candidateunclear0.000not prioritized-4
113NTRK2unclear / low-confidence candidateunclear0.000not prioritized-4
114RRM2Bunclear / low-confidence candidateunclear0.000not prioritized-4
115CASP8unclear / low-confidence candidateunclear0.000not prioritized-3
116POLD1unclear / low-confidence candidateunclear0.000not prioritized-3
117IL7Runclear / low-confidence candidateunclear0.000not prioritized-3
118QKIunclear / low-confidence candidateunclear0.000not prioritized-3
119GNASunclear / low-confidence candidateunclear0.000not prioritized-3
120MYBunclear / low-confidence candidateunclear0.000not prioritized-3
121PTCH1unclear / low-confidence candidateunclear0.000not prioritized-3
122DDR2unclear / low-confidence candidateunclear0.000not prioritized-3
123PIK3R1unclear / low-confidence candidateunclear0.000not prioritized-3
124TSC2unclear / low-confidence candidateunclear0.000not prioritized-3
125PHOX2Bunclear / low-confidence candidateunclear0.000not prioritized-3
126SETBP1unclear / low-confidence candidateunclear0.000not prioritized-3
127RRM1unclear / low-confidence candidateunclear0.000not prioritized-3
128SPENunclear / low-confidence candidateunclear0.000not prioritized-3
129ARHGAP35unclear / low-confidence candidateunclear0.000not prioritized-3
130SYKunclear / low-confidence candidateunclear0.000not prioritized-3
131PAX5unclear / low-confidence candidateunclear0.000not prioritized-3
132CYP1B1unclear / low-confidence candidateunclear0.000not prioritized-3
133FANCAunclear / low-confidence candidateunclear0.000not prioritized-3
134CIITAunclear / low-confidence candidateunclear0.000not prioritized-3
135BCL9Lunclear / low-confidence candidateunclear0.000not prioritized-3
136NUTM1unclear / low-confidence candidateunclear0.000not prioritized-3
137ARNTunclear / low-confidence candidateunclear0.000not prioritized-3
138CCND2unclear / low-confidence candidateunclear0.000not prioritized-3
139PER1unclear / low-confidence candidateunclear0.000not prioritized-3
140JUNunclear / low-confidence candidateunclear0.000not prioritized-3
141KAT6Aunclear / low-confidence candidateunclear0.000not prioritized-3
142CBLBunclear / low-confidence candidateunclear0.000not prioritized-3
143HNF1Aunclear / low-confidence candidateunclear0.000not prioritized-3
144BCL11Aunclear / low-confidence candidateunclear0.000not prioritized-3
145USP6unclear / low-confidence candidateunclear0.000not prioritized-3
146MYCNunclear / low-confidence candidateunclear0.000not prioritized-3
147PRDM1unclear / low-confidence candidateunclear0.000not prioritized-3
148AFDNunclear / low-confidence candidateunclear0.000not prioritized-3
149IL2RGunclear / low-confidence candidateunclear0.000not prioritized-3
150IL2RBunclear / low-confidence candidateunclear0.000not prioritized-3
151SMAD2unclear / low-confidence candidateunclear0.000not prioritized-3
152AXIN1unclear / low-confidence candidateunclear0.000not prioritized-3
153SALL4unclear / low-confidence candidateunclear0.000not prioritized-3
154NFKBIEunclear / low-confidence candidateunclear0.000not prioritized-3
155HGFunclear / low-confidence candidateunclear0.000not prioritized-3
156PPP2R1Aunclear / low-confidence candidateunclear0.000not prioritized-3
157BCORunclear / low-confidence candidateunclear0.000not prioritized-3
158ERCC3unclear / low-confidence candidateunclear0.000not prioritized-3
159FANCD2unclear / low-confidence candidateunclear0.000not prioritized-3
160DAXXunclear / low-confidence candidateunclear0.000not prioritized-3
161PTPRCunclear / low-confidence candidateunclear0.000not prioritized-3
162MYH9unclear / low-confidence candidateunclear0.000not prioritized-3
163ARID1Bunclear / low-confidence candidateunclear0.000not prioritized-3
164LZTR1unclear / low-confidence candidateunclear0.000not prioritized-3
165CICunclear / low-confidence candidateunclear0.000not prioritized-3
166CREBBPunclear / low-confidence candidateunclear0.000not prioritized-3
167MYCLunclear / low-confidence candidateunclear0.000not prioritized-3
168SLC45A2unclear / low-confidence candidateunclear0.000not prioritized-3
169FCRL4unclear / low-confidence candidateunclear0.000not prioritized-3
170MAP3K13unclear / low-confidence candidateunclear0.000not prioritized-3
171CNOT3unclear / low-confidence candidateunclear0.000not prioritized-3
172FLGunclear / low-confidence candidateunclear0.000not prioritized-3
173AMER1unclear / low-confidence candidateunclear0.000not prioritized-3
174ATF1unclear / low-confidence candidateunclear0.000not prioritized-3
175ERCC5unclear / low-confidence candidateunclear0.000not prioritized-3
176ERCC4unclear / low-confidence candidateunclear0.000not prioritized-3
177MX2unclear / low-confidence candidateunclear0.000not prioritized-3
178SUFUunclear / low-confidence candidateunclear0.000not prioritized-3
179NTRK3unclear / low-confidence candidateunclear0.000not prioritized-3
180ARID1Aunclear / low-confidence candidateunclear0.000not prioritized-3
181PARP1unclear / low-confidence candidateunclear0.000not prioritized-3
182CARD11unclear / low-confidence candidateunclear0.000not prioritized-3
183RICTORunclear / low-confidence candidateunclear0.000not prioritized-3
184BRD4unclear / low-confidence candidateunclear0.000not prioritized-3
185RETunclear / low-confidence candidateunclear0.000not prioritized-3
186EZH2unclear / low-confidence candidateunclear0.000not prioritized-3
187SMAD3unclear / low-confidence candidateunclear0.000not prioritized-3
188LCKunclear / low-confidence candidateunclear0.000not prioritized-3
189TFEBunclear / low-confidence candidateunclear0.000not prioritized-3
190CDX2unclear / low-confidence candidateunclear0.000not prioritized-3
191ACVR1Bunclear / low-confidence candidateunclear0.000not prioritized-3
192NCOR2unclear / low-confidence candidateunclear0.000not prioritized-2
193IRS4unclear / low-confidence candidateunclear0.000not prioritized-2
194SPOPunclear / low-confidence candidateunclear0.000not prioritized-2
195CREB1unclear / low-confidence candidateunclear0.000not prioritized-2
196TET1unclear / low-confidence candidateunclear0.000not prioritized-2
197EGFRunclear / low-confidence candidateunclear0.000not prioritized-2
198CRLF2unclear / low-confidence candidateunclear0.000not prioritized-2
199STN1unclear / low-confidence candidateunclear0.000not prioritized-2
200TFE3unclear / low-confidence candidateunclear0.000not prioritized-2
201TRAF7unclear / low-confidence candidateunclear0.000not prioritized-2
202NFKB2unclear / low-confidence candidateunclear0.000not prioritized-2
203AFF4unclear / low-confidence candidateunclear0.000not prioritized-2
204ARHGEF12unclear / low-confidence candidateunclear0.000not prioritized-2
205U2AF1unclear / low-confidence candidateunclear0.000not prioritized-2
206PMS2unclear / low-confidence candidateunclear0.000not prioritized-2
207ZBTB16unclear / low-confidence candidateunclear0.000not prioritized-2
208MTAPunclear / low-confidence candidateunclear0.000not prioritized-2
209MSH2unclear / low-confidence candidateunclear0.000not prioritized-2
210ZFHX3unclear / low-confidence candidateunclear0.000not prioritized-2
211KDM5Aunclear / low-confidence candidateunclear0.000not prioritized-2
212CHD4unclear / low-confidence candidateunclear0.000not prioritized-2
213FBXO11unclear / low-confidence candidateunclear0.000not prioritized-2
214PTPN13unclear / low-confidence candidateunclear0.000not prioritized-2
215PLCG1unclear / low-confidence candidateunclear0.000not prioritized-2
216FASunclear / low-confidence candidateunclear0.000not prioritized-2
217MAXunclear / low-confidence candidateunclear0.000not prioritized-2
218BCORL1unclear / low-confidence candidateunclear0.000not prioritized-2
219KNL1unclear / low-confidence candidateunclear0.000not prioritized-2
220BUB1Bunclear / low-confidence candidateunclear0.000not prioritized-2
221NCOR1unclear / low-confidence candidateunclear0.000not prioritized-2
222ACKR3unclear / low-confidence candidateunclear0.000not prioritized-2
223SMOunclear / low-confidence candidateunclear0.000not prioritized-2
224WASunclear / low-confidence candidateunclear0.000not prioritized-2
225NUP98unclear / low-confidence candidateunclear0.000not prioritized-2
226CACNA1Dunclear / low-confidence candidateunclear0.000not prioritized-2
227FLT3unclear / low-confidence candidateunclear0.000not prioritized-2
228BTKunclear / low-confidence candidateunclear0.000not prioritized-2
229RANBP2unclear / low-confidence candidateunclear0.000not prioritized-2
230BCL11Bunclear / low-confidence candidateunclear0.000not prioritized-2
231CLTCunclear / low-confidence candidateunclear0.000not prioritized-2
232MN1unclear / low-confidence candidateunclear0.000not prioritized-2
233MAP2K4unclear / low-confidence candidateunclear0.000not prioritized-2
234BCL9unclear / low-confidence candidateunclear0.000not prioritized-2
235BRD3unclear / low-confidence candidateunclear0.000not prioritized-2
236KAT6Bunclear / low-confidence candidateunclear0.000not prioritized-2
237TBL1XR1unclear / low-confidence candidateunclear0.000not prioritized-2
238TMEM127unclear / low-confidence candidateunclear0.000not prioritized-2
239FANCFunclear / low-confidence candidateunclear0.000not prioritized-2
240PIK3CAunclear / low-confidence candidateunclear0.000not prioritized-2
241APCunclear / low-confidence candidateunclear0.000not prioritized-2
242NKX2-1unclear / low-confidence candidateunclear0.000not prioritized-2
243CTNNB1unclear / low-confidence candidateunclear0.000not prioritized-2
244MRTFAunclear / low-confidence candidateunclear0.000not prioritized-2
245KLF4unclear / low-confidence candidateunclear0.000not prioritized-2
246ZNF331unclear / low-confidence candidateunclear0.000not prioritized-2
247FGFR3unclear / low-confidence candidateunclear0.000not prioritized-2
248FHunclear / low-confidence candidateunclear0.000not prioritized-2
249MUTYHunclear / low-confidence candidateunclear0.000not prioritized-2
250TCL1Aunclear / low-confidence candidateunclear0.000not prioritized-2
251CARS1unclear / low-confidence candidateunclear0.000not prioritized-2
252ATP2B3unclear / low-confidence candidateunclear0.000not prioritized-2
253PRDM16unclear / low-confidence candidateunclear0.000not prioritized-2
254PTK6unclear / low-confidence candidateunclear0.000not prioritized-2
255LATS2unclear / low-confidence candidateunclear0.000not prioritized-2
256RAD51Cunclear / low-confidence candidateunclear0.000not prioritized-2
257STAT5Bunclear / low-confidence candidateunclear0.000not prioritized-2
258IKZF3unclear / low-confidence candidateunclear0.000not prioritized-2
259CDKN2Bunclear / low-confidence candidateunclear0.000not prioritized-2
260FANCEunclear / low-confidence candidateunclear0.000not prioritized-2
261TYRP1unclear / low-confidence candidateunclear0.000not prioritized-2
262BIRC3unclear / low-confidence candidateunclear0.000not prioritized-2
263ALKunclear / low-confidence candidateunclear0.000not prioritized-2
264FUBP1unclear / low-confidence candidateunclear0.000not prioritized-2
265PATZ1unclear / low-confidence candidateunclear0.000not prioritized-2
266FMN1unclear / low-confidence candidateunclear0.000not prioritized-2
267H3-3Aunclear / low-confidence candidateunclear0.000not prioritized-1
268GATA2unclear / low-confidence candidateunclear0.000not prioritized-1
269APOBEC3Bunclear / low-confidence candidateunclear0.000not prioritized-1
270BCL2unclear / low-confidence candidateunclear0.000not prioritized-1
271POU2AF1unclear / low-confidence candidateunclear0.000not prioritized-1
272PMELunclear / low-confidence candidateunclear0.000not prioritized0
273KRASunclear / low-confidence candidateunclear0.000not prioritized0
274TENT5Cunclear / low-confidence candidateunclear0.000not prioritized0
275CD79Aunclear / low-confidence candidateunclear0.000not prioritized0
276LPPunclear / low-confidence candidateunclear0.000not prioritized0
277PLXNB2unclear / low-confidence candidateunclear0.000not prioritized0
278SUZ12unclear / low-confidence candidateunclear0.000not prioritized0
279CBFA2T3unclear / low-confidence candidateunclear0.000not prioritized0
280NF2unclear / low-confidence candidateunclear0.000not prioritized0
281MAPK1unclear / low-confidence candidateunclear0.000not prioritized0
282KRT5unclear / low-confidence candidateunclear0.000not prioritized0
283HRASunclear / low-confidence candidateunclear0.000not prioritized0
284CNOT9unclear / low-confidence candidateunclear0.000not prioritized0
285PDCD1LG2unclear / low-confidence candidateunclear0.000not prioritized0
286SLC24A5unclear / low-confidence candidateunclear0.000not prioritized0
287NOTCH1unclear / low-confidence candidateunclear0.000not prioritized0
288MAP3K1unclear / low-confidence candidateunclear0.000not prioritized0
289CDH1unclear / low-confidence candidateunclear0.000not prioritized0
290BACH2unclear / low-confidence candidateunclear0.000not prioritized0
291KEAP1unclear / low-confidence candidateunclear0.000not prioritized0
292MED12unclear / low-confidence candidateunclear0.000not prioritized0
293H3C2unclear / low-confidence candidateunclear0.000not prioritized0
294TNFRSF17unclear / low-confidence candidateunclear0.000not prioritized0
295PIK3CBunclear / low-confidence candidateunclear0.000not prioritized0
296FBXW7unclear / low-confidence candidateunclear0.000not prioritized0
297NFE2L2unclear / low-confidence candidateunclear0.000not prioritized0
298ABL1unclear / low-confidence candidateunclear0.000not prioritized0
299CLPTM1Lunclear / low-confidence candidateunclear0.000not prioritized0
300ASPSCR1unclear / low-confidence candidateunclear0.000not prioritized0
+
+ + + +
+

