Additional validation for disease ontology

src/cap_upload_validator/errors.py

@@ -114,6 +114,26 @@ def __init__(self, missing_columns: list[str] = None):
             self.message = msg
 
 
+class AnnDataMultipleOntologyIDs(CapException):
+    name = "AnnDataMultipleOntologyIDs"
+
+    def __init__(self, columns: Optional[List[str]] = None):
+        msg = (
+            "Ontology term columns must contain exactly one ontology ID per value. "
+            "Multiple IDs (e.g. comma-separated values) are not allowed."
+        )
+
+        if columns:
+            msg += "\nColumns with multiple IDs detected: " + ", ".join(sorted(columns))
+
+        self.message = msg
+
+
+class AnnDataInvalidDiseaseOntologyForHuman(CapException):
+    name = "AnnDataInvalidDiseaseOntologyForHuman"
+    message = "Unsupported disease ontology term. For Homo sapiens datasets, only `MONDO:` and `PATO:` ontology terms are supported."
+
+
 class AnnDataEmptyOrNoneInGeneralMetadata(CapException):
     name = "AnnDataEmptyOrNoneInGeneralMetadata"
 

src/cap_upload_validator/upload_validator.py

@@ -21,6 +21,8 @@
     AnnDataMissingEmbeddings,
     AnnDataMissingObs,
     AnnDataMissingObsColumns,
+    AnnDataMultipleOntologyIDs,
+    AnnDataInvalidDiseaseOntologyForHuman,
     AnnDataMissingVarIndex,
     AnnDataNumericVarIndex,
     AnnDataVarNotSubsetOfRawVar,
@@ -39,6 +41,7 @@
 ORGANISM_COLUMN = "organism"
 ORGANISM_ONT_ID_COLUMN = f"{ORGANISM_COLUMN}_ontology_term_id"
 GENERAL_METADATA = ["assay", "disease", ORGANISM_COLUMN, "tissue"]
+DISEASE_ONTOLOGY_HUMAN_PREFIXES = ("MONDO", "PATO")
 
 class UploadValidator:
 
@@ -78,8 +81,8 @@ def validate(self, report_success: bool = True) -> None:
             self._validate_x_and_raw_x_formats(cap_adata)
             self._check_X(cap_adata)
             self._check_obsm(cap_adata)
-            self._check_obs(cap_adata)
             self._check_var_index(cap_adata)
+            self._check_obs(cap_adata) # Must be called after organism detection in _check_var_index 
 
         # Check any errors were during validation stage and raise them
         if self._multi_exception.have_errors():
@@ -183,6 +186,7 @@ def _check_obs(self, cap_adata: CapAnnData) -> None:
         missing_columns: list[str] = []
         none_columns: set[str] = set()
         empty_columns: set[str] = set()
+        multiple_ontology_columns: set[str] = set()
 
         def _check_column(series: pd.Series, name: str):
             has_none, has_empty = self._classify_missing(series)
@@ -211,7 +215,27 @@ def _check_column(series: pd.Series, name: str):
                 if ont_id_col not in cap_adata.obs.columns:
                     cap_adata.read_obs(columns=[ont_id_col])
 
-                _check_column(cap_adata.obs[ont_id_col], ont_id_col)
+                series = cap_adata.obs[ont_id_col]
+                _check_column(series, ont_id_col)
+
+                # General validation (all ontology columns)
+                unique_values = (
+                    series
+                    .dropna()
+                    .astype(str)
+                    .str.strip()
+                    .unique()
+                )
+
+                for value_str in unique_values:
+                    if not value_str:
+                        continue
+                    if "," in value_str:
+                        multiple_ontology_columns.add(ont_id_col)
+
+                # Disease-specific validation
+                if col == "disease":
+                    self._validate_disease_ontology(series)
 
         # Report missing columns
         if missing_columns:
@@ -225,15 +249,43 @@ def _check_column(series: pd.Series, name: str):
                 ", ".join(sorted(empty_columns)) if empty_columns else "—",
                 ", ".join(sorted(none_columns)) if none_columns else "—",
             )
-            self._multi_exception.append(
-                AnnDataEmptyOrNoneInGeneralMetadata(
-                    none_columns=list(none_columns),
-                    empty_columns=list(empty_columns),
-                )
-            )
+            self._multi_exception.append(AnnDataEmptyOrNoneInGeneralMetadata(none_columns=list(none_columns), empty_columns=list(empty_columns)))
+
+        if multiple_ontology_columns:
+            self._multi_exception.append(AnnDataMultipleOntologyIDs(columns=list(multiple_ontology_columns)))
 
         logger.debug("Finished checking obs!")
 
