From 2e825ba205ae2b2ad4e03ae660b6e8257100828a Mon Sep 17 00:00:00 2001
From: nayib-jose-gloria <ngloria@chanzuckerberg.com>
Date: Fri, 15 Sep 2023 11:06:28 -0400
Subject: [PATCH 1/7] feat: require tissue_type field and add new validation
 rules for tissue_ontology_term_id and cell_type_ontology_term_id

---
 .../schema_definitions/schema_definition.yaml |  52 ++++++++++++++----
 .../tests/fixtures/examples_validate.py       |   8 ++-
 .../fixtures/h5ads/example_invalid_CL.h5ad    | Bin 573648 -> 575672 bytes
 .../tests/fixtures/h5ads/example_valid.h5ad   | Bin 573536 -> 575888 bytes
 .../tests/test_schema_compliance.py           |  29 +++++++---
 5 files changed, 68 insertions(+), 21 deletions(-)

diff --git a/cellxgene_schema_cli/cellxgene_schema/schema_definitions/schema_definition.yaml b/cellxgene_schema_cli/cellxgene_schema/schema_definitions/schema_definition.yaml
index 2ffd5aba1..bd5cac351 100644
--- a/cellxgene_schema_cli/cellxgene_schema/schema_definitions/schema_definition.yaml
+++ b/cellxgene_schema_cli/cellxgene_schema/schema_definitions/schema_definition.yaml
@@ -103,6 +103,10 @@ components:
                 curie_constraints:
                     ontologies:
                         - CL
+                    forbidden:
+                        - CL:0000255
+                        - CL:0000257
+                        - CL:0000548
                 add_labels:
                     -
                         type: curie
@@ -163,15 +167,35 @@ components:
                         to_column: sex
             tissue_ontology_term_id:
                 type: curie
-                curie_constraints:
-                    ontologies:
-                        - UBERON
-                        - CL
-                    suffixes:
-                        UBERON:
-                            - " (organoid)"
-                        CL:
-                            - " (cell culture)"
+                dependencies:
+                    -
+                        # If tissue_type is tissue OR organoid
+                        rule: "tissue_type == 'tissue' | tissue_type == 'organoid'"
+                        error_message_suffix: >-
+                            When 'tissue_type' is 'tissue' or 'organoid',
+                            'tissue_ontology_term_id' MUST be a child term id of 'UBERON:0001062' (anatomical entity).
+                        type: curie
+                        curie_constraints:
+                            ontologies:
+                                - UBERON
+                            ancestors:
+                                UBERON:
+                                    - UBERON:0001062
+                    -
+                        # If tissue_type is cell culture
+                        rule: "tissue_type == 'cell culture'"
+                        error_message_suffix: >-
+                            When 'tissue_type' is 'cell culture', 'tissue_ontology_term_id' MUST be a CL term
+                            and it can not be 'CL:0000255' (eukaryotic cell), 'CL:0000257' (Eumycetozoan cell),
+                            nor 'CL:0000548' (animal cell).
+                        type: curie
+                        curie_constraints:
+                            ontologies:
+                                - CL
+                            forbidden:
+                                - CL:0000255
+                                - CL:0000257
+                                - CL:0000548
                 add_labels:
                     -
                         type: curie
@@ -527,4 +551,12 @@ components:
                             when 'assay_ontology_term_id' is EFO:0009919
                         enum:
                             - "cell"
-                            - "nucleus"
\ No newline at end of file
+                            - "nucleus"
+            tissue_type:
+                type: categorical
+                error_message_suffix: >-
+                    Only 'cell culture', 'organoid', or 'tissue' are allowed.
+                enum:
+                    - "cell culture"
+                    - "organoid"
+                    - "tissue"
\ No newline at end of file
diff --git a/cellxgene_schema_cli/tests/fixtures/examples_validate.py b/cellxgene_schema_cli/tests/fixtures/examples_validate.py
index e38c81fde..fe39afa50 100644
--- a/cellxgene_schema_cli/tests/fixtures/examples_validate.py
+++ b/cellxgene_schema_cli/tests/fixtures/examples_validate.py
@@ -41,6 +41,7 @@
             "NCBITaxon:9606",
             "PATO:0000383",
             "UBERON:0002048",
+            "tissue",
             True,
             "HANCESTRO:0575",
             "HsapDv:0000003",
@@ -53,7 +54,8 @@
             "PATO:0000461",
             "NCBITaxon:10090",
             "unknown",
-            "CL:0000192 (cell culture)",
+            "CL:0000192",
+            "cell culture",
             False,
             "na",
             "MmusDv:0000003",
@@ -69,6 +71,7 @@
         "organism_ontology_term_id",
         "sex_ontology_term_id",
         "tissue_ontology_term_id",
+        "tissue_type",
         "is_primary_data",
         "self_reported_ethnicity_ontology_term_id",
         "development_stage_ontology_term_id",
@@ -79,6 +82,7 @@
 
 good_obs.loc[:, ["donor_id"]] = good_obs.astype("category")
 good_obs.loc[:, ["suspension_type"]] = good_obs.astype("category")
+good_obs.loc[:, ["tissue_type"]] = good_obs.astype("category")
 