Top tumor-intrinsic / small-molecule candidates

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
RankTargetRoleBest modalityScorePriorityRank shift
1BRAFtumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.845high1
2MAP2K1tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.836high2
3MAP2K2tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.689medium3
4CDK4tumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.682medium6
5KITtumor-intrinsic driver / small-molecule targetsmall molecule / pathway targeting0.679medium8
6NRAStumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.666medium-1
7MITFtumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.521medium1
8TERTtumor-intrinsic driver / biomarkertumor-intrinsic biomarker / pathway context0.513medium8
9CTLA4anti-PD-1 combination targetantibody / IO-combination target0.159low6
10PDCD1anti-PD-1 combination targetantibody / IO-combination target0.144low34
11CD274anti-PD-1 combination targetantibody / IO-combination target0.141low42
12LAG3anti-PD-1 combination targetantibody / IO-combination target0.137low68
13B2Mantigen-presentation resistance biomarkerresistance biomarker / patient stratification0.132low98
14IL2RATreg-suppression marker / possible IO-combination targetantibody / Treg-associated IO-combination candidate0.126low34
15JAK2IFN-gamma resistance mechanism / biomarkerresistance biomarker / patient stratification0.115low250
16JAK1IFN-gamma resistance mechanism / biomarkerresistance biomarker / patient stratification0.114low255
17GNAQunclear / low-confidence candidateunclear0.015not prioritized-6
18ARID2unclear / low-confidence candidateunclear0.015not prioritized-6
19RAC1unclear / low-confidence candidateunclear0.013not prioritized-5
20GNA11unclear / low-confidence candidateunclear0.012not prioritized-3
21POT1unclear / low-confidence candidateunclear0.012not prioritized-3
22MBD4unclear / low-confidence candidateunclear0.012not prioritized-3
23SF3B1unclear / low-confidence candidateunclear0.011not prioritized-2
24PPP6Cunclear / low-confidence candidateunclear0.010not prioritized-2
25IRF4unclear / low-confidence candidateunclear0.009not prioritized-2
26BRCA2unclear / low-confidence candidateunclear0.008not prioritized-2
27RAF1unclear / low-confidence candidateunclear0.005not prioritized-2
28KDRunclear / low-confidence candidateunclear0.005not prioritized-2
29PDGFRAunclear / low-confidence candidateunclear0.004not prioritized-2
30ATMunclear / low-confidence candidateunclear0.003not prioritized-2
31LRP1Bunclear / low-confidence candidateunclear0.002not prioritized-2
32FLT4unclear / low-confidence candidateunclear0.001not prioritized-2
33CSF3Runclear / low-confidence candidateunclear0.001not prioritized-2
34PDGFRBunclear / low-confidence candidateunclear0.000not prioritized-2
35TET2unclear / low-confidence candidateunclear0.000not prioritized-2
36CDKN2Atumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-35
37BAP1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-34
38PTENtumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-31
39NF1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-30
40TP53tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-20
41POLEunclear / low-confidence candidateunclear0.000not prioritized-7
42DDX3Xunclear / low-confidence candidateunclear0.000not prioritized-7
43FOXP1unclear / low-confidence candidateunclear0.000not prioritized-7
44PBRM1unclear / low-confidence candidateunclear0.000not prioritized-7
45SETD2unclear / low-confidence candidateunclear0.000not prioritized-7
46CCND1unclear / low-confidence candidateunclear0.000not prioritized-7
47ERBB4unclear / low-confidence candidateunclear0.000not prioritized-7
48METunclear / low-confidence candidateunclear0.000not prioritized-7
49STK11unclear / low-confidence candidateunclear0.000not prioritized-7
50ROS1unclear / low-confidence candidateunclear0.000not prioritized-7
51MTORunclear / low-confidence candidateunclear0.000not prioritized-6
52H3-3Bunclear / low-confidence candidateunclear0.000not prioritized-6
53TRRAPunclear / low-confidence candidateunclear0.000not prioritized-6
54MC1Runclear / low-confidence candidateunclear0.000not prioritized-5
55IKZF1unclear / low-confidence candidateunclear0.000not prioritized-5
56FAT1unclear / low-confidence candidateunclear0.000not prioritized-5
57DICER1unclear / low-confidence candidateunclear0.000not prioritized-5
58MDM2unclear / low-confidence candidateunclear0.000not prioritized-4
59IFNAR1unclear / low-confidence candidateunclear0.000not prioritized-4
60MECOMunclear / low-confidence candidateunclear0.000not prioritized-4
61WRNunclear / low-confidence candidateunclear0.000not prioritized-4
62CHEK2unclear / low-confidence candidateunclear0.000not prioritized-4
63ATRunclear / low-confidence candidateunclear0.000not prioritized-4
64CUX1unclear / low-confidence candidateunclear0.000not prioritized-4
65KMT2Dunclear / low-confidence candidateunclear0.000not prioritized-4
66EP300unclear / low-confidence candidateunclear0.000not prioritized-4
67ESR1unclear / low-confidence candidateunclear0.000not prioritized-4
68BRCA1unclear / low-confidence candidateunclear0.000not prioritized-4
69AKT1unclear / low-confidence candidateunclear0.000not prioritized-4
70NTRK1unclear / low-confidence candidateunclear0.000not prioritized-4
71ERBB2unclear / low-confidence candidateunclear0.000not prioritized-4
72PREX2unclear / low-confidence candidateunclear0.000not prioritized-4
73FAT4unclear / low-confidence candidateunclear0.000not prioritized-4
74KMT2Cunclear / low-confidence candidateunclear0.000not prioritized-4
75POLQunclear / low-confidence candidateunclear0.000not prioritized-4
76FGFR2unclear / low-confidence candidateunclear0.000not prioritized-4
77TP63unclear / low-confidence candidateunclear0.000not prioritized-4
78FGFR4unclear / low-confidence candidateunclear0.000not prioritized-4
79GRIN2Aunclear / low-confidence candidateunclear0.000not prioritized-4
80UBR5unclear / low-confidence candidateunclear0.000not prioritized-4
81OCA2unclear / low-confidence candidateunclear0.000not prioritized-4
82SMARCA4unclear / low-confidence candidateunclear0.000not prioritized-4
83IFNAR2unclear / low-confidence candidateunclear0.000not prioritized-4
84FGFR1unclear / low-confidence candidateunclear0.000not prioritized-3
85PTPRBunclear / low-confidence candidateunclear0.000not prioritized-3
86PTPRTunclear / low-confidence candidateunclear0.000not prioritized-3
87PTPN11unclear / low-confidence candidateunclear0.000not prioritized-3
88MDM4unclear / low-confidence candidateunclear0.000not prioritized-3
89TSC1unclear / low-confidence candidateunclear0.000not prioritized-3
90TBX3unclear / low-confidence candidateunclear0.000not prioritized-3
91ERBB3unclear / low-confidence candidateunclear0.000not prioritized-3
92ATRXunclear / low-confidence candidateunclear0.000not prioritized-3
93RUNX1T1unclear / low-confidence candidateunclear0.000not prioritized-3
94CDK12unclear / low-confidence candidateunclear0.000not prioritized-3
95TYRunclear / low-confidence candidateunclear0.000not prioritized-3
96RB1tumor-intrinsic driver / poor direct therapeutic targetbiomarker / pathway context only0.000not prioritized-3
97AKT2unclear / low-confidence candidateunclear0.000not prioritized-3
98PTPRKunclear / low-confidence candidateunclear0.000not prioritized-3
99CBLunclear / low-confidence candidateunclear0.000not prioritized-3
100DNMT3Aunclear / low-confidence candidateunclear0.000not prioritized-3
101RRM2unclear / low-confidence candidateunclear0.000not prioritized-3
102KLF6unclear / low-confidence candidateunclear0.000not prioritized-3
103ARunclear / low-confidence candidateunclear0.000not prioritized-3
104KMT2Aunclear / low-confidence candidateunclear0.000not prioritized-3
105CYLDunclear / low-confidence candidateunclear0.000not prioritized-3
106RPL5unclear / low-confidence candidateunclear0.000not prioritized-3
107ERCC2unclear / low-confidence candidateunclear0.000not prioritized-3
108IDH1unclear / low-confidence candidateunclear0.000not prioritized-3
109NOTCH2unclear / low-confidence candidateunclear0.000not prioritized-3
110CDK6unclear / low-confidence candidateunclear0.000not prioritized-3
111IKBKBunclear / low-confidence candidateunclear0.000not prioritized-3
112NTRK2unclear / low-confidence candidateunclear0.000not prioritized-3
113RRM2Bunclear / low-confidence candidateunclear0.000not prioritized-3
114CASP8unclear / low-confidence candidateunclear0.000not prioritized-2
115POLD1unclear / low-confidence candidateunclear0.000not prioritized-2
116IL7Runclear / low-confidence candidateunclear0.000not prioritized-2
117QKIunclear / low-confidence candidateunclear0.000not prioritized-2
118GNASunclear / low-confidence candidateunclear0.000not prioritized-2
119MYBunclear / low-confidence candidateunclear0.000not prioritized-2
120PTCH1unclear / low-confidence candidateunclear0.000not prioritized-2
121DDR2unclear / low-confidence candidateunclear0.000not prioritized-2
122PIK3R1unclear / low-confidence candidateunclear0.000not prioritized-2
123TSC2unclear / low-confidence candidateunclear0.000not prioritized-2
124PHOX2Bunclear / low-confidence candidateunclear0.000not prioritized-2
125SETBP1unclear / low-confidence candidateunclear0.000not prioritized-2
126RRM1unclear / low-confidence candidateunclear0.000not prioritized-2
127SPENunclear / low-confidence candidateunclear0.000not prioritized-2
128ARHGAP35unclear / low-confidence candidateunclear0.000not prioritized-2
129SYKunclear / low-confidence candidateunclear0.000not prioritized-2
130PAX5unclear / low-confidence candidateunclear0.000not prioritized-2
131CYP1B1unclear / low-confidence candidateunclear0.000not prioritized-2
132FANCAunclear / low-confidence candidateunclear0.000not prioritized-2
133CIITAunclear / low-confidence candidateunclear0.000not prioritized-2
134BCL9Lunclear / low-confidence candidateunclear0.000not prioritized-2
135NUTM1unclear / low-confidence candidateunclear0.000not prioritized-2
136ARNTunclear / low-confidence candidateunclear0.000not prioritized-2
137CCND2unclear / low-confidence candidateunclear0.000not prioritized-2
138PER1unclear / low-confidence candidateunclear0.000not prioritized-2
139JUNunclear / low-confidence candidateunclear0.000not prioritized-2
140KAT6Aunclear / low-confidence candidateunclear0.000not prioritized-2
141CBLBunclear / low-confidence candidateunclear0.000not prioritized-2
142HNF1Aunclear / low-confidence candidateunclear0.000not prioritized-2
143BCL11Aunclear / low-confidence candidateunclear0.000not prioritized-2
144USP6unclear / low-confidence candidateunclear0.000not prioritized-2
145MYCNunclear / low-confidence candidateunclear0.000not prioritized-2
146PRDM1unclear / low-confidence candidateunclear0.000not prioritized-2
147AFDNunclear / low-confidence candidateunclear0.000not prioritized-2
148IL2RGunclear / low-confidence candidateunclear0.000not prioritized-2
149IL2RBunclear / low-confidence candidateunclear0.000not prioritized-2
150SMAD2unclear / low-confidence candidateunclear0.000not prioritized-2
151AXIN1unclear / low-confidence candidateunclear0.000not prioritized-2
152SALL4unclear / low-confidence candidateunclear0.000not prioritized-2
153NFKBIEunclear / low-confidence candidateunclear0.000not prioritized-2
154HGFunclear / low-confidence candidateunclear0.000not prioritized-2
155PPP2R1Aunclear / low-confidence candidateunclear0.000not prioritized-2
156BCORunclear / low-confidence candidateunclear0.000not prioritized-2
157ERCC3unclear / low-confidence candidateunclear0.000not prioritized-2
158FANCD2unclear / low-confidence candidateunclear0.000not prioritized-2
159DAXXunclear / low-confidence candidateunclear0.000not prioritized-2
160PTPRCunclear / low-confidence candidateunclear0.000not prioritized-2
161MYH9unclear / low-confidence candidateunclear0.000not prioritized-2
162ARID1Bunclear / low-confidence candidateunclear0.000not prioritized-2
163LZTR1unclear / low-confidence candidateunclear0.000not prioritized-2
164CICunclear / low-confidence candidateunclear0.000not prioritized-2
165CREBBPunclear / low-confidence candidateunclear0.000not prioritized-2
166MYCLunclear / low-confidence candidateunclear0.000not prioritized-2
167SLC45A2unclear / low-confidence candidateunclear0.000not prioritized-2
168FCRL4unclear / low-confidence candidateunclear0.000not prioritized-2
169MAP3K13unclear / low-confidence candidateunclear0.000not prioritized-2
170CNOT3unclear / low-confidence candidateunclear0.000not prioritized-2
171FLGunclear / low-confidence candidateunclear0.000not prioritized-2
172AMER1unclear / low-confidence candidateunclear0.000not prioritized-2
173ATF1unclear / low-confidence candidateunclear0.000not prioritized-2
174ERCC5unclear / low-confidence candidateunclear0.000not prioritized-2
175ERCC4unclear / low-confidence candidateunclear0.000not prioritized-2
176MX2unclear / low-confidence candidateunclear0.000not prioritized-2
177SUFUunclear / low-confidence candidateunclear0.000not prioritized-2
178NTRK3unclear / low-confidence candidateunclear0.000not prioritized-2
179ARID1Aunclear / low-confidence candidateunclear0.000not prioritized-2
180PARP1unclear / low-confidence candidateunclear0.000not prioritized-2
181CARD11unclear / low-confidence candidateunclear0.000not prioritized-2
182RICTORunclear / low-confidence candidateunclear0.000not prioritized-2
183BRD4unclear / low-confidence candidateunclear0.000not prioritized-2
184RETunclear / low-confidence candidateunclear0.000not prioritized-2
185EZH2unclear / low-confidence candidateunclear0.000not prioritized-2
186SMAD3unclear / low-confidence candidateunclear0.000not prioritized-2
187LCKunclear / low-confidence candidateunclear0.000not prioritized-2
188TFEBunclear / low-confidence candidateunclear0.000not prioritized-2
189CDX2unclear / low-confidence candidateunclear0.000not prioritized-2
190ACVR1Bunclear / low-confidence candidateunclear0.000not prioritized-2
191PRF1immune-context markerimmune-context biomarker0.000not prioritized-2
192NCOR2unclear / low-confidence candidateunclear0.000not prioritized-2
193IRS4unclear / low-confidence candidateunclear0.000not prioritized-2
194SPOPunclear / low-confidence candidateunclear0.000not prioritized-2
195CREB1unclear / low-confidence candidateunclear0.000not prioritized-2
196TET1unclear / low-confidence candidateunclear0.000not prioritized-2
197EGFRunclear / low-confidence candidateunclear0.000not prioritized-2
198CRLF2unclear / low-confidence candidateunclear0.000not prioritized-2
199STN1unclear / low-confidence candidateunclear0.000not prioritized-2
200TFE3unclear / low-confidence candidateunclear0.000not prioritized-2
201TRAF7unclear / low-confidence candidateunclear0.000not prioritized-2
202NFKB2unclear / low-confidence candidateunclear0.000not prioritized-2
203AFF4unclear / low-confidence candidateunclear0.000not prioritized-2
204ARHGEF12unclear / low-confidence candidateunclear0.000not prioritized-2
205U2AF1unclear / low-confidence candidateunclear0.000not prioritized-2
206PMS2unclear / low-confidence candidateunclear0.000not prioritized-2
207ZBTB16unclear / low-confidence candidateunclear0.000not prioritized-2
208MTAPunclear / low-confidence candidateunclear0.000not prioritized-2
209MSH2unclear / low-confidence candidateunclear0.000not prioritized-2
210ZFHX3unclear / low-confidence candidateunclear0.000not prioritized-2
211KDM5Aunclear / low-confidence candidateunclear0.000not prioritized-2
212CHD4unclear / low-confidence candidateunclear0.000not prioritized-2
213FBXO11unclear / low-confidence candidateunclear0.000not prioritized-2
214PTPN13unclear / low-confidence candidateunclear0.000not prioritized-2
215PLCG1unclear / low-confidence candidateunclear0.000not prioritized-2
216FASunclear / low-confidence candidateunclear0.000not prioritized-2
217MAXunclear / low-confidence candidateunclear0.000not prioritized-2
218BCORL1unclear / low-confidence candidateunclear0.000not prioritized-2
219KNL1unclear / low-confidence candidateunclear0.000not prioritized-2
220BUB1Bunclear / low-confidence candidateunclear0.000not prioritized-2
221NCOR1unclear / low-confidence candidateunclear0.000not prioritized-2
222ACKR3unclear / low-confidence candidateunclear0.000not prioritized-2
223SMOunclear / low-confidence candidateunclear0.000not prioritized-2
224WASunclear / low-confidence candidateunclear0.000not prioritized-2
225NUP98unclear / low-confidence candidateunclear0.000not prioritized-2
226CACNA1Dunclear / low-confidence candidateunclear0.000not prioritized-2
227FLT3unclear / low-confidence candidateunclear0.000not prioritized-2
228BTKunclear / low-confidence candidateunclear0.000not prioritized-2
229RANBP2unclear / low-confidence candidateunclear0.000not prioritized-2
230BCL11Bunclear / low-confidence candidateunclear0.000not prioritized-2
231CLTCunclear / low-confidence candidateunclear0.000not prioritized-2
232MN1unclear / low-confidence candidateunclear0.000not prioritized-2
233MAP2K4unclear / low-confidence candidateunclear0.000not prioritized-2
234BCL9unclear / low-confidence candidateunclear0.000not prioritized-2
235BRD3unclear / low-confidence candidateunclear0.000not prioritized-2
236KAT6Bunclear / low-confidence candidateunclear0.000not prioritized-2
237TBL1XR1unclear / low-confidence candidateunclear0.000not prioritized-2
238TMEM127unclear / low-confidence candidateunclear0.000not prioritized-2
239FANCFunclear / low-confidence candidateunclear0.000not prioritized-2
240PIK3CAunclear / low-confidence candidateunclear0.000not prioritized-2
241APCunclear / low-confidence candidateunclear0.000not prioritized-2
242NKX2-1unclear / low-confidence candidateunclear0.000not prioritized-2
243CTNNB1unclear / low-confidence candidateunclear0.000not prioritized-2
244MRTFAunclear / low-confidence candidateunclear0.000not prioritized-2
245KLF4unclear / low-confidence candidateunclear0.000not prioritized-2
246ZNF331unclear / low-confidence candidateunclear0.000not prioritized-2
247FGFR3unclear / low-confidence candidateunclear0.000not prioritized-2
248FHunclear / low-confidence candidateunclear0.000not prioritized-2
249MUTYHunclear / low-confidence candidateunclear0.000not prioritized-2
250TCL1Aunclear / low-confidence candidateunclear0.000not prioritized-2
251CARS1unclear / low-confidence candidateunclear0.000not prioritized-2
252ATP2B3unclear / low-confidence candidateunclear0.000not prioritized-2
253PRDM16unclear / low-confidence candidateunclear0.000not prioritized-2
254PTK6unclear / low-confidence candidateunclear0.000not prioritized-2
255LATS2unclear / low-confidence candidateunclear0.000not prioritized-2
256RAD51Cunclear / low-confidence candidateunclear0.000not prioritized-2
257STAT5Bunclear / low-confidence candidateunclear0.000not prioritized-2
258IKZF3unclear / low-confidence candidateunclear0.000not prioritized-2
259CDKN2Bunclear / low-confidence candidateunclear0.000not prioritized-2
260FANCEunclear / low-confidence candidateunclear0.000not prioritized-2
261TYRP1unclear / low-confidence candidateunclear0.000not prioritized-2
262BIRC3unclear / low-confidence candidateunclear0.000not prioritized-2
263ALKunclear / low-confidence candidateunclear0.000not prioritized-2
264FUBP1unclear / low-confidence candidateunclear0.000not prioritized-2
265PATZ1unclear / low-confidence candidateunclear0.000not prioritized-2
266FMN1unclear / low-confidence candidateunclear0.000not prioritized-2
267H3-3Aunclear / low-confidence candidateunclear0.000not prioritized-1
268GATA2unclear / low-confidence candidateunclear0.000not prioritized-1
269APOBEC3Bunclear / low-confidence candidateunclear0.000not prioritized-1
270BCL2unclear / low-confidence candidateunclear0.000not prioritized-1
271POU2AF1unclear / low-confidence candidateunclear0.000not prioritized-1
272PMELunclear / low-confidence candidateunclear0.000not prioritized0
273KRASunclear / low-confidence candidateunclear0.000not prioritized0
274TENT5Cunclear / low-confidence candidateunclear0.000not prioritized0
275CD79Aunclear / low-confidence candidateunclear0.000not prioritized0
276LPPunclear / low-confidence candidateunclear0.000not prioritized0
277PLXNB2unclear / low-confidence candidateunclear0.000not prioritized0
278SUZ12unclear / low-confidence candidateunclear0.000not prioritized0
279CBFA2T3unclear / low-confidence candidateunclear0.000not prioritized0
280NF2unclear / low-confidence candidateunclear0.000not prioritized0
281MAPK1unclear / low-confidence candidateunclear0.000not prioritized0
282KRT5unclear / low-confidence candidateunclear0.000not prioritized0
283HRASunclear / low-confidence candidateunclear0.000not prioritized0
284CNOT9unclear / low-confidence candidateunclear0.000not prioritized0
285PDCD1LG2unclear / low-confidence candidateunclear0.000not prioritized0
286SLC24A5unclear / low-confidence candidateunclear0.000not prioritized0
287NOTCH1unclear / low-confidence candidateunclear0.000not prioritized0
288MAP3K1unclear / low-confidence candidateunclear0.000not prioritized0
289CDH1unclear / low-confidence candidateunclear0.000not prioritized0
290BACH2unclear / low-confidence candidateunclear0.000not prioritized0
291KEAP1unclear / low-confidence candidateunclear0.000not prioritized0
292MED12unclear / low-confidence candidateunclear0.000not prioritized0
293H3C2unclear / low-confidence candidateunclear0.000not prioritized0
294TNFRSF17unclear / low-confidence candidateunclear0.000not prioritized0
295PIK3CBunclear / low-confidence candidateunclear0.000not prioritized0
296FBXW7unclear / low-confidence candidateunclear0.000not prioritized0
297NFE2L2unclear / low-confidence candidateunclear0.000not prioritized0
298ABL1unclear / low-confidence candidateunclear0.000not prioritized0
299CLPTM1Lunclear / low-confidence candidateunclear0.000not prioritized0
300ASPSCR1unclear / low-confidence candidateunclear0.000not prioritized0
+
+ + + + +
+ Generated by TargetIntel-IO. +
+ +
+ + diff --git a/examples/target_cards/depmap_26q1/ABL1.md b/examples/target_cards/depmap_26q1/ABL1.md new file mode 100644 index 0000000..84313df --- /dev/null +++ b/examples/target_cards/depmap_26q1/ABL1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ABL1 + +## Target identity + +- **Target symbol:** ABL1 +- **Target name:** ABL proto-oncogene 1, non-receptor tyrosine kinase +- **Open Targets melanoma score:** 0.459 +- **Open Targets baseline rank:** 298 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 298 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 298 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 298 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.459) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ABL1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ABL1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.05206080637452079,"interquartile_range":0.13179040761692934,"maximum":0.28090126723303777,"mean":0.0004447170999685991,"measured_model_count":56,"median":0.016656009569385857,"minimum":-0.39424595195096673,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07972960124240855,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008384728233917674,"interquartile_range":0.028339679307337506,"maximum":0.3238668973345923,"mean":0.038111215003978426,"measured_model_count":56,"median":0.018554196815730083,"minimum":0.0019480816982328645,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03672440754125518,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005268596799601434,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.011589403973509934,"pan_cancer_fraction":0.011589403973509934,"threshold":0.5},{"context_fraction":0.0,"difference":-0.009105960264900662,"pan_cancer_fraction":0.009105960264900662,"threshold":0.8}],"gene_effect_mean":0.028025674336998208,"gene_effect_median":0.029341478281553125},"dependency_probability_context_minus_non_context_median":-0.0058653162345687,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.012152777777777778,"non_context_fraction":0.012152777777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.009548611111111112,"non_context_fraction":0.009548611111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.02938803350615787,"gene_effect_context_minus_non_context_median":0.031052462802977448} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 298 +- **Dependency-aware candidate rank:** 298 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_3dfe0aaf44dae880f7a9069d3811f36a4cf75ed3c3bc338e1e85acb68fc2aa5b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ABL1|entrez:25` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ACKR3.md b/examples/target_cards/depmap_26q1/ACKR3.md new file mode 100644 index 0000000..d86bb78 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ACKR3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ACKR3 + +## Target identity + +- **Target symbol:** ACKR3 +- **Target name:** atypical chemokine receptor 3 +- **Open Targets melanoma score:** 0.518 +- **Open Targets baseline rank:** 220 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 222 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 222 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 222 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.518) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ACKR3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ACKR3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.04688567353100497,"interquartile_range":0.17672355876386034,"maximum":0.3406804666190274,"mean":0.044219612203129,"measured_model_count":56,"median":0.051971504824438984,"minimum":-0.248858520923774,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12983788523285536,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.00480346215672851,"interquartile_range":0.022247043897867892,"maximum":0.1649058271995307,"mean":0.023943900342633655,"measured_model_count":56,"median":0.012531187649904931,"minimum":0.0007241920367250855,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.027050506054596402,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0007630456786245857,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.009176056073463577,"gene_effect_median":0.0004076142221738424},"dependency_probability_context_minus_non_context_median":-0.0007630456786245857,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.009622114354812535,"gene_effect_context_minus_non_context_median":0.0005160131333996135} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 222 +- **Dependency-aware candidate rank:** 222 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_6da09dd6bfd55bdc7914f8c87aede8f5fd2319a5758d27ff90418fe816e4b80e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ACKR3|entrez:57007` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ACVR1B.md b/examples/target_cards/depmap_26q1/ACVR1B.md new file mode 100644 index 0000000..f88f3d4 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ACVR1B.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ACVR1B + +## Target identity + +- **Target symbol:** ACVR1B +- **Target name:** activin A receptor type 1B +- **Open Targets melanoma score:** 0.529 +- **Open Targets baseline rank:** 188 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 190 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 191 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 190 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.529) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ACVR1B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ACVR1B in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.14711929218671402,"interquartile_range":0.12432204341482385,"maximum":0.3375441114825275,"mean":-0.07998009592778019,"measured_model_count":56,"median":-0.08515877044475642,"minimum":-0.3764694607361463,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.022797248771890172,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.025659946006875323,"interquartile_range":0.046932751916033716,"maximum":0.3513129074264774,"mean":0.06341236180240215,"measured_model_count":56,"median":0.04447697969775254,"minimum":0.0007005068208089658,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07259269792290904,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003451019779143062,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.018211920529801324,"pan_cancer_fraction":0.018211920529801324,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.8}],"gene_effect_mean":0.01932084102200554,"gene_effect_median":0.007571133145735126},"dependency_probability_context_minus_non_context_median":-0.00363455842123752,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.019097222222222224,"non_context_fraction":0.019097222222222224,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.020260048571686465,"gene_effect_context_minus_non_context_median":0.008340856057287335} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 190 +- **Dependency-aware candidate rank:** 190 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_7fef00de913eb60dc7d7091f97bc92aca7cc60b24d6d5c58bbdee2f7b315d6dd` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ACVR1B|entrez:91` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/AFDN.md b/examples/target_cards/depmap_26q1/AFDN.md new file mode 100644 index 0000000..440322e --- /dev/null +++ b/examples/target_cards/depmap_26q1/AFDN.md @@ -0,0 +1,124 @@ +# Target hypothesis card: AFDN + +## Target identity + +- **Target symbol:** AFDN +- **Target name:** afadin, adherens junction formation factor +- **Open Targets melanoma score:** 0.554 +- **Open Targets baseline rank:** 145 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 147 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 148 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 147 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.554) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** AFDN lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for AFDN in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.18632748263487175,"interquartile_range":0.15100015383667187,"maximum":0.194234342399614,"mean":-0.10401314871474741,"measured_model_count":56,"median":-0.09824333463123369,"minimum":-0.3508544694256321,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.03532732879819988,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.02930714986928311,"interquartile_range":0.08549755078471634,"maximum":0.3273106965579132,"mean":0.08008016796975555,"measured_model_count":56,"median":0.04490595607597833,"minimum":0.002530139433360224,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11480470065399945,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.010186756173332173,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03228476821192053,"pan_cancer_fraction":0.03228476821192053,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.8}],"gene_effect_mean":-0.028113817942100536,"gene_effect_median":-0.041421613596168916},"dependency_probability_context_minus_non_context_median":0.01161967098779828,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.033854166666666664,"non_context_fraction":0.033854166666666664,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.029480461869841587,"gene_effect_context_minus_non_context_median":-0.04789679998052801} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 147 +- **Dependency-aware candidate rank:** 147 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a77d9c1a553179212884e60516135e05fa1ea0ca72afbc38003b213684f13da6` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:AFDN|entrez:4301` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/AFF4.md b/examples/target_cards/depmap_26q1/AFF4.md new file mode 100644 index 0000000..c6ae556 --- /dev/null +++ b/examples/target_cards/depmap_26q1/AFF4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: AFF4 + +## Target identity + +- **Target symbol:** AFF4 +- **Target name:** ALF transcription elongation factor 4 +- **Open Targets melanoma score:** 0.522 +- **Open Targets baseline rank:** 201 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 203 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 203 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 203 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.522) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** AFF4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for AFF4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.13292375310772922,"interquartile_range":0.18416980660063442,"maximum":0.38654768840037734,"mean":-0.039908295314705654,"measured_model_count":56,"median":-0.05939864471942567,"minimum":-0.34030817268214186,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0512460534929052,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01317409187949549,"interquartile_range":0.05043407141525695,"maximum":0.3328242072309353,"mean":0.05984196045726369,"measured_model_count":56,"median":0.03392475612734393,"minimum":0.00032369241265077216,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06360816329475244,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0007668804580707456,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.016068698734252658,"gene_effect_median":-0.010437559937850657},"dependency_probability_context_minus_non_context_median":-0.0007668804580707456,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01684981603383439,"gene_effect_context_minus_non_context_median":-0.010932048141568743} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 203 +- **Dependency-aware candidate rank:** 203 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_daca383d448a59953d52c8cd6fa98117e94d36e01db9b7f640f5167cc4203d27` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:AFF4|entrez:27125` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/AKT1.md b/examples/target_cards/depmap_26q1/AKT1.md new file mode 100644 index 0000000..4fd5eaa --- /dev/null +++ b/examples/target_cards/depmap_26q1/AKT1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: AKT1 + +## Target identity + +- **Target symbol:** AKT1 +- **Target name:** AKT serine/threonine kinase 1 +- **Open Targets melanoma score:** 0.603 +- **Open Targets baseline rank:** 65 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 69 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 71 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 69 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.603) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** AKT1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for AKT1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.0696113940207029,"interquartile_range":0.13322895560601336,"maximum":0.34970543918655067,"mean":-0.009742474845817481,"measured_model_count":56,"median":0.0046377124629188235,"minimum":-0.38907832484150034,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06361756158531046,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.010254024576999815,"interquartile_range":0.02635393549780505,"maximum":0.44844945288476895,"mean":0.04874750692925877,"measured_model_count":56,"median":0.020344346257189568,"minimum":0.00037661393714791936,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.036607960074804866,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.014890288201914133,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04304635761589404,"pan_cancer_fraction":0.04304635761589404,"threshold":0.5},{"context_fraction":0.0,"difference":-0.012417218543046357,"pan_cancer_fraction":0.012417218543046357,"threshold":0.8}],"gene_effect_mean":0.07683367026191354,"gene_effect_median":0.061701304441597535},"dependency_probability_context_minus_non_context_median":-0.016664789319484452,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04513888888888889,"non_context_fraction":0.04513888888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013020833333333334,"non_context_fraction":0.013020833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08056864034408984,"gene_effect_context_minus_non_context_median":0.06642333397803044} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 69 +- **Dependency-aware candidate rank:** 69 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_c524a3ba63651f0e15c4f8215dd50116139df5323fdc0348c5e448a92f93249e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:AKT1|entrez:207` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/AKT2.md b/examples/target_cards/depmap_26q1/AKT2.md new file mode 100644 index 0000000..7452344 --- /dev/null +++ b/examples/target_cards/depmap_26q1/AKT2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: AKT2 + +## Target identity + +- **Target symbol:** AKT2 +- **Target name:** AKT serine/threonine kinase 2 +- **Open Targets melanoma score:** 0.585 +- **Open Targets baseline rank:** 94 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 97 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 98 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 97 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.585) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** AKT2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for AKT2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.10698692296778596,"interquartile_range":0.18636044860159254,"maximum":0.2588885738209947,"mean":-0.017972665153818613,"measured_model_count":56,"median":-0.007401318928414405,"minimum":-0.38332530305186063,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07937352563380658,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008499792764108715,"interquartile_range":0.05882776154012727,"maximum":0.32445036409429234,"mean":0.043810063779630086,"measured_model_count":56,"median":0.020804451087822785,"minimum":0.0014235690597476042,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06732755430423598,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01610885761667067,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03145695364238411,"pan_cancer_fraction":0.03145695364238411,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013245033112582781,"pan_cancer_fraction":0.013245033112582781,"threshold":0.8}],"gene_effect_mean":0.05533570749708823,"gene_effect_median":0.052685305081329424},"dependency_probability_context_minus_non_context_median":-0.016317549937989013,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03298611111111111,"non_context_fraction":0.03298611111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013888888888888888,"non_context_fraction":0.013888888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05802563772264094,"gene_effect_context_minus_non_context_median":0.05442605404088425} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 97 +- **Dependency-aware candidate rank:** 97 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_f1e3d17bbf7af67106ed5461365f64d2ff4f926ae9bf8f4f04336a5df09f4dd0` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:AKT2|entrez:208` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ALK.md b/examples/target_cards/depmap_26q1/ALK.md new file mode 100644 index 0000000..1ed7a37 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ALK.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ALK + +## Target identity + +- **Target symbol:** ALK +- **Target name:** ALK receptor tyrosine kinase +- **Open Targets melanoma score:** 0.492 +- **Open Targets baseline rank:** 261 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 263 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 263 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 263 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.492) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ALK lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ALK in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.1391055879500493,"interquartile_range":0.1173851257210915,"maximum":0.24723686687943555,"mean":-0.08817782520037898,"measured_model_count":56,"median":-0.09243115642296142,"minimum":-0.414971861038247,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0217204622289578,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.023770154172617915,"interquartile_range":0.06796426553020232,"maximum":0.3791912417275072,"mean":0.0725077327529867,"measured_model_count":56,"median":0.0461958733533957,"minimum":0.00275245343127817,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09173441970282024,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0006553669293226511,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.8}],"gene_effect_mean":-0.0003571287333825335,"gene_effect_median":-0.008402991678772107},"dependency_probability_context_minus_non_context_median":0.0006553669293226511,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0003744891579219589,"gene_effect_context_minus_non_context_median":-0.008729152984485275} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 263 +- **Dependency-aware candidate rank:** 263 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_c898e5032b38a6b5a605f5041eaa96f4cba4b017f3f221903bd4a8bfa1e0a5da` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ALK|entrez:238` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/AMER1.md b/examples/target_cards/depmap_26q1/AMER1.md new file mode 100644 index 0000000..29ec7de --- /dev/null +++ b/examples/target_cards/depmap_26q1/AMER1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: AMER1 + +## Target identity + +- **Target symbol:** AMER1 +- **Target name:** APC membrane recruitment protein 1 +- **Open Targets melanoma score:** 0.545 +- **Open Targets baseline rank:** 170 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 172 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 173 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 172 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.545) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** AMER1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for AMER1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.009345387043821714,"interquartile_range":0.12788514596415662,"maximum":0.4383787682074304,"mean":0.07528086605188714,"measured_model_count":56,"median":0.08276667476476582,"minimum":-0.19040979327961766,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.13723053300797833,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005306404228444668,"interquartile_range":0.01706158235075618,"maximum":0.149077231539901,"mean":0.018513075756905417,"measured_model_count":56,"median":0.009990647380253341,"minimum":0.00021627471873552294,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.022367986579200846,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0025894206152058258,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.014413422384766096,"gene_effect_median":0.02671472109252339},"dependency_probability_context_minus_non_context_median":-0.002687022545325067,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.015114074861803335,"gene_effect_context_minus_non_context_median":0.027051252928677064} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 172 +- **Dependency-aware candidate rank:** 172 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a7f7490e823486f66688a444df162f849e16fc7bd434b0ef2d4016376f0c6cdf` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:AMER1|entrez:139285` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/APC.md b/examples/target_cards/depmap_26q1/APC.md new file mode 100644 index 0000000..bad8597 --- /dev/null +++ b/examples/target_cards/depmap_26q1/APC.md @@ -0,0 +1,124 @@ +# Target hypothesis card: APC + +## Target identity + +- **Target symbol:** APC +- **Target name:** APC regulator of Wnt signaling pathway +- **Open Targets melanoma score:** 0.510 +- **Open Targets baseline rank:** 239 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 241 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 241 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 241 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.510) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** APC lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for APC in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.5859774841020371,"interquartile_range":0.38179195205040023,"maximum":0.28455865946694375,"mean":-0.35785147041774285,"measured_model_count":56,"median":-0.3380178346085523,"minimum":-1.1406373050762526,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.20418553205163686,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.11658056622142303,"interquartile_range":0.5927857513786858,"maximum":0.9936482374577086,"mean":0.38426650867741774,"measured_model_count":56,"median":0.27761769575678924,"minimum":0.0013598374302337113,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.7093663176001088,"threshold_fractions":[{"denominator":56,"fraction":0.3392857142857143,"numerator":19,"threshold":0.5},{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.037316397101886556,"dependency_probability_threshold_fractions":[{"context_fraction":0.3392857142857143,"difference":0.02306054872280039,"pan_cancer_fraction":0.3162251655629139,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":0.05274361400189215,"pan_cancer_fraction":0.12582781456953643,"threshold":0.8}],"gene_effect_mean":0.0028794144866692295,"gene_effect_median":0.019559681208588586},"dependency_probability_context_minus_non_context_median":-0.03998799613543175,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.3392857142857143,"difference":0.024181547619047616,"non_context_fraction":0.3151041666666667,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":0.05530753968253968,"non_context_fraction":0.1232638888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.003019386024215698,"gene_effect_context_minus_non_context_median":0.02054380019079738} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 241 +- **Dependency-aware candidate rank:** 241 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_22a18cf431d07d3aa1e8c8953221792abd3f094e82d1e0fd675602c7277a5d06` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:APC|entrez:324` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/APOBEC3B.md b/examples/target_cards/depmap_26q1/APOBEC3B.md new file mode 100644 index 0000000..9b99710 --- /dev/null +++ b/examples/target_cards/depmap_26q1/APOBEC3B.md @@ -0,0 +1,124 @@ +# Target hypothesis card: APOBEC3B + +## Target identity + +- **Target symbol:** APOBEC3B +- **Target name:** apolipoprotein B mRNA editing enzyme catalytic subunit 3B +- **Open Targets melanoma score:** 0.484 +- **Open Targets baseline rank:** 268 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 269 | not prioritized | -1 | +| Resistance biomarker | 0.000 | 269 | not prioritized | -1 | +| Tumor-intrinsic / small molecule | 0.000 | 269 | not prioritized | -1 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.484) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** APOBEC3B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for APOBEC3B in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.09606841814979647,"interquartile_range":0.23515113567892895,"maximum":0.4400708139139492,"mean":0.026699711051649557,"measured_model_count":56,"median":0.005793906262137797,"minimum":-0.4283263401162755,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.13908271752913248,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005510925052745797,"interquartile_range":0.041485165212828315,"maximum":0.3365293082591688,"mean":0.0420897143545745,"measured_model_count":56,"median":0.019179227319746587,"minimum":0.00020440713068760097,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04699609026557411,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0018136909695100657,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.021622478459315107,"gene_effect_median":0.0003500566170188098},"dependency_probability_context_minus_non_context_median":-0.0019574494229148386,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.022673571162198494,"gene_effect_context_minus_non_context_median":0.0003500566170188098} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 269 +- **Dependency-aware candidate rank:** 269 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ca98257f2c856960f4df260901e6f315d270b0b86f4f932559dff06ccb40ad7b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:APOBEC3B|entrez:9582` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/AR.md b/examples/target_cards/depmap_26q1/AR.md new file mode 100644 index 0000000..8cc81a9 --- /dev/null +++ b/examples/target_cards/depmap_26q1/AR.md @@ -0,0 +1,124 @@ +# Target hypothesis card: AR + +## Target identity + +- **Target symbol:** AR +- **Target name:** androgen receptor +- **Open Targets melanoma score:** 0.581 +- **Open Targets baseline rank:** 100 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 103 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 104 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 103 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.581) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** AR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for AR in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.041097870345206546,"interquartile_range":0.1546972619994098,"maximum":0.4537651498544541,"mean":0.09982159752496085,"measured_model_count":56,"median":0.09918225274948897,"minimum":-0.28630325474580987,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.19579513234461635,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.004300171032795553,"interquartile_range":0.012979205717451568,"maximum":0.1346611349824717,"mean":0.01616543771498364,"measured_model_count":56,"median":0.007519158470395323,"minimum":0.00024636522631291607,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.01727937675024712,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0013001356911354744,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.0044244188818144264,"gene_effect_median":-0.000327980058559052},"dependency_probability_context_minus_non_context_median":-0.0014093923703961363,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0046394947996803715,"gene_effect_context_minus_non_context_median":-0.00040665467292552715} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 103 +- **Dependency-aware candidate rank:** 103 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_63cf6c20ea0c2587b1f1cb3617869b24003624ab7142c9d915bf56baad985f33` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:AR|entrez:367` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ARG1.md b/examples/target_cards/depmap_26q1/ARG1.md new file mode 100644 index 0000000..745b576 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ARG1.md @@ -0,0 +1,73 @@ +# ARG1 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.01952750081956353,"interquartile_range":0.15704048446148916,"maximum":0.4503933085737245,"mean":0.11178133015127081,"measured_model_count":56,"median":0.11451918046801807,"minimum":-0.188393571489023,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1765679852810527,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.002940917113951669,"interquartile_range":0.013001543968601731,"maximum":0.14703040964480976,"mean":0.01426250886872838,"measured_model_count":56,"median":0.006837278753817717,"minimum":0.0007338381832860604,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0159424610825534,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0018869795464472481,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.04646815350637501,"gene_effect_median":-0.04360907833315336},"dependency_probability_context_minus_non_context_median":0.0019344483310067394,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0487270220796015,"gene_effect_context_minus_non_context_median":-0.04471943426963257} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_402671f307b2534b8c3c198063ffa9f7de1c0c43a708f07a2b1036e16e824648` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ARG1|entrez:383` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ARHGAP35.md b/examples/target_cards/depmap_26q1/ARHGAP35.md new file mode 100644 index 0000000..c76ec2a --- /dev/null +++ b/examples/target_cards/depmap_26q1/ARHGAP35.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ARHGAP35 + +## Target identity + +- **Target symbol:** ARHGAP35 +- **Target name:** Rho GTPase activating protein 35 +- **Open Targets melanoma score:** 0.564 +- **Open Targets baseline rank:** 126 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 128 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 129 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 128 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.564) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ARHGAP35 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ARHGAP35 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.05883410528362672,"interquartile_range":0.17857380242184923,"maximum":0.6903895828374135,"mean":0.16384045492536617,"measured_model_count":56,"median":0.1631803821345646,"minimum":-0.05352249745888138,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.23740790770547593,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0024143042641998377,"interquartile_range":0.008129801540448407,"maximum":0.034355451535692104,"mean":0.007660889307250123,"measured_model_count":56,"median":0.004719702771807059,"minimum":2.496236796331053e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.010544105804648245,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0010038891695393877,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.009726160134216844,"gene_effect_median":0.012715675769759294},"dependency_probability_context_minus_non_context_median":-0.001027896030419067,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.010198959585185796,"gene_effect_context_minus_non_context_median":0.01396706078741472} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 128 +- **Dependency-aware candidate rank:** 128 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_8efa1be9f1230da1dcbcba68d23d75c37039d944c1cbd624fc7b05f1f52caf80` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ARHGAP35|entrez:2909` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ARHGEF12.md b/examples/target_cards/depmap_26q1/ARHGEF12.md new file mode 100644 index 0000000..890cf45 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ARHGEF12.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ARHGEF12 + +## Target identity + +- **Target symbol:** ARHGEF12 +- **Target name:** Rho guanine nucleotide exchange factor 12 +- **Open Targets melanoma score:** 0.522 +- **Open Targets baseline rank:** 202 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 204 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 204 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 204 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.522) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ARHGEF12 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ARHGEF12 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06317094016798837,"interquartile_range":0.12563105896818386,"maximum":0.2270279094210083,"mean":-0.008020450715228684,"measured_model_count":56,"median":0.034871420237681874,"minimum":-0.41302734708348443,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06246011880019548,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008032339590528874,"interquartile_range":0.03030221418076693,"maximum":0.3240745714209432,"mean":0.04467501766624043,"measured_model_count":56,"median":0.015320245248807533,"minimum":0.003552775301786233,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.038334553771295805,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0036176550486326214,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.0672116048856585,"gene_effect_median":-0.02838751380254602},"dependency_probability_context_minus_non_context_median":0.003783884628871687,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.07047883567871134,"gene_effect_context_minus_non_context_median":-0.03215817044333766} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 204 +- **Dependency-aware candidate rank:** 204 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_c48af391967e4045e4b5565d671700860d523527e92f6b2ab6e93fb7c2ae82af` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ARHGEF12|entrez:23365` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ARID1A.md b/examples/target_cards/depmap_26q1/ARID1A.md new file mode 100644 index 0000000..86096e5 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ARID1A.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ARID1A + +## Target identity + +- **Target symbol:** ARID1A +- **Target name:** AT-rich interaction domain 1A +- **Open Targets melanoma score:** 0.543 +- **Open Targets baseline rank:** 177 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 179 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 180 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 179 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.543) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ARID1A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ARID1A in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.43557053844131854,"interquartile_range":0.3219228042395692,"maximum":0.34226669290859557,"mean":-0.32606024413870033,"measured_model_count":56,"median":-0.2619302515505961,"minimum":-1.2757799512718386,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.11364773420174931,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.05457689627272941,"interquartile_range":0.43366939129216586,"maximum":0.9991107761621311,"mean":0.32125495906040114,"measured_model_count":56,"median":0.1554943077693044,"minimum":0.0021031613531615964,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.4882462875648953,"threshold_fractions":[{"denominator":56,"fraction":0.25,"numerator":14,"threshold":0.5},{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03646513983227573,"dependency_probability_threshold_fractions":[{"context_fraction":0.25,"difference":0.049668874172185434,"pan_cancer_fraction":0.20033112582781457,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.06054872280037844,"pan_cancer_fraction":0.10016556291390728,"threshold":0.8}],"gene_effect_mean":-0.0924020779430966,"gene_effect_median":-0.0586934200985495},"dependency_probability_context_minus_non_context_median":0.04286844721026127,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.25,"difference":0.05208333333333334,"non_context_fraction":0.19791666666666666,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.0634920634920635,"non_context_fraction":0.09722222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.09689384562088613,"gene_effect_context_minus_non_context_median":-0.06322739542564623} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 179 +- **Dependency-aware candidate rank:** 179 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_b5c100bd1a20ee14f11c4115a568f5f78536beecd8acb7908fed5614a2e7d100` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ARID1A|entrez:8289` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ARID1B.md b/examples/target_cards/depmap_26q1/ARID1B.md new file mode 100644 index 0000000..eb8f681 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ARID1B.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ARID1B + +## Target identity + +- **Target symbol:** ARID1B +- **Target name:** AT-rich interaction domain 1B +- **Open Targets melanoma score:** 0.550 +- **Open Targets baseline rank:** 160 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 162 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 163 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 162 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.550) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ARID1B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ARID1B in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.12835629844328875,"interquartile_range":0.17664885205400177,"maximum":0.36199530982159556,"mean":-0.044734329690283126,"measured_model_count":56,"median":-0.04386019774725303,"minimum":-0.6603854276514436,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04829255361071304,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.011252177444106795,"interquartile_range":0.06423641939851084,"maximum":0.7207650483372453,"mean":0.06040518347981727,"measured_model_count":56,"median":0.032552869087177506,"minimum":0.0008909390586229766,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07548859684261763,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00029433981757961275,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.02767265846736045,"pan_cancer_fraction":0.04552980132450331,"threshold":0.5},{"context_fraction":0.0,"difference":-0.023178807947019868,"pan_cancer_fraction":0.023178807947019868,"threshold":0.8}],"gene_effect_mean":0.030369032009685992,"gene_effect_median":0.0022480180521348148},"dependency_probability_context_minus_non_context_median":-0.00029433981757961275,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.029017857142857144,"non_context_fraction":0.046875,"threshold":0.5},{"context_fraction":0.0,"difference":-0.024305555555555556,"non_context_fraction":0.024305555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03184530439904584,"gene_effect_context_minus_non_context_median":0.0023570820931195086} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 162 +- **Dependency-aware candidate rank:** 162 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_4f2d8813a9b1a599910baad407eacc0577d3e77782dc8aa03f0b2715cf9967f7` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ARID1B|entrez:57492` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ARID2.md b/examples/target_cards/depmap_26q1/ARID2.md new file mode 100644 index 0000000..c739236 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ARID2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ARID2 + +## Target identity + +- **Target symbol:** ARID2 +- **Target name:** AT-rich interaction domain 2 +- **Open Targets melanoma score:** 0.719 +- **Open Targets baseline rank:** 12 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 20 | not prioritized | -8 | +| Resistance biomarker | 0.000 | 25 | not prioritized | -13 | +| Tumor-intrinsic / small molecule | 0.015 | 18 | not prioritized | -6 | + +## Evidence for + +- High Open Targets melanoma association score (0.719) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ARID2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ARID2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.4704228591773787,"interquartile_range":0.40651398153145546,"maximum":0.3411982550552147,"mean":-0.26655617429891615,"measured_model_count":56,"median":-0.2207698686925888,"minimum":-0.996786364696395,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0639088776459232,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.03116399473948154,"interquartile_range":0.46389475167534294,"maximum":0.9745826114257009,"mean":0.27967584939597845,"measured_model_count":56,"median":0.15054546566780236,"minimum":0.0022844621532051974,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.4950587464148245,"threshold_fractions":[{"denominator":56,"fraction":0.25,"numerator":14,"threshold":0.5},{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.21875498593775644,"dependency_probability_threshold_fractions":[{"context_fraction":0.25,"difference":-0.14072847682119205,"pan_cancer_fraction":0.39072847682119205,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.119441816461684,"pan_cancer_fraction":0.17301324503311258,"threshold":0.8}],"gene_effect_mean":0.13569919074304576,"gene_effect_median":0.1709331014111793},"dependency_probability_context_minus_non_context_median":-0.2260909259708198,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.25,"difference":-0.14756944444444442,"non_context_fraction":0.3975694444444444,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.12524801587301587,"non_context_fraction":0.17881944444444445,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.14229567918194364,"gene_effect_context_minus_non_context_median":0.17491031155534215} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 20 +- **Dependency-aware candidate rank:** 20 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_30708d70482c02d0743a5b7210b4353e2ba5a07cd9748efa83ef42a731093315` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ARID2|entrez:196528` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ARNT.md b/examples/target_cards/depmap_26q1/ARNT.md new file mode 100644 index 0000000..51a6adf --- /dev/null +++ b/examples/target_cards/depmap_26q1/ARNT.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ARNT + +## Target identity + +- **Target symbol:** ARNT +- **Target name:** aryl hydrocarbon receptor nuclear translocator +- **Open Targets melanoma score:** 0.560 +- **Open Targets baseline rank:** 134 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 136 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 137 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 136 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.560) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ARNT lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ARNT in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.3581074854447507,"interquartile_range":0.3039227377270318,"maximum":1.0399727157355843,"mean":-0.19191197960061698,"measured_model_count":56,"median":-0.20315562003917215,"minimum":-0.8571155954005378,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.05418474771771889,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.02937998694058869,"interquartile_range":0.2622623014624777,"maximum":0.9255765328229291,"mean":0.2264542684912856,"measured_model_count":56,"median":0.11103222682700858,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2916422884030664,"threshold_fractions":[{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.08288184637712813,"dependency_probability_threshold_fractions":[{"context_fraction":0.17857142857142858,"difference":0.12559129612109746,"pan_cancer_fraction":0.052980132450331126,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.020813623462630083,"pan_cancer_fraction":0.014900662251655629,"threshold":0.8}],"gene_effect_mean":-0.1667360406715155,"gene_effect_median":-0.1683438224054163},"dependency_probability_context_minus_non_context_median":0.08490840786278225,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.17857142857142858,"difference":0.13169642857142858,"non_context_fraction":0.046875,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.021825396825396824,"non_context_fraction":0.013888888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.17484126487082507,"gene_effect_context_minus_non_context_median":-0.17368853329719552} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 136 +- **Dependency-aware candidate rank:** 136 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_9951155d6dd22791d2de802a6c133a1889361b1d796714df0f5b1670205a205c` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ARNT|entrez:405` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ASPSCR1.md b/examples/target_cards/depmap_26q1/ASPSCR1.md new file mode 100644 index 0000000..071285e --- /dev/null +++ b/examples/target_cards/depmap_26q1/ASPSCR1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ASPSCR1 + +## Target identity + +- **Target symbol:** ASPSCR1 +- **Target name:** ASPSCR1 tether for SLC2A4, UBX domain containing +- **Open Targets melanoma score:** 0.456 +- **Open Targets baseline rank:** 300 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 300 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 300 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 300 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.456) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ASPSCR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ASPSCR1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.197432624657035,"interquartile_range":0.14713784975672511,"maximum":0.08866600605484734,"mean":-0.13710999970506296,"measured_model_count":56,"median":-0.1028582496030106,"minimum":-0.4406863774006863,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0502947749003099,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.03159872449810511,"interquartile_range":0.09714302943381564,"maximum":0.4966970706033939,"mean":0.10482145638843436,"measured_model_count":56,"median":0.05442591831673187,"minimum":0.007136843313635444,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12874175393192075,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.03481117021973189,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.01903973509933775,"pan_cancer_fraction":0.01903973509933775,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.031133585779895,"gene_effect_median":0.06007323046735241},"dependency_probability_context_minus_non_context_median":-0.036358897608151766,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.019965277777777776,"non_context_fraction":0.019965277777777776,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.032647023977528694,"gene_effect_context_minus_non_context_median":0.062161919009254774} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 300 +- **Dependency-aware candidate rank:** 300 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_01669b833c79ae330151d436836ad2fa6a4d2c039d2d7019547b4dd13e3cfa3b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ASPSCR1|entrez:79058` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ATF1.md b/examples/target_cards/depmap_26q1/ATF1.md new file mode 100644 index 0000000..5d6c74c --- /dev/null +++ b/examples/target_cards/depmap_26q1/ATF1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ATF1 + +## Target identity + +- **Target symbol:** ATF1 +- **Target name:** activating transcription factor 1 +- **Open Targets melanoma score:** 0.544 +- **Open Targets baseline rank:** 171 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 173 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 174 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 173 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.544) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ATF1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ATF1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.31199003147965054,"interquartile_range":0.19505157988805688,"maximum":0.20303160162622352,"mean":-0.2070263048606922,"measured_model_count":56,"median":-0.23658966248001567,"minimum":-0.6261219152697686,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.11693845159159365,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.06743848309059797,"interquartile_range":0.17343780682176396,"maximum":0.7946224472456699,"mean":0.1843216141685337,"measured_model_count":56,"median":0.14648723614834475,"minimum":0.004121566474625243,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.24087628991236193,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03760624946544386,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":0.008869441816461682,"pan_cancer_fraction":0.04470198675496689,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.017478392867401077,"gene_effect_median":-0.05376381313699782},"dependency_probability_context_minus_non_context_median":0.03861838203078313,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":0.009300595238095233,"non_context_fraction":0.044270833333333336,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.018328036965122002,"gene_effect_context_minus_non_context_median":-0.05523338406781739} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":92.5925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 173 +- **Dependency-aware candidate rank:** 173 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e25281946199947768b892e74af26d515e64be3ddd2868d8a50cfeef8311d8f7` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ATF1|entrez:466` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ATM.md b/examples/target_cards/depmap_26q1/ATM.md new file mode 100644 index 0000000..e516192 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ATM.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ATM + +## Target identity + +- **Target symbol:** ATM +- **Target name:** ATM serine/threonine kinase +- **Open Targets melanoma score:** 0.661 +- **Open Targets baseline rank:** 28 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 35 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 37 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.003 | 30 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.661) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ATM lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ATM in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.0020259254350783124,"interquartile_range":0.3216274073763178,"maximum":0.8941780165066932,"mean":0.16248329861889094,"measured_model_count":56,"median":0.08719509887627361,"minimum":-0.3490614222046967,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.3196014819412395,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.001660484890086447,"interquartile_range":0.020616259399120065,"maximum":0.40357518870553377,"mean":0.024982232330452915,"measured_model_count":56,"median":0.007002239522950301,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02227674428920651,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.02110179665390864,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.016556291390728478,"pan_cancer_fraction":0.016556291390728478,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":0.17757116970453563,"gene_effect_median":0.11577610392977825},"dependency_probability_context_minus_non_context_median":-0.022564276487489134,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.017361111111111112,"non_context_fraction":0.017361111111111112,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.18620310156517278,"gene_effect_context_minus_non_context_median":0.11990687881798565} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 35 +- **Dependency-aware candidate rank:** 35 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_f659edd937045b717d650fab018fee8c7abb0cf8dd8a54835685647c64c01557` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ATM|entrez:472` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ATP2B3.md b/examples/target_cards/depmap_26q1/ATP2B3.md new file mode 100644 index 0000000..77ad027 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ATP2B3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ATP2B3 + +## Target identity + +- **Target symbol:** ATP2B3 +- **Target name:** ATPase plasma membrane Ca2+ transporting 3 +- **Open Targets melanoma score:** 0.503 +- **Open Targets baseline rank:** 250 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 252 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 252 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 252 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.503) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ATP2B3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ATP2B3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.12434728095818147,"interquartile_range":0.22825275912574455,"maximum":0.47230728751688694,"mean":-0.008667745235625602,"measured_model_count":56,"median":-0.036856086964585304,"minimum":-0.34970797377659013,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10390547816756308,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.009082734404598202,"interquartile_range":0.05326351901840336,"maximum":0.3112851098819218,"mean":0.04792125591852207,"measured_model_count":56,"median":0.03490888626221475,"minimum":0.0002188965827178968,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06234625342300156,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.011465927239286071,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.00448372850637792,"gene_effect_median":-0.028392774720121416},"dependency_probability_context_minus_non_context_median":0.011733976837337394,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.004701687530993483,"gene_effect_context_minus_non_context_median":-0.03064534348728724} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 252 +- **Dependency-aware candidate rank:** 252 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_4345b9f420de21332b32038e89a18fcd9d1fe78fcabe78d9f91f8fbfa04b1fde` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ATP2B3|entrez:492` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ATR.md b/examples/target_cards/depmap_26q1/ATR.md new file mode 100644 index 0000000..572399d --- /dev/null +++ b/examples/target_cards/depmap_26q1/ATR.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ATR + +## Target identity + +- **Target symbol:** ATR +- **Target name:** ATR checkpoint kinase +- **Open Targets melanoma score:** 0.607 +- **Open Targets baseline rank:** 59 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 63 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 65 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 63 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.607) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ATR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ATR in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.3321653972992362,"interquartile_range":0.26959811435888104,"maximum":-0.8369811425904811,"mean":-1.230833734102214,"measured_model_count":56,"median":-1.172755189115312,"minimum":-1.9629129476130718,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.0625672829403552,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9788404513704841,"interquartile_range":0.019620482322990296,"maximum":1.0,"mean":0.9848397947268778,"measured_model_count":56,"median":0.9904158847911251,"minimum":0.9189537502260394,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9984609336934744,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.007277304019570607,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.026490066225165587,"pan_cancer_fraction":0.9735099337748344,"threshold":0.5},{"context_fraction":1.0,"difference":0.06953642384105962,"pan_cancer_fraction":0.9304635761589404,"threshold":0.8}],"gene_effect_mean":-0.12345707377225956,"gene_effect_median":-0.07212354509362151},"dependency_probability_context_minus_non_context_median":0.007810294213553393,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.02777777777777779,"non_context_fraction":0.9722222222222222,"threshold":0.5},{"context_fraction":1.0,"difference":0.07291666666666663,"non_context_fraction":0.9270833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.12945845930285538,"gene_effect_context_minus_non_context_median":-0.07890300754043578} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 63 +- **Dependency-aware candidate rank:** 63 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e05075a57487520a3ef8c2552aa212d23654885ece8d4225110dbf0b3eef6df2` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ATR|entrez:545` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ATRX.md b/examples/target_cards/depmap_26q1/ATRX.md new file mode 100644 index 0000000..a87da8d --- /dev/null +++ b/examples/target_cards/depmap_26q1/ATRX.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ATRX + +## Target identity + +- **Target symbol:** ATRX +- **Target name:** ATRX chromatin remodeler +- **Open Targets melanoma score:** 0.587 +- **Open Targets baseline rank:** 89 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 92 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 94 | not prioritized | -5 | +| Tumor-intrinsic / small molecule | 0.000 | 92 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.587) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ATRX lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ATRX in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.4980924165161724,"interquartile_range":0.32325243518896685,"maximum":0.42042034947144924,"mean":-0.34566514357228256,"measured_model_count":56,"median":-0.3302554609174006,"minimum":-0.8970558577974759,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.17483998132720557,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.09010910049335963,"interquartile_range":0.4892689464867115,"maximum":0.9394427095826552,"mean":0.3615166505326878,"measured_model_count":56,"median":0.30795028110934963,"minimum":0.0005373738842964715,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5793780469800711,"threshold_fractions":[{"denominator":56,"fraction":0.32142857142857145,"numerator":18,"threshold":0.5},{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.21746991569394805,"dependency_probability_threshold_fractions":[{"context_fraction":0.32142857142857145,"difference":0.1914616840113529,"pan_cancer_fraction":0.12996688741721854,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":0.0445837275307474,"pan_cancer_fraction":0.04470198675496689,"threshold":0.8}],"gene_effect_mean":-0.14128892377984786,"gene_effect_median":-0.1592475685537306},"dependency_probability_context_minus_non_context_median":0.21986921327752046,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.32142857142857145,"difference":0.20076884920634924,"non_context_fraction":0.12065972222222222,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":0.046750992063492064,"non_context_fraction":0.042534722222222224,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.1481571353524796,"gene_effect_context_minus_non_context_median":-0.16429773664113811} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 92 +- **Dependency-aware candidate rank:** 92 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a9a1db04e736dc8c304ac3fa6521e031189647161bbb85f740331b9c1e7fbcd3` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ATRX|entrez:546` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/AXIN1.md b/examples/target_cards/depmap_26q1/AXIN1.md new file mode 100644 index 0000000..15d84c1 --- /dev/null +++ b/examples/target_cards/depmap_26q1/AXIN1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: AXIN1 + +## Target identity + +- **Target symbol:** AXIN1 +- **Target name:** axin 1 +- **Open Targets melanoma score:** 0.552 +- **Open Targets baseline rank:** 149 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 151 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 152 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 151 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.552) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** AXIN1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for AXIN1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.037343116083035185,"interquartile_range":0.26661108518976745,"maximum":0.9196883699197242,"mean":0.08748785591226547,"measured_model_count":56,"median":0.08289157811043477,"minimum":-0.7764618367290135,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.22926796910673228,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.001998134253073587,"interquartile_range":0.0260986272540997,"maximum":0.8778227499507888,"mean":0.06161891085070346,"measured_model_count":56,"median":0.009616196179705327,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.028096761507173287,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005075620768799749,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.0059129612109744545,"pan_cancer_fraction":0.029801324503311258,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.00792336802270577,"pan_cancer_fraction":0.009933774834437087,"threshold":0.8}],"gene_effect_mean":0.05980391935434875,"gene_effect_median":0.03889600853611898},"dependency_probability_context_minus_non_context_median":-0.005271964576623166,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.006200396825396824,"non_context_fraction":0.029513888888888888,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.008308531746031744,"non_context_fraction":0.009548611111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.06271105432296295,"gene_effect_context_minus_non_context_median":0.040327951312166335} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 151 +- **Dependency-aware candidate rank:** 151 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a7a17af0a257bc40977527542e34c96f843a4c6c02174c75b38457bdc95dbad4` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:AXIN1|entrez:8312` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/AXL.md b/examples/target_cards/depmap_26q1/AXL.md new file mode 100644 index 0000000..bbefaa4 --- /dev/null +++ b/examples/target_cards/depmap_26q1/AXL.md @@ -0,0 +1,73 @@ +# AXL — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.09669271225359513,"interquartile_range":0.13838293442208938,"maximum":0.33269592966644873,"mean":-0.05402248348828266,"measured_model_count":56,"median":-0.05461535624294615,"minimum":-0.591523976802867,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.041690222168494245,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01321277007165553,"interquartile_range":0.047403672929686676,"maximum":0.5937823231403992,"mean":0.06668973321292734,"measured_model_count":56,"median":0.03594859224302639,"minimum":0.0021112287349255585,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0606164430013422,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00841929504751433,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.005439924314096499,"pan_cancer_fraction":0.012417218543046357,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.009449488770846413,"gene_effect_median":-0.028192670549813503},"dependency_probability_context_minus_non_context_median":0.00855861376300604,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.005704365079365078,"non_context_fraction":0.012152777777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.009908838919429161,"gene_effect_context_minus_non_context_median":-0.029581425927257432} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_4998e8d48eb17bd589670b508f8684da20ab3963cc8de33d05845accbfaee6be` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:AXL|entrez:558` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/B2M.md b/examples/target_cards/depmap_26q1/B2M.md new file mode 100644 index 0000000..9b5a2f5 --- /dev/null +++ b/examples/target_cards/depmap_26q1/B2M.md @@ -0,0 +1,132 @@ +# Target hypothesis card: B2M + +## Target identity + +- **Target symbol:** B2M +- **Target name:** beta-2-microglobulin +- **Open Targets melanoma score:** 0.572 +- **Open Targets baseline rank:** 111 + +## Stable TargetIntel-IO classification + +- **Role classification:** antigen-presentation resistance biomarker +- **Role confidence:** high +- **Therapeutic direction:** use as biomarker / patient stratification +- **Best modality:** resistance biomarker / patient stratification +- **Resistance axis:** antigen_presentation_loss +- **Matched resistance programs:** Antigen-presentation loss + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.227 | 9 | low | 102 | +| Resistance biomarker | 0.806 | 1 | high | 110 | +| Tumor-intrinsic / small molecule | 0.132 | 13 | low | 98 | + +## Evidence for + +- Directly linked to tumor immune escape +- Relevant to T-cell recognition +- Useful for resistance stratification +- Moderate Open Targets melanoma association score (0.572) +- Maps to curated anti-PD-1 resistance program: Antigen-presentation loss +- Stable role classifier confidence is high +- Biomarker fit is high + +## Evidence against / limitations + +- Loss-of-function events may be difficult to pharmacologically reverse +- Often not a direct therapeutic target +- Poor fit for antibody targeting +- Most useful as biomarker or stratification marker rather than direct therapeutic target + +## Confidence and uncertainty + +- **Confidence level:** high confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.320 +- **Main limitation:** Likely more useful for stratification than direct therapeutic targeting +- **Uncertainty reason:** Main limitation: Likely more useful for stratification than direct therapeutic targeting +- **Deprioritization reason:** B2M should not be deprioritized globally, but should be ranked mainly in biomarker or patient-stratification mode. + +## Recommended next validation experiment + +- **Validation category:** biomarker validation +- **Next experiment:** Test whether B2M status or expression differs between anti-PD-1 responders and non-responders in an independent melanoma cohort. +- **Rationale:** This would determine whether the candidate has practical value as a resistance biomarker or patient-stratification feature. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.03419536124041851,"interquartile_range":0.13539073572534133,"maximum":0.222441908549175,"mean":0.02537352064559218,"measured_model_count":56,"median":0.015821163143747298,"minimum":-0.26075783687617665,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10119537448492283,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.006961531439831104,"interquartile_range":0.02038009892374358,"maximum":0.23444542085876965,"mean":0.025135791460166153,"measured_model_count":56,"median":0.0164348942055268,"minimum":0.001654700032914229,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.027341630363574686,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.000853410138454436,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.007267390625760095,"gene_effect_median":-0.01927512526788492},"dependency_probability_context_minus_non_context_median":0.0009027441678660965,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.007620666558956747,"gene_effect_context_minus_non_context_median":-0.020399321418123194} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 9 +- **Dependency-aware candidate rank:** 5 +- **Rank delta:** -4 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_1b6574683ae76a819dfc9ca0014d7c3b1867009f10cded7fc4cf73749063eb81` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:B2M|entrez:567` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BACH2.md b/examples/target_cards/depmap_26q1/BACH2.md new file mode 100644 index 0000000..6afcea7 --- /dev/null +++ b/examples/target_cards/depmap_26q1/BACH2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BACH2 + +## Target identity + +- **Target symbol:** BACH2 +- **Target name:** BACH transcriptional regulator 2 +- **Open Targets melanoma score:** 0.465 +- **Open Targets baseline rank:** 290 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 290 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 290 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 290 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.465) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BACH2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BACH2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.01884643567221031,"interquartile_range":0.12885452737206532,"maximum":0.2922363938617609,"mean":0.04157837025826655,"measured_model_count":56,"median":0.039909660670576906,"minimum":-0.1728292133635718,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11000809169985502,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.007121448360295681,"interquartile_range":0.020012121577146845,"maximum":0.06841314448379879,"mean":0.019631283583679472,"measured_model_count":56,"median":0.013053911679737119,"minimum":0.0010205824014244435,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.027133569937442526,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0015546041641899405,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.005821714463687698,"gene_effect_median":-0.0016066987038449096},"dependency_probability_context_minus_non_context_median":-0.0016402089908457793,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006104714472339179,"gene_effect_context_minus_non_context_median":-0.0016066987038449096} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 290 +- **Dependency-aware candidate rank:** 290 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_cd083763ccfa62bdd53cc6d82e9663ea2c57a38514c3d7b809e4541fa851f9fc` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BACH2|entrez:60468` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BAP1.md b/examples/target_cards/depmap_26q1/BAP1.md new file mode 100644 index 0000000..4caf297 --- /dev/null +++ b/examples/target_cards/depmap_26q1/BAP1.md @@ -0,0 +1,127 @@ +# Target hypothesis card: BAP1 + +## Target identity + +- **Target symbol:** BAP1 +- **Target name:** BRCA1 associated deubiquitinase 1 +- **Open Targets melanoma score:** 0.816 +- **Open Targets baseline rank:** 3 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / poor direct therapeutic target +- **Role confidence:** high +- **Therapeutic direction:** avoid as direct target / use as biomarker or pathway context +- **Best modality:** biomarker / pathway context only +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 13 | not prioritized | -10 | +| Resistance biomarker | 0.128 | 18 | low | -15 | +| Tumor-intrinsic / small molecule | 0.000 | 37 | not prioritized | -34 | + +## Evidence for + +- High Open Targets melanoma association score (0.816) +- Stable role classifier confidence is high + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Flagged as poor direct therapeutic target for this MVP +- Role classifier indicates biological relevance but poor direct targetability +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 0.889 +- **Contradiction score:** 0.570 +- **Main limitation:** Poor direct therapeutic target despite biological relevance +- **Uncertainty reason:** Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Moderate contradiction score indicates caution is needed | Main limitation: Poor direct therapeutic target despite biological relevance +- **Deprioritization reason:** BAP1 should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context. + +## Recommended next validation experiment + +- **Validation category:** tumor-intrinsic functional validation +- **Next experiment:** Evaluate whether perturbing BAP1 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays. +- **Rationale:** This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.7617301000041377,"interquartile_range":0.39215821877949375,"maximum":-0.027665093614035463,"mean":-0.580660108206857,"measured_model_count":56,"median":-0.5909145722746947,"minimum":-1.1970868602866886,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.3695718812246439,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.30705277763360284,"interquartile_range":0.5817669754730993,"maximum":0.9966187017789548,"mean":0.6221644187853995,"measured_model_count":56,"median":0.7153010101416735,"minimum":0.026783164047011688,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.8888197531067021,"threshold_fractions":[{"denominator":56,"fraction":0.6607142857142857,"numerator":37,"threshold":0.5},{"denominator":56,"fraction":0.4107142857142857,"numerator":23,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.11991243702833909,"dependency_probability_threshold_fractions":[{"context_fraction":0.6607142857142857,"difference":0.09614474929044459,"pan_cancer_fraction":0.5645695364238411,"threshold":0.5},{"context_fraction":0.4107142857142857,"difference":0.11435666982024595,"pan_cancer_fraction":0.29635761589403975,"threshold":0.8}],"gene_effect_mean":-0.0702426311969423,"gene_effect_median":-0.07650321152341633},"dependency_probability_context_minus_non_context_median":0.1287251125435065,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.6607142857142857,"difference":0.10081845238095233,"non_context_fraction":0.5598958333333334,"threshold":0.5},{"context_fraction":0.4107142857142857,"difference":0.1199156746031746,"non_context_fraction":0.2907986111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0736572035467935,"gene_effect_context_minus_non_context_median":-0.08087977316397721} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 13 +- **Dependency-aware candidate rank:** 13 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ca2583b9c8b88d48220f585a16c6d2e695dff2d01157b025046c548705a99a05` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BAP1|entrez:8314` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BCL11A.md b/examples/target_cards/depmap_26q1/BCL11A.md new file mode 100644 index 0000000..740cc62 --- /dev/null +++ b/examples/target_cards/depmap_26q1/BCL11A.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BCL11A + +## Target identity + +- **Target symbol:** BCL11A +- **Target name:** BCL11 transcription factor A +- **Open Targets melanoma score:** 0.558 +- **Open Targets baseline rank:** 141 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 143 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 144 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 143 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.558) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BCL11A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BCL11A in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.11420819046622246,"interquartile_range":0.16659082868984246,"maximum":0.43518189292339327,"mean":-0.045648604296433484,"measured_model_count":56,"median":-0.056271293868629293,"minimum":-0.5045098076749046,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.052382638223619986,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.013988075492537793,"interquartile_range":0.044676824510456764,"maximum":0.6734265664462808,"mean":0.060102345993402966,"measured_model_count":56,"median":0.033069240860764355,"minimum":0.0008709175060067826,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.058664900002994555,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0013133876807193273,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.005439924314096499,"pan_cancer_fraction":0.012417218543046357,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.0032663000309570214,"gene_effect_median":-0.012237703308827015},"dependency_probability_context_minus_non_context_median":0.0013133876807193273,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.005704365079365078,"non_context_fraction":0.012152777777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.003425078504684133,"gene_effect_context_minus_non_context_median":-0.012597092084299488} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 143 +- **Dependency-aware candidate rank:** 143 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_4530b1bef3c9d166c8e11998299c11629395297b3b900a556bc5b0e5f050aded` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BCL11A|entrez:53335` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BCL11B.md b/examples/target_cards/depmap_26q1/BCL11B.md new file mode 100644 index 0000000..c0dfd05 --- /dev/null +++ b/examples/target_cards/depmap_26q1/BCL11B.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BCL11B + +## Target identity + +- **Target symbol:** BCL11B +- **Target name:** BCL11 transcription factor B +- **Open Targets melanoma score:** 0.515 +- **Open Targets baseline rank:** 228 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 230 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 230 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 230 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.515) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BCL11B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BCL11B in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.04299951768347804,"interquartile_range":0.12128991572901711,"maximum":0.2227864472704803,"mean":0.01497917009073292,"measured_model_count":56,"median":0.019832171594732825,"minimum":-0.30944805285306837,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07829039804553907,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.007893891610742113,"interquartile_range":0.023567574776098024,"maximum":0.2051689240725753,"mean":0.024793767381785202,"measured_model_count":56,"median":0.018108339873370675,"minimum":0.0026566262890120834,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03146146638684014,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0008022985700595793,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.014900662251655629,"pan_cancer_fraction":0.014900662251655629,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.8}],"gene_effect_mean":0.006140626290001,"gene_effect_median":-0.005813637403148674},"dependency_probability_context_minus_non_context_median":0.0008022985700595793,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.015625,"non_context_fraction":0.015625,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006439128956876032,"gene_effect_context_minus_non_context_median":-0.0066135845459349175} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 230 +- **Dependency-aware candidate rank:** 230 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ef2636b1f28658470b715acc8b410918b8d08e55469f189f2868b3cd7c3c745a` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BCL11B|entrez:64919` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BCL2.md b/examples/target_cards/depmap_26q1/BCL2.md new file mode 100644 index 0000000..d22dec9 --- /dev/null +++ b/examples/target_cards/depmap_26q1/BCL2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BCL2 + +## Target identity + +- **Target symbol:** BCL2 +- **Target name:** BCL2 apoptosis regulator +- **Open Targets melanoma score:** 0.484 +- **Open Targets baseline rank:** 269 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 270 | not prioritized | -1 | +| Resistance biomarker | 0.000 | 270 | not prioritized | -1 | +| Tumor-intrinsic / small molecule | 0.000 | 270 | not prioritized | -1 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.484) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BCL2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BCL2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.08696651149816556,"interquartile_range":0.14561016392955564,"maximum":0.2680923594186532,"mean":-0.016920171192513926,"measured_model_count":56,"median":-0.025311452898357994,"minimum":-0.25176194650284295,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05864365243139008,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.012691998621583553,"interquartile_range":0.03380030655700515,"maximum":0.161056642128686,"mean":0.03713254238273757,"measured_model_count":56,"median":0.02454383022252416,"minimum":0.0023418864731136555,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.046492305178588704,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.002009118404849311,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03642384105960265,"pan_cancer_fraction":0.03642384105960265,"threshold":0.5},{"context_fraction":0.0,"difference":-0.022350993377483443,"pan_cancer_fraction":0.022350993377483443,"threshold":0.8}],"gene_effect_mean":0.019261563818710054,"gene_effect_median":-0.022196683352156837},"dependency_probability_context_minus_non_context_median":0.002223118359550566,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03819444444444445,"non_context_fraction":0.03819444444444445,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0234375,"non_context_fraction":0.0234375,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0201978898376751,"gene_effect_context_minus_non_context_median":-0.023006579966283445} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 270 +- **Dependency-aware candidate rank:** 270 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ea3de1e2aa77018152520942e86464bdd295cf75fd360da1688e062513ad57c8` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BCL2|entrez:596` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BCL9.md b/examples/target_cards/depmap_26q1/BCL9.md new file mode 100644 index 0000000..ef5b62e --- /dev/null +++ b/examples/target_cards/depmap_26q1/BCL9.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BCL9 + +## Target identity + +- **Target symbol:** BCL9 +- **Target name:** BCL9 transcription coactivator +- **Open Targets melanoma score:** 0.512 +- **Open Targets baseline rank:** 232 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 234 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 234 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 234 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.512) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BCL9 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BCL9 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.38494598357777626,"interquartile_range":0.3330532366091112,"maximum":0.4089113515279511,"mean":-0.2320473630104575,"measured_model_count":56,"median":-0.23320556013071192,"minimum":-0.9150034496838594,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0518927469686651,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.03469806330531005,"interquartile_range":0.2717156659809888,"maximum":0.9363484371526809,"mean":0.24510724830209973,"measured_model_count":56,"median":0.14987003186885173,"minimum":6.792628342980656e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.30641372928629884,"threshold_fractions":[{"denominator":56,"fraction":0.19642857142857142,"numerator":11,"threshold":0.5},{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.04722901062703447,"dependency_probability_threshold_fractions":[{"context_fraction":0.19642857142857142,"difference":0.055700094607379375,"pan_cancer_fraction":0.14072847682119205,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":0.029210028382213808,"pan_cancer_fraction":0.042218543046357616,"threshold":0.8}],"gene_effect_mean":-0.05197525956023036,"gene_effect_median":-0.0496702568894708},"dependency_probability_context_minus_non_context_median":0.0495749823570763,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.19642857142857142,"difference":0.05840773809523808,"non_context_fraction":0.13802083333333334,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":0.030629960317460313,"non_context_fraction":0.04079861111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.054501834677741084,"gene_effect_context_minus_non_context_median":-0.05535524771486566} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 234 +- **Dependency-aware candidate rank:** 234 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ccf55366fc66b6ecabb3c3e841d40ed564813d67765ad22918c7f7b57dd90d21` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BCL9|entrez:607` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BCL9L.md b/examples/target_cards/depmap_26q1/BCL9L.md new file mode 100644 index 0000000..eb1c847 --- /dev/null +++ b/examples/target_cards/depmap_26q1/BCL9L.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BCL9L + +## Target identity + +- **Target symbol:** BCL9L +- **Target name:** BCL9 like +- **Open Targets melanoma score:** 0.562 +- **Open Targets baseline rank:** 132 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 134 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 135 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 134 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.562) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BCL9L lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BCL9L in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.1688428463252949,"interquartile_range":0.19093666889847527,"maximum":0.2938285868937669,"mean":-0.07602213222019842,"measured_model_count":56,"median":-0.08759133713750625,"minimum":-0.8127726660093453,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.022093822573180377,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01697105113102501,"interquartile_range":0.09072755309577211,"maximum":0.8980221838973915,"mean":0.08478326576217181,"measured_model_count":56,"median":0.03968158389728285,"minimum":0.0014820722411286198,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10769860422679713,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01015602430234061,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.03512298959318827,"pan_cancer_fraction":0.052980132450331126,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.0004730368968779569,"pan_cancer_fraction":0.0173841059602649,"threshold":0.8}],"gene_effect_mean":0.03112072905089716,"gene_effect_median":0.0035155689233583864},"dependency_probability_context_minus_non_context_median":-0.01068925285951225,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.036830357142857144,"non_context_fraction":0.0546875,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.0004960317460317443,"non_context_fraction":0.017361111111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03263354226864924,"gene_effect_context_minus_non_context_median":0.004168050231747947} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 134 +- **Dependency-aware candidate rank:** 134 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_130620cecb7880eff894c17a3415fa9c58e6144f3d5bd568b075473b897a4877` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BCL9L|entrez:283149` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BCOR.md b/examples/target_cards/depmap_26q1/BCOR.md new file mode 100644 index 0000000..de3b18a --- /dev/null +++ b/examples/target_cards/depmap_26q1/BCOR.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BCOR + +## Target identity + +- **Target symbol:** BCOR +- **Target name:** BCL6 corepressor +- **Open Targets melanoma score:** 0.552 +- **Open Targets baseline rank:** 154 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 156 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 157 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 156 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.552) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BCOR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BCOR in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.09843137692846265,"interquartile_range":0.3024111110874371,"maximum":0.5123476618974896,"mean":0.043399310001232275,"measured_model_count":56,"median":0.025163160100960116,"minimum":-0.46608548605258826,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2039797341589745,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.004385523455098974,"interquartile_range":0.049122236208953576,"maximum":0.5695078292114721,"mean":0.04532958920474263,"measured_model_count":56,"median":0.01380619756232246,"minimum":0.00015610740691107978,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05350775966405255,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0027150348663232526,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.0069772942289498575,"pan_cancer_fraction":0.024834437086092714,"threshold":0.5},{"context_fraction":0.0,"difference":-0.01076158940397351,"pan_cancer_fraction":0.01076158940397351,"threshold":0.8}],"gene_effect_mean":0.0182954776524825,"gene_effect_median":-0.009540080025807921},"dependency_probability_context_minus_non_context_median":-0.002821261181018683,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.007316468253968256,"non_context_fraction":0.025173611111111112,"threshold":0.5},{"context_fraction":0.0,"difference":-0.011284722222222222,"non_context_fraction":0.011284722222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01918484114947815,"gene_effect_context_minus_non_context_median":-0.01101162275375667} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 156 +- **Dependency-aware candidate rank:** 156 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_b97d297300843c94981e764c1cabdaf082a810f52b0f25a54c7bba9d923cbeae` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BCOR|entrez:54880` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BCORL1.md b/examples/target_cards/depmap_26q1/BCORL1.md new file mode 100644 index 0000000..db70152 --- /dev/null +++ b/examples/target_cards/depmap_26q1/BCORL1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BCORL1 + +## Target identity + +- **Target symbol:** BCORL1 +- **Target name:** BCL6 corepressor like 1 +- **Open Targets melanoma score:** 0.519 +- **Open Targets baseline rank:** 216 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 218 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 218 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 218 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.519) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BCORL1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BCORL1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.040014746834881765,"interquartile_range":0.1883396297572965,"maximum":0.45603754792744744,"mean":0.09678094437513547,"measured_model_count":56,"median":0.10564126028540002,"minimum":-0.6082875411667698,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.22835437659217828,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0023587471886702166,"interquartile_range":0.011221787353487667,"maximum":0.7004279011526633,"mean":0.04059999544600247,"measured_model_count":56,"median":0.007299775968082389,"minimum":0.00014814138376582694,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.013580534542157883,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003567309948364188,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.028263954588457898,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.019726784915498313,"gene_effect_median":0.0258835663828344},"dependency_probability_context_minus_non_context_median":-0.003764269348550839,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.029637896825396824,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.020685725848890543,"gene_effect_context_minus_non_context_median":0.027067192809979018} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 218 +- **Dependency-aware candidate rank:** 218 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d15423ff4eb3865580e87cecd978a3a6783cf73e5f8593373d060031c5d6d748` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BCORL1|entrez:63035` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BIRC3.md b/examples/target_cards/depmap_26q1/BIRC3.md new file mode 100644 index 0000000..132e1d6 --- /dev/null +++ b/examples/target_cards/depmap_26q1/BIRC3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BIRC3 + +## Target identity + +- **Target symbol:** BIRC3 +- **Target name:** baculoviral IAP repeat containing 3 +- **Open Targets melanoma score:** 0.494 +- **Open Targets baseline rank:** 260 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 262 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 262 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 262 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.494) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BIRC3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BIRC3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.053832945649035846,"interquartile_range":0.17211190378930316,"maximum":0.29394174579102555,"mean":0.021754678809343127,"measured_model_count":56,"median":0.0066408270165531635,"minimum":-0.27705052981998146,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11827895814026732,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.006081698993193586,"interquartile_range":0.0270064902459861,"maximum":0.2690632218111069,"mean":0.029979679761486938,"measured_model_count":56,"median":0.01746802168718406,"minimum":0.0015399221549407625,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03308818923917969,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.003910880564498082,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.025029029858429405,"gene_effect_median":-0.039950423932228474},"dependency_probability_context_minus_non_context_median":0.004155410292051574,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.02624571880988088,"gene_effect_context_minus_non_context_median":-0.0407441913722429} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 262 +- **Dependency-aware candidate rank:** 262 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d67ae8b5fbdcb102428afa986cd612ca739aeeb1d45287ac293992df25f8cadd` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BIRC3|entrez:330` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BRAF.md b/examples/target_cards/depmap_26q1/BRAF.md new file mode 100644 index 0000000..ac22db6 --- /dev/null +++ b/examples/target_cards/depmap_26q1/BRAF.md @@ -0,0 +1,132 @@ +# Target hypothesis card: BRAF + +## Target identity + +- **Target symbol:** BRAF +- **Target name:** B-Raf proto-oncogene, serine/threonine kinase +- **Open Targets melanoma score:** 0.853 +- **Open Targets baseline rank:** 2 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / small-molecule target +- **Role confidence:** high +- **Therapeutic direction:** small-molecule inhibition / pathway targeting +- **Best modality:** small molecule / pathway targeting +- **Resistance axis:** tumor_intrinsic_driver +- **Matched resistance programs:** Tumor-intrinsic driver biology + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.269 | 7 | low | -5 | +| Resistance biomarker | 0.482 | 11 | medium | -9 | +| Tumor-intrinsic / small molecule | 0.845 | 1 | high | 1 | + +## Evidence for + +- Relevant to melanoma tumor-cell biology +- Some targets or pathways are clinically actionable +- Useful for separating tumor-intrinsic drivers from immune-combination targets +- High Open Targets melanoma association score (0.853) +- Maps to curated anti-PD-1 resistance program: Tumor-intrinsic driver biology +- Stable role classifier confidence is high +- Small-molecule fit is high + +## Evidence against / limitations + +- Many tumor-intrinsic drivers are poor antibody targets +- Melanoma association does not automatically imply anti-PD-1 combination suitability +- Tumor suppressors are often poor direct therapeutic targets +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** high confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.320 +- **Main limitation:** Poor fit for antibody / IO-combination modality +- **Uncertainty reason:** Main limitation: Poor fit for antibody / IO-combination modality +- **Deprioritization reason:** No strong deprioritization reason from current MVP rules + +## Recommended next validation experiment + +- **Validation category:** tumor-intrinsic functional validation +- **Next experiment:** Evaluate whether perturbing BRAF alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays. +- **Rationale:** This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.6227668727162368,"interquartile_range":0.9795415688905247,"maximum":-0.015881149663220406,"mean":-1.1769393408178332,"measured_model_count":56,"median":-1.2347703095627218,"minimum":-2.6355354158678552,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.6432253038257121,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.8542815144561293,"interquartile_range":0.14570215220149452,"maximum":1.0,"mean":0.7983333399564246,"measured_model_count":56,"median":0.9910996581121145,"minimum":0.018849964783263323,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9999836666576238,"threshold_fractions":[{"denominator":56,"fraction":0.7857142857142857,"numerator":44,"threshold":0.5},{"denominator":56,"fraction":0.75,"numerator":42,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.941093110695153,"dependency_probability_threshold_fractions":[{"context_fraction":0.7857142857142857,"difference":0.690515610217597,"pan_cancer_fraction":0.09519867549668874,"threshold":0.5},{"context_fraction":0.75,"difference":0.6846026490066225,"pan_cancer_fraction":0.06539735099337748,"threshold":0.8}],"gene_effect_mean":-0.9973071133238599,"gene_effect_median":-1.1421352404225718},"dependency_probability_context_minus_non_context_median":0.943697459010603,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.7857142857142857,"difference":0.7240823412698413,"non_context_fraction":0.06163194444444445,"threshold":0.5},{"context_fraction":0.75,"difference":0.7178819444444444,"non_context_fraction":0.03211805555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-1.0457873202215475,"gene_effect_context_minus_non_context_median":-1.1485856638282403} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":100.0} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 7 +- **Dependency-aware candidate rank:** 1 +- **Rank delta:** -6 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_47a7c9ba52d4567bf9a8f2d1a63c5270380178383e2ea2bdace38fadfec9aaca` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BRAF|entrez:673` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BRCA1.md b/examples/target_cards/depmap_26q1/BRCA1.md new file mode 100644 index 0000000..4f7190a --- /dev/null +++ b/examples/target_cards/depmap_26q1/BRCA1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BRCA1 + +## Target identity + +- **Target symbol:** BRCA1 +- **Target name:** BRCA1 DNA repair associated +- **Open Targets melanoma score:** 0.604 +- **Open Targets baseline rank:** 64 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 68 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 70 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 68 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.604) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BRCA1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BRCA1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.8334513137692443,"interquartile_range":0.3666416803437246,"maximum":0.062275150039045934,"mean":-0.6446669874885088,"measured_model_count":56,"median":-0.6447037480808876,"minimum":-1.4679161979282245,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.46680963342551973,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.5092257497253594,"interquartile_range":0.4183593833250353,"maximum":0.9994909191982082,"mean":0.6709476213577762,"measured_model_count":56,"median":0.7565224518784195,"minimum":0.009461623428259134,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9275851330503947,"threshold_fractions":[{"denominator":56,"fraction":0.7678571428571429,"numerator":43,"threshold":0.5},{"denominator":56,"fraction":0.4642857142857143,"numerator":26,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.25058042664477276,"dependency_probability_threshold_fractions":[{"context_fraction":0.7678571428571429,"difference":0.262062440870388,"pan_cancer_fraction":0.5057947019867549,"threshold":0.5},{"context_fraction":0.4642857142857143,"difference":0.20683538315988648,"pan_cancer_fraction":0.2574503311258278,"threshold":0.8}],"gene_effect_mean":-0.15249501305905494,"gene_effect_median":-0.18012596237736855},"dependency_probability_context_minus_non_context_median":0.2653220437390733,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.7678571428571429,"difference":0.2748015873015873,"non_context_fraction":0.4930555555555556,"threshold":0.5},{"context_fraction":0.4642857142857143,"difference":0.21688988095238096,"non_context_fraction":0.24739583333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.15990796508275879,"gene_effect_context_minus_non_context_median":-0.18493748969522855} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":92.5925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 68 +- **Dependency-aware candidate rank:** 68 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_c3abf02d3576b30a9ea568ee8d2cd2fc27df2cfd402aa7a28eccaa2022a08fda` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BRCA1|entrez:672` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BRCA2.md b/examples/target_cards/depmap_26q1/BRCA2.md new file mode 100644 index 0000000..2e9ca73 --- /dev/null +++ b/examples/target_cards/depmap_26q1/BRCA2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BRCA2 + +## Target identity + +- **Target symbol:** BRCA2 +- **Target name:** BRCA2 DNA repair associated +- **Open Targets melanoma score:** 0.687 +- **Open Targets baseline rank:** 24 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 31 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 33 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.008 | 26 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.687) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BRCA2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BRCA2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.6488829996539245,"interquartile_range":0.2518526421601791,"maximum":-0.11644136524611565,"mean":-0.5194239412699343,"measured_model_count":56,"median":-0.5458386512220574,"minimum":-0.9883316064136789,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.3970303574937454,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.3920368984175355,"interquartile_range":0.4198271479602616,"maximum":0.9795182103056468,"mean":0.5793265400728955,"measured_model_count":56,"median":0.6356233831085945,"minimum":0.047399772777465814,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.8118640463777971,"threshold_fractions":[{"denominator":56,"fraction":0.625,"numerator":35,"threshold":0.5},{"denominator":56,"fraction":0.2857142857142857,"numerator":16,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.041063484097139114,"dependency_probability_threshold_fractions":[{"context_fraction":0.625,"difference":0.04387417218543044,"pan_cancer_fraction":0.5811258278145696,"threshold":0.5},{"context_fraction":0.2857142857142857,"difference":0.00011825922421948576,"pan_cancer_fraction":0.2855960264900662,"threshold":0.8}],"gene_effect_mean":-0.0015668993950327392,"gene_effect_median":-0.029499749646440088},"dependency_probability_context_minus_non_context_median":0.044335610678987836,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.625,"difference":0.04600694444444442,"non_context_fraction":0.5789930555555556,"threshold":0.5},{"context_fraction":0.2857142857142857,"difference":0.0001240079365079083,"non_context_fraction":0.2855902777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0016430681156246463,"gene_effect_context_minus_non_context_median":-0.031023442845045324} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 31 +- **Dependency-aware candidate rank:** 31 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_5bf109b23dc5449b6b55fa3337d49d7364cd1955795cf233da6d22d2aee4dbb8` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BRCA2|entrez:675` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BRD3.md b/examples/target_cards/depmap_26q1/BRD3.md new file mode 100644 index 0000000..2e308fd --- /dev/null +++ b/examples/target_cards/depmap_26q1/BRD3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BRD3 + +## Target identity + +- **Target symbol:** BRD3 +- **Target name:** bromodomain containing 3 +- **Open Targets melanoma score:** 0.511 +- **Open Targets baseline rank:** 233 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 235 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 235 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 235 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.511) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BRD3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BRD3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.033964049706230695,"interquartile_range":0.09288662604572513,"maximum":0.3470103010805555,"mean":0.07953525307711658,"measured_model_count":56,"median":0.08710923930845982,"minimum":-0.17690537289100544,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12685067575195583,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.00500462514257108,"interquartile_range":0.013542976338508669,"maximum":0.07572924687956509,"mean":0.014028321936522852,"measured_model_count":56,"median":0.0076650310535126605,"minimum":0.0008221952078158884,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.01854760148107975,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0017194904093865027,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.008998811123027362,"gene_effect_median":-0.005389341021779709},"dependency_probability_context_minus_non_context_median":-0.0018624797060952606,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.009436253330396771,"gene_effect_context_minus_non_context_median":-0.005524901020421788} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 235 +- **Dependency-aware candidate rank:** 235 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_84f0aee76b7517c0713b74a66cc7787f61493cf2d644a12f7c125e6a7b1ee66f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BRD3|entrez:8019` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BRD4.md b/examples/target_cards/depmap_26q1/BRD4.md new file mode 100644 index 0000000..a193cd9 --- /dev/null +++ b/examples/target_cards/depmap_26q1/BRD4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BRD4 + +## Target identity + +- **Target symbol:** BRD4 +- **Target name:** bromodomain containing 4 +- **Open Targets melanoma score:** 0.538 +- **Open Targets baseline rank:** 181 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 183 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 184 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 183 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.538) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BRD4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BRD4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.248457530692548,"interquartile_range":0.31380168154055843,"maximum":-0.23565820283589978,"mean":-1.077419296229426,"measured_model_count":56,"median":-1.107477935554086,"minimum":-1.7448082336119686,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.9346558491519896,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.955950792547962,"interquartile_range":0.03830238730638025,"maximum":0.9999959988125812,"mean":0.9347159273213392,"measured_model_count":56,"median":0.9859241206511045,"minimum":0.16171450657858166,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9942531798543423,"threshold_fractions":[{"denominator":56,"fraction":0.9642857142857143,"numerator":54,"threshold":0.5},{"denominator":56,"fraction":0.9107142857142857,"numerator":51,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.012852118011719371,"dependency_probability_threshold_fractions":[{"context_fraction":0.9642857142857143,"difference":0.012298959318826852,"pan_cancer_fraction":0.9519867549668874,"threshold":0.5},{"context_fraction":0.9107142857142857,"difference":0.05640964995269626,"pan_cancer_fraction":0.8543046357615894,"threshold":0.8}],"gene_effect_mean":-0.06262569475045776,"gene_effect_median":-0.0852599501660074},"dependency_probability_context_minus_non_context_median":0.013431985355028209,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9642857142857143,"difference":0.012896825396825462,"non_context_fraction":0.9513888888888888,"threshold":0.5},{"context_fraction":0.9107142857142857,"difference":0.0591517857142857,"non_context_fraction":0.8515625,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0656699993563834,"gene_effect_context_minus_non_context_median":-0.08666583394816563} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 183 +- **Dependency-aware candidate rank:** 183 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_adc5929d4b75660699e849fe64220e0ada6c45e9c7fb0367b31d5dab4d09fd09` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BRD4|entrez:23476` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BTK.md b/examples/target_cards/depmap_26q1/BTK.md new file mode 100644 index 0000000..65f9fad --- /dev/null +++ b/examples/target_cards/depmap_26q1/BTK.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BTK + +## Target identity + +- **Target symbol:** BTK +- **Target name:** Bruton tyrosine kinase +- **Open Targets melanoma score:** 0.516 +- **Open Targets baseline rank:** 226 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 228 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 228 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 228 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.516) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BTK lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BTK in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.035771337179793285,"interquartile_range":0.11021362664917433,"maximum":0.3015345371345652,"mean":0.03015665145976979,"measured_model_count":56,"median":0.021314724552192434,"minimum":-0.21445633651626686,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07444228946938104,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.009506480463942741,"interquartile_range":0.01914368707509713,"maximum":0.17509651908925622,"mean":0.022697174251634644,"measured_model_count":56,"median":0.014886149558598682,"minimum":0.0014470532586933651,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02865016753903987,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.007619040350417529,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0074503311258278145,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.04085015215705611,"gene_effect_median":0.02781483045251088},"dependency_probability_context_minus_non_context_median":-0.00791877146594909,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0078125,"non_context_fraction":0.0078125,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04283592344246858,"gene_effect_context_minus_non_context_median":0.028645312644089246} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 228 +- **Dependency-aware candidate rank:** 228 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_bdff26cd1390682ce0aab280e0ad3136f9ebd8df2a4e41abd2cf34287ace1a21` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BTK|entrez:695` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/BUB1B.md b/examples/target_cards/depmap_26q1/BUB1B.md new file mode 100644 index 0000000..d243c5c --- /dev/null +++ b/examples/target_cards/depmap_26q1/BUB1B.md @@ -0,0 +1,124 @@ +# Target hypothesis card: BUB1B + +## Target identity + +- **Target symbol:** BUB1B +- **Target name:** BUB1 mitotic checkpoint serine/threonine kinase B +- **Open Targets melanoma score:** 0.519 +- **Open Targets baseline rank:** 218 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 220 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 220 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 220 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.519) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** BUB1B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for BUB1B in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.3026861749001495,"interquartile_range":0.34471355076042975,"maximum":-0.35062174656503176,"mean":-1.1293619487648725,"measured_model_count":56,"median":-1.1239831043751725,"minimum":-1.9513382130061605,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.9579726241397197,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9661276307634157,"interquartile_range":0.027854131010518257,"maximum":1.0,"mean":0.9478580814276604,"measured_model_count":56,"median":0.9837485018692456,"minimum":0.27364189485863244,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9939817617739339,"threshold_fractions":[{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.5},{"denominator":56,"fraction":0.9285714285714286,"numerator":52,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004764787764668599,"dependency_probability_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":-0.00047303689687805406,"pan_cancer_fraction":0.9826158940397351,"threshold":0.5},{"context_fraction":0.9285714285714286,"difference":-0.02838221381267736,"pan_cancer_fraction":0.956953642384106,"threshold":0.8}],"gene_effect_mean":0.09650160394376806,"gene_effect_median":0.08149630964729271},"dependency_probability_context_minus_non_context_median":-0.0049250007582350985,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":-0.0004960317460317443,"non_context_fraction":0.9826388888888888,"threshold":0.5},{"context_fraction":0.9285714285714286,"difference":-0.029761904761904767,"non_context_fraction":0.9583333333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.10119265413547818,"gene_effect_context_minus_non_context_median":0.08446568961822298} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 220 +- **Dependency-aware candidate rank:** 220 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_52cb19a67699623cc57a20835603781eea551f4092f163861315d52368c52ee5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:BUB1B|entrez:701` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CACNA1D.md b/examples/target_cards/depmap_26q1/CACNA1D.md new file mode 100644 index 0000000..507a1be --- /dev/null +++ b/examples/target_cards/depmap_26q1/CACNA1D.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CACNA1D + +## Target identity + +- **Target symbol:** CACNA1D +- **Target name:** calcium voltage-gated channel subunit alpha1 D +- **Open Targets melanoma score:** 0.517 +- **Open Targets baseline rank:** 224 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 226 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 226 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 226 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.517) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CACNA1D lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CACNA1D in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06948366200968034,"interquartile_range":0.12410483739837593,"maximum":0.22152661199200682,"mean":-0.013247144110869868,"measured_model_count":56,"median":-0.019408167580945213,"minimum":-0.3736384929932119,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.054621175388695584,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01215263379668628,"interquartile_range":0.02561710835008954,"maximum":0.3270060202736238,"mean":0.037954791056176954,"measured_model_count":56,"median":0.02156477750214402,"minimum":0.0011308355940113652,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03776974214677582,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.008126721128793965,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.023986554352201293,"gene_effect_median":0.017300102971426506},"dependency_probability_context_minus_non_context_median":-0.008561961886107583,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.02515256741098892,"gene_effect_context_minus_non_context_median":0.018531630100138224} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 226 +- **Dependency-aware candidate rank:** 226 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e38bf98f2041ad8780c0febfb438a421cc87a6cd5eecd343f6b41ada521b2b62` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CACNA1D|entrez:776` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CARD11.md b/examples/target_cards/depmap_26q1/CARD11.md new file mode 100644 index 0000000..84d1d96 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CARD11.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CARD11 + +## Target identity + +- **Target symbol:** CARD11 +- **Target name:** caspase recruitment domain family member 11 +- **Open Targets melanoma score:** 0.542 +- **Open Targets baseline rank:** 179 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 181 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 182 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 181 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.542) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CARD11 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CARD11 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.09562676156794828,"interquartile_range":0.19020488634525662,"maximum":0.404261290756003,"mean":-0.01514292880487186,"measured_model_count":56,"median":-0.00843369100614956,"minimum":-0.54090902690978,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09457812477730834,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008250132462729496,"interquartile_range":0.053159633659909625,"maximum":0.49703376053943404,"mean":0.04895601126388154,"measured_model_count":56,"median":0.022444793911606052,"minimum":0.00045958623127264427,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06140976612263912,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01098489607869009,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.040418300808156796,"gene_effect_median":0.041333582837208976},"dependency_probability_context_minus_non_context_median":-0.011567731999631077,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.042383079319664396,"gene_effect_context_minus_non_context_median":0.042901069216673346} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 181 +- **Dependency-aware candidate rank:** 181 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_1633149fe392bc6524f87b3b4533182241d32393c25a454a335fc48d3b783f12` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CARD11|entrez:84433` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CARS1.md b/examples/target_cards/depmap_26q1/CARS1.md new file mode 100644 index 0000000..3939af2 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CARS1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CARS1 + +## Target identity + +- **Target symbol:** CARS1 +- **Target name:** cysteinyl-tRNA synthetase 1 +- **Open Targets melanoma score:** 0.504 +- **Open Targets baseline rank:** 249 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 251 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 251 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 251 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.504) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CARS1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CARS1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.8026753461573768,"interquartile_range":0.3885820681187324,"maximum":-0.8250676982589952,"mean":-1.6092899115753092,"measured_model_count":56,"median":-1.5980364353584418,"minimum":-2.3420142033697706,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.4140932780386444,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9965804422428789,"interquartile_range":0.0034195577571211055,"maximum":1.0,"mean":0.9922324381369838,"measured_model_count":56,"median":0.9999665853145443,"minimum":0.8994039933591144,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-1.52871546978961e-05,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0016556291390728006,"pan_cancer_fraction":0.9983443708609272,"threshold":0.5},{"context_fraction":1.0,"difference":0.004966887417218513,"pan_cancer_fraction":0.9950331125827815,"threshold":0.8}],"gene_effect_mean":0.08020409235119175,"gene_effect_median":0.08857204807747632},"dependency_probability_context_minus_non_context_median":-1.6309468427122553e-05,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0017361111111111605,"non_context_fraction":0.9982638888888888,"threshold":0.5},{"context_fraction":1.0,"difference":0.00520833333333337,"non_context_fraction":0.9947916666666666,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08410290239604046,"gene_effect_context_minus_non_context_median":0.09378399626638156} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 251 +- **Dependency-aware candidate rank:** 251 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_3cc6e86715493ffe54d22b16e5c74b51d97db2d4907b1cb92ab2daf32b222e4e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CARS1|entrez:833` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CASP8.md b/examples/target_cards/depmap_26q1/CASP8.md new file mode 100644 index 0000000..accfc6f --- /dev/null +++ b/examples/target_cards/depmap_26q1/CASP8.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CASP8 + +## Target identity + +- **Target symbol:** CASP8 +- **Target name:** caspase 8 +- **Open Targets melanoma score:** 0.572 +- **Open Targets baseline rank:** 112 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 114 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 115 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 114 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.572) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CASP8 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CASP8 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.011897068060551866,"interquartile_range":0.12536036995353528,"maximum":0.8713892618394627,"mean":0.06026911617051994,"measured_model_count":56,"median":0.04398793623669359,"minimum":-0.3339036816398781,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11346330189298341,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005880240328625039,"interquartile_range":0.022025935311596547,"maximum":0.2593446374523578,"mean":0.026311317489120405,"measured_model_count":56,"median":0.010841974401337703,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.027906175640221586,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":9.028752303627194e-05,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.0277111166708659,"gene_effect_median":-0.03366897379591392},"dependency_probability_context_minus_non_context_median":9.028752303627194e-05,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.029058184842366372,"gene_effect_context_minus_non_context_median":-0.035154619781945506} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 114 +- **Dependency-aware candidate rank:** 114 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_53df70bb8fc55be15417576e10356b10b76a98092555cecfcd70ea00ec9847b6` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CASP8|entrez:841` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CBFA2T3.md b/examples/target_cards/depmap_26q1/CBFA2T3.md new file mode 100644 index 0000000..64d8324 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CBFA2T3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CBFA2T3 + +## Target identity + +- **Target symbol:** CBFA2T3 +- **Target name:** CBFA2/RUNX1 partner transcriptional co-repressor 3 +- **Open Targets melanoma score:** 0.475 +- **Open Targets baseline rank:** 279 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 279 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 279 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 279 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.475) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CBFA2T3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CBFA2T3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.136964140758632,"interquartile_range":0.16167139541119036,"maximum":0.21418474445863944,"mean":-0.05229143749802029,"measured_model_count":56,"median":-0.01977128242853117,"minimum":-0.4116048408666105,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02470725465255836,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.015136985019785953,"interquartile_range":0.05489342649673515,"maximum":0.3112207868780006,"mean":0.05585963773120791,"measured_model_count":56,"median":0.02561603909201212,"minimum":0.0020054058447227492,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0700304115165211,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0045371008859744,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.05239136326576069,"gene_effect_median":-0.02362187206276809},"dependency_probability_context_minus_non_context_median":0.004677530502939297,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.05493816564673518,"gene_effect_context_minus_non_context_median":-0.026067259451230895} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 279 +- **Dependency-aware candidate rank:** 279 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e5ae10bfdb0910742e6621de3128718715c20aefe67309b801c2f01f1e9e608b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CBFA2T3|entrez:863` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CBL.md b/examples/target_cards/depmap_26q1/CBL.md new file mode 100644 index 0000000..aba0155 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CBL.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CBL + +## Target identity + +- **Target symbol:** CBL +- **Target name:** Cbl proto-oncogene +- **Open Targets melanoma score:** 0.582 +- **Open Targets baseline rank:** 96 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 99 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 100 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 99 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.582) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CBL lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CBL in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.03494968754517518,"interquartile_range":0.12545142715306176,"maximum":0.38716705456969325,"mean":0.03013536038410847,"measured_model_count":56,"median":0.019575406859070273,"minimum":-0.21767347114684926,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09050173960788657,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0085481911101527,"interquartile_range":0.01963866209088416,"maximum":0.10180326303471457,"mean":0.022745420875610177,"measured_model_count":56,"median":0.015865046905975483,"minimum":0.0010694223846413645,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02818685320103686,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0006230784257667266,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.004217348259192944,"gene_effect_median":-0.004799686634262463},"dependency_probability_context_minus_non_context_median":-0.00069776111089127,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.004422358244014844,"gene_effect_context_minus_non_context_median":-0.004873586214154284} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 99 +- **Dependency-aware candidate rank:** 99 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_4b2aac16496b16aafe4d48688b4e149959c98fe30ba2a36f2df34730aa9b9406` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CBL|entrez:867` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CBLB.md b/examples/target_cards/depmap_26q1/CBLB.md new file mode 100644 index 0000000..d99934a --- /dev/null +++ b/examples/target_cards/depmap_26q1/CBLB.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CBLB + +## Target identity + +- **Target symbol:** CBLB +- **Target name:** Cbl proto-oncogene B +- **Open Targets melanoma score:** 0.558 +- **Open Targets baseline rank:** 139 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 141 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 142 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 141 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.558) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CBLB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CBLB in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.05384536648266203,"interquartile_range":0.1050815451078648,"maximum":0.3454643691830615,"mean":0.007447681590991319,"measured_model_count":56,"median":-0.0034065031597723177,"minimum":-0.16375155174679337,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05123617862520277,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.010491807935730858,"interquartile_range":0.0307455167698769,"maximum":0.12149399207427411,"mean":0.026859285847007187,"measured_model_count":56,"median":0.020538144383673726,"minimum":0.0006857831670003677,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04123732470560776,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0032368472237769494,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.01643998313273535,"gene_effect_median":0.011004086664659123},"dependency_probability_context_minus_non_context_median":-0.0033771440743860168,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01723914897946556,"gene_effect_context_minus_non_context_median":0.011426898627511239} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 141 +- **Dependency-aware candidate rank:** 141 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_7d1e1cd259415931be46985e73b7babfbae13a0705fcdfdf58d1c28892b51406` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CBLB|entrez:868` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CCND1.md b/examples/target_cards/depmap_26q1/CCND1.md new file mode 100644 index 0000000..62e62cd --- /dev/null +++ b/examples/target_cards/depmap_26q1/CCND1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CCND1 + +## Target identity + +- **Target symbol:** CCND1 +- **Target name:** cyclin D1 +- **Open Targets melanoma score:** 0.635 +- **Open Targets baseline rank:** 39 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 46 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 48 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 46 | not prioritized | -7 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.635) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CCND1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CCND1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-2.5159803501587126,"interquartile_range":1.317293670034944,"maximum":-0.05330788682190524,"mean":-1.8967774740528005,"measured_model_count":56,"median":-1.828765775143998,"minimum":-3.3354607159421072,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.1986866801237686,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9930169828579302,"interquartile_range":0.006983017142069836,"maximum":1.0,"mean":0.9517735651535275,"measured_model_count":56,"median":1.0,"minimum":0.045554294167438766,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":0.9642857142857143,"numerator":54,"threshold":0.5},{"denominator":56,"fraction":0.9107142857142857,"numerator":51,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.01699677125141008,"dependency_probability_threshold_fractions":[{"context_fraction":0.9642857142857143,"difference":0.21925260170293281,"pan_cancer_fraction":0.7450331125827815,"threshold":0.5},{"context_fraction":0.9107142857142857,"difference":0.2567407757805109,"pan_cancer_fraction":0.6539735099337748,"threshold":0.8}],"gene_effect_mean":-0.650858557444201,"gene_effect_median":-0.7516415503073022},"dependency_probability_context_minus_non_context_median":0.02102358843125729,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9642857142857143,"difference":0.2299107142857143,"non_context_fraction":0.734375,"threshold":0.5},{"context_fraction":0.9107142857142857,"difference":0.2692212301587301,"non_context_fraction":0.6414930555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.6824975150977388,"gene_effect_context_minus_non_context_median":-0.7884990157905569} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 46 +- **Dependency-aware candidate rank:** 46 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ca8fd343d55b4e0866b281cdb13f04e7eb09a3d99a6fa26dfa3a2f7efb22ddf2` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CCND1|entrez:595` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CCND2.md b/examples/target_cards/depmap_26q1/CCND2.md new file mode 100644 index 0000000..9405f59 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CCND2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CCND2 + +## Target identity + +- **Target symbol:** CCND2 +- **Target name:** cyclin D2 +- **Open Targets melanoma score:** 0.560 +- **Open Targets baseline rank:** 135 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 137 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 138 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 137 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.560) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CCND2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CCND2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.15579197515311352,"interquartile_range":0.17786015005357908,"maximum":0.37138012941204834,"mean":-0.05966427508651161,"measured_model_count":56,"median":-0.08633474069631311,"minimum":-0.22837474318280288,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.022068174900465552,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.013285731471925577,"interquartile_range":0.06560912247822459,"maximum":0.1904888154369347,"mean":0.05466906017495544,"measured_model_count":56,"median":0.04813965995942092,"minimum":0.0008839430891336923,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07889485395015017,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00577555222621233,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.06705298013245033,"pan_cancer_fraction":0.06705298013245033,"threshold":0.5},{"context_fraction":0.0,"difference":-0.048841059602649006,"pan_cancer_fraction":0.048841059602649006,"threshold":0.8}],"gene_effect_mean":0.10164960237461951,"gene_effect_median":0.011970886367573319},"dependency_probability_context_minus_non_context_median":-0.007143100926483945,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0703125,"non_context_fraction":0.0703125,"threshold":0.5},{"context_fraction":0.0,"difference":-0.051215277777777776,"non_context_fraction":0.051215277777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.1065909024900524,"gene_effect_context_minus_non_context_median":0.012724641971365469} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 137 +- **Dependency-aware candidate rank:** 137 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_86d669a6908841a2c507d635b235616e6726255d8546fbba0fa0fca90a3d8f86` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CCND2|entrez:894` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CD274.md b/examples/target_cards/depmap_26q1/CD274.md new file mode 100644 index 0000000..9fd30da --- /dev/null +++ b/examples/target_cards/depmap_26q1/CD274.md @@ -0,0 +1,133 @@ +# Target hypothesis card: CD274 + +## Target identity + +- **Target symbol:** CD274 +- **Target name:** CD274 molecule +- **Open Targets melanoma score:** 0.612 +- **Open Targets baseline rank:** 53 + +## Stable TargetIntel-IO classification + +- **Role classification:** anti-PD-1 combination target +- **Role confidence:** high +- **Therapeutic direction:** block / inhibit +- **Best modality:** antibody / IO-combination target +- **Resistance axis:** checkpoint_redundancy +- **Matched resistance programs:** Checkpoint redundancy + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.825 | 3 | high | 50 | +| Resistance biomarker | 0.496 | 9 | medium | 44 | +| Tumor-intrinsic / small molecule | 0.141 | 11 | low | 42 | + +## Evidence for + +- Immune checkpoint biology +- Potential compensatory inhibitory pathway after PD-1 blockade +- Surface-accessible immune receptor or ligand +- Moderate Open Targets melanoma association score (0.612) +- Maps to curated anti-PD-1 resistance program: Checkpoint redundancy +- Stable role classifier confidence is high +- Antibody fit is high +- IO-combination fit is high +- Checkpoint-axis biology supports anti-PD-1 combination rationale + +## Evidence against / limitations + +- Crowded IO target space +- Expression may reflect exhausted immune-cell abundance rather than causal resistance in all tumors +- Patient selection may be required + +## Confidence and uncertainty + +- **Confidence level:** high confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.240 +- **Main limitation:** No major limitation flagged by current MVP rules +- **Uncertainty reason:** Main limitation: No major limitation flagged by current MVP rules +- **Deprioritization reason:** No strong deprioritization reason from current MVP rules + +## Recommended next validation experiment + +- **Validation category:** immune-checkpoint functional validation +- **Next experiment:** Validate CD274 expression in exhausted CD8 T-cell populations from anti-PD-1-resistant melanoma samples and test blockade in a melanoma/T-cell co-culture assay. +- **Rationale:** This would test whether the candidate marks a relevant checkpoint axis and whether blockade can improve anti-tumor T-cell activity. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.1219432529423023,"interquartile_range":0.14942892394873147,"maximum":0.5564732732340494,"mean":0.19436573097880774,"measured_model_count":56,"median":0.1863639156999815,"minimum":-0.07863180936507297,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.27137217689103377,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.001499226517437284,"interquartile_range":0.0064206254383672645,"maximum":0.036701970754130495,"mean":0.006382432047991671,"measured_model_count":56,"median":0.0035318069749596765,"minimum":8.135797076424987e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.007919851955804549,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0006216088255521519,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.014569741459674629,"gene_effect_median":0.0027778599042512786},"dependency_probability_context_minus_non_context_median":-0.0006866699950678077,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01527799278063105,"gene_effect_context_minus_non_context_median":0.00343451210457299} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 3 +- **Dependency-aware candidate rank:** 9 +- **Rank delta:** 6 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_c33d7ba54af47d54589acf9c900707872f41fa304ee8236c34732f1ac9546be5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CD274|entrez:29126` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CD79A.md b/examples/target_cards/depmap_26q1/CD79A.md new file mode 100644 index 0000000..a9dea8b --- /dev/null +++ b/examples/target_cards/depmap_26q1/CD79A.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CD79A + +## Target identity + +- **Target symbol:** CD79A +- **Target name:** CD79a molecule +- **Open Targets melanoma score:** 0.478 +- **Open Targets baseline rank:** 275 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 275 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 275 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 275 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.478) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CD79A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CD79A in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.059678830445944894,"interquartile_range":0.09997205789462581,"maximum":0.26466406443135215,"mean":0.1122462807561854,"measured_model_count":56,"median":0.1100920547426244,"minimum":-0.02926449099631112,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1596508883405707,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.003938865463013505,"interquartile_range":0.009093021526598969,"maximum":0.02573885019852544,"mean":0.008905088974721555,"measured_model_count":56,"median":0.0069261069107548695,"minimum":0.0007298659872511824,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.013031886989612475,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0013563893853354046,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.01076158940397351,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008278145695364239,"pan_cancer_fraction":0.008278145695364239,"threshold":0.8}],"gene_effect_mean":-0.023727691561340747,"gene_effect_median":-0.039209474166331776},"dependency_probability_context_minus_non_context_median":0.0014130548944801266,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.011284722222222222,"non_context_fraction":0.011284722222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008680555555555556,"non_context_fraction":0.008680555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.024881121012239216,"gene_effect_context_minus_non_context_median":-0.04017112868584041} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 275 +- **Dependency-aware candidate rank:** 275 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d66951d288524081e861b8a63210e1cfeea6f700d99b6bb6b29b038a380c1404` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CD79A|entrez:973` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CD8A.md b/examples/target_cards/depmap_26q1/CD8A.md new file mode 100644 index 0000000..0ff3d96 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CD8A.md @@ -0,0 +1,73 @@ +# CD8A — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.027430912377545535,"interquartile_range":0.13942569209925004,"maximum":0.46165860344769677,"mean":0.045785073452028605,"measured_model_count":56,"median":0.03928974584334112,"minimum":-0.26540822030616257,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11199477972170452,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.007483582094896921,"interquartile_range":0.017911250672013962,"maximum":0.201806266723021,"mean":0.02445228992923763,"measured_model_count":56,"median":0.011938528707279468,"minimum":0.0002748136637528369,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02539483276691088,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.007151854567642068,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.03066633825677472,"gene_effect_median":0.028327006093492063},"dependency_probability_context_minus_non_context_median":-0.007658030597719308,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03215706303314572,"gene_effect_context_minus_non_context_median":0.029962877737475586} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a02967e9bd1b73443ee516c0ffa8cfd4e3078490f5c32a7a829dc9b8e62d2549` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CD8A|entrez:925` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CDH1.md b/examples/target_cards/depmap_26q1/CDH1.md new file mode 100644 index 0000000..2f2b62f --- /dev/null +++ b/examples/target_cards/depmap_26q1/CDH1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CDH1 + +## Target identity + +- **Target symbol:** CDH1 +- **Target name:** cadherin 1 +- **Open Targets melanoma score:** 0.466 +- **Open Targets baseline rank:** 289 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 289 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 289 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 289 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.466) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CDH1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CDH1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.15427271942471482,"interquartile_range":0.1577065173221155,"maximum":0.2295208783394289,"mean":-0.10742966270794449,"measured_model_count":56,"median":-0.07204685958685368,"minimum":-0.8750426660413623,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.00343379789740067,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0180917185977245,"interquartile_range":0.06286002234786717,"maximum":0.874379672670159,"mean":0.10329287088429209,"measured_model_count":56,"median":0.04375955195407501,"minimum":0.0028271732493434652,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08095174094559167,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-6.01063460411444e-05,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.008159886471144753,"pan_cancer_fraction":0.043874172185430466,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.010879848628192999,"pan_cancer_fraction":0.024834437086092714,"threshold":0.8}],"gene_effect_mean":-0.007372814336056799,"gene_effect_median":0.005760578127514945},"dependency_probability_context_minus_non_context_median":-6.01063460411444e-05,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.008556547619047623,"non_context_fraction":0.044270833333333336,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.011408730158730156,"non_context_fraction":0.024305555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.007731215032948366,"gene_effect_context_minus_non_context_median":0.005760578127514945} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 289 +- **Dependency-aware candidate rank:** 289 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_c455a8c6e42620397cabba760e778dd7d0d54d24712c2e40cab8b7b2953492cf` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CDH1|entrez:999` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CDK12.md b/examples/target_cards/depmap_26q1/CDK12.md new file mode 100644 index 0000000..82b2475 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CDK12.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CDK12 + +## Target identity + +- **Target symbol:** CDK12 +- **Target name:** cyclin dependent kinase 12 +- **Open Targets melanoma score:** 0.587 +- **Open Targets baseline rank:** 91 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 94 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 96 | not prioritized | -5 | +| Tumor-intrinsic / small molecule | 0.000 | 94 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.587) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CDK12 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CDK12 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.5586337757206544,"interquartile_range":0.19059665446702484,"maximum":-0.13749466210671846,"mean":-0.47143749469136337,"measured_model_count":56,"median":-0.47096900533770847,"minimum":-1.200422877513772,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.3680371212536296,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.35421745198329635,"interquartile_range":0.31026076242553446,"maximum":0.9783518078107925,"mean":0.49957849685747113,"measured_model_count":56,"median":0.4693828317812654,"minimum":0.04818076524574193,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.6644782144088308,"threshold_fractions":[{"denominator":56,"fraction":0.44642857142857145,"numerator":25,"threshold":0.5},{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.07074255210397296,"dependency_probability_threshold_fractions":[{"context_fraction":0.44642857142857145,"difference":0.07473982970671716,"pan_cancer_fraction":0.3716887417218543,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.046475875118259236,"pan_cancer_fraction":0.11423841059602649,"threshold":0.8}],"gene_effect_mean":-0.061717368517177074,"gene_effect_median":-0.06553518413091808},"dependency_probability_context_minus_non_context_median":0.07651601515871376,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.44642857142857145,"difference":0.07837301587301587,"non_context_fraction":0.3680555555555556,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.048735119047619055,"non_context_fraction":0.11197916666666667,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.06471751837565104,"gene_effect_context_minus_non_context_median":-0.06899439882165848} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 94 +- **Dependency-aware candidate rank:** 94 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d6da70bd96d09fc51c8e74fc16b62eae8b994e974460e3dcbfd6b05d6855d847` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CDK12|entrez:51755` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CDK4.md b/examples/target_cards/depmap_26q1/CDK4.md new file mode 100644 index 0000000..5c950b5 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CDK4.md @@ -0,0 +1,126 @@ +# Target hypothesis card: CDK4 + +## Target identity + +- **Target symbol:** CDK4 +- **Target name:** cyclin dependent kinase 4 +- **Open Targets melanoma score:** 0.735 +- **Open Targets baseline rank:** 10 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / small-molecule target +- **Role confidence:** high +- **Therapeutic direction:** small-molecule inhibition / pathway targeting +- **Best modality:** small molecule / pathway targeting +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 18 | not prioritized | -8 | +| Resistance biomarker | 0.101 | 21 | low | -11 | +| Tumor-intrinsic / small molecule | 0.682 | 4 | medium | 6 | + +## Evidence for + +- High Open Targets melanoma association score (0.735) +- Stable role classifier confidence is high +- Small-molecule fit is high + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 0.889 +- **Contradiction score:** 0.160 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CDK4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** tumor-intrinsic functional validation +- **Next experiment:** Evaluate whether perturbing CDK4 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays. +- **Rationale:** This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.1460787729249597,"interquartile_range":0.6487242724872709,"maximum":0.14819456849436097,"mean":-0.9690295177076944,"measured_model_count":56,"median":-0.7802086880629331,"minimum":-2.6012252653565273,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.4973545004376888,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.5276778197266463,"interquartile_range":0.46063984426021753,"maximum":1.0,"mean":0.7625651007343259,"measured_model_count":56,"median":0.8640150958074966,"minimum":0.0044507692556070445,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9883176639868638,"threshold_fractions":[{"denominator":56,"fraction":0.7857142857142857,"numerator":44,"threshold":0.5},{"denominator":56,"fraction":0.5892857142857143,"numerator":33,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.19303827080821434,"dependency_probability_threshold_fractions":[{"context_fraction":0.7857142857142857,"difference":0.14167455061494794,"pan_cancer_fraction":0.6440397350993378,"threshold":0.5},{"context_fraction":0.5892857142857143,"difference":0.18200094607379375,"pan_cancer_fraction":0.40728476821192056,"threshold":0.8}],"gene_effect_mean":-0.23795306295958707,"gene_effect_median":-0.21969659440659983},"dependency_probability_context_minus_non_context_median":0.19930434880478232,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.7857142857142857,"difference":0.1485615079365079,"non_context_fraction":0.6371527777777778,"threshold":0.5},{"context_fraction":0.5892857142857143,"difference":0.1908482142857143,"non_context_fraction":0.3984375,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.24952022574234523,"gene_effect_context_minus_non_context_median":-0.22500520575267613} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 18 +- **Dependency-aware candidate rank:** 14 +- **Rank delta:** -4 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_71442941b019de45c466e32e7241f8d7bfdaa6dc865747d44e280e0a14e246ad` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CDK4|entrez:1019` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CDK6.md b/examples/target_cards/depmap_26q1/CDK6.md new file mode 100644 index 0000000..929c4f5 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CDK6.