+    def _validate_disease_ontology(self, series: pd.Series) -> None:
+        if series is None or self._organism is not HomoSapiens:
+            return
+
+        has_invalid_prefix_for_human = False
+
+        unique_values = (
+            series
+            .dropna()
+            .astype(str)
+            .str.strip()
+            .unique()
+        )
+
+        delimiter = ":"
+        for value_str in unique_values:
+            if not value_str:
+                continue
+
+            if delimiter not in value_str:
+                has_invalid_prefix_for_human = True
+                continue
+
+            prefix = value_str.split(delimiter, 1)[0]
+            if prefix not in DISEASE_ONTOLOGY_HUMAN_PREFIXES:
+                has_invalid_prefix_for_human = True
+
+        if has_invalid_prefix_for_human:
+            self._multi_exception.append(AnnDataInvalidDiseaseOntologyForHuman())
+
     @staticmethod
     def _classify_missing(series: pd.Series) -> tuple[bool, bool]:
         """

test/test_upload_validator.py

@@ -31,6 +31,8 @@
     CapMultiException,
     AnnDataEmptyOrNoneInGeneralMetadata,
     CSCMatrixInX,
+    AnnDataMultipleOntologyIDs,
+    AnnDataInvalidDiseaseOntologyForHuman,
 )
 
 TMP_DIR = Path(tempfile.mkdtemp())
@@ -338,3 +340,93 @@ def test_dense_and_csr_pass(tmp_path):
 
     with read_h5ad(p, edit=False) as cap_adata:
         v._validate_x_and_raw_x_formats(cap_adata) # should not raise
+
+
+def add_required_obs_columns(adata):
+    adata.obs[ORGANISM_COLUMN] = pd.Categorical(
+        [HomoSapiens.name] * adata.n_obs
+    )
+    adata.obs["assay_ontology_term_id"] = pd.Categorical(
+        ["EFO:0000001"] * adata.n_obs
+    )
+    adata.obs["organism_ontology_term_id"] = pd.Categorical(
+        [HomoSapiens.ontology_id] * adata.n_obs
+    )
+    adata.obs["disease_ontology_term_id"] = pd.Categorical(
+        ["MONDO:0000001"] * adata.n_obs
+    )
+    adata.obs["tissue_ontology_term_id"] = pd.Categorical(
+        ["UBERON:0000001"] * adata.n_obs
+    )
+
+
+def test_multiple_ontology_ids_raises(tmp_path, monkeypatch):
+    file_path = tmp_path / "test_multiple_ids.h5ad"
+
+    adata = ad.AnnData(X=np.eye(3))
+    add_required_obs_columns(adata)
+
+    # Add invalid multi-ID category
+    adata.obs["tissue_ontology_term_id"] = (
+        adata.obs["tissue_ontology_term_id"]
+        .cat.add_categories(["UBERON:0001,UBERON:0002"])
+    )
+
+    adata.obs.iloc[0, adata.obs.columns.get_loc("tissue_ontology_term_id")] = \
+        "UBERON:0001,UBERON:0002"
+
+    adata.write_h5ad(file_path)
+
+    validator = UploadValidator(file_path)
+    validator._multi_exception.raise_on_append = True
+
+    # Mock var validation
+    def mock_check_var_index(self, cap_adata):
+        self._organism = HomoSapiens
+
+    monkeypatch.setattr(
+        UploadValidator,
+        "_check_var_index",
+        mock_check_var_index,
+    )
+
+    with read_h5ad(file_path) as cap_adata:
+        cap_adata.read_obs()
+        validator._check_var_index(cap_adata)
+
+        with pytest.raises(AnnDataMultipleOntologyIDs):
+            validator._check_obs(cap_adata)
+
+
+def test_invalid_disease_prefix_for_human_raises(tmp_path, monkeypatch):
+    file_path = tmp_path / "test_invalid_disease_prefix.h5ad"
+
+    adata = ad.AnnData(X=np.eye(3))
+    add_required_obs_columns(adata)
+
+    # Replace disease column with invalid prefix
+    adata.obs["disease_ontology_term_id"] = pd.Categorical(
+        ["DOID:1234"] * adata.n_obs
+    )
+
+    adata.write_h5ad(file_path)
+
+    validator = UploadValidator(file_path)
+    validator._multi_exception.raise_on_append = True
+
+    # Mock var validation
+    def mock_check_var_index(self, cap_adata):
+        self._organism = HomoSapiens
+
+    monkeypatch.setattr(
+        UploadValidator,
+        "_check_var_index",
+        mock_check_var_index,
+    )
+
+    with read_h5ad(file_path) as cap_adata:
+        cap_adata.read_obs()
+        validator._check_var_index(cap_adata)
+
+        with pytest.raises(AnnDataInvalidDiseaseOntologyForHuman):
+            validator._check_obs(cap_adata)