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17 changes: 17 additions & 0 deletions .gitignore
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# 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
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11 changes: 11 additions & 0 deletions CHANGELOG.md
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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.
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9 changes: 6 additions & 3 deletions README.md
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Expand Up @@ -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

Expand Down Expand Up @@ -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.
Expand Down Expand Up @@ -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

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9 changes: 9 additions & 0 deletions data/releases/depmap/DepMap_Public_26Q1/README.md
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# 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.
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{"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"}
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{"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}}
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{"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}
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{"profiled_target_count":56,"ranked_target_count":25,"reconciliation_counts":{"profiled_not_ranked":31,"ranked_and_profiled":25},"total_benchmark_targets":56}
3 changes: 3 additions & 0 deletions data/releases/depmap/DepMap_Public_26Q1/benchmark_report.md
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# 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.
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