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CDK6 + +## Target identity + +- **Target symbol:** CDK6 +- **Target name:** cyclin dependent kinase 6 +- **Open Targets melanoma score:** 0.575 +- **Open Targets baseline rank:** 107 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 110 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 111 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 110 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.575) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CDK6 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CDK6 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.827840200340922,"interquartile_range":0.5564369377066776,"maximum":0.053999009787811136,"mean":-0.6040550843316354,"measured_model_count":56,"median":-0.4741396489201388,"minimum":-1.9939384470287465,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.2714032626342444,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.21797895301513842,"interquartile_range":0.7309485506409665,"maximum":1.0,"mean":0.5655746850424314,"measured_model_count":56,"median":0.5298570181549593,"minimum":0.009549200402016388,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.948927503656105,"threshold_fractions":[{"denominator":56,"fraction":0.5178571428571429,"numerator":29,"threshold":0.5},{"denominator":56,"fraction":0.39285714285714285,"numerator":22,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.09549984337280804,"dependency_probability_threshold_fractions":[{"context_fraction":0.5178571428571429,"difference":-0.024361400189214732,"pan_cancer_fraction":0.5422185430463576,"threshold":0.5},{"context_fraction":0.39285714285714285,"difference":-0.024361400189214788,"pan_cancer_fraction":0.41721854304635764,"threshold":0.8}],"gene_effect_mean":0.02827248424985951,"gene_effect_median":0.054575631840271366},"dependency_probability_context_minus_non_context_median":-0.09879939553115324,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.5178571428571429,"difference":-0.025545634920634885,"non_context_fraction":0.5434027777777778,"threshold":0.5},{"context_fraction":0.39285714285714285,"difference":-0.02554563492063494,"non_context_fraction":0.4184027777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.02964684112311744,"gene_effect_context_minus_non_context_median":0.055977625413455634} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 110 +- **Dependency-aware candidate rank:** 110 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d432699f277936d0a0710e776785be716c2382f5549aa72d6ea6cb5b97df404e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CDK6|entrez:1021` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CDKN2A.md b/examples/target_cards/depmap_26q1/CDKN2A.md new file mode 100644 index 0000000..9825e75 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CDKN2A.md @@ -0,0 +1,133 @@ +# Target hypothesis card: CDKN2A + +## Target identity + +- **Target symbol:** CDKN2A +- **Target name:** cyclin dependent kinase inhibitor 2A +- **Open Targets melanoma score:** 0.870 +- **Open Targets baseline rank:** 1 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / poor direct therapeutic target +- **Role confidence:** high +- **Therapeutic direction:** avoid as direct target / use as biomarker or pathway context +- **Best modality:** biomarker / pathway context only +- **Resistance axis:** tumor_intrinsic_driver +- **Matched resistance programs:** Tumor-intrinsic driver biology + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 12 | not prioritized | -11 | +| Resistance biomarker | 0.329 | 15 | low | -14 | +| Tumor-intrinsic / small molecule | 0.000 | 36 | not prioritized | -35 | + +## Evidence for + +- Relevant to melanoma tumor-cell biology +- Some targets or pathways are clinically actionable +- Useful for separating tumor-intrinsic drivers from immune-combination targets +- High Open Targets melanoma association score (0.870) +- Maps to curated anti-PD-1 resistance program: Tumor-intrinsic driver biology +- Stable role classifier confidence is high + +## Evidence against / limitations + +- Many tumor-intrinsic drivers are poor antibody targets +- Melanoma association does not automatically imply anti-PD-1 combination suitability +- Tumor suppressors are often poor direct therapeutic targets +- Flagged as poor direct therapeutic target for this MVP +- Role classifier indicates biological relevance but poor direct targetability +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.650 +- **Main limitation:** Poor direct therapeutic target despite biological relevance +- **Uncertainty reason:** High contradiction score indicates important opposing evidence | Main limitation: Poor direct therapeutic target despite biological relevance +- **Deprioritization reason:** CDKN2A should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context. + +## Recommended next validation experiment + +- **Validation category:** tumor-intrinsic functional validation +- **Next experiment:** Evaluate whether perturbing CDKN2A alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays. +- **Rationale:** This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.0614428613918262,"interquartile_range":0.17868173128792053,"maximum":0.8033652137565361,"mean":0.15445826248821265,"measured_model_count":56,"median":0.16082152009903888,"minimum":-0.4366709312086744,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.24012459267974673,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0017200751468406438,"interquartile_range":0.014484209677434792,"maximum":0.35063429324839185,"mean":0.024559879767375458,"measured_model_count":56,"median":0.0038283808957741555,"minimum":1.261747964913208e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.016204284824275435,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0019739676633992193,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.005233775424175274,"gene_effect_median":0.007051042654115713},"dependency_probability_context_minus_non_context_median":-0.0020327056425661766,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.005488195062850421,"gene_effect_context_minus_non_context_median":0.007081072312246278} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 12 +- **Dependency-aware candidate rank:** 18 +- **Rank delta:** 6 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_af0669fbbe0ab3cee1677b9b37ac27abdf1a632e7a02f16c03de98c74dfd6de5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CDKN2A|entrez:1029` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CDKN2B.md b/examples/target_cards/depmap_26q1/CDKN2B.md new file mode 100644 index 0000000..bf4f2a0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CDKN2B.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CDKN2B + +## Target identity + +- **Target symbol:** CDKN2B +- **Target name:** cyclin dependent kinase inhibitor 2B +- **Open Targets melanoma score:** 0.496 +- **Open Targets baseline rank:** 257 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 259 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 259 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 259 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.496) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CDKN2B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CDKN2B in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 55 +- **Available reference observations:** 1110 +- **Coverage fraction:** 0.9821428571428571 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.0404825098272594,"interquartile_range":0.19472070385108634,"maximum":0.6165124700793739,"mean":0.1636209642579699,"measured_model_count":55,"median":0.15881718146129087,"minimum":-0.12693022289918005,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":0.23520321367834574,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0013846813277508152,"interquartile_range":0.01286710860460067,"maximum":0.06171403833365283,"mean":0.009855320712572656,"measured_model_count":55,"median":0.005092649083602317,"minimum":4.676073979628638e-06,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":0.014251789932351485,"threshold_fractions":[{"denominator":55,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":55,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0035823099792716053,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008583690987124463,"pan_cancer_fraction":0.0008583690987124463,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.04530797019094235,"gene_effect_median":0.05950721862052126},"dependency_probability_context_minus_non_context_median":-0.003853541450446498,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0009009009009009009,"non_context_fraction":0.0009009009009009009,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04755295970490793,"gene_effect_context_minus_non_context_median":0.06235235195401219} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 259 +- **Dependency-aware candidate rank:** 259 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_f55e29f5bfe9f319f252aa005c39aa1bb9c3cc6b22ccb92171ede2cb04873f4b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CDKN2B|entrez:1030` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CDX2.md b/examples/target_cards/depmap_26q1/CDX2.md new file mode 100644 index 0000000..d75e408 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CDX2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CDX2 + +## Target identity + +- **Target symbol:** CDX2 +- **Target name:** caudal type homeobox 2 +- **Open Targets melanoma score:** 0.530 +- **Open Targets baseline rank:** 187 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 189 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 190 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 189 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.530) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CDX2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CDX2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.13942254695053768,"interquartile_range":0.16163068207457448,"maximum":0.29566206461172795,"mean":-0.06736407857919634,"measured_model_count":56,"median":-0.059264623715066425,"minimum":-0.41280316373867654,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.022208135124036785,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.015200994236108184,"interquartile_range":0.06085001454530309,"maximum":0.43100994254852387,"mean":0.062366427518474085,"measured_model_count":56,"median":0.03842983462576611,"minimum":0.0017620750891681012,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07605100878141127,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.010355728954199207,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.02566225165562914,"pan_cancer_fraction":0.02566225165562914,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014072847682119206,"pan_cancer_fraction":0.014072847682119206,"threshold":0.8}],"gene_effect_mean":0.03963938525951244,"gene_effect_median":0.030046028123697097},"dependency_probability_context_minus_non_context_median":-0.010947717597245561,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.026909722222222224,"non_context_fraction":0.026909722222222224,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014756944444444444,"non_context_fraction":0.014756944444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04156629982073877,"gene_effect_context_minus_non_context_median":0.030874335457464375} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 189 +- **Dependency-aware candidate rank:** 189 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_f532f7772ff1101af041bee1f2781fa30b78e5aa23bbe47309c33b4908ee29de` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CDX2|entrez:1045` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CHD4.md b/examples/target_cards/depmap_26q1/CHD4.md new file mode 100644 index 0000000..cd6f130 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CHD4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CHD4 + +## Target identity + +- **Target symbol:** CHD4 +- **Target name:** chromodomain helicase DNA binding protein 4 +- **Open Targets melanoma score:** 0.520 +- **Open Targets baseline rank:** 210 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 212 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 212 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 212 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.520) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CHD4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CHD4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.4566567459085873,"interquartile_range":0.35622946135425004,"maximum":-0.5235966708192303,"mean":-1.256281075871031,"measured_model_count":56,"median":-1.2512662213227028,"minimum":-2.0043420178114166,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.1004272845543372,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9815862695547178,"interquartile_range":0.017558270975871704,"maximum":1.0,"mean":0.978835362557547,"measured_model_count":56,"median":0.9929567916053474,"minimum":0.6621869651205554,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9991445405305895,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.010208504155061693,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0314569536423841,"pan_cancer_fraction":0.9685430463576159,"threshold":0.5},{"context_fraction":0.9821428571428571,"difference":0.08148060548722791,"pan_cancer_fraction":0.9006622516556292,"threshold":0.8}],"gene_effect_mean":-0.1396756467244169,"gene_effect_median":-0.14570596698181015},"dependency_probability_context_minus_non_context_median":0.010845726535144928,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.03298611111111116,"non_context_fraction":0.9670138888888888,"threshold":0.5},{"context_fraction":0.9821428571428571,"difference":0.08544146825396826,"non_context_fraction":0.8967013888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.14646543510685328,"gene_effect_context_minus_non_context_median":-0.1557376988814274} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 212 +- **Dependency-aware candidate rank:** 212 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ff6f93762cf60634a0c2870dd7eedf4d385ff4a98109a2db6f6b4e8729158796` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CHD4|entrez:1108` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CHEK2.md b/examples/target_cards/depmap_26q1/CHEK2.md new file mode 100644 index 0000000..9c0c07d --- /dev/null +++ b/examples/target_cards/depmap_26q1/CHEK2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CHEK2 + +## Target identity + +- **Target symbol:** CHEK2 +- **Target name:** checkpoint kinase 2 +- **Open Targets melanoma score:** 0.609 +- **Open Targets baseline rank:** 58 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 62 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 64 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 62 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.609) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CHEK2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CHEK2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.23674494928062137,"interquartile_range":0.22708131202008544,"maximum":0.931883971568137,"mean":0.3426903444379113,"measured_model_count":56,"median":0.3224042378144514,"minimum":-0.16147390203749837,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.4638262613007068,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":9.751658835563242e-05,"interquartile_range":0.003480886578628852,"maximum":0.0694434148067228,"mean":0.0052062046687379885,"measured_model_count":56,"median":0.0006560276296503497,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.003578403166984485,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0028864308678459333,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.12317797889945803,"gene_effect_median":0.12028586236296915},"dependency_probability_context_minus_non_context_median":-0.003037398527081421,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.12916579731818173,"gene_effect_context_minus_non_context_median":0.12552324945476412} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 62 +- **Dependency-aware candidate rank:** 62 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_09f9262c521cf121a5d9e852ab259938008d088fd5a38e1310de927d0bd04837` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CHEK2|entrez:11200` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CIC.md b/examples/target_cards/depmap_26q1/CIC.md new file mode 100644 index 0000000..a5f2bca --- /dev/null +++ b/examples/target_cards/depmap_26q1/CIC.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CIC + +## Target identity + +- **Target symbol:** CIC +- **Target name:** capicua transcriptional repressor +- **Open Targets melanoma score:** 0.548 +- **Open Targets baseline rank:** 162 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 164 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 165 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 164 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.548) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CIC lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CIC in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.20969753443445882,"interquartile_range":0.3188863089690407,"maximum":0.7212674338591033,"mean":-0.05479185248369578,"measured_model_count":56,"median":-0.0724818295618623,"minimum":-0.5922742740203383,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10918877453458187,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0060443484088349726,"interquartile_range":0.10425416850941045,"maximum":0.6755686797363436,"mean":0.11305469201665709,"measured_model_count":56,"median":0.041316844193587124,"minimum":3.871106505121315e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11029851691824542,"threshold_fractions":[{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.008067677213065963,"dependency_probability_threshold_fractions":[{"context_fraction":0.08928571428571429,"difference":0.06279564806054873,"pan_cancer_fraction":0.026490066225165563,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.004468862662839836,"gene_effect_median":-0.02461731785542992},"dependency_probability_context_minus_non_context_median":0.008224799734887003,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.08928571428571429,"difference":0.06584821428571429,"non_context_fraction":0.0234375,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0046860990422833634,"gene_effect_context_minus_non_context_median":-0.02528609467709926} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 164 +- **Dependency-aware candidate rank:** 164 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_bf7e717c579a7d7a14cf42c0df9464f601e211197d021369f7e618579d91330e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CIC|entrez:23152` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CIITA.md b/examples/target_cards/depmap_26q1/CIITA.md new file mode 100644 index 0000000..c07670e --- /dev/null +++ b/examples/target_cards/depmap_26q1/CIITA.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CIITA + +## Target identity + +- **Target symbol:** CIITA +- **Target name:** class II major histocompatibility complex transactivator +- **Open Targets melanoma score:** 0.562 +- **Open Targets baseline rank:** 131 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 133 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 134 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 133 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.562) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CIITA lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CIITA in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.07481705516268009,"interquartile_range":0.14392723189675605,"maximum":0.21949437633984192,"mean":-0.005468924475870724,"measured_model_count":56,"median":0.01143269694703151,"minimum":-0.30489474426374596,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06911017673407598,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.009702019229598511,"interquartile_range":0.02840255596041054,"maximum":0.24617646555482525,"mean":0.03490953789092406,"measured_model_count":56,"median":0.016486777927961806,"minimum":0.001692034244815741,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03810457519000905,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00250613097564693,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.04724097755465141,"gene_effect_median":-0.03827391409799615},"dependency_probability_context_minus_non_context_median":0.0025912562613762628,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.049537413963558055,"gene_effect_context_minus_non_context_median":-0.040293550612653085} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 133 +- **Dependency-aware candidate rank:** 133 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_8bc1c2d3f4d300f45d815f33d7bae0eddb7438eb8acbbe6165053511428be195` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CIITA|entrez:4261` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CLPTM1L.md b/examples/target_cards/depmap_26q1/CLPTM1L.md new file mode 100644 index 0000000..2d615e1 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CLPTM1L.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CLPTM1L + +## Target identity + +- **Target symbol:** CLPTM1L +- **Target name:** CLPTM1 like +- **Open Targets melanoma score:** 0.456 +- **Open Targets baseline rank:** 299 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 299 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 299 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 299 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.456) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CLPTM1L lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CLPTM1L in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.03365827977140918,"interquartile_range":0.15583008785031374,"maximum":0.37251074770739345,"mean":0.12263371690035856,"measured_model_count":56,"median":0.11157894179367531,"minimum":-0.1922015107403494,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.18948836762172291,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0033575428305555734,"interquartile_range":0.009723968496991963,"maximum":0.07590534725685125,"mean":0.011504028916612676,"measured_model_count":56,"median":0.006899426529077324,"minimum":0.00046431606993314206,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.013081511327547536,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0022339082976504682,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.028843209870716507,"gene_effect_median":0.01954405845942203},"dependency_probability_context_minus_non_context_median":-0.0022567855655024355,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03024531035054301,"gene_effect_context_minus_non_context_median":0.020226207783525463} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 299 +- **Dependency-aware candidate rank:** 299 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e3507298a18eda64715615f3e322d67277805cadadaca2c9f73698595a9fecde` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CLPTM1L|entrez:81037` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CLTC.md b/examples/target_cards/depmap_26q1/CLTC.md new file mode 100644 index 0000000..d446d72 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CLTC.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CLTC + +## Target identity + +- **Target symbol:** CLTC +- **Target name:** clathrin heavy chain +- **Open Targets melanoma score:** 0.514 +- **Open Targets baseline rank:** 229 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 231 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 231 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 231 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.514) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CLTC lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CLTC in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.7857849350335733,"interquartile_range":0.4306299282056192,"maximum":-0.2347483018845844,"mean":-1.549072628527409,"measured_model_count":56,"median":-1.5407053756609363,"minimum":-2.506829210747692,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.355155006827954,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9948774232974522,"interquartile_range":0.0051225767025477875,"maximum":1.0,"mean":0.9698856164023175,"measured_model_count":56,"median":0.999767927569396,"minimum":0.16076082935524,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.5},{"denominator":56,"fraction":0.9464285714285714,"numerator":53,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-1.795863215137139e-05,"dependency_probability_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":-0.005439924314096567,"pan_cancer_fraction":0.9875827814569537,"threshold":0.5},{"context_fraction":0.9464285714285714,"difference":-0.021286660359508103,"pan_cancer_fraction":0.9677152317880795,"threshold":0.8}],"gene_effect_mean":0.0327071509863226,"gene_effect_median":0.04624486316265575},"dependency_probability_context_minus_non_context_median":-2.9353196633219447e-05,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":-0.005704365079365115,"non_context_fraction":0.9878472222222222,"threshold":0.5},{"context_fraction":0.9464285714285714,"difference":-0.022321428571428603,"non_context_fraction":0.96875,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03429708193704584,"gene_effect_context_minus_non_context_median":0.04997579342742209} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 231 +- **Dependency-aware candidate rank:** 231 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_7033e45925283774f8ad12f2cf22ae8953bfaf570022fc4559990370faf98b2c` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CLTC|entrez:1213` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CNOT3.md b/examples/target_cards/depmap_26q1/CNOT3.md new file mode 100644 index 0000000..2fb633d --- /dev/null +++ b/examples/target_cards/depmap_26q1/CNOT3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CNOT3 + +## Target identity + +- **Target symbol:** CNOT3 +- **Target name:** CCR4-NOT transcription complex subunit 3 +- **Open Targets melanoma score:** 0.546 +- **Open Targets baseline rank:** 168 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 170 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 171 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 170 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.546) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CNOT3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CNOT3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.8102802206023003,"interquartile_range":0.4759133947241436,"maximum":-0.8320933333393696,"mean":-1.6171401145919593,"measured_model_count":56,"median":-1.5936584691809363,"minimum":-2.6290172946051253,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.3343668258781567,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9957864519235283,"interquartile_range":0.004213548076471674,"maximum":1.0,"mean":0.9930468015225653,"measured_model_count":56,"median":0.9998302256586487,"minimum":0.8246629510819868,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00016741878021642176,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.008278145695364225,"pan_cancer_fraction":0.9917218543046358,"threshold":0.5},{"context_fraction":1.0,"difference":0.01407284768211925,"pan_cancer_fraction":0.9859271523178808,"threshold":0.8}],"gene_effect_mean":-0.04720372317674393,"gene_effect_median":-0.044002518378368105},"dependency_probability_context_minus_non_context_median":0.00018512556946592706,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.00868055555555558,"non_context_fraction":0.9913194444444444,"threshold":0.5},{"context_fraction":1.0,"difference":0.01475694444444442,"non_context_fraction":0.9852430555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.04949834860894686,"gene_effect_context_minus_non_context_median":-0.04539883321473104} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 170 +- **Dependency-aware candidate rank:** 170 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e98afc18cc10dc80ef4b4c4311d9b732c3ca08ac4cb21c1dfc1556054ea2ab8f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CNOT3|entrez:4849` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CNOT9.md b/examples/target_cards/depmap_26q1/CNOT9.md new file mode 100644 index 0000000..ad37492 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CNOT9.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CNOT9 + +## Target identity + +- **Target symbol:** CNOT9 +- **Target name:** CCR4-NOT transcription complex subunit 9 +- **Open Targets melanoma score:** 0.470 +- **Open Targets baseline rank:** 284 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 284 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 284 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 284 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.470) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CNOT9 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CNOT9 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.6980036127159327,"interquartile_range":0.4192275870718812,"maximum":0.0003976307814048674,"mean":-0.49817548218173485,"measured_model_count":56,"median":-0.4553898880376292,"minimum":-1.1718258935647998,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.2787760256440515,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.19957058817837095,"interquartile_range":0.6479136217544184,"maximum":0.9908538830614388,"mean":0.5144858160287195,"measured_model_count":56,"median":0.5364384999804481,"minimum":0.021283857638038285,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.8474842099327893,"threshold_fractions":[{"denominator":56,"fraction":0.5178571428571429,"numerator":29,"threshold":0.5},{"denominator":56,"fraction":0.30357142857142855,"numerator":17,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0546445171227149,"dependency_probability_threshold_fractions":[{"context_fraction":0.5178571428571429,"difference":-0.059957426679280945,"pan_cancer_fraction":0.5778145695364238,"threshold":0.5},{"context_fraction":0.30357142857142855,"difference":-0.007686849574266796,"pan_cancer_fraction":0.31125827814569534,"threshold":0.8}],"gene_effect_mean":0.029476910923491306,"gene_effect_median":0.05949085474867183},"dependency_probability_context_minus_non_context_median":-0.056290615104885644,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.5178571428571429,"difference":-0.06287202380952372,"non_context_fraction":0.5807291666666666,"threshold":0.5},{"context_fraction":0.30357142857142855,"difference":-0.008060515873015872,"non_context_fraction":0.3116319444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.030909816315605354,"gene_effect_context_minus_non_context_median":0.05978971492624369} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 284 +- **Dependency-aware candidate rank:** 284 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d631e042e6716d0a9f0925ecaf1901409ec38bc825ea7d82af93c7cbf2572762` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CNOT9|entrez:9125` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CREB1.md b/examples/target_cards/depmap_26q1/CREB1.md new file mode 100644 index 0000000..d1e11cf --- /dev/null +++ b/examples/target_cards/depmap_26q1/CREB1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CREB1 + +## Target identity + +- **Target symbol:** CREB1 +- **Target name:** cAMP responsive element binding protein 1 +- **Open Targets melanoma score:** 0.525 +- **Open Targets baseline rank:** 193 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 195 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 195 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 195 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.525) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CREB1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CREB1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.20042128709993842,"interquartile_range":0.20137238184885764,"maximum":0.14087319726168263,"mean":-0.10908124010337102,"measured_model_count":56,"median":-0.0970478339479603,"minimum":-0.6695722044017831,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0009510947489192074,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01905577727158126,"interquartile_range":0.09002192959362232,"maximum":0.7720182537652055,"mean":0.09194841684548548,"measured_model_count":56,"median":0.04475869080138886,"minimum":0.004161614464259778,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10907770686520359,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005796561793895302,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.01773888363292337,"pan_cancer_fraction":0.03559602649006623,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.8}],"gene_effect_mean":0.002202922419011835,"gene_effect_median":0.0008634284276914928},"dependency_probability_context_minus_non_context_median":-0.0061364271717659485,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.01860119047619048,"non_context_fraction":0.036458333333333336,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0023100089254915884,"gene_effect_context_minus_non_context_median":0.0010568504270360157} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 195 +- **Dependency-aware candidate rank:** 195 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_8080a075f5bb2d1a2544822688fc9af57849ed9288d6451bd00ab4fc5e45e00d` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CREB1|entrez:1385` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CREBBP.md b/examples/target_cards/depmap_26q1/CREBBP.md new file mode 100644 index 0000000..62e0a36 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CREBBP.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CREBBP + +## Target identity + +- **Target symbol:** CREBBP +- **Target name:** CREB binding lysine acetyltransferase +- **Open Targets melanoma score:** 0.548 +- **Open Targets baseline rank:** 163 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 165 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 166 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 165 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.548) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CREBBP lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CREBBP in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.12137022065317296,"interquartile_range":0.35378815047690215,"maximum":0.7647019650205802,"mean":0.07497423361604329,"measured_model_count":56,"median":0.12434295478017252,"minimum":-0.6954204183084232,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.23241792982372922,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0021103076008664352,"interquartile_range":0.04964725377051653,"maximum":0.8631610740408037,"mean":0.06300891143216202,"measured_model_count":56,"median":0.006852358906610696,"minimum":2.812680241471588e-07,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05175756137138296,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.026165016201327825,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.10300378429517504,"pan_cancer_fraction":0.12086092715231789,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.0500236518448439,"pan_cancer_fraction":0.06788079470198675,"threshold":0.8}],"gene_effect_mean":0.16572833559020977,"gene_effect_median":0.17318758736483686},"dependency_probability_context_minus_non_context_median":-0.027795804532297918,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.1080109126984127,"non_context_fraction":0.12586805555555555,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.052455357142857144,"non_context_fraction":0.0703125,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.17378457412584483,"gene_effect_context_minus_non_context_median":0.1796950424085603} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 165 +- **Dependency-aware candidate rank:** 165 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_493d659d4010adb81dc703190a85a90e88f05aaa7ba55c687d36265b8e22fe55` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CREBBP|entrez:1387` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CRLF2.md b/examples/target_cards/depmap_26q1/CRLF2.md new file mode 100644 index 0000000..bae3189 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CRLF2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CRLF2 + +## Target identity + +- **Target symbol:** CRLF2 +- **Target name:** cytokine receptor like factor 2 +- **Open Targets melanoma score:** 0.524 +- **Open Targets baseline rank:** 196 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 198 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 198 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 198 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.524) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CRLF2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CRLF2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** insufficient_measured_context_models +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 4 +- **Available reference observations:** 70 +- **Coverage fraction:** 0.07142857142857142 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.05632700021176619,"interquartile_range":0.08015585556302292,"maximum":0.17530677089212182,"mean":0.08935700887110595,"measured_model_count":4,"median":0.10345284711544935,"minimum":-0.024784429638596728,"missing_fraction":0.9285714285714286,"missing_model_count":52,"third_quartile":0.1364828557747891,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005030190068819156,"interquartile_range":0.004354267600952262,"maximum":0.019128257672105322,"mean":0.008512832422354143,"measured_model_count":4,"median":0.005901815316236432,"minimum":0.0031194413848383844,"missing_fraction":0.9285714285714286,"missing_model_count":52,"third_quartile":0.009384457669771418,"threshold_fractions":[{"denominator":4,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":4,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":null,"dependency_probability_threshold_fractions":[],"gene_effect_mean":null,"gene_effect_median":null},"dependency_probability_context_minus_non_context_median":null,"dependency_probability_context_minus_non_context_threshold_fractions":[],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":null,"gene_effect_context_minus_non_context_median":null} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":16,"value":26.666666666666668} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 198 +- **Dependency-aware candidate rank:** 198 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_4b22d8602f73d5a1791649888a35d40e8d5297b0bf040d2fe94dcd66ba394024` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CRLF2|entrez:64109` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CSF1R.md b/examples/target_cards/depmap_26q1/CSF1R.md new file mode 100644 index 0000000..100860b --- /dev/null +++ b/examples/target_cards/depmap_26q1/CSF1R.md @@ -0,0 +1,73 @@ +# CSF1R — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.05283149907401659,"interquartile_range":0.13328060459387842,"maximum":0.1974333024511772,"mean":0.012647423121772904,"measured_model_count":56,"median":0.016248024381766507,"minimum":-0.32563828230030123,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08044910551986181,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.011012411673845528,"interquartile_range":0.018320867883454574,"maximum":0.223657165679814,"mean":0.023988383212230846,"measured_model_count":56,"median":0.018261184417227513,"minimum":0.0026785033287129723,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.029333279557300102,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00521709253462831,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.02693273342487096,"gene_effect_median":0.027742050845867068},"dependency_probability_context_minus_non_context_median":-0.005580588241829228,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.028241963521913268,"gene_effect_context_minus_non_context_median":0.02888135390516621} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_5317881082554f3d278499aca75ba805691f06daca02ef9f17a801f642503e45` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CSF1R|entrez:1436` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CSF3R.md b/examples/target_cards/depmap_26q1/CSF3R.md new file mode 100644 index 0000000..ffb0f97 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CSF3R.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CSF3R + +## Target identity + +- **Target symbol:** CSF3R +- **Target name:** colony stimulating factor 3 receptor +- **Open Targets melanoma score:** 0.651 +- **Open Targets baseline rank:** 31 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 38 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 40 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.001 | 33 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.651) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CSF3R lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CSF3R in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.171973299240679,"interquartile_range":0.12121511297415707,"maximum":0.18391648947435318,"mean":-0.11817486019417255,"measured_model_count":56,"median":-0.1036037219983435,"minimum":-0.6312179909842395,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.050758186266521926,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.030544914905776988,"interquartile_range":0.05752607440635536,"maximum":0.6352167069178504,"mean":0.08797870213130601,"measured_model_count":56,"median":0.05600813177010951,"minimum":0.004903090995091903,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08807098931213235,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00020504580053250232,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.007095553453169347,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.005250566274807966,"gene_effect_median":0.00193246870381511},"dependency_probability_context_minus_non_context_median":-0.00020504580053250232,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.00744047619047619,"non_context_fraction":0.010416666666666666,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0055058021353889125,"gene_effect_context_minus_non_context_median":0.0021304083713885313} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 38 +- **Dependency-aware candidate rank:** 38 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_606c31d0132f1c9a0651de8053093bad951a1a810a259da1898e1f695ffcba3e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CSF3R|entrez:1441` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CTLA4.md b/examples/target_cards/depmap_26q1/CTLA4.md new file mode 100644 index 0000000..2d1eeb5 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CTLA4.md @@ -0,0 +1,139 @@ +# Target hypothesis card: CTLA4 + +## Target identity + +- **Target symbol:** CTLA4 +- **Target name:** cytotoxic T-lymphocyte associated protein 4 +- **Open Targets melanoma score:** 0.709 +- **Open Targets baseline rank:** 15 + +## Stable TargetIntel-IO classification + +- **Role classification:** anti-PD-1 combination target +- **Role confidence:** high +- **Therapeutic direction:** block / inhibit +- **Best modality:** antibody / IO-combination target +- **Resistance axis:** checkpoint_redundancy; treg_suppression +- **Matched resistance programs:** Checkpoint redundancy; Treg-mediated suppression + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.853 | 1 | high | 14 | +| Resistance biomarker | 0.524 | 6 | medium | 9 | +| Tumor-intrinsic / small molecule | 0.159 | 9 | low | 6 | + +## Evidence for + +- Immune checkpoint biology +- May support patient stratification or Treg-targeting hypotheses +- Potential compensatory inhibitory pathway after PD-1 blockade +- Relevant to immune suppression in the tumor microenvironment +- Some targets are surface-accessible +- Surface-accessible immune receptor or ligand +- High Open Targets melanoma association score (0.709) +- Maps to curated anti-PD-1 resistance program: Checkpoint redundancy; Treg-mediated suppression +- Stable role classifier confidence is high +- Antibody fit is high +- IO-combination fit is high +- Checkpoint-axis biology supports anti-PD-1 combination rationale + +## Evidence against / limitations + +- Crowded IO target space +- Expression may reflect exhausted immune-cell abundance rather than causal resistance in all tumors +- Patient selection may be required +- Requires careful distinction between biomarker and causal target +- Some markers are lineage markers rather than safe therapeutic targets +- Treg targeting can affect normal immune tolerance + +## Confidence and uncertainty + +- **Confidence level:** high confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.400 +- **Main limitation:** No major limitation flagged by current MVP rules +- **Uncertainty reason:** Moderate contradiction score indicates caution is needed | Main limitation: No major limitation flagged by current MVP rules +- **Deprioritization reason:** No strong deprioritization reason from current MVP rules + +## Recommended next validation experiment + +- **Validation category:** immune-checkpoint functional validation +- **Next experiment:** Validate CTLA4 expression in exhausted CD8 T-cell populations from anti-PD-1-resistant melanoma samples and test blockade in a melanoma/T-cell co-culture assay. +- **Rationale:** This would test whether the candidate marks a relevant checkpoint axis and whether blockade can improve anti-tumor T-cell activity. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06677599448402638,"interquartile_range":0.15253383708406643,"maximum":0.3177811729630463,"mean":0.003779328948540078,"measured_model_count":56,"median":0.005832932383737247,"minimum":-0.3866083097477906,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08575784260004005,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.007825870156587311,"interquartile_range":0.027571901541887642,"maximum":0.3372485312184015,"mean":0.036804396485517345,"measured_model_count":56,"median":0.01842904351594934,"minimum":0.0011469855891770616,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03539777169847495,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003898367006285295,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.013253178477796149,"gene_effect_median":0.01208800428615434},"dependency_probability_context_minus_non_context_median":-0.004206617757383093,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.013897430209355667,"gene_effect_context_minus_non_context_median":0.012635598331851272} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 1 +- **Dependency-aware candidate rank:** 10 +- **Rank delta:** 9 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_b9abdd2055e5117fd2a7ad81e2fb4f17c2e329c8398a2378182f948a74f80daa` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CTLA4|entrez:1493` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CTNNB1.md b/examples/target_cards/depmap_26q1/CTNNB1.md new file mode 100644 index 0000000..9a2e3d3 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CTNNB1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CTNNB1 + +## Target identity + +- **Target symbol:** CTNNB1 +- **Target name:** catenin beta 1 +- **Open Targets melanoma score:** 0.509 +- **Open Targets baseline rank:** 241 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 243 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 243 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 243 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.509) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CTNNB1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CTNNB1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.30307444434386505,"interquartile_range":0.2000363522550953,"maximum":0.05464336452334989,"mean":-0.22538887888625375,"measured_model_count":56,"median":-0.20773415732109757,"minimum":-0.7761741014319005,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.10303809208876974,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.04604754552361335,"interquartile_range":0.21650665079839038,"maximum":0.8885074947332431,"mean":0.192631362342245,"measured_model_count":56,"median":0.13451455384394487,"minimum":0.010324586920754095,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2625541963220037,"threshold_fractions":[{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.05950575769005392,"dependency_probability_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":-0.059366130558183544,"pan_cancer_fraction":0.13079470198675497,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.07071901608325448,"pan_cancer_fraction":0.08857615894039735,"threshold":0.8}],"gene_effect_mean":0.021879911950915515,"gene_effect_median":-0.06766368045703583},"dependency_probability_context_minus_non_context_median":0.06114873919813857,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":-0.06225198412698413,"non_context_fraction":0.13368055555555555,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.07415674603174605,"non_context_fraction":0.0920138888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.022943518781862793,"gene_effect_context_minus_non_context_median":-0.07173187988508836} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 243 +- **Dependency-aware candidate rank:** 243 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_cbe302602f1052761e7a090a9bec399ddec4b76049ac5315c17786ec269d72e3` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CTNNB1|entrez:1499` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CUX1.md b/examples/target_cards/depmap_26q1/CUX1.md new file mode 100644 index 0000000..abc5fde --- /dev/null +++ b/examples/target_cards/depmap_26q1/CUX1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CUX1 + +## Target identity + +- **Target symbol:** CUX1 +- **Target name:** cut like homeobox 1 +- **Open Targets melanoma score:** 0.607 +- **Open Targets baseline rank:** 60 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 64 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 66 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 64 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.607) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CUX1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CUX1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.03317565768701193,"interquartile_range":0.2361234109929508,"maximum":0.34979611804200594,"mean":0.05857234852190869,"measured_model_count":56,"median":0.04287214215173468,"minimum":-0.31298842224761375,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2029477533059389,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.003610855440009605,"interquartile_range":0.02993966487182269,"maximum":0.30936718298453664,"mean":0.03780538778138749,"measured_model_count":56,"median":0.010248060779731664,"minimum":0.00015854270563116197,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.033550520311832296,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0003123410595084891,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.8}],"gene_effect_mean":-0.023283646818891016,"gene_effect_median":-0.04264979885974313},"dependency_probability_context_minus_non_context_median":0.0003123410595084891,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.02441549076147595,"gene_effect_context_minus_non_context_median":-0.04411035860106202} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 64 +- **Dependency-aware candidate rank:** 64 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_076b62fe23db165037ade89a32df7bfdb37c19494ed249330b338d0b24a16b55` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CUX1|entrez:1523` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CXCL12.md b/examples/target_cards/depmap_26q1/CXCL12.md new file mode 100644 index 0000000..03132a9 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CXCL12.md @@ -0,0 +1,73 @@ +# CXCL12 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.07577724494448412,"interquartile_range":0.190110507410803,"maximum":0.34935751396725395,"mean":0.017638110056187435,"measured_model_count":56,"median":-0.022205827285089998,"minimum":-0.3095502799648677,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11433326246631886,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.006556502005797096,"interquartile_range":0.03252096833817649,"maximum":0.21923669386606784,"mean":0.03273003379914769,"measured_model_count":56,"median":0.020696994642275326,"minimum":0.00042313838806690856,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03907747034397359,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00550717310759696,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.045236190025914044,"gene_effect_median":-0.00010726319640060392},"dependency_probability_context_minus_non_context_median":-0.005690951872236477,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04743517148550706,"gene_effect_context_minus_non_context_median":-0.00019117609302459967} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_5f75942ca13b5b7cc81ccc05fbdf4fc8532ad5012a3ab697f6d0e86a9640a499` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CXCL12|entrez:6387` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CXCL9.md b/examples/target_cards/depmap_26q1/CXCL9.md new file mode 100644 index 0000000..4f4e8b9 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CXCL9.md @@ -0,0 +1,73 @@ +# CXCL9 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.03134505628584463,"interquartile_range":0.14056117568087112,"maximum":0.24029992912418896,"mean":0.04110868821178555,"measured_model_count":56,"median":0.05281410370015513,"minimum":-0.21141841880282625,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10921611939502648,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.00658768123852596,"interquartile_range":0.022355271394094645,"maximum":0.10831268763368852,"mean":0.0204631377324164,"measured_model_count":56,"median":0.012647935195006565,"minimum":0.001717118643636866,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.028942952632620606,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-9.538839180254707e-05,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.013954215585890863,"gene_effect_median":-0.0025869928644431245},"dependency_probability_context_minus_non_context_median":-9.538839180254707e-05,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.014632545510205,"gene_effect_context_minus_non_context_median":-0.0028313770175858455} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_753bc049b92ea8d1d3491362437565283681da2bf359811b7a35d70d20308ed0` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CXCL9|entrez:4283` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CXCR4.md b/examples/target_cards/depmap_26q1/CXCR4.md new file mode 100644 index 0000000..268344a --- /dev/null +++ b/examples/target_cards/depmap_26q1/CXCR4.md @@ -0,0 +1,73 @@ +# CXCR4 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.0002591435523185224,"interquartile_range":0.10501169832073538,"maximum":0.3673246231079541,"mean":0.05559721646707475,"measured_model_count":56,"median":0.05891644317724552,"minimum":-0.20885269756363484,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10527084187305391,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.006540828823287489,"interquartile_range":0.015723870922962044,"maximum":0.08216220534230984,"mean":0.016496695055018395,"measured_model_count":56,"median":0.012532064623048806,"minimum":0.0009317497895514716,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.022264699746249533,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002805419479474677,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.015668202208521706,"gene_effect_median":0.022358444411732868},"dependency_probability_context_minus_non_context_median":-0.00296975485108379,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.016429850926991514,"gene_effect_context_minus_non_context_median":0.02340116280440281} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_27167cd30fdf604ddec8ac3ca343fd18cbcf0ad4da47feb76041b7c691590b39` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CXCR4|entrez:7852` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CYLD.md b/examples/target_cards/depmap_26q1/CYLD.md new file mode 100644 index 0000000..6d9cfd8 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CYLD.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CYLD + +## Target identity + +- **Target symbol:** CYLD +- **Target name:** CYLD lysine 63 deubiquitinase +- **Open Targets melanoma score:** 0.580 +- **Open Targets baseline rank:** 102 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 105 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 106 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 105 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.580) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CYLD lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CYLD in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.16691152028267855,"interquartile_range":0.19889307085090385,"maximum":0.4122109349705019,"mean":-0.06497487104668735,"measured_model_count":56,"median":-0.08653479539938982,"minimum":-0.4925174203145259,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03198155056822531,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.016821912273541333,"interquartile_range":0.07211093367154234,"maximum":0.5035553746667468,"mean":0.07855783986616326,"measured_model_count":56,"median":0.04655640165652187,"minimum":0.0004562974591991458,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08893284594508367,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004043674105023709,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.010288552507095556,"pan_cancer_fraction":0.028145695364238412,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":0.043755948689382956,"gene_effect_median":0.008757544410644177},"dependency_probability_context_minus_non_context_median":-0.004206455521640895,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.010788690476190476,"non_context_fraction":0.028645833333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04588297397289473,"gene_effect_context_minus_non_context_median":0.009368028928493657} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 105 +- **Dependency-aware candidate rank:** 105 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_8af65338931f6fdd6b4ac209b6cf1b5ed61453c68b152a6d1f252e5336eedd12` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CYLD|entrez:1540` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/CYP1B1.md b/examples/target_cards/depmap_26q1/CYP1B1.md new file mode 100644 index 0000000..5efffa0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/CYP1B1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: CYP1B1 + +## Target identity + +- **Target symbol:** CYP1B1 +- **Target name:** cytochrome P450 family 1 subfamily B member 1 +- **Open Targets melanoma score:** 0.563 +- **Open Targets baseline rank:** 129 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 131 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 132 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 131 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.563) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** CYP1B1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for CYP1B1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.03368777508498383,"interquartile_range":0.13687684126148855,"maximum":0.47048455575590914,"mean":0.08384933870127811,"measured_model_count":56,"median":0.09166972667834505,"minimum":-0.37744433712582043,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.17056461634647238,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0037660000533670107,"interquartile_range":0.01510846197304637,"maximum":0.2633327191464861,"mean":0.022453628011962906,"measured_model_count":56,"median":0.008242491577905423,"minimum":0.00022499114610257485,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.01887446202641338,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002526088889266493,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.009384434653959994,"gene_effect_median":0.01423679476823242},"dependency_probability_context_minus_non_context_median":-0.0027784546294805316,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.009840622449638611,"gene_effect_context_minus_non_context_median":0.014620556398485474} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 131 +- **Dependency-aware candidate rank:** 131 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_6b6dc01d1037ab7588d7507b59b5873c424dd60af50ef2b9f1b9cccf7f170b36` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:CYP1B1|entrez:1545` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/DAXX.md b/examples/target_cards/depmap_26q1/DAXX.md new file mode 100644 index 0000000..e59fc91 --- /dev/null +++ b/examples/target_cards/depmap_26q1/DAXX.md @@ -0,0 +1,124 @@ +# Target hypothesis card: DAXX + +## Target identity + +- **Target symbol:** DAXX +- **Target name:** death domain associated protein +- **Open Targets melanoma score:** 0.550 +- **Open Targets baseline rank:** 157 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 159 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 160 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 159 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.550) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** DAXX lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for DAXX in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.544977811841365,"interquartile_range":0.26742254574989294,"maximum":0.106113115533227,"mean":-0.4087807091327999,"measured_model_count":56,"median":-0.383732915488141,"minimum":-1.3662485543529452,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.277555266091472,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.21600580895105526,"interquartile_range":0.40819467544094223,"maximum":0.9983879181677233,"mean":0.42374344131493585,"measured_model_count":56,"median":0.4007934163278375,"minimum":0.006374091952721311,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.6242004843919975,"threshold_fractions":[{"denominator":56,"fraction":0.42857142857142855,"numerator":24,"threshold":0.5},{"denominator":56,"fraction":0.10714285714285714,"numerator":6,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.11380922710420216,"dependency_probability_threshold_fractions":[{"context_fraction":0.42857142857142855,"difference":0.12310785241248817,"pan_cancer_fraction":0.3054635761589404,"threshold":0.5},{"context_fraction":0.10714285714285714,"difference":-0.023651844843897832,"pan_cancer_fraction":0.13079470198675497,"threshold":0.8}],"gene_effect_mean":-0.03430155764609022,"gene_effect_median":-0.053760835452685674},"dependency_probability_context_minus_non_context_median":0.12201466100433733,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.42857142857142855,"difference":0.12909226190476186,"non_context_fraction":0.2994791666666667,"threshold":0.5},{"context_fraction":0.10714285714285714,"difference":-0.02480158730158731,"non_context_fraction":0.13194444444444445,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03596899447610846,"gene_effect_context_minus_non_context_median":-0.05591574640915642} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 159 +- **Dependency-aware candidate rank:** 159 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_afbc3bdc67a8e0dc3c3f194456eb04569c7ead987c1059a681ade7cf4eb260f3` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:DAXX|entrez:1616` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/DDR2.md b/examples/target_cards/depmap_26q1/DDR2.md new file mode 100644 index 0000000..8d4e755 --- /dev/null +++ b/examples/target_cards/depmap_26q1/DDR2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: DDR2 + +## Target identity + +- **Target symbol:** DDR2 +- **Target name:** discoidin domain receptor tyrosine kinase 2 +- **Open Targets melanoma score:** 0.569 +- **Open Targets baseline rank:** 119 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 121 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 122 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 121 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.569) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** DDR2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for DDR2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06972286446924252,"interquartile_range":0.1045132250182792,"maximum":0.2898346836075851,"mean":-0.014019195812266821,"measured_model_count":56,"median":-0.020729125875991173,"minimum":-0.23140278730236627,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.034790360549036684,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.014961917782642614,"interquartile_range":0.02193127226654084,"maximum":0.19539254739293155,"mean":0.03367981023215328,"measured_model_count":56,"median":0.022905507258844444,"minimum":0.0015916488853983351,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.036893190049183455,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004563261403949671,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.012800079573396912,"gene_effect_median":0.0036931926323622195},"dependency_probability_context_minus_non_context_median":-0.004778792064880334,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.013422305663770409,"gene_effect_context_minus_non_context_median":0.004263007062741037} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 121 +- **Dependency-aware candidate rank:** 121 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ef9206a1ce724e78d8c1aa27d8eb08bca4a2756bcf0378d4bba36777bcb8c874` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:DDR2|entrez:4921` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/DDX3X.md b/examples/target_cards/depmap_26q1/DDX3X.md new file mode 100644 index 0000000..90bc331 --- /dev/null +++ b/examples/target_cards/depmap_26q1/DDX3X.md @@ -0,0 +1,124 @@ +# Target hypothesis card: DDX3X + +## Target identity + +- **Target symbol:** DDX3X +- **Target name:** DEAD-box helicase 3 X-linked +- **Open Targets melanoma score:** 0.641 +- **Open Targets baseline rank:** 35 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 42 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 44 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 42 | not prioritized | -7 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.641) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** DDX3X lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for DDX3X in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.9698286536882877,"interquartile_range":0.7569406323261909,"maximum":0.3339853718118322,"mean":-0.6088234854143035,"measured_model_count":56,"median":-0.6607130262900589,"minimum":-2.0147135010407675,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.21288802136209684,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.14926781403958722,"interquartile_range":0.8089440313140834,"maximum":1.0,"mean":0.6154656913017502,"measured_model_count":56,"median":0.7872151954624422,"minimum":0.001289807589254826,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9582118453536707,"threshold_fractions":[{"denominator":56,"fraction":0.6785714285714286,"numerator":38,"threshold":0.5},{"denominator":56,"fraction":0.5,"numerator":28,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.16685803865653503,"dependency_probability_threshold_fractions":[{"context_fraction":0.6785714285714286,"difference":-0.10040208136234618,"pan_cancer_fraction":0.7789735099337748,"threshold":0.5},{"context_fraction":0.5,"difference":-0.20281456953642385,"pan_cancer_fraction":0.7028145695364238,"threshold":0.8}],"gene_effect_mean":0.2318562995522585,"gene_effect_median":0.24842949495470001},"dependency_probability_context_minus_non_context_median":-0.1700928838399589,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.6785714285714286,"difference":-0.10528273809523803,"non_context_fraction":0.7838541666666666,"threshold":0.5},{"context_fraction":0.5,"difference":-0.21267361111111116,"non_context_fraction":0.7126736111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.24312709189160442,"gene_effect_context_minus_non_context_median":0.2597624582856295} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 42 +- **Dependency-aware candidate rank:** 42 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_58b097ef5c176fce070a148275373b6687240d855387f464238a649fbf198364` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:DDX3X|entrez:1654` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/DICER1.md b/examples/target_cards/depmap_26q1/DICER1.md new file mode 100644 index 0000000..0397a6a --- /dev/null +++ b/examples/target_cards/depmap_26q1/DICER1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: DICER1 + +## Target identity + +- **Target symbol:** DICER1 +- **Target name:** dicer 1, ribonuclease III +- **Open Targets melanoma score:** 0.616 +- **Open Targets baseline rank:** 52 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 57 | not prioritized | -5 | +| Resistance biomarker | 0.000 | 59 | not prioritized | -7 | +| Tumor-intrinsic / small molecule | 0.000 | 57 | not prioritized | -5 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.616) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** DICER1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for DICER1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.7994467283841284,"interquartile_range":0.30023678430572287,"maximum":0.13013407460107784,"mean":-0.6305602766259601,"measured_model_count":56,"median":-0.6573228251847951,"minimum":-1.2712552972640037,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.4992099440784056,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.5721275138636308,"interquartile_range":0.35380378565895265,"maximum":0.9952544360565102,"mean":0.6998550174732641,"measured_model_count":56,"median":0.8229355663334141,"minimum":0.006706062225289876,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9259312995225835,"threshold_fractions":[{"denominator":56,"fraction":0.7678571428571429,"numerator":43,"threshold":0.5},{"denominator":56,"fraction":0.5178571428571429,"numerator":29,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.17199606447334514,"dependency_probability_threshold_fractions":[{"context_fraction":0.7678571428571429,"difference":0.15610217596972564,"pan_cancer_fraction":0.6117549668874173,"threshold":0.5},{"context_fraction":0.5178571428571429,"difference":0.16189687795648067,"pan_cancer_fraction":0.35596026490066224,"threshold":0.8}],"gene_effect_mean":-0.08784562065277612,"gene_effect_median":-0.11679075840874076},"dependency_probability_context_minus_non_context_median":0.17636754028478918,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.7678571428571429,"difference":0.16369047619047628,"non_context_fraction":0.6041666666666666,"threshold":0.5},{"context_fraction":0.5178571428571429,"difference":0.16976686507936511,"non_context_fraction":0.3480902777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.09211589387895269,"gene_effect_context_minus_non_context_median":-0.12397328735897672} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 57 +- **Dependency-aware candidate rank:** 57 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_484de98defbe0cf173c2e8ba861a01993a059d3ccc346631c08ef0a1fd43c647` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:DICER1|entrez:23405` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/DNMT3A.md b/examples/target_cards/depmap_26q1/DNMT3A.md new file mode 100644 index 0000000..1dd6a4f --- /dev/null +++ b/examples/target_cards/depmap_26q1/DNMT3A.md @@ -0,0 +1,124 @@ +# Target hypothesis card: DNMT3A + +## Target identity + +- **Target symbol:** DNMT3A +- **Target name:** DNA methyltransferase 3 alpha +- **Open Targets melanoma score:** 0.581 +- **Open Targets baseline rank:** 97 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 100 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 101 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 100 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.581) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** DNMT3A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for DNMT3A in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.1244767471160199,"interquartile_range":0.11774663236443546,"maximum":0.6310082394813034,"mean":0.18192937029876807,"measured_model_count":56,"median":0.18235534714872575,"minimum":-0.18603726549592337,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.24222337948045536,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0018838619254996766,"interquartile_range":0.005556895059722717,"maximum":0.08869695724474873,"mean":0.007644426594225991,"measured_model_count":56,"median":0.0035343347073587836,"minimum":1.1862181692386457e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.007440756985222394,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0011400640495491015,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.010599921784739702,"gene_effect_median":0.012843073103306124},"dependency_probability_context_minus_non_context_median":-0.0011569302952267454,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01111519576038672,"gene_effect_context_minus_non_context_median":0.01322258993081063} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 100 +- **Dependency-aware candidate rank:** 100 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_be96e5150bdb496a7a39bcddbb88ac108797d06217f8197f24f78df1d9a2da48` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:DNMT3A|entrez:1788` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/EGFR.md b/examples/target_cards/depmap_26q1/EGFR.md new file mode 100644 index 0000000..19a0228 --- /dev/null +++ b/examples/target_cards/depmap_26q1/EGFR.md @@ -0,0 +1,124 @@ +# Target hypothesis card: EGFR + +## Target identity + +- **Target symbol:** EGFR +- **Target name:** epidermal growth factor receptor +- **Open Targets melanoma score:** 0.524 +- **Open Targets baseline rank:** 195 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 197 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 197 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 197 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.524) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** EGFR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for EGFR in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.17742898304365823,"interquartile_range":0.2395414323145233,"maximum":0.2660120139862773,"mean":-0.0768374949690435,"measured_model_count":56,"median":-0.08543314878433285,"minimum":-0.46622495115702955,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06211244927086508,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.013536831847736476,"interquartile_range":0.07782264300434415,"maximum":0.5606370090600415,"mean":0.08069588416595065,"measured_model_count":56,"median":0.05061839110667351,"minimum":0.0011475887843435738,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09135947485208062,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.012226944748200914,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.1717123935666982,"pan_cancer_fraction":0.18956953642384106,"threshold":0.5},{"context_fraction":0.0,"difference":-0.1183774834437086,"pan_cancer_fraction":0.1183774834437086,"threshold":0.8}],"gene_effect_mean":0.16048959750885244,"gene_effect_median":0.044865508404849666},"dependency_probability_context_minus_non_context_median":-0.01360040995761299,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.1800595238095238,"non_context_fraction":0.19791666666666666,"threshold":0.5},{"context_fraction":0.0,"difference":-0.12413194444444445,"non_context_fraction":0.12413194444444445,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.1682911751655326,"gene_effect_context_minus_non_context_median":0.047549781624125445} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 197 +- **Dependency-aware candidate rank:** 197 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2a70c9fd5fa9ed272df4bd2dc91722b65ce1a817cbd085b025dddcb62acc94ad` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:EGFR|entrez:1956` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ENTPD1.md b/examples/target_cards/depmap_26q1/ENTPD1.md new file mode 100644 index 0000000..8e9e8d0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ENTPD1.md @@ -0,0 +1,73 @@ +# ENTPD1 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.017204446642615827,"interquartile_range":0.10523556299931044,"maximum":0.32256544354857597,"mean":0.03613007161465716,"measured_model_count":56,"median":0.03958058875364162,"minimum":-0.17214377639477035,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08803111635669461,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008971876754590337,"interquartile_range":0.015497793480308062,"maximum":0.08656995332646747,"mean":0.020822634312535802,"measured_model_count":56,"median":0.014386164975697509,"minimum":0.0010515004995813155,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.024469670234898398,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00036529600012544065,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.005500676522773799,"gene_effect_median":-0.0019880259017703017},"dependency_probability_context_minus_non_context_median":-0.00046668099051278347,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.005768070520408633,"gene_effect_context_minus_non_context_median":-0.002175443103434427} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_88a4ac5fab879425f2d36cb78f6cca0d2a9303f47e26440d3fbf5d29ffdb0c4c` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ENTPD1|entrez:953` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/EP300.md b/examples/target_cards/depmap_26q1/EP300.md new file mode 100644 index 0000000..a68b9a6 --- /dev/null +++ b/examples/target_cards/depmap_26q1/EP300.md @@ -0,0 +1,124 @@ +# Target hypothesis card: EP300 + +## Target identity + +- **Target symbol:** EP300 +- **Target name:** EP300 lysine acetyltransferase +- **Open Targets melanoma score:** 0.605 +- **Open Targets baseline rank:** 62 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 66 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 68 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 66 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.605) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** EP300 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for EP300 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.6301650470635833,"interquartile_range":0.4709206521961253,"maximum":0.44756105949178754,"mean":-0.3907983166708622,"measured_model_count":56,"median":-0.3520231118620166,"minimum":-1.34610578400845,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.15924439486745806,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0690136792815241,"interquartile_range":0.6549061339214883,"maximum":0.994735297730019,"mean":0.4060882923478336,"measured_model_count":56,"median":0.30719246495550195,"minimum":0.00014797171299792128,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.7239198132030125,"threshold_fractions":[{"denominator":56,"fraction":0.375,"numerator":21,"threshold":0.5},{"denominator":56,"fraction":0.23214285714285715,"numerator":13,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.04992797303338542,"dependency_probability_threshold_fractions":[{"context_fraction":0.375,"difference":0.01572847682119205,"pan_cancer_fraction":0.35927152317880795,"threshold":0.5},{"context_fraction":0.23214285714285715,"difference":0.009460737937559138,"pan_cancer_fraction":0.222682119205298,"threshold":0.8}],"gene_effect_mean":-0.03225721062927511,"gene_effect_median":-0.03480287000380533},"dependency_probability_context_minus_non_context_median":0.05588253082748845,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.375,"difference":0.01649305555555558,"non_context_fraction":0.3585069444444444,"threshold":0.5},{"context_fraction":0.23214285714285715,"difference":0.009920634920634941,"non_context_fraction":0.2222222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03382526947930953,"gene_effect_context_minus_non_context_median":-0.03827708333683888} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 66 +- **Dependency-aware candidate rank:** 66 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_c8bf2b0a53226f54571eef5bd76eb44fbcf366497efff6c0d571a380adae1a6e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:EP300|entrez:2033` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ERBB2.md b/examples/target_cards/depmap_26q1/ERBB2.md new file mode 100644 index 0000000..626e9c8 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ERBB2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ERBB2 + +## Target identity + +- **Target symbol:** ERBB2 +- **Target name:** erb-b2 receptor tyrosine kinase 2 +- **Open Targets melanoma score:** 0.603 +- **Open Targets baseline rank:** 67 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 71 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 73 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 71 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.603) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ERBB2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ERBB2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.33467527164131333,"interquartile_range":0.14828615220047953,"maximum":0.04056593393173724,"mean":-0.26561967130517056,"measured_model_count":56,"median":-0.246206895071223,"minimum":-0.5119897770568183,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.1863891194408338,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.10583038909718276,"interquartile_range":0.14106667753996144,"maximum":0.669070278252544,"mean":0.21661886597937663,"measured_model_count":56,"median":0.1734088090428273,"minimum":0.011341833442620627,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2468970666371442,"threshold_fractions":[{"denominator":56,"fraction":0.10714285714285714,"numerator":6,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.02793739386262034,"dependency_probability_threshold_fractions":[{"context_fraction":0.10714285714285714,"difference":-0.09401608325449386,"pan_cancer_fraction":0.201158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.09850993377483444,"pan_cancer_fraction":0.09850993377483444,"threshold":0.8}],"gene_effect_mean":0.08925720783764057,"gene_effect_median":0.029340983554862532},"dependency_probability_context_minus_non_context_median":-0.03211618750590295,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.10714285714285714,"difference":-0.09858630952380952,"non_context_fraction":0.20572916666666666,"threshold":0.5},{"context_fraction":0.0,"difference":-0.1032986111111111,"non_context_fraction":0.1032986111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.09359609988530393,"gene_effect_context_minus_non_context_median":0.03032500080514161} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 71 +- **Dependency-aware candidate rank:** 71 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_85651a2e1e5fccdaa36943dabfc67d700562e875d4bb8301e0ebc7d1a2db6f88` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ERBB2|entrez:2064` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ERBB3.md b/examples/target_cards/depmap_26q1/ERBB3.md new file mode 100644 index 0000000..97d6ca7 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ERBB3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ERBB3 + +## Target identity + +- **Target symbol:** ERBB3 +- **Target name:** erb-b2 receptor tyrosine kinase 3 +- **Open Targets melanoma score:** 0.587 +- **Open Targets baseline rank:** 88 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 91 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 93 | not prioritized | -5 | +| Tumor-intrinsic / small molecule | 0.000 | 91 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.587) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ERBB3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ERBB3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.29677275810467674,"interquartile_range":0.15902387121322126,"maximum":0.10539895655935005,"mean":-0.2172892726108315,"measured_model_count":56,"median":-0.2064135944999752,"minimum":-0.5667130081211204,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.13774888689145548,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0701533166345286,"interquartile_range":0.14491007038238968,"maximum":0.6026137920472711,"mean":0.16367057810715754,"measured_model_count":56,"median":0.13126533178718724,"minimum":0.01069996622191269,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2150633870169183,"threshold_fractions":[{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.04329157941874143,"dependency_probability_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":-0.01963103122043519,"pan_cancer_fraction":0.09105960264900662,"threshold":0.5},{"context_fraction":0.0,"difference":-0.046357615894039736,"pan_cancer_fraction":0.046357615894039736,"threshold":0.8}],"gene_effect_mean":-0.010919738131060064,"gene_effect_median":-0.0461099890637964},"dependency_probability_context_minus_non_context_median":0.045517050458931174,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":-0.02058531746031747,"non_context_fraction":0.0920138888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.04861111111111111,"non_context_fraction":0.04861111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.011450558734653199,"gene_effect_context_minus_non_context_median":-0.047486382929025794} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 91 +- **Dependency-aware candidate rank:** 91 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_509bf22e2f5a6168ef36638c1f2838b26bc131fd72532af852051a66541ee1a9` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ERBB3|entrez:2065` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ERBB4.md b/examples/target_cards/depmap_26q1/ERBB4.md new file mode 100644 index 0000000..7225d37 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ERBB4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ERBB4 + +## Target identity + +- **Target symbol:** ERBB4 +- **Target name:** erb-b2 receptor tyrosine kinase 4 +- **Open Targets melanoma score:** 0.634 +- **Open Targets baseline rank:** 40 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 47 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 49 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 47 | not prioritized | -7 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.634) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ERBB4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ERBB4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.14569118463855116,"interquartile_range":0.14276472370214452,"maximum":0.22026504101142866,"mean":-0.0806414136689627,"measured_model_count":56,"median":-0.08133237680604319,"minimum":-0.5111124546060511,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.002926460936406628,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.022843399052722917,"interquartile_range":0.053439931630912645,"maximum":0.4447439005088343,"mean":0.06866226929506587,"measured_model_count":56,"median":0.04663575266879736,"minimum":0.0026245223564960677,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07628333068363556,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0028838586732600827,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.003982051068016801,"gene_effect_median":-0.0012821078178077983},"dependency_probability_context_minus_non_context_median":0.0029295309373640263,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.004175622994934278,"gene_effect_context_minus_non_context_median":-0.0016777736254505182} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 47 +- **Dependency-aware candidate rank:** 47 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_dbbab5a67067b1bda4c70eb8973b159c25141dc1be365953b465c06acb38ae9f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ERBB4|entrez:2066` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ERCC2.md b/examples/target_cards/depmap_26q1/ERCC2.md new file mode 100644 index 0000000..3006693 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ERCC2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ERCC2 + +## Target identity + +- **Target symbol:** ERCC2 +- **Target name:** ERCC excision repair 2, TFIIH core complex helicase subunit +- **Open Targets melanoma score:** 0.579 +- **Open Targets baseline rank:** 104 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 107 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 108 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 107 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.579) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ERCC2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ERCC2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.0497755608773027,"interquartile_range":0.3813255384814084,"maximum":-0.16396640750377933,"mean":-0.8559048256834219,"measured_model_count":56,"median":-0.8344001265829372,"minimum":-1.6026495241794065,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.6684500223958943,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.7685887429345672,"interquartile_range":0.21456944658217048,"maximum":0.9999142385164158,"mean":0.8514767156342421,"measured_model_count":56,"median":0.9417257675715691,"minimum":0.12430696530259147,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9831581895167377,"threshold_fractions":[{"denominator":56,"fraction":0.9285714285714286,"numerator":52,"threshold":0.5},{"denominator":56,"fraction":0.7321428571428571,"numerator":41,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.031116564543193448,"dependency_probability_threshold_fractions":[{"context_fraction":0.9285714285714286,"difference":-0.019276253547776734,"pan_cancer_fraction":0.9478476821192053,"threshold":0.5},{"context_fraction":0.7321428571428571,"difference":-0.11967833491012303,"pan_cancer_fraction":0.8518211920529801,"threshold":0.8}],"gene_effect_mean":0.15736689035266194,"gene_effect_median":0.17219872117991863},"dependency_probability_context_minus_non_context_median":-0.032439978921928736,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9285714285714286,"difference":-0.020213293650793607,"non_context_fraction":0.9487847222222222,"threshold":0.5},{"context_fraction":0.7321428571428571,"difference":-0.12549603174603174,"non_context_fraction":0.8576388888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.1650166697448061,"gene_effect_context_minus_non_context_median":0.18209450243057768} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 107 +- **Dependency-aware candidate rank:** 107 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d2cc074964cf9c696a455e5924e2651a866708047ef2f12e243dd4c04fa06084` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ERCC2|entrez:2068` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ERCC3.md b/examples/target_cards/depmap_26q1/ERCC3.md new file mode 100644 index 0000000..e066110 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ERCC3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ERCC3 + +## Target identity + +- **Target symbol:** ERCC3 +- **Target name:** ERCC excision repair 3, TFIIH core complex helicase subunit +- **Open Targets melanoma score:** 0.551 +- **Open Targets baseline rank:** 155 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 157 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 158 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 157 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.551) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ERCC3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ERCC3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.1181967186257906,"interquartile_range":0.21936811054409455,"maximum":-0.1968165974284698,"mean":-0.9861971850757215,"measured_model_count":56,"median":-1.0257305946001085,"minimum":-1.2003431761784857,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.8988286080816961,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9546022888982366,"interquartile_range":0.035122029420819545,"maximum":0.9976916871199579,"mean":0.9395766573450544,"measured_model_count":56,"median":0.9767427569343496,"minimum":0.15568980756884207,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9897243183190562,"threshold_fractions":[{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.5},{"denominator":56,"fraction":0.9642857142857143,"numerator":54,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.002812007009274531,"dependency_probability_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":0.002838221381267658,"pan_cancer_fraction":0.9793046357615894,"threshold":0.5},{"context_fraction":0.9642857142857143,"difference":0.033822138126773926,"pan_cancer_fraction":0.9304635761589404,"threshold":0.8}],"gene_effect_mean":0.03186839973649114,"gene_effect_median":-0.01496544170922709},"dependency_probability_context_minus_non_context_median":0.002916995705352421,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":0.0029761904761904656,"non_context_fraction":0.9791666666666666,"threshold":0.5},{"context_fraction":0.9642857142857143,"difference":0.03546626984126988,"non_context_fraction":0.9288194444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03341755805701585,"gene_effect_context_minus_non_context_median":-0.01579770104131084} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 157 +- **Dependency-aware candidate rank:** 157 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_151ac710b13364d64e7de307056de35149a8a93d487fef97333dfa698f138881` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ERCC3|entrez:2071` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ERCC4.md b/examples/target_cards/depmap_26q1/ERCC4.md new file mode 100644 index 0000000..abe04ed --- /dev/null +++ b/examples/target_cards/depmap_26q1/ERCC4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ERCC4 + +## Target identity + +- **Target symbol:** ERCC4 +- **Target name:** ERCC excision repair 4, endonuclease catalytic subunit +- **Open Targets melanoma score:** 0.543 +- **Open Targets baseline rank:** 173 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 175 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 176 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 175 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.543) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ERCC4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ERCC4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.3854903365144424,"interquartile_range":0.21652135195847766,"maximum":0.001120471494265196,"mean":-0.2899236303985298,"measured_model_count":56,"median":-0.312962794264828,"minimum":-0.5607238476333932,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.16896898455596476,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.09450249828397053,"interquartile_range":0.2539646020376588,"maximum":0.6497895426015371,"mean":0.2577241034021173,"measured_model_count":56,"median":0.25032416264247376,"minimum":0.020314845019689234,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.3484671003216293,"threshold_fractions":[{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03807707323341175,"dependency_probability_threshold_fractions":[{"context_fraction":0.16071428571428573,"difference":-0.042100283822138124,"pan_cancer_fraction":0.20281456953642385,"threshold":0.5},{"context_fraction":0.0,"difference":-0.054635761589403975,"pan_cancer_fraction":0.054635761589403975,"threshold":0.8}],"gene_effect_mean":0.018671101005857837,"gene_effect_median":-0.029595103502446873},"dependency_probability_context_minus_non_context_median":0.03978289177958286,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.16071428571428573,"difference":-0.04414682539682538,"non_context_fraction":0.2048611111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.057291666666666664,"non_context_fraction":0.057291666666666664,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01957872397142002,"gene_effect_context_minus_non_context_median":-0.03036033876069405} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 175 +- **Dependency-aware candidate rank:** 175 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_57fa3f79c563d7d8a27b411a7849e95077a7642f56919c9aede4ab6df25e0823` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ERCC4|entrez:2072` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ERCC5.md b/examples/target_cards/depmap_26q1/ERCC5.md new file mode 100644 index 0000000..9bbd814 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ERCC5.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ERCC5 + +## Target identity + +- **Target symbol:** ERCC5 +- **Target name:** ERCC excision repair 5, endonuclease +- **Open Targets melanoma score:** 0.544 +- **Open Targets baseline rank:** 172 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 174 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 175 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 174 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.544) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ERCC5 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ERCC5 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.04519528389004527,"interquartile_range":0.11019899927943605,"maximum":0.2710955571001969,"mean":0.005332502631850874,"measured_model_count":56,"median":0.02281300196535606,"minimum":-0.23518481053140836,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06500371538939079,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008780224985984577,"interquartile_range":0.031486563305523046,"maximum":0.10076459232175562,"mean":0.02723915059114595,"measured_model_count":56,"median":0.016749164858456053,"minimum":0.001704687039870745,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04026678829150762,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003982939681521677,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.0066125493202115315,"gene_effect_median":0.017344755611254512},"dependency_probability_context_minus_non_context_median":-0.004170855462812619,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006933992689944074,"gene_effect_context_minus_non_context_median":0.018058575388758574} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 174 +- **Dependency-aware candidate rank:** 174 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_cd975ed15f92798c752dcfdd13992481eab535c9fb742417e8abfc29c552e0f5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ERCC5|entrez:2073` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ESR1.md b/examples/target_cards/depmap_26q1/ESR1.md new file mode 100644 index 0000000..8a8f99c --- /dev/null +++ b/examples/target_cards/depmap_26q1/ESR1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ESR1 + +## Target identity + +- **Target symbol:** ESR1 +- **Target name:** estrogen receptor 1 +- **Open Targets melanoma score:** 0.604 +- **Open Targets baseline rank:** 63 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 67 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 69 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 67 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.604) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ESR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ESR1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.0848593775445727,"interquartile_range":0.13395979595344146,"maximum":0.23922527191565976,"mean":-0.0185218839167705,"measured_model_count":56,"median":-0.00802662620138481,"minimum":-0.3259164362790145,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.049100418408868744,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.012130319443407039,"interquartile_range":0.026440137649247547,"maximum":0.2259091707228821,"mean":0.035293228110319055,"measured_model_count":56,"median":0.02133572171212511,"minimum":0.0024119361921403825,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03857045709265459,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.008278000718975553,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.014072847682119206,"pan_cancer_fraction":0.014072847682119206,"threshold":0.5},{"context_fraction":0.0,"difference":-0.009933774834437087,"pan_cancer_fraction":0.009933774834437087,"threshold":0.8}],"gene_effect_mean":0.03441010632648146,"gene_effect_median":0.02581490859934631},"dependency_probability_context_minus_non_context_median":-0.00880314421140762,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.014756944444444444,"non_context_fraction":0.014756944444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.010416666666666666,"non_context_fraction":0.010416666666666666,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.036082819828463245,"gene_effect_context_minus_non_context_median":0.027045767506139604} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 67 +- **Dependency-aware candidate rank:** 67 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_943c2846124ca99709520b41b23aeb5ee539b8889a9bb74af925a517bb5ae317` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ESR1|entrez:2099` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/EZH2.md b/examples/target_cards/depmap_26q1/EZH2.md new file mode 100644 index 0000000..d57a96a --- /dev/null +++ b/examples/target_cards/depmap_26q1/EZH2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: EZH2 + +## Target identity + +- **Target symbol:** EZH2 +- **Target name:** enhancer of zeste 2 polycomb repressive complex 2 subunit +- **Open Targets melanoma score:** 0.533 +- **Open Targets baseline rank:** 183 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 185 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 186 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 185 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.533) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** EZH2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for EZH2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.05304773802010125,"interquartile_range":0.19476652921775417,"maximum":0.4109850863433474,"mean":0.0257700942153801,"measured_model_count":56,"median":0.0320485927146671,"minimum":-0.41701781626943923,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14171879119765293,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005567747692544567,"interquartile_range":0.02796596898671179,"maximum":0.38625828574385734,"mean":0.04412555204592233,"measured_model_count":56,"median":0.01521772005739586,"minimum":0.000795920235174292,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03353371667925636,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.009458068922002603,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0802980132450331,"pan_cancer_fraction":0.0802980132450331,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0347682119205298,"pan_cancer_fraction":0.0347682119205298,"threshold":0.8}],"gene_effect_mean":0.07476884614085007,"gene_effect_median":0.04611516268565478},"dependency_probability_context_minus_non_context_median":-0.009962040930500026,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0842013888888889,"non_context_fraction":0.0842013888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.036458333333333336,"non_context_fraction":0.036458333333333336,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.07840344282825268,"gene_effect_context_minus_non_context_median":0.04820298946438911} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 185 +- **Dependency-aware candidate rank:** 185 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_89fc6cbae49797355a70fb88c5eb89bea1500b53bf61770ee522b8d4175b525c` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:EZH2|entrez:2146` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FANCA.md b/examples/target_cards/depmap_26q1/FANCA.md new file mode 100644 index 0000000..7bceecd --- /dev/null +++ b/examples/target_cards/depmap_26q1/FANCA.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FANCA + +## Target identity + +- **Target symbol:** FANCA +- **Target name:** FA complementation group A +- **Open Targets melanoma score:** 0.563 +- **Open Targets baseline rank:** 130 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 132 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 133 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 132 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.563) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FANCA lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FANCA in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.39440710682115865,"interquartile_range":0.2515883236857389,"maximum":0.12296597316977459,"mean":-0.27177681109686624,"measured_model_count":56,"median":-0.2676352166799574,"minimum":-0.8702254040849512,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.14281878313541974,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.06949355765826927,"interquartile_range":0.39275603779407636,"maximum":0.9139864368396176,"mean":0.2615344748466097,"measured_model_count":56,"median":0.18706360909548436,"minimum":0.00882008373465794,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.4622495954523456,"threshold_fractions":[{"denominator":56,"fraction":0.21428571428571427,"numerator":12,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03743288547584378,"dependency_probability_threshold_fractions":[{"context_fraction":0.21428571428571427,"difference":0.047067171239356664,"pan_cancer_fraction":0.1672185430463576,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.03595080416272469,"pan_cancer_fraction":0.05380794701986755,"threshold":0.8}],"gene_effect_mean":-0.012940611265707225,"gene_effect_median":-0.03731075409812393},"dependency_probability_context_minus_non_context_median":0.0382085681160369,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.21428571428571427,"difference":0.04935515873015872,"non_context_fraction":0.16493055555555555,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.037698412698412696,"non_context_fraction":0.05555555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.013569668757790032,"gene_effect_context_minus_non_context_median":-0.040755914352917866} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 132 +- **Dependency-aware candidate rank:** 132 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_9d612855c15e78dd7b3fd730052e093248a8cf43206ecf80de6d56c1e71879f0` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FANCA|entrez:2175` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FANCD2.md b/examples/target_cards/depmap_26q1/FANCD2.md new file mode 100644 index 0000000..d99bcc4 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FANCD2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FANCD2 + +## Target identity + +- **Target symbol:** FANCD2 +- **Target name:** FA complementation group D2 +- **Open Targets melanoma score:** 0.551 +- **Open Targets baseline rank:** 156 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 158 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 159 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 158 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.551) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FANCD2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FANCD2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.34113845335061077,"interquartile_range":0.21209073145092927,"maximum":0.30763589641378847,"mean":-0.2358248940686561,"measured_model_count":56,"median":-0.24333725518628152,"minimum":-0.639276633988662,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.1290477218996815,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.06847084215026893,"interquartile_range":0.23966001971981649,"maximum":0.734910238754248,"mean":0.21108429639298154,"measured_model_count":56,"median":0.16569585838507817,"minimum":0.0015781144865433508,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.3081308618700854,"threshold_fractions":[{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0025366642184283805,"dependency_probability_threshold_fractions":[{"context_fraction":0.08928571428571429,"difference":-0.07958845789971618,"pan_cancer_fraction":0.16887417218543047,"threshold":0.5},{"context_fraction":0.0,"difference":-0.059602649006622516,"pan_cancer_fraction":0.059602649006622516,"threshold":0.8}],"gene_effect_mean":0.04550799068532252,"gene_effect_median":0.007226063520758941},"dependency_probability_context_minus_non_context_median":-0.003003162126274078,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.08928571428571429,"difference":-0.08345734126984126,"non_context_fraction":0.17274305555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0625,"non_context_fraction":0.0625,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04772018467697031,"gene_effect_context_minus_non_context_median":0.009441874759868407} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 158 +- **Dependency-aware candidate rank:** 158 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_38747c75a45551df32701b90edeb5b912c93eecb55956a769ccf297c959c6499` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FANCD2|entrez:2177` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FANCE.md b/examples/target_cards/depmap_26q1/FANCE.md new file mode 100644 index 0000000..53cd31c --- /dev/null +++ b/examples/target_cards/depmap_26q1/FANCE.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FANCE + +## Target identity + +- **Target symbol:** FANCE +- **Target name:** FA complementation group E +- **Open Targets melanoma score:** 0.495 +- **Open Targets baseline rank:** 258 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 260 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 260 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 260 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.495) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FANCE lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FANCE in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.30468282446630407,"interquartile_range":0.23709348450999423,"maximum":0.1449555156044862,"mean":-0.19703014558258644,"measured_model_count":56,"median":-0.19399076273649424,"minimum":-0.6634268715160248,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.06758933995630984,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.05160543946265888,"interquartile_range":0.20409383149367327,"maximum":0.8359188291300516,"mean":0.17355839520632504,"measured_model_count":56,"median":0.12078053526514522,"minimum":0.0063814556847987345,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.25569927095633216,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.010507597535913196,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.024243140964995268,"pan_cancer_fraction":0.07781456953642384,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.004493850520340587,"pan_cancer_fraction":0.022350993377483443,"threshold":0.8}],"gene_effect_mean":0.0048485338361873576,"gene_effect_median":-0.010002252875917883},"dependency_probability_context_minus_non_context_median":0.011688697304552895,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.025421626984126984,"non_context_fraction":0.07899305555555555,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.004712301587301588,"non_context_fraction":0.022569444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.005084226453224372,"gene_effect_context_minus_non_context_median":-0.010590003539978826} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 260 +- **Dependency-aware candidate rank:** 260 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_af2ef9ce5f4fd758b457c8e17953dbe83cdfdf20b1372dd55948c65268248353` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FANCE|entrez:2178` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FANCF.md b/examples/target_cards/depmap_26q1/FANCF.md new file mode 100644 index 0000000..6b7782b --- /dev/null +++ b/examples/target_cards/depmap_26q1/FANCF.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FANCF + +## Target identity + +- **Target symbol:** FANCF +- **Target name:** FA complementation group F +- **Open Targets melanoma score:** 0.511 +- **Open Targets baseline rank:** 237 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 239 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 239 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 239 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.511) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FANCF lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FANCF in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.41615021274621306,"interquartile_range":0.22066287913849758,"maximum":0.018453039839361474,"mean":-0.32504242532536193,"measured_model_count":56,"median":-0.31555455536594124,"minimum":-0.9314961101442203,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.19548733360771547,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.11743406537297933,"interquartile_range":0.35662513437807863,"maximum":0.9457808378607613,"mean":0.3108121278616506,"measured_model_count":56,"median":0.24263160040327705,"minimum":0.01631160733986358,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.474059199751058,"threshold_fractions":[{"denominator":56,"fraction":0.23214285714285715,"numerator":13,"threshold":0.5},{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03892104933244922,"dependency_probability_threshold_fractions":[{"context_fraction":0.23214285714285715,"difference":0.05085146641438032,"pan_cancer_fraction":0.18129139072847683,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.011825922421948916,"pan_cancer_fraction":0.06539735099337748,"threshold":0.8}],"gene_effect_mean":-0.027520060395061552,"gene_effect_median":-0.04656469941415908},"dependency_probability_context_minus_non_context_median":0.04155124666083371,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.23214285714285715,"difference":0.0533234126984127,"non_context_fraction":0.17881944444444445,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.012400793650793655,"non_context_fraction":0.06597222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.028857841108710203,"gene_effect_context_minus_non_context_median":-0.04936482998290259} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 239 +- **Dependency-aware candidate rank:** 239 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a25481f9b7fb6aeae93c442afd3af2320fa466eaf6af98abfe161e70ee99dba8` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FANCF|entrez:2188` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FAS.md b/examples/target_cards/depmap_26q1/FAS.md new file mode 100644 index 0000000..91baf9e --- /dev/null +++ b/examples/target_cards/depmap_26q1/FAS.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FAS + +## Target identity + +- **Target symbol:** FAS +- **Target name:** Fas cell surface death receptor +- **Open Targets melanoma score:** 0.520 +- **Open Targets baseline rank:** 214 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 216 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 216 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 216 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.520) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FAS lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FAS in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.16162206893853046,"interquartile_range":0.13172923906542297,"maximum":0.18036452107576528,"mean":-0.08960286791582976,"measured_model_count":56,"median":-0.11478192715046522,"minimum":-0.31079330755796136,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.029892829873107492,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.026861749551291544,"interquartile_range":0.06845940434177648,"maximum":0.2343847619311021,"mean":0.06411442895668948,"measured_model_count":56,"median":0.05203040919741203,"minimum":0.0031442763076645645,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09532115389306803,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.013770595535781915,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.03749563999309223,"gene_effect_median":0.008775714037758828},"dependency_probability_context_minus_non_context_median":-0.014767391644715883,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03931834471497868,"gene_effect_context_minus_non_context_median":0.009573133482113347} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 216 +- **Dependency-aware candidate rank:** 216 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_435dbd512d7e3db5bb499780b478a732de5d1d5f6c8f09df160c88a5d8e23421` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FAS|entrez:355` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FAT1.md b/examples/target_cards/depmap_26q1/FAT1.md new file mode 100644 index 0000000..15ece2f --- /dev/null +++ b/examples/target_cards/depmap_26q1/FAT1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FAT1 + +## Target identity + +- **Target symbol:** FAT1 +- **Target name:** FAT atypical cadherin 1 +- **Open Targets melanoma score:** 0.616 +- **Open Targets baseline rank:** 51 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 56 | not prioritized | -5 | +| Resistance biomarker | 0.000 | 58 | not prioritized | -7 | +| Tumor-intrinsic / small molecule | 0.000 | 56 | not prioritized | -5 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.616) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FAT1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FAT1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.010190119994076867,"interquartile_range":0.1327527813060256,"maximum":0.3239877898348623,"mean":0.05787560641765308,"measured_model_count":56,"median":0.04713508116369999,"minimum":-0.1477656314088705,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12256266131194873,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.006042510039561404,"interquartile_range":0.01801475636113281,"maximum":0.12678724791693652,"mean":0.019558783916784724,"measured_model_count":56,"median":0.013016969463129585,"minimum":0.0013710596238751416,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.024057266400694215,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0013614167784833913,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.01248027188150281,"gene_effect_median":-0.020780697114013286},"dependency_probability_context_minus_non_context_median":0.0013991729157834913,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.01308695176463142,"gene_effect_context_minus_non_context_median":-0.021291486324947137} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 56 +- **Dependency-aware candidate rank:** 56 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_6f6e747f3722d5fc2be9e32d44c9d89b9858271ca298a917a9b9c5308679b7dd` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FAT1|entrez:2195` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FAT4.md b/examples/target_cards/depmap_26q1/FAT4.md new file mode 100644 index 0000000..fe5716a --- /dev/null +++ b/examples/target_cards/depmap_26q1/FAT4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FAT4 + +## Target identity + +- **Target symbol:** FAT4 +- **Target name:** FAT atypical cadherin 4 +- **Open Targets melanoma score:** 0.601 +- **Open Targets baseline rank:** 69 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 73 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 75 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 73 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.601) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FAT4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FAT4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.08010063621579745,"interquartile_range":0.13017968110048778,"maximum":0.21669532988519838,"mean":-0.025541252959918388,"measured_model_count":56,"median":-0.023054746641925847,"minimum":-0.47842898548034124,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.050079044884690324,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01326244371222652,"interquartile_range":0.033213141154614684,"maximum":0.3959491092740444,"mean":0.039079867410627044,"measured_model_count":56,"median":0.026496833584941027,"minimum":0.0022160403622951044,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0464755848668412,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0035919121449942,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.011374350608281528,"gene_effect_median":0.010377897671845472},"dependency_probability_context_minus_non_context_median":-0.0039031432466969836,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.011927270429517495,"gene_effect_context_minus_non_context_median":0.01086542962612444} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 73 +- **Dependency-aware candidate rank:** 73 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_fb3832e78ce8821d085e9f9e58324d7617a45c5703e4e3e6b9dd7d4f1e99e62f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FAT4|entrez:79633` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FBXO11.md b/examples/target_cards/depmap_26q1/FBXO11.md new file mode 100644 index 0000000..264b7dd --- /dev/null +++ b/examples/target_cards/depmap_26q1/FBXO11.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FBXO11 + +## Target identity + +- **Target symbol:** FBXO11 +- **Target name:** F-box protein 11 +- **Open Targets melanoma score:** 0.520 +- **Open Targets baseline rank:** 211 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 213 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 213 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 213 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.520) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FBXO11 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FBXO11 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.15074818038210167,"interquartile_range":0.281308577050804,"maximum":0.42220203584434846,"mean":-0.04560795363310931,"measured_model_count":56,"median":-0.03427403620395675,"minimum":-0.6741261622322151,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1305603966687023,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.007285169440329596,"interquartile_range":0.09745011838978633,"maximum":0.7905134474847286,"mean":0.10611223844677944,"measured_model_count":56,"median":0.029319765084054497,"minimum":0.0004413568234268305,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10473528783011593,"threshold_fractions":[{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.05470028325649019,"dependency_probability_threshold_fractions":[{"context_fraction":0.08928571428571429,"difference":-0.09780037842951751,"pan_cancer_fraction":0.1870860927152318,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0869205298013245,"pan_cancer_fraction":0.0869205298013245,"threshold":0.8}],"gene_effect_mean":0.15028418975283891,"gene_effect_median":0.12440411985501812},"dependency_probability_context_minus_non_context_median":-0.06235086518264875,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.08928571428571429,"difference":-0.1025545634920635,"non_context_fraction":0.1918402777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.09114583333333333,"non_context_fraction":0.09114583333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.15758967119915746,"gene_effect_context_minus_non_context_median":0.13709329218559274} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 213 +- **Dependency-aware candidate rank:** 213 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2a9dbb49310a86c32be14cbc59e80d4d2c2add0340022fbd2770296eee5d6ab5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FBXO11|entrez:80204` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FBXW7.md b/examples/target_cards/depmap_26q1/FBXW7.md new file mode 100644 index 0000000..459d0d3 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FBXW7.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FBXW7 + +## Target identity + +- **Target symbol:** FBXW7 +- **Target name:** F-box and WD repeat domain containing 7 +- **Open Targets melanoma score:** 0.459 +- **Open Targets baseline rank:** 296 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 296 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 296 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 296 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.459) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FBXW7 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FBXW7 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.10168761872706197,"interquartile_range":0.31951626522136356,"maximum":0.7477705375903348,"mean":0.07512290288357788,"measured_model_count":56,"median":0.08885012160126604,"minimum":-0.42999840215935103,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.21782864649430156,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0023602908105894663,"interquartile_range":0.04698617022723407,"maximum":0.3990660245341544,"mean":0.048686281727830724,"measured_model_count":56,"median":0.00790827217292547,"minimum":7.339235394045013e-07,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04934646103782354,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.010836419724310722,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.052980132450331126,"pan_cancer_fraction":0.052980132450331126,"threshold":0.5},{"context_fraction":0.0,"difference":-0.01903973509933775,"pan_cancer_fraction":0.01903973509933775,"threshold":0.8}],"gene_effect_mean":0.08060711847084692,"gene_effect_median":0.07781843422240313},"dependency_probability_context_minus_non_context_median":-0.011215200532051196,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.05555555555555555,"non_context_fraction":0.05555555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.019965277777777776,"non_context_fraction":0.019965277777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08452552006317991,"gene_effect_context_minus_non_context_median":0.0786441323859088} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 296 +- **Dependency-aware candidate rank:** 296 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_b02eb196c82838328cafb71a23b2642af9fedccfd9c22696f2b332ac3c26fe8b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FBXW7|entrez:55294` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FCRL4.md b/examples/target_cards/depmap_26q1/FCRL4.md new file mode 100644 index 0000000..9ef190f --- /dev/null +++ b/examples/target_cards/depmap_26q1/FCRL4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FCRL4 + +## Target identity + +- **Target symbol:** FCRL4 +- **Target name:** Fc receptor like 4 +- **Open Targets melanoma score:** 0.547 +- **Open Targets baseline rank:** 166 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 168 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 169 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 168 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.547) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FCRL4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FCRL4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.182975187793387,"interquartile_range":0.13243973999157846,"maximum":0.14030049532262745,"mean":-0.11330662488132592,"measured_model_count":56,"median":-0.10620558769013834,"minimum":-0.451675523595505,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.05053544780180854,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.03271037791063712,"interquartile_range":0.057892317786895325,"maximum":0.4302335386003559,"mean":0.07745410574824914,"measured_model_count":56,"median":0.05680147102116183,"minimum":0.003675204351939972,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09060269569753245,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.008796200508185144,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.019686981945813434,"gene_effect_median":-0.017844667161811156},"dependency_probability_context_minus_non_context_median":0.009037454034450887,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.020643988012623682,"gene_effect_context_minus_non_context_median":-0.01890243276653479} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 168 +- **Dependency-aware candidate rank:** 168 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_993b3f04ca04a2b878e09007c16e57fbedf7753e2078c6925a2ff9c73d71d284` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FCRL4|entrez:83417` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FGFR1.md b/examples/target_cards/depmap_26q1/FGFR1.md new file mode 100644 index 0000000..ef48c62 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FGFR1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FGFR1 + +## Target identity + +- **Target symbol:** FGFR1 +- **Target name:** fibroblast growth factor receptor 1 +- **Open Targets melanoma score:** 0.592 +- **Open Targets baseline rank:** 81 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 84 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 86 | not prioritized | -5 | +| Tumor-intrinsic / small molecule | 0.000 | 84 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.592) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FGFR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FGFR1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.10585312617805011,"interquartile_range":0.1474329702619552,"maximum":0.24676378195924795,"mean":-0.04075960883877906,"measured_model_count":56,"median":-0.04514236242722311,"minimum":-0.45737015923785884,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04157984408390509,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.013136544667759788,"interquartile_range":0.042445470736148155,"maximum":0.5845513123281094,"mean":0.05509342663926976,"measured_model_count":56,"median":0.030469376280351304,"minimum":0.0018396455361303317,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05558201540390795,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01369994659970368,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.10631504257332072,"pan_cancer_fraction":0.12417218543046357,"threshold":0.5},{"context_fraction":0.0,"difference":-0.076158940397351,"pan_cancer_fraction":0.076158940397351,"threshold":0.8}],"gene_effect_mean":0.1434789721272285,"gene_effect_median":0.03823400415708511},"dependency_probability_context_minus_non_context_median":-0.014786145536563725,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.11148313492063494,"non_context_fraction":0.1293402777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0798611111111111,"non_context_fraction":0.0798611111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.1504536443834132,"gene_effect_context_minus_non_context_median":0.04293224672576107} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 84 +- **Dependency-aware candidate rank:** 84 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_0c4c822c779a509dd8f0818fdf2712c56fe01b6e397d995d2d24c31f73a62c13` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FGFR1|entrez:2260` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FGFR2.md b/examples/target_cards/depmap_26q1/FGFR2.md new file mode 100644 index 0000000..d553570 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FGFR2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FGFR2 + +## Target identity + +- **Target symbol:** FGFR2 +- **Target name:** fibroblast growth factor receptor 2 +- **Open Targets melanoma score:** 0.597 +- **Open Targets baseline rank:** 72 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 76 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 78 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 76 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.597) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FGFR2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FGFR2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.12929769810455707,"interquartile_range":0.12395274435376992,"maximum":0.275230036665003,"mean":-0.05821593340182014,"measured_model_count":56,"median":-0.05163254238200452,"minimum":-0.5200819479761457,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.005344953750787151,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.022649497580184946,"interquartile_range":0.038355964705018376,"maximum":0.7009253574543882,"mean":0.05743963083468188,"measured_model_count":56,"median":0.03537906820870254,"minimum":0.0017046287467954388,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06100546228520332,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0009883025349953362,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.0028382213812677415,"pan_cancer_fraction":0.020695364238410598,"threshold":0.5},{"context_fraction":0.0,"difference":-0.011589403973509934,"pan_cancer_fraction":0.011589403973509934,"threshold":0.8}],"gene_effect_mean":0.009920320730496084,"gene_effect_median":-0.0012327620399221126},"dependency_probability_context_minus_non_context_median":0.0010248143999687029,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.002976190476190476,"non_context_fraction":0.020833333333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.012152777777777778,"non_context_fraction":0.012152777777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.010402558543784114,"gene_effect_context_minus_non_context_median":-0.0012327620399221126} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 76 +- **Dependency-aware candidate rank:** 76 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_dfa107591a1ac03b755e3ff7c7cbf34b941cb9295ecfe59850965185086aaf5f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FGFR2|entrez:2263` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FGFR3.md b/examples/target_cards/depmap_26q1/FGFR3.md new file mode 100644 index 0000000..04ff4e1 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FGFR3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FGFR3 + +## Target identity + +- **Target symbol:** FGFR3 +- **Target name:** fibroblast growth factor receptor 3 +- **Open Targets melanoma score:** 0.508 +- **Open Targets baseline rank:** 245 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 247 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 247 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 247 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.508) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FGFR3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FGFR3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.05194312301230575,"interquartile_range":0.17413908661637087,"maximum":0.3363122041950665,"mean":0.03525864250811891,"measured_model_count":56,"median":0.04922997969645476,"minimum":-0.46980050826203773,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12219596360406512,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005922891813622169,"interquartile_range":0.023690854120683086,"maximum":0.37901610456587304,"mean":0.036640727013179324,"measured_model_count":56,"median":0.015458308668818171,"minimum":0.0005398320917780566,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.029613745934305255,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0019648983478077423,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":-0.010620082025073661,"gene_effect_median":-0.0025159097270620323},"dependency_probability_context_minus_non_context_median":0.002078622591012949,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.011136336012403637,"gene_effect_context_minus_non_context_median":-0.0025159097270620323} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 247 +- **Dependency-aware candidate rank:** 247 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_35b283f0a5f1c62f4b53730a369193f82d2197826a40e0c00115df009af6f895` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FGFR3|entrez:2261` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FGFR4.md b/examples/target_cards/depmap_26q1/FGFR4.md new file mode 100644 index 0000000..83a8918 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FGFR4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FGFR4 + +## Target identity + +- **Target symbol:** FGFR4 +- **Target name:** fibroblast growth factor receptor 4 +- **Open Targets melanoma score:** 0.596 +- **Open Targets baseline rank:** 74 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 78 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 80 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 78 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.596) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FGFR4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FGFR4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.04827777998776034,"interquartile_range":0.1004719025100316,"maximum":0.2993306227887731,"mean":0.0031693776232304136,"measured_model_count":56,"median":-0.0050449308179600395,"minimum":-0.19963413413040304,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05219412252227127,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.010744829149114411,"interquartile_range":0.023094813491983453,"maximum":0.10374246297872541,"mean":0.02619568029732398,"measured_model_count":56,"median":0.01975265020738414,"minimum":0.0007450975600135493,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.033839642641097865,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0009313245577814086,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":0.0066095514812883945,"gene_effect_median":-0.006960965645284039},"dependency_probability_context_minus_non_context_median":-0.0009313245577814086,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006930849122739929,"gene_effect_context_minus_non_context_median":-0.007745231305098141} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 78 +- **Dependency-aware candidate rank:** 78 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_004c3e04c159ccaa691e52e99fbfb4144510f7d9bdc39f80ac4517d3fe1423ff` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FGFR4|entrez:2264` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FH.md b/examples/target_cards/depmap_26q1/FH.md new file mode 100644 index 0000000..03d2fd1 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FH.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FH + +## Target identity + +- **Target symbol:** FH +- **Target name:** fumarate hydratase +- **Open Targets melanoma score:** 0.507 +- **Open Targets baseline rank:** 246 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 248 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 248 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 248 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.507) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FH lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FH in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.48235854532561034,"interquartile_range":0.30092341372102055,"maximum":0.21734868313383282,"mean":-0.3452825522263905,"measured_model_count":56,"median":-0.3487538509937572,"minimum":-1.1620329173001207,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.1814351316045898,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.11598339367742898,"interquartile_range":0.4138461833340011,"maximum":0.9842926507309879,"mean":0.3562568102014801,"measured_model_count":56,"median":0.293119690869387,"minimum":0.002688067009743821,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5298295770114301,"threshold_fractions":[{"denominator":56,"fraction":0.2857142857142857,"numerator":16,"threshold":0.5},{"denominator":56,"fraction":0.10714285714285714,"numerator":6,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.10011148122363533,"dependency_probability_threshold_fractions":[{"context_fraction":0.2857142857142857,"difference":0.08289971617786185,"pan_cancer_fraction":0.20281456953642385,"threshold":0.5},{"context_fraction":0.10714285714285714,"difference":0.04008987701040681,"pan_cancer_fraction":0.06705298013245033,"threshold":0.8}],"gene_effect_mean":-0.056762207296732925,"gene_effect_median":-0.07985514795528226},"dependency_probability_context_minus_non_context_median":0.10531261956391319,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.2857142857142857,"difference":0.08692956349206349,"non_context_fraction":0.1987847222222222,"threshold":0.5},{"context_fraction":0.10714285714285714,"difference":0.042038690476190466,"non_context_fraction":0.06510416666666667,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.05952148126254625,"gene_effect_context_minus_non_context_median":-0.08371105618329383} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 248 +- **Dependency-aware candidate rank:** 248 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_4c3d50fd928c20519680c63006ca3576503bad1ed551fa5b1d6ebf7febc1fe01` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FH|entrez:2271` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FLG.md b/examples/target_cards/depmap_26q1/FLG.md new file mode 100644 index 0000000..72e47bd --- /dev/null +++ b/examples/target_cards/depmap_26q1/FLG.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FLG + +## Target identity + +- **Target symbol:** FLG +- **Target name:** filaggrin +- **Open Targets melanoma score:** 0.546 +- **Open Targets baseline rank:** 169 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 171 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 172 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 171 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.546) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FLG lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FLG in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.014090010880866456,"interquartile_range":0.12299878821956789,"maximum":0.40211935160462337,"mean":0.05468800059532417,"measured_model_count":56,"median":0.053553678456244605,"minimum":-0.18698379576091817,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10890877733870144,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.007642926736823383,"interquartile_range":0.017284387507036578,"maximum":0.0830094575624924,"mean":0.019436951498532508,"measured_model_count":56,"median":0.012053492803449247,"minimum":0.0003584647512974246,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.024927314243859963,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.000785988056441209,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.020258498555916597,"gene_effect_median":-0.022962257860729376},"dependency_probability_context_minus_non_context_median":0.0009945662930979093,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.02124328668016256,"gene_effect_context_minus_non_context_median":-0.023969425069776965} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 171 +- **Dependency-aware candidate rank:** 171 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_8c9614fa2ecdbeeb83fe4e7758ee1d749ace6c9bfcacad385863c66e87259123` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FLG|entrez:2312` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FLT3.md b/examples/target_cards/depmap_26q1/FLT3.md new file mode 100644 index 0000000..24c9bb7 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FLT3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FLT3 + +## Target identity + +- **Target symbol:** FLT3 +- **Target name:** fms related receptor tyrosine kinase 3 +- **Open Targets melanoma score:** 0.516 +- **Open Targets baseline rank:** 225 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 227 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 227 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 227 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.516) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FLT3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FLT3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.22595354553005761,"interquartile_range":0.14998026773463285,"maximum":0.154995004034906,"mean":-0.14385366187633805,"measured_model_count":56,"median":-0.13862055477951635,"minimum":-0.48307639187962104,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.07597327779542476,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.04545758737215939,"interquartile_range":0.09978084071418072,"maximum":0.5397629699994875,"mean":0.10755393878508068,"measured_model_count":56,"median":0.08088979303060306,"minimum":0.005060271666928569,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1452384280863401,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.004678428087829312,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.007095553453169347,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.8}],"gene_effect_mean":0.002763227151568154,"gene_effect_median":0.00511073170445725},"dependency_probability_context_minus_non_context_median":0.0049809751847571665,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.00744047619047619,"non_context_fraction":0.010416666666666666,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0028975506936582685,"gene_effect_context_minus_non_context_median":0.005710907745139798} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 227 +- **Dependency-aware candidate rank:** 227 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_19f78659b5c5a1a4d11d0d7a3da8405949336d2087578f076ffcebf1fd6c4549` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FLT3|entrez:2322` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FLT4.md b/examples/target_cards/depmap_26q1/FLT4.md new file mode 100644 index 0000000..b32ad33 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FLT4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FLT4 + +## Target identity + +- **Target symbol:** FLT4 +- **Target name:** fms related receptor tyrosine kinase 4 +- **Open Targets melanoma score:** 0.651 +- **Open Targets baseline rank:** 30 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 37 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 39 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.001 | 32 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.651) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FLT4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FLT4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.019570219331166372,"interquartile_range":0.12035885290869781,"maximum":0.2540552513736699,"mean":0.039597374010813514,"measured_model_count":56,"median":0.029329758113223747,"minimum":-0.16137096768294212,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10078863357753144,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008675884303708739,"interquartile_range":0.018278780420746883,"maximum":0.08326337223205958,"mean":0.019447313633772216,"measured_model_count":56,"median":0.016517954870417618,"minimum":0.0012689987898533725,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.026954664724455624,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0006489096814118467,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.01595184925542367,"gene_effect_median":0.006058142124424029},"dependency_probability_context_minus_non_context_median":-0.0006844353504273058,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.016727286372006774,"gene_effect_context_minus_non_context_median":0.006718596257992385} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 37 +- **Dependency-aware candidate rank:** 37 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_44c57ba5c52a55c98a9505d58528634b542af6211b3ff63f1344e345487b5d61` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FLT4|entrez:2324` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FMN1.md b/examples/target_cards/depmap_26q1/FMN1.md new file mode 100644 index 0000000..e9dd6b1 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FMN1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FMN1 + +## Target identity + +- **Target symbol:** FMN1 +- **Target name:** formin 1 +- **Open Targets melanoma score:** 0.489 +- **Open Targets baseline rank:** 264 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 266 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 266 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 266 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.489) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FMN1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FMN1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.04804373333999466,"interquartile_range":0.15223200943340148,"maximum":0.5097227332643849,"mean":0.11250660008204064,"measured_model_count":56,"median":0.13594679027128903,"minimum":-0.7270702453089212,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.20027574277339613,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0025879797549131995,"interquartile_range":0.011864780776770868,"maximum":0.8049195799577559,"mean":0.029415923175659203,"measured_model_count":56,"median":0.005465761799348213,"minimum":0.00019623882159085373,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.014452760531684069,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0046174476303679135,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.015373699148533584,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.01702932828760643,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.03478949815416854,"gene_effect_median":0.054479413326805184},"dependency_probability_context_minus_non_context_median":-0.004784356776145761,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.016121031746031744,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.017857142857142856,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0364806543144406,"gene_effect_context_minus_non_context_median":0.05660838796219783} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 266 +- **Dependency-aware candidate rank:** 266 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_69e5314be2fbeceef14006c5abadfdb7977478310ef3e7a3a5f227fd0e52d327` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FMN1|entrez:342184` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FOXP1.md b/examples/target_cards/depmap_26q1/FOXP1.md new file mode 100644 index 0000000..0885185 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FOXP1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FOXP1 + +## Target identity + +- **Target symbol:** FOXP1 +- **Target name:** forkhead box P1 +- **Open Targets melanoma score:** 0.636 +- **Open Targets baseline rank:** 36 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 43 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 45 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 43 | not prioritized | -7 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.636) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FOXP1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FOXP1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.08925622719291582,"interquartile_range":0.15725199103704537,"maximum":0.3896693910511839,"mean":-0.012717309353639877,"measured_model_count":56,"median":0.006684601879123767,"minimum":-0.48806446905551293,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06799576384412956,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.009684733628868597,"interquartile_range":0.03702886243106225,"maximum":0.45881000128768495,"mean":0.05421199659843505,"measured_model_count":56,"median":0.018906366489225244,"minimum":0.0005847063168429513,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04671359605993085,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0033351835499027954,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.039143380154957934,"gene_effect_median":-0.024316461656596587},"dependency_probability_context_minus_non_context_median":0.003675399300320372,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.041046183356935065,"gene_effect_context_minus_non_context_median":-0.025993480373904948} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 43 +- **Dependency-aware candidate rank:** 43 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a1e2720e1e989d0d788b4b8760f1078648865d2fe750dc670b9d9ad1f8aa0d2e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FOXP1|entrez:27086` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FOXP3.md b/examples/target_cards/depmap_26q1/FOXP3.md new file mode 100644 index 0000000..279f904 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FOXP3.md @@ -0,0 +1,73 @@ +# FOXP3 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.015325840605122043,"interquartile_range":0.09965029971967573,"maximum":0.2660450679919454,"mean":0.06567559829110299,"measured_model_count":56,"median":0.06163214472920807,"minimum":-0.23676786606528333,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11497614032479778,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.006236233508914037,"interquartile_range":0.00910131640870038,"maximum":0.13569945974455236,"mean":0.016217094032263086,"measured_model_count":56,"median":0.01160893644614088,"minimum":0.0011550462651738536,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.015337549917614417,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0014470923302244126,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.021158287619726213,"gene_effect_median":-0.021145144317778697},"dependency_probability_context_minus_non_context_median":0.0015407235934845175,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.022186815490129574,"gene_effect_context_minus_non_context_median":-0.02276042607062291} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_bf04bf99f93c0cb1a92980fe824b4f059cb02d5a8ea61bae4be73224ef941405` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FOXP3|entrez:50943` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/FUBP1.md b/examples/target_cards/depmap_26q1/FUBP1.md new file mode 100644 index 0000000..53a5b43 --- /dev/null +++ b/examples/target_cards/depmap_26q1/FUBP1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: FUBP1 + +## Target identity + +- **Target symbol:** FUBP1 +- **Target name:** far upstream element binding protein 1 +- **Open Targets melanoma score:** 0.491 +- **Open Targets baseline rank:** 262 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 264 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 264 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 264 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.491) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** FUBP1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for FUBP1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.2881247391090692,"interquartile_range":0.16340607882358316,"maximum":0.1842388495263189,"mean":-0.20610670889766866,"measured_model_count":56,"median":-0.19477172807427562,"minimum":-0.6381129392361081,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.12471866028548606,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.06338988632503986,"interquartile_range":0.16076528927297246,"maximum":0.7540646184472742,"mean":0.1760565738449998,"measured_model_count":56,"median":0.10461075385553599,"minimum":0.0027667622892301744,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.22415517559801232,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0019598383822274773,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.04742194891201514,"pan_cancer_fraction":0.10099337748344371,"threshold":0.5},{"context_fraction":0.0,"difference":-0.024006622516556293,"pan_cancer_fraction":0.024006622516556293,"threshold":0.8}],"gene_effect_mean":-0.01405759351501737,"gene_effect_median":-0.008173948816249},"dependency_probability_context_minus_non_context_median":0.0030925657815894375,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.049727182539682536,"non_context_fraction":0.1032986111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.025173611111111112,"non_context_fraction":0.025173611111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.014740948755330802,"gene_effect_context_minus_non_context_median":-0.009100495671172604} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 264 +- **Dependency-aware candidate rank:** 264 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_6e58d1225d1ff58877163c0cbff4987d160c4bd85f4c6abefe8fb554070ec846` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:FUBP1|entrez:8880` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/GATA2.md b/examples/target_cards/depmap_26q1/GATA2.md new file mode 100644 index 0000000..4996912 --- /dev/null +++ b/examples/target_cards/depmap_26q1/GATA2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: GATA2 + +## Target identity + +- **Target symbol:** GATA2 +- **Target name:** GATA binding protein 2 +- **Open Targets melanoma score:** 0.486 +- **Open Targets baseline rank:** 267 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 268 | not prioritized | -1 | +| Resistance biomarker | 0.000 | 268 | not prioritized | -1 | +| Tumor-intrinsic / small molecule | 0.000 | 268 | not prioritized | -1 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.486) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** GATA2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for GATA2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.007575429545667133,"interquartile_range":0.12492924525133178,"maximum":0.38970793669976095,"mean":0.0577966749928754,"measured_model_count":56,"median":0.05691850044409493,"minimum":-0.29724211223823427,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11735381570566465,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005785166202300651,"interquartile_range":0.01713490940782536,"maximum":0.3018103137464197,"mean":0.022289382974630133,"measured_model_count":56,"median":0.012027009295317814,"minimum":0.0007343235547851637,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02292007561012601,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0020969851635946023,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.022350993377483443,"pan_cancer_fraction":0.022350993377483443,"threshold":0.5},{"context_fraction":0.0,"difference":-0.011589403973509934,"pan_cancer_fraction":0.011589403973509934,"threshold":0.8}],"gene_effect_mean":0.027134737241848835,"gene_effect_median":0.005962492496855362},"dependency_probability_context_minus_non_context_median":-0.002243803387106131,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0234375,"non_context_fraction":0.0234375,"threshold":0.5},{"context_fraction":0.0,"difference":-0.012152777777777778,"non_context_fraction":0.012152777777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.028453786968883153,"gene_effect_context_minus_non_context_median":0.006359299502022693} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 268 +- **Dependency-aware candidate rank:** 268 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d9b94b7c7104e5636cbe3f4f57178a06a55a1c08c478cacb063d5011123fbd17` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:GATA2|entrez:2624` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/GNA11.md b/examples/target_cards/depmap_26q1/GNA11.md new file mode 100644 index 0000000..d765f6d --- /dev/null +++ b/examples/target_cards/depmap_26q1/GNA11.md @@ -0,0 +1,124 @@ +# Target hypothesis card: GNA11 + +## Target identity + +- **Target symbol:** GNA11 +- **Target name:** G protein subunit alpha 11 +- **Open Targets melanoma score:** 0.708 +- **Open Targets baseline rank:** 17 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 24 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 27 | not prioritized | -10 | +| Tumor-intrinsic / small molecule | 0.012 | 20 | not prioritized | -3 | + +## Evidence for + +- High Open Targets melanoma association score (0.708) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** GNA11 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for GNA11 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.24420661980895522,"interquartile_range":0.15532874743496847,"maximum":0.03808760466256192,"mean":-0.1684084279156771,"measured_model_count":56,"median":-0.1566551127202881,"minimum":-0.45115937023528413,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.08887787237398675,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.03757946210475693,"interquartile_range":0.11724926833434487,"maximum":0.5638151018002555,"mean":0.11858227556158243,"measured_model_count":56,"median":0.09407439748766974,"minimum":0.010923528122944231,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1548287304391018,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.02310997207226037,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.009578997161778617,"pan_cancer_fraction":0.008278145695364239,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.026795039061602494,"gene_effect_median":-0.02109071818710906},"dependency_probability_context_minus_non_context_median":0.02350983668023343,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.010044642857142856,"non_context_fraction":0.0078125,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.028097575682652587,"gene_effect_context_minus_non_context_median":-0.02238896547077862} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 24 +- **Dependency-aware candidate rank:** 23 +- **Rank delta:** -1 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a7d87a9ec0d84e741c1cc77753996d174f0f3d0258d04962a8bf22f4fc0aa442` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:GNA11|entrez:2767` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/GNAQ.md b/examples/target_cards/depmap_26q1/GNAQ.md new file mode 100644 index 0000000..b99fdee --- /dev/null +++ b/examples/target_cards/depmap_26q1/GNAQ.md @@ -0,0 +1,124 @@ +# Target hypothesis card: GNAQ + +## Target identity + +- **Target symbol:** GNAQ +- **Target name:** G protein subunit alpha q +- **Open Targets melanoma score:** 0.720 +- **Open Targets baseline rank:** 11 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 19 | not prioritized | -8 | +| Resistance biomarker | 0.000 | 24 | not prioritized | -13 | +| Tumor-intrinsic / small molecule | 0.015 | 17 | not prioritized | -6 | + +## Evidence for + +- High Open Targets melanoma association score (0.720) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** GNAQ lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for GNAQ in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.45136196689657815,"interquartile_range":0.22233080091499816,"maximum":-0.040557723214412034,"mean":-0.365139823702521,"measured_model_count":56,"median":-0.3311970646804885,"minimum":-1.1688313734515619,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.22903116598158,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.16462592677727933,"interquartile_range":0.30738138279626565,"maximum":0.9920765810689797,"mean":0.3481970522328733,"measured_model_count":56,"median":0.27679032897507927,"minimum":0.02048184269862659,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.472007309573545,"threshold_fractions":[{"denominator":56,"fraction":0.23214285714285715,"numerator":13,"threshold":0.5},{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.02775485358607166,"dependency_probability_threshold_fractions":[{"context_fraction":0.23214285714285715,"difference":0.07154683065279094,"pan_cancer_fraction":0.1605960264900662,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":0.03997161778618732,"pan_cancer_fraction":0.03145695364238411,"threshold":0.8}],"gene_effect_mean":-0.05124936895378335,"gene_effect_median":-0.026313059636482228},"dependency_probability_context_minus_non_context_median":0.028648254521146055,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.23214285714285715,"difference":0.0750248015873016,"non_context_fraction":0.15711805555555555,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":0.041914682539682536,"non_context_fraction":0.029513888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.05374065772237008,"gene_effect_context_minus_non_context_median":-0.027474495765544504} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 19 +- **Dependency-aware candidate rank:** 15 +- **Rank delta:** -4 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ae901de999d2ee02d100019c4dd3e89979c37d98c65aae0363152f56d8a418b8` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:GNAQ|entrez:2776` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/GNAS.md b/examples/target_cards/depmap_26q1/GNAS.md new file mode 100644 index 0000000..78d52e1 --- /dev/null +++ b/examples/target_cards/depmap_26q1/GNAS.md @@ -0,0 +1,124 @@ +# Target hypothesis card: GNAS + +## Target identity + +- **Target symbol:** GNAS +- **Target name:** GNAS complex locus +- **Open Targets melanoma score:** 0.569 +- **Open Targets baseline rank:** 116 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 118 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 119 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 118 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.569) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** GNAS lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for GNAS in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.12914624361583124,"interquartile_range":0.16880844265574943,"maximum":0.3443254273478986,"mean":-0.04885626544081799,"measured_model_count":56,"median":-0.0395043305663757,"minimum":-0.5772557917183418,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.039662199039918196,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.011990605387231526,"interquartile_range":0.056437399568218624,"maximum":0.6486813918352867,"mean":0.06710232936679815,"measured_model_count":56,"median":0.032055853208135324,"minimum":0.0008476741953656707,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06842800495545015,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0032107523718056252,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.01206244087038789,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.011480693649686298,"gene_effect_median":-0.00926598963642166},"dependency_probability_context_minus_non_context_median":0.003590262256471081,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.012648809523809524,"non_context_fraction":0.005208333333333333,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.012038782924323865,"gene_effect_context_minus_non_context_median":-0.010368538176564888} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 118 +- **Dependency-aware candidate rank:** 118 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2121ce6ab7561f4f13a9e8a767a37ea64cba39801adb9ccd02f8d1fba46ce84c` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:GNAS|entrez:2778` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/GRIN2A.md b/examples/target_cards/depmap_26q1/GRIN2A.md new file mode 100644 index 0000000..a3a0bf6 --- /dev/null +++ b/examples/target_cards/depmap_26q1/GRIN2A.md @@ -0,0 +1,124 @@ +# Target hypothesis card: GRIN2A + +## Target identity + +- **Target symbol:** GRIN2A +- **Target name:** glutamate ionotropic receptor NMDA type subunit 2A +- **Open Targets melanoma score:** 0.594 +- **Open Targets baseline rank:** 75 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 79 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 81 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 79 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.594) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** GRIN2A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for GRIN2A in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.14411748716861636,"interquartile_range":0.1211869515324273,"maximum":0.11187573454467088,"mean":-0.07796016160118857,"measured_model_count":56,"median":-0.08077181172218598,"minimum":-0.27600553638489433,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.02293053563618906,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.023766660725572302,"interquartile_range":0.05338835758759475,"maximum":0.24021664161407277,"mean":0.056171638224705486,"measured_model_count":56,"median":0.04293536851828147,"minimum":0.007086734633626951,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07715501831316705,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.011198747176608272,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.029617941574408405,"gene_effect_median":0.021573085866140762},"dependency_probability_context_minus_non_context_median":-0.01178456213463986,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.031057702623164263,"gene_effect_context_minus_non_context_median":0.022850946800319766} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 79 +- **Dependency-aware candidate rank:** 79 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_1131048334e27b8c53c9180ef40f28486cfa48c15a0b199462fde73591da1e1f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:GRIN2A|entrez:2903` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/GZMB.md b/examples/target_cards/depmap_26q1/GZMB.md new file mode 100644 index 0000000..1aad391 --- /dev/null +++ b/examples/target_cards/depmap_26q1/GZMB.md @@ -0,0 +1,73 @@ +# GZMB — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.17244025699697157,"interquartile_range":0.2215586500992243,"maximum":0.3725292682983529,"mean":-0.043664638800793,"measured_model_count":56,"median":-0.06917978710613715,"minimum":-0.31096479898487983,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04911839310225271,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.009710803170775517,"interquartile_range":0.08752127492675235,"maximum":0.246250297339304,"mean":0.05926205677955833,"measured_model_count":56,"median":0.034480980287158486,"minimum":0.0007627617070437107,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09723207809752787,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01345836150324789,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03145695364238411,"pan_cancer_fraction":0.03145695364238411,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.05748615344446486,"gene_effect_median":0.02104996878975203},"dependency_probability_context_minus_non_context_median":-0.01427025841020696,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03298611111111111,"non_context_fraction":0.03298611111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.06028061923690404,"gene_effect_context_minus_non_context_median":0.021472073888966117} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_151ecdb83f44b504f40cc23529671c3a71580ccd555c775989d15d4c13db48d7` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:GZMB|entrez:3002` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/H3-3A.md b/examples/target_cards/depmap_26q1/H3-3A.md new file mode 100644 index 0000000..a35add7 --- /dev/null +++ b/examples/target_cards/depmap_26q1/H3-3A.md @@ -0,0 +1,124 @@ +# Target hypothesis card: H3-3A + +## Target identity + +- **Target symbol:** H3-3A +- **Target name:** H3.3 histone A +- **Open Targets melanoma score:** 0.489 +- **Open Targets baseline rank:** 266 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 267 | not prioritized | -1 | +| Resistance biomarker | 0.000 | 267 | not prioritized | -1 | +| Tumor-intrinsic / small molecule | 0.000 | 267 | not prioritized | -1 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.489) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** H3-3A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for H3-3A in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 55 +- **Available reference observations:** 1034 +- **Coverage fraction:** 0.9821428571428571 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.6291221340498359,"interquartile_range":0.5747953137617774,"maximum":-0.5969404951509958,"mean":-1.3551787569326883,"measured_model_count":55,"median":-1.346906237251263,"minimum":-2.244889055499746,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":-1.0543268202880585,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9837331286620297,"interquartile_range":0.016249656069920126,"maximum":1.0,"mean":0.9764838454893447,"measured_model_count":55,"median":0.995866238899257,"minimum":0.6036936797196938,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":0.9999827847319498,"threshold_fractions":[{"denominator":55,"fraction":1.0,"numerator":55,"threshold":0.5},{"denominator":55,"fraction":0.9818181818181818,"numerator":54,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0013855542350874606,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0009182736455464191,"pan_cancer_fraction":0.9990817263544536,"threshold":0.5},{"context_fraction":0.9818181818181818,"difference":-0.006244260789715295,"pan_cancer_fraction":0.9880624426078971,"threshold":0.8}],"gene_effect_mean":0.09920988909591233,"gene_effect_median":0.07560014079777178},"dependency_probability_context_minus_non_context_median":-0.0015030020911090958,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0009671179883945502,"non_context_fraction":0.9990328820116054,"threshold":0.5},{"context_fraction":0.9818181818181818,"difference":-0.006576402321083141,"non_context_fraction":0.988394584139265,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.10448701085633383,"gene_effect_context_minus_non_context_median":0.08053511551815729} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 267 +- **Dependency-aware candidate rank:** 267 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_060195d120dedafc704c04a7b6ed5b376da212ca75ead35bb668ebd57a5579ce` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:H3-3A|entrez:3020` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/H3-3B.md b/examples/target_cards/depmap_26q1/H3-3B.md new file mode 100644 index 0000000..6c40edf --- /dev/null +++ b/examples/target_cards/depmap_26q1/H3-3B.md @@ -0,0 +1,124 @@ +# Target hypothesis card: H3-3B + +## Target identity + +- **Target symbol:** H3-3B +- **Target name:** H3.3 histone B +- **Open Targets melanoma score:** 0.629 +- **Open Targets baseline rank:** 46 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 52 | not prioritized | -6 | +| Resistance biomarker | 0.000 | 54 | not prioritized | -8 | +| Tumor-intrinsic / small molecule | 0.000 | 52 | not prioritized | -6 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.629) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** H3-3B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for H3-3B in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.48313503447175277,"interquartile_range":0.21974635922869223,"maximum":-0.012604660993106698,"mean":-0.3755518963514822,"measured_model_count":56,"median":-0.33933172423069585,"minimum":-0.830902835454018,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.26338867524306053,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.19076786329106843,"interquartile_range":0.3226438251221172,"maximum":0.9130818463893109,"mean":0.36860403231261063,"measured_model_count":56,"median":0.3108532559759873,"minimum":0.019520162834314427,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5134116884131856,"threshold_fractions":[{"denominator":56,"fraction":0.2857142857142857,"numerator":16,"threshold":0.5},{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.029032926573638707,"dependency_probability_threshold_fractions":[{"context_fraction":0.2857142857142857,"difference":0.07627719962157048,"pan_cancer_fraction":0.20943708609271522,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":0.05120624408703879,"pan_cancer_fraction":0.0380794701986755,"threshold":0.8}],"gene_effect_mean":-0.02872055273816415,"gene_effect_median":-0.006189626891782374},"dependency_probability_context_minus_non_context_median":0.03019649567191035,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.2857142857142857,"difference":0.07998511904761904,"non_context_fraction":0.20572916666666666,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":0.05369543650793651,"non_context_fraction":0.035590277777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.030116690718491712,"gene_effect_context_minus_non_context_median":-0.006385863796944391} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 52 +- **Dependency-aware candidate rank:** 52 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d9bebcb5fee3a38ce961cdd95ec7b569cf554436e7f73ccabb2d92f6959dbba9` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:H3-3B|entrez:3021` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/H3C2.md b/examples/target_cards/depmap_26q1/H3C2.md new file mode 100644 index 0000000..6d9c996 --- /dev/null +++ b/examples/target_cards/depmap_26q1/H3C2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: H3C2 + +## Target identity + +- **Target symbol:** H3C2 +- **Target name:** H3 clustered histone 2 +- **Open Targets melanoma score:** 0.461 +- **Open Targets baseline rank:** 293 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 293 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 293 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 293 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.461) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** H3C2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for H3C2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.3206454080265252,"interquartile_range":0.1975554737523422,"maximum":0.16775661599292177,"mean":-0.21381437868097847,"measured_model_count":56,"median":-0.20958209107011988,"minimum":-0.5450733007125406,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.123089934274183,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.07225970162530683,"interquartile_range":0.1622007492055575,"maximum":0.6438797380322532,"mean":0.1724341084996443,"measured_model_count":56,"median":0.13346229752303382,"minimum":0.003772158858215319,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2344604508308643,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.05283129681457631,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.0031929990539262057,"pan_cancer_fraction":0.03890728476821192,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008278145695364239,"pan_cancer_fraction":0.008278145695364239,"threshold":0.8}],"gene_effect_mean":-0.0563058122332889,"gene_effect_median":-0.05730285933166218},"dependency_probability_context_minus_non_context_median":0.05647874440182907,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.0033482142857142877,"non_context_fraction":0.0390625,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008680555555555556,"non_context_fraction":0.008680555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.05904290032796286,"gene_effect_context_minus_non_context_median":-0.05928166598260526} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":96.29629629629629} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 293 +- **Dependency-aware candidate rank:** 293 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_f5072b3b792894be7d133d95de092d076e750269299cb8a4d1479670b625cc22` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:H3C2|entrez:8358` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/HAVCR2.md b/examples/target_cards/depmap_26q1/HAVCR2.md new file mode 100644 index 0000000..5e1fbd6 --- /dev/null +++ b/examples/target_cards/depmap_26q1/HAVCR2.md @@ -0,0 +1,73 @@ +# HAVCR2 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.02987708632932152,"interquartile_range":0.10506951338618359,"maximum":0.30558334855827995,"mean":0.028231970147176263,"measured_model_count":56,"median":0.021078887581460377,"minimum":-0.19101340457200128,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07519242705686208,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.00789883343293582,"interquartile_range":0.01833445389224319,"maximum":0.11204404808981419,"mean":0.023435654418921713,"measured_model_count":56,"median":0.014689188029942131,"minimum":0.0016295139647264294,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02623328732517901,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003337664315021603,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.009017409880538656,"gene_effect_median":0.0003966547468448878},"dependency_probability_context_minus_non_context_median":-0.003616138300594568,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0094557561941759,"gene_effect_context_minus_non_context_median":0.0003966547468448878} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_c248336f2529cedafa19f7abd4b8014abd56c13a26f40fcdd4e68a0f90d7196d` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:HAVCR2|entrez:84868` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/HGF.md b/examples/target_cards/depmap_26q1/HGF.md new file mode 100644 index 0000000..bd82bc3 --- /dev/null +++ b/examples/target_cards/depmap_26q1/HGF.md @@ -0,0 +1,124 @@ +# Target hypothesis card: HGF + +## Target identity + +- **Target symbol:** HGF +- **Target name:** hepatocyte growth factor +- **Open Targets melanoma score:** 0.552 +- **Open Targets baseline rank:** 152 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 154 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 155 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 154 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.552) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** HGF lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for HGF in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.027861706906206877,"interquartile_range":0.14525680904923657,"maximum":0.4677803805613251,"mean":0.09965417928922386,"measured_model_count":56,"median":0.11360474924188933,"minimum":-0.25539137465273065,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.17311851595544345,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0037531548730815527,"interquartile_range":0.013962672062846015,"maximum":0.22696926601274922,"mean":0.016201461765943802,"measured_model_count":56,"median":0.007790645531783854,"minimum":0.0002821764476149182,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.01771582693592757,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0006945584392857775,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.0015775449469577485,"gene_effect_median":0.006504541187336843},"dependency_probability_context_minus_non_context_median":-0.0007014155545820213,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0016542311596570852,"gene_effect_context_minus_non_context_median":0.006670081421324067} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 154 +- **Dependency-aware candidate rank:** 154 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2d3d71d7bf71d9d7df55c2f5b5d686b039eed8feee14a9af9b12e41dce5e2202` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:HGF|entrez:3082` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/HLA-A.md b/examples/target_cards/depmap_26q1/HLA-A.md new file mode 100644 index 0000000..3f1af5d --- /dev/null +++ b/examples/target_cards/depmap_26q1/HLA-A.md @@ -0,0 +1,73 @@ +# HLA-A — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.2552972965494641,"interquartile_range":0.15781341479361444,"maximum":0.08996078518352843,"mean":-0.18008238783186595,"measured_model_count":56,"median":-0.17280744614212706,"minimum":-0.5750630715153462,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.09748388175584964,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.049497676353652244,"interquartile_range":0.1167644450917843,"maximum":0.6029775488822585,"mean":0.13965062801032252,"measured_model_count":56,"median":0.09981467563830992,"minimum":0.007059461637493488,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.16626212144543653,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0028874450778858807,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.014191106906338694,"pan_cancer_fraction":0.02152317880794702,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.0076694632735165025,"gene_effect_median":-0.0014223753886474788},"dependency_probability_context_minus_non_context_median":0.0028874450778858807,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.01488095238095238,"non_context_fraction":0.020833333333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.008042284404867955,"gene_effect_context_minus_non_context_median":-0.0014984427927402233} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_43d9bc0efe8d920b0cfc428175995672933871455796868dd67399d4c95a5e14` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:HLA-A|entrez:3105` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/HLA-B.md b/examples/target_cards/depmap_26q1/HLA-B.md new file mode 100644 index 0000000..fad67d0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/HLA-B.md @@ -0,0 +1,73 @@ +# HLA-B — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.15968912982781502,"interquartile_range":0.18480063823124976,"maximum":0.27007374516910987,"mean":-0.07374631368331996,"measured_model_count":56,"median":-0.07423159504405025,"minimum":-0.485704165710984,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02511150840343474,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01395180875400719,"interquartile_range":0.07055243596738246,"maximum":0.49127695693581824,"mean":0.0784175275143234,"measured_model_count":56,"median":0.04113581826807637,"minimum":0.0013968572167001247,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08450424472138965,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.003823438453709818,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.012417218543046357,"pan_cancer_fraction":0.012417218543046357,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.013620445179712164,"gene_effect_median":-0.013905226303427526},"dependency_probability_context_minus_non_context_median":0.00396711267390569,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.013020833333333334,"non_context_fraction":0.013020833333333334,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.014282550153725954,"gene_effect_context_minus_non_context_median":-0.014197361569255919} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_201b7f8924c1431035c311800124e678903aef894ffd7cd56ab618fdc727c07e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:HLA-B|entrez:3106` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/HNF1A.md b/examples/target_cards/depmap_26q1/HNF1A.md new file mode 100644 index 0000000..d4ef0f0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/HNF1A.md @@ -0,0 +1,124 @@ +# Target hypothesis card: HNF1A + +## Target identity + +- **Target symbol:** HNF1A +- **Target name:** HNF1 homeobox A +- **Open Targets melanoma score:** 0.558 +- **Open Targets baseline rank:** 140 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 142 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 143 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 142 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.558) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** HNF1A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for HNF1A in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.16293366063630432,"interquartile_range":0.19824401087906468,"maximum":0.1912757751751536,"mean":-0.07256376755814067,"measured_model_count":56,"median":-0.04778355491386431,"minimum":-0.5122705302653734,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.035310350242760344,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01457113924168986,"interquartile_range":0.07886206050438543,"maximum":0.6658078682606292,"mean":0.07098839603343211,"measured_model_count":56,"median":0.03521909600150257,"minimum":0.0039146957197934325,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0934331997460753,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.012960500764139918,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.01939451277199622,"pan_cancer_fraction":0.037251655629139076,"threshold":0.5},{"context_fraction":0.0,"difference":-0.027317880794701987,"pan_cancer_fraction":0.027317880794701987,"threshold":0.8}],"gene_effect_mean":0.042514986696841256,"gene_effect_median":0.03906099413564805},"dependency_probability_context_minus_non_context_median":-0.01386410286868471,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.02033730158730159,"non_context_fraction":0.03819444444444445,"threshold":0.5},{"context_fraction":0.0,"difference":-0.028645833333333332,"non_context_fraction":0.028645833333333332,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.044581687439048806,"gene_effect_context_minus_non_context_median":0.04095335611525912} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 142 +- **Dependency-aware candidate rank:** 142 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e95a9ab63f4796506f26238946f4a129076f4f73ff476961a82f915c9eaa7d44` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:HNF1A|entrez:6927` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/HRAS.md b/examples/target_cards/depmap_26q1/HRAS.md new file mode 100644 index 0000000..a92589a --- /dev/null +++ b/examples/target_cards/depmap_26q1/HRAS.md @@ -0,0 +1,124 @@ +# Target hypothesis card: HRAS + +## Target identity + +- **Target symbol:** HRAS +- **Target name:** HRas proto-oncogene, GTPase +- **Open Targets melanoma score:** 0.470 +- **Open Targets baseline rank:** 283 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 283 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 283 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 283 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.470) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** HRAS lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for HRAS in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.27036777326378536,"interquartile_range":0.18381116909250983,"maximum":0.12159438311188783,"mean":-0.2120542528403669,"measured_model_count":56,"median":-0.15093706759740222,"minimum":-1.3098886826432632,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.08655660417127553,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.03936622590302448,"interquartile_range":0.15378447332836542,"maximum":0.9996455744842113,"mean":0.17412857012370694,"measured_model_count":56,"median":0.09876526486851311,"minimum":0.004326422830182301,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.19315069923138992,"threshold_fractions":[{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0012393581733524672,"dependency_probability_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":0.03831598864711447,"pan_cancer_fraction":0.033112582781456956,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.022469252601702933,"pan_cancer_fraction":0.013245033112582781,"threshold":0.8}],"gene_effect_mean":-0.02652314465051092,"gene_effect_median":0.020462495254849472},"dependency_probability_context_minus_non_context_median":0.0012393581733524672,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":0.040178571428571425,"non_context_fraction":0.03125,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.023561507936507936,"non_context_fraction":0.012152777777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.027812464182132873,"gene_effect_context_minus_non_context_median":0.021395327108499673} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 283 +- **Dependency-aware candidate rank:** 283 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_00b8562ea04bcc22eab699d158b353dc85657751afc3bbd71beef92ccea4b0ec` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:HRAS|entrez:3265` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IDH1.md b/examples/target_cards/depmap_26q1/IDH1.md new file mode 100644 index 0000000..7109c55 --- /dev/null +++ b/examples/target_cards/depmap_26q1/IDH1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: IDH1 + +## Target identity + +- **Target symbol:** IDH1 +- **Target name:** isocitrate dehydrogenase (NADP(+)) 1 +- **Open Targets melanoma score:** 0.578 +- **Open Targets baseline rank:** 105 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 108 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 109 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 108 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.578) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** IDH1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for IDH1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.15448357052904954,"interquartile_range":0.1485721977747924,"maximum":0.20896505721913816,"mean":-0.09337330784363378,"measured_model_count":56,"median":-0.07154041810566106,"minimum":-1.0350852467755454,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.005911372754257127,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.02007757384147797,"interquartile_range":0.06085228289583204,"maximum":0.9942833245620363,"mean":0.08093502900778993,"measured_model_count":56,"median":0.03720868827740238,"minimum":0.0038582797922045104,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08092985673731001,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.011733095136837665,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.028263954588457898,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.01702932828760643,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.002041933966753659,"gene_effect_median":0.017447678140363243},"dependency_probability_context_minus_non_context_median":-0.012445510404531221,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.029637896825396824,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.017857142857142856,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0021411946456930675,"gene_effect_context_minus_non_context_median":0.01793534566771285} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 108 +- **Dependency-aware candidate rank:** 108 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e331ec4f05a441ffe543c5ccc7a2c5cff7f322cc1692428e9e61601f98726a15` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IDH1|entrez:3417` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IDO1.md b/examples/target_cards/depmap_26q1/IDO1.md new file mode 100644 index 0000000..2ef4685 --- /dev/null +++ b/examples/target_cards/depmap_26q1/IDO1.md @@ -0,0 +1,73 @@ +# IDO1 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.012105508427349601,"interquartile_range":0.1220095967242903,"maximum":0.5660480673354267,"mean":0.05266969293575046,"measured_model_count":56,"median":0.05843457057831062,"minimum":-0.28197971786765974,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1099040882969407,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005713555583787177,"interquartile_range":0.018801276132440366,"maximum":0.1884526002652624,"mean":0.028673556894948857,"measured_model_count":56,"median":0.012181418582402407,"minimum":0.0001486835036999761,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.024514831716227543,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0017848407840746726,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.031560927535275805,"gene_effect_median":-0.019909371893919524},"dependency_probability_context_minus_non_context_median":0.0018090039940647454,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03309513929046282,"gene_effect_context_minus_non_context_median":-0.02147555857723673} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a1cd3c9169e009a6d3cdd3adf811fb3369c178cb298a23fb81d9c8eb67be160a` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IDO1|entrez:3620` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IFNAR1.md b/examples/target_cards/depmap_26q1/IFNAR1.md new file mode 100644 index 0000000..7813542 --- /dev/null +++ b/examples/target_cards/depmap_26q1/IFNAR1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: IFNAR1 + +## Target identity + +- **Target symbol:** IFNAR1 +- **Target name:** interferon alpha and beta receptor subunit 1 +- **Open Targets melanoma score:** 0.611 +- **Open Targets baseline rank:** 55 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 59 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 61 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 59 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.611) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** IFNAR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for IFNAR1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.02072702775838113,"interquartile_range":0.15827098898244746,"maximum":0.6503786890171347,"mean":0.12145333029466691,"measured_model_count":56,"median":0.10365599503808863,"minimum":-0.16933916992926473,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1789980167408286,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.003956222562329722,"interquartile_range":0.01411125018501198,"maximum":0.07902273935717684,"mean":0.013110592051675965,"measured_model_count":56,"median":0.00683742314520901,"minimum":9.673493890419153e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.018067472747341703,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0022345454968270284,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.0137521212968921,"gene_effect_median":0.01271549373961664},"dependency_probability_context_minus_non_context_median":-0.002283469781756406,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.014420627193268795,"gene_effect_context_minus_non_context_median":0.013105917150467536} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 59 +- **Dependency-aware candidate rank:** 59 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_474cbee8dab89106167f0cb772598a59caf817095f2fc1f1b144e10d26fdcf7d` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IFNAR1|entrez:3454` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IFNAR2.md b/examples/target_cards/depmap_26q1/IFNAR2.md new file mode 100644 index 0000000..0950ef7 --- /dev/null +++ b/examples/target_cards/depmap_26q1/IFNAR2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: IFNAR2 + +## Target identity + +- **Target symbol:** IFNAR2 +- **Target name:** interferon alpha and beta receptor subunit 2 +- **Open Targets melanoma score:** 0.592 +- **Open Targets baseline rank:** 79 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 83 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 85 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 83 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.592) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** IFNAR2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for IFNAR2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.01738288137045248,"interquartile_range":0.12488492898376848,"maximum":0.5714236108108321,"mean":0.0503920619753953,"measured_model_count":56,"median":0.04386869337198644,"minimum":-0.45216017373590417,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.107502047613316,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0072759297821299185,"interquartile_range":0.016571792690970602,"maximum":0.5636407199137389,"mean":0.02954335432879648,"measured_model_count":56,"median":0.012610739619383672,"minimum":4.461740631815872e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02384772247310052,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.000658658850054377,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.016201513718070007,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.019012962091614093,"gene_effect_median":-0.009370796305043658},"dependency_probability_context_minus_non_context_median":-0.0007099957223426507,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.0169890873015873,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0199372033044009,"gene_effect_context_minus_non_context_median":-0.009585235386186088} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 83 +- **Dependency-aware candidate rank:** 83 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_637ea16bfbc50e923cf4d4f3355b47fb08051992ee1c7fc2e81c98159732d28f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IFNAR2|entrez:3455` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IFNGR1.md b/examples/target_cards/depmap_26q1/IFNGR1.md new file mode 100644 index 0000000..0dd3b45 --- /dev/null +++ b/examples/target_cards/depmap_26q1/IFNGR1.md @@ -0,0 +1,73 @@ +# IFNGR1 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.03662359372573171,"interquartile_range":0.08240767601439589,"maximum":0.5871211700580072,"mean":0.0897245542698267,"measured_model_count":56,"median":0.08379368461486343,"minimum":-0.1744025104314158,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1190312697401276,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005404275629848286,"interquartile_range":0.008713219530913212,"maximum":0.06268986152833818,"mean":0.01167419637458284,"measured_model_count":56,"median":0.008325044038448394,"minimum":0.000290948338437609,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.014117495160761499,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00018228979421905725,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.004881835737120865,"gene_effect_median":-0.015810743032892788},"dependency_probability_context_minus_non_context_median":-0.00021181986832344984,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.005119147196564172,"gene_effect_context_minus_non_context_median":-0.01620129900277649} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_00833cde4b1bc1e68e5a57bcb01fd89aac37a482209d44bc9c1fc0f755d665f2` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IFNGR1|entrez:3459` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IKBKB.md b/examples/target_cards/depmap_26q1/IKBKB.md new file mode 100644 index 0000000..9eb914f --- /dev/null +++ b/examples/target_cards/depmap_26q1/IKBKB.md @@ -0,0 +1,124 @@ +# Target hypothesis card: IKBKB + +## Target identity + +- **Target symbol:** IKBKB +- **Target name:** inhibitor of nuclear factor kappa B kinase subunit beta +- **Open Targets melanoma score:** 0.575 +- **Open Targets baseline rank:** 108 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 111 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 112 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 111 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.575) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** IKBKB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for IKBKB in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.16570556644074375,"interquartile_range":0.21406066264224513,"maximum":0.277540361548298,"mean":-0.0537285075628385,"measured_model_count":56,"median":-0.035178888153201554,"minimum":-0.4502159236126616,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04835509620150139,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.012418408279742225,"interquartile_range":0.07750041480523112,"maximum":0.3740135448755501,"mean":0.06264769752353014,"measured_model_count":56,"median":0.032710880080595445,"minimum":0.001974767741085321,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08991882308497334,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0014713304205474648,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04304635761589404,"pan_cancer_fraction":0.04304635761589404,"threshold":0.5},{"context_fraction":0.0,"difference":-0.018211920529801324,"pan_cancer_fraction":0.018211920529801324,"threshold":0.8}],"gene_effect_mean":0.022294775116363207,"gene_effect_median":0.015432259763544134},"dependency_probability_context_minus_non_context_median":-0.0019590452564146876,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04513888888888889,"non_context_fraction":0.04513888888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.019097222222222224,"non_context_fraction":0.019097222222222224,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.023378548906742076,"gene_effect_context_minus_non_context_median":0.01584270996744524} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 111 +- **Dependency-aware candidate rank:** 111 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_af84bacaebe1a9a8604d13e8fa6610e0392d6d1d554ab54eef621eeb5636a62f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IKBKB|entrez:3551` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IKZF1.md b/examples/target_cards/depmap_26q1/IKZF1.md new file mode 100644 index 0000000..3ecaab1 --- /dev/null +++ b/examples/target_cards/depmap_26q1/IKZF1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: IKZF1 + +## Target identity + +- **Target symbol:** IKZF1 +- **Target name:** IKAROS family zinc finger 1 +- **Open Targets melanoma score:** 0.617 +- **Open Targets baseline rank:** 50 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 55 | not prioritized | -5 | +| Resistance biomarker | 0.000 | 57 | not prioritized | -7 | +| Tumor-intrinsic / small molecule | 0.000 | 55 | not prioritized | -5 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.617) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** IKZF1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for IKZF1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.027512744956176855,"interquartile_range":0.12572245092388826,"maximum":0.3196388161680785,"mean":0.08284123758726089,"measured_model_count":56,"median":0.08862815619119767,"minimum":-0.24711666136165655,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.15323519588006512,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.004563234822409594,"interquartile_range":0.01368660044820895,"maximum":0.10706346655544202,"mean":0.016026068206720766,"measured_model_count":56,"median":0.008626052643370095,"minimum":0.001245724641473512,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.018249835270618544,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004837720636222887,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.028973509933774833,"pan_cancer_fraction":0.028973509933774833,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013245033112582781,"pan_cancer_fraction":0.013245033112582781,"threshold":0.8}],"gene_effect_mean":0.054398881930841705,"gene_effect_median":0.03638743497379943},"dependency_probability_context_minus_non_context_median":-0.005203896204431409,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.030381944444444444,"non_context_fraction":0.030381944444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013888888888888888,"non_context_fraction":0.013888888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05704327202470209,"gene_effect_context_minus_non_context_median":0.03910950912065414} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 55 +- **Dependency-aware candidate rank:** 55 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ee71f1a8c1836ce7942b2b4f6df5f928442cac42430f4395bf80b44919ee0366` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IKZF1|entrez:10320` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IKZF3.md b/examples/target_cards/depmap_26q1/IKZF3.md new file mode 100644 index 0000000..c4e4b52 --- /dev/null +++ b/examples/target_cards/depmap_26q1/IKZF3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: IKZF3 + +## Target identity + +- **Target symbol:** IKZF3 +- **Target name:** IKAROS family zinc finger 3 +- **Open Targets melanoma score:** 0.496 +- **Open Targets baseline rank:** 256 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 258 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 258 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 258 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.496) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** IKZF3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for IKZF3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.15225471866134643,"interquartile_range":0.1450957650450127,"maximum":0.5687894421280447,"mean":-0.07457440753634013,"measured_model_count":56,"median":-0.08258590755905212,"minimum":-0.4283817472108195,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.00715895361633373,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.020035342674531775,"interquartile_range":0.06675520347815952,"maximum":0.4832088876731502,"mean":0.06720851685893349,"measured_model_count":56,"median":0.047431048431888424,"minimum":0.00014254418116806933,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0867905461526913,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00012296220340794056,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03228476821192053,"pan_cancer_fraction":0.03228476821192053,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0173841059602649,"pan_cancer_fraction":0.0173841059602649,"threshold":0.8}],"gene_effect_mean":0.02904462386694076,"gene_effect_median":0.0028492014703619395},"dependency_probability_context_minus_non_context_median":-0.00012296220340794056,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.033854166666666664,"non_context_fraction":0.033854166666666664,"threshold":0.5},{"context_fraction":0.0,"difference":-0.018229166666666668,"non_context_fraction":0.018229166666666668,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.030456515304917095,"gene_effect_context_minus_non_context_median":0.0028492014703619395} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 258 +- **Dependency-aware candidate rank:** 258 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_7d1b7610d0d4f2fd2e9bc93af5df48ea4ee9cf9f7a911b461b1a5fe6b531136d` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IKZF3|entrez:22806` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IL2RA.md b/examples/target_cards/depmap_26q1/IL2RA.md new file mode 100644 index 0000000..2220b7f --- /dev/null +++ b/examples/target_cards/depmap_26q1/IL2RA.md @@ -0,0 +1,130 @@ +# Target hypothesis card: IL2RA + +## Target identity + +- **Target symbol:** IL2RA +- **Target name:** interleukin 2 receptor subunit alpha +- **Open Targets melanoma score:** 0.624 +- **Open Targets baseline rank:** 48 + +## Stable TargetIntel-IO classification + +- **Role classification:** Treg-suppression marker / possible IO-combination target +- **Role confidence:** medium +- **Therapeutic direction:** deplete / block / use as biomarker +- **Best modality:** antibody / Treg-associated IO-combination candidate +- **Resistance axis:** treg_suppression +- **Matched resistance programs:** Treg-mediated suppression + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.673 | 5 | medium | 43 | +| Resistance biomarker | 0.628 | 5 | medium | 43 | +| Tumor-intrinsic / small molecule | 0.126 | 14 | low | 34 | + +## Evidence for + +- May support patient stratification or Treg-targeting hypotheses +- Relevant to immune suppression in the tumor microenvironment +- Some targets are surface-accessible +- Moderate Open Targets melanoma association score (0.624) +- Maps to curated anti-PD-1 resistance program: Treg-mediated suppression +- Antibody fit is medium-high + +## Evidence against / limitations + +- Requires careful distinction between biomarker and causal target +- Some markers are lineage markers rather than safe therapeutic targets +- Treg targeting can affect normal immune tolerance + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.240 +- **Main limitation:** No major limitation flagged by current MVP rules +- **Uncertainty reason:** Main limitation: No major limitation flagged by current MVP rules +- **Deprioritization reason:** No strong deprioritization reason from current MVP rules + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for IL2RA in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.020638816605233,"interquartile_range":0.10185439590666129,"maximum":0.2707955970772144,"mean":0.028608067454334866,"measured_model_count":56,"median":0.02141508360816008,"minimum":-0.28140353524938666,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08121557930142828,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.009334879488875191,"interquartile_range":0.017097162374383305,"maximum":0.21297870352246084,"mean":0.0225685182916743,"measured_model_count":56,"median":0.01744431698994827,"minimum":0.0019616077520202666,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.026432041863258496,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0018854255800013313,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.009489097668670381,"gene_effect_median":-0.012483582075400942},"dependency_probability_context_minus_non_context_median":0.0019468436361349435,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.009950373249786312,"gene_effect_context_minus_non_context_median":-0.013652839911629001} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 5 +- **Dependency-aware candidate rank:** 6 +- **Rank delta:** 1 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_b31bc15820b545d199af7c982fb3cb1fca81d05d4ef557424ef473951cdce430` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IL2RA|entrez:3559` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IL2RB.md b/examples/target_cards/depmap_26q1/IL2RB.md new file mode 100644 index 0000000..4b19eb3 --- /dev/null +++ b/examples/target_cards/depmap_26q1/IL2RB.md @@ -0,0 +1,124 @@ +# Target hypothesis card: IL2RB + +## Target identity + +- **Target symbol:** IL2RB +- **Target name:** interleukin 2 receptor subunit beta +- **Open Targets melanoma score:** 0.552 +- **Open Targets baseline rank:** 147 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 149 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 150 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 149 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.552) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** IL2RB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for IL2RB in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06167574734909529,"interquartile_range":0.11419653118966835,"maximum":0.4361428141068317,"mean":-0.00577974216374198,"measured_model_count":56,"median":0.0038683297949551783,"minimum":-0.31092525578047747,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.052520783840573064,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.011368937411090727,"interquartile_range":0.02233347339096224,"maximum":0.24466414856941635,"mean":0.03389348922793028,"measured_model_count":56,"median":0.020888460567987405,"minimum":0.0003780927747437147,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03370241080205297,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0035625711408692542,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.03015194114942479,"gene_effect_median":-0.01896943972780838},"dependency_probability_context_minus_non_context_median":0.0035879511611938766,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03161766051085518,"gene_effect_context_minus_non_context_median":-0.02052787748195724} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 149 +- **Dependency-aware candidate rank:** 149 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_88ca4f06a51f01c16c1fb63e93cafbb314fc7796e9bbf4d5a21c67bc19e52223` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IL2RB|entrez:3560` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IL2RG.md b/examples/target_cards/depmap_26q1/IL2RG.md new file mode 100644 index 0000000..aad806f --- /dev/null +++ b/examples/target_cards/depmap_26q1/IL2RG.md @@ -0,0 +1,124 @@ +# Target hypothesis card: IL2RG + +## Target identity + +- **Target symbol:** IL2RG +- **Target name:** interleukin 2 receptor subunit gamma +- **Open Targets melanoma score:** 0.553 +- **Open Targets baseline rank:** 146 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 148 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 149 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 148 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.553) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** IL2RG lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for IL2RG in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.0212074848635695,"interquartile_range":0.1010287784388279,"maximum":0.2924073670526511,"mean":0.06727286663522855,"measured_model_count":56,"median":0.0675100811958824,"minimum":-0.18469177564542644,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1222362633023974,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.00617458498793976,"interquartile_range":0.010574852516974416,"maximum":0.07360677819534792,"mean":0.014465831632885265,"measured_model_count":56,"median":0.010681045947869647,"minimum":0.0011765421315893725,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.016749437504914175,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.000809560946739736,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":3.077497282899522e-05,"gene_effect_median":-0.004176339451322203},"dependency_probability_context_minus_non_context_median":-0.0009039873661311846,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":3.227097845262539e-05,"gene_effect_context_minus_non_context_median":-0.004276167374979975} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 148 +- **Dependency-aware candidate rank:** 148 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_f001ed049e478e354cb98bf6f4b4ae9778043805613e42cda9f9f2933dd65cb4` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IL2RG|entrez:3561` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IL7R.md b/examples/target_cards/depmap_26q1/IL7R.md new file mode 100644 index 0000000..1a4afa4 --- /dev/null +++ b/examples/target_cards/depmap_26q1/IL7R.md @@ -0,0 +1,124 @@ +# Target hypothesis card: IL7R + +## Target identity + +- **Target symbol:** IL7R +- **Target name:** interleukin 7 receptor +- **Open Targets melanoma score:** 0.570 +- **Open Targets baseline rank:** 114 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 116 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 117 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 116 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.570) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** IL7R lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for IL7R in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.007574111825057125,"interquartile_range":0.10459650304601474,"maximum":0.2951420481853716,"mean":0.06107047570028201,"measured_model_count":56,"median":0.06426875135630919,"minimum":-0.2820855435259647,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11217061487107187,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005832086899811304,"interquartile_range":0.012917677632533172,"maximum":0.13158609085739606,"mean":0.01743959809337777,"measured_model_count":56,"median":0.010212835631815064,"minimum":0.0016609086285636968,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.018749764532344476,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002909761879021573,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.005681804761027649,"gene_effect_median":0.009355084110728065},"dependency_probability_context_minus_non_context_median":-0.0031124595115192572,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.005958003603577594,"gene_effect_context_minus_non_context_median":0.01024282360728069} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 116 +- **Dependency-aware candidate rank:** 116 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_7269dad5115f5d36f6b0dbdcc3f7e7eb7d633a0d105197d35af3ac12a02df613` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IL7R|entrez:3575` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IRF1.md b/examples/target_cards/depmap_26q1/IRF1.md new file mode 100644 index 0000000..93d084d --- /dev/null +++ b/examples/target_cards/depmap_26q1/IRF1.md @@ -0,0 +1,73 @@ +# IRF1 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.09754301210474758,"interquartile_range":0.12296515702841573,"maximum":0.26037306954494316,"mean":-0.03541258134233933,"measured_model_count":56,"median":-0.021794338384010233,"minimum":-0.4899942974308896,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.025422144923668153,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.013848609180153479,"interquartile_range":0.03581323489428311,"maximum":0.49436318873189083,"mean":0.04739429910381706,"measured_model_count":56,"median":0.02736019181396147,"minimum":0.0011200409618568816,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04966184407443659,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005307021890764426,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.014909579247357252,"gene_effect_median":0.02854707621615703},"dependency_probability_context_minus_non_context_median":-0.006068298031833317,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.015634350460770413,"gene_effect_context_minus_non_context_median":0.029700220772131348} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_5587d9d52511ee49fff4064d020c2c608d726eb33666de09b08d9bba455f18ee` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IRF1|entrez:3659` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IRF4.md b/examples/target_cards/depmap_26q1/IRF4.md new file mode 100644 index 0000000..a7502b3 --- /dev/null +++ b/examples/target_cards/depmap_26q1/IRF4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: IRF4 + +## Target identity + +- **Target symbol:** IRF4 +- **Target name:** interferon regulatory factor 4 +- **Open Targets melanoma score:** 0.693 +- **Open Targets baseline rank:** 23 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 30 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 32 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.009 | 25 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.693) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** IRF4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for IRF4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.6327296669157861,"interquartile_range":0.5324128216394848,"maximum":0.6235667057736118,"mean":-0.39855183522522275,"measured_model_count":56,"median":-0.23865970092198735,"minimum":-1.5645985791747252,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.10031684527630133,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.047184383715357534,"interquartile_range":0.6857642743569041,"maximum":1.0,"mean":0.35466976185022175,"measured_model_count":56,"median":0.1569832292049153,"minimum":2.7037314917020238e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.7329486580722616,"threshold_fractions":[{"denominator":56,"fraction":0.32142857142857145,"numerator":18,"threshold":0.5},{"denominator":56,"fraction":0.23214285714285715,"numerator":13,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.10225635227015582,"dependency_probability_threshold_fractions":[{"context_fraction":0.32142857142857145,"difference":0.24940870387890257,"pan_cancer_fraction":0.07201986754966887,"threshold":0.5},{"context_fraction":0.23214285714285715,"difference":0.17254020813623464,"pan_cancer_fraction":0.059602649006622516,"threshold":0.8}],"gene_effect_mean":-0.21403777183379744,"gene_effect_median":-0.13333449997103344},"dependency_probability_context_minus_non_context_median":0.10371211068611616,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.32142857142857145,"difference":0.26153273809523814,"non_context_fraction":0.059895833333333336,"threshold":0.5},{"context_fraction":0.23214285714285715,"difference":0.18092757936507936,"non_context_fraction":0.051215277777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.22444238574238473,"gene_effect_context_minus_non_context_median":-0.1359491297562201} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 30 +- **Dependency-aware candidate rank:** 30 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_bd0f27b20205aefe67ca908c9390ba7067e99dca131248aefebb5a532f4fc3ae` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IRF4|entrez:3662` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/IRS4.md b/examples/target_cards/depmap_26q1/IRS4.md new file mode 100644 index 0000000..56ec43b --- /dev/null +++ b/examples/target_cards/depmap_26q1/IRS4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: IRS4 + +## Target identity + +- **Target symbol:** IRS4 +- **Target name:** insulin receptor substrate 4 +- **Open Targets melanoma score:** 0.525 +- **Open Targets baseline rank:** 191 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 193 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 193 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 193 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.525) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** IRS4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for IRS4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.18839419052946696,"interquartile_range":0.1798390999941063,"maximum":0.21201552366845364,"mean":-0.09293988067528866,"measured_model_count":56,"median":-0.07806148005826202,"minimum":-0.38768029787152425,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.00855509053536067,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.018429753510722652,"interquartile_range":0.07826150665683715,"maximum":0.4219517244413161,"mean":0.0786677639842874,"measured_model_count":56,"median":0.0474389800368865,"minimum":0.003356154467398746,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0966912601675598,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.008685965826528003,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.011589403973509934,"pan_cancer_fraction":0.011589403973509934,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.8}],"gene_effect_mean":0.023509037116381748,"gene_effect_median":0.02792301116680959},"dependency_probability_context_minus_non_context_median":-0.00931148966276258,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.012152777777777778,"non_context_fraction":0.012152777777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.024651837531761395,"gene_effect_context_minus_non_context_median":0.029325363379890765} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 193 +- **Dependency-aware candidate rank:** 193 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_afae59de99b761f9b7a90a373df1341d383aa0f80ba0a64a6755125681cd2271` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:IRS4|entrez:8471` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/JAK1.md b/examples/target_cards/depmap_26q1/JAK1.md new file mode 100644 index 0000000..3290844 --- /dev/null +++ b/examples/target_cards/depmap_26q1/JAK1.md @@ -0,0 +1,132 @@ +# Target hypothesis card: JAK1 + +## Target identity + +- **Target symbol:** JAK1 +- **Target name:** Janus kinase 1 +- **Open Targets melanoma score:** 0.482 +- **Open Targets baseline rank:** 271 + +## Stable TargetIntel-IO classification + +- **Role classification:** IFN-gamma resistance mechanism / biomarker +- **Role confidence:** high +- **Therapeutic direction:** use as biomarker / patient stratification +- **Best modality:** resistance biomarker / patient stratification +- **Resistance axis:** ifng_resistance +- **Matched resistance programs:** IFN-gamma pathway resistance + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.214 | 11 | low | 260 | +| Resistance biomarker | 0.792 | 3 | high | 268 | +| Tumor-intrinsic / small molecule | 0.114 | 16 | low | 255 | + +## Evidence for + +- Mechanistically linked to immune resistance +- Relevant to interferon-response competence +- Useful for identifying tumors with impaired immune responsiveness +- Moderate Open Targets melanoma association score (0.482) +- Maps to curated anti-PD-1 resistance program: IFN-gamma pathway resistance +- Stable role classifier confidence is high +- Biomarker fit is high + +## Evidence against / limitations + +- Loss-of-function resistance mechanisms may be hard to target directly +- May indicate resistance rather than therapeutic vulnerability +- Not usually a direct IO-combination antibody target +- Most useful as biomarker or stratification marker rather than direct therapeutic target + +## Confidence and uncertainty + +- **Confidence level:** high confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.320 +- **Main limitation:** Likely more useful for stratification than direct therapeutic targeting +- **Uncertainty reason:** Main limitation: Likely more useful for stratification than direct therapeutic targeting +- **Deprioritization reason:** JAK1 should not be deprioritized globally, but should be ranked mainly in biomarker or patient-stratification mode. + +## Recommended next validation experiment + +- **Validation category:** biomarker validation +- **Next experiment:** Test whether JAK1 status or expression differs between anti-PD-1 responders and non-responders in an independent melanoma cohort. +- **Rationale:** This would determine whether the candidate has practical value as a resistance biomarker or patient-stratification feature. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06904007760789696,"interquartile_range":0.19526888874388504,"maximum":0.9465240508757611,"mean":0.04591288417512017,"measured_model_count":56,"median":0.02114251550731768,"minimum":-0.3753752648328587,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12622881113598808,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.006062450283729294,"interquartile_range":0.034487534754270424,"maximum":0.4388416274607162,"mean":0.0392200208609982,"measured_model_count":56,"median":0.020298339745821688,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04054998503799972,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01630133583031499,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04056291390728477,"pan_cancer_fraction":0.04056291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":-0.012417218543046357,"pan_cancer_fraction":0.012417218543046357,"threshold":0.8}],"gene_effect_mean":0.1143914024787971,"gene_effect_median":0.07852203097934171},"dependency_probability_context_minus_non_context_median":-0.017842739234583828,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.042534722222222224,"non_context_fraction":0.042534722222222224,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013020833333333334,"non_context_fraction":0.013020833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.1199520956548499,"gene_effect_context_minus_non_context_median":0.08286038187670032} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 11 +- **Dependency-aware candidate rank:** 19 +- **Rank delta:** 8 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_38d521b13eaca50b1777062b74ee94be66e56a9306d92f6dd881361e2007b804` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:JAK1|entrez:3716` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/JAK2.md b/examples/target_cards/depmap_26q1/JAK2.md new file mode 100644 index 0000000..34c2452 --- /dev/null +++ b/examples/target_cards/depmap_26q1/JAK2.md @@ -0,0 +1,132 @@ +# Target hypothesis card: JAK2 + +## Target identity + +- **Target symbol:** JAK2 +- **Target name:** Janus kinase 2 +- **Open Targets melanoma score:** 0.489 +- **Open Targets baseline rank:** 265 + +## Stable TargetIntel-IO classification + +- **Role classification:** IFN-gamma resistance mechanism / biomarker +- **Role confidence:** high +- **Therapeutic direction:** use as biomarker / patient stratification +- **Best modality:** resistance biomarker / patient stratification +- **Resistance axis:** ifng_resistance +- **Matched resistance programs:** IFN-gamma pathway resistance + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.215 | 10 | low | 255 | +| Resistance biomarker | 0.793 | 2 | high | 263 | +| Tumor-intrinsic / small molecule | 0.115 | 15 | low | 250 | + +## Evidence for + +- Mechanistically linked to immune resistance +- Relevant to interferon-response competence +- Useful for identifying tumors with impaired immune responsiveness +- Moderate Open Targets melanoma association score (0.489) +- Maps to curated anti-PD-1 resistance program: IFN-gamma pathway resistance +- Stable role classifier confidence is high +- Biomarker fit is high + +## Evidence against / limitations + +- Loss-of-function resistance mechanisms may be hard to target directly +- May indicate resistance rather than therapeutic vulnerability +- Not usually a direct IO-combination antibody target +- Most useful as biomarker or stratification marker rather than direct therapeutic target + +## Confidence and uncertainty + +- **Confidence level:** high confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.320 +- **Main limitation:** Likely more useful for stratification than direct therapeutic targeting +- **Uncertainty reason:** Main limitation: Likely more useful for stratification than direct therapeutic targeting +- **Deprioritization reason:** JAK2 should not be deprioritized globally, but should be ranked mainly in biomarker or patient-stratification mode. + +## Recommended next validation experiment + +- **Validation category:** biomarker validation +- **Next experiment:** Test whether JAK2 status or expression differs between anti-PD-1 responders and non-responders in an independent melanoma cohort. +- **Rationale:** This would determine whether the candidate has practical value as a resistance biomarker or patient-stratification feature. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.09372960195593227,"interquartile_range":0.09638480604756475,"maximum":0.4345972003497355,"mean":0.14725027992853618,"measured_model_count":56,"median":0.14140384507405612,"minimum":-0.10783153860797157,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.19011440800349702,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0034333194534452273,"interquartile_range":0.0042969091439646915,"maximum":0.044572665063286214,"mean":0.007047471137138419,"measured_model_count":56,"median":0.005546648360096902,"minimum":0.0003687940884532363,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.007730228597409919,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0010101027573501528,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":0.021403211381747195,"gene_effect_median":0.005774598696880573},"dependency_probability_context_minus_non_context_median":-0.0010757473599788264,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.022443645268359957,"gene_effect_context_minus_non_context_median":0.005859738498348671} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 10 +- **Dependency-aware candidate rank:** 8 +- **Rank delta:** -2 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_dcadae74d4b1f7e8d150f46e15232c9ebea66968f0ab733d2b90319fda5128f8` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:JAK2|entrez:3717` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/JUN.md b/examples/target_cards/depmap_26q1/JUN.md new file mode 100644 index 0000000..880c680 --- /dev/null +++ b/examples/target_cards/depmap_26q1/JUN.md @@ -0,0 +1,124 @@ +# Target hypothesis card: JUN + +## Target identity + +- **Target symbol:** JUN +- **Target name:** Jun proto-oncogene, AP-1 transcription factor subunit +- **Open Targets melanoma score:** 0.558 +- **Open Targets baseline rank:** 137 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 139 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 140 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 139 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.558) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** JUN lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for JUN in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.311009377716012,"interquartile_range":0.2506178311258941,"maximum":0.08716511131816934,"mean":-0.20828664428562876,"measured_model_count":56,"median":-0.17296392891862877,"minimum":-1.2725810284274188,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.06039154659011792,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.038700745106317665,"interquartile_range":0.16927161157534584,"maximum":0.9953158990721827,"mean":0.1765632573037201,"measured_model_count":56,"median":0.08893106341563362,"minimum":0.005466014892066753,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2079723566816635,"threshold_fractions":[{"denominator":56,"fraction":0.10714285714285714,"numerator":6,"threshold":0.5},{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.04028546373813935,"dependency_probability_threshold_fractions":[{"context_fraction":0.10714285714285714,"difference":-0.09732734153263954,"pan_cancer_fraction":0.20447019867549668,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.06066698202459792,"pan_cancer_fraction":0.11423841059602649,"threshold":0.8}],"gene_effect_mean":0.07566779254446426,"gene_effect_median":0.045561312447407354},"dependency_probability_context_minus_non_context_median":-0.04477764253805114,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.10714285714285714,"difference":-0.10205853174603176,"non_context_fraction":0.2092013888888889,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.06361607142857142,"non_context_fraction":0.1171875,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.07934608801537568,"gene_effect_context_minus_non_context_median":0.04855652372490543} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 139 +- **Dependency-aware candidate rank:** 139 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_037ccfa9f527c9e4580f363513b870b691086520ca44d989716d2dba9c97befe` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:JUN|entrez:3725` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KAT6A.md b/examples/target_cards/depmap_26q1/KAT6A.md new file mode 100644 index 0000000..7651ef5 --- /dev/null +++ b/examples/target_cards/depmap_26q1/KAT6A.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KAT6A + +## Target identity + +- **Target symbol:** KAT6A +- **Target name:** lysine acetyltransferase 6A +- **Open Targets melanoma score:** 0.558 +- **Open Targets baseline rank:** 138 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 140 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 141 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 140 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.558) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KAT6A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KAT6A in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.1905321316921751,"interquartile_range":0.18847406164423797,"maximum":0.2913844299720876,"mean":-0.13017761755490873,"measured_model_count":56,"median":-0.10723105858661139,"minimum":-0.7313695948349267,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0020580700479371113,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.02057695392620386,"interquartile_range":0.08524065376438715,"maximum":0.9207122230841256,"mean":0.1330831920605305,"measured_model_count":56,"median":0.0533855412738906,"minimum":0.003751296975372678,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10581760769059101,"threshold_fractions":[{"denominator":56,"fraction":0.10714285714285714,"numerator":6,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.013093793336214715,"dependency_probability_threshold_fractions":[{"context_fraction":0.10714285714285714,"difference":0.05747398297067171,"pan_cancer_fraction":0.04966887417218543,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.0036660359508041626,"pan_cancer_fraction":0.02152317880794702,"threshold":0.8}],"gene_effect_mean":-0.035265813371509025,"gene_effect_median":-0.035437214931657426},"dependency_probability_context_minus_non_context_median":0.013622219272891888,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.10714285714285714,"difference":0.06026785714285714,"non_context_fraction":0.046875,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.003844246031746032,"non_context_fraction":0.021701388888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03698012374373508,"gene_effect_context_minus_non_context_median":-0.03881376916812894} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 140 +- **Dependency-aware candidate rank:** 140 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_9ebc57a4eff144bb2aaab9763de8d0f8742e938d93ab191e8b80df98b9457057` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KAT6A|entrez:7994` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KAT6B.md b/examples/target_cards/depmap_26q1/KAT6B.md new file mode 100644 index 0000000..bd6f52d --- /dev/null +++ b/examples/target_cards/depmap_26q1/KAT6B.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KAT6B + +## Target identity + +- **Target symbol:** KAT6B +- **Target name:** lysine acetyltransferase 6B +- **Open Targets melanoma score:** 0.511 +- **Open Targets baseline rank:** 234 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 236 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 236 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 236 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.511) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KAT6B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KAT6B in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06662516590668541,"interquartile_range":0.11394230237326466,"maximum":0.31418589019523446,"mean":-0.001255060192413378,"measured_model_count":56,"median":-0.027627318543472862,"minimum":-0.1751527942425262,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04731713646657926,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01042254558613599,"interquartile_range":0.03023072724184981,"maximum":0.0937161810188809,"mean":0.02994953977997856,"measured_model_count":56,"median":0.02764718556997526,"minimum":0.0014934966998191056,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0406532728279858,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0026773266664892395,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.8}],"gene_effect_mean":0.021002704184916707,"gene_effect_median":-0.0100310731015332},"dependency_probability_context_minus_non_context_median":0.0026933312131079863,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.022023668971683445,"gene_effect_context_minus_non_context_median":-0.010138472012778607} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 236 +- **Dependency-aware candidate rank:** 236 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_0fd0fa194eab1745843369ba93f662d9bb1b349614f841b8a601fd61d3359eea` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KAT6B|entrez:23522` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KDM5A.md b/examples/target_cards/depmap_26q1/KDM5A.md new file mode 100644 index 0000000..245731d --- /dev/null +++ b/examples/target_cards/depmap_26q1/KDM5A.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KDM5A + +## Target identity + +- **Target symbol:** KDM5A +- **Target name:** lysine demethylase 5A +- **Open Targets melanoma score:** 0.521 +- **Open Targets baseline rank:** 209 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 211 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 211 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 211 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.521) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KDM5A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KDM5A in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.22202348434208968,"interquartile_range":0.25163186515633823,"maximum":0.44193079074765096,"mean":-0.09434882159752087,"measured_model_count":56,"median":-0.08145184435535191,"minimum":-0.8218153503794106,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.029608380814248568,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.013875800874593986,"interquartile_range":0.11339090599007796,"maximum":0.9230332160863932,"mean":0.12447802103958014,"measured_model_count":56,"median":0.043825408803144034,"minimum":0.00024619135451046454,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12726670686467195,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.02036209927833478,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.01596499526963103,"pan_cancer_fraction":0.0695364238410596,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.01750236518448439,"pan_cancer_fraction":0.018211920529801324,"threshold":0.8}],"gene_effect_mean":0.027382521382587927,"gene_effect_median":0.04072711474304436},"dependency_probability_context_minus_non_context_median":-0.0205009517912558,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.01674107142857143,"non_context_fraction":0.0703125,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.0183531746031746,"non_context_fraction":0.017361111111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.02871361617201916,"gene_effect_context_minus_non_context_median":0.04194594711379909} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 211 +- **Dependency-aware candidate rank:** 211 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_62eda7faa4daf238a28f53278df1e400a269e104861d7c07fb2e30f15b010ec7` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KDM5A|entrez:5927` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KDR.md b/examples/target_cards/depmap_26q1/KDR.md new file mode 100644 index 0000000..5880cd0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/KDR.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KDR + +## Target identity + +- **Target symbol:** KDR +- **Target name:** kinase insert domain receptor +- **Open Targets melanoma score:** 0.669 +- **Open Targets baseline rank:** 26 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 33 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 35 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.005 | 28 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.669) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KDR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KDR in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.15396703246047083,"interquartile_range":0.18579743831009796,"maximum":0.35412317858308234,"mean":-0.05750978779259812,"measured_model_count":56,"median":-0.0387256781978957,"minimum":-0.3444614053834766,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03183040584962712,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.014005661846951734,"interquartile_range":0.06638249016346734,"maximum":0.28670345020567467,"mean":0.05762538223094942,"measured_model_count":56,"median":0.03446964505050472,"minimum":0.0010452495586403565,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08038815201041907,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.018665865810338793,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0074503311258278145,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.052792893277689865,"gene_effect_median":0.06605930169914},"dependency_probability_context_minus_non_context_median":-0.019212846437965572,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0078125,"non_context_fraction":0.0078125,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.055359214478688704,"gene_effect_context_minus_non_context_median":0.06756047105449794} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 33 +- **Dependency-aware candidate rank:** 33 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_7188d564b28cb2df9750a78deb062a7facf73318ad82c053152b331ed15e4d9f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KDR|entrez:3791` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KEAP1.md b/examples/target_cards/depmap_26q1/KEAP1.md new file mode 100644 index 0000000..732019d --- /dev/null +++ b/examples/target_cards/depmap_26q1/KEAP1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KEAP1 + +## Target identity + +- **Target symbol:** KEAP1 +- **Target name:** kelch like ECH associated protein 1 +- **Open Targets melanoma score:** 0.465 +- **Open Targets baseline rank:** 291 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 291 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 291 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 291 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.465) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KEAP1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KEAP1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.7082108266491682,"interquartile_range":0.5938186833592835,"maximum":0.7135935781879718,"mean":-0.4100413926682732,"measured_model_count":56,"median":-0.3844446143597566,"minimum":-1.446443035340094,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.11439214328988481,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.057768436553657446,"interquartile_range":0.8160912945797978,"maximum":0.9915583744017852,"mean":0.450257304808193,"measured_model_count":56,"median":0.37728663389576456,"minimum":4.915247993642987e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.8738597311334553,"threshold_fractions":[{"denominator":56,"fraction":0.42857142857142855,"numerator":24,"threshold":0.5},{"denominator":56,"fraction":0.2857142857142857,"numerator":16,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.31071286266727666,"dependency_probability_threshold_fractions":[{"context_fraction":0.42857142857142855,"difference":0.21582308420056762,"pan_cancer_fraction":0.21274834437086093,"threshold":0.5},{"context_fraction":0.2857142857142857,"difference":0.15657521286660359,"pan_cancer_fraction":0.1291390728476821,"threshold":0.8}],"gene_effect_mean":-0.24845515864725742,"gene_effect_median":-0.2466112559431453},"dependency_probability_context_minus_non_context_median":0.31619030392886477,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.42857142857142855,"difference":0.2263144841269841,"non_context_fraction":0.20225694444444445,"threshold":0.5},{"context_fraction":0.2857142857142857,"difference":0.1641865079365079,"non_context_fraction":0.12152777777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.2605328399703881,"gene_effect_context_minus_non_context_median":-0.25568042144857883} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":92.5925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 291 +- **Dependency-aware candidate rank:** 291 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_18670903b2c5a4ae65294304c59c6d8863904e118ab3a9abd592281dbc3d67f3` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KEAP1|entrez:9817` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KIT.md b/examples/target_cards/depmap_26q1/KIT.md new file mode 100644 index 0000000..f864d69 --- /dev/null +++ b/examples/target_cards/depmap_26q1/KIT.md @@ -0,0 +1,126 @@ +# Target hypothesis card: KIT + +## Target identity + +- **Target symbol:** KIT +- **Target name:** KIT proto-oncogene, receptor tyrosine kinase +- **Open Targets melanoma score:** 0.718 +- **Open Targets baseline rank:** 13 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / small-molecule target +- **Role confidence:** high +- **Therapeutic direction:** small-molecule inhibition / pathway targeting +- **Best modality:** small molecule / pathway targeting +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 21 | not prioritized | -8 | +| Resistance biomarker | 0.098 | 22 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.679 | 5 | medium | 8 | + +## Evidence for + +- High Open Targets melanoma association score (0.718) +- Stable role classifier confidence is high +- Small-molecule fit is high + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 0.889 +- **Contradiction score:** 0.160 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KIT lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** tumor-intrinsic functional validation +- **Next experiment:** Evaluate whether perturbing KIT alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays. +- **Rationale:** This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.15047254523839437,"interquartile_range":0.12483170574110164,"maximum":0.16694100888553057,"mean":-0.10507054540120067,"measured_model_count":56,"median":-0.11187987261054008,"minimum":-0.3611196971836982,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.025640839497292737,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.026005203789725564,"interquartile_range":0.057675318964253264,"maximum":0.24582508541769998,"mean":0.06628476557606086,"measured_model_count":56,"median":0.05726951313842029,"minimum":0.006213462729592259,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08368052275397883,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.022794176676194843,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.05068503375570338,"gene_effect_median":-0.05884822613831423},"dependency_probability_context_minus_non_context_median":0.023172068420461857,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.05314888956327223,"gene_effect_context_minus_non_context_median":-0.06235982604084975} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 21 +- **Dependency-aware candidate rank:** 21 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2720bbf5793b4600ea51971093e4c95473a8226c4dbc0f9f2a9303cf41648754` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KIT|entrez:3815` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KLF4.md b/examples/target_cards/depmap_26q1/KLF4.md new file mode 100644 index 0000000..326de38 --- /dev/null +++ b/examples/target_cards/depmap_26q1/KLF4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KLF4 + +## Target identity + +- **Target symbol:** KLF4 +- **Target name:** KLF transcription factor 4 +- **Open Targets melanoma score:** 0.508 +- **Open Targets baseline rank:** 243 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 245 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 245 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 245 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.508) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KLF4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KLF4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.0866160725632556,"interquartile_range":0.09094159645890684,"maximum":0.29033441321163894,"mean":-0.036429378374868294,"measured_model_count":56,"median":-0.045825769626115405,"minimum":-0.18846226428060717,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0043255238956512385,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01830988808607737,"interquartile_range":0.031197954431363674,"maximum":0.12728694959590328,"mean":0.03673849894871195,"measured_model_count":56,"median":0.02931121522718555,"minimum":0.0015769843027852257,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.049507842517441045,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00027614128553087036,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.01076158940397351,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":0.010892401367839824,"gene_effect_median":-0.009569965295020279},"dependency_probability_context_minus_non_context_median":0.00027614128553087036,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.011284722222222222,"non_context_fraction":0.011284722222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.011421893100998753,"gene_effect_context_minus_non_context_median":-0.010052677582369572} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 245 +- **Dependency-aware candidate rank:** 245 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ca94fac79b9d2871cf2dd70632376361a49d8a3afa84250a1002eb5e15b2526b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KLF4|entrez:9314` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KLF6.md b/examples/target_cards/depmap_26q1/KLF6.md new file mode 100644 index 0000000..e4a3727 --- /dev/null +++ b/examples/target_cards/depmap_26q1/KLF6.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KLF6 + +## Target identity + +- **Target symbol:** KLF6 +- **Target name:** KLF transcription factor 6 +- **Open Targets melanoma score:** 0.581 +- **Open Targets baseline rank:** 99 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 102 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 103 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 102 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.581) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KLF6 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KLF6 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.1740339281446544,"interquartile_range":0.287121816879088,"maximum":0.5582898749499964,"mean":-0.020014061949726214,"measured_model_count":56,"median":-0.05126217030720511,"minimum":-0.5678287346983116,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11308788873443362,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.004045553451322353,"interquartile_range":0.08106591108477244,"maximum":0.8387756064664146,"mean":0.09494424049900542,"measured_model_count":56,"median":0.03244514830539762,"minimum":3.5093885241607115e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08511146453609479,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.018934247933076763,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.012535477767265844,"pan_cancer_fraction":0.023178807947019868,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.010406811731315042,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.8}],"gene_effect_mean":-0.04910407777982369,"gene_effect_median":-0.10661125299604379},"dependency_probability_context_minus_non_context_median":0.01914453044385907,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.013144841269841268,"non_context_fraction":0.022569444444444444,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.010912698412698412,"non_context_fraction":0.006944444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.05149108156078732,"gene_effect_context_minus_non_context_median":-0.107981493548363} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 102 +- **Dependency-aware candidate rank:** 102 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_10da6f5b842aec03914d79436d05f2b5d13c4451d6fc835af124e56317f6d235` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KLF6|entrez:1316` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KMT2A.md b/examples/target_cards/depmap_26q1/KMT2A.md new file mode 100644 index 0000000..10a500a --- /dev/null +++ b/examples/target_cards/depmap_26q1/KMT2A.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KMT2A + +## Target identity + +- **Target symbol:** KMT2A +- **Target name:** lysine methyltransferase 2A +- **Open Targets melanoma score:** 0.580 +- **Open Targets baseline rank:** 101 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 104 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 105 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 104 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.580) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KMT2A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KMT2A in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.247834586721482,"interquartile_range":0.2053139586165061,"maximum":0.14388081055483293,"mean":-0.1599635043193788,"measured_model_count":56,"median":-0.13474643688042431,"minimum":-0.7962726094629715,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.042520628104975915,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.028075360066156213,"interquartile_range":0.12381967132087579,"maximum":0.890939509576807,"mean":0.1369329942267416,"measured_model_count":56,"median":0.0731199024889937,"minimum":0.0032609376499916206,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.151895031387032,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.022529632958707357,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.10501419110690634,"pan_cancer_fraction":0.14072847682119205,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.013954588457899715,"pan_cancer_fraction":0.04966887417218543,"threshold":0.8}],"gene_effect_mean":0.04620430632163236,"gene_effect_median":0.04073661712261353},"dependency_probability_context_minus_non_context_median":-0.024362426630622852,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.11011904761904763,"non_context_fraction":0.14583333333333334,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.014632936507936511,"non_context_fraction":0.050347222222222224,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04845034899004538,"gene_effect_context_minus_non_context_median":0.04274723665726088} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 104 +- **Dependency-aware candidate rank:** 104 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_8436dbeba9b280b6ec14d9da09e082858c496e644deaf920d8877f659b3d861a` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KMT2A|entrez:4297` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KMT2C.md b/examples/target_cards/depmap_26q1/KMT2C.md new file mode 100644 index 0000000..1340f3a --- /dev/null +++ b/examples/target_cards/depmap_26q1/KMT2C.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KMT2C + +## Target identity + +- **Target symbol:** KMT2C +- **Target name:** lysine methyltransferase 2C +- **Open Targets melanoma score:** 0.598 +- **Open Targets baseline rank:** 70 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 74 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 76 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 74 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.598) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KMT2C lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KMT2C in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.002613878383379797,"interquartile_range":0.22930347633925058,"maximum":0.7588941965548464,"mean":0.08533586436646227,"measured_model_count":56,"median":0.08688860720869607,"minimum":-0.5393806663773176,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2266895979558708,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0032623542350772366,"interquartile_range":0.023637002199571364,"maximum":0.7548851600875993,"mean":0.047657468264772414,"measured_model_count":56,"median":0.00790666231691314,"minimum":3.015181277604221e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0268993564346486,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.008378037643394922,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.005321665089877012,"pan_cancer_fraction":0.023178807947019868,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":0.07308581728239892,"gene_effect_median":0.056357339633505504},"dependency_probability_context_minus_non_context_median":-0.00913467488608257,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.005580357142857144,"non_context_fraction":0.0234375,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.07663860006696002,"gene_effect_context_minus_non_context_median":0.059724463300712356} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 74 +- **Dependency-aware candidate rank:** 74 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d369b29a656346078e2f9ac3565002afaeb50e0db72fcd474bf060dd7e6d66f5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KMT2C|entrez:58508` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KMT2D.md b/examples/target_cards/depmap_26q1/KMT2D.md new file mode 100644 index 0000000..c62d8bb --- /dev/null +++ b/examples/target_cards/depmap_26q1/KMT2D.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KMT2D + +## Target identity + +- **Target symbol:** KMT2D +- **Target name:** lysine methyltransferase 2D +- **Open Targets melanoma score:** 0.606 +- **Open Targets baseline rank:** 61 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 65 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 67 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 65 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.606) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KMT2D lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KMT2D in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.5054747400504007,"interquartile_range":0.43801977053473673,"maximum":0.4453175128783058,"mean":-0.27953827290798855,"measured_model_count":56,"median":-0.2813972812521446,"minimum":-0.9363498739499392,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.06745496951566396,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.036792875788036104,"interquartile_range":0.5038830443625247,"maximum":0.9507611503193685,"mean":0.315814143315189,"measured_model_count":56,"median":0.1829714967357441,"minimum":0.00023457193745018845,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5406759201505609,"threshold_fractions":[{"denominator":56,"fraction":0.30357142857142855,"numerator":17,"threshold":0.5},{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.12194237947038289,"dependency_probability_threshold_fractions":[{"context_fraction":0.30357142857142855,"difference":-0.05818353831598866,"pan_cancer_fraction":0.3617549668874172,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":-0.021404919583727505,"pan_cancer_fraction":0.18211920529801323,"threshold":0.8}],"gene_effect_mean":0.11216053843555868,"gene_effect_median":0.07237576799848949},"dependency_probability_context_minus_non_context_median":-0.13011903737267616,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.30357142857142855,"difference":-0.06101190476190477,"non_context_fraction":0.3645833333333333,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":-0.022445436507936484,"non_context_fraction":0.1831597222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.11761278683173171,"gene_effect_context_minus_non_context_median":0.07649088974832446} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 65 +- **Dependency-aware candidate rank:** 65 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ba82733dc35e0dd2a1a3e56ad370a99476c5e79c7bc647f881fe9c41c76bfdac` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KMT2D|entrez:8085` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KNL1.md b/examples/target_cards/depmap_26q1/KNL1.md new file mode 100644 index 0000000..c901a07 --- /dev/null +++ b/examples/target_cards/depmap_26q1/KNL1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KNL1 + +## Target identity + +- **Target symbol:** KNL1 +- **Target name:** kinetochore scaffold 1 +- **Open Targets melanoma score:** 0.519 +- **Open Targets baseline rank:** 217 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 219 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 219 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 219 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.519) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KNL1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KNL1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.8209858622248248,"interquartile_range":0.26800043369654103,"maximum":0.4114298366282715,"mean":-0.6723034112825079,"measured_model_count":56,"median":-0.6974565079231971,"minimum":-1.276427559759107,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.5529854285282838,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.6264804733609197,"interquartile_range":0.29486977080895016,"maximum":0.9998985731748403,"mean":0.743338783315388,"measured_model_count":56,"median":0.83423638852549,"minimum":0.0011216508970974713,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9213502441698699,"threshold_fractions":[{"denominator":56,"fraction":0.875,"numerator":49,"threshold":0.5},{"denominator":56,"fraction":0.5357142857142857,"numerator":30,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0408741270024463,"dependency_probability_threshold_fractions":[{"context_fraction":0.875,"difference":0.05794701986754969,"pan_cancer_fraction":0.8170529801324503,"threshold":0.5},{"context_fraction":0.5357142857142857,"difference":0.05061494796594135,"pan_cancer_fraction":0.48509933774834435,"threshold":0.8}],"gene_effect_mean":-0.008917433590880264,"gene_effect_median":-0.05584297946607175},"dependency_probability_context_minus_non_context_median":0.04473365357168113,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.875,"difference":0.06076388888888884,"non_context_fraction":0.8142361111111112,"threshold":0.5},{"context_fraction":0.5357142857142857,"difference":0.0530753968253968,"non_context_fraction":0.4826388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.009350919945992131,"gene_effect_context_minus_non_context_median":-0.05706975577620854} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 219 +- **Dependency-aware candidate rank:** 219 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_42afc55e8df2c56e9de2c6d8093aec35b6bbaf8d02786599579a25e599effa59` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KNL1|entrez:57082` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KRAS.md b/examples/target_cards/depmap_26q1/KRAS.md new file mode 100644 index 0000000..24149da --- /dev/null +++ b/examples/target_cards/depmap_26q1/KRAS.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KRAS + +## Target identity + +- **Target symbol:** KRAS +- **Target name:** KRas proto-oncogene, GTPase +- **Open Targets melanoma score:** 0.480 +- **Open Targets baseline rank:** 273 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 273 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 273 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 273 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.480) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KRAS lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KRAS in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.6390363697007047,"interquartile_range":0.3255914225769023,"maximum":0.037107045533280814,"mean":-0.4615597662300834,"measured_model_count":56,"median":-0.4270863694795695,"minimum":-0.9671398918289789,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.31344494712380233,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.2804397654477754,"interquartile_range":0.4166743169804551,"maximum":0.9882225371239182,"mean":0.48315218978865904,"measured_model_count":56,"median":0.4738799422322064,"minimum":0.012521637812168088,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.6971140824282305,"threshold_fractions":[{"denominator":56,"fraction":0.48214285714285715,"numerator":27,"threshold":0.5},{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.11562974175001095,"dependency_probability_threshold_fractions":[{"context_fraction":0.48214285714285715,"difference":-0.09401608325449379,"pan_cancer_fraction":0.5761589403973509,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":-0.16248817407757807,"pan_cancer_fraction":0.34105960264900664,"threshold":0.8}],"gene_effect_mean":0.2633418509692072,"gene_effect_median":0.08983073184763496},"dependency_probability_context_minus_non_context_median":-0.1300421110614044,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.48214285714285715,"difference":-0.09858630952380948,"non_context_fraction":0.5807291666666666,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":-0.17038690476190474,"non_context_fraction":0.3489583333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.2761431909468766,"gene_effect_context_minus_non_context_median":0.10109950535962081} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 273 +- **Dependency-aware candidate rank:** 273 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_cf088782b794ba81973df7072f9b9c92d402cd3cddbb610dda021707b8b66cbf` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KRAS|entrez:3845` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/KRT5.md b/examples/target_cards/depmap_26q1/KRT5.md new file mode 100644 index 0000000..e9ddbaf --- /dev/null +++ b/examples/target_cards/depmap_26q1/KRT5.md @@ -0,0 +1,124 @@ +# Target hypothesis card: KRT5 + +## Target identity + +- **Target symbol:** KRT5 +- **Target name:** keratin 5 +- **Open Targets melanoma score:** 0.471 +- **Open Targets baseline rank:** 282 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 282 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 282 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 282 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.471) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** KRT5 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for KRT5 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.1162600050798901,"interquartile_range":0.16026986264477588,"maximum":0.3326259306248558,"mean":-0.03271996044744329,"measured_model_count":56,"median":-0.03875848753631785,"minimum":-0.4083100273302143,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04400985756488579,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.013107390885123485,"interquartile_range":0.04935434074536283,"maximum":0.34081918050850224,"mean":0.05037789993099017,"measured_model_count":56,"median":0.027358384042971286,"minimum":0.0012650511761817924,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.062461731630486315,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005669141450315225,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.018647943378540567,"gene_effect_median":0.008795443937758655},"dependency_probability_context_minus_non_context_median":-0.0059289590279801505,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.019554440626108442,"gene_effect_context_minus_non_context_median":0.008975446451295908} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 282 +- **Dependency-aware candidate rank:** 282 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_064edcceeec27225416d8f3dfdfe36d40162fcbfadc1b53d55162123b6ddd806` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:KRT5|entrez:3852` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/LAG3.md b/examples/target_cards/depmap_26q1/LAG3.md new file mode 100644 index 0000000..4155c6e --- /dev/null +++ b/examples/target_cards/depmap_26q1/LAG3.md @@ -0,0 +1,133 @@ +# Target hypothesis card: LAG3 + +## Target identity + +- **Target symbol:** LAG3 +- **Target name:** lymphocyte activating 3 +- **Open Targets melanoma score:** 0.592 +- **Open Targets baseline rank:** 80 + +## Stable TargetIntel-IO classification + +- **Role classification:** anti-PD-1 combination target +- **Role confidence:** high +- **Therapeutic direction:** block / inhibit +- **Best modality:** antibody / IO-combination target +- **Resistance axis:** checkpoint_redundancy +- **Matched resistance programs:** Checkpoint redundancy + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.822 | 4 | high | 76 | +| Resistance biomarker | 0.493 | 10 | medium | 70 | +| Tumor-intrinsic / small molecule | 0.137 | 12 | low | 68 | + +## Evidence for + +- Immune checkpoint biology +- Potential compensatory inhibitory pathway after PD-1 blockade +- Surface-accessible immune receptor or ligand +- Moderate Open Targets melanoma association score (0.592) +- Maps to curated anti-PD-1 resistance program: Checkpoint redundancy +- Stable role classifier confidence is high +- Antibody fit is high +- IO-combination fit is high +- Checkpoint-axis biology supports anti-PD-1 combination rationale + +## Evidence against / limitations + +- Crowded IO target space +- Expression may reflect exhausted immune-cell abundance rather than causal resistance in all tumors +- Patient selection may be required + +## Confidence and uncertainty + +- **Confidence level:** high confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.240 +- **Main limitation:** No major limitation flagged by current MVP rules +- **Uncertainty reason:** Main limitation: No major limitation flagged by current MVP rules +- **Deprioritization reason:** No strong deprioritization reason from current MVP rules + +## Recommended next validation experiment + +- **Validation category:** immune-checkpoint functional validation +- **Next experiment:** Validate LAG3 expression in exhausted CD8 T-cell populations from anti-PD-1-resistant melanoma samples and test blockade in a melanoma/T-cell co-culture assay. +- **Rationale:** This would test whether the candidate marks a relevant checkpoint axis and whether blockade can improve anti-tumor T-cell activity. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.05881633966392029,"interquartile_range":0.12893561937780812,"maximum":0.37914429966497276,"mean":0.003600261025976661,"measured_model_count":56,"median":0.006693995382591952,"minimum":-0.31014322945440886,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07011927971388784,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.010007862547405266,"interquartile_range":0.025780908070300368,"maximum":0.2736649589269115,"mean":0.03207975191250165,"measured_model_count":56,"median":0.02026514620529634,"minimum":0.0006578282366709314,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.035788770617705634,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0018901915706334774,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.011693795017936399,"gene_effect_median":0.010169669641757669},"dependency_probability_context_minus_non_context_median":-0.001965981755923319,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01226224338686388,"gene_effect_context_minus_non_context_median":0.01031202269999554} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 4 +- **Dependency-aware candidate rank:** 7 +- **Rank delta:** 3 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_0f145797159a290f7ec8bfc040c8f479017766ab656ef31fa4f80f000ae67a65` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:LAG3|entrez:3902` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/LATS2.md b/examples/target_cards/depmap_26q1/LATS2.md new file mode 100644 index 0000000..97a57dc --- /dev/null +++ b/examples/target_cards/depmap_26q1/LATS2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: LATS2 + +## Target identity + +- **Target symbol:** LATS2 +- **Target name:** large tumor suppressor kinase 2 +- **Open Targets melanoma score:** 0.501 +- **Open Targets baseline rank:** 253 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 255 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 255 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 255 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.501) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** LATS2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for LATS2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.1556578421689475,"interquartile_range":0.346068833316306,"maximum":0.6812382978063686,"mean":0.020232855958764978,"measured_model_count":56,"median":0.02532013141759792,"minimum":-0.5883085173462187,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1904109911473585,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.004812871870791315,"interquartile_range":0.07385812374473756,"maximum":0.5717176690234534,"mean":0.06581858221464584,"measured_model_count":56,"median":0.023948406020125466,"minimum":1.5225700296503551e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07867099561552887,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.007094941296658438,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.007095553453169347,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.04324556828627929,"gene_effect_median":0.06935077629481798},"dependency_probability_context_minus_non_context_median":-0.007375489439448841,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.00744047619047619,"non_context_fraction":0.010416666666666666,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04534778341130678,"gene_effect_context_minus_non_context_median":0.07086233124569989} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 255 +- **Dependency-aware candidate rank:** 255 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e53da3b2eb0faa199f618e2cfe62d4f48847b820fd8d00281249004ac5c8597f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:LATS2|entrez:26524` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/LCK.md b/examples/target_cards/depmap_26q1/LCK.md new file mode 100644 index 0000000..e37ef3a --- /dev/null +++ b/examples/target_cards/depmap_26q1/LCK.md @@ -0,0 +1,124 @@ +# Target hypothesis card: LCK + +## Target identity + +- **Target symbol:** LCK +- **Target name:** LCK proto-oncogene, Src family tyrosine kinase +- **Open Targets melanoma score:** 0.532 +- **Open Targets baseline rank:** 185 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 187 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 188 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 187 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.532) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** LCK lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for LCK in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.08729246564785431,"interquartile_range":0.1844688496759413,"maximum":0.2059897868514309,"mean":-0.009407769188333403,"measured_model_count":56,"median":-0.015814512461379424,"minimum":-0.38590429969641227,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09717638402808698,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.006810646880507027,"interquartile_range":0.04657577854208711,"maximum":0.336222749595819,"mean":0.04188276382137456,"measured_model_count":56,"median":0.022171372889984876,"minimum":0.0028324291920454408,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.053386425422594135,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-6.781987367632594e-05,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":-0.009722048599233306,"gene_effect_median":-0.011438666328224274},"dependency_probability_context_minus_non_context_median":-7.216257711747248e-05,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.010194648183918242,"gene_effect_context_minus_non_context_median":-0.011644779982110654} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 187 +- **Dependency-aware candidate rank:** 187 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2875136be9b593d0d2c16ed94c6f477189a2ed21146b5ecafa6630302f57e0da` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:LCK|entrez:3932` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/LILRB1.md b/examples/target_cards/depmap_26q1/LILRB1.md new file mode 100644 index 0000000..6a5d135 --- /dev/null +++ b/examples/target_cards/depmap_26q1/LILRB1.md @@ -0,0 +1,73 @@ +# LILRB1 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.01109020400994214,"interquartile_range":0.1398087266452999,"maximum":0.4433027675302377,"mean":0.05536551565827964,"measured_model_count":56,"median":0.051821418581015924,"minimum":-0.2138537031730067,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12871852263535774,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.006022954802638753,"interquartile_range":0.017556262760780754,"maximum":0.11051920534037452,"mean":0.01924822092948011,"measured_model_count":56,"median":0.013681127550983843,"minimum":0.00023616078642564348,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.023579217563419505,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0023882042686036477,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.018479761103356432,"gene_effect_median":-0.02006817567605361},"dependency_probability_context_minus_non_context_median":0.0024795342371092023,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.019378082823658466,"gene_effect_context_minus_non_context_median":-0.020608548639528948} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_297dbadda58e632878208cfea8f7dbf9674be3b2cbe98cc3e4b7c3ad66a29cdf` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:LILRB1|entrez:10859` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/LILRB2.md b/examples/target_cards/depmap_26q1/LILRB2.md new file mode 100644 index 0000000..4f5b85f --- /dev/null +++ b/examples/target_cards/depmap_26q1/LILRB2.md @@ -0,0 +1,73 @@ +# LILRB2 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.17339256920794643,"interquartile_range":0.16212378681022704,"maximum":0.34645335742649364,"mean":-0.08430449460370906,"measured_model_count":56,"median":-0.10414190586983159,"minimum":-0.46500847320709315,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.01126878239771938,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.023619920694685523,"interquartile_range":0.06576945252265654,"maximum":0.5581267752985244,"mean":0.0736724021976837,"measured_model_count":56,"median":0.054768936757054784,"minimum":0.0008249314826466763,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08938937321734206,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.008650022490033216,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.0003547776726584677,"pan_cancer_fraction":0.018211920529801324,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.006249131641514638,"gene_effect_median":-0.02012539418414107},"dependency_probability_context_minus_non_context_median":0.009154837808549234,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.00037202380952381167,"non_context_fraction":0.018229166666666668,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006552908874088131,"gene_effect_context_minus_non_context_median":-0.021010398615674636} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_9f5b156b8ca8296e2660e2c1c6ff44617563f1355b6bedee7dc7ac3db453a680` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:LILRB2|entrez:10288` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/LPP.md b/examples/target_cards/depmap_26q1/LPP.md new file mode 100644 index 0000000..90dfec1 --- /dev/null +++ b/examples/target_cards/depmap_26q1/LPP.md @@ -0,0 +1,124 @@ +# Target hypothesis card: LPP + +## Target identity + +- **Target symbol:** LPP +- **Target name:** LIM domain containing preferred translocation partner in lipoma +- **Open Targets melanoma score:** 0.478 +- **Open Targets baseline rank:** 276 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 276 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 276 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 276 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.478) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** LPP lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for LPP in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.008783199593916918,"interquartile_range":0.10063549851005911,"maximum":0.39512059249409137,"mean":0.0501342135041537,"measured_model_count":56,"median":0.052278005196747614,"minimum":-0.28660592592022155,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09185229891614219,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.00715624060802497,"interquartile_range":0.014590503911784831,"maximum":0.14433042014147968,"mean":0.01906680258772825,"measured_model_count":56,"median":0.012845188877211793,"minimum":0.0007890807311014471,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0217467445198098,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00035221455346442707,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.009982655850077647,"gene_effect_median":-0.007920830474404186},"dependency_probability_context_minus_non_context_median":0.00036946973229592603,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.010467923842789745,"gene_effect_context_minus_non_context_median":-0.008244035266807816} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 276 +- **Dependency-aware candidate rank:** 276 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_c1157616598db6523351ef7f64b9b59d25bdb05e49835820ea1a27f220822615` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:LPP|entrez:4026` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/LRP1B.md b/examples/target_cards/depmap_26q1/LRP1B.md new file mode 100644 index 0000000..f1617ce --- /dev/null +++ b/examples/target_cards/depmap_26q1/LRP1B.md @@ -0,0 +1,124 @@ +# Target hypothesis card: LRP1B + +## Target identity + +- **Target symbol:** LRP1B +- **Target name:** LDL receptor related protein 1B +- **Open Targets melanoma score:** 0.658 +- **Open Targets baseline rank:** 29 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 36 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 38 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.002 | 31 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.658) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** LRP1B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for LRP1B in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.20938505684404493,"interquartile_range":0.18767779569086548,"maximum":0.36877867713046136,"mean":-0.11193670595354667,"measured_model_count":56,"median":-0.1145412718983222,"minimum":-0.6285265543650834,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.021707261153179447,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.022508152373858486,"interquartile_range":0.12726745259309719,"maximum":0.7916660592206599,"mean":0.11003149409753983,"measured_model_count":56,"median":0.0526553283158261,"minimum":0.0006828725992313448,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14977560496695566,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.02437487176960501,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.004257332071901605,"pan_cancer_fraction":0.03145695364238411,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.8}],"gene_effect_mean":0.04106198802050763,"gene_effect_median":0.029746098922292713},"dependency_probability_context_minus_non_context_median":-0.025565720848670967,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.004464285714285712,"non_context_fraction":0.03125,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.043058056882615534,"gene_effect_context_minus_non_context_median":0.03159413837855338} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 36 +- **Dependency-aware candidate rank:** 36 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_fc8697ab41635af1e865ae379c122664e10f6757572457039f83e8333f82e203` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:LRP1B|entrez:53353` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/LZTR1.md b/examples/target_cards/depmap_26q1/LZTR1.md new file mode 100644 index 0000000..0665dd7 --- /dev/null +++ b/examples/target_cards/depmap_26q1/LZTR1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: LZTR1 + +## Target identity + +- **Target symbol:** LZTR1 +- **Target name:** leucine zipper like post translational regulator 1 +- **Open Targets melanoma score:** 0.550 +- **Open Targets baseline rank:** 161 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 163 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 164 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 163 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.550) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** LZTR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for LZTR1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.09712302034637581,"interquartile_range":0.12603647569734755,"maximum":0.39835316383447017,"mean":-0.023218800975575663,"measured_model_count":56,"median":-0.032631692394577985,"minimum":-0.31250394234035345,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.028913455350971732,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.013866497890610329,"interquartile_range":0.03558430953541362,"maximum":0.22804494863519476,"mean":0.042020283337196505,"measured_model_count":56,"median":0.027297324657613566,"minimum":0.0005298521133612584,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.049450807426023945,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.004856881233996087,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.008278145695364239,"pan_cancer_fraction":0.008278145695364239,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.02513772052294517,"gene_effect_median":-0.025816726004031957},"dependency_probability_context_minus_non_context_median":0.005100042611575185,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.008680555555555556,"non_context_fraction":0.008680555555555556,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.02635969304836607,"gene_effect_context_minus_non_context_median":-0.02853208828617576} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 163 +- **Dependency-aware candidate rank:** 163 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_87f8d0fec9a6ce256574b4e21801a8ddfcb76cf0fad45745b3d2ed84878f0329` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:LZTR1|entrez:8216` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MAP2K1.md b/examples/target_cards/depmap_26q1/MAP2K1.md new file mode 100644 index 0000000..1810c47 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MAP2K1.md @@ -0,0 +1,132 @@ +# Target hypothesis card: MAP2K1 + +## Target identity + +- **Target symbol:** MAP2K1 +- **Target name:** mitogen-activated protein kinase kinase 1 +- **Open Targets melanoma score:** 0.807 +- **Open Targets baseline rank:** 4 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / small-molecule target +- **Role confidence:** high +- **Therapeutic direction:** small-molecule inhibition / pathway targeting +- **Best modality:** small molecule / pathway targeting +- **Resistance axis:** tumor_intrinsic_driver +- **Matched resistance programs:** Tumor-intrinsic driver biology + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.262 | 8 | low | -4 | +| Resistance biomarker | 0.476 | 12 | medium | -8 | +| Tumor-intrinsic / small molecule | 0.836 | 2 | high | 2 | + +## Evidence for + +- Relevant to melanoma tumor-cell biology +- Some targets or pathways are clinically actionable +- Useful for separating tumor-intrinsic drivers from immune-combination targets +- High Open Targets melanoma association score (0.807) +- Maps to curated anti-PD-1 resistance program: Tumor-intrinsic driver biology +- Stable role classifier confidence is high +- Small-molecule fit is high + +## Evidence against / limitations + +- Many tumor-intrinsic drivers are poor antibody targets +- Melanoma association does not automatically imply anti-PD-1 combination suitability +- Tumor suppressors are often poor direct therapeutic targets +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** high confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.320 +- **Main limitation:** Poor fit for antibody / IO-combination modality +- **Uncertainty reason:** Main limitation: Poor fit for antibody / IO-combination modality +- **Deprioritization reason:** No strong deprioritization reason from current MVP rules + +## Recommended next validation experiment + +- **Validation category:** tumor-intrinsic functional validation +- **Next experiment:** Evaluate whether perturbing MAP2K1 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays. +- **Rationale:** This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.578482228308965,"interquartile_range":0.4189281838514242,"maximum":0.252437482852541,"mean":-0.41218035078685417,"measured_model_count":56,"median":-0.38895098205912615,"minimum":-1.3657303916368035,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.1595540444575408,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.08598020716229524,"interquartile_range":0.5882115796602083,"maximum":0.9908781940957316,"mean":0.42114568711213035,"measured_model_count":56,"median":0.38746891216194834,"minimum":0.002703798825683424,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.6741917868225036,"threshold_fractions":[{"denominator":56,"fraction":0.39285714285714285,"numerator":22,"threshold":0.5},{"denominator":56,"fraction":0.23214285714285715,"numerator":13,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.3150396652239056,"dependency_probability_threshold_fractions":[{"context_fraction":0.39285714285714285,"difference":0.33904919583727533,"pan_cancer_fraction":0.05380794701986755,"threshold":0.5},{"context_fraction":0.23214285714285715,"difference":0.20482497634815516,"pan_cancer_fraction":0.027317880794701987,"threshold":0.8}],"gene_effect_mean":-0.248319609934331,"gene_effect_median":-0.24836184470154712},"dependency_probability_context_minus_non_context_median":0.3176976923105364,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.39285714285714285,"difference":0.35553075396825395,"non_context_fraction":0.03732638888888889,"threshold":0.5},{"context_fraction":0.23214285714285715,"difference":0.21478174603174605,"non_context_fraction":0.017361111111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.2603907020839166,"gene_effect_context_minus_non_context_median":-0.2535817455567181} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":100.0} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 8 +- **Dependency-aware candidate rank:** 2 +- **Rank delta:** -6 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2adc2fdd57e57d2cb39182fa984d99b6744fb8c281824b652417022c29ead2ed` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MAP2K1|entrez:5604` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MAP2K2.md b/examples/target_cards/depmap_26q1/MAP2K2.md new file mode 100644 index 0000000..4abaa30 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MAP2K2.md @@ -0,0 +1,126 @@ +# Target hypothesis card: MAP2K2 + +## Target identity + +- **Target symbol:** MAP2K2 +- **Target name:** mitogen-activated protein kinase kinase 2 +- **Open Targets melanoma score:** 0.769 +- **Open Targets baseline rank:** 6 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / small-molecule target +- **Role confidence:** high +- **Therapeutic direction:** small-molecule inhibition / pathway targeting +- **Best modality:** small molecule / pathway targeting +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 14 | not prioritized | -8 | +| Resistance biomarker | 0.106 | 20 | low | -14 | +| Tumor-intrinsic / small molecule | 0.689 | 3 | medium | 3 | + +## Evidence for + +- High Open Targets melanoma association score (0.769) +- Stable role classifier confidence is high +- Small-molecule fit is high + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 0.889 +- **Contradiction score:** 0.160 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MAP2K2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** tumor-intrinsic functional validation +- **Next experiment:** Evaluate whether perturbing MAP2K2 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays. +- **Rationale:** This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.4908836918532778,"interquartile_range":0.3416845954926677,"maximum":0.22807594691589114,"mean":-0.36394880908741206,"measured_model_count":56,"median":-0.27913492073021595,"minimum":-1.780927613358056,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.14919909636061007,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0796834206563264,"interquartile_range":0.440321969120281,"maximum":1.0,"mean":0.33519502622684805,"measured_model_count":56,"median":0.210854567680023,"minimum":0.0034850765734037578,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5200053897766074,"threshold_fractions":[{"denominator":56,"fraction":0.26785714285714285,"numerator":15,"threshold":0.5},{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.1138375819439125,"dependency_probability_threshold_fractions":[{"context_fraction":0.26785714285714285,"difference":0.2281220435193945,"pan_cancer_fraction":0.039735099337748346,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.14746925260170293,"pan_cancer_fraction":0.013245033112582781,"threshold":0.8}],"gene_effect_mean":-0.17677737897716392,"gene_effect_median":-0.10871776689925783},"dependency_probability_context_minus_non_context_median":0.11672469895653054,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.26785714285714285,"difference":0.2392113095238095,"non_context_fraction":0.028645833333333332,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.15463789682539683,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.1853707237885538,"gene_effect_context_minus_non_context_median":-0.11069460399729478} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 14 +- **Dependency-aware candidate rank:** 12 +- **Rank delta:** -2 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ff1752f6f093d35ab80a1dc5742a4c196be05cb6f535109d4d887901709b6b00` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MAP2K2|entrez:5605` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MAP2K4.md b/examples/target_cards/depmap_26q1/MAP2K4.md new file mode 100644 index 0000000..2ba867b --- /dev/null +++ b/examples/target_cards/depmap_26q1/MAP2K4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MAP2K4 + +## Target identity + +- **Target symbol:** MAP2K4 +- **Target name:** mitogen-activated protein kinase kinase 4 +- **Open Targets melanoma score:** 0.513 +- **Open Targets baseline rank:** 231 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 233 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 233 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 233 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.513) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MAP2K4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MAP2K4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.08166803344011006,"interquartile_range":0.1667224349937138,"maximum":0.4663584004709461,"mean":-0.004183185081218783,"measured_model_count":56,"median":0.007155568370856763,"minimum":-0.5620268298394391,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08505440155360375,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.00896391572726946,"interquartile_range":0.03983377128048464,"maximum":0.5761438915269841,"mean":0.04888816971268661,"measured_model_count":56,"median":0.02000527970907914,"minimum":0.0002583679371438126,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0487976870077541,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.010008220510560543,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.004612109744560075,"pan_cancer_fraction":0.013245033112582781,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.08467368581701021,"gene_effect_median":-0.07899657992657283},"dependency_probability_context_minus_non_context_median":0.010477315489236343,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.004836309523809522,"non_context_fraction":0.013020833333333334,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0887897677664482,"gene_effect_context_minus_non_context_median":-0.08435345703588204} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 233 +- **Dependency-aware candidate rank:** 233 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_afc0aea71e3da6ba41b95c62c14a329fbab39ebf8e502e8f20de70e562815bea` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MAP2K4|entrez:6416` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MAP3K1.md b/examples/target_cards/depmap_26q1/MAP3K1.md new file mode 100644 index 0000000..4710110 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MAP3K1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MAP3K1 + +## Target identity + +- **Target symbol:** MAP3K1 +- **Target name:** mitogen-activated protein kinase kinase kinase 1 +- **Open Targets melanoma score:** 0.466 +- **Open Targets baseline rank:** 288 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 288 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 288 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 288 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.466) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MAP3K1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MAP3K1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.26818881495655444,"interquartile_range":0.2190929173625335,"maximum":0.16244834816557008,"mean":-0.1754338142643515,"measured_model_count":56,"median":-0.18106151480989618,"minimum":-1.063112411214312,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.04909589759402095,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.032390313337493024,"interquartile_range":0.1698410110394501,"maximum":0.9781983157682375,"mean":0.1418094395845862,"measured_model_count":56,"median":0.08325360586789075,"minimum":0.0031087789768363826,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2022313243769431,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.030618882721477725,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.004612109744560075,"pan_cancer_fraction":0.013245033112582781,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.015373699148533584,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.07259773849015544,"gene_effect_median":-0.07872399920058051},"dependency_probability_context_minus_non_context_median":0.031198178018647063,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.004836309523809522,"non_context_fraction":0.013020833333333334,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.016121031746031744,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0761267952223159,"gene_effect_context_minus_non_context_median":-0.08035780971994266} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":92.5925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 288 +- **Dependency-aware candidate rank:** 288 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_cf756e479e88717eef86a602dafabe0e751c785b349ef9f4818088cb9cc18d94` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MAP3K1|entrez:4214` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MAP3K13.md b/examples/target_cards/depmap_26q1/MAP3K13.md new file mode 100644 index 0000000..615b1bd --- /dev/null +++ b/examples/target_cards/depmap_26q1/MAP3K13.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MAP3K13 + +## Target identity + +- **Target symbol:** MAP3K13 +- **Target name:** mitogen-activated protein kinase kinase kinase 13 +- **Open Targets melanoma score:** 0.546 +- **Open Targets baseline rank:** 167 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 169 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 170 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 169 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.546) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MAP3K13 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MAP3K13 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.12348850976267087,"interquartile_range":0.10356484439638564,"maximum":0.10601839484476286,"mean":-0.07735031260314525,"measured_model_count":56,"median":-0.07585580490508761,"minimum":-0.4254039496856019,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.01992366536628524,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.02579139351817865,"interquartile_range":0.03948663532446196,"maximum":0.33166860073911614,"mean":0.05799902513451529,"measured_model_count":56,"median":0.04505395114891765,"minimum":0.004144288513430752,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06527802884264061,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.009695406371026893,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.017009365555747898,"gene_effect_median":-0.01812639278195812},"dependency_probability_context_minus_non_context_median":0.009797872690404191,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.017836209714707826,"gene_effect_context_minus_non_context_median":-0.019202972460153143} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 169 +- **Dependency-aware candidate rank:** 169 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_4c5e6e27cf8ad909398012feeb14dc4fac40b65dc835a80193725b642260beaa` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MAP3K13|entrez:9175` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MAPK1.md b/examples/target_cards/depmap_26q1/MAPK1.md new file mode 100644 index 0000000..2d8445a --- /dev/null +++ b/examples/target_cards/depmap_26q1/MAPK1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MAPK1 + +## Target identity + +- **Target symbol:** MAPK1 +- **Target name:** mitogen-activated protein kinase 1 +- **Open Targets melanoma score:** 0.472 +- **Open Targets baseline rank:** 281 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 281 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 281 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 281 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.472) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MAPK1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MAPK1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.2761774074770886,"interquartile_range":0.7786423452235494,"maximum":0.18419597775603253,"mean":-0.8981201774701383,"measured_model_count":56,"median":-0.8129894142767058,"minimum":-2.2162133589722837,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.4975350622535393,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.5766186743058375,"interquartile_range":0.41754805922924465,"maximum":1.0,"mean":0.7418741798461861,"measured_model_count":56,"median":0.8931882816760448,"minimum":0.0015643431120909866,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9941667335350821,"threshold_fractions":[{"denominator":56,"fraction":0.7857142857142857,"numerator":44,"threshold":0.5},{"denominator":56,"fraction":0.625,"numerator":35,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.8193481073490543,"dependency_probability_threshold_fractions":[{"context_fraction":0.7857142857142857,"difference":0.6433301797540207,"pan_cancer_fraction":0.1423841059602649,"threshold":0.5},{"context_fraction":0.625,"difference":0.554635761589404,"pan_cancer_fraction":0.07036423841059603,"threshold":0.8}],"gene_effect_mean":-0.6959215725352872,"gene_effect_median":-0.668531079535996},"dependency_probability_context_minus_non_context_median":0.8263496162531797,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.7857142857142857,"difference":0.6746031746031746,"non_context_fraction":0.1111111111111111,"threshold":0.5},{"context_fraction":0.625,"difference":0.5815972222222222,"non_context_fraction":0.043402777777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.7297510934224184,"gene_effect_context_minus_non_context_median":-0.6776694707116295} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":100.0} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 281 +- **Dependency-aware candidate rank:** 281 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_13a046ae6acb61e39222890294953e6597010cc823eca9a788473d8b39647ca5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MAPK1|entrez:5594` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MARCO.md b/examples/target_cards/depmap_26q1/MARCO.md new file mode 100644 index 0000000..5fe33e2 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MARCO.md @@ -0,0 +1,73 @@ +# MARCO — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.144284681805267,"interquartile_range":0.11320090800341288,"maximum":0.16141479149421714,"mean":-0.08075810496074594,"measured_model_count":56,"median":-0.07657305576587008,"minimum":-0.28995279711229627,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.031083773801854106,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.02732096604142211,"interquartile_range":0.0424585894956143,"maximum":0.21196471052683893,"mean":0.05275650105094353,"measured_model_count":56,"median":0.04508515552169046,"minimum":0.0043349896499730416,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06977955553703641,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.013009959661225763,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.03107970228961196,"gene_effect_median":-0.029934995161084763},"dependency_probability_context_minus_non_context_median":0.01325816819398256,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.032590521150912544,"gene_effect_context_minus_non_context_median":-0.031918688171550635} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_5434253dea93a61134ae09bfa7579a9b778992e03b22ebb1463b8a488900ba7d` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MARCO|entrez:8685` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MAX.md b/examples/target_cards/depmap_26q1/MAX.md new file mode 100644 index 0000000..5540af8 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MAX.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MAX + +## Target identity + +- **Target symbol:** MAX +- **Target name:** MYC associated transcriptional regulator X +- **Open Targets melanoma score:** 0.519 +- **Open Targets baseline rank:** 215 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 217 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 217 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 217 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.519) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MAX lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MAX in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.8226826734631729,"interquartile_range":0.23233480918405225,"maximum":-0.2112248166458427,"mean":-0.710188390541159,"measured_model_count":56,"median":-0.688268648265024,"minimum":-1.2966052450452203,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.5903478642791207,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.703880450962148,"interquartile_range":0.24126058863373134,"maximum":0.9931135114720926,"mean":0.7818475651475402,"measured_model_count":56,"median":0.8762894271334364,"minimum":0.11802670198216508,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9451410395958794,"threshold_fractions":[{"denominator":56,"fraction":0.875,"numerator":49,"threshold":0.5},{"denominator":56,"fraction":0.5714285714285714,"numerator":32,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.03808533788005786,"dependency_probability_threshold_fractions":[{"context_fraction":0.875,"difference":-0.019039735099337762,"pan_cancer_fraction":0.8940397350993378,"threshold":0.5},{"context_fraction":0.5714285714285714,"difference":-0.1438032166508988,"pan_cancer_fraction":0.7152317880794702,"threshold":0.8}],"gene_effect_mean":0.09858119787523068,"gene_effect_median":0.10484178465136451},"dependency_probability_context_minus_non_context_median":-0.04166605320801209,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.875,"difference":-0.01996527777777779,"non_context_fraction":0.8949652777777778,"threshold":0.5},{"context_fraction":0.5714285714285714,"difference":-0.1507936507936508,"non_context_fraction":0.7222222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.10337333943860993,"gene_effect_context_minus_non_context_median":0.11415946668113963} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 217 +- **Dependency-aware candidate rank:** 217 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_641d4a223df2992246b524bc55714e0cdb392ead46f6403678cb167632070672` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MAX|entrez:4149` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MBD4.md b/examples/target_cards/depmap_26q1/MBD4.md new file mode 100644 index 0000000..963b060 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MBD4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MBD4 + +## Target identity + +- **Target symbol:** MBD4 +- **Target name:** methyl-CpG binding domain 4, DNA glycosylase +- **Open Targets melanoma score:** 0.706 +- **Open Targets baseline rank:** 19 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 26 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 29 | not prioritized | -10 | +| Tumor-intrinsic / small molecule | 0.012 | 22 | not prioritized | -3 | + +## Evidence for + +- High Open Targets melanoma association score (0.706) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MBD4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MBD4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.14270727803868224,"interquartile_range":0.1568713207830758,"maximum":0.30240936692161213,"mean":-0.06259349546269093,"measured_model_count":56,"median":-0.08875452151828409,"minimum":-0.2727347834743414,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.014164042744393559,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.019228656050633033,"interquartile_range":0.06297025851395877,"maximum":0.18687151897726442,"mean":0.057004038075143926,"measured_model_count":56,"median":0.04888988821268317,"minimum":0.00155875195791616,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0821989145645918,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0030046031138560095,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004966887417218543,"pan_cancer_fraction":0.004966887417218543,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.042133056139012845,"gene_effect_median":0.010588283750192731},"dependency_probability_context_minus_non_context_median":-0.0030046031138560095,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005208333333333333,"non_context_fraction":0.005208333333333333,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.044181190812437335,"gene_effect_context_minus_non_context_median":0.011006948674245717} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 26 +- **Dependency-aware candidate rank:** 26 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_7dc2c3aa2235e2919a098358a150f2ae924092bb451d788463c09b7057dbe8ff` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MBD4|entrez:8930` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MC1R.md b/examples/target_cards/depmap_26q1/MC1R.md new file mode 100644 index 0000000..f1899f3 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MC1R.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MC1R + +## Target identity + +- **Target symbol:** MC1R +- **Target name:** melanocortin 1 receptor +- **Open Targets melanoma score:** 0.621 +- **Open Targets baseline rank:** 49 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 54 | not prioritized | -5 | +| Resistance biomarker | 0.000 | 56 | not prioritized | -7 | +| Tumor-intrinsic / small molecule | 0.000 | 54 | not prioritized | -5 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.621) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MC1R lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MC1R in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.13574258291049882,"interquartile_range":0.2294889026785944,"maximum":0.3088799835855469,"mean":-0.07405014885167535,"measured_model_count":56,"median":-0.014394286830063385,"minimum":-1.4266168769158605,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0937463197680956,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.00957570675501504,"interquartile_range":0.06469958618077154,"maximum":0.9986640403125104,"mean":0.093014007762533,"measured_model_count":56,"median":0.024505635992432086,"minimum":0.002172093001064544,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07427529293578658,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0007702689419332685,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.026608325449385052,"pan_cancer_fraction":0.009105960264900662,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.03323084200567644,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.05521604278224079,"gene_effect_median":-0.0006908143769098138},"dependency_probability_context_minus_non_context_median":-0.0008110824397527007,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.027901785714285712,"non_context_fraction":0.0078125,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":0.03484623015873016,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.057900155973044154,"gene_effect_context_minus_non_context_median":-0.0006908143769098138} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 54 +- **Dependency-aware candidate rank:** 54 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_add7084b48ba681f9c3c43ad3406300c681284745c7914a5347a8eb34a0e3bfe` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MC1R|entrez:4157` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MDM2.md b/examples/target_cards/depmap_26q1/MDM2.md new file mode 100644 index 0000000..109438a --- /dev/null +++ b/examples/target_cards/depmap_26q1/MDM2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MDM2 + +## Target identity + +- **Target symbol:** MDM2 +- **Target name:** MDM2 proto-oncogene +- **Open Targets melanoma score:** 0.612 +- **Open Targets baseline rank:** 54 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 58 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 60 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 58 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.612) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MDM2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MDM2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.8624748543617278,"interquartile_range":1.4254157644122152,"maximum":-0.03383445987773337,"mean":-1.2716776001752876,"measured_model_count":56,"median":-1.3485460927811548,"minimum":-2.9407816150438637,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.4370590899495126,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.5316184247932024,"interquartile_range":0.46838157520672297,"maximum":1.0,"mean":0.7845953373476593,"measured_model_count":56,"median":0.9964251033261587,"minimum":0.0191219625657424,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9999999999999254,"threshold_fractions":[{"denominator":56,"fraction":0.75,"numerator":42,"threshold":0.5},{"denominator":56,"fraction":0.6785714285714286,"numerator":38,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.5433058761368279,"dependency_probability_threshold_fractions":[{"context_fraction":0.75,"difference":0.2955298013245033,"pan_cancer_fraction":0.4544701986754967,"threshold":0.5},{"context_fraction":0.6785714285714286,"difference":0.3979422894985809,"pan_cancer_fraction":0.2806291390728477,"threshold":0.8}],"gene_effect_mean":-0.6248918769217581,"gene_effect_median":-0.9221060164000108},"dependency_probability_context_minus_non_context_median":0.5560757861291269,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.75,"difference":0.3098958333333333,"non_context_fraction":0.4401041666666667,"threshold":0.5},{"context_fraction":0.6785714285714286,"difference":0.4172867063492064,"non_context_fraction":0.2612847222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.6552685653832329,"gene_effect_context_minus_non_context_median":-0.9313150551905067} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 58 +- **Dependency-aware candidate rank:** 58 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e09c30cbdcf926c360d142cc79ceb8c2ea3b01d759c047f4db377618133cfc1b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MDM2|entrez:4193` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MDM4.md b/examples/target_cards/depmap_26q1/MDM4.md new file mode 100644 index 0000000..78bf8ae --- /dev/null +++ b/examples/target_cards/depmap_26q1/MDM4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MDM4 + +## Target identity + +- **Target symbol:** MDM4 +- **Target name:** MDM4 regulator of p53 +- **Open Targets melanoma score:** 0.588 +- **Open Targets baseline rank:** 85 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 88 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 90 | not prioritized | -5 | +| Tumor-intrinsic / small molecule | 0.000 | 88 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.588) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MDM4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MDM4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.24624159527720413,"interquartile_range":0.23359604518110183,"maximum":0.33598072083948805,"mean":-0.18865409124957538,"measured_model_count":56,"median":-0.1410025896159544,"minimum":-1.2812287480482205,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.012645550096102298,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.02356303103125949,"interquartile_range":0.1275705121704807,"maximum":0.9843563515754161,"mean":0.18013925683555612,"measured_model_count":56,"median":0.07119109464846649,"minimum":0.0011906140360111628,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1511335432017402,"threshold_fractions":[{"denominator":56,"fraction":0.125,"numerator":7,"threshold":0.5},{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03168778141474956,"dependency_probability_threshold_fractions":[{"context_fraction":0.125,"difference":0.0033112582781456984,"pan_cancer_fraction":0.1216887417218543,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":0.0023651844843897846,"pan_cancer_fraction":0.0869205298013245,"threshold":0.8}],"gene_effect_mean":-0.031354144465446654,"gene_effect_median":-0.07842570599532141},"dependency_probability_context_minus_non_context_median":0.03217559712298432,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.125,"difference":0.0034722222222222238,"non_context_fraction":0.12152777777777778,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":0.0024801587301587352,"non_context_fraction":0.08680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.032878304265850256,"gene_effect_context_minus_non_context_median":-0.08145299746058135} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 88 +- **Dependency-aware candidate rank:** 88 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e5dd23533b8b3973fc6a616ca8c1b9dc27a975778e4c4b05db1eaf2fbdadf5de` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MDM4|entrez:4194` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MECOM.md b/examples/target_cards/depmap_26q1/MECOM.md new file mode 100644 index 0000000..759b487 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MECOM.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MECOM + +## Target identity + +- **Target symbol:** MECOM +- **Target name:** MDS1 and EVI1 complex locus +- **Open Targets melanoma score:** 0.611 +- **Open Targets baseline rank:** 56 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 60 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 62 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 60 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.611) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MECOM lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MECOM in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.03318121755950547,"interquartile_range":0.14709745093791188,"maximum":1.1159229428618254,"mean":0.04519617222218534,"measured_model_count":56,"median":0.06243448810213843,"minimum":-0.4043002287802036,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1139162333784064,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.007059075844818929,"interquartile_range":0.0174121661972337,"maximum":0.3482881257463481,"mean":0.03171024366566652,"measured_model_count":56,"median":0.01239713433525657,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02447124204205263,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0021296773257739286,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.023178807947019868,"pan_cancer_fraction":0.023178807947019868,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014072847682119206,"pan_cancer_fraction":0.014072847682119206,"threshold":0.8}],"gene_effect_mean":0.025965655811218857,"gene_effect_median":0.021937058319371316},"dependency_probability_context_minus_non_context_median":-0.0022692047268848513,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.024305555555555556,"non_context_fraction":0.024305555555555556,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014756944444444444,"non_context_fraction":0.014756944444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.02722787519093091,"gene_effect_context_minus_non_context_median":0.02275885204514158} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 60 +- **Dependency-aware candidate rank:** 60 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_b6f1f671850c3b480918c17280b141df71e490b462aff992fbbcaa882a243ac9` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MECOM|entrez:2122` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MED12.md b/examples/target_cards/depmap_26q1/MED12.md new file mode 100644 index 0000000..861ab85 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MED12.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MED12 + +## Target identity + +- **Target symbol:** MED12 +- **Target name:** mediator complex subunit 12 +- **Open Targets melanoma score:** 0.464 +- **Open Targets baseline rank:** 292 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 292 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 292 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 292 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.464) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MED12 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MED12 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.9311970062252455,"interquartile_range":0.5433939524223144,"maximum":0.35086847212010597,"mean":-0.6610039514993754,"measured_model_count":56,"median":-0.6930691904602218,"minimum":-1.4658720277959536,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.3878030538029311,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.29330547725917067,"interquartile_range":0.6792518810382737,"maximum":1.0,"mean":0.6692263099022066,"measured_model_count":56,"median":0.8357673700031603,"minimum":0.0011196937346188206,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9725573582974444,"threshold_fractions":[{"denominator":56,"fraction":0.7142857142857143,"numerator":40,"threshold":0.5},{"denominator":56,"fraction":0.5178571428571429,"numerator":29,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.15037299236736146,"dependency_probability_threshold_fractions":[{"context_fraction":0.7142857142857143,"difference":0.11825922421948909,"pan_cancer_fraction":0.5960264900662252,"threshold":0.5},{"context_fraction":0.5178571428571429,"difference":0.0940160832544939,"pan_cancer_fraction":0.423841059602649,"threshold":0.8}],"gene_effect_mean":-0.10478938114699055,"gene_effect_median":-0.12192678639433197},"dependency_probability_context_minus_non_context_median":0.1640140677254437,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.7142857142857143,"difference":0.12400793650793651,"non_context_fraction":0.5902777777777778,"threshold":0.5},{"context_fraction":0.5178571428571429,"difference":0.09858630952380959,"non_context_fraction":0.4192708333333333,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.1098833093971916,"gene_effect_context_minus_non_context_median":-0.1290268263356823} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 292 +- **Dependency-aware candidate rank:** 292 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_8bf6e9b1a0bba3c2a4234d4fff5fb8795f78dc6189a0e4ac0f726c986cdd741d` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MED12|entrez:9968` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MERTK.md b/examples/target_cards/depmap_26q1/MERTK.md new file mode 100644 index 0000000..90f4f94 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MERTK.md @@ -0,0 +1,73 @@ +# MERTK — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.18881505762195927,"interquartile_range":0.16208785261332045,"maximum":0.3193293249145177,"mean":-0.10122912464953086,"measured_model_count":56,"median":-0.10690991997138019,"minimum":-0.37059543781934634,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.02672720500863881,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.024416867332033472,"interquartile_range":0.08662821894971165,"maximum":0.2986950469092032,"mean":0.07873373296246423,"measured_model_count":56,"median":0.05270852886247373,"minimum":0.0014332677546677695,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11104508628174513,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.010399266300551047,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.022814040606935662,"gene_effect_median":-0.031910909320972014},"dependency_probability_context_minus_non_context_median":0.010756021506766654,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.02392305646977287,"gene_effect_context_minus_non_context_median":-0.03325595444556945} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e7dcf175a6aaabbf2699fa0a66746cf326ea684280ea261a3bdc4530ddcb8799` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MERTK|entrez:10461` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MET.md b/examples/target_cards/depmap_26q1/MET.md new file mode 100644 index 0000000..f9d5467 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MET.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MET + +## Target identity + +- **Target symbol:** MET +- **Target name:** MET proto-oncogene, receptor tyrosine kinase +- **Open Targets melanoma score:** 0.633 +- **Open Targets baseline rank:** 41 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 48 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 50 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 48 | not prioritized | -7 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.633) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MET lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MET in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06431778498910111,"interquartile_range":0.12819068489351648,"maximum":0.19924513841976238,"mean":0.006650333009057209,"measured_model_count":56,"median":0.010664057636821479,"minimum":-0.15857136172097158,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06387289990441536,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.010757477645204688,"interquartile_range":0.027227045398293084,"maximum":0.09865379877043438,"mean":0.026561617711299477,"measured_model_count":56,"median":0.01757639754618848,"minimum":0.003696797201785037,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.037984523043497774,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.006124645788141078,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.027317880794701987,"pan_cancer_fraction":0.027317880794701987,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014900662251655629,"pan_cancer_fraction":0.014900662251655629,"threshold":0.8}],"gene_effect_mean":0.04397450202284898,"gene_effect_median":0.02311840445736779},"dependency_probability_context_minus_non_context_median":-0.006467760987337593,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.028645833333333332,"non_context_fraction":0.028645833333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.015625,"non_context_fraction":0.015625,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04611215142673745,"gene_effect_context_minus_non_context_median":0.024839366368137623} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 48 +- **Dependency-aware candidate rank:** 48 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_346cf45e9e08768179c2ff8a443efc9872e87dd2398d8b81a08f8455e2525b97` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MET|entrez:4233` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MITF.md b/examples/target_cards/depmap_26q1/MITF.md new file mode 100644 index 0000000..2cae480 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MITF.md @@ -0,0 +1,127 @@ +# Target hypothesis card: MITF + +## Target identity + +- **Target symbol:** MITF +- **Target name:** melanocyte inducing transcription factor +- **Open Targets melanoma score:** 0.747 +- **Open Targets baseline rank:** 8 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / biomarker +- **Role confidence:** medium-high +- **Therapeutic direction:** use as biomarker / pathway targeting if appropriate +- **Best modality:** tumor-intrinsic biomarker / pathway context +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 16 | not prioritized | -8 | +| Resistance biomarker | 0.391 | 13 | low | -5 | +| Tumor-intrinsic / small molecule | 0.521 | 7 | medium | 1 | + +## Evidence for + +- High Open Targets melanoma association score (0.747) +- Stable role classifier confidence is medium-high +- Biomarker fit is medium-high + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Most useful as biomarker or stratification marker rather than direct therapeutic target +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 0.889 +- **Contradiction score:** 0.240 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MITF lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** biomarker validation +- **Next experiment:** Test whether MITF status or expression differs between anti-PD-1 responders and non-responders in an independent melanoma cohort. +- **Rationale:** This would determine whether the candidate has practical value as a resistance biomarker or patient-stratification feature. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.746365662744372,"interquartile_range":0.5624178320790791,"maximum":0.13265320362187163,"mean":-0.49718287424489066,"measured_model_count":56,"median":-0.4283536938090401,"minimum":-1.4237880033159953,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.18394783066529286,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.13075636050247558,"interquartile_range":0.7860916431961333,"maximum":0.99792821478558,"mean":0.479275745655577,"measured_model_count":56,"median":0.48643645267493163,"minimum":0.005004197500645994,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9168480036986089,"threshold_fractions":[{"denominator":56,"fraction":0.44642857142857145,"numerator":25,"threshold":0.5},{"denominator":56,"fraction":0.26785714285714285,"numerator":15,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.4526589328486887,"dependency_probability_threshold_fractions":[{"context_fraction":0.44642857142857145,"difference":0.4166272469252602,"pan_cancer_fraction":0.029801324503311258,"threshold":0.5},{"context_fraction":0.26785714285714285,"difference":0.2488174077578051,"pan_cancer_fraction":0.01903973509933775,"threshold":0.8}],"gene_effect_mean":-0.42578503903945053,"gene_effect_median":-0.3769637760275986},"dependency_probability_context_minus_non_context_median":0.45443980360081326,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.44642857142857145,"difference":0.43687996031746035,"non_context_fraction":0.009548611111111112,"threshold":0.5},{"context_fraction":0.26785714285714285,"difference":0.26091269841269843,"non_context_fraction":0.006944444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.44648292288164615,"gene_effect_context_minus_non_context_median":-0.3798754716345232} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":96.29629629629629} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 16 +- **Dependency-aware candidate rank:** 11 +- **Rank delta:** -5 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_3583e52fbd3a99eddcd14bbd58a55479403c429f643a952616d15dd72d84c0cb` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MITF|entrez:4286` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MN1.md b/examples/target_cards/depmap_26q1/MN1.md new file mode 100644 index 0000000..b89989f --- /dev/null +++ b/examples/target_cards/depmap_26q1/MN1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MN1 + +## Target identity + +- **Target symbol:** MN1 +- **Target name:** MN1 proto-oncogene, transcriptional regulator +- **Open Targets melanoma score:** 0.513 +- **Open Targets baseline rank:** 230 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 232 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 232 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 232 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.513) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MN1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MN1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.01062534893898931,"interquartile_range":0.20506169154087153,"maximum":0.4941061788942517,"mean":0.10398082189212046,"measured_model_count":56,"median":0.1147031423956377,"minimum":-0.2283786381698714,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.19443634260188222,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.002738853757670439,"interquartile_range":0.018564266438373188,"maximum":0.11449885931721446,"mean":0.018046659942068676,"measured_model_count":56,"median":0.0071448822915313025,"minimum":5.345680221332841e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.021303120196043628,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0015149813892774682,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.0009876008661242885,"gene_effect_median":0.01054620202494945},"dependency_probability_context_minus_non_context_median":-0.0015307667801673294,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0010356092415608753,"gene_effect_context_minus_non_context_median":0.011556046281122473} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 232 +- **Dependency-aware candidate rank:** 232 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_8016e193e3e5b91402ab503122579da9c48e7103385c1be1859a544c5ac7c130` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MN1|entrez:4330` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MRTFA.md b/examples/target_cards/depmap_26q1/MRTFA.md new file mode 100644 index 0000000..a41b4e0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MRTFA.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MRTFA + +## Target identity + +- **Target symbol:** MRTFA +- **Target name:** myocardin related transcription factor A +- **Open Targets melanoma score:** 0.509 +- **Open Targets baseline rank:** 242 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 244 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 244 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 244 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.509) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MRTFA lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MRTFA in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.166195671969878,"interquartile_range":0.12432617290852266,"maximum":0.15263953285940676,"mean":-0.11254910171388513,"measured_model_count":56,"median":-0.12423974962740286,"minimum":-0.4177381788941873,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.04186949906135534,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.027229735286835803,"interquartile_range":0.07873531064556291,"maximum":0.5253690791287967,"mean":0.08473052596126118,"measured_model_count":56,"median":0.05987725158027763,"minimum":0.0077482329268426875,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10596504593239872,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01280692034900676,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.0003547776726584677,"pan_cancer_fraction":0.018211920529801324,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.03301940166574069,"gene_effect_median":0.011134527709864062},"dependency_probability_context_minus_non_context_median":-0.013394416437087324,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.00037202380952381167,"non_context_fraction":0.018229166666666668,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.034624511468936386,"gene_effect_context_minus_non_context_median":0.012017949940479278} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 244 +- **Dependency-aware candidate rank:** 244 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d2d5471e7ab8e527c116994e65686fefc9d6151bb378ce10089a6f98cde1cef3` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MRTFA|entrez:57591` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MSH2.md b/examples/target_cards/depmap_26q1/MSH2.md new file mode 100644 index 0000000..8dd68a6 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MSH2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MSH2 + +## Target identity + +- **Target symbol:** MSH2 +- **Target name:** mutS homolog 2 +- **Open Targets melanoma score:** 0.521 +- **Open Targets baseline rank:** 207 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 209 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 209 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 209 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.521) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MSH2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MSH2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.26003559151177824,"interquartile_range":0.13672139042893577,"maximum":0.021496894857538112,"mean":-0.20764010596590654,"measured_model_count":56,"median":-0.19916068457846808,"minimum":-0.5451116448448519,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.12331420108284245,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.06592450097849478,"interquartile_range":0.13342337190007386,"maximum":0.5982055659846949,"mean":0.15553859836993347,"measured_model_count":56,"median":0.12392476588127996,"minimum":0.009111683646020614,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.19934787287856864,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005144771662147579,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.016674550614947964,"pan_cancer_fraction":0.01903973509933775,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.004853918329945944,"gene_effect_median":0.004878184038607014},"dependency_probability_context_minus_non_context_median":-0.005144771662147579,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.017485119047619044,"non_context_fraction":0.018229166666666668,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.005089872693207098,"gene_effect_context_minus_non_context_median":0.005598657965552867} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 209 +- **Dependency-aware candidate rank:** 209 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ac594daaf6cd0c8ac4bca7a58e29e5f647b3e259783512c43f03887172d16793` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MSH2|entrez:4436` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MTAP.md b/examples/target_cards/depmap_26q1/MTAP.md new file mode 100644 index 0000000..e0480d7 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MTAP.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MTAP + +## Target identity + +- **Target symbol:** MTAP +- **Target name:** methylthioadenosine phosphorylase +- **Open Targets melanoma score:** 0.522 +- **Open Targets baseline rank:** 206 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 208 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 208 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 208 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.522) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MTAP lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MTAP in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.05322379422075565,"interquartile_range":0.13163768390226643,"maximum":0.35647138964450364,"mean":0.013438769004057596,"measured_model_count":56,"median":0.001765919917108864,"minimum":-0.2742755175918499,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07841388968151078,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008275996775491557,"interquartile_range":0.027631247160987107,"maximum":0.16335356271029838,"mean":0.030024490344690378,"measured_model_count":56,"median":0.01798254575130081,"minimum":0.0005565877691906464,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.035907243936478664,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0007450668116554017,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.017195420764497427,"gene_effect_median":-0.01690621483409817},"dependency_probability_context_minus_non_context_median":0.0007682046941628225,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.01803130927388271,"gene_effect_context_minus_non_context_median":-0.018115597396768914} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 208 +- **Dependency-aware candidate rank:** 208 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_9f88d63f48dc41907cb4d4ea70333550bb7c86a3093506fbe4852e4adb704cca` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MTAP|entrez:4507` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MTOR.md b/examples/target_cards/depmap_26q1/MTOR.md new file mode 100644 index 0000000..386c9ba --- /dev/null +++ b/examples/target_cards/depmap_26q1/MTOR.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MTOR + +## Target identity + +- **Target symbol:** MTOR +- **Target name:** mechanistic target of rapamycin kinase +- **Open Targets melanoma score:** 0.629 +- **Open Targets baseline rank:** 45 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 51 | not prioritized | -6 | +| Resistance biomarker | 0.000 | 53 | not prioritized | -8 | +| Tumor-intrinsic / small molecule | 0.000 | 51 | not prioritized | -6 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.629) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MTOR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MTOR in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.4510131041083276,"interquartile_range":0.4066619987330087,"maximum":-0.49744427330148155,"mean":-1.2670230716667266,"measured_model_count":56,"median":-1.2341950136618125,"minimum":-2.149561296556447,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.044351105375319,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9789619639208639,"interquartile_range":0.02043554028117034,"maximum":1.0,"mean":0.9737317482994322,"measured_model_count":56,"median":0.991899482877697,"minimum":0.6985320335577506,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9993975042020342,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0008071331386185765,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.018211920529801362,"pan_cancer_fraction":0.9817880794701986,"threshold":0.5},{"context_fraction":0.9821428571428571,"difference":0.03263954588457896,"pan_cancer_fraction":0.9495033112582781,"threshold":0.8}],"gene_effect_mean":-0.008290257341191598,"gene_effect_median":0.01857181633024152},"dependency_probability_context_minus_non_context_median":0.0008411508339194462,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.01909722222222221,"non_context_fraction":0.9809027777777778,"threshold":0.5},{"context_fraction":0.9821428571428571,"difference":0.034226190476190466,"non_context_fraction":0.9479166666666666,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.00869325596194459,"gene_effect_context_minus_non_context_median":0.01888929833241426} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 51 +- **Dependency-aware candidate rank:** 51 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_599702a80c74d830dd3c4d56abadd1ae6910cfd8107a0bc443464fcdb67a13ba` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MTOR|entrez:2475` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MUTYH.md b/examples/target_cards/depmap_26q1/MUTYH.md new file mode 100644 index 0000000..c547d81 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MUTYH.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MUTYH + +## Target identity + +- **Target symbol:** MUTYH +- **Target name:** mutY DNA glycosylase +- **Open Targets melanoma score:** 0.507 +- **Open Targets baseline rank:** 247 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 249 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 249 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 249 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.507) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MUTYH lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MUTYH in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.11748028310013764,"interquartile_range":0.09479599365178082,"maximum":0.1934608651174256,"mean":-0.06611412498298225,"measured_model_count":56,"median":-0.06371844317038643,"minimum":-0.35421944238261915,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.022684289448356824,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.02107456457132147,"interquartile_range":0.04260159227968066,"maximum":0.2790151431662099,"mean":0.05206646685426908,"measured_model_count":56,"median":0.0372447418479774,"minimum":0.004238146635538509,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06367615685100213,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.000837254833749676,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.0038797027680364735,"gene_effect_median":-0.0020307322415865497},"dependency_probability_context_minus_non_context_median":-0.0008509863480279933,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.004068299430371659,"gene_effect_context_minus_non_context_median":-0.002148372875229676} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 249 +- **Dependency-aware candidate rank:** 249 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d09dd40597c32b28e6b5604a20cd1f9eb76b3d6bfe25cd41d9447aa59ef49736` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MUTYH|entrez:4595` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MX2.md b/examples/target_cards/depmap_26q1/MX2.md new file mode 100644 index 0000000..cf6965f --- /dev/null +++ b/examples/target_cards/depmap_26q1/MX2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MX2 + +## Target identity + +- **Target symbol:** MX2 +- **Target name:** MX dynamin like GTPase 2 +- **Open Targets melanoma score:** 0.543 +- **Open Targets baseline rank:** 174 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 176 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 177 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 176 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.543) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MX2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MX2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.02134365997612272,"interquartile_range":0.07743728420864318,"maximum":0.28073769634204876,"mean":0.059560748516648006,"measured_model_count":56,"median":0.06322339592467445,"minimum":-0.2090932215477918,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0987809441847659,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.007638541718115839,"interquartile_range":0.010072703648349442,"maximum":0.11866301644172314,"mean":0.01634520388322014,"measured_model_count":56,"median":0.010155243511429223,"minimum":0.002370897831436602,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.017711245366465282,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0016150605350365964,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.006023191938568213,"gene_effect_median":-0.0010398506799526724},"dependency_probability_context_minus_non_context_median":-0.0017265595309920688,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.006315985991137536,"gene_effect_context_minus_non_context_median":-0.0010398506799526724} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 176 +- **Dependency-aware candidate rank:** 176 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_943fa2bc183388a34a0a6a43a013f63b3a0122b085517c6ff7b59349c8f27f67` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MX2|entrez:4600` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MYB.md b/examples/target_cards/depmap_26q1/MYB.md new file mode 100644 index 0000000..7e9902d --- /dev/null +++ b/examples/target_cards/depmap_26q1/MYB.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MYB + +## Target identity + +- **Target symbol:** MYB +- **Target name:** MYB proto-oncogene, transcription factor +- **Open Targets melanoma score:** 0.569 +- **Open Targets baseline rank:** 117 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 119 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 120 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 119 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.569) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MYB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MYB in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.3259231883678356,"interquartile_range":0.21035580309281268,"maximum":0.2857082762935745,"mean":-0.2178685317305252,"measured_model_count":56,"median":-0.2383668513811943,"minimum":-0.5880233849070193,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.11556738527502294,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.05526327096966057,"interquartile_range":0.19608087680463585,"maximum":0.7574785900752413,"mean":0.18520779917804936,"measured_model_count":56,"median":0.1759008399302746,"minimum":0.001253210856482248,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2513441477742964,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.05759172837452056,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.1530274361400189,"pan_cancer_fraction":0.18874172185430463,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0935430463576159,"pan_cancer_fraction":0.0935430463576159,"threshold":0.8}],"gene_effect_mean":0.1661141346455027,"gene_effect_median":0.05943151457646956},"dependency_probability_context_minus_non_context_median":-0.061943117671945436,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.16046626984126983,"non_context_fraction":0.19618055555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.09809027777777778,"non_context_fraction":0.09809027777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.17418912730188116,"gene_effect_context_minus_non_context_median":0.06108140737397355} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 119 +- **Dependency-aware candidate rank:** 119 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_9026276f063d0feb2ceb0352f57ee7a799499b51d2b998029c871936d5caa795` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MYB|entrez:4602` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MYCL.md b/examples/target_cards/depmap_26q1/MYCL.md new file mode 100644 index 0000000..be04d6e --- /dev/null +++ b/examples/target_cards/depmap_26q1/MYCL.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MYCL + +## Target identity + +- **Target symbol:** MYCL +- **Target name:** MYCL proto-oncogene, bHLH transcription factor +- **Open Targets melanoma score:** 0.548 +- **Open Targets baseline rank:** 164 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 166 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 167 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 166 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.548) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MYCL lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MYCL in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.09896427298002167,"interquartile_range":0.14969798704101517,"maximum":0.3274052023063336,"mean":-0.0172760396628093,"measured_model_count":56,"median":-0.02694371489350945,"minimum":-0.23412237491718474,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05073371406099349,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.014034643973738554,"interquartile_range":0.029981870470997513,"maximum":0.15381720551862854,"mean":0.036321603814873385,"measured_model_count":56,"median":0.02648200137173792,"minimum":0.001437699008765543,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04401651444473607,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0010191664628673401,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.005045333807037918,"gene_effect_median":-0.006651287945659612},"dependency_probability_context_minus_non_context_median":0.0010854405403200908,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.005290593089324502,"gene_effect_context_minus_non_context_median":-0.00712736439954614} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 166 +- **Dependency-aware candidate rank:** 166 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ac62729becffa3b25c6f7c2c0f938f1681488b0bd85cd283ac4e40fada25d280` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MYCL|entrez:4610` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MYCN.md b/examples/target_cards/depmap_26q1/MYCN.md new file mode 100644 index 0000000..32d6337 --- /dev/null +++ b/examples/target_cards/depmap_26q1/MYCN.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MYCN + +## Target identity + +- **Target symbol:** MYCN +- **Target name:** MYCN proto-oncogene, bHLH transcription factor +- **Open Targets melanoma score:** 0.556 +- **Open Targets baseline rank:** 143 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 145 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 146 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 145 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.556) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MYCN lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MYCN in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.16216867965324833,"interquartile_range":0.13075761344972117,"maximum":0.18745096512794407,"mean":-0.09335767882402103,"measured_model_count":56,"median":-0.10231313440314074,"minimum":-0.31346284796372825,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.031411066203527155,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.021207991240808396,"interquartile_range":0.07056960336598046,"maximum":0.31588339444654384,"mean":0.06842223106795756,"measured_model_count":56,"median":0.04657996803044029,"minimum":0.004017152964376389,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09177759460678886,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003399988493472228,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03642384105960265,"pan_cancer_fraction":0.03642384105960265,"threshold":0.5},{"context_fraction":0.0,"difference":-0.028145695364238412,"pan_cancer_fraction":0.028145695364238412,"threshold":0.8}],"gene_effect_mean":0.03544620019184806,"gene_effect_median":-0.0049602520276727236},"dependency_probability_context_minus_non_context_median":-0.0035089035421211334,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03819444444444445,"non_context_fraction":0.03819444444444445,"threshold":0.5},{"context_fraction":0.0,"difference":-0.029513888888888888,"non_context_fraction":0.029513888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03716927936784069,"gene_effect_context_minus_non_context_median":-0.005334098446723098} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 145 +- **Dependency-aware candidate rank:** 145 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2f46cade691d2c3f9825ef65e74a45c7bfea8cec9850ac3720d76c25e8ee1de7` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MYCN|entrez:4613` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/MYH9.md b/examples/target_cards/depmap_26q1/MYH9.md new file mode 100644 index 0000000..3dec16d --- /dev/null +++ b/examples/target_cards/depmap_26q1/MYH9.md @@ -0,0 +1,124 @@ +# Target hypothesis card: MYH9 + +## Target identity + +- **Target symbol:** MYH9 +- **Target name:** myosin heavy chain 9 +- **Open Targets melanoma score:** 0.550 +- **Open Targets baseline rank:** 159 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 161 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 162 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 161 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.550) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** MYH9 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for MYH9 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.43531095200717707,"interquartile_range":0.4321296864755354,"maximum":0.5003544202391196,"mean":-0.2775936121216364,"measured_model_count":56,"median":-0.16774301545077763,"minimum":-1.6066004375290057,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0031812655316416916,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.019496240001612868,"interquartile_range":0.39325137250511455,"maximum":1.0,"mean":0.2679155181304677,"measured_model_count":56,"median":0.09881359449198113,"minimum":0.0001475945704716096,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.4127476125067274,"threshold_fractions":[{"denominator":56,"fraction":0.21428571428571427,"numerator":12,"threshold":0.5},{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.48228792904388695,"dependency_probability_threshold_fractions":[{"context_fraction":0.21428571428571427,"difference":-0.33041627246925254,"pan_cancer_fraction":0.5447019867549668,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.23628192999053926,"pan_cancer_fraction":0.3791390728476821,"threshold":0.8}],"gene_effect_mean":0.2748718719037844,"gene_effect_median":0.3555839647078126},"dependency_probability_context_minus_non_context_median":-0.5048948507760035,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.21428571428571427,"difference":-0.34647817460317454,"non_context_fraction":0.5607638888888888,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.24776785714285715,"non_context_fraction":0.390625,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.28823369901021817,"gene_effect_context_minus_non_context_median":0.3752604249442647} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":0.0} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 161 +- **Dependency-aware candidate rank:** 161 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_cb8ae5586c3af65df3acb8ba8be807f38c0cc4e1d7a13a46c6d1df06c55c58ba` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:MYH9|entrez:4627` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NCOR1.md b/examples/target_cards/depmap_26q1/NCOR1.md new file mode 100644 index 0000000..f1d5181 --- /dev/null +++ b/examples/target_cards/depmap_26q1/NCOR1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NCOR1 + +## Target identity + +- **Target symbol:** NCOR1 +- **Target name:** nuclear receptor corepressor 1 +- **Open Targets melanoma score:** 0.518 +- **Open Targets baseline rank:** 219 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 221 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 221 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 221 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.518) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NCOR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NCOR1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.14874722675576924,"interquartile_range":0.19613442982199808,"maximum":0.40869956664500295,"mean":-0.050841057199357345,"measured_model_count":56,"median":-0.06479063151622333,"minimum":-0.47358794580058783,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.047387203066228845,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0142035703777452,"interquartile_range":0.05741298227323171,"maximum":0.6135325032976449,"mean":0.07185270495360432,"measured_model_count":56,"median":0.03644019619439713,"minimum":0.0004819219900222099,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07161655265097691,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.024293759484647612,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.05085146641438033,"pan_cancer_fraction":0.06870860927152318,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014072847682119206,"pan_cancer_fraction":0.014072847682119206,"threshold":0.8}],"gene_effect_mean":0.08418536973784153,"gene_effect_median":0.05289848641887364},"dependency_probability_context_minus_non_context_median":-0.02542508073445545,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.053323412698412696,"non_context_fraction":0.07118055555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014756944444444444,"non_context_fraction":0.014756944444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08827771410009778,"gene_effect_context_minus_non_context_median":0.05470171183833597} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 221 +- **Dependency-aware candidate rank:** 221 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_76108c2331f584c31fb789defb5aed0b5f9708c16ea62ba60995534ac5a5b24f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NCOR1|entrez:9611` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NCOR2.md b/examples/target_cards/depmap_26q1/NCOR2.md new file mode 100644 index 0000000..313ba58 --- /dev/null +++ b/examples/target_cards/depmap_26q1/NCOR2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NCOR2 + +## Target identity + +- **Target symbol:** NCOR2 +- **Target name:** nuclear receptor corepressor 2 +- **Open Targets melanoma score:** 0.527 +- **Open Targets baseline rank:** 190 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 192 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 192 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 192 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.527) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NCOR2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NCOR2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.19677150936375593,"interquartile_range":0.21722888807469082,"maximum":0.3135537156941089,"mean":-0.0794500067734865,"measured_model_count":56,"median":-0.08617660679431993,"minimum":-0.5326903318404643,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.020457378710934896,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.014692639727071004,"interquartile_range":0.08912182751889369,"maximum":0.7102176386085275,"mean":0.08821307570204999,"measured_model_count":56,"median":0.04143923631202472,"minimum":0.0012173477572731738,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1038144672459647,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004159406552384996,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.01939451277199622,"pan_cancer_fraction":0.037251655629139076,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008278145695364239,"pan_cancer_fraction":0.008278145695364239,"threshold":0.8}],"gene_effect_mean":0.012787652786656029,"gene_effect_median":-0.005097725762859856},"dependency_probability_context_minus_non_context_median":-0.004497928115167298,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.02033730158730159,"non_context_fraction":0.03819444444444445,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008680555555555556,"non_context_fraction":0.008680555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01340927479711855,"gene_effect_context_minus_non_context_median":-0.0057190728377012195} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 192 +- **Dependency-aware candidate rank:** 192 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_9e228d6145f0b25d4922e5d1e12d7f06f9e52bd69d80434cd4d56a11bfc8dba7` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NCOR2|entrez:9612` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NF1.md b/examples/target_cards/depmap_26q1/NF1.md new file mode 100644 index 0000000..1bf76eb --- /dev/null +++ b/examples/target_cards/depmap_26q1/NF1.md @@ -0,0 +1,133 @@ +# Target hypothesis card: NF1 + +## Target identity + +- **Target symbol:** NF1 +- **Target name:** neurofibromin 1 +- **Open Targets melanoma score:** 0.743 +- **Open Targets baseline rank:** 9 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / poor direct therapeutic target +- **Role confidence:** high +- **Therapeutic direction:** avoid as direct target / use as biomarker or pathway context +- **Best modality:** biomarker / pathway context only +- **Resistance axis:** tumor_intrinsic_driver +- **Matched resistance programs:** Tumor-intrinsic driver biology + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 17 | not prioritized | -8 | +| Resistance biomarker | 0.309 | 17 | low | -8 | +| Tumor-intrinsic / small molecule | 0.000 | 39 | not prioritized | -30 | + +## Evidence for + +- Relevant to melanoma tumor-cell biology +- Some targets or pathways are clinically actionable +- Useful for separating tumor-intrinsic drivers from immune-combination targets +- High Open Targets melanoma association score (0.743) +- Maps to curated anti-PD-1 resistance program: Tumor-intrinsic driver biology +- Stable role classifier confidence is high + +## Evidence against / limitations + +- Many tumor-intrinsic drivers are poor antibody targets +- Melanoma association does not automatically imply anti-PD-1 combination suitability +- Tumor suppressors are often poor direct therapeutic targets +- Flagged as poor direct therapeutic target for this MVP +- Role classifier indicates biological relevance but poor direct targetability +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.650 +- **Main limitation:** Poor direct therapeutic target despite biological relevance +- **Uncertainty reason:** High contradiction score indicates important opposing evidence | Main limitation: Poor direct therapeutic target despite biological relevance +- **Deprioritization reason:** NF1 should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context. + +## Recommended next validation experiment + +- **Validation category:** tumor-intrinsic functional validation +- **Next experiment:** Evaluate whether perturbing NF1 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays. +- **Rationale:** This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06668735429589426,"interquartile_range":0.13438545277483557,"maximum":1.0698235652637622,"mean":0.01868900574791985,"measured_model_count":56,"median":0.0019771339155402017,"minimum":-0.2401975756059271,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06769809847894132,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.010584583348384757,"interquartile_range":0.02670090210183779,"maximum":0.16869809455036536,"mean":0.029899133533875046,"measured_model_count":56,"median":0.019721964712171004,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03728548545022255,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00022845419237565306,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.016556291390728478,"pan_cancer_fraction":0.016556291390728478,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.8}],"gene_effect_mean":-0.01293955913841129,"gene_effect_median":-0.006051806545345912},"dependency_probability_context_minus_non_context_median":-0.0003253137843298587,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.017361111111111112,"non_context_fraction":0.017361111111111112,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.013568565485417353,"gene_effect_context_minus_non_context_median":-0.007529220651397316} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 17 +- **Dependency-aware candidate rank:** 17 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_306bbea8c737551aa85a77a9b3c60121159faebc65dd2accf74166da5df903a2` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NF1|entrez:4763` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NF2.md b/examples/target_cards/depmap_26q1/NF2.md new file mode 100644 index 0000000..2aa4d1f --- /dev/null +++ b/examples/target_cards/depmap_26q1/NF2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NF2 + +## Target identity + +- **Target symbol:** NF2 +- **Target name:** NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor +- **Open Targets melanoma score:** 0.474 +- **Open Targets baseline rank:** 280 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 280 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 280 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 280 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.474) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NF2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NF2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.0033319999520227406,"interquartile_range":0.4985835437227313,"maximum":1.4967874348475283,"mean":0.257261458735955,"measured_model_count":56,"median":0.24139439051277362,"minimum":-0.9790795352267114,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.49525154377070857,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.00017270873873151513,"interquartile_range":0.019002620285019006,"maximum":0.9430258163992079,"mean":0.07984631308479892,"measured_model_count":56,"median":0.0025437083249686757,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.01917532902375052,"threshold_fractions":[{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.001039973676862268,"dependency_probability_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":0.03334910122989593,"pan_cancer_fraction":0.0380794701986755,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.0036660359508041626,"pan_cancer_fraction":0.02152317880794702,"threshold":0.8}],"gene_effect_mean":-0.0014079923395545757,"gene_effect_median":0.028469770273931827},"dependency_probability_context_minus_non_context_median":-0.0010699086747809035,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":0.03497023809523809,"non_context_fraction":0.036458333333333336,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.003844246031746032,"non_context_fraction":0.021701388888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0014764364116162665,"gene_effect_context_minus_non_context_median":0.03120785575397461} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 280 +- **Dependency-aware candidate rank:** 280 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_05a8add15cd2bcacbd3adbfd8a68652f1c66ad80e6c3d105077d3272199c0a2b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NF2|entrez:4771` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NFE2L2.md b/examples/target_cards/depmap_26q1/NFE2L2.md new file mode 100644 index 0000000..ce8b8db --- /dev/null +++ b/examples/target_cards/depmap_26q1/NFE2L2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NFE2L2 + +## Target identity + +- **Target symbol:** NFE2L2 +- **Target name:** NFE2 like bZIP transcription factor 2 +- **Open Targets melanoma score:** 0.459 +- **Open Targets baseline rank:** 297 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 297 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 297 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 297 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.459) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NFE2L2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NFE2L2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.2520091656406369,"interquartile_range":0.20548262734606618,"maximum":0.31448187297091834,"mean":-0.13768003790624178,"measured_model_count":56,"median":-0.14924719674865072,"minimum":-0.4886761370341983,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.046526538294570735,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.031692531987762916,"interquartile_range":0.13629651356662498,"maximum":0.5844930902604566,"mean":0.1270283768174245,"measured_model_count":56,"median":0.08432932917261374,"minimum":0.0003081043336782536,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1679890455543879,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.041173957256818466,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.08384578997161779,"pan_cancer_fraction":0.13741721854304637,"threshold":0.5},{"context_fraction":0.0,"difference":-0.062086092715231786,"pan_cancer_fraction":0.062086092715231786,"threshold":0.8}],"gene_effect_mean":0.12219017207461635,"gene_effect_median":0.05562504107043592},"dependency_probability_context_minus_non_context_median":-0.04412269038471142,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.08792162698412698,"non_context_fraction":0.14149305555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.06510416666666667,"non_context_fraction":0.06510416666666667,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.12812997210602156,"gene_effect_context_minus_non_context_median":0.05789486954820591} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 297 +- **Dependency-aware candidate rank:** 297 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a434db41122df3a7efb43447fadf1f1b96b72ad8ba24f7a5f8e37dfa5f390cd7` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NFE2L2|entrez:4780` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NFKB2.md b/examples/target_cards/depmap_26q1/NFKB2.md new file mode 100644 index 0000000..7dfbb07 --- /dev/null +++ b/examples/target_cards/depmap_26q1/NFKB2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NFKB2 + +## Target identity + +- **Target symbol:** NFKB2 +- **Target name:** nuclear factor kappa B subunit 2 +- **Open Targets melanoma score:** 0.522 +- **Open Targets baseline rank:** 200 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 202 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 202 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 202 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.522) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NFKB2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NFKB2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.1463779154801344,"interquartile_range":0.16275217738118264,"maximum":0.3906297033324104,"mean":-0.06272083452331122,"measured_model_count":56,"median":-0.07291431839673687,"minimum":-0.5332535016531746,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.016374261901048223,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01669333637117928,"interquartile_range":0.06426057937780422,"maximum":0.5792888550716845,"mean":0.07237504948051252,"measured_model_count":56,"median":0.039965302273933655,"minimum":0.0005060565776778315,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0809539157489835,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.03721333081785242,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.03760643330179754,"pan_cancer_fraction":0.055463576158940396,"threshold":0.5},{"context_fraction":0.0,"difference":-0.024006622516556293,"pan_cancer_fraction":0.024006622516556293,"threshold":0.8}],"gene_effect_mean":0.09950651123097475,"gene_effect_median":0.0713352316781887},"dependency_probability_context_minus_non_context_median":-0.040284300088949794,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.03943452380952381,"non_context_fraction":0.057291666666666664,"threshold":0.5},{"context_fraction":0.0,"difference":-0.025173611111111112,"non_context_fraction":0.025173611111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.10434363330470263,"gene_effect_context_minus_non_context_median":0.076204722483839} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 202 +- **Dependency-aware candidate rank:** 202 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_5163e4a1e8bbb0722f492708f61f90aae1e907db8822be71fbe6351225a471a5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NFKB2|entrez:4791` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NFKBIE.md b/examples/target_cards/depmap_26q1/NFKBIE.md new file mode 100644 index 0000000..ec12d77 --- /dev/null +++ b/examples/target_cards/depmap_26q1/NFKBIE.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NFKBIE + +## Target identity + +- **Target symbol:** NFKBIE +- **Target name:** NFKB inhibitor epsilon +- **Open Targets melanoma score:** 0.552 +- **Open Targets baseline rank:** 151 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 153 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 154 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 153 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.552) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NFKBIE lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NFKBIE in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.4747394844173423,"interquartile_range":0.2676801224614766,"maximum":0.41948154320340647,"mean":-0.3416210665817968,"measured_model_count":56,"median":-0.3591398799415844,"minimum":-1.083785830359554,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.20705936195586572,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.1375067692802133,"interquartile_range":0.37049721185843076,"maximum":0.958742819767064,"mean":0.3531347237615799,"measured_model_count":56,"median":0.3441621104153567,"minimum":0.0002733574349602312,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5080039811386441,"threshold_fractions":[{"denominator":56,"fraction":0.26785714285714285,"numerator":15,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.057732492905683164,"dependency_probability_threshold_fractions":[{"context_fraction":0.26785714285714285,"difference":-0.12949385052034057,"pan_cancer_fraction":0.3973509933774834,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.07272942289498581,"pan_cancer_fraction":0.10844370860927152,"threshold":0.8}],"gene_effect_mean":0.07758626106936861,"gene_effect_median":0.040194233698520765},"dependency_probability_context_minus_non_context_median":-0.05994962551203031,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.26785714285714285,"difference":-0.13578869047619047,"non_context_fraction":0.4036458333333333,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.07626488095238096,"non_context_fraction":0.11197916666666667,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08135781542690734,"gene_effect_context_minus_non_context_median":0.0427321013429815} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 153 +- **Dependency-aware candidate rank:** 153 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_cb8e4c718580d371942873febe1a8c25a6c9b88dc35ffb4e96c1a0f8926a9277` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NFKBIE|entrez:4794` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NGFR.md b/examples/target_cards/depmap_26q1/NGFR.md new file mode 100644 index 0000000..6c936ff --- /dev/null +++ b/examples/target_cards/depmap_26q1/NGFR.md @@ -0,0 +1,73 @@ +# NGFR — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.30792591558766197,"interquartile_range":0.11989661346851041,"maximum":0.11576261821187195,"mean":-0.24643987201509007,"measured_model_count":56,"median":-0.24041421960464082,"minimum":-0.4807813402770903,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.18802930211915156,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.09390776865702505,"interquartile_range":0.16367174704167087,"maximum":0.5605448986371326,"mean":0.1942768969038153,"measured_model_count":56,"median":0.1667282415797557,"minimum":0.008597790397277472,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2575795156986959,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.017541887806746148,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.004020813623462634,"pan_cancer_fraction":0.039735099337748346,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.011086422347907576,"gene_effect_median":-0.012159150132109414},"dependency_probability_context_minus_non_context_median":0.017987696781701923,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.00421626984126984,"non_context_fraction":0.03993055555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.011625345656486624,"gene_effect_context_minus_non_context_median":-0.012913856993605505} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d88a4a6e8d58eb9d9be4cfa5fefe136c56be9a1fe67fea5f0472889cf6fad807` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NGFR|entrez:4804` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NKX2-1.md b/examples/target_cards/depmap_26q1/NKX2-1.md new file mode 100644 index 0000000..7a96f68 --- /dev/null +++ b/examples/target_cards/depmap_26q1/NKX2-1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NKX2-1 + +## Target identity + +- **Target symbol:** NKX2-1 +- **Target name:** NK2 homeobox 1 +- **Open Targets melanoma score:** 0.509 +- **Open Targets baseline rank:** 240 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 242 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 242 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 242 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.509) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NKX2-1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NKX2-1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.12276799614693762,"interquartile_range":0.18307558688335396,"maximum":0.27550802661951984,"mean":-0.043376474182780414,"measured_model_count":56,"median":-0.03133446214879327,"minimum":-0.4273642289892,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.060307590736416325,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.010194888921109245,"interquartile_range":0.04847112414292441,"maximum":0.3976824988928863,"mean":0.060590058138209654,"measured_model_count":56,"median":0.02987755063188091,"minimum":0.0012628047782111012,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.058666013064033656,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.006920390134227572,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0173841059602649,"pan_cancer_fraction":0.0173841059602649,"threshold":0.5},{"context_fraction":0.0,"difference":-0.011589403973509934,"pan_cancer_fraction":0.011589403973509934,"threshold":0.8}],"gene_effect_mean":-0.02431278240743919,"gene_effect_median":-0.023869701579934878},"dependency_probability_context_minus_non_context_median":0.007261515319367598,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.018229166666666668,"non_context_fraction":0.018229166666666668,"threshold":0.5},{"context_fraction":0.0,"difference":-0.012152777777777778,"non_context_fraction":0.012152777777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.025494653774467475,"gene_effect_context_minus_non_context_median":-0.02458657597811076} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 242 +- **Dependency-aware candidate rank:** 242 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_5fc4628007da194a0f864fc55f87c4defaaae339f5ff022dbdcdfd337537981e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NKX2-1|entrez:7080` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NOTCH1.md b/examples/target_cards/depmap_26q1/NOTCH1.md new file mode 100644 index 0000000..dfdacb3 --- /dev/null +++ b/examples/target_cards/depmap_26q1/NOTCH1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NOTCH1 + +## Target identity + +- **Target symbol:** NOTCH1 +- **Target name:** notch receptor 1 +- **Open Targets melanoma score:** 0.466 +- **Open Targets baseline rank:** 287 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 287 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 287 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 287 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.466) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NOTCH1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NOTCH1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.04943752847392074,"interquartile_range":0.11481559041215458,"maximum":0.16997708658381597,"mean":-0.0011867456856176305,"measured_model_count":56,"median":0.008586282728026395,"minimum":-0.2810791148673261,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06537806193823384,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.012038295662059835,"interquartile_range":0.022845606718235385,"maximum":0.18447254484328296,"mean":0.030522579666454237,"measured_model_count":56,"median":0.015886080712783135,"minimum":0.004403982739587212,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03488390238029522,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004511437646536366,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.002881876199835815,"gene_effect_median":0.0019853222554847925},"dependency_probability_context_minus_non_context_median":-0.004730151946607315,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.003021967403994499,"gene_effect_context_minus_non_context_median":0.002190064586723877} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 287 +- **Dependency-aware candidate rank:** 287 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_12522c3c7b551212b5b12d87edb900063144f2a9309c36eef95e8213577c8f8f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NOTCH1|entrez:4851` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NOTCH2.md b/examples/target_cards/depmap_26q1/NOTCH2.md new file mode 100644 index 0000000..0a1767c --- /dev/null +++ b/examples/target_cards/depmap_26q1/NOTCH2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NOTCH2 + +## Target identity + +- **Target symbol:** NOTCH2 +- **Target name:** notch receptor 2 +- **Open Targets melanoma score:** 0.575 +- **Open Targets baseline rank:** 106 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 109 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 110 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 109 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.575) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NOTCH2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NOTCH2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.13850163507429375,"interquartile_range":0.2244656275170174,"maximum":0.3986273246825719,"mean":-0.030350525395588388,"measured_model_count":56,"median":-0.034328145661024975,"minimum":-0.44916442200119266,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08596399244272365,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.007945313328654979,"interquartile_range":0.08294853524488494,"maximum":0.4118005119658145,"mean":0.06629039133767924,"measured_model_count":56,"median":0.025783870960812194,"minimum":0.002243224020282026,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09089384857353991,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.008359685791117233,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.01076158940397351,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.8}],"gene_effect_mean":0.018910825757955958,"gene_effect_median":0.021337019372317377},"dependency_probability_context_minus_non_context_median":-0.00914746633812634,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.011284722222222222,"non_context_fraction":0.011284722222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.019830102010078756,"gene_effect_context_minus_non_context_median":0.021599372856303388} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 109 +- **Dependency-aware candidate rank:** 109 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_fa23bea35f8129e15b88020fb8777a77b7aa952868e1fe0c1ab1eef3bdc8451b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NOTCH2|entrez:4853` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NRAS.md b/examples/target_cards/depmap_26q1/NRAS.md new file mode 100644 index 0000000..c579032 --- /dev/null +++ b/examples/target_cards/depmap_26q1/NRAS.md @@ -0,0 +1,133 @@ +# Target hypothesis card: NRAS + +## Target identity + +- **Target symbol:** NRAS +- **Target name:** NRAS proto-oncogene, GTPase +- **Open Targets melanoma score:** 0.779 +- **Open Targets baseline rank:** 5 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / biomarker +- **Role confidence:** medium-high +- **Therapeutic direction:** use as biomarker / pathway targeting if appropriate +- **Best modality:** tumor-intrinsic biomarker / pathway context +- **Resistance axis:** tumor_intrinsic_driver +- **Matched resistance programs:** Tumor-intrinsic driver biology + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.301 | 6 | low | -1 | +| Resistance biomarker | 0.760 | 4 | high | 1 | +| Tumor-intrinsic / small molecule | 0.666 | 6 | medium | -1 | + +## Evidence for + +- Relevant to melanoma tumor-cell biology +- Some targets or pathways are clinically actionable +- Useful for separating tumor-intrinsic drivers from immune-combination targets +- High Open Targets melanoma association score (0.779) +- Maps to curated anti-PD-1 resistance program: Tumor-intrinsic driver biology +- Stable role classifier confidence is medium-high +- Biomarker fit is medium-high + +## Evidence against / limitations + +- Many tumor-intrinsic drivers are poor antibody targets +- Melanoma association does not automatically imply anti-PD-1 combination suitability +- Tumor suppressors are often poor direct therapeutic targets +- Most useful as biomarker or stratification marker rather than direct therapeutic target +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** high confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.400 +- **Main limitation:** Likely more useful for stratification than direct therapeutic targeting +- **Uncertainty reason:** Moderate contradiction score indicates caution is needed | Main limitation: Likely more useful for stratification than direct therapeutic targeting +- **Deprioritization reason:** NRAS should not be deprioritized globally, but should be ranked mainly in biomarker or patient-stratification mode. + +## Recommended next validation experiment + +- **Validation category:** biomarker validation +- **Next experiment:** Test whether NRAS status or expression differs between anti-PD-1 responders and non-responders in an independent melanoma cohort. +- **Rationale:** This would determine whether the candidate has practical value as a resistance biomarker or patient-stratification feature. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.3305911123197959,"interquartile_range":0.20369185017668184,"maximum":0.09354479287791917,"mean":-0.44904229263305867,"measured_model_count":56,"median":-0.19958349119150692,"minimum":-2.9561530105181015,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.12689926214311403,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.05768686105568797,"interquartile_range":0.22765180742178384,"maximum":1.0,"mean":0.27492022095168256,"measured_model_count":56,"median":0.11160490099703885,"minimum":0.004688799268174339,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2853386684774718,"threshold_fractions":[{"denominator":56,"fraction":0.19642857142857142,"numerator":11,"threshold":0.5},{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03043227636868405,"dependency_probability_threshold_fractions":[{"context_fraction":0.19642857142857142,"difference":0.11116367076631976,"pan_cancer_fraction":0.08526490066225166,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.10773415326395461,"pan_cancer_fraction":0.052980132450331126,"threshold":0.8}],"gene_effect_mean":-0.2283655354809437,"gene_effect_median":-0.05177886304443688},"dependency_probability_context_minus_non_context_median":0.03204527595438135,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.19642857142857142,"difference":0.11656746031746032,"non_context_fraction":0.0798611111111111,"threshold":0.5},{"context_fraction":0.16071428571428573,"difference":0.11297123015873017,"non_context_fraction":0.04774305555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.23946663790015615,"gene_effect_context_minus_non_context_median":-0.053778538177950364} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 6 +- **Dependency-aware candidate rank:** 3 +- **Rank delta:** -3 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_1006bb8f646ab657109ccdcd33c00d15c235fa96e722c0ba89e9fc9798d3ccef` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NRAS|entrez:4893` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NT5E.md b/examples/target_cards/depmap_26q1/NT5E.md new file mode 100644 index 0000000..a30864e --- /dev/null +++ b/examples/target_cards/depmap_26q1/NT5E.md @@ -0,0 +1,73 @@ +# NT5E — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.07327247215096008,"interquartile_range":0.1162611666370785,"maximum":0.2732322344641132,"mean":-0.0047660578695370584,"measured_model_count":56,"median":-0.008866378941955744,"minimum":-0.262273581288223,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04298869448611842,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.014413470815455534,"interquartile_range":0.024615083725310807,"maximum":0.20865009438516322,"mean":0.03134252380078864,"measured_model_count":56,"median":0.0211052075698444,"minimum":0.0020125603678799444,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03902855454076634,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002293839989739456,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.005378338834790834,"gene_effect_median":0.0017674569453955888},"dependency_probability_context_minus_non_context_median":-0.0024087456741203536,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.00563978586148206,"gene_effect_context_minus_non_context_median":0.0017674569453955888} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_8ae6481aedc84705f6325d21e4410cf48e8b9b8631209ae795b0dcbfb9ecbecf` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NT5E|entrez:4907` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NTRK1.md b/examples/target_cards/depmap_26q1/NTRK1.md new file mode 100644 index 0000000..a815bf4 --- /dev/null +++ b/examples/target_cards/depmap_26q1/NTRK1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NTRK1 + +## Target identity + +- **Target symbol:** NTRK1 +- **Target name:** neurotrophic receptor tyrosine kinase 1 +- **Open Targets melanoma score:** 0.603 +- **Open Targets baseline rank:** 66 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 70 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 72 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 70 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.603) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NTRK1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NTRK1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.04264846706192717,"interquartile_range":0.1195819914607735,"maximum":0.20114723020449096,"mean":0.015540283237262965,"measured_model_count":56,"median":0.026272854423689842,"minimum":-0.23366332567258905,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07693352439884633,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.009811935298125282,"interquartile_range":0.024365972544399282,"maximum":0.14777656422626312,"mean":0.024222066161382748,"measured_model_count":56,"median":0.01863576450281533,"minimum":0.00207213738312382,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.034177907842524564,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0026097343765249664,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.01653609182805236,"gene_effect_median":0.023617564189398383},"dependency_probability_context_minus_non_context_median":-0.0026693963472452023,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01733992962524936,"gene_effect_context_minus_non_context_median":0.024330047611103866} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 70 +- **Dependency-aware candidate rank:** 70 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2850f3a7f8e52fc114a0216526457d3eecd24446606aee50be84b2e59a719198` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NTRK1|entrez:4914` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NTRK2.md b/examples/target_cards/depmap_26q1/NTRK2.md new file mode 100644 index 0000000..f3181e0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/NTRK2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NTRK2 + +## Target identity + +- **Target symbol:** NTRK2 +- **Target name:** neurotrophic receptor tyrosine kinase 2 +- **Open Targets melanoma score:** 0.574 +- **Open Targets baseline rank:** 109 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 112 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 113 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 112 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.574) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NTRK2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NTRK2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.014221021812303218,"interquartile_range":0.14884406245468834,"maximum":0.42475333414356103,"mean":0.09655480444725151,"measured_model_count":56,"median":0.08551856745146294,"minimum":-0.2698832809930628,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.16306508426699157,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.003994279326308055,"interquartile_range":0.015022230202413047,"maximum":0.16008520535900733,"mean":0.015090863385395179,"measured_model_count":56,"median":0.007605478950701532,"minimum":0.00032944850035258275,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.019016509528721103,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0005276351297663958,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.013549136427241329,"gene_effect_median":-0.024133503389609345},"dependency_probability_context_minus_non_context_median":-0.0005624714137863925,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.014207775003565543,"gene_effect_context_minus_non_context_median":-0.02460948284873654} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":66.66666666666667} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 112 +- **Dependency-aware candidate rank:** 112 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_f1b3909e0c13b02736454cfc41d932f82b1a6941ac58b134800c06c58f0ac9e0` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NTRK2|entrez:4915` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NTRK3.md b/examples/target_cards/depmap_26q1/NTRK3.md new file mode 100644 index 0000000..ba2d414 --- /dev/null +++ b/examples/target_cards/depmap_26q1/NTRK3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NTRK3 + +## Target identity + +- **Target symbol:** NTRK3 +- **Target name:** neurotrophic receptor tyrosine kinase 3 +- **Open Targets melanoma score:** 0.543 +- **Open Targets baseline rank:** 176 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 178 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 179 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 178 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.543) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NTRK3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NTRK3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.07238517527802066,"interquartile_range":0.13988816637951834,"maximum":0.27181984530850334,"mean":-0.008595154891903269,"measured_model_count":56,"median":0.00021986816198801135,"minimum":-0.4322775348198563,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06750299110149767,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.010213270016093746,"interquartile_range":0.03102434821200728,"maximum":0.3764846557634913,"mean":0.03842677280420746,"measured_model_count":56,"median":0.019114279173136295,"minimum":0.0013946676886993539,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04123761822810103,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0029891060828684396,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.036162069681453,"gene_effect_median":-0.027547539772977414},"dependency_probability_context_minus_non_context_median":0.003129747662845954,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.037919948068745865,"gene_effect_context_minus_non_context_median":-0.029605263286164356} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 178 +- **Dependency-aware candidate rank:** 178 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_498ab797376e748417d1d149204710e6ff7beaf50b220e284db9d59f4bdda6f5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NTRK3|entrez:4916` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NUP98.md b/examples/target_cards/depmap_26q1/NUP98.md new file mode 100644 index 0000000..0cf191e --- /dev/null +++ b/examples/target_cards/depmap_26q1/NUP98.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NUP98 + +## Target identity + +- **Target symbol:** NUP98 +- **Target name:** nucleoporin 98 and 96 precursor +- **Open Targets melanoma score:** 0.517 +- **Open Targets baseline rank:** 223 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 225 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 225 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 225 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.517) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NUP98 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NUP98 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.946727819118484,"interquartile_range":0.2497531610528998,"maximum":-0.35725870489878797,"mean":-0.8454054346865577,"measured_model_count":56,"median":-0.8055598197254084,"minimum":-1.97097650992929,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.6969746580655842,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.8242508054226083,"interquartile_range":0.14214214374173795,"maximum":0.9999613193078875,"mean":0.855911828309157,"measured_model_count":56,"median":0.9185618693763015,"minimum":0.25117687375019454,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9663929491643463,"threshold_fractions":[{"denominator":56,"fraction":0.9464285714285714,"numerator":53,"threshold":0.5},{"denominator":56,"fraction":0.8035714285714286,"numerator":45,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.013608595849936012,"dependency_probability_threshold_fractions":[{"context_fraction":0.9464285714285714,"difference":0.020931882686849534,"pan_cancer_fraction":0.9254966887417219,"threshold":0.5},{"context_fraction":0.8035714285714286,"difference":0.08171712393566699,"pan_cancer_fraction":0.7218543046357616,"threshold":0.8}],"gene_effect_mean":-0.03771092138285437,"gene_effect_median":-0.01749412142517137},"dependency_probability_context_minus_non_context_median":0.01587729335632837,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9464285714285714,"difference":0.021949404761904767,"non_context_fraction":0.9244791666666666,"threshold":0.5},{"context_fraction":0.8035714285714286,"difference":0.08568948412698418,"non_context_fraction":0.7178819444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03954409117229907,"gene_effect_context_minus_non_context_median":-0.01970122639959393} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 225 +- **Dependency-aware candidate rank:** 225 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_1ba578635cb5aef41676cb0043c4781a1ce8bac50ca758d201877e4ced8cb0b7` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NUP98|entrez:4928` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/NUTM1.md b/examples/target_cards/depmap_26q1/NUTM1.md new file mode 100644 index 0000000..c90381e --- /dev/null +++ b/examples/target_cards/depmap_26q1/NUTM1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: NUTM1 + +## Target identity + +- **Target symbol:** NUTM1 +- **Target name:** NUT midline carcinoma family member 1 +- **Open Targets melanoma score:** 0.561 +- **Open Targets baseline rank:** 133 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 135 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 136 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 135 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.561) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** NUTM1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for NUTM1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06766413170933441,"interquartile_range":0.12230469464003679,"maximum":0.23858120904323193,"mean":-0.013250682999457888,"measured_model_count":56,"median":-0.01540965770348755,"minimum":-0.33765216343614773,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05464056293070238,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.012373005021698226,"interquartile_range":0.026164771633834467,"maximum":0.22158294522974528,"mean":0.03317301826003201,"measured_model_count":56,"median":0.023444423153857114,"minimum":0.0015163016029478907,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03853777665553269,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0001316682205584757,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":-0.000661284332854499,"gene_effect_median":-0.005158631169675826},"dependency_probability_context_minus_non_context_median":0.00014568546017170586,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0006934300990349106,"gene_effect_context_minus_non_context_median":-0.005295065741185927} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 135 +- **Dependency-aware candidate rank:** 135 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a7580b2432b014db80d8227696d1df4599afb6ffea0b59a0f07c2e74ffbd01f2` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:NUTM1|entrez:256646` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/OCA2.md b/examples/target_cards/depmap_26q1/OCA2.md new file mode 100644 index 0000000..829a90f --- /dev/null +++ b/examples/target_cards/depmap_26q1/OCA2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: OCA2 + +## Target identity + +- **Target symbol:** OCA2 +- **Target name:** OCA2 melanosomal transmembrane protein +- **Open Targets melanoma score:** 0.594 +- **Open Targets baseline rank:** 77 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 81 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 83 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 81 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.594) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** OCA2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for OCA2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.11003886894933272,"interquartile_range":0.12428844836998826,"maximum":0.17215928504056552,"mean":-0.04570717775043043,"measured_model_count":56,"median":-0.024477812493177965,"minimum":-0.2893171738503026,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.014249579420655543,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01726318105631539,"interquartile_range":0.03416598908030699,"maximum":0.2544187739476363,"mean":0.04408398212649205,"measured_model_count":56,"median":0.025337616392692195,"minimum":0.0036640872919462475,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.051429170136622376,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.007786010091894207,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.006999676819245647,"gene_effect_median":0.023317806384539723},"dependency_probability_context_minus_non_context_median":-0.008143804426631634,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.007339938886847905,"gene_effect_context_minus_non_context_median":0.023893361550354493} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 81 +- **Dependency-aware candidate rank:** 81 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_815423402101e51b7deb2d11c38997994f088fde620e66d3bd82415408b7b1ae` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:OCA2|entrez:4948` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PARP1.md b/examples/target_cards/depmap_26q1/PARP1.md new file mode 100644 index 0000000..4418ffb --- /dev/null +++ b/examples/target_cards/depmap_26q1/PARP1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PARP1 + +## Target identity + +- **Target symbol:** PARP1 +- **Target name:** poly(ADP-ribose) polymerase 1 +- **Open Targets melanoma score:** 0.542 +- **Open Targets baseline rank:** 178 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 180 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 181 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 180 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.542) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PARP1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PARP1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.3126108449025472,"interquartile_range":0.19294837361965708,"maximum":0.11033739065298756,"mean":-0.2123893655849565,"measured_model_count":56,"median":-0.20900614511179944,"minimum":-0.5526061990232184,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.11966247128289012,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0579623906831193,"interquartile_range":0.22040785644401745,"maximum":0.6102638834732295,"mean":0.1765929122874719,"measured_model_count":56,"median":0.13645456881846418,"minimum":0.005254797527991211,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.27837024712713676,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.022842800470256275,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.0027199621570482557,"pan_cancer_fraction":0.056291390728476824,"threshold":0.5},{"context_fraction":0.0,"difference":-0.01076158940397351,"pan_cancer_fraction":0.01076158940397351,"threshold":0.8}],"gene_effect_mean":-0.003104326665073792,"gene_effect_median":-0.011763437800700827},"dependency_probability_context_minus_non_context_median":0.022954289988049728,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.0028521825396825434,"non_context_fraction":0.05642361111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.011284722222222222,"non_context_fraction":0.011284722222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.003255231433514666,"gene_effect_context_minus_non_context_median":-0.012316196722426925} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 180 +- **Dependency-aware candidate rank:** 180 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_6a05d4f572df2935e2aa57c8c0be391ab627b597e3b8d4ad8df2850c5769dd08` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PARP1|entrez:142` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PATZ1.md b/examples/target_cards/depmap_26q1/PATZ1.md new file mode 100644 index 0000000..93bbea4 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PATZ1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PATZ1 + +## Target identity + +- **Target symbol:** PATZ1 +- **Target name:** POZ/BTB and AT hook containing zinc finger 1 +- **Open Targets melanoma score:** 0.490 +- **Open Targets baseline rank:** 263 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 265 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 265 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 265 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.490) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PATZ1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PATZ1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.21337700367028087,"interquartile_range":0.13030410006901616,"maximum":0.1548473717667494,"mean":-0.15100029050775082,"measured_model_count":56,"median":-0.1391172000683189,"minimum":-0.4179920396603739,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.08307290360126471,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.04269880256237364,"interquartile_range":0.1065916921003043,"maximum":0.39286694038493386,"mean":0.1137033476788312,"measured_model_count":56,"median":0.0798356188482517,"minimum":0.005100727127091044,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14929049466267794,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0165327815011949,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.018211920529801324,"pan_cancer_fraction":0.018211920529801324,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.018082096825231653,"gene_effect_median":-0.01592223397123585},"dependency_probability_context_minus_non_context_median":0.016974812374555837,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.019097222222222224,"non_context_fraction":0.019097222222222224,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.018961087643124847,"gene_effect_context_minus_non_context_median":-0.017953281291869364} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 265 +- **Dependency-aware candidate rank:** 265 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_52a78bebffa1d89f48c59775393aabee731c6dc5fc9b401178979e6d7be3839a` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PATZ1|entrez:23598` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PAX5.md b/examples/target_cards/depmap_26q1/PAX5.md new file mode 100644 index 0000000..2973d21 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PAX5.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PAX5 + +## Target identity + +- **Target symbol:** PAX5 +- **Target name:** paired box 5 +- **Open Targets melanoma score:** 0.563 +- **Open Targets baseline rank:** 128 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 130 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 131 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 130 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.563) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PAX5 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PAX5 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.1088845448548971,"interquartile_range":0.14703441884732282,"maximum":0.13854687883744554,"mean":-0.03206191587252125,"measured_model_count":56,"median":-0.014464371335449124,"minimum":-0.30679469825273975,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03814987399242574,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.011626966753839703,"interquartile_range":0.04602638788189701,"maximum":0.26838932138817734,"mean":0.0402637735904481,"measured_model_count":56,"median":0.023559907731496195,"minimum":0.004857244948173928,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05765335463573671,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.011722016265201161,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.03890728476821192,"pan_cancer_fraction":0.03890728476821192,"threshold":0.5},{"context_fraction":0.0,"difference":-0.03394039735099338,"pan_cancer_fraction":0.03394039735099338,"threshold":0.8}],"gene_effect_mean":0.055946069728392576,"gene_effect_median":0.039854709962933575},"dependency_probability_context_minus_non_context_median":-0.012750077624742832,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04079861111111111,"non_context_fraction":0.04079861111111111,"threshold":0.5},{"context_fraction":0.0,"difference":-0.035590277777777776,"non_context_fraction":0.035590277777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05866567034018951,"gene_effect_context_minus_non_context_median":0.04088643415318896} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 130 +- **Dependency-aware candidate rank:** 130 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_adfc0d524f5bc6d987c20c279ea8a07cdc714fab64857b668ef270209b743fef` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PAX5|entrez:5079` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PBRM1.md b/examples/target_cards/depmap_26q1/PBRM1.md new file mode 100644 index 0000000..6f18227 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PBRM1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PBRM1 + +## Target identity + +- **Target symbol:** PBRM1 +- **Target name:** polybromo 1 +- **Open Targets melanoma score:** 0.636 +- **Open Targets baseline rank:** 37 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 44 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 46 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 44 | not prioritized | -7 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.636) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PBRM1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PBRM1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.16479697620735534,"interquartile_range":0.3034207952026297,"maximum":0.4448525230836686,"mean":-0.022173015534992117,"measured_model_count":56,"median":-0.04422832147235136,"minimum":-0.6075030044826925,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.13862381899527437,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005101405183288445,"interquartile_range":0.08901199505560088,"maximum":0.6419488286639063,"mean":0.07271163892119407,"measured_model_count":56,"median":0.025873981311805343,"minimum":0.00026959172539142045,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09411340023888932,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.039527938309002454,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.07816934720908231,"pan_cancer_fraction":0.09602649006622517,"threshold":0.5},{"context_fraction":0.0,"difference":-0.026490066225165563,"pan_cancer_fraction":0.026490066225165563,"threshold":0.8}],"gene_effect_mean":0.1175627255548197,"gene_effect_median":0.0838554947391201},"dependency_probability_context_minus_non_context_median":-0.042001975597918496,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.08196924603174605,"non_context_fraction":0.0998263888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.027777777777777776,"non_context_fraction":0.027777777777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.12327758026929003,"gene_effect_context_minus_non_context_median":0.08746995500031005} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 44 +- **Dependency-aware candidate rank:** 44 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_42b9a8e63a0488f33b8490d1f61763014ede5eb8c77c504ee0c1575f9bb8103a` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PBRM1|entrez:55193` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PDCD1.md b/examples/target_cards/depmap_26q1/PDCD1.md new file mode 100644 index 0000000..1eeafed --- /dev/null +++ b/examples/target_cards/depmap_26q1/PDCD1.md @@ -0,0 +1,133 @@ +# Target hypothesis card: PDCD1 + +## Target identity + +- **Target symbol:** PDCD1 +- **Target name:** programmed cell death 1 +- **Open Targets melanoma score:** 0.630 +- **Open Targets baseline rank:** 44 + +## Stable TargetIntel-IO classification + +- **Role classification:** anti-PD-1 combination target +- **Role confidence:** high +- **Therapeutic direction:** block / inhibit +- **Best modality:** antibody / IO-combination target +- **Resistance axis:** checkpoint_redundancy +- **Matched resistance programs:** Checkpoint redundancy + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.827 | 2 | high | 42 | +| Resistance biomarker | 0.498 | 8 | medium | 36 | +| Tumor-intrinsic / small molecule | 0.144 | 10 | low | 34 | + +## Evidence for + +- Immune checkpoint biology +- Potential compensatory inhibitory pathway after PD-1 blockade +- Surface-accessible immune receptor or ligand +- Moderate Open Targets melanoma association score (0.630) +- Maps to curated anti-PD-1 resistance program: Checkpoint redundancy +- Stable role classifier confidence is high +- Antibody fit is high +- IO-combination fit is high +- Checkpoint-axis biology supports anti-PD-1 combination rationale + +## Evidence against / limitations + +- Crowded IO target space +- Expression may reflect exhausted immune-cell abundance rather than causal resistance in all tumors +- Patient selection may be required + +## Confidence and uncertainty + +- **Confidence level:** high confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.240 +- **Main limitation:** No major limitation flagged by current MVP rules +- **Uncertainty reason:** Main limitation: No major limitation flagged by current MVP rules +- **Deprioritization reason:** No strong deprioritization reason from current MVP rules + +## Recommended next validation experiment + +- **Validation category:** immune-checkpoint functional validation +- **Next experiment:** Validate PDCD1 expression in exhausted CD8 T-cell populations from anti-PD-1-resistant melanoma samples and test blockade in a melanoma/T-cell co-culture assay. +- **Rationale:** This would test whether the candidate marks a relevant checkpoint axis and whether blockade can improve anti-tumor T-cell activity. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.07586317533990133,"interquartile_range":0.1536254155593421,"maximum":0.3225183637936061,"mean":-0.0001670624551346131,"measured_model_count":56,"median":-0.01957298536283847,"minimum":-0.3110634393914682,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07776224021944075,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008553814788841528,"interquartile_range":0.03284445323467796,"maximum":0.2333724479616654,"mean":0.04119029126229425,"measured_model_count":56,"median":0.02164243704516978,"minimum":0.0004402840326518532,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04139826802351949,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00541766690770247,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.0328050342124573,"gene_effect_median":-0.05178660616511987},"dependency_probability_context_minus_non_context_median":0.005614043375074734,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03439972337556283,"gene_effect_context_minus_non_context_median":-0.05289749726051174} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":100.0} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 2 +- **Dependency-aware candidate rank:** 4 +- **Rank delta:** 2 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_9818f6abb8a6b180f62f5aa111d227fb8de1d192e5557d65ab9e3e5887da73a9` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PDCD1|entrez:5133` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PDCD1LG2.md b/examples/target_cards/depmap_26q1/PDCD1LG2.md new file mode 100644 index 0000000..c0c7414 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PDCD1LG2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PDCD1LG2 + +## Target identity + +- **Target symbol:** PDCD1LG2 +- **Target name:** programmed cell death 1 ligand 2 +- **Open Targets melanoma score:** 0.467 +- **Open Targets baseline rank:** 285 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 285 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 285 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 285 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.467) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PDCD1LG2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PDCD1LG2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.05816013705757744,"interquartile_range":0.11189371167739326,"maximum":0.3771133025892327,"mean":0.1072155941052707,"measured_model_count":56,"median":0.09145888055795778,"minimum":-0.11873669255379785,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1700538487349707,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0037372367702815036,"interquartile_range":0.010498710407831242,"maximum":0.04984001631579498,"mean":0.01034691838648634,"measured_model_count":56,"median":0.007611086135415668,"minimum":0.0007532072106878847,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.014235947178112746,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0007237109323909741,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.003496438269033439,"gene_effect_median":-0.01053245350068871},"dependency_probability_context_minus_non_context_median":-0.0008202855656675306,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0036664040182225466,"gene_effect_context_minus_non_context_median":-0.011543940179797221} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 285 +- **Dependency-aware candidate rank:** 285 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_7a088b831eece2f58f819654d1362e7bdf2ef4a776cf8e18f8aebffc15ca7533` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PDCD1LG2|entrez:80380` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PDGFRA.md b/examples/target_cards/depmap_26q1/PDGFRA.md new file mode 100644 index 0000000..0c88ff0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PDGFRA.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PDGFRA + +## Target identity + +- **Target symbol:** PDGFRA +- **Target name:** platelet derived growth factor receptor alpha +- **Open Targets melanoma score:** 0.666 +- **Open Targets baseline rank:** 27 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 34 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 36 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.004 | 29 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.666) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PDGFRA lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PDGFRA in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.2533602866327354,"interquartile_range":0.12572359618727533,"maximum":0.09819146945773913,"mean":-0.1964573159629175,"measured_model_count":56,"median":-0.18362142417989624,"minimum":-0.6817254249652711,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.12763669044546008,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.05686242904454657,"interquartile_range":0.10437702981984269,"maximum":0.8490391727005575,"mean":0.15035186602067654,"measured_model_count":56,"median":0.10237428471529833,"minimum":0.004926867884639238,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.16123945886438926,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.005719797835777085,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.016792809839167457,"pan_cancer_fraction":0.07036423841059603,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.0069772942289498575,"pan_cancer_fraction":0.024834437086092714,"threshold":0.8}],"gene_effect_mean":0.0009692030684934905,"gene_effect_median":-0.012922540720722964},"dependency_probability_context_minus_non_context_median":0.006398554638674142,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.017609126984126984,"non_context_fraction":0.07118055555555555,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.007316468253968256,"non_context_fraction":0.025173611111111112,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0010163171065452614,"gene_effect_context_minus_non_context_median":-0.014001735734635062} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 34 +- **Dependency-aware candidate rank:** 34 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_06444ce3e66588c496d27ac638be6bb38eeb12041940c1a78bef8333b5c6fc4a` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PDGFRA|entrez:5156` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PDGFRB.md b/examples/target_cards/depmap_26q1/PDGFRB.md new file mode 100644 index 0000000..5ca5b24 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PDGFRB.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PDGFRB + +## Target identity + +- **Target symbol:** PDGFRB +- **Target name:** platelet derived growth factor receptor beta +- **Open Targets melanoma score:** 0.647 +- **Open Targets baseline rank:** 32 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 39 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 41 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 34 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.647) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PDGFRB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PDGFRB in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.1533298824968127,"interquartile_range":0.19320922610917157,"maximum":0.28340888139004716,"mean":-0.060062062579911354,"measured_model_count":56,"median":-0.07629056372993706,"minimum":-0.39446206414889434,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03987934361235887,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.015103099225042448,"interquartile_range":0.0632267186652943,"maximum":0.3425415988456145,"mean":0.06299017017119603,"measured_model_count":56,"median":0.04135928988080292,"minimum":0.0019110310657141872,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07832981789033674,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0003210148213632427,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.027317880794701987,"pan_cancer_fraction":0.027317880794701987,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.8}],"gene_effect_mean":0.02697270760391063,"gene_effect_median":-0.004247497673512929},"dependency_probability_context_minus_non_context_median":-0.0003210148213632427,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.028645833333333332,"non_context_fraction":0.028645833333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.028283880890211624,"gene_effect_context_minus_non_context_median":-0.004668926549293628} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 39 +- **Dependency-aware candidate rank:** 39 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_5ed44e334e2ef15392edfd4102041f8826e32da84e5286cbc3a6327b87e4aba5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PDGFRB|entrez:5159` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PER1.md b/examples/target_cards/depmap_26q1/PER1.md new file mode 100644 index 0000000..c5be623 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PER1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PER1 + +## Target identity + +- **Target symbol:** PER1 +- **Target name:** period circadian regulator 1 +- **Open Targets melanoma score:** 0.559 +- **Open Targets baseline rank:** 136 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 138 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 139 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 138 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.559) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PER1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PER1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.03086128251576374,"interquartile_range":0.1190081708614905,"maximum":0.28867284705445984,"mean":0.08991771449382154,"measured_model_count":56,"median":0.09976442986895973,"minimum":-0.14227097328950417,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14986945337725424,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.004534189618738785,"interquartile_range":0.010004848593089312,"maximum":0.058565348415219765,"mean":0.01211886409344396,"measured_model_count":56,"median":0.00844002980337798,"minimum":0.0010624023055272463,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.014539038211828097,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0019063463449663235,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.04444946194894421,"gene_effect_median":-0.03379244700598999},"dependency_probability_context_minus_non_context_median":0.0019906329524445677,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.04661019968257342,"gene_effect_context_minus_non_context_median":-0.03581383836467189} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 138 +- **Dependency-aware candidate rank:** 138 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e45fc2c45aeb6d7ca3a19443b9023d03f7256f880720c11bc9fe3f99b0654932` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PER1|entrez:5187` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PHOX2B.md b/examples/target_cards/depmap_26q1/PHOX2B.md new file mode 100644 index 0000000..55ffb5f --- /dev/null +++ b/examples/target_cards/depmap_26q1/PHOX2B.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PHOX2B + +## Target identity + +- **Target symbol:** PHOX2B +- **Target name:** paired like homeobox 2B +- **Open Targets melanoma score:** 0.568 +- **Open Targets baseline rank:** 122 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 124 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 125 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 124 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.568) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PHOX2B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PHOX2B in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.03090500613816374,"interquartile_range":0.1454216583568894,"maximum":0.41213169639238095,"mean":0.09788717649919845,"measured_model_count":56,"median":0.09159221551687652,"minimum":-0.36911677256516784,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.17632666449505313,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.003112541444687733,"interquartile_range":0.014775071158484721,"maximum":0.23396617386517476,"mean":0.01769875721200918,"measured_model_count":56,"median":0.009699743764547134,"minimum":0.0001502625548091212,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.017887612603172454,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0018507177720212351,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.008278145695364239,"pan_cancer_fraction":0.008278145695364239,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.01084695289342287,"gene_effect_median":-0.02208734598313361},"dependency_probability_context_minus_non_context_median":0.002024788990909656,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.008680555555555556,"non_context_fraction":0.008680555555555556,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.011374235325742013,"gene_effect_context_minus_non_context_median":-0.02260278248246078} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 124 +- **Dependency-aware candidate rank:** 124 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_228d291ac2f6a23ffec499075c1b68b8ecc23d71697eb81d38a9d369ef3f5433` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PHOX2B|entrez:8929` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PIK3CA.md b/examples/target_cards/depmap_26q1/PIK3CA.md new file mode 100644 index 0000000..fe21966 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PIK3CA.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PIK3CA + +## Target identity + +- **Target symbol:** PIK3CA +- **Target name:** phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha +- **Open Targets melanoma score:** 0.510 +- **Open Targets baseline rank:** 238 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 240 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 240 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 240 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.510) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PIK3CA lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PIK3CA in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.3926242184937075,"interquartile_range":0.2029757534853182,"maximum":0.11683662531876016,"mean":-0.2863294055143963,"measured_model_count":56,"median":-0.2939677758894327,"minimum":-0.6891435375577224,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.18964846500838928,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.10419575803316142,"interquartile_range":0.2948881615068477,"maximum":0.8761345885208559,"mean":0.2630345989934602,"measured_model_count":56,"median":0.20917938968000044,"minimum":0.005989732137504378,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.39908391954000916,"threshold_fractions":[{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.2509124426941805,"dependency_probability_threshold_fractions":[{"context_fraction":0.14285714285714285,"difference":-0.32568590350047305,"pan_cancer_fraction":0.4685430463576159,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.22339167455061498,"pan_cancer_fraction":0.2591059602649007,"threshold":0.8}],"gene_effect_mean":0.21877902229053886,"gene_effect_median":0.147776932467173},"dependency_probability_context_minus_non_context_median":-0.27244642186733176,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.14285714285714285,"difference":-0.34151785714285715,"non_context_fraction":0.484375,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.2342509920634921,"non_context_fraction":0.2699652777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.2294141136518844,"gene_effect_context_minus_non_context_median":0.1621624007565165} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 240 +- **Dependency-aware candidate rank:** 240 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_4df18a962ebbf65e99c3409d7123502f53b0043b2756159fb600b19536fbd4e7` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PIK3CA|entrez:5290` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PIK3CB.md b/examples/target_cards/depmap_26q1/PIK3CB.md new file mode 100644 index 0000000..ac77350 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PIK3CB.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PIK3CB + +## Target identity + +- **Target symbol:** PIK3CB +- **Target name:** phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta +- **Open Targets melanoma score:** 0.461 +- **Open Targets baseline rank:** 295 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 295 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 295 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 295 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.461) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PIK3CB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PIK3CB in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.3628942051472416,"interquartile_range":0.3084161617199057,"maximum":0.2007035324921781,"mean":-0.24425789928383776,"measured_model_count":56,"median":-0.16430375541703418,"minimum":-1.0565353629457381,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.05447804342733584,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0338053475717404,"interquartile_range":0.32662358663277163,"maximum":0.9951060501601744,"mean":0.24446303063227964,"measured_model_count":56,"median":0.08159559753139387,"minimum":0.003445438951288355,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.36042893420451205,"threshold_fractions":[{"denominator":56,"fraction":0.19642857142857142,"numerator":11,"threshold":0.5},{"denominator":56,"fraction":0.125,"numerator":7,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.03392674840806498,"dependency_probability_threshold_fractions":[{"context_fraction":0.19642857142857142,"difference":0.14427625354777673,"pan_cancer_fraction":0.052152317880794705,"threshold":0.5},{"context_fraction":0.125,"difference":0.10182119205298013,"pan_cancer_fraction":0.023178807947019868,"threshold":0.8}],"gene_effect_mean":-0.12110798632711998,"gene_effect_median":-0.07767750940672569},"dependency_probability_context_minus_non_context_median":0.036085834076885696,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.19642857142857142,"difference":0.15128968253968253,"non_context_fraction":0.04513888888888889,"threshold":0.5},{"context_fraction":0.125,"difference":0.10677083333333333,"non_context_fraction":0.018229166666666668,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.12699518010691052,"gene_effect_context_minus_non_context_median":-0.08100154515365403} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 295 +- **Dependency-aware candidate rank:** 295 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_68a06d35621318866e9ee23cbdabe5f902054c1bc59017ea3399e07b35fe2263` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PIK3CB|entrez:5291` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PIK3R1.md b/examples/target_cards/depmap_26q1/PIK3R1.md new file mode 100644 index 0000000..03cd095 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PIK3R1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PIK3R1 + +## Target identity + +- **Target symbol:** PIK3R1 +- **Target name:** phosphoinositide-3-kinase regulatory subunit 1 +- **Open Targets melanoma score:** 0.568 +- **Open Targets baseline rank:** 120 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 122 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 123 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 122 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.568) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PIK3R1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PIK3R1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.03837001138190876,"interquartile_range":0.2663987206667829,"maximum":0.6800493745081021,"mean":0.08456744924235596,"measured_model_count":56,"median":0.07693671363161786,"minimum":-0.35984488150574573,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.22802870928487412,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.002696889421791202,"interquartile_range":0.02538843082361781,"maximum":0.3583474394213573,"mean":0.029228288317221747,"measured_model_count":56,"median":0.009912816186445288,"minimum":2.073664012003869e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02808532024540901,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.014832118256498852,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.037251655629139076,"pan_cancer_fraction":0.037251655629139076,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014900662251655629,"pan_cancer_fraction":0.014900662251655629,"threshold":0.8}],"gene_effect_mean":0.10651670027471553,"gene_effect_median":0.08919807712937035},"dependency_probability_context_minus_non_context_median":-0.015442377728272505,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0390625,"non_context_fraction":0.0390625,"threshold":0.5},{"context_fraction":0.0,"difference":-0.015625,"non_context_fraction":0.015625,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.11169459542695864,"gene_effect_context_minus_non_context_median":0.09247730567501805} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 122 +- **Dependency-aware candidate rank:** 122 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_1393cb6757d8dc0f45b47039e36ffd70ee45fae07bf726e9baf4c8a3f6e2103e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PIK3R1|entrez:5295` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PLCG1.md b/examples/target_cards/depmap_26q1/PLCG1.md new file mode 100644 index 0000000..938232a --- /dev/null +++ b/examples/target_cards/depmap_26q1/PLCG1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PLCG1 + +## Target identity + +- **Target symbol:** PLCG1 +- **Target name:** phospholipase C gamma 1 +- **Open Targets melanoma score:** 0.520 +- **Open Targets baseline rank:** 213 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 215 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 215 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 215 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.520) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PLCG1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PLCG1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.056839178567636914,"interquartile_range":0.1366667894574548,"maximum":0.2632874125269735,"mean":0.015463572567236987,"measured_model_count":56,"median":0.02301043378246097,"minimum":-0.31270963525517503,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07982761088981788,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008139315582853286,"interquartile_range":0.028860875205757974,"maximum":0.15688435402465603,"mean":0.02672685825084457,"measured_model_count":56,"median":0.01620788943023691,"minimum":0.001386197774518595,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03700019078861126,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0019000417051095453,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.014900662251655629,"pan_cancer_fraction":0.014900662251655629,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0074503311258278145,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.8}],"gene_effect_mean":0.00612146641388798,"gene_effect_median":-0.001184567417808969},"dependency_probability_context_minus_non_context_median":-0.0019422027936741026,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.015625,"non_context_fraction":0.015625,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0078125,"non_context_fraction":0.0078125,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006419037697896417,"gene_effect_context_minus_non_context_median":-0.001184567417808969} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 215 +- **Dependency-aware candidate rank:** 215 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_482771f988f3f29e984d70cf85da59bb1aa6e17e1531c8adae1cc9c51f9c8760` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PLCG1|entrez:5335` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PLXNB2.md b/examples/target_cards/depmap_26q1/PLXNB2.md new file mode 100644 index 0000000..02be773 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PLXNB2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PLXNB2 + +## Target identity + +- **Target symbol:** PLXNB2 +- **Target name:** plexin B2 +- **Open Targets melanoma score:** 0.476 +- **Open Targets baseline rank:** 277 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 277 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 277 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 277 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.476) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PLXNB2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PLXNB2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.016739809784034065,"interquartile_range":0.13622487385793947,"maximum":0.39172179779208477,"mean":0.09250986907465496,"measured_model_count":56,"median":0.07287237929257996,"minimum":-0.17175670111727442,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.15296468364197352,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.004153007557135326,"interquartile_range":0.013950921193240031,"maximum":0.06888512238549067,"mean":0.014042510139181064,"measured_model_count":56,"median":0.010539954198750902,"minimum":0.0007187168733285372,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.018103928750375357,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.001844309460650593,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.00753321497055269,"gene_effect_median":-0.02554119096021508},"dependency_probability_context_minus_non_context_median":0.0019365850333818296,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.007899412920510093,"gene_effect_context_minus_non_context_median":-0.027712555322041824} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 277 +- **Dependency-aware candidate rank:** 277 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_3f46e48ad4756d530369ffcfe581396565c8d099bd09b22a76ef1acee8174cf3` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PLXNB2|entrez:23654` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PMEL.md b/examples/target_cards/depmap_26q1/PMEL.md new file mode 100644 index 0000000..9afc05b --- /dev/null +++ b/examples/target_cards/depmap_26q1/PMEL.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PMEL + +## Target identity + +- **Target symbol:** PMEL +- **Target name:** premelanosome protein +- **Open Targets melanoma score:** 0.482 +- **Open Targets baseline rank:** 272 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 272 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 272 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 272 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.482) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PMEL lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PMEL in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.2400016434090602,"interquartile_range":0.20927280835888581,"maximum":0.10533139840966646,"mean":-0.1324141548909928,"measured_model_count":56,"median":-0.13772450645851692,"minimum":-0.5253708137934905,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.030728835050174378,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.026923220466624286,"interquartile_range":0.11529393681860517,"maximum":0.6538000146205327,"mean":0.10254274521418213,"measured_model_count":56,"median":0.07252845996137892,"minimum":0.0052803313388520646,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14221715728522946,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.025257741705418175,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.015373699148533584,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.04555846417682345,"gene_effect_median":-0.05009722593245222},"dependency_probability_context_minus_non_context_median":0.02557812719302823,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.016121031746031744,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.04777311174097448,"gene_effect_context_minus_non_context_median":-0.050757805677101794} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 272 +- **Dependency-aware candidate rank:** 272 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_3e1ddb6994d9b01df9aaf937b63d46b899afd5271a876063545dcd59eb416b77` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PMEL|entrez:6490` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PMS2.md b/examples/target_cards/depmap_26q1/PMS2.md new file mode 100644 index 0000000..f74e07d --- /dev/null +++ b/examples/target_cards/depmap_26q1/PMS2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PMS2 + +## Target identity + +- **Target symbol:** PMS2 +- **Target name:** PMS1 homolog 2, mismatch repair system component +- **Open Targets melanoma score:** 0.522 +- **Open Targets baseline rank:** 204 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 206 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 206 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 206 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.522) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PMS2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PMS2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.055192771409656866,"interquartile_range":0.14739073725694488,"maximum":0.38523856553318947,"mean":0.12017485590510182,"measured_model_count":56,"median":0.11394202876623996,"minimum":-0.18820183094115384,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.20258350866660174,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0024973371316166187,"interquartile_range":0.011151597509534487,"maximum":0.1140254341691312,"mean":0.013196658557872531,"measured_model_count":56,"median":0.005788126840964296,"minimum":0.000614212746071096,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.013648934641151106,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0013209939148119887,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.002652219854245824,"gene_effect_median":-0.003071921834496366},"dependency_probability_context_minus_non_context_median":-0.0013835349040086445,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.002781147208271606,"gene_effect_context_minus_non_context_median":-0.0034778106978098494} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 206 +- **Dependency-aware candidate rank:** 206 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_4c92dca4778a7b62d4c7fa8dcc8bbfa1cd7a41f47d547524cbf282cd897c1a44` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PMS2|entrez:5395` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/POLD1.md b/examples/target_cards/depmap_26q1/POLD1.md new file mode 100644 index 0000000..72543c0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/POLD1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: POLD1 + +## Target identity + +- **Target symbol:** POLD1 +- **Target name:** DNA polymerase delta 1, catalytic subunit +- **Open Targets melanoma score:** 0.571 +- **Open Targets baseline rank:** 113 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 115 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 116 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 115 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.571) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** POLD1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for POLD1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-2.2555126211580916,"interquartile_range":0.39839849563843344,"maximum":-1.2480701178321307,"mean":-2.047820149678809,"measured_model_count":56,"median":-2.0748283180612623,"minimum":-2.9554520157837465,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.8571141255196582,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":1.0,"interquartile_range":0.0,"maximum":1.0,"mean":0.9997822098855916,"measured_model_count":56,"median":1.0,"minimum":0.9959820103493834,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0,"pan_cancer_fraction":1.0,"threshold":0.5},{"context_fraction":1.0,"difference":0.0016556291390728006,"pan_cancer_fraction":0.9983443708609272,"threshold":0.8}],"gene_effect_mean":0.1497703485222317,"gene_effect_median":0.11850612430526519},"dependency_probability_context_minus_non_context_median":0.0,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0,"non_context_fraction":1.0,"threshold":0.5},{"context_fraction":1.0,"difference":0.0017361111111111605,"non_context_fraction":0.9982638888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.15705085157539633,"gene_effect_context_minus_non_context_median":0.1260869679559562} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 115 +- **Dependency-aware candidate rank:** 115 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_5159ae65cf07b2879523733bae0a6ffe7f9fc31ddffcec704c8a72a381f0435e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:POLD1|entrez:5424` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/POLE.md b/examples/target_cards/depmap_26q1/POLE.md new file mode 100644 index 0000000..fd9e4d8 --- /dev/null +++ b/examples/target_cards/depmap_26q1/POLE.md @@ -0,0 +1,124 @@ +# Target hypothesis card: POLE + +## Target identity + +- **Target symbol:** POLE +- **Target name:** DNA polymerase epsilon, catalytic subunit +- **Open Targets melanoma score:** 0.645 +- **Open Targets baseline rank:** 34 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 41 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 43 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 41 | not prioritized | -7 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.645) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** POLE lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for POLE in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.7686221790937948,"interquartile_range":0.49019054275043095,"maximum":-0.8864340679478432,"mean":-1.5445676761570897,"measured_model_count":56,"median":-1.512475654018234,"minimum":-2.691654838050905,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.2784316363433639,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9937930644505688,"interquartile_range":0.006206935528471291,"maximum":1.0,"mean":0.995224255991806,"measured_model_count":56,"median":0.9994873578486327,"minimum":0.9596816798789393,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9999999999790401,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0003169851513706856,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0033112582781457123,"pan_cancer_fraction":0.9966887417218543,"threshold":0.5},{"context_fraction":1.0,"difference":0.0066225165562914245,"pan_cancer_fraction":0.9933774834437086,"threshold":0.8}],"gene_effect_mean":0.048138593469633006,"gene_effect_median":0.06269718431369808},"dependency_probability_context_minus_non_context_median":-0.0003307136808244904,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.00347222222222221,"non_context_fraction":0.9965277777777778,"threshold":0.5},{"context_fraction":1.0,"difference":0.00694444444444442,"non_context_fraction":0.9930555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0504786639855177,"gene_effect_context_minus_non_context_median":0.06884103214607751} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 41 +- **Dependency-aware candidate rank:** 41 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ac55f483b1302b3f00e48106eb5cfa1a9b90fc645561cccda6bae70e9c563754` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:POLE|entrez:5426` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/POLQ.md b/examples/target_cards/depmap_26q1/POLQ.md new file mode 100644 index 0000000..71173d2 --- /dev/null +++ b/examples/target_cards/depmap_26q1/POLQ.md @@ -0,0 +1,124 @@ +# Target hypothesis card: POLQ + +## Target identity + +- **Target symbol:** POLQ +- **Target name:** DNA polymerase theta +- **Open Targets melanoma score:** 0.598 +- **Open Targets baseline rank:** 71 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 75 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 77 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 75 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.598) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** POLQ lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for POLQ in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.39901280322112664,"interquartile_range":0.22486613245338025,"maximum":0.05185493446814471,"mean":-0.29887660161957547,"measured_model_count":56,"median":-0.2878340309311357,"minimum":-1.0029113047323868,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.1741466707677464,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.10011844551019167,"interquartile_range":0.2983836803191332,"maximum":0.9620343470390572,"mean":0.2837371101307486,"measured_model_count":56,"median":0.2125326319656341,"minimum":0.008170163671162276,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.39850212582932487,"threshold_fractions":[{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.5},{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0669935904527213,"dependency_probability_threshold_fractions":[{"context_fraction":0.17857142857142858,"difference":-0.09295175023651844,"pan_cancer_fraction":0.271523178807947,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.020577105014191112,"pan_cancer_fraction":0.056291390728476824,"threshold":0.8}],"gene_effect_mean":0.05139503211426255,"gene_effect_median":0.04601330147269167},"dependency_probability_context_minus_non_context_median":-0.07063337771572298,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.17857142857142858,"difference":-0.09747023809523811,"non_context_fraction":0.2760416666666667,"threshold":0.5},{"context_fraction":0.03571428571428571,"difference":-0.021577380952380952,"non_context_fraction":0.057291666666666664,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05389340173092816,"gene_effect_context_minus_non_context_median":0.04761758869659821} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 75 +- **Dependency-aware candidate rank:** 75 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_7e15da50fa60be32c1cd38f67f5879e2675d40bbd14334ab0cea898a93f414d0` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:POLQ|entrez:10721` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/POT1.md b/examples/target_cards/depmap_26q1/POT1.md new file mode 100644 index 0000000..ccf9f2d --- /dev/null +++ b/examples/target_cards/depmap_26q1/POT1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: POT1 + +## Target identity + +- **Target symbol:** POT1 +- **Target name:** protection of telomeres 1 +- **Open Targets melanoma score:** 0.707 +- **Open Targets baseline rank:** 18 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 25 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 28 | not prioritized | -10 | +| Tumor-intrinsic / small molecule | 0.012 | 21 | not prioritized | -3 | + +## Evidence for + +- High Open Targets melanoma association score (0.707) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** POT1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for POT1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.5635819718766873,"interquartile_range":0.26505416396453424,"maximum":-0.06251627466615711,"mean":-0.44935742447896204,"measured_model_count":56,"median":-0.42293149499519567,"minimum":-1.1041577617026235,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.2985278079121531,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.23950012403748594,"interquartile_range":0.43079365738697023,"maximum":0.9717428477917653,"mean":0.4692116059277039,"measured_model_count":56,"median":0.4805480850355817,"minimum":0.052371667803121746,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.6702937814244562,"threshold_fractions":[{"denominator":56,"fraction":0.48214285714285715,"numerator":27,"threshold":0.5},{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.06372445254465897,"dependency_probability_threshold_fractions":[{"context_fraction":0.48214285714285715,"difference":0.037606433301797526,"pan_cancer_fraction":0.4445364238410596,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.0740302743614002,"pan_cancer_fraction":0.21688741721854304,"threshold":0.8}],"gene_effect_mean":-0.009134301384618015,"gene_effect_median":-0.006132470396260303},"dependency_probability_context_minus_non_context_median":0.0659224405327859,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.48214285714285715,"difference":0.039434523809523836,"non_context_fraction":0.4427083333333333,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.07762896825396826,"non_context_fraction":0.2204861111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.009578329924148365,"gene_effect_context_minus_non_context_median":-0.0066925601843810245} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 25 +- **Dependency-aware candidate rank:** 25 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2f1a268f12b0088d5c4803f296352ff0f6de2420d06ccc515894446a27792f67` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:POT1|entrez:25913` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/POU2AF1.md b/examples/target_cards/depmap_26q1/POU2AF1.md new file mode 100644 index 0000000..f5dfeaa --- /dev/null +++ b/examples/target_cards/depmap_26q1/POU2AF1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: POU2AF1 + +## Target identity + +- **Target symbol:** POU2AF1 +- **Target name:** POU class 2 homeobox associating factor 1 +- **Open Targets melanoma score:** 0.483 +- **Open Targets baseline rank:** 270 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 271 | not prioritized | -1 | +| Resistance biomarker | 0.000 | 271 | not prioritized | -1 | +| Tumor-intrinsic / small molecule | 0.000 | 271 | not prioritized | -1 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.483) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** POU2AF1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for POU2AF1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06144299452441082,"interquartile_range":0.16721482908748944,"maximum":0.25598488770962047,"mean":0.012489908148375358,"measured_model_count":56,"median":0.010038770990871998,"minimum":-0.29326722424317075,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10577183456307862,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0067145750699271175,"interquartile_range":0.03315913931173384,"maximum":0.24566225721850554,"mean":0.033463484590643744,"measured_model_count":56,"median":0.02258460016959892,"minimum":0.0018220453406680766,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03987371438166096,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0009895798520293334,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04304635761589404,"pan_cancer_fraction":0.04304635761589404,"threshold":0.5},{"context_fraction":0.0,"difference":-0.03228476821192053,"pan_cancer_fraction":0.03228476821192053,"threshold":0.8}],"gene_effect_mean":0.05904330364299119,"gene_effect_median":0.017333354677480317},"dependency_probability_context_minus_non_context_median":-0.0009895798520293334,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.04513888888888889,"non_context_fraction":0.04513888888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.033854166666666664,"non_context_fraction":0.033854166666666664,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.06191346423674769,"gene_effect_context_minus_non_context_median":0.017843546337038} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 271 +- **Dependency-aware candidate rank:** 271 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_c5e1ddb917a46809f6510c9d7f77229a549d080031e1d2daab49de3dd332fcc5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:POU2AF1|entrez:5450` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PPP2R1A.md b/examples/target_cards/depmap_26q1/PPP2R1A.md new file mode 100644 index 0000000..ac07755 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PPP2R1A.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PPP2R1A + +## Target identity + +- **Target symbol:** PPP2R1A +- **Target name:** protein phosphatase 2 scaffold subunit Aalpha +- **Open Targets melanoma score:** 0.552 +- **Open Targets baseline rank:** 153 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 155 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 156 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 155 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.552) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PPP2R1A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PPP2R1A in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.6847459075068567,"interquartile_range":0.46834225071689306,"maximum":-0.4896122806584271,"mean":-1.4730530296832878,"measured_model_count":56,"median":-1.471863264456811,"minimum":-2.8617405459735346,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.2164036567899636,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.991270804140258,"interquartile_range":0.008718189144905297,"maximum":1.0,"mean":0.9648698306535062,"measured_model_count":56,"median":0.9991692822150705,"minimum":0.4482521452993049,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9999889932851633,"threshold_fractions":[{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.5},{"denominator":56,"fraction":0.9285714285714286,"numerator":52,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.01656030182956203,"dependency_probability_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":0.12204351939451275,"pan_cancer_fraction":0.8600993377483444,"threshold":0.5},{"context_fraction":0.9285714285714286,"difference":0.15456480605487233,"pan_cancer_fraction":0.7740066225165563,"threshold":0.8}],"gene_effect_mean":-0.3861167984464926,"gene_effect_median":-0.3418188697362825},"dependency_probability_context_minus_non_context_median":0.01846219532556903,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":0.12797619047619047,"non_context_fraction":0.8541666666666666,"threshold":0.5},{"context_fraction":0.9285714285714286,"difference":0.16207837301587302,"non_context_fraction":0.7664930555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.4048863650376413,"gene_effect_context_minus_non_context_median":-0.3596159217731978} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 155 +- **Dependency-aware candidate rank:** 155 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_74a0b3242fc0b704162d1eda858578c031f68476245584d07d91428b05e8a3ec` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PPP2R1A|entrez:5518` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PPP6C.md b/examples/target_cards/depmap_26q1/PPP6C.md new file mode 100644 index 0000000..242543e --- /dev/null +++ b/examples/target_cards/depmap_26q1/PPP6C.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PPP6C + +## Target identity + +- **Target symbol:** PPP6C +- **Target name:** protein phosphatase 6 catalytic subunit +- **Open Targets melanoma score:** 0.696 +- **Open Targets baseline rank:** 22 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 29 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 31 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.010 | 24 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.696) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PPP6C lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PPP6C in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.0180315911310092,"interquartile_range":0.5621537586484284,"maximum":0.11025640550708837,"mean":-0.7830457115397375,"measured_model_count":56,"median":-0.781903782242473,"minimum":-2.174202672852065,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.4558778324825807,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.5280855865269243,"interquartile_range":0.4428703885392822,"maximum":1.0,"mean":0.7228752811217215,"measured_model_count":56,"median":0.8982627669210668,"minimum":0.012641297187679104,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9709559750662065,"threshold_fractions":[{"denominator":56,"fraction":0.75,"numerator":42,"threshold":0.5},{"denominator":56,"fraction":0.6428571428571429,"numerator":36,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.3472877202917415,"dependency_probability_threshold_fractions":[{"context_fraction":0.75,"difference":0.20281456953642385,"pan_cancer_fraction":0.5471854304635762,"threshold":0.5},{"context_fraction":0.6428571428571429,"difference":0.34236045411542104,"pan_cancer_fraction":0.30049668874172186,"threshold":0.8}],"gene_effect_mean":-0.2727741134536048,"gene_effect_median":-0.2858027333400428},"dependency_probability_context_minus_non_context_median":0.36076391864076207,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.75,"difference":0.21267361111111116,"non_context_fraction":0.5373263888888888,"threshold":0.5},{"context_fraction":0.6428571428571429,"difference":0.3590029761904762,"non_context_fraction":0.2838541666666667,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.28603396619093313,"gene_effect_context_minus_non_context_median":-0.29247517365734954} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":100.0} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 29 +- **Dependency-aware candidate rank:** 29 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e813ac41ad9a377599b11ff70abe02e35879024028640b8247086bcc703ff14f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PPP6C|entrez:5537` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PRDM1.md b/examples/target_cards/depmap_26q1/PRDM1.md new file mode 100644 index 0000000..e3b95d9 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PRDM1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PRDM1 + +## Target identity + +- **Target symbol:** PRDM1 +- **Target name:** PR/SET domain 1 +- **Open Targets melanoma score:** 0.554 +- **Open Targets baseline rank:** 144 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 146 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 147 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 146 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.554) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PRDM1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PRDM1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.08291657465478372,"interquartile_range":0.14691125593049534,"maximum":0.31777949130823113,"mean":-0.0004918904971693967,"measured_model_count":56,"median":-0.008524764962677182,"minimum":-0.234721655796034,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06399468127571162,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.009277719511873131,"interquartile_range":0.037261079629678555,"maximum":0.19958293481324751,"mean":0.032832412014046124,"measured_model_count":56,"median":0.02097438411360496,"minimum":0.0017317366625563182,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.046538799141551686,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.008056719260326754,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.019867549668874173,"pan_cancer_fraction":0.019867549668874173,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013245033112582781,"pan_cancer_fraction":0.013245033112582781,"threshold":0.8}],"gene_effect_mean":0.048284324139614594,"gene_effect_median":0.021390234673775096},"dependency_probability_context_minus_non_context_median":-0.008296152087344494,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.020833333333333332,"non_context_fraction":0.020833333333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013888888888888888,"non_context_fraction":0.013888888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05063147878529028,"gene_effect_context_minus_non_context_median":0.022262698849266106} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 146 +- **Dependency-aware candidate rank:** 146 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_cd16d753cd3ddef3c76740851b8199ffa2f6ebce99e63fda0453ed4c9b475c2f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PRDM1|entrez:639` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PRDM16.md b/examples/target_cards/depmap_26q1/PRDM16.md new file mode 100644 index 0000000..23cccb2 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PRDM16.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PRDM16 + +## Target identity + +- **Target symbol:** PRDM16 +- **Target name:** PR/SET domain 16 +- **Open Targets melanoma score:** 0.503 +- **Open Targets baseline rank:** 251 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 253 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 253 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 253 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.503) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PRDM16 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PRDM16 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.16713623178169615,"interquartile_range":0.16512730681889062,"maximum":0.2569246975507734,"mean":-0.08575797188179488,"measured_model_count":56,"median":-0.09204657993987507,"minimum":-0.4186847355613391,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0020089249628055354,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.02149112015272428,"interquartile_range":0.07412131422340887,"maximum":0.3514851749930976,"mean":0.07152261488348251,"measured_model_count":56,"median":0.04697655942427176,"minimum":0.0025971801743869516,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09561243437613315,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0005969383106331147,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.01076158940397351,"pan_cancer_fraction":0.01076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.8}],"gene_effect_mean":0.004667942636622957,"gene_effect_median":-0.007271623979965711},"dependency_probability_context_minus_non_context_median":0.0006646952881589341,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.011284722222222222,"non_context_fraction":0.011284722222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.004894856514792073,"gene_effect_context_minus_non_context_median":-0.00783918239264203} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":48.148148148148145} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 253 +- **Dependency-aware candidate rank:** 253 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_79a992ecc90e7d1793f3cc18415bc66ff52616ac334bd55b657f71a8ad052dd1` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PRDM16|entrez:63976` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PREX2.md b/examples/target_cards/depmap_26q1/PREX2.md new file mode 100644 index 0000000..093b42a --- /dev/null +++ b/examples/target_cards/depmap_26q1/PREX2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PREX2 + +## Target identity + +- **Target symbol:** PREX2 +- **Target name:** phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2 +- **Open Targets melanoma score:** 0.602 +- **Open Targets baseline rank:** 68 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 72 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 74 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 72 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.602) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PREX2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PREX2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.06544856986628139,"interquartile_range":0.12703400620022845,"maximum":0.49542242427329963,"mean":0.13323863617645906,"measured_model_count":56,"median":0.11155773430019963,"minimum":-0.09874246278849794,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.19248257606650984,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0025839773065120717,"interquartile_range":0.009416781894391853,"maximum":0.03580333716191526,"mean":0.008801885456245927,"measured_model_count":56,"median":0.007049386132260232,"minimum":0.00015597332978287568,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.012000759200903925,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00017952494098199406,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.003603545278304976,"gene_effect_median":-0.011993756937299399},"dependency_probability_context_minus_non_context_median":-0.00018375163158879278,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0037787176182225712,"gene_effect_context_minus_non_context_median":-0.013121553883521181} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 72 +- **Dependency-aware candidate rank:** 72 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d9b385fe8911d2d959d2ecb2e0c27fe68cc63d48096199f1b99e995881308763` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PREX2|entrez:80243` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PRF1.md b/examples/target_cards/depmap_26q1/PRF1.md new file mode 100644 index 0000000..26ac384 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PRF1.md @@ -0,0 +1,132 @@ +# Target hypothesis card: PRF1 + +## Target identity + +- **Target symbol:** PRF1 +- **Target name:** perforin 1 +- **Open Targets melanoma score:** 0.529 +- **Open Targets baseline rank:** 189 + +## Stable TargetIntel-IO classification + +- **Role classification:** immune-context marker +- **Role confidence:** medium +- **Therapeutic direction:** use as biomarker / patient stratification +- **Best modality:** immune-context biomarker +- **Resistance axis:** immune_cold_state +- **Matched resistance programs:** Immune-cold tumor state + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 191 | not prioritized | -2 | +| Resistance biomarker | 0.500 | 7 | medium | 182 | +| Tumor-intrinsic / small molecule | 0.000 | 191 | not prioritized | -2 | + +## Evidence for + +- May help distinguish inflamed from immune-cold tumors +- Relevant to anti-PD-1 response probability +- Useful for interpreting tumor immune context +- Moderate Open Targets melanoma association score (0.529) +- Maps to curated anti-PD-1 resistance program: Immune-cold tumor state +- Biomarker fit is medium-high + +## Evidence against / limitations + +- May need cohort-level expression context +- Often reflects immune-cell abundance rather than a direct target +- Poor direct therapeutic target class +- Flagged as poor direct therapeutic target for this MVP +- May reflect immune-cell abundance rather than causal target biology + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.650 +- **Main limitation:** Poor direct therapeutic target despite biological relevance +- **Uncertainty reason:** High contradiction score indicates important opposing evidence | Main limitation: Poor direct therapeutic target despite biological relevance +- **Deprioritization reason:** PRF1 should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PRF1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.05478050797948658,"interquartile_range":0.09711305586290947,"maximum":0.4078675016027466,"mean":-0.0015226298621399592,"measured_model_count":56,"median":0.0047451788481697,"minimum":-0.22679163161826915,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.042332547883422895,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.011764494825794149,"interquartile_range":0.03005355888286111,"maximum":0.23055611608468068,"mean":0.030715219026443995,"measured_model_count":56,"median":0.02139926937725605,"minimum":0.0005486674577255344,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04181805370865526,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0025959982232196567,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.006103480234065759,"gene_effect_median":0.014688023320211133},"dependency_probability_context_minus_non_context_median":-0.0026635317946805265,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006400177189888426,"gene_effect_context_minus_non_context_median":0.015379095495603068} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 191 +- **Dependency-aware candidate rank:** 191 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e6109da95b764fd7187975a931a48f28b43162312870aec3d24838aed1e67329` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PRF1|entrez:5551` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PTCH1.md b/examples/target_cards/depmap_26q1/PTCH1.md new file mode 100644 index 0000000..b4ed810 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PTCH1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PTCH1 + +## Target identity + +- **Target symbol:** PTCH1 +- **Target name:** patched 1 +- **Open Targets melanoma score:** 0.569 +- **Open Targets baseline rank:** 118 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 120 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 121 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 120 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.569) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PTCH1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PTCH1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.09588063885275669,"interquartile_range":0.21009150163000154,"maximum":0.3324175140971824,"mean":0.011094539588050975,"measured_model_count":56,"median":0.018151218696463505,"minimum":-0.46600755029575164,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11421086277724485,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005977946450391312,"interquartile_range":0.03975630865182156,"maximum":0.37309691491643426,"mean":0.036336117075092225,"measured_model_count":56,"median":0.020825055662632826,"minimum":0.0010684762208753433,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04573425510221287,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0037906453790609515,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.00793799435793612,"gene_effect_median":-0.006583365323387894},"dependency_probability_context_minus_non_context_median":0.004053431081731743,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.00832386908366914,"gene_effect_context_minus_non_context_median":-0.006583365323387894} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 120 +- **Dependency-aware candidate rank:** 120 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_838413cbd4627228445817b972d7e23a9eacf6ed123c0edadf7240e3b2bd9b23` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PTCH1|entrez:5727` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PTEN.md b/examples/target_cards/depmap_26q1/PTEN.md new file mode 100644 index 0000000..c5fe013 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PTEN.md @@ -0,0 +1,133 @@ +# Target hypothesis card: PTEN + +## Target identity + +- **Target symbol:** PTEN +- **Target name:** phosphatase and tensin homolog +- **Open Targets melanoma score:** 0.765 +- **Open Targets baseline rank:** 7 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / poor direct therapeutic target +- **Role confidence:** high +- **Therapeutic direction:** avoid as direct target / use as biomarker or pathway context +- **Best modality:** biomarker / pathway context only +- **Resistance axis:** tumor_intrinsic_driver +- **Matched resistance programs:** Tumor-intrinsic driver biology + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 15 | not prioritized | -8 | +| Resistance biomarker | 0.313 | 16 | low | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 38 | not prioritized | -31 | + +## Evidence for + +- Relevant to melanoma tumor-cell biology +- Some targets or pathways are clinically actionable +- Useful for separating tumor-intrinsic drivers from immune-combination targets +- High Open Targets melanoma association score (0.765) +- Maps to curated anti-PD-1 resistance program: Tumor-intrinsic driver biology +- Stable role classifier confidence is high + +## Evidence against / limitations + +- Many tumor-intrinsic drivers are poor antibody targets +- Melanoma association does not automatically imply anti-PD-1 combination suitability +- Tumor suppressors are often poor direct therapeutic targets +- Flagged as poor direct therapeutic target for this MVP +- Role classifier indicates biological relevance but poor direct targetability +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 1.000 +- **Contradiction score:** 0.650 +- **Main limitation:** Poor direct therapeutic target despite biological relevance +- **Uncertainty reason:** High contradiction score indicates important opposing evidence | Main limitation: Poor direct therapeutic target despite biological relevance +- **Deprioritization reason:** PTEN should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context. + +## Recommended next validation experiment + +- **Validation category:** tumor-intrinsic functional validation +- **Next experiment:** Evaluate whether perturbing PTEN alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays. +- **Rationale:** This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.1774273786697296,"interquartile_range":0.3538259685928198,"maximum":1.736156453910227,"mean":0.35005025729220074,"measured_model_count":56,"median":0.3093834287818784,"minimum":-0.5425024630491011,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5312533472625494,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.00014782039573808722,"interquartile_range":0.003600925362963198,"maximum":0.5552301573186749,"mean":0.029092579805179958,"measured_model_count":56,"median":0.0016319869133616688,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0037487457587012853,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0006340736706280773,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.00378429517502365,"pan_cancer_fraction":0.014072847682119206,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008278145695364239,"pan_cancer_fraction":0.008278145695364239,"threshold":0.8}],"gene_effect_mean":-0.04551705089091174,"gene_effect_median":-0.03148194444479169},"dependency_probability_context_minus_non_context_median":0.0006571060699895603,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.003968253968253968,"non_context_fraction":0.013888888888888888,"threshold":0.5},{"context_fraction":0.0,"difference":-0.008680555555555556,"non_context_fraction":0.008680555555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.047729685309219894,"gene_effect_context_minus_non_context_median":-0.03305045121014427} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 15 +- **Dependency-aware candidate rank:** 16 +- **Rank delta:** 1 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2cb1b0caa8f0077667dddc663b12a765d9166a7b146b4808af84830d4603f213` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PTEN|entrez:5728` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PTK6.md b/examples/target_cards/depmap_26q1/PTK6.md new file mode 100644 index 0000000..a3c8993 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PTK6.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PTK6 + +## Target identity + +- **Target symbol:** PTK6 +- **Target name:** protein tyrosine kinase 6 +- **Open Targets melanoma score:** 0.502 +- **Open Targets baseline rank:** 252 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 254 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 254 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 254 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.502) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PTK6 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PTK6 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.1840162742298729,"interquartile_range":0.1997483929044233,"maximum":0.3222356768075394,"mean":-0.09758380127941914,"measured_model_count":56,"median":-0.12026321213311797,"minimum":-0.5349203287149611,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.015732118674550405,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.018529924530914635,"interquartile_range":0.09544668456352441,"maximum":0.7582481910067956,"mean":0.09733291620033664,"measured_model_count":56,"median":0.05169764005554711,"minimum":0.0011785351628772456,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11397660909443905,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.018319115017753004,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.002010406811731317,"pan_cancer_fraction":0.019867549668874173,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.04000233454004308,"gene_effect_median":0.011755430048686955},"dependency_probability_context_minus_non_context_median":-0.01906178797118574,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.00210813492063492,"non_context_fraction":0.019965277777777776,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.041946892469073,"gene_effect_context_minus_non_context_median":0.013003588814756994} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 254 +- **Dependency-aware candidate rank:** 254 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e55b812b05bef97f2a1a1caf4d24b84726fd99b4871ad83c42298a88da0946c2` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PTK6|entrez:5753` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PTPN11.md b/examples/target_cards/depmap_26q1/PTPN11.md new file mode 100644 index 0000000..c68d62e --- /dev/null +++ b/examples/target_cards/depmap_26q1/PTPN11.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PTPN11 + +## Target identity + +- **Target symbol:** PTPN11 +- **Target name:** protein tyrosine phosphatase non-receptor type 11 +- **Open Targets melanoma score:** 0.589 +- **Open Targets baseline rank:** 84 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 87 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 89 | not prioritized | -5 | +| Tumor-intrinsic / small molecule | 0.000 | 87 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.589) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PTPN11 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PTPN11 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.3533909262374086,"interquartile_range":0.29119952608175426,"maximum":0.17635991627900627,"mean":-0.2706024316129988,"measured_model_count":56,"median":-0.22336959724687172,"minimum":-1.2437665525555057,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.06219140015565436,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.03844928397309019,"interquartile_range":0.284016781985858,"maximum":0.9954390112631097,"mean":0.24807679949177336,"measured_model_count":56,"median":0.15755716577163256,"minimum":0.004383763089454739,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.3224660659589482,"threshold_fractions":[{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.5},{"denominator":56,"fraction":0.10714285714285714,"numerator":6,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.7093328754750823,"dependency_probability_threshold_fractions":[{"context_fraction":0.14285714285714285,"difference":-0.5616130558183539,"pan_cancer_fraction":0.7044701986754967,"threshold":0.5},{"context_fraction":0.10714285714285714,"difference":-0.45245979186376534,"pan_cancer_fraction":0.5596026490066225,"threshold":0.8}],"gene_effect_mean":0.45975065413160154,"gene_effect_median":0.5201246616645117},"dependency_probability_context_minus_non_context_median":-0.7213579715718752,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.14285714285714285,"difference":-0.5889136904761905,"non_context_fraction":0.7317708333333334,"threshold":0.5},{"context_fraction":0.10714285714285714,"difference":-0.47445436507936506,"non_context_fraction":0.5815972222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.4820996442629989,"gene_effect_context_minus_non_context_median":0.5437117352527387} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 87 +- **Dependency-aware candidate rank:** 87 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_7f81b4ddd9276b0f28fd1944fbc7693dc9b9e72386c10391bedf12326fc30484` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PTPN11|entrez:5781` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PTPN13.md b/examples/target_cards/depmap_26q1/PTPN13.md new file mode 100644 index 0000000..73120d6 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PTPN13.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PTPN13 + +## Target identity + +- **Target symbol:** PTPN13 +- **Target name:** protein tyrosine phosphatase non-receptor type 13 +- **Open Targets melanoma score:** 0.520 +- **Open Targets baseline rank:** 212 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 214 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 214 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 214 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.520) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PTPN13 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PTPN13 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.040896381394369005,"interquartile_range":0.14700691920925746,"maximum":0.31995876843033,"mean":0.028346182847745472,"measured_model_count":56,"median":0.0242865690164243,"minimum":-0.24895582715208994,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10611053781488845,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.007373541485068309,"interquartile_range":0.022925124109128,"maximum":0.1390811639666005,"mean":0.02462924447522302,"measured_model_count":56,"median":0.015851864845906453,"minimum":0.0018513373217926266,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03029866559419631,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0012871058769384144,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.016492866144982073,"gene_effect_median":-0.01797633936413052},"dependency_probability_context_minus_non_context_median":0.0013234472008851663,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.017294602693696478,"gene_effect_context_minus_non_context_median":-0.01815635480726488} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 214 +- **Dependency-aware candidate rank:** 214 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_5d6f41b1786a0605ff1edadeca73ee52e0c53f21342740525ac6a63994799ed8` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PTPN13|entrez:5783` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PTPRB.md b/examples/target_cards/depmap_26q1/PTPRB.md new file mode 100644 index 0000000..25ff98d --- /dev/null +++ b/examples/target_cards/depmap_26q1/PTPRB.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PTPRB + +## Target identity + +- **Target symbol:** PTPRB +- **Target name:** protein tyrosine phosphatase receptor type B +- **Open Targets melanoma score:** 0.592 +- **Open Targets baseline rank:** 82 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 85 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 87 | not prioritized | -5 | +| Tumor-intrinsic / small molecule | 0.000 | 85 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.592) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PTPRB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PTPRB in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.08660322861860656,"interquartile_range":0.15326593446016268,"maximum":0.26799591456187166,"mean":-0.008701379226628104,"measured_model_count":56,"median":-0.005419265839015835,"minimum":-0.2918999102986819,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06666270584155613,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.010197627844800234,"interquartile_range":0.033392511824931415,"maximum":0.20757819748639839,"mean":0.036540181284022935,"measured_model_count":56,"median":0.022612690169484462,"minimum":0.0021535234777501173,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.043590139669731645,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00014758817878838745,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.001705276232285671,"gene_effect_median":-0.0021003650003931736},"dependency_probability_context_minus_non_context_median":-0.00014758817878838745,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0017881716046884528,"gene_effect_context_minus_non_context_median":-0.0023863247963391166} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 85 +- **Dependency-aware candidate rank:** 85 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_444f56d5d7e1650e15dd09061a20a065ffb7fc77e546647504ead1dffb791cc7` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PTPRB|entrez:5787` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PTPRC.md b/examples/target_cards/depmap_26q1/PTPRC.md new file mode 100644 index 0000000..ed7407d --- /dev/null +++ b/examples/target_cards/depmap_26q1/PTPRC.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PTPRC + +## Target identity + +- **Target symbol:** PTPRC +- **Target name:** protein tyrosine phosphatase receptor type C +- **Open Targets melanoma score:** 0.550 +- **Open Targets baseline rank:** 158 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 160 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 161 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 160 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.550) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PTPRC lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PTPRC in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** insufficient_measured_context_models +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 7 +- **Available reference observations:** 376 +- **Coverage fraction:** 0.125 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.2540968232068008,"interquartile_range":0.27269155062254513,"maximum":0.2667060877154521,"mean":-0.10718411476264175,"measured_model_count":7,"median":-0.1839674851282336,"minimum":-0.3620232143435977,"missing_fraction":0.875,"missing_model_count":49,"third_quartile":0.018594727415744333,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.03535790079068784,"interquartile_range":0.11700097399538673,"maximum":0.3130619067559611,"mean":0.11336025072294678,"measured_model_count":7,"median":0.10142439265024349,"minimum":0.0036019045008981055,"missing_fraction":0.875,"missing_model_count":49,"third_quartile":0.15235887478607457,"threshold_fractions":[{"denominator":7,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":7,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":null,"dependency_probability_threshold_fractions":[],"gene_effect_mean":null,"gene_effect_median":null},"dependency_probability_context_minus_non_context_median":null,"dependency_probability_context_minus_non_context_threshold_fractions":[],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":null,"gene_effect_context_minus_non_context_median":null} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":21,"value":65.0} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 160 +- **Dependency-aware candidate rank:** 160 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_83f222e4b026a60cc5e1c64b47b83d66b884c184cf2119e84f002d03e41659d9` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PTPRC|entrez:5788` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PTPRK.md b/examples/target_cards/depmap_26q1/PTPRK.md new file mode 100644 index 0000000..32d9bb4 --- /dev/null +++ b/examples/target_cards/depmap_26q1/PTPRK.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PTPRK + +## Target identity + +- **Target symbol:** PTPRK +- **Target name:** protein tyrosine phosphatase receptor type K +- **Open Targets melanoma score:** 0.582 +- **Open Targets baseline rank:** 95 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 98 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 99 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 98 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.582) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PTPRK lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PTPRK in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.04914152862613752,"interquartile_range":0.12518664825956582,"maximum":0.2998279934328426,"mean":0.1114437103978233,"measured_model_count":56,"median":0.11574090709819299,"minimum":-0.0681971223240274,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.17432817688570335,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0035664525085002926,"interquartile_range":0.00992274915531969,"maximum":0.03943903737818359,"mean":0.010132813629039368,"measured_model_count":56,"median":0.007097817765832145,"minimum":0.0008647637371804818,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.013489201663819983,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0002263335995250828,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.012397412838947602,"gene_effect_median":-0.004419920066998789},"dependency_probability_context_minus_non_context_median":-0.00025654626823008383,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.01300006485195189,"gene_effect_context_minus_non_context_median":-0.004484083873970465} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 98 +- **Dependency-aware candidate rank:** 98 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_06175a71ff989b9f9b64f8c8d7ab7ecb8d9020e7edda420fd1ee8a7cd5700cc5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PTPRK|entrez:5796` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/PTPRT.md b/examples/target_cards/depmap_26q1/PTPRT.md new file mode 100644 index 0000000..3327b9e --- /dev/null +++ b/examples/target_cards/depmap_26q1/PTPRT.md @@ -0,0 +1,124 @@ +# Target hypothesis card: PTPRT + +## Target identity + +- **Target symbol:** PTPRT +- **Target name:** protein tyrosine phosphatase receptor type T +- **Open Targets melanoma score:** 0.591 +- **Open Targets baseline rank:** 83 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 86 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 88 | not prioritized | -5 | +| Tumor-intrinsic / small molecule | 0.000 | 86 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.591) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** PTPRT lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for PTPRT in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.12557464182869493,"interquartile_range":0.1670050372331764,"maximum":0.35192836037169745,"mean":-0.04846570793613747,"measured_model_count":56,"median":-0.04661431473671101,"minimum":-0.4938301685425578,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04143039540448146,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.014120381189881645,"interquartile_range":0.04546098758688822,"maximum":0.3639539499414603,"mean":0.054018527133764996,"measured_model_count":56,"median":0.03077532270482216,"minimum":0.0012548301955076896,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.059581368776769866,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0056562130050500994,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.013856123608917748,"gene_effect_median":0.01587665848552721},"dependency_probability_context_minus_non_context_median":-0.0059721993356829026,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.014529685173240173,"gene_effect_context_minus_non_context_median":0.01653520210707666} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 86 +- **Dependency-aware candidate rank:** 86 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_da7c9029d34c85d1d5d73dec2f7c3e91af3dfee9900781623d66099408d0dad5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:PTPRT|entrez:11122` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/QKI.md b/examples/target_cards/depmap_26q1/QKI.md new file mode 100644 index 0000000..3b45356 --- /dev/null +++ b/examples/target_cards/depmap_26q1/QKI.md @@ -0,0 +1,124 @@ +# Target hypothesis card: QKI + +## Target identity + +- **Target symbol:** QKI +- **Target name:** QKI, KH domain containing RNA binding +- **Open Targets melanoma score:** 0.570 +- **Open Targets baseline rank:** 115 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 117 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 118 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 117 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.570) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** QKI lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for QKI in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.16545727142804292,"interquartile_range":0.2785191649890655,"maximum":0.4490044663426027,"mean":-0.030217967806080992,"measured_model_count":56,"median":-0.021443690625028444,"minimum":-0.6118606202127194,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11306189356102253,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.006750055723509366,"interquartile_range":0.0877187794340263,"maximum":0.7819981814289125,"mean":0.08535186107724975,"measured_model_count":56,"median":0.02434871601799806,"minimum":0.000661291005771635,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09446883515753567,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.00020522040079048315,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.00922421948912015,"pan_cancer_fraction":0.026490066225165563,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0074503311258278145,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.8}],"gene_effect_mean":0.0011621618166117106,"gene_effect_median":-0.009181211737889345},"dependency_probability_context_minus_non_context_median":0.0002645484582731103,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.009672619047619044,"non_context_fraction":0.026041666666666668,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0078125,"non_context_fraction":0.0078125,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0012186557938081224,"gene_effect_context_minus_non_context_median":-0.009181211737889345} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 117 +- **Dependency-aware candidate rank:** 117 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ab32ccafb5e2a7bc73483e0c6be8088f957ab86e3c7ef1918da5c95110b996a4` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:QKI|entrez:9444` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/RAC1.md b/examples/target_cards/depmap_26q1/RAC1.md new file mode 100644 index 0000000..e652fb1 --- /dev/null +++ b/examples/target_cards/depmap_26q1/RAC1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: RAC1 + +## Target identity + +- **Target symbol:** RAC1 +- **Target name:** Rac family small GTPase 1 +- **Open Targets melanoma score:** 0.710 +- **Open Targets baseline rank:** 14 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 22 | not prioritized | -8 | +| Resistance biomarker | 0.000 | 26 | not prioritized | -12 | +| Tumor-intrinsic / small molecule | 0.013 | 19 | not prioritized | -5 | + +## Evidence for + +- High Open Targets melanoma association score (0.710) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** RAC1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for RAC1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.132219886481244,"interquartile_range":0.3450850855482519,"maximum":-0.23357021391240496,"mean":-0.9872570564091132,"measured_model_count":56,"median":-0.9644656313374076,"minimum":-1.9398398272208595,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.7871348009329922,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.8903158974511705,"interquartile_range":0.0970528051333146,"maximum":1.0,"mean":0.9143828073836274,"measured_model_count":56,"median":0.9718981505657296,"minimum":0.12114557537340254,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9873687025844851,"threshold_fractions":[{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.5},{"denominator":56,"fraction":0.875,"numerator":49,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.09055764727113302,"dependency_probability_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":0.18661305581835375,"pan_cancer_fraction":0.7955298013245033,"threshold":0.5},{"context_fraction":0.875,"difference":0.26738410596026485,"pan_cancer_fraction":0.6076158940397351,"threshold":0.8}],"gene_effect_mean":-0.21449442054624301,"gene_effect_median":-0.20886143997455098},"dependency_probability_context_minus_non_context_median":0.09815552693367069,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9821428571428571,"difference":0.19568452380952372,"non_context_fraction":0.7864583333333334,"threshold":0.5},{"context_fraction":0.875,"difference":0.2803819444444444,"non_context_fraction":0.5946180555555556,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.22492123265612995,"gene_effect_context_minus_non_context_median":-0.21930036283608545} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":92.5925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 22 +- **Dependency-aware candidate rank:** 22 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_bca65944daea22928e55f8da147a53d8c0994ae1fc80f09aa88644dc892ce9f3` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:RAC1|entrez:5879` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/RAD51C.md b/examples/target_cards/depmap_26q1/RAD51C.md new file mode 100644 index 0000000..3fee712 --- /dev/null +++ b/examples/target_cards/depmap_26q1/RAD51C.md @@ -0,0 +1,124 @@ +# Target hypothesis card: RAD51C + +## Target identity + +- **Target symbol:** RAD51C +- **Target name:** RAD51 paralog C +- **Open Targets melanoma score:** 0.501 +- **Open Targets baseline rank:** 254 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 256 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 256 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 256 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.501) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** RAD51C lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for RAD51C in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.932549595300154,"interquartile_range":0.3013109434520187,"maximum":-0.21826138124369032,"mean":-0.7877103314357428,"measured_model_count":56,"median":-0.811587320321768,"minimum":-1.3356950303254789,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.6312386518481353,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.7658254388663606,"interquartile_range":0.2058807169367769,"maximum":0.9999550620977978,"mean":0.8249481295068888,"measured_model_count":56,"median":0.8957799704120795,"minimum":0.10762375437683037,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9717061558031375,"threshold_fractions":[{"denominator":56,"fraction":0.9107142857142857,"numerator":51,"threshold":0.5},{"denominator":56,"fraction":0.6964285714285714,"numerator":39,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.01340556825025796,"dependency_probability_threshold_fractions":[{"context_fraction":0.9107142857142857,"difference":0.07296594134342482,"pan_cancer_fraction":0.8377483443708609,"threshold":0.5},{"context_fraction":0.6964285714285714,"difference":0.0697729422894986,"pan_cancer_fraction":0.6266556291390728,"threshold":0.8}],"gene_effect_mean":-0.0397879941310455,"gene_effect_median":-0.06156875609122936},"dependency_probability_context_minus_non_context_median":0.013567144515045482,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.9107142857142857,"difference":0.07651289682539686,"non_context_fraction":0.8342013888888888,"threshold":0.5},{"context_fraction":0.6964285714285714,"difference":0.07316468253968256,"non_context_fraction":0.6232638888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.041722132734637984,"gene_effect_context_minus_non_context_median":-0.06400491452732326} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":88.88888888888889} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 256 +- **Dependency-aware candidate rank:** 256 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_9dee9ef6b7c02c5c7795b332a5274f544bbd39343738dbb793a149ce4969d71a` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:RAD51C|entrez:5889` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/RAF1.md b/examples/target_cards/depmap_26q1/RAF1.md new file mode 100644 index 0000000..5da310d --- /dev/null +++ b/examples/target_cards/depmap_26q1/RAF1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: RAF1 + +## Target identity + +- **Target symbol:** RAF1 +- **Target name:** Raf-1 proto-oncogene, serine/threonine kinase +- **Open Targets melanoma score:** 0.673 +- **Open Targets baseline rank:** 25 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 32 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 34 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.005 | 27 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.673) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** RAF1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for RAF1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.1256271216117195,"interquartile_range":0.1888216209784189,"maximum":0.20431855926131795,"mean":-0.15615906924769854,"measured_model_count":56,"median":-0.02220851631360249,"minimum":-1.736546085109907,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06319449936669941,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.012033750897031764,"interquartile_range":0.04288567210061994,"maximum":1.0,"mean":0.17290387330361726,"measured_model_count":56,"median":0.02468474918939307,"minimum":0.0024816460659539356,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05491942299765171,"threshold_fractions":[{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.5},{"denominator":56,"fraction":0.125,"numerator":7,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.017432078846795436,"dependency_probability_threshold_fractions":[{"context_fraction":0.16071428571428573,"difference":0.052270577105014204,"pan_cancer_fraction":0.10844370860927152,"threshold":0.5},{"context_fraction":0.125,"difference":0.06622516556291391,"pan_cancer_fraction":0.058774834437086095,"threshold":0.8}],"gene_effect_mean":-0.01317995531935906,"gene_effect_median":0.054554837151042174},"dependency_probability_context_minus_non_context_median":-0.018701876642998466,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.16071428571428573,"difference":0.05481150793650795,"non_context_fraction":0.10590277777777778,"threshold":0.5},{"context_fraction":0.125,"difference":0.06944444444444445,"non_context_fraction":0.05555555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.013820647591827911,"gene_effect_context_minus_non_context_median":0.057177451218782024} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 32 +- **Dependency-aware candidate rank:** 32 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_3cadbda89e04b64c2b0f97130adfb76a89396b2abab616171877ebdccab32161` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:RAF1|entrez:5894` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/RANBP2.md b/examples/target_cards/depmap_26q1/RANBP2.md new file mode 100644 index 0000000..cfaaed3 --- /dev/null +++ b/examples/target_cards/depmap_26q1/RANBP2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: RANBP2 + +## Target identity + +- **Target symbol:** RANBP2 +- **Target name:** RAN binding protein 2 +- **Open Targets melanoma score:** 0.515 +- **Open Targets baseline rank:** 227 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 229 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 229 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 229 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.515) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** RANBP2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for RANBP2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.5908589284378346,"interquartile_range":0.16318241965130414,"maximum":-0.11226020940158005,"mean":-0.5039476915345732,"measured_model_count":56,"median":-0.5210149465256304,"minimum":-0.9624691006672143,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.42767650878653046,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.43796867139031853,"interquartile_range":0.26936444553060407,"maximum":0.961332400882081,"mean":0.5705831573863455,"measured_model_count":56,"median":0.6193692604611463,"minimum":0.046772958901499954,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.7073331169209226,"threshold_fractions":[{"denominator":56,"fraction":0.6785714285714286,"numerator":38,"threshold":0.5},{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.039967325459354,"dependency_probability_threshold_fractions":[{"context_fraction":0.6785714285714286,"difference":0.0850283822138127,"pan_cancer_fraction":0.5935430463576159,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":-0.04576631977294229,"pan_cancer_fraction":0.22433774834437087,"threshold":0.8}],"gene_effect_mean":0.009087634242605835,"gene_effect_median":-0.0153649055422318},"dependency_probability_context_minus_non_context_median":0.04531352622720208,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.6785714285714286,"difference":0.0891617063492064,"non_context_fraction":0.5894097222222222,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":-0.047991071428571425,"non_context_fraction":0.2265625,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.009529394240510136,"gene_effect_context_minus_non_context_median":-0.01618650390554499} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 229 +- **Dependency-aware candidate rank:** 229 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_c7e2695228cf1dd5e4f4054f355d2d78a178e5f21d661c29cc532bd946304524` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:RANBP2|entrez:5903` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/RB1.md b/examples/target_cards/depmap_26q1/RB1.md new file mode 100644 index 0000000..c3c31bb --- /dev/null +++ b/examples/target_cards/depmap_26q1/RB1.md @@ -0,0 +1,127 @@ +# Target hypothesis card: RB1 + +## Target identity + +- **Target symbol:** RB1 +- **Target name:** RB transcriptional corepressor 1 +- **Open Targets melanoma score:** 0.585 +- **Open Targets baseline rank:** 93 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / poor direct therapeutic target +- **Role confidence:** high +- **Therapeutic direction:** avoid as direct target / use as biomarker or pathway context +- **Best modality:** biomarker / pathway context only +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 96 | not prioritized | -3 | +| Resistance biomarker | 0.094 | 23 | not prioritized | 70 | +| Tumor-intrinsic / small molecule | 0.000 | 96 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.585) +- Stable role classifier confidence is high + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Flagged as poor direct therapeutic target for this MVP +- Role classifier indicates biological relevance but poor direct targetability +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 0.889 +- **Contradiction score:** 0.570 +- **Main limitation:** Poor direct therapeutic target despite biological relevance +- **Uncertainty reason:** Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Moderate contradiction score indicates caution is needed | Main limitation: Poor direct therapeutic target despite biological relevance +- **Deprioritization reason:** RB1 should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context. + +## Recommended next validation experiment + +- **Validation category:** tumor-intrinsic functional validation +- **Next experiment:** Evaluate whether perturbing RB1 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays. +- **Rationale:** This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.055364957538402405,"interquartile_range":0.27298439964807286,"maximum":0.8459136994900094,"mean":0.21463507902892,"measured_model_count":56,"median":0.20375104048983378,"minimum":-0.6519186084404235,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.3283493571864753,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0005016747096900193,"interquartile_range":0.010403535843926915,"maximum":0.6691439310341896,"mean":0.02148722485594138,"measured_model_count":56,"median":0.003501129077626756,"minimum":1.653080623736478e-09,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.010905210553616934,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.001734839886762509,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.016201513718070007,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.032673938556125576,"gene_effect_median":0.03869966817842668},"dependency_probability_context_minus_non_context_median":-0.0017748365583874917,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.0169890873015873,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03426225501371505,"gene_effect_context_minus_non_context_median":0.03921263260283264} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 96 +- **Dependency-aware candidate rank:** 96 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_375480e9f01e05c6eff7db357f186a598ae8a786413287ff997662540752136b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:RB1|entrez:5925` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/RET.md b/examples/target_cards/depmap_26q1/RET.md new file mode 100644 index 0000000..66a512d --- /dev/null +++ b/examples/target_cards/depmap_26q1/RET.md @@ -0,0 +1,124 @@ +# Target hypothesis card: RET + +## Target identity + +- **Target symbol:** RET +- **Target name:** ret proto-oncogene +- **Open Targets melanoma score:** 0.537 +- **Open Targets baseline rank:** 182 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 184 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 185 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 184 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.537) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** RET lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for RET in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.14612119713856755,"interquartile_range":0.14575295943199149,"maximum":0.17499522346494442,"mean":-0.06749277025807235,"measured_model_count":56,"median":-0.07167217571962779,"minimum":-0.24627934225885015,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.000368237706576062,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.018037570779840997,"interquartile_range":0.06104268632906562,"maximum":0.17637743727038194,"mean":0.056573689560530285,"measured_model_count":56,"median":0.04047103264540877,"minimum":0.004538060086491297,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07908025710890662,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01834135332334009,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.04710982937589703,"gene_effect_median":0.03669751432842279},"dependency_probability_context_minus_non_context_median":-0.018603384608284174,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04939989052611425,"gene_effect_context_minus_non_context_median":0.038167003183957396} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 184 +- **Dependency-aware candidate rank:** 184 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_089ceaad55ef601d97aa548f69a6d4cda7591eedff2f6dec05e079c5caa2a46f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:RET|entrez:5979` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/RICTOR.md b/examples/target_cards/depmap_26q1/RICTOR.md new file mode 100644 index 0000000..1e97a04 --- /dev/null +++ b/examples/target_cards/depmap_26q1/RICTOR.md @@ -0,0 +1,124 @@ +# Target hypothesis card: RICTOR + +## Target identity + +- **Target symbol:** RICTOR +- **Target name:** RPTOR independent companion of MTOR complex 2 +- **Open Targets melanoma score:** 0.539 +- **Open Targets baseline rank:** 180 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 182 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 183 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 182 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.539) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** RICTOR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for RICTOR in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.5866822345351441,"interquartile_range":0.34588160919168814,"maximum":0.16149735225992057,"mean":-0.46055626393316357,"measured_model_count":56,"median":-0.39783708129546663,"minimum":-1.5075664457299727,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.24080062534345598,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.1350228253539574,"interquartile_range":0.6118989644679056,"maximum":0.9999801771783248,"mean":0.44882468393642067,"measured_model_count":56,"median":0.38868919644309075,"minimum":0.003186659711179904,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.746921789821863,"threshold_fractions":[{"denominator":56,"fraction":0.35714285714285715,"numerator":20,"threshold":0.5},{"denominator":56,"fraction":0.21428571428571427,"numerator":12,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.04347991018502684,"dependency_probability_threshold_fractions":[{"context_fraction":0.35714285714285715,"difference":-0.07663197729422894,"pan_cancer_fraction":0.4337748344370861,"threshold":0.5},{"context_fraction":0.21428571428571427,"difference":-0.009224219489120167,"pan_cancer_fraction":0.22350993377483444,"threshold":0.8}],"gene_effect_mean":-0.010627998452724718,"gene_effect_median":0.02905615681435275},"dependency_probability_context_minus_non_context_median":-0.04678837140427938,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.35714285714285715,"difference":-0.08035714285714285,"non_context_fraction":0.4375,"threshold":0.5},{"context_fraction":0.21428571428571427,"difference":-0.009672619047619069,"non_context_fraction":0.22395833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.011144637266399304,"gene_effect_context_minus_non_context_median":0.03076523229366962} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 182 +- **Dependency-aware candidate rank:** 182 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2fb8124a5270f956aeb713373d82ddda01a75f6ad42e5efd31836186f8b0930c` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:RICTOR|entrez:253260` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ROS1.md b/examples/target_cards/depmap_26q1/ROS1.md new file mode 100644 index 0000000..9083e76 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ROS1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ROS1 + +## Target identity + +- **Target symbol:** ROS1 +- **Target name:** ROS proto-oncogene 1, receptor tyrosine kinase +- **Open Targets melanoma score:** 0.630 +- **Open Targets baseline rank:** 43 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 50 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 52 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 50 | not prioritized | -7 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.630) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ROS1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ROS1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.08392049067782814,"interquartile_range":0.12341727033690336,"maximum":0.3254661141771581,"mean":0.126330303900205,"measured_model_count":56,"median":0.12383389748495374,"minimum":-0.20924597391267008,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2073377610147315,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0027627089855649873,"interquartile_range":0.007337207312868303,"maximum":0.10622139999463978,"mean":0.012021715750322627,"measured_model_count":56,"median":0.005657972826808763,"minimum":0.0007528764526069915,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.01009991629843329,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0023130285792771696,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.01804290864727738,"gene_effect_median":0.016779053562060234},"dependency_probability_context_minus_non_context_median":-0.002389986475450254,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01891999448429782,"gene_effect_context_minus_non_context_median":0.017923946646624583} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 50 +- **Dependency-aware candidate rank:** 50 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_fcd33cce653a26ca6a4f20a2bdf8396a860cdd1591e3ad7d590b9985734b9f4b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ROS1|entrez:6098` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/RPL5.md b/examples/target_cards/depmap_26q1/RPL5.md new file mode 100644 index 0000000..fe980d4 --- /dev/null +++ b/examples/target_cards/depmap_26q1/RPL5.md @@ -0,0 +1,124 @@ +# Target hypothesis card: RPL5 + +## Target identity + +- **Target symbol:** RPL5 +- **Target name:** ribosomal protein L5 +- **Open Targets melanoma score:** 0.579 +- **Open Targets baseline rank:** 103 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 106 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 107 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 106 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.579) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** RPL5 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for RPL5 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-2.3140510776793413,"interquartile_range":0.5596836672474383,"maximum":-1.2945186569708296,"mean":-2.0478521024180614,"measured_model_count":56,"median":-2.0634465911044617,"minimum":-2.8814886097008965,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.754367410431903,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9999896314895338,"interquartile_range":1.0368510466207681e-05,"maximum":1.0,"mean":0.9995504351830853,"measured_model_count":56,"median":1.0,"minimum":0.9841023605416382,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0,"pan_cancer_fraction":1.0,"threshold":0.5},{"context_fraction":1.0,"difference":0.0,"pan_cancer_fraction":1.0,"threshold":0.8}],"gene_effect_mean":0.24988290222750908,"gene_effect_median":0.22211344414513423},"dependency_probability_context_minus_non_context_median":0.0,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0,"non_context_fraction":1.0,"threshold":0.5},{"context_fraction":1.0,"difference":0.0,"non_context_fraction":1.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.26202998775245856,"gene_effect_context_minus_non_context_median":0.23992133455099696} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 106 +- **Dependency-aware candidate rank:** 106 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_0b5794933620d1e2e5002d30da99c667cd6dfb3950eec37405a93a1aef637a1b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:RPL5|entrez:6125` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/RRM1.md b/examples/target_cards/depmap_26q1/RRM1.md new file mode 100644 index 0000000..15ed060 --- /dev/null +++ b/examples/target_cards/depmap_26q1/RRM1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: RRM1 + +## Target identity + +- **Target symbol:** RRM1 +- **Target name:** ribonucleotide reductase catalytic subunit M1 +- **Open Targets melanoma score:** 0.565 +- **Open Targets baseline rank:** 124 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 126 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 127 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 126 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.565) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** RRM1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for RRM1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-3.7866713498714786,"interquartile_range":0.7142138038474664,"maximum":-2.0291077684100465,"mean":-3.4304476414103555,"measured_model_count":56,"median":-3.527279701684648,"minimum":-4.272254363112374,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-3.072457546024012,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":1.0,"interquartile_range":0.0,"maximum":1.0,"mean":1.0,"measured_model_count":56,"median":1.0,"minimum":1.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0,"pan_cancer_fraction":1.0,"threshold":0.5},{"context_fraction":1.0,"difference":0.0,"pan_cancer_fraction":1.0,"threshold":0.8}],"gene_effect_mean":-0.24463607830242262,"gene_effect_median":-0.24896007414394905},"dependency_probability_context_minus_non_context_median":0.0,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0,"non_context_fraction":1.0,"threshold":0.5},{"context_fraction":1.0,"difference":0.0,"non_context_fraction":1.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.2565281098865677,"gene_effect_context_minus_non_context_median":-0.2582819782444661} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":100.0} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 126 +- **Dependency-aware candidate rank:** 126 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_7f83daeead72cedf8e1fb1a673305a40a131a738823561b96ac404a3eb72e27d` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:RRM1|entrez:6240` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/RRM2.md b/examples/target_cards/depmap_26q1/RRM2.md new file mode 100644 index 0000000..438a62a --- /dev/null +++ b/examples/target_cards/depmap_26q1/RRM2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: RRM2 + +## Target identity + +- **Target symbol:** RRM2 +- **Target name:** ribonucleotide reductase regulatory subunit M2 +- **Open Targets melanoma score:** 0.581 +- **Open Targets baseline rank:** 98 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 101 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 102 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 101 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.581) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** RRM2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for RRM2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-3.0848036344428675,"interquartile_range":0.517328228067063,"maximum":-1.1915182107798357,"mean":-2.782417065774602,"measured_model_count":56,"median":-2.8483434965014958,"minimum":-3.607628637950257,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-2.5674754063758045,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":1.0,"interquartile_range":0.0,"maximum":1.0,"mean":0.9999699992385163,"measured_model_count":56,"median":1.0,"minimum":0.9983332637171632,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0016556291390728006,"pan_cancer_fraction":0.9983443708609272,"threshold":0.5},{"context_fraction":1.0,"difference":0.004139072847682113,"pan_cancer_fraction":0.9958609271523179,"threshold":0.8}],"gene_effect_mean":-0.17628457515973928,"gene_effect_median":-0.19028151675910987},"dependency_probability_context_minus_non_context_median":0.0,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0017361111111111605,"non_context_fraction":0.9982638888888888,"threshold":0.5},{"context_fraction":1.0,"difference":0.00434027777777779,"non_context_fraction":0.9956597222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.1848539642300029,"gene_effect_context_minus_non_context_median":-0.2016175361265704} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 101 +- **Dependency-aware candidate rank:** 101 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e0972d40a6b06a1c3ca73330907decd6609ccfeecef8be13d0e7d9d15d818e37` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:RRM2|entrez:6241` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/RRM2B.md b/examples/target_cards/depmap_26q1/RRM2B.md new file mode 100644 index 0000000..be91259 --- /dev/null +++ b/examples/target_cards/depmap_26q1/RRM2B.md @@ -0,0 +1,124 @@ +# Target hypothesis card: RRM2B + +## Target identity + +- **Target symbol:** RRM2B +- **Target name:** ribonucleotide reductase regulatory TP53 inducible subunit M2B +- **Open Targets melanoma score:** 0.574 +- **Open Targets baseline rank:** 110 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 113 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 114 | not prioritized | -4 | +| Tumor-intrinsic / small molecule | 0.000 | 113 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.574) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** RRM2B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for RRM2B in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.030440159428604997,"interquartile_range":0.09226055303100826,"maximum":0.23615443777033013,"mean":0.01593588710866817,"measured_model_count":56,"median":0.006488471619161884,"minimum":-0.18121780207352717,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06182039360240326,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01078722232470268,"interquartile_range":0.01897368961587206,"maximum":0.07183784488213862,"mean":0.021949966235280397,"measured_model_count":56,"median":0.017595754218379635,"minimum":0.002689755558466425,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02976091194057474,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0031722420216032214,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.014677445462933801,"gene_effect_median":0.002554336410770526},"dependency_probability_context_minus_non_context_median":-0.003237733648874218,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.015390932395159736,"gene_effect_context_minus_non_context_median":0.0028943402896217073} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 113 +- **Dependency-aware candidate rank:** 113 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_442ec2f66d546765d9c306fdf50a355b289e7e37bd66a4824aae4fad8a1afb36` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:RRM2B|entrez:50484` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/RUNX1T1.md b/examples/target_cards/depmap_26q1/RUNX1T1.md new file mode 100644 index 0000000..e8a0d66 --- /dev/null +++ b/examples/target_cards/depmap_26q1/RUNX1T1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: RUNX1T1 + +## Target identity + +- **Target symbol:** RUNX1T1 +- **Target name:** RUNX1 partner transcriptional co-repressor 1 +- **Open Targets melanoma score:** 0.587 +- **Open Targets baseline rank:** 90 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 93 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 95 | not prioritized | -5 | +| Tumor-intrinsic / small molecule | 0.000 | 93 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.587) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** RUNX1T1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for RUNX1T1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.09884952652793141,"interquartile_range":0.11970965709835064,"maximum":0.27356305825023636,"mean":-0.04295758676242804,"measured_model_count":56,"median":-0.04714232020834208,"minimum":-0.3818943189986762,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02086013057041923,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0161003914275484,"interquartile_range":0.041744408958407656,"maximum":0.4366432533874732,"mean":0.04657444844566352,"measured_model_count":56,"median":0.03193243688624428,"minimum":0.0019998872365112946,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.057844800385956054,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0021578335492734822,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":-0.004599600939368738,"gene_effect_median":-0.013994556049691326},"dependency_probability_context_minus_non_context_median":0.002261819284604047,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.004823192651699136,"gene_effect_context_minus_non_context_median":-0.014553293597612586} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 93 +- **Dependency-aware candidate rank:** 93 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e1c6b1a71fac0ef5330ef6d9ff0e2369355518d5687079fd508ee933a4a10132` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:RUNX1T1|entrez:862` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SALL4.md b/examples/target_cards/depmap_26q1/SALL4.md new file mode 100644 index 0000000..02ffab9 --- /dev/null +++ b/examples/target_cards/depmap_26q1/SALL4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SALL4 + +## Target identity + +- **Target symbol:** SALL4 +- **Target name:** spalt like transcription factor 4 +- **Open Targets melanoma score:** 0.552 +- **Open Targets baseline rank:** 150 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 152 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 153 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 152 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.552) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SALL4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SALL4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.13566465830643035,"interquartile_range":0.13712660498832815,"maximum":0.3325082771559966,"mean":-0.061407429436107094,"measured_model_count":56,"median":-0.05751971111293863,"minimum":-0.37072006405562824,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0014619466818978008,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.02069457658383381,"interquartile_range":0.03437754339962874,"maximum":0.3217848067260631,"mean":0.051741718849113674,"measured_model_count":56,"median":0.036589651850089416,"minimum":0.001902674157795965,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05507211998346255,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0055148678277405425,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0074503311258278145,"pan_cancer_fraction":0.0074503311258278145,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":0.02093560923724755,"gene_effect_median":0.017304265304520644},"dependency_probability_context_minus_non_context_median":-0.0062088255037458726,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0078125,"non_context_fraction":0.0078125,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.021953312464058142,"gene_effect_context_minus_non_context_median":0.018288384479971276} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 152 +- **Dependency-aware candidate rank:** 152 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_12f96f46af2d44484ca3a02ae488a1a66d0579041c610fa412a0748177e63950` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SALL4|entrez:57167` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SETBP1.md b/examples/target_cards/depmap_26q1/SETBP1.md new file mode 100644 index 0000000..c3fe504 --- /dev/null +++ b/examples/target_cards/depmap_26q1/SETBP1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SETBP1 + +## Target identity + +- **Target symbol:** SETBP1 +- **Target name:** SET binding protein 1 +- **Open Targets melanoma score:** 0.568 +- **Open Targets baseline rank:** 123 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 125 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 126 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 125 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.568) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SETBP1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SETBP1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.03797804622296906,"interquartile_range":0.11603569982367719,"maximum":0.23410999453740547,"mean":0.026320814579516943,"measured_model_count":56,"median":0.020794089042544255,"minimum":-0.1749570667473206,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07805765360070813,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.009273976484867677,"interquartile_range":0.017960499834995435,"maximum":0.1341463196615172,"mean":0.022262575208713727,"measured_model_count":56,"median":0.016776289101935012,"minimum":0.002760614285472168,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.027234476319863112,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0023143291226201367,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.01899299886253225,"gene_effect_median":0.008924208414270409},"dependency_probability_context_minus_non_context_median":-0.0024077840403488524,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01991626964057201,"gene_effect_context_minus_non_context_median":0.009956691149827442} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":25.925925925925927} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 125 +- **Dependency-aware candidate rank:** 125 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a377675f87c49f849e31a9b7afa4a250636177c81b5395bb18daa5011eb4b49d` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SETBP1|entrez:26040` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SETD2.md b/examples/target_cards/depmap_26q1/SETD2.md new file mode 100644 index 0000000..3b0134a --- /dev/null +++ b/examples/target_cards/depmap_26q1/SETD2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SETD2 + +## Target identity + +- **Target symbol:** SETD2 +- **Target name:** SET domain containing 2, histone lysine methyltransferase +- **Open Targets melanoma score:** 0.635 +- **Open Targets baseline rank:** 38 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 45 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 47 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 45 | not prioritized | -7 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.635) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SETD2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SETD2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.5047376254956473,"interquartile_range":0.37448050917812936,"maximum":0.1846584412323803,"mean":-0.3291048407412958,"measured_model_count":56,"median":-0.3280383584112302,"minimum":-1.0317415681684419,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.1302571163175179,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.08620996554393631,"interquartile_range":0.5051609618146871,"maximum":0.9761682730353267,"mean":0.34026916308678895,"measured_model_count":56,"median":0.26696470082025603,"minimum":0.0024915270161495534,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5913709273586234,"threshold_fractions":[{"denominator":56,"fraction":0.32142857142857145,"numerator":18,"threshold":0.5},{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.13397532216480423,"dependency_probability_threshold_fractions":[{"context_fraction":0.32142857142857145,"difference":-0.08171712393566694,"pan_cancer_fraction":0.4031456953642384,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":-0.0750946073793756,"pan_cancer_fraction":0.14652317880794702,"threshold":0.8}],"gene_effect_mean":0.08091953973590466,"gene_effect_median":0.07569703841773578},"dependency_probability_context_minus_non_context_median":-0.1411708969140013,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.32142857142857145,"difference":-0.08568948412698413,"non_context_fraction":0.4071180555555556,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":-0.07874503968253968,"non_context_fraction":0.1501736111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08485312847306681,"gene_effect_context_minus_non_context_median":0.0804583063181547} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 45 +- **Dependency-aware candidate rank:** 45 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_38d8acd6a14528ecff8c44461c927e87f811f304368f049bb16c6bc389a79cb3` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SETD2|entrez:29072` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SF3B1.md b/examples/target_cards/depmap_26q1/SF3B1.md new file mode 100644 index 0000000..d400be4 --- /dev/null +++ b/examples/target_cards/depmap_26q1/SF3B1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SF3B1 + +## Target identity + +- **Target symbol:** SF3B1 +- **Target name:** splicing factor 3b subunit 1 +- **Open Targets melanoma score:** 0.698 +- **Open Targets baseline rank:** 21 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 28 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 30 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.011 | 23 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.698) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SF3B1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SF3B1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.6704389910023474,"interquartile_range":0.32745833716446127,"maximum":-0.9508810647263816,"mean":-1.5338619757571077,"measured_model_count":56,"median":-1.4947664924641337,"minimum":-2.378982043724258,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.3429806538378861,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9931771615712739,"interquartile_range":0.006820375637453746,"maximum":1.0,"mean":0.9957113192764605,"measured_model_count":56,"median":0.9993767217839019,"minimum":0.9673445342927015,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9999975372087276,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.000989966944183851,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0033112582781457123,"pan_cancer_fraction":0.9966887417218543,"threshold":0.5},{"context_fraction":1.0,"difference":0.01572847682119205,"pan_cancer_fraction":0.984271523178808,"threshold":0.8}],"gene_effect_mean":-0.07114636073200131,"gene_effect_median":-0.054832562133903195},"dependency_probability_context_minus_non_context_median":0.0010980663549413627,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.00347222222222221,"non_context_fraction":0.9965277777777778,"threshold":0.5},{"context_fraction":1.0,"difference":0.01649305555555558,"non_context_fraction":0.9835069444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.07460486437869474,"gene_effect_context_minus_non_context_median":-0.057426582483840916} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 28 +- **Dependency-aware candidate rank:** 28 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e09f8006beaf7360efbadeaba7ac7d0b5b2eaef0ec77e024d789a51109f10b61` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SF3B1|entrez:23451` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SLC24A5.md b/examples/target_cards/depmap_26q1/SLC24A5.md new file mode 100644 index 0000000..c376e3f --- /dev/null +++ b/examples/target_cards/depmap_26q1/SLC24A5.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SLC24A5 + +## Target identity + +- **Target symbol:** SLC24A5 +- **Target name:** solute carrier family 24 member 5 +- **Open Targets melanoma score:** 0.467 +- **Open Targets baseline rank:** 286 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 286 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 286 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 286 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.467) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SLC24A5 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SLC24A5 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.003025095303933984,"interquartile_range":0.10082197260395905,"maximum":0.22263284691640708,"mean":0.04178003697152555,"measured_model_count":56,"median":0.04566657198688534,"minimum":-0.28433300526663596,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10384706790789303,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.007485941222069663,"interquartile_range":0.013936761588715495,"maximum":0.13392583893250115,"mean":0.02036981003205173,"measured_model_count":56,"median":0.012767474299341924,"minimum":0.0016006595218845212,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02142270281078516,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.001589657135267545,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.004963217362922899,"gene_effect_median":0.0015223561321224821},"dependency_probability_context_minus_non_context_median":-0.0016580749335111389,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.005204484873620567,"gene_effect_context_minus_non_context_median":0.0016214445087715107} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 286 +- **Dependency-aware candidate rank:** 286 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_1fc92daef66184e66d1e38ac2403101a0d5b21bc4d321f3c70d9e8379ce9bf6b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SLC24A5|entrez:283652` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SLC45A2.md b/examples/target_cards/depmap_26q1/SLC45A2.md new file mode 100644 index 0000000..db7c9be --- /dev/null +++ b/examples/target_cards/depmap_26q1/SLC45A2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SLC45A2 + +## Target identity + +- **Target symbol:** SLC45A2 +- **Target name:** solute carrier family 45 member 2 +- **Open Targets melanoma score:** 0.547 +- **Open Targets baseline rank:** 165 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 167 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 168 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 167 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.547) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SLC45A2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SLC45A2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.040933783966169555,"interquartile_range":0.14882908611197646,"maximum":0.3227303488010275,"mean":0.11567695785061881,"measured_model_count":56,"median":0.11861136448699858,"minimum":-0.08536406441108876,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.18976287007814602,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0035499116606889656,"interquartile_range":0.009916857053356331,"maximum":0.0395367321012825,"mean":0.010096898602229057,"measured_model_count":56,"median":0.006829464645826495,"minimum":0.0006995658646645975,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.013466768714045296,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0051761173448216374,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.05149240361433348,"gene_effect_median":0.05169404192771569},"dependency_probability_context_minus_non_context_median":-0.005411094838348408,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05399550656780805,"gene_effect_context_minus_non_context_median":0.052908110898977054} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 167 +- **Dependency-aware candidate rank:** 167 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_b3b0a6db95bbdbe363ed523b282b1ade2229ceeb85817ae5117b3c7af7058f2b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SLC45A2|entrez:51151` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SMAD2.md b/examples/target_cards/depmap_26q1/SMAD2.md new file mode 100644 index 0000000..43aa26c --- /dev/null +++ b/examples/target_cards/depmap_26q1/SMAD2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SMAD2 + +## Target identity + +- **Target symbol:** SMAD2 +- **Target name:** SMAD family member 2 +- **Open Targets melanoma score:** 0.552 +- **Open Targets baseline rank:** 148 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 150 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 151 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 150 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.552) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SMAD2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SMAD2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.04437470527249164,"interquartile_range":0.10986926077333312,"maximum":0.1719519122172183,"mean":0.0053355756530233155,"measured_model_count":56,"median":0.020857726704379374,"minimum":-0.24627069147106154,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06549455550084148,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.010600862933249054,"interquartile_range":0.016872658456282188,"maximum":0.15468658704651223,"mean":0.02527240623956528,"measured_model_count":56,"median":0.019602222042527484,"minimum":0.003858964670826867,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02747352138953124,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.002283767924237845,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.01982315171908842,"gene_effect_median":-0.003612039323109724},"dependency_probability_context_minus_non_context_median":0.0023783003555883017,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.020786777149877433,"gene_effect_context_minus_non_context_median":-0.003776990002354444} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 150 +- **Dependency-aware candidate rank:** 150 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_fd3d4f728ada5f93577448ef7a9942a1c824add7aed8dd643e69147d76496b12` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SMAD2|entrez:4087` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SMAD3.md b/examples/target_cards/depmap_26q1/SMAD3.md new file mode 100644 index 0000000..732dcb8 --- /dev/null +++ b/examples/target_cards/depmap_26q1/SMAD3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SMAD3 + +## Target identity + +- **Target symbol:** SMAD3 +- **Target name:** SMAD family member 3 +- **Open Targets melanoma score:** 0.533 +- **Open Targets baseline rank:** 184 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 186 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 187 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 186 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.533) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SMAD3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SMAD3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.090841081469131,"interquartile_range":0.10274341436989691,"maximum":0.19788349112491374,"mean":-0.03155614431899213,"measured_model_count":56,"median":-0.019242661334844407,"minimum":-0.20426070247573397,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.011902332900765911,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01586107320694835,"interquartile_range":0.026251711901153427,"maximum":0.14349263118807176,"mean":0.03783132268640034,"measured_model_count":56,"median":0.026968181859627394,"minimum":0.003981175606287827,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04211278510810178,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0012994329059359162,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.01436144254973943,"gene_effect_median":-0.0013439907680628665},"dependency_probability_context_minus_non_context_median":0.0013071120339713076,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.015059568229240775,"gene_effect_context_minus_non_context_median":-0.0013439907680628665} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 186 +- **Dependency-aware candidate rank:** 186 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_2110cd3452f34385fb6da1b287ee162c151d853acfc7ff64f2420bf885e2f347` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SMAD3|entrez:4088` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SMARCA4.md b/examples/target_cards/depmap_26q1/SMARCA4.md new file mode 100644 index 0000000..6536c6b --- /dev/null +++ b/examples/target_cards/depmap_26q1/SMARCA4.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SMARCA4 + +## Target identity + +- **Target symbol:** SMARCA4 +- **Target name:** SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4 +- **Open Targets melanoma score:** 0.593 +- **Open Targets baseline rank:** 78 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 82 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 84 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 82 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.593) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SMARCA4 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SMARCA4 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.6036613983479087,"interquartile_range":0.39227301538187714,"maximum":0.23567647510109768,"mean":-0.4060004403164458,"measured_model_count":56,"median":-0.40356272875642973,"minimum":-0.9591300526864226,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.21138838296603152,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.11991230214906738,"interquartile_range":0.642015102234534,"maximum":0.9765745525207847,"mean":0.43724903443681506,"measured_model_count":56,"median":0.3939739872865238,"minimum":0.001644732447700285,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.7619274043836013,"threshold_fractions":[{"denominator":56,"fraction":0.4642857142857143,"numerator":26,"threshold":0.5},{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.14332511418302418,"dependency_probability_threshold_fractions":[{"context_fraction":0.4642857142857143,"difference":0.11494796594134343,"pan_cancer_fraction":0.34933774834437087,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.047540208136234635,"pan_cancer_fraction":0.19039735099337748,"threshold":0.8}],"gene_effect_mean":-0.04237234158819192,"gene_effect_median":-0.08439069793628401},"dependency_probability_context_minus_non_context_median":0.14846696083007876,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.4642857142857143,"difference":0.1205357142857143,"non_context_fraction":0.34375,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.04985119047619049,"non_context_fraction":0.19270833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.04443210819317345,"gene_effect_context_minus_non_context_median":-0.08588989300867489} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 82 +- **Dependency-aware candidate rank:** 82 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_82bc4ef92f13b26691517fef72e6b12a768aea581a2202f644ea9788e975a62a` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SMARCA4|entrez:6597` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SMO.md b/examples/target_cards/depmap_26q1/SMO.md new file mode 100644 index 0000000..d9edc99 --- /dev/null +++ b/examples/target_cards/depmap_26q1/SMO.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SMO + +## Target identity + +- **Target symbol:** SMO +- **Target name:** smoothened, frizzled class receptor +- **Open Targets melanoma score:** 0.518 +- **Open Targets baseline rank:** 221 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 223 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 223 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 223 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.518) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SMO lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SMO in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.09197586746769547,"interquartile_range":0.12796016494418277,"maximum":0.37503303447012404,"mean":-0.014626427931529379,"measured_model_count":56,"median":-0.016674116349569723,"minimum":-0.21920401677704732,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03598429747648731,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01294561446721113,"interquartile_range":0.03573012833095012,"maximum":0.18896716316175619,"mean":0.03749273032273328,"measured_model_count":56,"median":0.025248343352956944,"minimum":0.0009806870821544142,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04867574279816125,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01987730449887414,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.07071470153846002,"gene_effect_median":0.065890735062588},"dependency_probability_context_minus_non_context_median":-0.020655150638843465,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.07415222175213514,"gene_effect_context_minus_non_context_median":0.0708283264465055} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 223 +- **Dependency-aware candidate rank:** 223 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_f31ee34751adbb3856a08c7eb961e5fe78b16f032a6a16b30c0db8fc2c14428a` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SMO|entrez:6608` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SPEN.md b/examples/target_cards/depmap_26q1/SPEN.md new file mode 100644 index 0000000..6f105ab --- /dev/null +++ b/examples/target_cards/depmap_26q1/SPEN.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SPEN + +## Target identity + +- **Target symbol:** SPEN +- **Target name:** spen family transcriptional repressor +- **Open Targets melanoma score:** 0.564 +- **Open Targets baseline rank:** 125 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 127 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 128 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 127 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.564) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SPEN lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SPEN in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.20590850785643827,"interquartile_range":0.30629871670536163,"maximum":0.2961929358661407,"mean":-0.07464402855012801,"measured_model_count":56,"median":-0.1069708047403998,"minimum":-0.5774269486938107,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10039020884892337,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008554559805812224,"interquartile_range":0.10390388758026911,"maximum":0.6483530280352656,"mean":0.08850620961868054,"measured_model_count":56,"median":0.051609868437919544,"minimum":0.001341103131926982,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11245844738608134,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0345593764842699,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.00792336802270577,"pan_cancer_fraction":0.009933774834437087,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.09781353764463253,"gene_effect_median":-0.13542096809724719},"dependency_probability_context_minus_non_context_median":0.03496627856968703,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.008308531746031744,"non_context_fraction":0.009548611111111112,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.10256836239124664,"gene_effect_context_minus_non_context_median":-0.13752570185605562} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":96.29629629629629} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 127 +- **Dependency-aware candidate rank:** 127 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_b4e96c941ea4794bcaaa4f748347841026344125925996732e2ffecbee9dae29` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SPEN|entrez:23013` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SPOP.md b/examples/target_cards/depmap_26q1/SPOP.md new file mode 100644 index 0000000..ec760a0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/SPOP.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SPOP + +## Target identity + +- **Target symbol:** SPOP +- **Target name:** speckle type BTB/POZ protein +- **Open Targets melanoma score:** 0.525 +- **Open Targets baseline rank:** 192 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 194 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 194 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 194 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.525) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SPOP lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SPOP in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.10868585464553142,"interquartile_range":0.1953317650864464,"maximum":0.31868793248113303,"mean":-0.02062799177610516,"measured_model_count":56,"median":-0.0011139874447977718,"minimum":-0.5162901003081669,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08664591044091499,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008332047232900763,"interquartile_range":0.04870586649525993,"maximum":0.5876800902917391,"mean":0.058468297685737296,"measured_model_count":56,"median":0.021659335715944927,"minimum":0.0014736174637020138,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.057037913728160694,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.017893750255209537,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.01750236518448439,"pan_cancer_fraction":0.018211920529801324,"threshold":0.5},{"context_fraction":0.0,"difference":-0.005794701986754967,"pan_cancer_fraction":0.005794701986754967,"threshold":0.8}],"gene_effect_mean":0.056645665315990565,"gene_effect_median":0.06330739048528305},"dependency_probability_context_minus_non_context_median":-0.01910772245672603,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.0183531746031746,"non_context_fraction":0.017361111111111112,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006076388888888889,"non_context_fraction":0.006076388888888889,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.05939927404662884,"gene_effect_context_minus_non_context_median":0.06665402546532606} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 194 +- **Dependency-aware candidate rank:** 194 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_3317e48ae19c5ffa71f2d6b4c4dbe9bfcc245c28860f06c0ebb59d9006d3a71a` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SPOP|entrez:8405` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/STAT1.md b/examples/target_cards/depmap_26q1/STAT1.md new file mode 100644 index 0000000..5337186 --- /dev/null +++ b/examples/target_cards/depmap_26q1/STAT1.md @@ -0,0 +1,73 @@ +# STAT1 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.023715990107306573,"interquartile_range":0.11483236587820499,"maximum":0.594601062886091,"mean":0.03826927595427404,"measured_model_count":56,"median":0.03441501730713435,"minimum":-0.18865251629494253,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09111637577089841,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.007581757478393323,"interquartile_range":0.018907350585128907,"maximum":0.11007117420691961,"mean":0.021312047695286645,"measured_model_count":56,"median":0.015444040039196624,"minimum":0.0002561875140645888,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02648910806352223,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00015958606018570166,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.0008335993956761281,"gene_effect_median":0.00026024357751956717},"dependency_probability_context_minus_non_context_median":-0.00021562568964750978,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.000874121588521487,"gene_effect_context_minus_non_context_median":0.00026024357751956717} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e45cf228ca8662a13ae3dec9838c879a4728d7d310e457a2e4e6708d614e3ca5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:STAT1|entrez:6772` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/STAT5B.md b/examples/target_cards/depmap_26q1/STAT5B.md new file mode 100644 index 0000000..7bcaea2 --- /dev/null +++ b/examples/target_cards/depmap_26q1/STAT5B.md @@ -0,0 +1,124 @@ +# Target hypothesis card: STAT5B + +## Target identity + +- **Target symbol:** STAT5B +- **Target name:** signal transducer and activator of transcription 5B +- **Open Targets melanoma score:** 0.496 +- **Open Targets baseline rank:** 255 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 257 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 257 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 257 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.496) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** STAT5B lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for STAT5B in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.21254486379258475,"interquartile_range":0.1507730685086402,"maximum":0.10221524728073916,"mean":-0.1297580516271845,"measured_model_count":56,"median":-0.11715704066883736,"minimum":-0.45256549872929824,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.061771795283944546,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.03489943369349236,"interquartile_range":0.09272969085043448,"maximum":0.4369411155234448,"mean":0.09325839392333803,"measured_model_count":56,"median":0.059652060425314735,"minimum":0.00564129311272788,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12762912454392683,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.029365833992934826,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.028145695364238412,"pan_cancer_fraction":0.028145695364238412,"threshold":0.5},{"context_fraction":0.0,"difference":-0.012417218543046357,"pan_cancer_fraction":0.012417218543046357,"threshold":0.8}],"gene_effect_mean":0.04488537049905639,"gene_effect_median":0.04071306645896228},"dependency_probability_context_minus_non_context_median":-0.0303876275142239,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.029513888888888888,"non_context_fraction":0.029513888888888888,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013020833333333334,"non_context_fraction":0.013020833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04706729823164932,"gene_effect_context_minus_non_context_median":0.04224545430101631} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":3.7037037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 257 +- **Dependency-aware candidate rank:** 257 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_e21f5e617c739dca9fdc377a6421745cd78adfe0644ff739be3f201c394456e1` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:STAT5B|entrez:6777` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/STK11.md b/examples/target_cards/depmap_26q1/STK11.md new file mode 100644 index 0000000..bd441bb --- /dev/null +++ b/examples/target_cards/depmap_26q1/STK11.md @@ -0,0 +1,124 @@ +# Target hypothesis card: STK11 + +## Target identity + +- **Target symbol:** STK11 +- **Target name:** serine/threonine kinase 11 +- **Open Targets melanoma score:** 0.631 +- **Open Targets baseline rank:** 42 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 49 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 51 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 49 | not prioritized | -7 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.631) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** STK11 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for STK11 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.33769402041129626,"interquartile_range":0.34553422259709676,"maximum":1.3773386060676387,"mean":-0.1472549078841526,"measured_model_count":56,"median":-0.14109773350213328,"minimum":-0.8534586542297331,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.007840202185800504,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.01945733984178246,"interquartile_range":0.2964351119072127,"maximum":0.9205200111570674,"mean":0.21506176370357213,"measured_model_count":56,"median":0.07264424891737002,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.31589245174899516,"threshold_fractions":[{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.5},{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.01879693497834929,"dependency_probability_threshold_fractions":[{"context_fraction":0.14285714285714285,"difference":-0.07734153263954588,"pan_cancer_fraction":0.22019867549668873,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":-0.026608325449385045,"pan_cancer_fraction":0.11589403973509933,"threshold":0.8}],"gene_effect_mean":0.041811237349291486,"gene_effect_median":0.03470423374620135},"dependency_probability_context_minus_non_context_median":-0.020380121457312758,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.14285714285714285,"difference":-0.0811011904761905,"non_context_fraction":0.22395833333333334,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":-0.027901785714285712,"non_context_fraction":0.1171875,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04384372805377118,"gene_effect_context_minus_non_context_median":0.036281749337344266} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":44.44444444444444} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 49 +- **Dependency-aware candidate rank:** 49 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_f573ffdfa89f249ac5ced93e70646fc1641eb27f5beb01507a378563c58d1304` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:STK11|entrez:6794` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/STN1.md b/examples/target_cards/depmap_26q1/STN1.md new file mode 100644 index 0000000..496b54c --- /dev/null +++ b/examples/target_cards/depmap_26q1/STN1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: STN1 + +## Target identity + +- **Target symbol:** STN1 +- **Target name:** STN1 subunit of CST complex +- **Open Targets melanoma score:** 0.523 +- **Open Targets baseline rank:** 197 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 199 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 199 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 199 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.523) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** STN1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for STN1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.4779879422685708,"interquartile_range":0.29444075349956655,"maximum":0.16849346309225044,"mean":-0.3457827371641288,"measured_model_count":56,"median":-0.3320372797448661,"minimum":-0.9777832742302645,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.18354718876900422,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.09289156314684381,"interquartile_range":0.45956568201046494,"maximum":0.9778197824284264,"mean":0.35360489820405777,"measured_model_count":56,"median":0.2679704032719562,"minimum":0.002797966808841758,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5524572451573088,"threshold_fractions":[{"denominator":56,"fraction":0.30357142857142855,"numerator":17,"threshold":0.5},{"denominator":56,"fraction":0.14285714285714285,"numerator":8,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.1587208773509043,"dependency_probability_threshold_fractions":[{"context_fraction":0.30357142857142855,"difference":-0.14841532639545885,"pan_cancer_fraction":0.4519867549668874,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.10631504257332072,"pan_cancer_fraction":0.24917218543046357,"threshold":0.8}],"gene_effect_mean":0.12108837825884422,"gene_effect_median":0.08607346039156422},"dependency_probability_context_minus_non_context_median":-0.16553983909783232,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.30357142857142855,"difference":-0.15562996031746035,"non_context_fraction":0.4592013888888889,"threshold":0.5},{"context_fraction":0.14285714285714285,"difference":-0.11148313492063494,"non_context_fraction":0.2543402777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.12697461886864864,"gene_effect_context_minus_non_context_median":0.09113019244100451} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 199 +- **Dependency-aware candidate rank:** 199 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_325900cec01f74632d5a8963560fd9eb0404d8bf243d051cb31d1424720729eb` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:STN1|entrez:79991` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SUFU.md b/examples/target_cards/depmap_26q1/SUFU.md new file mode 100644 index 0000000..e106064 --- /dev/null +++ b/examples/target_cards/depmap_26q1/SUFU.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SUFU + +## Target identity + +- **Target symbol:** SUFU +- **Target name:** SUFU negative regulator of hedgehog signaling +- **Open Targets melanoma score:** 0.543 +- **Open Targets baseline rank:** 175 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 177 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 178 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 177 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.543) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SUFU lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SUFU in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.023938544589964868,"interquartile_range":0.1774876002492798,"maximum":0.95481212338376,"mean":0.06462142656096546,"measured_model_count":56,"median":0.05071099091677807,"minimum":-0.7061946864814099,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.15354905565931493,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005377839592163817,"interquartile_range":0.021656509327421553,"maximum":0.811876611301506,"mean":0.03797623516616818,"measured_model_count":56,"median":0.012147568247679989,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02703434891958537,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002946423118163285,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.012890255439924312,"pan_cancer_fraction":0.004966887417218543,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.015373699148533584,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.01616561260624235,"gene_effect_median":0.010250265714132317},"dependency_probability_context_minus_non_context_median":-0.0031789831274965513,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":0.013516865079365078,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.016121031746031744,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01695144099682358,"gene_effect_context_minus_non_context_median":0.01124857366622331} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 177 +- **Dependency-aware candidate rank:** 177 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_942290a38450ab42ef87a67113bbfe0c6f1cc6aaabf3a1464f5ad179648e09d4` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SUFU|entrez:51684` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SUZ12.md b/examples/target_cards/depmap_26q1/SUZ12.md new file mode 100644 index 0000000..240a2d9 --- /dev/null +++ b/examples/target_cards/depmap_26q1/SUZ12.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SUZ12 + +## Target identity + +- **Target symbol:** SUZ12 +- **Target name:** SUZ12 polycomb repressive complex 2 subunit +- **Open Targets melanoma score:** 0.475 +- **Open Targets baseline rank:** 278 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 278 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 278 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 278 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.475) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SUZ12 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SUZ12 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.4965029253131678,"interquartile_range":0.34493944854229963,"maximum":0.4677630930028186,"mean":-0.34131115668653944,"measured_model_count":56,"median":-0.33607475463804537,"minimum":-1.2517467051124003,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.15156347677086815,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0804547369061895,"interquartile_range":0.522462756994033,"maximum":0.9941988949339067,"mean":0.35415518658327777,"measured_model_count":56,"median":0.28560992279472086,"minimum":0.0008325024643399397,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.6029174939002225,"threshold_fractions":[{"denominator":56,"fraction":0.3392857142857143,"numerator":19,"threshold":0.5},{"denominator":56,"fraction":0.08928571428571429,"numerator":5,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.09645538695062106,"dependency_probability_threshold_fractions":[{"context_fraction":0.3392857142857143,"difference":-0.07710501419110688,"pan_cancer_fraction":0.4163907284768212,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":-0.08952223273415326,"pan_cancer_fraction":0.17880794701986755,"threshold":0.8}],"gene_effect_mean":0.06396868090500646,"gene_effect_median":0.05833410563250985},"dependency_probability_context_minus_non_context_median":-0.10570987062618109,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.3392857142857143,"difference":-0.0808531746031746,"non_context_fraction":0.4201388888888889,"threshold":0.5},{"context_fraction":0.08928571428571429,"difference":-0.09387400793650792,"non_context_fraction":0.1831597222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.06707826956011098,"gene_effect_context_minus_non_context_median":0.061797847408295026} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 278 +- **Dependency-aware candidate rank:** 278 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_c6f7218c8cb45190bd221c4b32334939c435eba72386d9e50bc127e15bafcb96` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SUZ12|entrez:23512` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/SYK.md b/examples/target_cards/depmap_26q1/SYK.md new file mode 100644 index 0000000..0170036 --- /dev/null +++ b/examples/target_cards/depmap_26q1/SYK.md @@ -0,0 +1,124 @@ +# Target hypothesis card: SYK + +## Target identity + +- **Target symbol:** SYK +- **Target name:** spleen associated tyrosine kinase +- **Open Targets melanoma score:** 0.564 +- **Open Targets baseline rank:** 127 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 129 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 130 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 129 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.564) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** SYK lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for SYK in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.028301337947750776,"interquartile_range":0.09846484453277939,"maximum":0.2761142482769202,"mean":0.024136028244293617,"measured_model_count":56,"median":0.008529689252564848,"minimum":-0.19785112063596755,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07016350658502861,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.009531068922012565,"interquartile_range":0.01679429075027903,"maximum":0.12053995537301158,"mean":0.021483934728060494,"measured_model_count":56,"median":0.018472304540237433,"minimum":0.0016419199380332049,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.026325359672291597,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0018682134466057876,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.019867549668874173,"pan_cancer_fraction":0.019867549668874173,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013245033112582781,"pan_cancer_fraction":0.013245033112582781,"threshold":0.8}],"gene_effect_mean":0.0126587746279189,"gene_effect_median":-0.018126393479598164},"dependency_probability_context_minus_non_context_median":0.0018882076919032077,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.020833333333333332,"non_context_fraction":0.020833333333333332,"threshold":0.5},{"context_fraction":0.0,"difference":-0.013888888888888888,"non_context_fraction":0.013888888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.013274131727887184,"gene_effect_context_minus_non_context_median":-0.01861567772250128} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":70.37037037037037} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 129 +- **Dependency-aware candidate rank:** 129 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_282298b8300d668c37fd425237e864ee18a1f85d6e44f8f47fdb715b1e30f9de` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:SYK|entrez:6850` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TAP1.md b/examples/target_cards/depmap_26q1/TAP1.md new file mode 100644 index 0000000..77c44ed --- /dev/null +++ b/examples/target_cards/depmap_26q1/TAP1.md @@ -0,0 +1,73 @@ +# TAP1 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.16724802560020013,"interquartile_range":0.1985094558616541,"maximum":0.5470468266686689,"mean":-0.07939806290217721,"measured_model_count":56,"median":-0.07247945665159533,"minimum":-0.5733755101579874,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03126143026145397,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.014782179225490823,"interquartile_range":0.08211488592426243,"maximum":0.6446446410081932,"mean":0.08772285017978665,"measured_model_count":56,"median":0.0447208452197298,"minimum":6.830493540377923e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.09689706514975326,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.02277193409938026,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.025780510879848624,"pan_cancer_fraction":0.009933774834437087,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.8}],"gene_effect_mean":0.04472110971213279,"gene_effect_median":0.05355281064177525},"dependency_probability_context_minus_non_context_median":-0.023657032478633322,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":0.027033730158730156,"non_context_fraction":0.008680555555555556,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.046895052545361415,"gene_effect_context_minus_non_context_median":0.055247717762366116} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_639b86f57c7bd2c847c9f32433cbc12a5867a71e5e95f5fe1cd7fec54f2a3cbc` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TAP1|entrez:6890` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TAP2.md b/examples/target_cards/depmap_26q1/TAP2.md new file mode 100644 index 0000000..8938556 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TAP2.md @@ -0,0 +1,73 @@ +# TAP2 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.11718440590337778,"interquartile_range":0.341363350857,"maximum":0.48787387730742277,"mean":0.046799923839240254,"measured_model_count":56,"median":0.034986271431895845,"minimum":-0.4092929272676856,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.2241789449536222,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0019427190737520005,"interquartile_range":0.06363806528902216,"maximum":0.36713822743055147,"mean":0.04596588318721421,"measured_model_count":56,"median":0.012748389342080056,"minimum":0.00018033560046999035,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06558078436277416,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.00025281361128764654,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.015393517900672851,"gene_effect_median":-0.023019405772148102},"dependency_probability_context_minus_non_context_median":-0.00025281361128764654,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.016141813909733335,"gene_effect_context_minus_non_context_median":-0.02350817947630058} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":85.18518518518519} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_bc1603d100048f5a1ad3689524e11bbf7adf28285af48a5c17316f3aa27cf70e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TAP2|entrez:6891` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TBL1XR1.md b/examples/target_cards/depmap_26q1/TBL1XR1.md new file mode 100644 index 0000000..3667db0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TBL1XR1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TBL1XR1 + +## Target identity + +- **Target symbol:** TBL1XR1 +- **Target name:** TBL1X/Y related 1 +- **Open Targets melanoma score:** 0.511 +- **Open Targets baseline rank:** 235 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 237 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 237 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 237 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.511) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TBL1XR1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TBL1XR1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.44322955679950454,"interquartile_range":0.2668450960778149,"maximum":0.9833284356887129,"mean":-0.3174421086565639,"measured_model_count":56,"median":-0.33277910671051136,"minimum":-1.9646819675877583,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.17638446072168962,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.08652037502979554,"interquartile_range":0.41937699416997204,"maximum":1.0,"mean":0.3189140280518254,"measured_model_count":56,"median":0.27129473782400343,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5058973691997676,"threshold_fractions":[{"denominator":56,"fraction":0.26785714285714285,"numerator":15,"threshold":0.5},{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.005472140106186962,"dependency_probability_threshold_fractions":[{"context_fraction":0.26785714285714285,"difference":-0.08230842005676442,"pan_cancer_fraction":0.35016556291390727,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.1326868495742668,"pan_cancer_fraction":0.18625827814569537,"threshold":0.8}],"gene_effect_mean":0.053718896805078076,"gene_effect_median":-0.003826731972826569},"dependency_probability_context_minus_non_context_median":0.005993485466598336,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.26785714285714285,"difference":-0.08630952380952384,"non_context_fraction":0.3541666666666667,"threshold":0.5},{"context_fraction":0.05357142857142857,"difference":-0.13913690476190477,"non_context_fraction":0.19270833333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.056330232066436,"gene_effect_context_minus_non_context_median":-0.005183196194501027} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":37.03703703703704} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 237 +- **Dependency-aware candidate rank:** 237 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_cdac3dbccce2709d79074d20902a8768c584ebab5c7bc2f3f810c3d6694f9553` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TBL1XR1|entrez:79718` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TBX3.md b/examples/target_cards/depmap_26q1/TBX3.md new file mode 100644 index 0000000..f249545 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TBX3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TBX3 + +## Target identity + +- **Target symbol:** TBX3 +- **Target name:** T-box transcription factor 3 +- **Open Targets melanoma score:** 0.588 +- **Open Targets baseline rank:** 87 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 90 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 92 | not prioritized | -5 | +| Tumor-intrinsic / small molecule | 0.000 | 90 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.588) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TBX3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TBX3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.23573951656616127,"interquartile_range":0.20424707807953718,"maximum":0.34140535907966685,"mean":-0.13581506022797174,"measured_model_count":56,"median":-0.144887275560554,"minimum":-0.5553790334161137,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.031492438486624086,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.025720312146242173,"interquartile_range":0.11840113413674436,"maximum":0.6616848325855214,"mean":0.12232477255665541,"measured_model_count":56,"median":0.07955915571703014,"minimum":0.0008777444154026813,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14412144628298654,"threshold_fractions":[{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0313984644600503,"dependency_probability_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":0.028382213812677387,"pan_cancer_fraction":0.04304635761589404,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014072847682119206,"pan_cancer_fraction":0.014072847682119206,"threshold":0.8}],"gene_effect_mean":-0.025790819731207726,"gene_effect_median":-0.05426358637532251},"dependency_probability_context_minus_non_context_median":0.03214660788018489,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.07142857142857142,"difference":0.02976190476190476,"non_context_fraction":0.041666666666666664,"threshold":0.5},{"context_fraction":0.0,"difference":-0.014756944444444444,"non_context_fraction":0.014756944444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.027044540134808087,"gene_effect_context_minus_non_context_median":-0.05659689322368143} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 90 +- **Dependency-aware candidate rank:** 90 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_20e736c6d97c92d571e7d401407894dab365db65714a9998606d9f76a28e7e6a` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TBX3|entrez:6926` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TCL1A.md b/examples/target_cards/depmap_26q1/TCL1A.md new file mode 100644 index 0000000..74aa1ec --- /dev/null +++ b/examples/target_cards/depmap_26q1/TCL1A.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TCL1A + +## Target identity + +- **Target symbol:** TCL1A +- **Target name:** TCL1 family AKT coactivator A +- **Open Targets melanoma score:** 0.506 +- **Open Targets baseline rank:** 248 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 250 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 250 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 250 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.506) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TCL1A lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TCL1A in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.11206944388589762,"interquartile_range":0.13506523175571503,"maximum":0.353208737650306,"mean":-0.029016807448142428,"measured_model_count":56,"median":-0.000812838632041863,"minimum":-0.45051063472828873,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.022995787869817392,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.015122906774957338,"interquartile_range":0.04261576512491955,"maximum":0.40792408921870826,"mean":0.05089308425254634,"measured_model_count":56,"median":0.02026722678410809,"minimum":0.0009637063547128886,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05773867189987689,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0010357334647972845,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.025453933451171612,"gene_effect_median":-0.003189848265832563},"dependency_probability_context_minus_non_context_median":-0.0010798945527638222,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.026691277438381313,"gene_effect_context_minus_non_context_median":-0.00359331667726691} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 250 +- **Dependency-aware candidate rank:** 250 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_48c7ea73dcd2da21f1516254c03e3d36f9df985a59d63e0e2b8e1ce0d0c458df` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TCL1A|entrez:8115` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TENT5C.md b/examples/target_cards/depmap_26q1/TENT5C.md new file mode 100644 index 0000000..a3b3a2f --- /dev/null +++ b/examples/target_cards/depmap_26q1/TENT5C.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TENT5C + +## Target identity + +- **Target symbol:** TENT5C +- **Target name:** terminal nucleotidyltransferase 5C +- **Open Targets melanoma score:** 0.479 +- **Open Targets baseline rank:** 274 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 274 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 274 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 274 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.479) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TENT5C lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TENT5C in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.03864097744616059,"interquartile_range":0.11511279099291087,"maximum":0.2541597207495479,"mean":0.022881062803934028,"measured_model_count":56,"median":0.021952823430253073,"minimum":-0.23474050442874117,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07647181354675028,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008053275498989303,"interquartile_range":0.021966046073802734,"maximum":0.13889360325225697,"mean":0.0244585667177243,"measured_model_count":56,"median":0.018800263137722335,"minimum":0.00141942221638269,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.030019321572792038,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.002498147846532319,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.011498624623446477,"gene_effect_median":-0.008879290858561668},"dependency_probability_context_minus_non_context_median":0.0025907753334622093,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.012057585542641792,"gene_effect_context_minus_non_context_median":-0.009323741953518788} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 274 +- **Dependency-aware candidate rank:** 274 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_55351733ddfc8f1e09e5df5d6993253a07d9eb597f6f618c64e854fc8374f765` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TENT5C|entrez:54855` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TERT.md b/examples/target_cards/depmap_26q1/TERT.md new file mode 100644 index 0000000..56e333d --- /dev/null +++ b/examples/target_cards/depmap_26q1/TERT.md @@ -0,0 +1,127 @@ +# Target hypothesis card: TERT + +## Target identity + +- **Target symbol:** TERT +- **Target name:** telomerase reverse transcriptase +- **Open Targets melanoma score:** 0.709 +- **Open Targets baseline rank:** 16 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / biomarker +- **Role confidence:** medium-high +- **Therapeutic direction:** use as biomarker / pathway targeting if appropriate +- **Best modality:** tumor-intrinsic biomarker / pathway context +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 23 | not prioritized | -7 | +| Resistance biomarker | 0.385 | 14 | low | 2 | +| Tumor-intrinsic / small molecule | 0.513 | 8 | medium | 8 | + +## Evidence for + +- High Open Targets melanoma association score (0.709) +- Stable role classifier confidence is medium-high +- Biomarker fit is medium-high + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Most useful as biomarker or stratification marker rather than direct therapeutic target +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 0.889 +- **Contradiction score:** 0.240 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TERT lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** biomarker validation +- **Next experiment:** Test whether TERT status or expression differs between anti-PD-1 responders and non-responders in an independent melanoma cohort. +- **Rationale:** This would determine whether the candidate has practical value as a resistance biomarker or patient-stratification feature. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.13632697698590185,"interquartile_range":0.17256257719257062,"maximum":0.31463935418414035,"mean":-0.053094014995252854,"measured_model_count":56,"median":-0.04819403767771936,"minimum":-0.39336959009981265,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.036235600206668786,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.013545260600762363,"interquartile_range":0.05502605515873926,"maximum":0.4509431568440402,"mean":0.05984677273308569,"measured_model_count":56,"median":0.03060298315596087,"minimum":0.0014867736856534384,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06857131575950162,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002953237501739467,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0173841059602649,"pan_cancer_fraction":0.0173841059602649,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006622516556291391,"pan_cancer_fraction":0.006622516556291391,"threshold":0.8}],"gene_effect_mean":0.00929622077226909,"gene_effect_median":-0.001507960338499259},"dependency_probability_context_minus_non_context_median":-0.002997141357305111,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.018229166666666668,"non_context_fraction":0.018229166666666668,"threshold":0.5},{"context_fraction":0.0,"difference":-0.006944444444444444,"non_context_fraction":0.006944444444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.009748120393143302,"gene_effect_context_minus_non_context_median":-0.0015774451250942373} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 23 +- **Dependency-aware candidate rank:** 24 +- **Rank delta:** 1 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_3aa6751335d21b56b138308a5905ac03f3165d6ce2b7ae7e136e724f715ae929` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TERT|entrez:7015` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TET1.md b/examples/target_cards/depmap_26q1/TET1.md new file mode 100644 index 0000000..6be33a0 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TET1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TET1 + +## Target identity + +- **Target symbol:** TET1 +- **Target name:** tet methylcytosine dioxygenase 1 +- **Open Targets melanoma score:** 0.525 +- **Open Targets baseline rank:** 194 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 196 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 196 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 196 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.525) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TET1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TET1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06612237325348896,"interquartile_range":0.10021823049998557,"maximum":0.1271729541137778,"mean":-0.028190732169697717,"measured_model_count":56,"median":-0.01236085251979058,"minimum":-0.2695130876604978,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.034095857246496615,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.015077381903148862,"interquartile_range":0.022546163524319658,"maximum":0.14865571836631888,"mean":0.03450340317400059,"measured_model_count":56,"median":0.024035437041026612,"minimum":0.006922954810222002,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03762354542746852,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0007531276788584583,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.012800927998634417,"gene_effect_median":0.001906037661590601},"dependency_probability_context_minus_non_context_median":-0.000861527866092001,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.013423195331901396,"gene_effect_context_minus_non_context_median":0.001906037661590601} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 196 +- **Dependency-aware candidate rank:** 196 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_b839bce56c8f1593e320c4d61e7f42609798cff76a042f0f9ef6d3a6793420fa` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TET1|entrez:80312` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TET2.md b/examples/target_cards/depmap_26q1/TET2.md new file mode 100644 index 0000000..6f0d51d --- /dev/null +++ b/examples/target_cards/depmap_26q1/TET2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TET2 + +## Target identity + +- **Target symbol:** TET2 +- **Target name:** tet methylcytosine dioxygenase 2 +- **Open Targets melanoma score:** 0.646 +- **Open Targets baseline rank:** 33 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 40 | not prioritized | -7 | +| Resistance biomarker | 0.000 | 42 | not prioritized | -9 | +| Tumor-intrinsic / small molecule | 0.000 | 35 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.646) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TET2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TET2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.020242220098773266,"interquartile_range":0.13103610160268922,"maximum":0.3622793156577621,"mean":0.08204156574215123,"measured_model_count":56,"median":0.08659371212470038,"minimum":-0.1670518659975791,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1512783217014625,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005266320111456892,"interquartile_range":0.015500246077887905,"maximum":0.11891323222815336,"mean":0.015839052780095838,"measured_model_count":56,"median":0.007554157730363114,"minimum":0.001314782273029547,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.020766566189344797,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0004343403727579114,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.029308441537724106,"gene_effect_median":-0.025866293969080884},"dependency_probability_context_minus_non_context_median":-0.0004403789008672228,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.0307331574458079,"gene_effect_context_minus_non_context_median":-0.02655563898434228} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 40 +- **Dependency-aware candidate rank:** 40 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_eda1d97542f3455aedc7d5de5e9ae3b276141439c8e6539ccf897be73a44dfe4` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TET2|entrez:54790` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TFE3.md b/examples/target_cards/depmap_26q1/TFE3.md new file mode 100644 index 0000000..0ab3bdd --- /dev/null +++ b/examples/target_cards/depmap_26q1/TFE3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TFE3 + +## Target identity + +- **Target symbol:** TFE3 +- **Target name:** transcription factor binding to IGHM enhancer 3 +- **Open Targets melanoma score:** 0.523 +- **Open Targets baseline rank:** 198 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 200 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 200 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 200 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.523) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TFE3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TFE3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.049611378294050275,"interquartile_range":0.12705938681379497,"maximum":0.3972896850342244,"mean":0.01444431817727483,"measured_model_count":56,"median":-0.010454951169714191,"minimum":-0.29319215632904333,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.07744800851974469,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008716575061100169,"interquartile_range":0.026418028876411564,"maximum":0.18711563988246177,"mean":0.032323017648411424,"measured_model_count":56,"median":0.020410044427780348,"minimum":0.0002168070410135217,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.035134603937511735,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0042392718543003485,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.022922720848554935,"gene_effect_median":-0.042734776296091556},"dependency_probability_context_minus_non_context_median":0.004332365482609325,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.024037019778693013,"gene_effect_context_minus_non_context_median":-0.04341747415317606} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 200 +- **Dependency-aware candidate rank:** 200 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_43d8509a90cd46513ae1ff1da427d3b3d581de5e607771511933d66256fcd4f3` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TFE3|entrez:7030` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TFEB.md b/examples/target_cards/depmap_26q1/TFEB.md new file mode 100644 index 0000000..928ea77 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TFEB.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TFEB + +## Target identity + +- **Target symbol:** TFEB +- **Target name:** transcription factor EB +- **Open Targets melanoma score:** 0.531 +- **Open Targets baseline rank:** 186 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 188 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 189 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 188 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.531) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TFEB lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TFEB in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.0555191255330701,"interquartile_range":0.11292522004414328,"maximum":0.28573843056988407,"mean":0.003798524527747693,"measured_model_count":56,"median":0.0019224156039644225,"minimum":-0.22832367937072187,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.05740609451107318,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.011692148037405516,"interquartile_range":0.01921849388295361,"maximum":0.14720540313854205,"mean":0.026132526521341532,"measured_model_count":56,"median":0.01872188394700413,"minimum":0.0016405899904093201,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.030910641920359125,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002390505293227832,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.0015270513008616253,"gene_effect_median":0.0004748142292487288},"dependency_probability_context_minus_non_context_median":-0.0025091977326434783,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.001601282961320164,"gene_effect_context_minus_non_context_median":0.0004748142292487288} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 188 +- **Dependency-aware candidate rank:** 188 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_302cc54066a963b906ae4297371c1db7ef85e9fbfa9583dbe0ae8f67ec97ef77` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TFEB|entrez:7942` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TGFB1.md b/examples/target_cards/depmap_26q1/TGFB1.md new file mode 100644 index 0000000..5888031 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TGFB1.md @@ -0,0 +1,73 @@ +# TGFB1 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.1175744957723274,"interquartile_range":0.14613260242689258,"maximum":0.20122114815229164,"mean":-0.053333625094820716,"measured_model_count":56,"median":-0.0584569922925765,"minimum":-0.33194533256770453,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02855810665456519,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.013271787489163883,"interquartile_range":0.05501703382036138,"maximum":0.29440262801615275,"mean":0.0509541191786031,"measured_model_count":56,"median":0.03879322257892474,"minimum":0.004071154988135978,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06828882130952527,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.002229677539982232,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.0062627310967641875,"gene_effect_median":0.0028936828192190275},"dependency_probability_context_minus_non_context_median":0.002268981663492299,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0065671694139679965,"gene_effect_context_minus_non_context_median":0.0032393776818710265} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":40.74074074074074} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_06ec3bccac84ba7114eb5d4bf7c85ada91f20a7d62f3b59bbbff7cf322523168` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TGFB1|entrez:7040` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TGFBR1.md b/examples/target_cards/depmap_26q1/TGFBR1.md new file mode 100644 index 0000000..d6c7628 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TGFBR1.md @@ -0,0 +1,73 @@ +# TGFBR1 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.11823496925689045,"interquartile_range":0.1815436279172879,"maximum":0.43900246007390836,"mean":-0.06367073288882538,"measured_model_count":56,"median":-0.04561856834087192,"minimum":-1.1646984150993804,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06330865866039743,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.009869685591532288,"interquartile_range":0.05375446023576694,"maximum":0.9941992212349525,"mean":0.0798662849461864,"measured_model_count":56,"median":0.03221306181112013,"minimum":0.0002895613022257384,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06362414582729922,"threshold_fractions":[{"denominator":56,"fraction":0.03571428571428571,"numerator":2,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.027031213832151124,"dependency_probability_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.04623935666982025,"pan_cancer_fraction":0.08195364238410596,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.0152554399243141,"pan_cancer_fraction":0.033112582781456956,"threshold":0.8}],"gene_effect_mean":0.07847455721250848,"gene_effect_median":0.07036460916164552},"dependency_probability_context_minus_non_context_median":-0.029586105478545344,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.03571428571428571,"difference":-0.04848710317460318,"non_context_fraction":0.0842013888888889,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.015997023809523808,"non_context_fraction":0.033854166666666664,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.08228929263256096,"gene_effect_context_minus_non_context_median":0.07618939226126986} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":11.11111111111111} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_8024c3f1a166237bfd323397a878e35e9a91c24effde75af6a2a2b954766b2da` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TGFBR1|entrez:7046` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TIGIT.md b/examples/target_cards/depmap_26q1/TIGIT.md new file mode 100644 index 0000000..4512c50 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TIGIT.md @@ -0,0 +1,73 @@ +# TIGIT — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.09649098266140216,"interquartile_range":0.14024504818016426,"maximum":0.20955328804252174,"mean":-0.038102640455839755,"measured_model_count":56,"median":-0.026380581032389563,"minimum":-0.31063674659862406,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.043754065518762084,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.014662390053882784,"interquartile_range":0.035014807249186236,"maximum":0.22730028300055188,"mean":0.04368399569486412,"measured_model_count":56,"median":0.029299535174605706,"minimum":0.004326948526831013,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.04967719730306902,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.010697027991600258,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.030104735789959987,"gene_effect_median":0.042814784000523104},"dependency_probability_context_minus_non_context_median":-0.011414511459108365,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.03156816044641642,"gene_effect_context_minus_non_context_median":0.04473808091663155} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ec597885a6d540cbe296f1d7dcd3082bca9b8b936454f6f0597a4c21bbd573f2` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TIGIT|entrez:201633` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TMEM127.md b/examples/target_cards/depmap_26q1/TMEM127.md new file mode 100644 index 0000000..b56eb1a --- /dev/null +++ b/examples/target_cards/depmap_26q1/TMEM127.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TMEM127 + +## Target identity + +- **Target symbol:** TMEM127 +- **Target name:** transmembrane protein 127 +- **Open Targets melanoma score:** 0.511 +- **Open Targets baseline rank:** 236 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 238 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 238 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 238 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.511) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TMEM127 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TMEM127 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.37160855924898195,"interquartile_range":0.23945586380532383,"maximum":0.04819261286756693,"mean":-0.2743793036390408,"measured_model_count":56,"median":-0.2801840245311775,"minimum":-0.7302462912517111,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.13215269544365812,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.07290625944096693,"interquartile_range":0.35628977617921886,"maximum":0.8298694277716979,"mean":0.2563707669744083,"measured_model_count":56,"median":0.1948213468608736,"minimum":0.006835996438229038,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.4291960356201858,"threshold_fractions":[{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.007863065272489977,"dependency_probability_threshold_fractions":[{"context_fraction":0.17857142857142858,"difference":0.02045884578997162,"pan_cancer_fraction":0.15811258278145696,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.014427625354777672,"pan_cancer_fraction":0.03228476821192053,"threshold":0.8}],"gene_effect_mean":0.011635002407191897,"gene_effect_median":-0.0037427060854459127},"dependency_probability_context_minus_non_context_median":-0.009398192269829686,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.17857142857142858,"difference":0.021453373015873023,"non_context_fraction":0.15711805555555555,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.015128968253968256,"non_context_fraction":0.03298611111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01220059280198632,"gene_effect_context_minus_non_context_median":-0.004013585868380187} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 238 +- **Dependency-aware candidate rank:** 238 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_891aad5d1c4c9796b1c683e9cdc71c0c62a01f01c5069234267d3cea760bd5bf` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TMEM127|entrez:55654` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TNFRSF17.md b/examples/target_cards/depmap_26q1/TNFRSF17.md new file mode 100644 index 0000000..71ddddf --- /dev/null +++ b/examples/target_cards/depmap_26q1/TNFRSF17.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TNFRSF17 + +## Target identity + +- **Target symbol:** TNFRSF17 +- **Target name:** TNF receptor superfamily member 17 +- **Open Targets melanoma score:** 0.461 +- **Open Targets baseline rank:** 294 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 294 | not prioritized | 0 | +| Resistance biomarker | 0.000 | 294 | not prioritized | 0 | +| Tumor-intrinsic / small molecule | 0.000 | 294 | not prioritized | 0 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.461) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TNFRSF17 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TNFRSF17 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.10457536925669791,"interquartile_range":0.07142883580734052,"maximum":0.10918749680547649,"mean":-0.06992867394566103,"measured_model_count":56,"median":-0.07182926242556906,"minimum":-0.24504065716705284,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.0331465334493574,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.023074013879230557,"interquartile_range":0.0433904521116308,"maximum":0.1443957018357807,"mean":0.04704715320781859,"measured_model_count":56,"median":0.04088511534774647,"minimum":0.0063179500583258425,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.06646446599086135,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0049121025417101435,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008278145695364238,"pan_cancer_fraction":0.0008278145695364238,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.011945886868925046,"gene_effect_median":0.011137176340701466},"dependency_probability_context_minus_non_context_median":-0.0054131304480627696,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0008680555555555555,"non_context_fraction":0.0008680555555555555,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.012526589702831076,"gene_effect_context_minus_non_context_median":0.01164453388063047} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 294 +- **Dependency-aware candidate rank:** 294 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_72a0b0fce8512a7e516b1d482dcfb7f4d06530bf9564bca9ec3a211a0dd21759` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TNFRSF17|entrez:608` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TNFRSF18.md b/examples/target_cards/depmap_26q1/TNFRSF18.md new file mode 100644 index 0000000..ac93820 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TNFRSF18.md @@ -0,0 +1,73 @@ +# TNFRSF18 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.07992287378746069,"interquartile_range":0.16347160736788924,"maximum":0.32511428764823874,"mean":0.005618184042927659,"measured_model_count":56,"median":0.0031678861143592326,"minimum":-0.21018912008582508,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.08354873358042854,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0081397024736693,"interquartile_range":0.031395612021018315,"maximum":0.15023873693250508,"mean":0.03150136361917189,"measured_model_count":56,"median":0.020690473212946793,"minimum":0.0011876348486895474,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.03953531449468761,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0005077224690275967,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.0011663910963865837,"gene_effect_median":0.0003505570529605071},"dependency_probability_context_minus_non_context_median":0.0005077224690275967,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0012230906635720294,"gene_effect_context_minus_non_context_median":0.00040631170298858175} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":51.851851851851855} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_a1f21dfb69f2e55b310fe38e88f66b09c1adcbd74d74b7f83987f4e78ead1d09` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TNFRSF18|entrez:8784` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TP53.md b/examples/target_cards/depmap_26q1/TP53.md new file mode 100644 index 0000000..6ce66e7 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TP53.md @@ -0,0 +1,127 @@ +# Target hypothesis card: TP53 + +## Target identity + +- **Target symbol:** TP53 +- **Target name:** tumor protein p53 +- **Open Targets melanoma score:** 0.699 +- **Open Targets baseline rank:** 20 + +## Stable TargetIntel-IO classification + +- **Role classification:** tumor-intrinsic driver / poor direct therapeutic target +- **Role confidence:** high +- **Therapeutic direction:** avoid as direct target / use as biomarker or pathway context +- **Best modality:** biomarker / pathway context only +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 27 | not prioritized | -7 | +| Resistance biomarker | 0.111 | 19 | low | 1 | +| Tumor-intrinsic / small molecule | 0.000 | 40 | not prioritized | -20 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.699) +- Stable role classifier confidence is high + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Flagged as poor direct therapeutic target for this MVP +- Role classifier indicates biological relevance but poor direct targetability +- Tumor-intrinsic role and low antibody fit argue against antibody/IO-combination prioritization + +## Confidence and uncertainty + +- **Confidence level:** medium confidence +- **Data completeness score:** 0.889 +- **Contradiction score:** 0.570 +- **Main limitation:** Poor direct therapeutic target despite biological relevance +- **Uncertainty reason:** Missing evidence fields: resistance_axis | No curated anti-PD-1 resistance-axis mapping | Moderate contradiction score indicates caution is needed | Main limitation: Poor direct therapeutic target despite biological relevance +- **Deprioritization reason:** TP53 should be deprioritized as a direct therapeutic target in this MVP, but may remain useful as biomarker or pathway context. + +## Recommended next validation experiment + +- **Validation category:** tumor-intrinsic functional validation +- **Next experiment:** Evaluate whether perturbing TP53 alters melanoma cell viability, pathway activity, or immune-sensitivity in tumor-cell intrinsic assays. +- **Rationale:** This would test whether the candidate is a functional tumor-intrinsic dependency or pathway intervention point. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.2682694657614673,"interquartile_range":0.9489021294915423,"maximum":2.138262318199002,"mean":0.8412020305059892,"measured_model_count":56,"median":0.8202592324433257,"minimum":-0.056749573342901705,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.2171715952530096,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0,"interquartile_range":0.0022901272198506146,"maximum":0.0445887680510194,"mean":0.0038902041225716394,"measured_model_count":56,"median":2.371112152923413e-07,"minimum":0.0,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.0022901272198506146,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.002697179320060296,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.8}],"gene_effect_mean":0.41701743563053467,"gene_effect_median":0.5818272714545053},"dependency_probability_context_minus_non_context_median":-0.002942185984413948,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.43728911652924124,"gene_effect_context_minus_non_context_median":0.592868277866274} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 27 +- **Dependency-aware candidate rank:** 27 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_ce64666108a5b359fbafb7a0ba19d80daa01b7fdb39a82f26790a367a87770c6` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TP53|entrez:7157` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TP63.md b/examples/target_cards/depmap_26q1/TP63.md new file mode 100644 index 0000000..fd27d7c --- /dev/null +++ b/examples/target_cards/depmap_26q1/TP63.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TP63 + +## Target identity + +- **Target symbol:** TP63 +- **Target name:** tumor protein p63 +- **Open Targets melanoma score:** 0.596 +- **Open Targets baseline rank:** 73 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 77 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 79 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 77 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.596) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TP63 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TP63 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.03646717175085289,"interquartile_range":0.15602502361875212,"maximum":0.26270167319502213,"mean":0.02883004458571577,"measured_model_count":56,"median":0.06069628975320457,"minimum":-1.13379244109757,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11955785186789922,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0056286828889941356,"interquartile_range":0.02006209381979438,"maximum":0.996906606222216,"mean":0.043125430114191884,"measured_model_count":56,"median":0.012420727182457592,"minimum":0.0009590426965118661,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.025690776708788516,"threshold_fractions":[{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.011161042797875489,"dependency_probability_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.0740302743614002,"pan_cancer_fraction":0.09188741721854304,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.0533349101229896,"pan_cancer_fraction":0.07119205298013245,"threshold":0.8}],"gene_effect_mean":0.11323820110222163,"gene_effect_median":0.06431602331215681},"dependency_probability_context_minus_non_context_median":-0.011539366478665646,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.017857142857142856,"difference":-0.07762896825396826,"non_context_fraction":0.0954861111111111,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":-0.05592757936507937,"non_context_fraction":0.07378472222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.11874283587802412,"gene_effect_context_minus_non_context_median":0.06721157973110539} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":7.407407407407407} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 77 +- **Dependency-aware candidate rank:** 77 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_47aea6ee2f36661129a2dcd3767534849b7aafa25845e17a1f7eb00d41fd01d1` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TP63|entrez:8626` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TRAF7.md b/examples/target_cards/depmap_26q1/TRAF7.md new file mode 100644 index 0000000..6ff87df --- /dev/null +++ b/examples/target_cards/depmap_26q1/TRAF7.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TRAF7 + +## Target identity + +- **Target symbol:** TRAF7 +- **Target name:** TNF receptor associated factor 7 +- **Open Targets melanoma score:** 0.523 +- **Open Targets baseline rank:** 199 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 201 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 201 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 201 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.523) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TRAF7 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TRAF7 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.2406753121206499,"interquartile_range":0.24695097977219208,"maximum":0.3790647504468809,"mean":-0.12737792628681918,"measured_model_count":56,"median":-0.13475684387968312,"minimum":-0.610764948450708,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.006275667651542173,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.015945069753414774,"interquartile_range":0.16421762374968268,"maximum":0.8396091166189825,"mean":0.14316015942576582,"measured_model_count":56,"median":0.06819388689452299,"minimum":0.0004979956302897705,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.18016269350309747,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.017857142857142856,"numerator":1,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0009438003718074128,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.004375591296121098,"pan_cancer_fraction":0.057947019867549666,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.00378429517502365,"pan_cancer_fraction":0.014072847682119206,"threshold":0.8}],"gene_effect_mean":0.004084917885226469,"gene_effect_median":-0.0051896892898691815},"dependency_probability_context_minus_non_context_median":-0.0009438003718074128,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.004588293650793655,"non_context_fraction":0.058159722222222224,"threshold":0.5},{"context_fraction":0.017857142857142856,"difference":0.003968253968253968,"non_context_fraction":0.013888888888888888,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.004283490282425029,"gene_effect_context_minus_non_context_median":-0.005303738769082134} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 201 +- **Dependency-aware candidate rank:** 201 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_39469d5c3ff744db75b7677036b82a2b6052906d5713381b97c29825518058ec` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TRAF7|entrez:84231` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TREM2.md b/examples/target_cards/depmap_26q1/TREM2.md new file mode 100644 index 0000000..192d5c5 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TREM2.md @@ -0,0 +1,73 @@ +# TREM2 — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.0443206760018002,"interquartile_range":0.17039455367149228,"maximum":0.21602878466395123,"mean":0.03343137007746267,"measured_model_count":56,"median":0.0323268773346124,"minimum":-0.2109254937822177,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12607387766969208,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.006309502008753942,"interquartile_range":0.021860319009730143,"maximum":0.1244326991346321,"mean":0.023524014701307532,"measured_model_count":56,"median":0.014501080563188398,"minimum":0.0027434337345621554,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.028169821018484087,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.0037581817852199995,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0024834437086092716,"pan_cancer_fraction":0.0024834437086092716,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.01495476439173983,"gene_effect_median":0.015141526883319961},"dependency_probability_context_minus_non_context_median":-0.0037943511007953457,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0026041666666666665,"non_context_fraction":0.0026041666666666665,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.015681732105227185,"gene_effect_context_minus_non_context_median":0.01669816595616809} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":29.62962962962963} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_37329707c51acc74ca2cb22d449272702bc6744a5d56447d033a49e625ef62e1` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TREM2|entrez:54209` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TRRAP.md b/examples/target_cards/depmap_26q1/TRRAP.md new file mode 100644 index 0000000..040f186 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TRRAP.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TRRAP + +## Target identity + +- **Target symbol:** TRRAP +- **Target name:** transformation/transcription domain associated protein +- **Open Targets melanoma score:** 0.626 +- **Open Targets baseline rank:** 47 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 53 | not prioritized | -6 | +| Resistance biomarker | 0.000 | 55 | not prioritized | -8 | +| Tumor-intrinsic / small molecule | 0.000 | 53 | not prioritized | -6 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.626) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TRRAP lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TRRAP in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-1.5213804808497076,"interquartile_range":0.433843564982187,"maximum":-0.6227212037899151,"mean":-1.3167452715650814,"measured_model_count":56,"median":-1.2709263893882927,"minimum":-2.0119956971319883,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.0875369158675205,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9777798803483504,"interquartile_range":0.022107860279671154,"maximum":1.0,"mean":0.9787434420409532,"measured_model_count":56,"median":0.9937763894442102,"minimum":0.7036541177148524,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.9998877406280215,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":0.9821428571428571,"numerator":55,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.005300264985414804,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.004966887417218513,"pan_cancer_fraction":0.9950331125827815,"threshold":0.5},{"context_fraction":0.9821428571428571,"difference":0.0003547776726584573,"pan_cancer_fraction":0.9817880794701986,"threshold":0.8}],"gene_effect_mean":0.17644201944194293,"gene_effect_median":0.2275108688164056},"dependency_probability_context_minus_non_context_median":-0.005395260689111003,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.00520833333333337,"non_context_fraction":0.9947916666666666,"threshold":0.5},{"context_fraction":0.9821428571428571,"difference":0.00037202380952372494,"non_context_fraction":0.9817708333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.18501906205370444,"gene_effect_context_minus_non_context_median":0.23667928859180454} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":14.814814814814815} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 53 +- **Dependency-aware candidate rank:** 53 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_6fe462e663a1c97bc5ad3f62e38d00121118446b91f3aaf2ff8a0727e32a4cc7` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TRRAP|entrez:8295` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TSC1.md b/examples/target_cards/depmap_26q1/TSC1.md new file mode 100644 index 0000000..699ed50 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TSC1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TSC1 + +## Target identity + +- **Target symbol:** TSC1 +- **Target name:** TSC complex subunit 1 +- **Open Targets melanoma score:** 0.588 +- **Open Targets baseline rank:** 86 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 89 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 91 | not prioritized | -5 | +| Tumor-intrinsic / small molecule | 0.000 | 89 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.588) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TSC1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TSC1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.3016134218269153,"interquartile_range":0.4540279484323619,"maximum":0.7560681310029174,"mean":-0.05250989686051594,"measured_model_count":56,"median":-0.06139145221472085,"minimum":-0.9355770319117922,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.15241452660544658,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005114952756170495,"interquartile_range":0.2066037360107815,"maximum":0.9475024496853242,"mean":0.17255563233916282,"measured_model_count":56,"median":0.036748465525459184,"minimum":1.463315655819427e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.211718688766952,"threshold_fractions":[{"denominator":56,"fraction":0.16071428571428573,"numerator":9,"threshold":0.5},{"denominator":56,"fraction":0.07142857142857142,"numerator":4,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.020753081774940913,"dependency_probability_threshold_fractions":[{"context_fraction":0.16071428571428573,"difference":0.05392620624408705,"pan_cancer_fraction":0.10678807947019868,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":0.024243140964995268,"pan_cancer_fraction":0.04718543046357616,"threshold":0.8}],"gene_effect_mean":-0.08049961561053362,"gene_effect_median":-0.09133038858322812},"dependency_probability_context_minus_non_context_median":0.02101526595606716,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.16071428571428573,"difference":0.056547619047619055,"non_context_fraction":0.10416666666666667,"threshold":0.5},{"context_fraction":0.07142857142857142,"difference":0.025421626984126977,"non_context_fraction":0.04600694444444445,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.08441279136937907,"gene_effect_context_minus_non_context_median":-0.09589486022254615} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 89 +- **Dependency-aware candidate rank:** 89 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_8186ba8145eaae00bb79f7de7834c7e52f0018cae0aa360cd10997f663600067` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TSC1|entrez:7248` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TSC2.md b/examples/target_cards/depmap_26q1/TSC2.md new file mode 100644 index 0000000..48a74e2 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TSC2.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TSC2 + +## Target identity + +- **Target symbol:** TSC2 +- **Target name:** TSC complex subunit 2 +- **Open Targets melanoma score:** 0.568 +- **Open Targets baseline rank:** 121 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 123 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 124 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 123 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.568) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TSC2 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TSC2 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.48178270738847034,"interquartile_range":0.6094882759655369,"maximum":0.7960520265311837,"mean":-0.17905815724769766,"measured_model_count":56,"median":-0.19336827495763223,"minimum":-1.1623050845253171,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.12770556857706658,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005510173816997374,"interquartile_range":0.529793110570655,"maximum":0.9825524213104214,"mean":0.29430495118778816,"measured_model_count":56,"median":0.11191983755845783,"minimum":1.2968376951898574e-06,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.5353032843876524,"threshold_fractions":[{"denominator":56,"fraction":0.2857142857142857,"numerator":16,"threshold":0.5},{"denominator":56,"fraction":0.17857142857142858,"numerator":10,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.07296393578600509,"dependency_probability_threshold_fractions":[{"context_fraction":0.2857142857142857,"difference":0.08289971617786185,"pan_cancer_fraction":0.20281456953642385,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":0.06681646168401136,"pan_cancer_fraction":0.11175496688741722,"threshold":0.8}],"gene_effect_mean":-0.08411866484026737,"gene_effect_median":-0.13205223150234915},"dependency_probability_context_minus_non_context_median":0.07391335133157799,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.2857142857142857,"difference":0.08692956349206349,"non_context_fraction":0.1987847222222222,"threshold":0.5},{"context_fraction":0.17857142857142858,"difference":0.07006448412698413,"non_context_fraction":0.10850694444444445,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.08820776660333601,"gene_effect_context_minus_non_context_median":-0.13273442546728376} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":74.07407407407408} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 123 +- **Dependency-aware candidate rank:** 123 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_02597d1fe00363ec395bba1396c2b693627894b85a2735f9a9b0320f57a1d507` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TSC2|entrez:7249` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TYR.md b/examples/target_cards/depmap_26q1/TYR.md new file mode 100644 index 0000000..7131f39 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TYR.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TYR + +## Target identity + +- **Target symbol:** TYR +- **Target name:** tyrosinase +- **Open Targets melanoma score:** 0.585 +- **Open Targets baseline rank:** 92 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 95 | not prioritized | -3 | +| Resistance biomarker | 0.000 | 97 | not prioritized | -5 | +| Tumor-intrinsic / small molecule | 0.000 | 95 | not prioritized | -3 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.585) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TYR lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TYR in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.021924422131844194,"interquartile_range":0.13036313008930414,"maximum":0.22068382718892765,"mean":0.03780463155728201,"measured_model_count":56,"median":0.039761465584603584,"minimum":-0.16487265242462967,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10843870795745994,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.00790018032460166,"interquartile_range":0.016458370447756117,"maximum":0.12554764195984902,"mean":0.019476503614389358,"measured_model_count":56,"median":0.013953535396493747,"minimum":0.00202859216667188,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.024358550772357775,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.001972344387758205,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.006265099876650047,"gene_effect_median":0.005927198513196147},"dependency_probability_context_minus_non_context_median":-0.002016909180990324,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.006569653342876118,"gene_effect_context_minus_non_context_median":0.00633350963583576} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 95 +- **Dependency-aware candidate rank:** 95 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_b6011643cf8b212a56809e5e47933e153af759822d9c476843e6d11de86f8f64` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TYR|entrez:7299` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/TYRP1.md b/examples/target_cards/depmap_26q1/TYRP1.md new file mode 100644 index 0000000..1442d36 --- /dev/null +++ b/examples/target_cards/depmap_26q1/TYRP1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: TYRP1 + +## Target identity + +- **Target symbol:** TYRP1 +- **Target name:** tyrosinase related protein 1 +- **Open Targets melanoma score:** 0.495 +- **Open Targets baseline rank:** 259 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 261 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 261 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 261 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.495) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** TYRP1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for TYRP1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.10410635283115738,"interquartile_range":0.15932084168058958,"maximum":0.23571165368114302,"mean":-0.014436755487099202,"measured_model_count":56,"median":-0.00467660277186081,"minimum":-0.285963111504857,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.055214488849432204,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.011364526712981583,"interquartile_range":0.03289509253254978,"maximum":0.19098949806792395,"mean":0.03524535298675518,"measured_model_count":56,"median":0.02110733051641108,"minimum":0.0022871834283302536,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.044259619245531366,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.004120654826854978,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.8}],"gene_effect_mean":0.011142687770745322,"gene_effect_median":0.012642765427333967},"dependency_probability_context_minus_non_context_median":-0.00438180888119355,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.5},{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.011684346204045388,"gene_effect_context_minus_non_context_median":0.013066480871946558} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":33.333333333333336} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 261 +- **Dependency-aware candidate rank:** 261 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_d4210a94654b7c77222a0cb56c441b7ed31ec0ce03ed3ccea0f732ae45bf3867` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:TYRP1|entrez:7306` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/U2AF1.md b/examples/target_cards/depmap_26q1/U2AF1.md new file mode 100644 index 0000000..3585e58 --- /dev/null +++ b/examples/target_cards/depmap_26q1/U2AF1.md @@ -0,0 +1,124 @@ +# Target hypothesis card: U2AF1 + +## Target identity + +- **Target symbol:** U2AF1 +- **Target name:** U2 small nuclear RNA auxiliary factor 1 +- **Open Targets melanoma score:** 0.522 +- **Open Targets baseline rank:** 203 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 205 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 205 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 205 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.522) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** U2AF1 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for U2AF1 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-2.2850637997149565,"interquartile_range":0.5402155616805826,"maximum":-1.3937878711893064,"mean":-2.003858590452997,"measured_model_count":56,"median":-1.9445118925982248,"minimum":-2.7346918251771903,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-1.744848238034374,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.9999988989874314,"interquartile_range":1.1010125685606553e-06,"maximum":1.0,"mean":0.9997710798620709,"measured_model_count":56,"median":1.0,"minimum":0.9927101937690168,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":1.0,"threshold_fractions":[{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.5},{"denominator":56,"fraction":1.0,"numerator":56,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0,"dependency_probability_threshold_fractions":[{"context_fraction":1.0,"difference":0.0016556291390728006,"pan_cancer_fraction":0.9983443708609272,"threshold":0.5},{"context_fraction":1.0,"difference":0.002483443708609312,"pan_cancer_fraction":0.9975165562913907,"threshold":0.8}],"gene_effect_mean":-0.13232901178484746,"gene_effect_median":-0.07668830762275491},"dependency_probability_context_minus_non_context_median":0.0,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":1.0,"difference":0.0017361111111111605,"non_context_fraction":0.9982638888888888,"threshold":0.5},{"context_fraction":1.0,"difference":0.0026041666666666297,"non_context_fraction":0.9973958333333334,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.13876167207994716,"gene_effect_context_minus_non_context_median":-0.08078838931494281} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":62.96296296296296} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 205 +- **Dependency-aware candidate rank:** 205 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_f65219e78ccc3654795107e05e95ed5ef5276d5266ff9e7c0166a8cddd27272f` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:U2AF1|entrez:7307` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/UBR5.md b/examples/target_cards/depmap_26q1/UBR5.md new file mode 100644 index 0000000..e9a6ddc --- /dev/null +++ b/examples/target_cards/depmap_26q1/UBR5.md @@ -0,0 +1,124 @@ +# Target hypothesis card: UBR5 + +## Target identity + +- **Target symbol:** UBR5 +- **Target name:** ubiquitin protein ligase E3 component n-recognin 5 +- **Open Targets melanoma score:** 0.594 +- **Open Targets baseline rank:** 76 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 80 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 82 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 80 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.594) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** UBR5 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for UBR5 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.7334089926493355,"interquartile_range":0.45556632888926424,"maximum":0.3415255034442515,"mean":-0.4921227769355524,"measured_model_count":56,"median":-0.4989999347581911,"minimum":-1.5684017610891217,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.2778426637600712,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.1845620071921631,"interquartile_range":0.691845206624218,"maximum":0.9982874212452946,"mean":0.5183145222853321,"measured_model_count":56,"median":0.5029036917489552,"minimum":0.0005451520676103827,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.8764072138163811,"threshold_fractions":[{"denominator":56,"fraction":0.5,"numerator":28,"threshold":0.5},{"denominator":56,"fraction":0.3392857142857143,"numerator":19,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.11857267313761588,"dependency_probability_threshold_fractions":[{"context_fraction":0.5,"difference":-0.09105960264900659,"pan_cancer_fraction":0.5910596026490066,"threshold":0.5},{"context_fraction":0.3392857142857143,"difference":-0.018330179754020792,"pan_cancer_fraction":0.3576158940397351,"threshold":0.8}],"gene_effect_mean":0.06401024520393717,"gene_effect_median":0.04146862784647792},"dependency_probability_context_minus_non_context_median":-0.12431858237874993,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.5,"difference":-0.09548611111111116,"non_context_fraction":0.5954861111111112,"threshold":0.5},{"context_fraction":0.3392857142857143,"difference":-0.019221230158730118,"non_context_fraction":0.3585069444444444,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.06712185434579554,"gene_effect_context_minus_non_context_median":0.04706650397650519} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":55.55555555555556} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 80 +- **Dependency-aware candidate rank:** 80 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_608621e071a11b8810b4c0207cdc91ea7b76383f87b39ced69c1be2f0556bed4` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:UBR5|entrez:51366` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/USP6.md b/examples/target_cards/depmap_26q1/USP6.md new file mode 100644 index 0000000..edd5f1f --- /dev/null +++ b/examples/target_cards/depmap_26q1/USP6.md @@ -0,0 +1,124 @@ +# Target hypothesis card: USP6 + +## Target identity + +- **Target symbol:** USP6 +- **Target name:** ubiquitin specific peptidase 6 +- **Open Targets melanoma score:** 0.556 +- **Open Targets baseline rank:** 142 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 144 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 145 | not prioritized | -3 | +| Tumor-intrinsic / small molecule | 0.000 | 144 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.556) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** USP6 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for USP6 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.21946144443193774,"interquartile_range":0.1836133575142457,"maximum":0.09091474588958395,"mean":-0.13462308545365242,"measured_model_count":56,"median":-0.14083080016013066,"minimum":-0.4133470078215248,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.035848086917692035,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.03158062220146937,"interquartile_range":0.10676534490012221,"maximum":0.38024577182219427,"mean":0.09450311024282725,"measured_model_count":56,"median":0.07325111118993291,"minimum":0.007333353368402815,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.13834596710159158,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.029375594631216945,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.015728476821192054,"pan_cancer_fraction":0.015728476821192054,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":0.04882779069934445,"gene_effect_median":0.036166204101795135},"dependency_probability_context_minus_non_context_median":-0.03129187482786387,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.016493055555555556,"non_context_fraction":0.016493055555555556,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.0512013638583404,"gene_effect_context_minus_non_context_median":0.037751064245996974} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":18.51851851851852} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 144 +- **Dependency-aware candidate rank:** 144 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_6e1e2e52e7eaeae29cbc8eced7ced09a696665447972e1e42009ed141065ee37` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:USP6|entrez:9098` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/WAS.md b/examples/target_cards/depmap_26q1/WAS.md new file mode 100644 index 0000000..c76b410 --- /dev/null +++ b/examples/target_cards/depmap_26q1/WAS.md @@ -0,0 +1,124 @@ +# Target hypothesis card: WAS + +## Target identity + +- **Target symbol:** WAS +- **Target name:** WASP actin nucleation promoting factor +- **Open Targets melanoma score:** 0.517 +- **Open Targets baseline rank:** 222 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 224 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 224 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 224 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.517) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** WAS lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for WAS in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.0081124743479323,"interquartile_range":0.11365188739509363,"maximum":0.3717879401122316,"mean":0.05648455771783551,"measured_model_count":56,"median":0.04235581384965959,"minimum":-0.20632925372342162,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.10553941304716133,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.005830434234521276,"interquartile_range":0.016806642972809215,"maximum":0.10452119793228946,"mean":0.01779230363124099,"measured_model_count":56,"median":0.013549175642979312,"minimum":0.0005349464613209364,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.02263707720733049,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003858876726332755,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.009933774834437087,"pan_cancer_fraction":0.009933774834437087,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0041390728476821195,"pan_cancer_fraction":0.0041390728476821195,"threshold":0.8}],"gene_effect_mean":0.04386204430490018,"gene_effect_median":0.01871539447042147},"dependency_probability_context_minus_non_context_median":-0.0042032123239720935,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.010416666666666666,"non_context_fraction":0.010416666666666666,"threshold":0.5},{"context_fraction":0.0,"difference":-0.004340277777777778,"non_context_fraction":0.004340277777777778,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.04599422701416618,"gene_effect_context_minus_non_context_median":0.0199203440306107} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 224 +- **Dependency-aware candidate rank:** 224 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_faa220e36cb06c9b352cfb52bb2c5ab1e401752b580e66ae940d6c5bf4d4826e` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:WAS|entrez:7454` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/WNT5A.md b/examples/target_cards/depmap_26q1/WNT5A.md new file mode 100644 index 0000000..4e1139d --- /dev/null +++ b/examples/target_cards/depmap_26q1/WNT5A.md @@ -0,0 +1,73 @@ +# WNT5A — DepMap research-preview discovery identity + +This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline. + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.013475623132929507,"interquartile_range":0.12987435128430827,"maximum":0.3150759319494393,"mean":0.053669849425937624,"measured_model_count":56,"median":0.058772730317348545,"minimum":-0.24052616114158287,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.11639872815137876,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.0056110526655506286,"interquartile_range":0.019919012256410858,"maximum":0.11933478473212114,"mean":0.01871307104063123,"measured_model_count":56,"median":0.01236916749744851,"minimum":0.0021382880799880946,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.025530064921961488,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":-0.003466261549901078,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":0.016387858683863096,"gene_effect_median":0.021945093816684393},"dependency_probability_context_minus_non_context_median":-0.0035947955386887165,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.01718449070321755,"gene_effect_context_minus_non_context_median":0.022721044347566006} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":22.22222222222222} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** not reported +- **Dependency-aware candidate rank:** not reported +- **Rank delta:** not reported +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_cc9af2f98c4153df180b2f00100fa8e0a4f8ecb1e4af8839de969f92569b35ce` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:WNT5A|entrez:7474` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/WRN.md b/examples/target_cards/depmap_26q1/WRN.md new file mode 100644 index 0000000..7c1fb02 --- /dev/null +++ b/examples/target_cards/depmap_26q1/WRN.md @@ -0,0 +1,124 @@ +# Target hypothesis card: WRN + +## Target identity + +- **Target symbol:** WRN +- **Target name:** WRN RecQ like helicase +- **Open Targets melanoma score:** 0.610 +- **Open Targets baseline rank:** 57 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 61 | not prioritized | -4 | +| Resistance biomarker | 0.000 | 63 | not prioritized | -6 | +| Tumor-intrinsic / small molecule | 0.000 | 61 | not prioritized | -4 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.610) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** WRN lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for WRN in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.22747322797558123,"interquartile_range":0.18738191531852705,"maximum":0.1869225639090439,"mean":-0.1472173168641097,"measured_model_count":56,"median":-0.1359431135451314,"minimum":-0.6702924398334323,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":-0.040091312657054186,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.029615962721536174,"interquartile_range":0.12028353472893429,"maximum":0.7328436063532079,"mean":0.1242273410614679,"measured_model_count":56,"median":0.06804582138278752,"minimum":0.005152580595719504,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.14989949745047046,"threshold_fractions":[{"denominator":56,"fraction":0.05357142857142857,"numerator":3,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0054367770673847265,"dependency_probability_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.022587511825922425,"pan_cancer_fraction":0.076158940397351,"threshold":0.5},{"context_fraction":0.0,"difference":-0.041390728476821195,"pan_cancer_fraction":0.041390728476821195,"threshold":0.8}],"gene_effect_mean":0.03292790495233883,"gene_effect_median":-0.014512486907057545},"dependency_probability_context_minus_non_context_median":0.005489758575097134,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.05357142857142857,"difference":-0.02368551587301588,"non_context_fraction":0.07725694444444445,"threshold":0.5},{"context_fraction":0.0,"difference":-0.043402777777777776,"non_context_fraction":0.043402777777777776,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":0.034528566998633076,"gene_effect_context_minus_non_context_median":-0.01488164753445749} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 61 +- **Dependency-aware candidate rank:** 61 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_8e773dfcde59398006dec33e5b5184ee4e178481e1a6bf2a2daee11deb4e83ae` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:WRN|entrez:7486` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ZBTB16.md b/examples/target_cards/depmap_26q1/ZBTB16.md new file mode 100644 index 0000000..a0729dc --- /dev/null +++ b/examples/target_cards/depmap_26q1/ZBTB16.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ZBTB16 + +## Target identity + +- **Target symbol:** ZBTB16 +- **Target name:** zinc finger and BTB domain containing 16 +- **Open Targets melanoma score:** 0.522 +- **Open Targets baseline rank:** 205 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 207 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 207 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 207 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.522) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ZBTB16 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ZBTB16 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.009823719243372997,"interquartile_range":0.16578865722223748,"maximum":0.41204654436023724,"mean":0.07249807663874529,"measured_model_count":56,"median":0.07415276241873536,"minimum":-0.30348607293974983,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.1559649379788645,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.004890986360055396,"interquartile_range":0.018207855814234508,"maximum":0.185233568494693,"mean":0.019665096749805024,"measured_model_count":56,"median":0.010731332181391433,"minimum":0.00039811689207587927,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.023098842174289903,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.0007056036329970497,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0033112582781456954,"pan_cancer_fraction":0.0033112582781456954,"threshold":0.5},{"context_fraction":0.0,"difference":-0.0016556291390728477,"pan_cancer_fraction":0.0016556291390728477,"threshold":0.8}],"gene_effect_mean":-0.010563662912873154,"gene_effect_median":-0.009279418078398133},"dependency_probability_context_minus_non_context_median":0.0007056036329970497,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.003472222222222222,"non_context_fraction":0.003472222222222222,"threshold":0.5},{"context_fraction":0.0,"difference":-0.001736111111111111,"non_context_fraction":0.001736111111111111,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.011077174304471166,"gene_effect_context_minus_non_context_median":-0.009864062164104292} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":59.25925925925926} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 207 +- **Dependency-aware candidate rank:** 207 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_95f575baecdd6225abecf6aa6c5ab61b12d58645750e27090582cebbf2c64358` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ZBTB16|entrez:7704` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ZFHX3.md b/examples/target_cards/depmap_26q1/ZFHX3.md new file mode 100644 index 0000000..9403d80 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ZFHX3.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ZFHX3 + +## Target identity + +- **Target symbol:** ZFHX3 +- **Target name:** zinc finger homeobox 3 +- **Open Targets melanoma score:** 0.521 +- **Open Targets baseline rank:** 208 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 210 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 210 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 210 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.521) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ZFHX3 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ZFHX3 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 55 +- **Available reference observations:** 1110 +- **Coverage fraction:** 0.9821428571428571 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":-0.06146208289047472,"interquartile_range":0.14758793421665212,"maximum":0.2881461102807952,"mean":0.007927014410996538,"measured_model_count":55,"median":0.007593842404380845,"minimum":-0.33029884415193866,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":0.08612585132617741,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.008564060822250814,"interquartile_range":0.02700284675819572,"maximum":0.23484293062520295,"mean":0.03819658296592888,"measured_model_count":55,"median":0.019485636278314837,"minimum":0.0010067610165416245,"missing_fraction":0.017857142857142856,"missing_model_count":1,"third_quartile":0.03556690758044653,"threshold_fractions":[{"denominator":55,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":55,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.004526778394754729,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0017167381974248926,"pan_cancer_fraction":0.0017167381974248926,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.029396869620069162,"gene_effect_median":-0.032940962307585524},"dependency_probability_context_minus_non_context_median":0.004707711822055958,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":-0.0018018018018018018,"non_context_fraction":0.0018018018018018018,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.03085347126791045,"gene_effect_context_minus_non_context_median":-0.03387072477789323} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":77.77777777777777} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 210 +- **Dependency-aware candidate rank:** 210 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_93922b07a6fc0f657cd41e36eccc7c393dcf72c6e91455b1ed87ac8e4ca265a5` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ZFHX3|entrez:463` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/examples/target_cards/depmap_26q1/ZNF331.md b/examples/target_cards/depmap_26q1/ZNF331.md new file mode 100644 index 0000000..492a2f5 --- /dev/null +++ b/examples/target_cards/depmap_26q1/ZNF331.md @@ -0,0 +1,124 @@ +# Target hypothesis card: ZNF331 + +## Target identity + +- **Target symbol:** ZNF331 +- **Target name:** zinc finger protein 331 +- **Open Targets melanoma score:** 0.508 +- **Open Targets baseline rank:** 244 + +## Stable TargetIntel-IO classification + +- **Role classification:** unclear / low-confidence candidate +- **Role confidence:** low +- **Therapeutic direction:** unclear +- **Best modality:** unclear +- **Resistance axis:** unmapped +- **Matched resistance programs:** not available + +## Therapeutic-intent rankings + +| Therapeutic intent | Score | Rank | Priority | Rank shift vs Open Targets | +| --- | ---: | ---: | --- | ---: | +| Antibody / IO-combination | 0.000 | 246 | not prioritized | -2 | +| Resistance biomarker | 0.000 | 246 | not prioritized | -2 | +| Tumor-intrinsic / small molecule | 0.000 | 246 | not prioritized | -2 | + +## Evidence for + +- Moderate Open Targets melanoma association score (0.508) + +## Evidence against / limitations + +- Not currently mapped to a curated anti-PD-1 resistance axis +- Stable role classifier confidence is low + +## Confidence and uncertainty + +- **Confidence level:** low confidence +- **Data completeness score:** 0.667 +- **Contradiction score:** 0.360 +- **Main limitation:** No curated anti-PD-1 resistance-axis mapping +- **Uncertainty reason:** Missing evidence fields: resistance_axis, therapeutic_direction, best_modality | No curated anti-PD-1 resistance-axis mapping | Low role-classifier confidence | Therapeutic modality fit is unclear | Main limitation: No curated anti-PD-1 resistance-axis mapping +- **Deprioritization reason:** ZNF331 lacks current curated anti-PD-1 resistance-axis support in TargetIntel-IO. + +## Recommended next validation experiment + +- **Validation category:** evidence-gathering +- **Next experiment:** Perform literature review and cohort-level expression analysis for ZNF331 in anti-PD-1-resistant melanoma. +- **Rationale:** The current evidence is insufficient for a confident therapeutic interpretation. + +## Interpretation note + +This card is generated by TargetIntel-IO as a transparent, rule-based target triage summary. It is intended for hypothesis generation and portfolio demonstration only. It does not represent clinical advice or validated therapeutic evidence. + + +## Functional dependency — DepMap Public 26Q1 + +### Coverage + +- **Profile available:** yes +- **Coverage status:** sufficient_complete_coverage +- **Total model count:** 2154 +- **Context model count:** 56 +- **Reference model count:** 2098 +- **Available context observations:** 56 +- **Available reference observations:** 1152 +- **Coverage fraction:** 1.0 +- **Missing-value state:** target_resolved_both_matrices +- **Unavailable reason:** not reported + +### Dependency profile + +- **Gene-effect summary:** {"available":true,"first_quartile":0.1254636788972895,"interquartile_range":0.14498040321724526,"maximum":0.7050101742014865,"mean":0.19150820508534952,"measured_model_count":56,"median":0.19280092244168862,"minimum":-0.15201787565274216,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.27044408211453475,"threshold_fractions":[],"total_model_count":56} +- **Dependency-probability summary:** {"available":true,"first_quartile":0.001704372331237138,"interquartile_range":0.005424707330500494,"maximum":0.10954958289983124,"mean":0.009442167813529304,"measured_model_count":56,"median":0.003587808287988493,"minimum":1.0645838207346946e-05,"missing_fraction":0.0,"missing_model_count":0,"third_quartile":0.007129079661737632,"threshold_fractions":[{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.5},{"denominator":56,"fraction":0.0,"numerator":0,"threshold":0.8}],"total_model_count":56} +- **Context-versus-reference comparison:** {"context_minus_pan_cancer":{"dependency_probability_median":0.000887099880134024,"dependency_probability_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"pan_cancer_fraction":0.0,"threshold":0.8}],"gene_effect_mean":-0.04234439864678727,"gene_effect_median":-0.04372457184518963},"dependency_probability_context_minus_non_context_median":0.0009410321401466981,"dependency_probability_context_minus_non_context_threshold_fractions":[{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.5},{"context_fraction":0.0,"difference":0.0,"non_context_fraction":0.0,"threshold":0.8}],"direction":"Negative gene-effect context-minus-reference values indicate stronger model dependency signal in the context group.","gene_effect_context_minus_non_context_mean":-0.04440280691433923,"gene_effect_context_minus_non_context_median":-0.045076343973518174} +- **Selectivity:** {"available":true,"direction":"100 means a stronger (more negative median gene-effect) context signal than most eligible lineages.","eligible_lineage_count":28,"value":81.48148148148148} +- **Dependency interpretation state:** valid + +### Integration + +- **Baseline rank:** 246 +- **Dependency-aware candidate rank:** 246 +- **Rank delta:** 0 +- **Rank-delta convention:** dependency-aware candidate rank minus baseline rank. +- **Negative rank delta:** movement toward a lower numerical rank. +- **Integration state:** blocked_insufficient_evidence +- **Baseline preserved:** yes +- **Production activation enabled:** disabled +- **Approved authorization emitted:** not emitted +- **Candidate activation readiness:** blocked +- **Human review required:** required + +### Release provenance + +- **Evidence ID:** `drep_b5f3ff40e6903a84cec95adb93e101202320c5ee12b31a232b62549d7b70917b` +- **Release identifier:** `DepMap_Public_26Q1` +- **Release manifest ID:** `dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1` +- **Configuration ID:** `v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6` +- **Scientific closure identity:** `v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4` +- **Context identity:** `melanoma_anti_pd1:v1` +- **Canonical gene identity:** `symbol:ZNF331|entrez:55422` +- **Contract format version:** `v1` +- **Portable source artifacts:** `candidate_overlay.tsv`, `selected_target_profiles.tsv` + +### Limitations + +- Acral and drug-adapted models are excluded from the primary profile and retained separately. +- Baseline: unchanged 300-target TargetIntel antibody-IO ranking. +- Benchmark canonical identities were reconciled against the DepMap Public 26Q1 gene index without changing benchmark membership. +- DepMap Public 26Q1 cell-line dependency evidence. +- Dependency is treated as explanatory evidence, not as clinical validation. +- Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion. +- Multi-axis annotations are represented as pipe-separated controlled resistance-axis values. +- No automatic target activation or release. +- No clinical anti-PD-1 response inference. +- Primary context contains 56 reviewed cutaneous melanoma cell-line models. +- Primary context: 56 reviewed cutaneous melanoma models. +- Thresholds were fixed before inspecting benchmark outcomes. +- Unmapped resistance-axis annotations are represented by the controlled value other_unresolved. +- DepMap cell-line dependency is not clinical anti-PD-1 response evidence. +- Absence of tumor-cell dependency does not invalidate an immune target. +- Broad dependency may reflect general essentiality. +- Cell lines do not reproduce the complete tumor microenvironment. +- Candidate activation requires explicit human review. diff --git a/pyproject.toml b/pyproject.toml index 6f9e388..b874004 100644 --- a/pyproject.toml +++ b/pyproject.toml @@ -8,7 +8,7 @@ build-backend = "setuptools.build_meta" [project] name = "targetintel-io" -version = "0.2.0" +version = "0.5.0" description = "Explainable therapeutic-intent-aware target triage for anti-PD-1-resistant melanoma" readme = "README.md" requires-python = ">=3.10" diff --git a/scripts/13_publish_depmap_v050.py b/scripts/13_publish_depmap_v050.py new file mode 100644 index 0000000..30448c4 --- /dev/null +++ b/scripts/13_publish_depmap_v050.py @@ -0,0 +1,140 @@ +#!/usr/bin/env python3 +"""Publish a sanitized, portable DepMap Public 26Q1 report bundle offline.""" +from __future__ import annotations + +import argparse +import csv +from html import escape +from pathlib import Path +import json +import sys + +PROJECT_ROOT = Path(__file__).resolve().parents[1] +if str(PROJECT_ROOT) not in sys.path: + sys.path.insert(0, str(PROJECT_ROOT)) + +import pandas as pd + +from targetintel.functional_dependency.publication import publish_depmap_v050, validate_publication_tree +from targetintel.functional_dependency.report_loader import load_dependency_report_evidence_bundle +from targetintel.functional_dependency.presentation import render_dependency_html, render_dependency_markdown +from targetintel.hypothesis_cards import write_top_target_cards +from targetintel.html_reports import write_html_index, write_top_html_reports + + +_SYNTHETIC_FIXTURE_LIMITATION = ( + "Descriptive synthetic-fixture evidence only; no therapeutic, clinical, " + "safety, or causal conclusion." +) +_REAL_RELEASE_LIMITATION = ( + "Descriptive real-release aggregate evidence only; no therapeutic, clinical, " + "safety, or causal conclusion." +) + + +def _real_release_markdown(evidence_item: object) -> str: + """Keep inherited fixture wording out of a real-release publication.""" + return render_dependency_markdown(evidence_item).replace( + _SYNTHETIC_FIXTURE_LIMITATION, _REAL_RELEASE_LIMITATION + ) + + +def _real_release_html(evidence_item: object) -> str: + """Render the same truthful limitation in the HTML publication boundary.""" + return render_dependency_html(evidence_item).replace( + _SYNTHETIC_FIXTURE_LIMITATION, _REAL_RELEASE_LIMITATION + ) + + +def main() -> int: + parser = argparse.ArgumentParser(description=__doc__) + for name in ("run-dir", "config-dir", "manifest-dir", "output-dir", "html-output-dir", "ranked-targets", "cards-output-dir"): + parser.add_argument("--" + name, type=Path, required=True) + args = parser.parse_args() + bundle = publish_depmap_v050(run_dir=args.run_dir, config_dir=args.config_dir, + manifest_dir=args.manifest_dir, output_dir=args.output_dir, + ranked_targets=args.ranked_targets) + evidence = load_dependency_report_evidence_bundle(bundle) + ranked = pd.read_csv(args.ranked_targets, sep=None, engine="python") + if "target_symbol" not in ranked and "original_target_identifier" in ranked: + ranked = ranked.rename(columns={"original_target_identifier": "target_symbol"}) + if "target_symbol" not in ranked: + raise ValueError("ranked-targets must contain target_symbol") + productive = set(ranked["target_symbol"].astype(str)) + args.cards_output_dir.mkdir(parents=True, exist_ok=True) + benchmark_membership: dict[str, str] = {} + with (bundle / "benchmark_universe.tsv").open(encoding="utf-8", newline="") as handle: + for row in csv.DictReader(handle, delimiter="\t"): + symbol = row.get("original_identifier") + if symbol: + benchmark_membership[symbol] = row.get("partition") or "recorded; partition unavailable" + # The published real-release reports require the frozen authoritative + # three-intent productive baseline. The closure overlay is not a + # substitute for any of these independently calculated score/rank pairs. + top_n = len(ranked) + target_dir = args.html_output_dir / "targets" + target_dir.mkdir(parents=True, exist_ok=True) + required_baseline_columns = { + "antibody_io_final_score", "antibody_io_rank", + "biomarker_final_score", "biomarker_rank", + "small_molecule_final_score", "small_molecule_rank", + } + missing_baseline_columns = sorted(required_baseline_columns - set(ranked.columns)) + if missing_baseline_columns: + raise ValueError( + "ranked-targets must contain the complete authoritative three-intent " + f"baseline; missing: {', '.join(missing_baseline_columns)}" + ) + write_top_target_cards(ranked, output_dir=args.cards_output_dir, top_n_per_mode=top_n, + dependency_evidence_by_symbol={key: value for key, value in evidence.items() if key in productive}) + write_top_html_reports(ranked, output_dir=target_dir, top_n_per_mode=top_n, + dependency_evidence_by_symbol={key: value for key, value in evidence.items() if key in productive}) + write_html_index(ranked, output_dir=args.html_output_dir, top_n_per_mode=top_n, + dependency_evidence_by_symbol=evidence, target_report_href_prefix="targets/") + discovery = [{"target_symbol": symbol, "profile_available": item.profile_available, + "coverage_status": item.coverage_status, "baseline_rank": item.baseline_rank, + "dependency_aware_candidate_rank": item.dependency_aware_candidate_rank, "rank_delta": item.rank_delta, + "productive_baseline": symbol in productive, + "benchmark_member": "yes" if symbol in benchmark_membership else "no", + "holdout_member": "yes" if benchmark_membership.get(symbol) == "holdout" else ("no" if symbol in benchmark_membership else "not recorded")} + for symbol, item in evidence.items()] + for symbol, item in evidence.items(): + if symbol in productive: + continue + markdown = ("# " + symbol + " — DepMap research-preview discovery identity\n\n" + "This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.\n\n" + + _real_release_markdown(item)) + (args.cards_output_dir / f"{symbol}.md").write_text(markdown, encoding="utf-8") + html = ("" + symbol + + " — DepMap research preview

" + symbol + + "

This identity is part of the research-preview discovery universe and is not part of the authoritative productive baseline.

" + + _real_release_html(item)) + (target_dir / f"{symbol}.html").write_text(html, encoding="utf-8") + available = [row for row in discovery if row["profile_available"]] + unavailable = [row for row in discovery if not row["profile_available"]] + moved = [row for row in discovery if row["rank_delta"] is not None] + upward = sorted(moved, key=lambda row: (row["rank_delta"], row["target_symbol"]))[:10] + downward = sorted(moved, key=lambda row: (-row["rank_delta"], row["target_symbol"]))[:10] + def table(rows: list[dict[str, object]]) -> str: + cells = [] + for row in rows: + membership = "productive baseline" if row["productive_baseline"] else "discovery-only" + cells.append("" + "".join("" + escape(str(value if value is not None else "not available")) + "" for value in (row["target_symbol"], membership, row["profile_available"], row["coverage_status"], row["baseline_rank"], row["dependency_aware_candidate_rank"], row["rank_delta"], row["benchmark_member"], row["holdout_member"])) + "") + return "" + "".join(cells) + "
TargetMembershipProfile availableCoverageBaseline rankResearch-preview DepMap overlay rankRank deltaBenchmarkHoldout
" + overlay_html = ("DepMap discovery overlay" + "

DepMap functional-dependency research preview — discovery overlay

" + "

Complete 331-identity discovery universe. The productive 300-gene baseline remains authoritative; discovery-only identities are not promoted into it.

" + f"

Coverage: {len(available)} available profiles; {len(unavailable)} unavailable profiles. Benchmark and holdout membership is not available in this portable overlay unless explicitly recorded.

" + "

Rank delta = dependency-aware candidate rank minus baseline rank. Negative deltas move toward a lower numerical rank and are not biological validation. DepMap cell-line dependency is not clinical anti-PD-1 response evidence; broad dependency may reflect general essentiality, and cell lines do not reproduce the complete tumor microenvironment.

" + "

Baseline and DepMap overlay views

" + table(discovery) + + "

Strongest upward rank movements

" + table(upward) + + "

Strongest downward rank movements

" + table(downward)) + (args.html_output_dir / "depmap_discovery_overlay.html").write_text(overlay_html, encoding="utf-8", newline="") + (args.html_output_dir / "report_manifest.json").write_text(json.dumps({"discovery_count": len(evidence), "productive_baseline_count": len(productive), "human_review_required": True}, sort_keys=True) + "\n", encoding="utf-8") + validate_publication_tree(args.cards_output_dir, bundle_limit=False) + validate_publication_tree(args.html_output_dir, bundle_limit=False) + return 0 + + +if __name__ == "__main__": + raise SystemExit(main()) diff --git a/targetintel/cli.py b/targetintel/cli.py index 293a1fd..b728327 100644 --- a/targetintel/cli.py +++ b/targetintel/cli.py @@ -83,6 +83,15 @@ def build_parser() -> argparse.ArgumentParser: "decorate reports after deterministic ranking." ), ) + run_parser.add_argument( + "--depmap-snapshot", + type=Path, + default=None, + help=( + "Optional portable DepMap Public 26Q1 publication bundle used " + "only to decorate reports after deterministic ranking." + ), + ) return parser @@ -168,6 +177,8 @@ def main( ) if args.evidence_store is not None: pipeline_kwargs["evidence_store_path"] = args.evidence_store + if args.depmap_snapshot is not None: + pipeline_kwargs["depmap_snapshot_path"] = args.depmap_snapshot outputs = run_pipeline( **pipeline_kwargs, ) diff --git a/targetintel/functional_dependency/publication.py b/targetintel/functional_dependency/publication.py new file mode 100644 index 0000000..9a14956 --- /dev/null +++ b/targetintel/functional_dependency/publication.py @@ -0,0 +1,407 @@ +"""Deterministic, repository-safe publication of a completed DepMap closure.""" +from __future__ import annotations + +import csv +from hashlib import sha256 +import json +from pathlib import Path +import re +import shutil +import tempfile +from typing import Any, Iterable, Mapping + +from .report_contract import build_dependency_report_evidence +from .report_snapshot import export_depmap_report_snapshot + +IDENTITIES = { + "release_identifier": "DepMap_Public_26Q1", + "release_manifest_id": "dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1", + "configuration_id": "v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6", + "scientific_closure_identity": "v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4", + "context_identity": "melanoma_anti_pd1:v1", +} +FORBIDDEN_NAMES = re.compile(r"(?:CRISPRGeneEffect|CRISPRGeneDependency|Model\.csv|ScreenGeneEffect|ScreenGeneDependency|dependency_profiles\.jsonl|\.parquet$|\.h5$|\.h5ad$|\.rds$|\.loom$|\.mtx$|\.tar(?:\.gz)?$|\.zip$)", re.I) +# These are deliberately value-based checks. Publication must not depend on +# the machine which ran the closure in order to know which local operational +# identifiers to remove. +PATH_LEAK = re.compile(r"(?:/home/|/media/|/mnt/|/tmp/|/Users/|/Volumes/|(?:^|[^A-Za-z])[A-Za-z]:[\\/]|\brso12\b|\bS6445-MD61213\b|\b5EC8-12FA\b|\b[0-9A-F]{4}-[0-9A-F]{4}\b)", re.I) +# A drive-letter path may occur within prose, but a POSIX operational path must +# begin at a path boundary. In particular, do not treat the ``s://`` portion +# of an HTTPS URL as a local path. +_LOCAL_PATH_VALUE = re.compile(r"(?:\b[A-Za-z]:[\\/][^\s`'\"<>]+|(?]+)") +_SYNTHETIC_FIXTURE_LIMITATION = "Descriptive synthetic-fixture evidence only; no therapeutic, clinical, safety, or causal conclusion." +_REAL_RELEASE_LIMITATION = "Descriptive real-release aggregate evidence only; no therapeutic, clinical, safety, or causal conclusion." + + +class DepMapPublicationError(ValueError): + pass + + +def _json(path: Path) -> dict[str, Any]: + try: + data = json.loads(path.read_text(encoding="utf-8")) + except (OSError, UnicodeError, json.JSONDecodeError) as exc: + raise DepMapPublicationError("required validated artifact is malformed") from exc + if not isinstance(data, dict): + raise DepMapPublicationError("required validated artifact must be an object") + return data + + +def _sha(path: Path) -> str: + return sha256(path.read_bytes()).hexdigest() + + +def _assert_safe_output(output: Path, inputs: Iterable[Path]) -> None: + if output == Path("/") or output.is_symlink() or any(p.is_symlink() for p in (output, *output.parents)): + raise DepMapPublicationError("unsafe publication output") + for source in inputs: + if output == source or output.is_relative_to(source) or source.is_relative_to(output): + raise DepMapPublicationError("publication output overlaps an input") + + +def _profiles(path: Path) -> list[dict[str, Any]]: + rows: list[dict[str, Any]] = [] + try: + with path.open(encoding="utf-8") as handle: + for line in handle: + if line.strip(): rows.append(json.loads(line)) + except (OSError, UnicodeError, json.JSONDecodeError) as exc: + raise DepMapPublicationError("validated dependency profiles are malformed") from exc + symbols = [row.get("target_identity", {}).get("normalized_request") for row in rows] + if len(rows) != 331 or any(not isinstance(symbol, str) or not symbol for symbol in symbols) or len(set(symbols)) != 331: + raise DepMapPublicationError("validated discovery universe must contain exactly 331 unique identities") + return sorted(rows, key=lambda row: row["target_identity"]["normalized_request"]) + + +def _attach_frozen_canonical_identities(profiles: list[dict[str, Any]], universe_path: Path) -> None: + """Supply the frozen discovery identity omitted by profile payloads.""" + if not universe_path.is_file(): + return + with universe_path.open(encoding="utf-8", newline="") as handle: + rows = list(csv.DictReader(handle, delimiter="\t")) + identities = {row.get("original_identifier"): row.get("canonical_identity") for row in rows} + for profile in profiles: + target = profile.get("target_identity") + if not isinstance(target, dict): + raise DepMapPublicationError("validated dependency profile target identity is malformed") + symbol = target.get("normalized_request") + canonical = identities.get(symbol) + if canonical is not None: + target["canonical_identity"] = canonical + + +def _replace_fixture_limitation(profiles: list[dict[str, Any]]) -> None: + """Correct inherited fixture wording only in the portable real-release view. + + The validated profile calculation remains untouched. This publication-time + correction prevents an inherited fixture label from being represented as a + property of the real DepMap release. + """ + for profile in profiles: + payload = profile.get("payload") + if not isinstance(payload, dict): + continue + limitations = payload.get("limitations") + if isinstance(limitations, list): + payload["limitations"] = [ + _REAL_RELEASE_LIMITATION if item == _SYNTHETIC_FIXTURE_LIMITATION else item + for item in limitations + ] + + +def _overlay(path: Path) -> dict[str, dict[str, Any]]: + with path.open(encoding="utf-8", newline="") as handle: + rows = list(csv.DictReader(handle, delimiter="\t")) + result: dict[str, dict[str, Any]] = {} + for row in rows: + symbol = row.get("original_target_identifier") or row.get("target") + if symbol: + result[symbol] = {key: (int(value) if key in {"baseline_rank", "candidate_rank"} and value and value.lstrip("-").isdigit() else value or None) for key, value in row.items()} + return result + + +def _source_files(preflight: Mapping[str, Any]) -> list[dict[str, Any]]: + candidates = preflight.get("source_files") or preflight.get("input_files") or preflight.get("release_files") + if not isinstance(candidates, list): + raise DepMapPublicationError("validated release does not declare source filenames and checksums") + result = [] + for item in candidates: + if not isinstance(item, Mapping): raise DepMapPublicationError("source manifest entry is malformed") + name = item.get("filename") or item.get("name") + checksum = item.get("sha256") or item.get("checksum") + size = item.get("byte_size") or item.get("size") + if not isinstance(name, str) or not isinstance(checksum, str) or not isinstance(size, int): + raise DepMapPublicationError("source manifest lacks filename, checksum, or size") + result.append({"filename": name, "sha256": checksum, "byte_size": size, "role": item.get("role", "validated DepMap input")}) + return sorted(result, key=lambda value: value["filename"]) + + +def _source_files_from_checksums(manifests: Path) -> list[dict[str, Any]]: + """Read the validated download checksum ledger when preflight is concise.""" + path = manifests / "downloaded_files.sha256.tsv" + if not path.is_file(): + raise DepMapPublicationError("validated release does not declare source filenames and checksums") + with path.open(encoding="utf-8", newline="") as handle: + values = list(csv.reader(handle, delimiter="\t")) + if values and values[0] == ["filename", "bytes", "sha256"]: + values = values[1:] + result = [] + for row in values: + if len(row) != 3: + raise DepMapPublicationError("source checksum ledger is malformed") + name, size, checksum = row + if not isinstance(name, str) or not re.fullmatch(r"[0-9a-f]{64}", checksum or "") or not str(size).isdigit(): + raise DepMapPublicationError("source checksum ledger is malformed") + role = { + "CRISPRGeneEffect.csv": "CRISPR gene-effect matrix", + "CRISPRGeneDependency.csv": "CRISPR dependency-probability matrix", + "Model.csv": "model metadata", + }.get(name, "validated DepMap release input") + result.append({"filename": name, "sha256": checksum, "byte_size": int(size), "role": role}) + if not result: + raise DepMapPublicationError("source checksum ledger is empty") + return sorted(result, key=lambda value: value["filename"]) + + +def _sanitize_text(text: str) -> str: + """Remove operational locations and identifiers without changing science.""" + text = _LOCAL_PATH_VALUE.sub("", text) + return PATH_LEAK.sub("", text) + + +def _sanitize_tree(root: Path) -> None: + for path in root.rglob("*"): + if path.is_file() and path.suffix in {".json", ".tsv", ".md", ".html", ".jsonl"}: + text = path.read_text(encoding="utf-8") + sanitized = _sanitize_text(text) + if sanitized != text: + path.write_text(sanitized, encoding="utf-8", newline="") + + +def validate_publication_tree(root: Path, *, bundle_limit: bool = True) -> None: + """Validate portable content and size boundaries without reading any raw data.""" + total = 0 + for path in root.rglob("*"): + if not path.is_file(): continue + if FORBIDDEN_NAMES.search(path.name) or any(part in {"raw", "cache"} for part in path.relative_to(root).parts): + raise DepMapPublicationError("forbidden raw artifact in publication output") + size = path.stat().st_size; total += size + if size > 5 * 1024 * 1024: raise DepMapPublicationError("publication data artifact exceeds 5 MiB") + if path.suffix == ".html" and size > 2 * 1024 * 1024: raise DepMapPublicationError("publication HTML exceeds 2 MiB") + if path.suffix in {".json", ".tsv", ".md", ".html", ".jsonl"} and PATH_LEAK.search(path.read_text(encoding="utf-8")): + raise DepMapPublicationError("publication output contains a local path") + if bundle_limit and total > 30 * 1024 * 1024: raise DepMapPublicationError("publication bundle exceeds 30 MiB") + + +def _copy_useful_closure_artifacts(run: Path, config: Path, manifests: Path, destination: Path) -> None: + """Retain every small closure state artifact under stable portable names.""" + sources = { + "release_preflight.json": run / "release_preflight.json", + "artifact_compatibility.json": run / "artifact_compatibility.json", + "reproducibility_summary.json": run / "reproducibility_summary.json", + "release_readiness.json": run / "release_readiness.json", + "activation_readiness_summary.json": run / "activation_readiness_summary.json", + "baseline_preservation.json": run / "integration" / "baseline_preservation.json", + "integration_gate_decision.json": run / "integration" / "integration_gate_decision.json", + "benchmark_coverage.json": run / "benchmark" / "benchmark_coverage.json", + "benchmark_universe.tsv": run / "universes" / "benchmark_universe.tsv", + "discovery_universe.tsv": run / "universes" / "discovery_universe.tsv", + "release_closure_manifest.json": run / "release_closure_manifest.json", + "release_configuration_identity.json": config / "release_configuration_identity.json", + } + for name, source in sources.items(): + if source.is_file() and source.stat().st_size <= 5 * 1024 * 1024: + shutil.copyfile(source, destination / name) + + +def _source_inventory(run: Path, config: Path, manifests: Path) -> list[dict[str, Any]]: + rows: list[dict[str, Any]] = [] + roots = (("run", run, sorted(run.rglob("*"))), ("manifest", manifests, sorted(manifests.rglob("*")))) + # A real publication may use the repository root as ``config_dir``. Only + # identity artifacts are closure candidates; traversing the repository (or + # its .git directory) would make inventory depend on unrelated work. + config_files = [config / name for name in ("release_configuration_identity.json", "real_run_config.json")] + for label, root, paths in (*roots, ("config", config, config_files)): + for path in paths: + if not path.is_file(): + continue + name = f"{label}/{path.relative_to(root).as_posix()}" + raw = bool(FORBIDDEN_NAMES.search(path.name) or any(part in {"raw", "cache"} for part in path.relative_to(root).parts)) + rows.append({"source_artifact_name": name, "artifact_category": "raw_or_redistributable" if raw else "closure_artifact", "source_size": path.stat().st_size, "source_checksum": _sha(path), "publication_action": "excluded", "exclusion_reason": "raw or redistributable DepMap source data" if raw else "not a repository-safe aggregate publication artifact", "published_relative_path": "", "published_checksum": ""}) + return rows + + +def _read_ranked_targets(path: Path) -> set[str]: + try: + with path.open(encoding="utf-8", newline="") as handle: + rows = list(csv.DictReader(handle, delimiter="\t" if path.suffix == ".tsv" else ",")) + except (OSError, UnicodeError, csv.Error) as exc: + raise DepMapPublicationError("ranked targets are malformed") from exc + # The immutable integration overlay is an accepted explicit baseline + # source for publication. It labels the same stable symbol field + # ``original_target_identifier`` rather than ``target_symbol``. + symbols = [row.get("target_symbol") or row.get("original_target_identifier") for row in rows] + if len(symbols) != 300 or any(not isinstance(symbol, str) or not symbol for symbol in symbols) or len(set(symbols)) != 300: + raise DepMapPublicationError("productive baseline must contain exactly 300 unique targets") + return set(symbols) + + +def _validated_counts(run: Path) -> dict[str, int]: + compatibility = _json(run / "artifact_compatibility.json") + metrics = compatibility.get("metrics") + coverage = _json(run / "benchmark" / "benchmark_coverage.json") + if not isinstance(metrics, Mapping): + raise DepMapPublicationError("validated aggregate counts are missing") + counts = { + "benchmark_count": coverage.get("total_benchmark_targets", metrics.get("benchmark_count")), + "discovery_count": metrics.get("discovery_count"), + "background_count": metrics.get("background_count"), + } + expected = {"benchmark_count": 56, "discovery_count": 331, "background_count": 18531} + if counts != expected: + raise DepMapPublicationError("validated aggregate universe count mismatch") + return {name: int(value) for name, value in counts.items()} + + +def publish_depmap_v050(*, run_dir: str | Path, config_dir: str | Path, manifest_dir: str | Path, output_dir: str | Path, ranked_targets: str | Path) -> Path: + """Publish only derived aggregate records from an already validated closure.""" + run, config, manifests, output = (Path(value).resolve() for value in (run_dir, config_dir, manifest_dir, output_dir)) + ranked_path = Path(ranked_targets).resolve() + if not all(path.is_dir() for path in (run, config, manifests)) or not ranked_path.is_file(): + raise DepMapPublicationError("explicit validated inputs are required") + # ``config_dir`` may be the repository root, so it is deliberately not an + # overlap guard. It is read-only input; the run and manifest roots contain + # the validated closure and must never overlap publication output. + _assert_safe_output(output, (run, manifests)) + productive_symbols = _read_ranked_targets(ranked_path) + preflight = _json(run / "release_preflight.json") + for key, expected in IDENTITIES.items(): + if key in {"scientific_closure_identity", "context_identity"}: continue + if preflight.get(key) != expected: raise DepMapPublicationError("validated release identity mismatch: " + key) + closure = _json(run / "release_closure_manifest.json") + closure_summary = _json(manifests / "real-v6-release-closure-summary.json") + reproducibility = _json(run / "reproducibility_summary.json") + reproducible_identity = reproducibility.get("excluded_artifact_invariants", {}).get("closure_scientific_identity", {}) + if isinstance(reproducible_identity, Mapping) and reproducible_identity.get("first") != reproducible_identity.get("second"): + raise DepMapPublicationError("validated release has inconsistent scientific closure identities") + closure_identity = closure.get("scientific_closure_identity", closure.get("closure_scientific_identity", closure_summary.get("scientific_closure_identity", reproducible_identity.get("first") if isinstance(reproducible_identity, Mapping) else None))) + if closure_identity != IDENTITIES["scientific_closure_identity"]: + raise DepMapPublicationError("validated release identity mismatch: scientific_closure_identity") + profiles = _profiles(run / "profiles" / "dependency_profiles.jsonl") + _attach_frozen_canonical_identities(profiles, run / "universes" / "discovery_universe.tsv") + _replace_fixture_limitation(profiles) + source_files = _source_files(preflight) if any(key in preflight for key in ("source_files", "input_files", "release_files")) else _source_files_from_checksums(manifests) + overlay = _overlay(run / "integration" / "candidate_overlay.tsv") + if set(overlay) != productive_symbols: + raise DepMapPublicationError("validated overlay and productive baseline targets differ") + counts = _validated_counts(run) + output.parent.mkdir(parents=True, exist_ok=True) + temporary = Path(tempfile.mkdtemp(prefix=".depmap-publication-", dir=output.parent)) + try: + # Issue 508 remains the sole snapshot exporter. Its selected-output + # table is replaced below with the complete discovery aggregate table. + # The release configuration supplied for real publication is the + # repository root. The exporter needs only its frozen identity, so use + # an ephemeral identity-only view rather than modifying that input. + export_config = temporary / "export_config" + export_config.mkdir() + (export_config / "release_configuration_identity.json").write_text(json.dumps({"configuration_id": IDENTITIES["configuration_id"]}), encoding="utf-8") + export_depmap_report_snapshot(run_dir=run, config_dir=export_config, manifest_dir=manifests, + output_dir=temporary / "snapshot", selected_targets=[p["target_identity"]["normalized_request"] for p in profiles]) + shutil.rmtree(export_config) + for item in (temporary / "snapshot").iterdir(): shutil.move(str(item), temporary / item.name) + (temporary / "snapshot").rmdir() + _copy_useful_closure_artifacts(run, config, manifests, temporary) + summary = _json(temporary / "release_summary.json") + if summary.get("context_identity") != IDENTITIES["context_identity"]: + raise DepMapPublicationError("validated release identity mismatch: context_identity") + summary.update(IDENTITIES) + summary.update({"productive_baseline_count": len(productive_symbols), **counts}) + (temporary / "release_summary.json").write_text(json.dumps(summary, sort_keys=True, separators=(",", ":")) + "\n", encoding="utf-8") + evidence = [] + for profile in profiles: + symbol = profile["target_identity"]["normalized_request"] + record = build_dependency_report_evidence(release_summary=summary, profile_record=profile, + overlay_record=overlay.get(symbol), provenance={"source_artifact_names": ["selected_target_profiles.tsv", "candidate_overlay.tsv"]}) + evidence.append(record) + (temporary / "dependency_report_evidence.jsonl").write_text("".join(item.canonical_json() + "\n" for item in evidence), encoding="utf-8") + with (temporary / "selected_target_profiles.tsv").open("w", encoding="utf-8", newline="") as handle: + fields = ["target", "canonical_gene_identity", "profile_available", "coverage_status", "context_model_count", "reference_model_count", "gene_effect", "dependency_probability", "context_reference_comparison", "selectivity", "interpretation_state", "portable_provenance"] + writer = csv.DictWriter(handle, fieldnames=fields, delimiter="\t"); writer.writeheader() + for item in evidence: + record = item.to_dict() + writer.writerow({"target": item.gene_symbol, "canonical_gene_identity": item.canonical_gene_identity or "", "profile_available": str(item.profile_available).lower(), "coverage_status": item.coverage_status, "context_model_count": item.context_model_count if item.context_model_count is not None else "", "reference_model_count": item.reference_model_count if item.reference_model_count is not None else "", "gene_effect": json.dumps(record["gene_effect"] or {}, sort_keys=True), "dependency_probability": json.dumps(record["dependency_probability"] or {}, sort_keys=True), "context_reference_comparison": json.dumps(record["context_reference_comparison"] or {}, sort_keys=True), "selectivity": json.dumps(record["selectivity"] or {}, sort_keys=True), "interpretation_state": item.dependency_interpretation_state or "", "portable_provenance": ";".join(item.provenance["source_artifact_names"])}) + source_manifest = {"source_project": "DepMap", "source_release": "DepMap Public 26Q1", "official_download_url": "https://depmap.org/portal/data_page/?release=DepMap+Public+26Q1", "official_release_notes_url": "https://forum.depmap.org/t/announcing-the-26q1-release/4606", "source_files": source_files, **IDENTITIES, "derivation": "Validated aggregate functional-dependency closure; no recalculation.", "redistributability_boundary": "Raw DepMap matrices are not committed."} + (temporary / "source_manifest.json").write_text(json.dumps(source_manifest, sort_keys=True, separators=(",", ":")) + "\n", encoding="utf-8") + manifest = {"publication_format_version": "v1", **IDENTITIES, "selected_target_profile_count": len(profiles), "productive_baseline_count": len(productive_symbols), **counts, "raw_matrices_committed": False} + (temporary / "publication_manifest.json").write_text(json.dumps(manifest, sort_keys=True, separators=(",", ":")) + "\n", encoding="utf-8") + _sanitize_tree(temporary) + candidates = [path for path in temporary.iterdir() if path.is_file()] + inventory = _source_inventory(run, config, manifests) + with ( + temporary / "publication_inventory.tsv" + ).open( + "w", + encoding="utf-8", + newline="", + ) as handle: + fields = [ + "source_artifact_name", + "artifact_category", + "source_size", + "source_checksum", + "publication_action", + "exclusion_reason", + "published_relative_path", + "published_checksum", + ] + writer = csv.DictWriter( + handle, + fieldnames=fields, + delimiter="\t", + quoting=csv.QUOTE_ALL, + lineterminator="\n", + ) + writer.writeheader() + + for candidate in sorted(candidates): + writer.writerow( + { + "source_artifact_name": candidate.name, + "artifact_category": "derived_aggregate", + "source_size": candidate.stat().st_size, + "source_checksum": _sha(candidate), + "publication_action": "published", + "exclusion_reason": "", + "published_relative_path": candidate.name, + "published_checksum": _sha(candidate), + } + ) + + for row in inventory: + writer.writerow(row) + + for source in source_files: + writer.writerow( + { + "source_artifact_name": source["filename"], + "artifact_category": "raw_source", + "source_size": source["byte_size"], + "source_checksum": source["sha256"], + "publication_action": "excluded", + "exclusion_reason": ( + "raw or redistributable DepMap source data" + ), + "published_relative_path": "", + "published_checksum": "", + } + ) + checksums = [{"name": path.name, "sha256": _sha(path), "byte_size": path.stat().st_size} for path in sorted(temporary.iterdir()) if path.is_file() and path.name != "checksums.json"] + (temporary / "checksums.json").write_text(json.dumps({"artifacts": checksums}, sort_keys=True, separators=(",", ":")) + "\n", encoding="utf-8") + _sanitize_tree(temporary) + validate_publication_tree(temporary) + if output.exists(): shutil.rmtree(output) + temporary.replace(output) + except Exception: + shutil.rmtree(temporary, ignore_errors=True); raise + return output diff --git a/targetintel/functional_dependency/report_loader.py b/targetintel/functional_dependency/report_loader.py new file mode 100644 index 0000000..86a81f5 --- /dev/null +++ b/targetintel/functional_dependency/report_loader.py @@ -0,0 +1,127 @@ +"""Offline loader for the sanitized DepMap report publication bundle. + +The loader deliberately has a much narrower boundary than the local DepMap +workflow: it reads the checked, aggregate report records only. In particular +it never follows provenance into a run directory or a raw release download. +""" +from __future__ import annotations + +from collections import OrderedDict +from hashlib import sha256 +import json +from pathlib import Path +import re +from types import MappingProxyType +from typing import Mapping, Iterable + +from .report_contract import DependencyReportEvidence + + +_REQUIRED = {"release_summary.json", "publication_manifest.json", "source_manifest.json", "checksums.json", "dependency_report_evidence.jsonl"} +_IDENTITIES = { + "release_identifier": "DepMap_Public_26Q1", + "release_manifest_id": "dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1", + "configuration_id": "v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6", + "scientific_closure_identity": "v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4", + "context_identity": "melanoma_anti_pd1:v1", +} +_PATH_LEAK = re.compile(r"(?:/home/|/media/|/mnt/|/tmp/|/Users/|/Volumes/|(?:^|[^A-Za-z])[A-Za-z]:[\\/]|\brso12\b|\bS6445-MD61213\b|\b5EC8-12FA\b|\b[0-9A-F]{4}-[0-9A-F]{4}\b)", re.I) + + +class DependencyReportLoaderError(ValueError): + """A portable bundle failed its publication contract.""" + + +def _read_json(path: Path) -> object: + try: + return json.loads(path.read_text(encoding="utf-8")) + except (OSError, UnicodeError, json.JSONDecodeError) as exc: + raise DependencyReportLoaderError("portable publication JSON is malformed") from exc + + +def _validate_checksum_inventory(root: Path) -> None: + inventory = _read_json(root / "checksums.json") + rows = inventory.get("artifacts") if isinstance(inventory, dict) else inventory + if not isinstance(rows, list): + raise DependencyReportLoaderError("checksums inventory is malformed") + seen: set[str] = set() + for row in rows: + if not isinstance(row, dict) or not {"name", "sha256", "byte_size"} <= set(row): + raise DependencyReportLoaderError("checksums inventory entry is malformed") + name = row["name"] + if not isinstance(name, str) or name in seen or "/" in name or "\\" in name: + raise DependencyReportLoaderError("checksums inventory contains an unsafe name") + seen.add(name) + path = root / name + if not path.is_file() or path.stat().st_size != row["byte_size"]: + raise DependencyReportLoaderError("portable publication checksum size mismatch") + if sha256(path.read_bytes()).hexdigest() != row["sha256"]: + raise DependencyReportLoaderError("portable publication checksum mismatch") + if not _REQUIRED <= seen | {"checksums.json"}: + raise DependencyReportLoaderError("checksums inventory omits a required artifact") + + +def _validate_identities(summary: object, manifest: object) -> None: + if not isinstance(summary, dict) or not isinstance(manifest, dict): + raise DependencyReportLoaderError("publication identity artifact is malformed") + for name, expected in _IDENTITIES.items(): + if summary.get(name) != expected or manifest.get(name) != expected: + raise DependencyReportLoaderError("portable publication identity mismatch: " + name) + if manifest.get("publication_format_version") != "v1": + raise DependencyReportLoaderError("unsupported publication format") + + +def load_dependency_report_evidence_bundle(snapshot_dir: str | Path, target_symbols: Iterable[str] | None = None) -> Mapping[str, DependencyReportEvidence]: + """Load validated immutable evidence, without raw DepMap data access. + + ``target_symbols`` is an optional deterministic selection. Unknown names + are rejected rather than silently treated as unavailable profiles. + """ + root = Path(snapshot_dir) + if not root.is_dir() or root.is_symlink() or any(part.is_symlink() for part in (root, *root.parents)): + raise DependencyReportLoaderError("snapshot directory is unsafe") + if not _REQUIRED <= {path.name for path in root.iterdir() if path.is_file()}: + raise DependencyReportLoaderError("portable publication is incomplete") + for path in root.rglob("*"): + if path.is_file() and path.suffix in {".json", ".tsv", ".md", ".html", ".jsonl"}: + if _PATH_LEAK.search(path.read_text(encoding="utf-8")): + raise DependencyReportLoaderError("portable publication contains local operational metadata") + _validate_checksum_inventory(root) + summary = _read_json(root / "release_summary.json") + manifest = _read_json(root / "publication_manifest.json") + source_manifest = _read_json(root / "source_manifest.json") + _validate_identities(summary, manifest) + if not isinstance(source_manifest, dict) or source_manifest.get("source_project") != "DepMap": + raise DependencyReportLoaderError("source manifest is malformed") + for name, expected in _IDENTITIES.items(): + if source_manifest.get(name) != expected: + raise DependencyReportLoaderError("source manifest identity mismatch: " + name) + records: dict[str, DependencyReportEvidence] = {} + try: + lines = (root / "dependency_report_evidence.jsonl").read_text(encoding="utf-8").splitlines() + except (OSError, UnicodeError) as exc: + raise DependencyReportLoaderError("portable evidence records cannot be read") from exc + for line in lines: + if not line.strip(): + continue + if _PATH_LEAK.search(line): + raise DependencyReportLoaderError("portable evidence contains a local path") + try: + evidence = DependencyReportEvidence.from_dict(json.loads(line)) + except (json.JSONDecodeError, TypeError, ValueError) as exc: + raise DependencyReportLoaderError("portable evidence record is invalid") from exc + for name, expected in _IDENTITIES.items(): + if getattr(evidence, name) != expected: + raise DependencyReportLoaderError("evidence identity mismatch: " + name) + if evidence.gene_symbol in records: + raise DependencyReportLoaderError("duplicate portable evidence gene") + records[evidence.gene_symbol] = evidence + requested = None if target_symbols is None else tuple(target_symbols) + if requested is not None: + if any(not isinstance(symbol, str) or not symbol for symbol in requested): + raise DependencyReportLoaderError("target symbols must be non-empty strings") + unknown = sorted(set(requested) - set(records)) + if unknown: + raise DependencyReportLoaderError("unknown target symbols: " + ",".join(unknown)) + records = {symbol: records[symbol] for symbol in sorted(set(requested))} + return MappingProxyType(OrderedDict((symbol, records[symbol]) for symbol in sorted(records))) diff --git a/targetintel/functional_dependency/report_snapshot.py b/targetintel/functional_dependency/report_snapshot.py index fc09124..736696c 100644 --- a/targetintel/functional_dependency/report_snapshot.py +++ b/targetintel/functional_dependency/report_snapshot.py @@ -191,7 +191,18 @@ def export_depmap_report_snapshot(*, run_dir: Path | str, config_dir: Path | str _need(compatibility, "compatible", True); _need(compatibility, "expected_context_identity", "melanoma_anti_pd1:v1") configuration_id = _one_of((_configuration_id(config), _need(preflight, "configuration_id"), _need(readiness, "configuration_id"), _need(closure, "configuration_id"), reproducibility.get("configuration_id"), closure_summary.get("configuration_id")), "configuration IDs") manifest_id = _one_of((_need(preflight, "release_manifest_id"), closure_summary.get("release_manifest_id"), external.get("release_manifest_id")), "release manifest IDs") - scientific_identity = _one_of((closure_summary.get("scientific_closure_identity"), external.get("scientific_closure_identity")), "scientific closure identities") + # Some validated v0.5.0 closures deliberately omit this operationally + # excluded field from their summaries. In that case its reproducibility + # invariant is the authoritative frozen identity. + closure_identity = closure_summary.get("scientific_closure_identity") + external_identity = external.get("scientific_closure_identity") + if closure_identity is None or external_identity is None: + invariant = reproducibility.get("excluded_artifact_invariants", {}).get("closure_scientific_identity", {}) + if not isinstance(invariant, Mapping) or invariant.get("first") != invariant.get("second"): + _fail("scientific closure identity is missing") + scientific_identity = invariant["first"] + else: + scientific_identity = _one_of((closure_identity, external_identity), "scientific closure identities") if not scientific_identity: _fail("scientific closure identity is missing") _need(reproducibility, "result", "reproducible") diff --git a/targetintel/html_reports.py b/targetintel/html_reports.py index 50c8809..119d285 100644 --- a/targetintel/html_reports.py +++ b/targetintel/html_reports.py @@ -625,10 +625,11 @@ def write_target_html_report( return output_path -def _make_target_link(symbol: str) -> str: +def _make_target_link(symbol: str, target_report_href_prefix: str = "") -> str: """Create an HTML link to a target report.""" safe_symbol = escape(symbol) - return f'{safe_symbol}' + safe_prefix = escape(target_report_href_prefix, quote=True) + return f'{safe_symbol}' def _make_mode_table( @@ -636,6 +637,7 @@ def _make_mode_table( mode: str, label: str, top_n: int, + target_report_href_prefix: str = "", ) -> str: """ Create an HTML table for one therapeutic-intent mode. @@ -657,7 +659,7 @@ def _make_mode_table( f""" {_safe_int(row.get(rank_col))} - {_make_target_link(symbol)} + {_make_target_link(symbol, target_report_href_prefix)} {escape(_safe_str(row.get("role_classification")))} {escape(_safe_str(row.get("best_modality")))} {_safe_float(row.get(score_col))} @@ -693,6 +695,8 @@ def _make_mode_table( def make_html_index( ranked_df: pd.DataFrame, top_n_per_mode: int = 10, + dependency_evidence_by_symbol: Mapping[str, DependencyReportEvidence] | None = None, + target_report_href_prefix: str = "", ) -> str: """ Generate an HTML index page for the target reports. @@ -702,6 +706,7 @@ def make_html_index( mode="antibody_io", label="Top antibody / IO-combination targets", top_n=top_n_per_mode, + target_report_href_prefix=target_report_href_prefix, ) biomarker_table = _make_mode_table( @@ -709,6 +714,7 @@ def make_html_index( mode="biomarker", label="Top resistance biomarker candidates", top_n=top_n_per_mode, + target_report_href_prefix=target_report_href_prefix, ) small_molecule_table = _make_mode_table( @@ -716,7 +722,38 @@ def make_html_index( mode="small_molecule", label="Top tumor-intrinsic / small-molecule candidates", top_n=top_n_per_mode, + target_report_href_prefix=target_report_href_prefix, ) + dependency_section = "" + if dependency_evidence_by_symbol: + rows: list[str] = [] + for symbol, evidence in sorted(dependency_evidence_by_symbol.items()): + row = ranked_df.loc[ranked_df["target_symbol"] == symbol] + baseline_score = ( + "antibody / IO: " + _safe_float(row.iloc[0].get("antibody_io_final_score")) + + "; biomarker: " + _safe_float(row.iloc[0].get("biomarker_final_score")) + + "; small molecule: " + _safe_float(row.iloc[0].get("small_molecule_final_score")) + if not row.empty else "not in productive baseline" + ) + role = _safe_str(row.iloc[0].get("role_classification")) if not row.empty else "research-preview discovery identity" + rows.append("" + "".join([ + f"{escape(symbol)}", f"{escape(role)}", + f"{baseline_score}", f"{'available' if evidence.profile_available else 'unavailable'}", + f"{escape(evidence.coverage_status)}", f"{_safe_int(evidence.context_model_count)}", + f"{_safe_int(evidence.reference_model_count)}", + f"{escape(str(evidence.gene_effect) if evidence.gene_effect else 'not available')}", + f"{escape(str(evidence.dependency_probability) if evidence.dependency_probability else 'not available')}", + f"{escape(str(evidence.selectivity) if evidence.selectivity else 'not available')}", + f"{_safe_int(evidence.baseline_rank)}", f"{_safe_int(evidence.dependency_aware_candidate_rank)}", + f"{_safe_int(evidence.rank_delta)}", f"{escape(_safe_str(evidence.integration_state))}", + "required", + ]) + "") + dependency_section = """ +
+

DepMap functional-dependency research preview

+

Research-preview DepMap overlay rank is not the productive rank. Rank delta = dependency-aware candidate rank minus baseline rank. Negative deltas indicate movement toward a lower numerical rank, not biological validation.

+

DepMap cell-line dependency is not clinical anti-PD-1 response evidence; human review remains required.

+ """ + "".join(rows) + "
TargetRoleBaseline scoreProfileCoverageContext modelsReference modelsGene effectDependency probabilitySelectivityBaseline rankResearch-preview DepMap overlay rankRank deltaIntegrationHuman review
" return f""" @@ -756,6 +793,8 @@ def make_html_index( {small_molecule_table} +{dependency_section} + @@ -770,6 +809,8 @@ def write_html_index( ranked_df: pd.DataFrame, output_dir: str | Path = DEFAULT_HTML_REPORT_DIR, top_n_per_mode: int = 10, + dependency_evidence_by_symbol: Mapping[str, DependencyReportEvidence] | None = None, + target_report_href_prefix: str = "", ) -> Path: """ Write the HTML index page. @@ -779,8 +820,23 @@ def write_html_index( output_path = output_dir / "index.html" + html = make_html_index( + ranked_df, + top_n_per_mode=top_n_per_mode, + dependency_evidence_by_symbol=dependency_evidence_by_symbol, + target_report_href_prefix=target_report_href_prefix, + ) + + normalized_html = ( + "\n".join( + line.rstrip(" \t") + for line in html.splitlines() + ).rstrip("\n") + + "\n" + ) + output_path.write_text( - make_html_index(ranked_df, top_n_per_mode=top_n_per_mode), + normalized_html, encoding="utf-8", ) @@ -795,6 +851,7 @@ def write_top_html_reports( feasibility_annotations: Mapping[str, tuple[object, ...] | list[object]] | None = None, feasibility_target_identifier_type: str | None = None, dependency_evidence_by_symbol: Mapping[str, DependencyReportEvidence] | None = None, + include_dependency_index: bool = False, ) -> list[Path]: """ Write HTML reports for the union of top-N targets across all modes. @@ -851,6 +908,7 @@ def write_top_html_reports( ranked_df, output_dir=output_dir, top_n_per_mode=top_n_per_mode, + dependency_evidence_by_symbol=(dependency_evidence_by_symbol if include_dependency_index else None), ) return [index_path] + written_paths diff --git a/targetintel/hypothesis_cards.py b/targetintel/hypothesis_cards.py index 5879315..8adc7b4 100644 --- a/targetintel/hypothesis_cards.py +++ b/targetintel/hypothesis_cards.py @@ -316,13 +316,16 @@ def write_target_card( symbol = _safe_str(row.get("target_symbol")) output_path = output_dir / f"{symbol}.md" + card_text = make_target_card( + row, + evidence_card=evidence_card, + feasibility_annotations=feasibility_annotations, + feasibility_target_identifier_type=feasibility_target_identifier_type, + dependency_evidence=dependency_evidence, + ) + output_path.write_text( - make_target_card( - row, evidence_card=evidence_card, - feasibility_annotations=feasibility_annotations, - feasibility_target_identifier_type=feasibility_target_identifier_type, - dependency_evidence=dependency_evidence, - ), + card_text.rstrip("\r\n") + "\n", encoding="utf-8", ) diff --git a/targetintel/pipeline.py b/targetintel/pipeline.py index b63f0af..6cf9fa3 100644 --- a/targetintel/pipeline.py +++ b/targetintel/pipeline.py @@ -8,7 +8,7 @@ import sys from dataclasses import dataclass from pathlib import Path -from typing import Sequence +from typing import Mapping, Sequence os.environ.setdefault( "MPLBACKEND", @@ -26,6 +26,9 @@ from targetintel.hypothesis_cards import ( write_top_target_cards, ) +from targetintel.functional_dependency.report_loader import ( + load_dependency_report_evidence_bundle, +) from targetintel.intent_ranking import ( build_intent_rankings, save_ranked_targets, @@ -61,6 +64,30 @@ def _validate_positive_integer( ) +def _report_dependency_coverage( + dependency_evidence: Mapping[str, object], +) -> None: + """Print the descriptive coverage of an optional portable bundle.""" + profiles = tuple(dependency_evidence.values()) + available = sum( + bool(getattr(profile, "profile_available", False)) + for profile in profiles + ) + by_coverage: dict[str, int] = {} + for profile in profiles: + status = str(getattr(profile, "coverage_status", "unknown")) + by_coverage[status] = by_coverage.get(status, 0) + 1 + coverage_summary = ", ".join( + f"{status}={count}" + for status, count in sorted(by_coverage.items()) + ) + print( + "DepMap research-preview coverage: " + f"{available}/{len(profiles)} profiles available" + + (f" ({coverage_summary})" if coverage_summary else "") + ) + + def _run_command( command: Sequence[str], *, @@ -98,6 +125,7 @@ def run_core_pipeline( refresh: bool = False, top_n_per_mode: int = 10, evidence_store_path: str | Path | None = None, + depmap_snapshot_path: str | Path | None = None, project_root: Path = PROJECT_ROOT, ) -> PipelineOutputs: """ @@ -206,6 +234,15 @@ def run_core_pipeline( if evidence_store_path is not None else {} ) + dependency_evidence = ( + load_dependency_report_evidence_bundle( + depmap_snapshot_path, ranked_df["target_symbol"].tolist() + ) + if depmap_snapshot_path is not None + else {} + ) + if depmap_snapshot_path is not None: + _report_dependency_coverage(dependency_evidence) card_kwargs = { "output_dir": target_cards_dir, @@ -213,6 +250,8 @@ def run_core_pipeline( } if evidence_cards: card_kwargs["evidence_cards"] = evidence_cards + if dependency_evidence: + card_kwargs["dependency_evidence_by_symbol"] = dependency_evidence card_paths = write_top_target_cards(ranked_df, **card_kwargs) print( @@ -229,6 +268,9 @@ def run_core_pipeline( } if evidence_cards: html_kwargs["evidence_cards"] = evidence_cards + if dependency_evidence: + html_kwargs["dependency_evidence_by_symbol"] = dependency_evidence + html_kwargs["include_dependency_index"] = True html_paths = write_top_html_reports(ranked_df, **html_kwargs) print( @@ -397,6 +439,7 @@ def run_pipeline( top_n_per_mode: int = 10, validate: bool = False, evidence_store_path: str | Path | None = None, + depmap_snapshot_path: str | Path | None = None, project_root: Path = PROJECT_ROOT, ) -> PipelineOutputs: """Run the complete workflow, optionally including validation.""" @@ -406,6 +449,7 @@ def run_pipeline( refresh=refresh, top_n_per_mode=top_n_per_mode, evidence_store_path=evidence_store_path, + depmap_snapshot_path=depmap_snapshot_path, project_root=project_root, ) diff --git a/tests/test_depmap_html_publication.py b/tests/test_depmap_html_publication.py new file mode 100644 index 0000000..37ebc41 --- /dev/null +++ b/tests/test_depmap_html_publication.py @@ -0,0 +1,27 @@ +from __future__ import annotations + +from pathlib import Path +import re + + +def test_publication_script_contains_complete_discovery_overlay_contract() -> None: + source = Path("scripts/13_publish_depmap_v050.py").read_text() + for text in ("Complete 331-identity discovery universe", "Strongest upward rank movements", "Strongest downward rank movements", "Research-preview DepMap overlay rank", "not biological validation"): + assert text in source + + +def test_publication_script_does_not_label_real_reports_as_synthetic_fixtures() -> None: + source = Path("scripts/13_publish_depmap_v050.py").read_text() + assert "Descriptive real-release aggregate evidence only" in source + assert "_real_release_markdown(item)" in source + + +def test_published_main_index_target_links_resolve_to_target_reports() -> None: + """The outer published index must link into its targets/ subdirectory.""" + report_root = Path("examples/html_reports/depmap_26q1") + index_html = (report_root / "index.html").read_text(encoding="utf-8") + hrefs = re.findall(r'href="([^"]+\.html)"', index_html) + target_hrefs = [href for href in hrefs if href.startswith("targets/")] + + assert target_hrefs + assert all((report_root / href).is_file() for href in target_hrefs) diff --git a/tests/test_depmap_pipeline_wiring.py b/tests/test_depmap_pipeline_wiring.py new file mode 100644 index 0000000..ee44357 --- /dev/null +++ b/tests/test_depmap_pipeline_wiring.py @@ -0,0 +1,50 @@ +from __future__ import annotations + +import inspect +from types import SimpleNamespace + +from targetintel.cli import build_parser +import targetintel.pipeline as pipeline_module +from targetintel.pipeline import ( + _report_dependency_coverage, + run_core_pipeline, + run_pipeline, +) + + +def test_pipeline_and_cli_make_the_snapshot_strictly_optional() -> None: + assert inspect.signature(run_core_pipeline).parameters["depmap_snapshot_path"].default is None + assert inspect.signature(run_pipeline).parameters["depmap_snapshot_path"].default is None + assert build_parser().parse_args(["run", "--depmap-snapshot", "bundle"]).depmap_snapshot.name == "bundle" + + +def test_snapshot_coverage_is_reported_descriptively(capsys) -> None: + _report_dependency_coverage({ + "AVAILABLE": SimpleNamespace( + profile_available=True, + coverage_status="complete", + ), + "UNAVAILABLE": SimpleNamespace( + profile_available=False, + coverage_status="not_available", + ), + }) + + assert capsys.readouterr().out == ( + "DepMap research-preview coverage: 1/2 profiles available " + "(complete=1, not_available=1)\n" + ) + + +def test_pipeline_relays_the_optional_snapshot_to_core(monkeypatch) -> None: + captured = {} + sentinel = object() + + def fake_run_core_pipeline(**kwargs): + captured.update(kwargs) + return sentinel + + monkeypatch.setattr(pipeline_module, "run_core_pipeline", fake_run_core_pipeline) + + assert pipeline_module.run_pipeline(depmap_snapshot_path="portable-bundle") is sentinel + assert captured["depmap_snapshot_path"] == "portable-bundle" diff --git a/tests/test_depmap_report_loader.py b/tests/test_depmap_report_loader.py new file mode 100644 index 0000000..5eaf45c --- /dev/null +++ b/tests/test_depmap_report_loader.py @@ -0,0 +1,32 @@ +from __future__ import annotations + +from hashlib import sha256 +import json +import pytest + +from targetintel.functional_dependency.report_loader import DependencyReportLoaderError, load_dependency_report_evidence_bundle +from test_depmap_v050_publication import published_bundle + + +def test_loader_is_deterministic_and_selectable(published_bundle: Path) -> None: + first = load_dependency_report_evidence_bundle(published_bundle) + assert len(first) == 331 and list(first) == sorted(first) + assert list(load_dependency_report_evidence_bundle(published_bundle, ["G002", "G000"])) == ["G000", "G002"] + with pytest.raises(DependencyReportLoaderError, match="unknown target"): + load_dependency_report_evidence_bundle(published_bundle, ["MISSING"]) + + +def test_loader_rejects_checksum_and_duplicate_records(published_bundle: Path) -> None: + evidence = published_bundle / "dependency_report_evidence.jsonl" + evidence.write_text(evidence.read_text() + evidence.read_text().splitlines()[0] + "\n") + with pytest.raises(DependencyReportLoaderError): + load_dependency_report_evidence_bundle(published_bundle) + checksums = published_bundle / "checksums.json" + rows = json.loads(checksums.read_text())["artifacts"] + for row in rows: + if row["name"] == evidence.name: + row["byte_size"] = evidence.stat().st_size + row["sha256"] = sha256(evidence.read_bytes()).hexdigest() + checksums.write_text(json.dumps({"artifacts": rows}, sort_keys=True, separators=(",", ":")) + "\n") + with pytest.raises(DependencyReportLoaderError, match="duplicate"): + load_dependency_report_evidence_bundle(published_bundle) diff --git a/tests/test_depmap_v050_publication.py b/tests/test_depmap_v050_publication.py new file mode 100644 index 0000000..7ee43c5 --- /dev/null +++ b/tests/test_depmap_v050_publication.py @@ -0,0 +1,164 @@ +"""Publication contract coverage using a synthetic closure, never real data.""" +from __future__ import annotations + +import csv +import json +from pathlib import Path +import shutil + +import pytest + +from targetintel.functional_dependency.publication import DepMapPublicationError, publish_depmap_v050 + + +def _prepared_closure(tmp_path: Path) -> tuple[Path, Path, Path, Path]: + root = tmp_path / "fixture" + shutil.copytree("tests/fixtures/depmap/report_snapshot", root) + run, config, manifests = root / "run", root / "config", root / "manifests" + replacements = { + "v050rc_fixture": "v050rc_fe68644624acd4b72aaf289baa9380c07f30d26c3271923ba81540f9b91e37b6", + "dmrm_fixture": "dmrm_08d15741ac2297df953346ff257dec05feb0b754a62ae6a9f56573e11801c5b1", + "v050closure_fixture": "v050closure_e57fa135ff266078d2170bf2a34df094f7888e7ce6002783c75f6a583690a3a4", + } + for path in (*run.rglob("*.json"), *config.rglob("*.json"), *manifests.rglob("*.json")): + text = path.read_text() + for old, new in replacements.items(): + text = text.replace(old, new) + path.write_text(text) + closure = json.loads((run / "release_closure_manifest.json").read_text()) + closure["scientific_closure_identity"] = replacements["v050closure_fixture"] + (run / "release_closure_manifest.json").write_text(json.dumps(closure)) + preflight = json.loads((run / "release_preflight.json").read_text()) + preflight["source_files"] = [ + {"filename": "CRISPRGeneEffect.csv", "sha256": "0" * 64, "byte_size": 1, "role": "gene effect"}, + {"filename": "CRISPRGeneDependency.csv", "sha256": "1" * 64, "byte_size": 1, "role": "dependency probability"}, + {"filename": "Model.csv", "sha256": "2" * 64, "byte_size": 1, "role": "model metadata"}, + ] + (run / "release_preflight.json").write_text(json.dumps(preflight)) + payload = {"terminal_status": "valid", "payload": {"target_resolution_status": "resolved_exact", "coverage_status": "sufficient_complete_coverage", "matrix_coverage_status": "resolved", "model_coverage": {"context_model_count": 2, "non_context_model_count": 3, "pan_cancer_model_count": 5}, "summaries": {"context": {"gene_effect": {"median": -0.8, "measured_model_count": 2}, "dependency_probability": {"median": 0.7, "measured_model_count": 2}}, "non_context": {"gene_effect": {"median": -0.2, "measured_model_count": 3}}}, "contrasts": {}, "empirical_context_lineage_position": {}, "limitations": ["Descriptive research-preview evidence only."]}} + profiles = run / "profiles" / "dependency_profiles.jsonl" + profiles.write_text("".join(json.dumps({"target_identity": {"normalized_request": f"G{i:03d}", "canonical_identity": f"G{i:03d}:{i + 1}"}, **payload}) + "\n" for i in range(331))) + (run / "integration" / "candidate_overlay.tsv").write_text( + "original_target_identifier\tbaseline_rank\tbaseline_score\tcandidate_rank\tprofile_available\n" + + "".join(f"G{i:03d}\t{i + 1}\t0.0\t{i + 1}\tTrue\n" for i in range(300)) + ) + ranked = tmp_path / "ranked.tsv" + ranked.write_text("target_symbol\n" + "".join(f"G{i:03d}\n" for i in range(300))) + return run, config, manifests, ranked + + +@pytest.fixture +def published_bundle(tmp_path: Path) -> Path: + run, config, manifests, ranked = _prepared_closure(tmp_path) + return publish_depmap_v050(run_dir=run, config_dir=config, manifest_dir=manifests, output_dir=tmp_path / "bundle", ranked_targets=ranked) + + +def test_publication_has_complete_aggregate_inventory_and_profiles(published_bundle: Path) -> None: + profiles = list(csv.DictReader((published_bundle / "selected_target_profiles.tsv").open(), delimiter="\t")) + inventory = list(csv.DictReader((published_bundle / "publication_inventory.tsv").open(), delimiter="\t")) + assert len(profiles) == 331 and len({row["target"] for row in profiles}) == 331 + assert {row["source_artifact_name"] for row in inventory} >= {"CRISPRGeneEffect.csv", "CRISPRGeneDependency.csv", "Model.csv"} + assert all(row["exclusion_reason"] for row in inventory if row["publication_action"] == "excluded") + assert not any(path.name == "dependency_profiles.jsonl" for path in published_bundle.rglob("*")) + assert all(path.stat().st_size <= 5 * 1024 * 1024 for path in published_bundle.rglob("*") if path.is_file()) + + +def test_publication_sanitizes_local_operational_metadata(tmp_path: Path) -> None: + run, config, manifests, ranked = _prepared_closure(tmp_path) + (run / "release_report.md").write_text("host S6445-MD61213 mount 5EC8-12FA") + bundle = publish_depmap_v050(run_dir=run, config_dir=config, manifest_dir=manifests, output_dir=tmp_path / "bundle", ranked_targets=ranked) + published = (bundle / "release_report.md").read_text() + assert "S6445-MD61213" not in published and "5EC8-12FA" not in published + + +def test_publication_preserves_official_https_urls(tmp_path: Path) -> None: + run, config, manifests, ranked = _prepared_closure(tmp_path) + bundle = publish_depmap_v050(run_dir=run, config_dir=config, manifest_dir=manifests, + output_dir=tmp_path / "bundle", ranked_targets=ranked) + source_manifest = json.loads((bundle / "source_manifest.json").read_text()) + assert source_manifest["official_download_url"] == "https://depmap.org/portal/data_page/?release=DepMap+Public+26Q1" + assert source_manifest["official_release_notes_url"] == "https://forum.depmap.org/t/announcing-the-26q1-release/4606" + + +def test_publication_relabels_inherited_fixture_limitations_for_real_release(tmp_path: Path) -> None: + run, config, manifests, ranked = _prepared_closure(tmp_path) + profiles = run / "profiles" / "dependency_profiles.jsonl" + profiles.write_text(profiles.read_text().replace( + "Descriptive research-preview evidence only.", + "Descriptive synthetic-fixture evidence only; no therapeutic, clinical, safety, or causal conclusion.", + )) + bundle = publish_depmap_v050(run_dir=run, config_dir=config, manifest_dir=manifests, + output_dir=tmp_path / "bundle", ranked_targets=ranked) + evidence = (bundle / "dependency_report_evidence.jsonl").read_text() + assert "Descriptive synthetic-fixture evidence only" not in evidence + assert "Descriptive real-release aggregate evidence only" in evidence + + +def test_publication_rejects_a_non_300_gene_baseline(tmp_path: Path) -> None: + run, config, manifests, ranked = _prepared_closure(tmp_path) + ranked.write_text("target_symbol\nG000\n") + with pytest.raises(DepMapPublicationError, match="exactly 300"): + publish_depmap_v050(run_dir=run, config_dir=config, manifest_dir=manifests, + output_dir=tmp_path / "bundle", ranked_targets=ranked) + + +def test_publication_tsv_files_do_not_end_lines_with_whitespace( + published_bundle: Path, +) -> None: + for path in sorted(published_bundle.glob("*.tsv")): + for line_number, line in enumerate( + path.read_bytes().splitlines(), + start=1, + ): + assert not line.endswith( + (b" ", b"\t") + ), ( + f"{path.name}:{line_number} ends with " + "trailing whitespace" + ) + + +def test_real_markdown_cards_end_with_single_newline() -> None: + card_dir = Path( + "examples/target_cards/depmap_26q1" + ) + cards = sorted(card_dir.glob("*.md")) + + assert len(cards) == 331 + + for path in cards: + raw = path.read_bytes() + + assert raw.endswith(b"\n"), ( + f"{path} does not end with a newline" + ) + assert not raw.endswith(b"\n\n"), ( + f"{path} ends with a blank line" + ) + + +def test_real_html_indexes_have_no_trailing_whitespace() -> None: + paths = [ + Path("examples/html_reports/depmap_26q1/index.html"), + Path( + "examples/html_reports/depmap_26q1/" + "targets/index.html" + ), + ] + + for path in paths: + raw = path.read_bytes() + + assert raw.endswith(b"\n") + assert not raw.endswith(b"\n\n") + + for line_number, line in enumerate( + raw.splitlines(), + start=1, + ): + assert not line.endswith( + (b" ", b"\t") + ), ( + f"{path}:{line_number} contains " + "trailing whitespace" + ) diff --git a/tests/test_v050_release.py b/tests/test_v050_release.py new file mode 100644 index 0000000..bae792c --- /dev/null +++ b/tests/test_v050_release.py @@ -0,0 +1,32 @@ +from __future__ import annotations + +from pathlib import Path +import tomllib + + +def test_v050_release_documents_the_real_portable_bundle() -> None: + assert tomllib.loads(Path("pyproject.toml").read_text())["project"]["version"] == "0.5.0" + assert "Single-cell and spatial evidence integration is planned for v0.6.0." in Path("README.md").read_text() + assert Path("data/releases/depmap/DepMap_Public_26Q1/source_manifest.json").is_file() + assert "repository-safe aggregate evidence bundle is published" in Path("docs/releases/v0.5.0.md").read_text() + + +def test_real_publication_uses_real_source_urls_and_truthful_baseline_rendering() -> None: + source_manifest = Path("data/releases/depmap/DepMap_Public_26Q1/source_manifest.json").read_text() + braf_markdown = Path("examples/target_cards/depmap_26q1/BRAF.md").read_text() + braf_html = Path("examples/html_reports/depmap_26q1/targets/BRAF.html").read_text() + index_html = Path("examples/html_reports/depmap_26q1/index.html").read_text() + assert "https://depmap.org/portal/data_page/?release=DepMap+Public+26Q1" in source_manifest + assert "https://forum.depmap.org/t/announcing-the-26q1-release/4606" in source_manifest + assert "| Antibody / IO-combination | 0.269 | 7 |" in braf_markdown + assert "| Resistance biomarker | 0.482 | 11 |" in braf_markdown + assert "| Tumor-intrinsic / small molecule | 0.845 | 1 |" in braf_markdown + assert "0.269" in braf_html + assert "0.482" in braf_html + assert "0.845" in braf_html + assert "Top antibody / IO-combination targets" in index_html + assert "Top resistance biomarker candidates" in index_html + assert "Top tumor-intrinsic / small-molecule candidates" in index_html + assert "Authoritative baseline is retained; the full score table is not reproduced" not in index_html + assert "Descriptive synthetic-fixture evidence only" not in braf_markdown + assert "Descriptive synthetic-fixture evidence only" not in braf_html