 # Expected obs, this is what the obs above should look like after adding the necessary columns with the validator,
 # these columns are defined in the schema
@@ -100,7 +104,7 @@
             "normal",
             "Mus musculus",
             "unknown",
-            "smooth muscle cell (cell culture)",
+            "smooth muscle cell",
             "na",
             "Theiler stage 01",
         ],
diff --git a/cellxgene_schema_cli/tests/fixtures/h5ads/example_invalid_CL.h5ad b/cellxgene_schema_cli/tests/fixtures/h5ads/example_invalid_CL.h5ad
index e219b619bc853349e8ac6edc1138edddc71b9f25..53ea1b189db7e596efe157f00475ab28832b829c 100644
GIT binary patch
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diff --git a/cellxgene_schema_cli/tests/fixtures/h5ads/example_valid.h5ad b/cellxgene_schema_cli/tests/fixtures/h5ads/example_valid.h5ad
index 26ae0dcab4abf24d13528b1537323dc4e778d1be..05b90951da329e8b3cddb359ce38096ec0772c19 100644
GIT binary patch
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diff --git a/cellxgene_schema_cli/tests/test_schema_compliance.py b/cellxgene_schema_cli/tests/test_schema_compliance.py
index 32188ec43..56af22d6c 100644
--- a/cellxgene_schema_cli/tests/test_schema_compliance.py
+++ b/cellxgene_schema_cli/tests/test_schema_compliance.py
@@ -493,43 +493,54 @@ def test_tissue_ontology_term_id_base(self):
         """
 
         self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "tissue_ontology_term_id"] = "EFO:0000001"
+        self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "tissue_type"] = "tissue"
         self.validator.validate_adata()
         self.assertEqual(
             self.validator.errors,
-            ["ERROR: 'EFO:0000001' in 'tissue_ontology_term_id' is not a " "valid ontology term id of 'UBERON, CL'."],
+            [
+                "ERROR: 'EFO:0000001' in 'tissue_ontology_term_id' is not a valid ontology term id of "
+                "'UBERON'. When 'tissue_type' is 'tissue' or 'organoid', 'tissue_ontology_term_id' MUST be a "
+                "child term id of 'UBERON:0001062' (anatomical entity)."
+            ],
         )
 
     def test_tissue_ontology_term_id_cell_culture(self):
         """
-        Cell Culture - MUST be a CL term appended with " (cell culture)"
+        Cell Culture - must not accept suffixes like "(cell culture)"
         """
 
         self.validator.adata.obs.loc[
             self.validator.adata.obs.index[0], "tissue_ontology_term_id"
-        ] = "CL:0000057 (CELL culture)"
+        ] = "CL:0000057 (cell culture)"
+        self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "tissue_type"] = "cell culture"
         self.validator.validate_adata()
         self.assertEqual(
             self.validator.errors,
             [
-                "ERROR: 'CL:0000057 (CELL culture)' in 'tissue_ontology_term_id' is "
-                "not a valid ontology term id of 'UBERON, CL'."
+                "ERROR: 'CL:0000057 (cell culture)' in 'tissue_ontology_term_id' is not a valid ontology term id of "
+                "'CL'. When 'tissue_type' is 'cell culture', 'tissue_ontology_term_id' MUST be a CL term "
+                "and it can not be 'CL:0000255' (eukaryotic cell), 'CL:0000257' (Eumycetozoan cell), "
+                "nor 'CL:0000548' (animal cell)."
             ],
         )
 
     def test_tissue_ontology_term_id_organoid(self):
         """
-        Organoid - MUST be an UBERON term appended with " (organoid)"
+        Organoid - must not accept suffixes like "(organoid)"
         """
 
         self.validator.adata.obs.loc[
             self.validator.adata.obs.index[0], "tissue_ontology_term_id"
-        ] = "CL:0000057 (ORGANOID)"
+        ] = "UBERON:0000057 (organoid)"
+        self.validator.adata.obs.tissue_type = self.validator.adata.obs.tissue_type.cat.add_categories(["organoid"])
+        self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "tissue_type"] = "organoid"
         self.validator.validate_adata()
         self.assertEqual(
             self.validator.errors,
             [
-                "ERROR: 'CL:0000057 (ORGANOID)' in 'tissue_ontology_term_id' is "
-                "not a valid ontology term id of 'UBERON, CL'."
+                "ERROR: 'UBERON:0000057 (organoid)' in 'tissue_ontology_term_id' is not a valid ontology term id of "
+                "'UBERON'. When 'tissue_type' is 'tissue' or 'organoid', 'tissue_ontology_term_id' MUST be a "
+                "child term id of 'UBERON:0001062' (anatomical entity)."
             ],
         )
 

From c3bfb99d5a990050dadccaa7766276d3b1df0009 Mon Sep 17 00:00:00 2001
From: nayib-jose-gloria <ngloria@chanzuckerberg.com>
Date: Fri, 15 Sep 2023 11:08:23 -0400
Subject: [PATCH 2/7] validate raw.var and raw.X dimension consistency if raw
 exists

---
 .../cellxgene_schema/validate.py              |  7 +++++++
 cellxgene_schema_cli/tests/test_validate.py   | 19 +++++++++++++++----
 2 files changed, 22 insertions(+), 4 deletions(-)

diff --git a/cellxgene_schema_cli/cellxgene_schema/validate.py b/cellxgene_schema_cli/cellxgene_schema/validate.py
index 62d987101..964c1982c 100644
--- a/cellxgene_schema_cli/cellxgene_schema/validate.py
+++ b/cellxgene_schema_cli/cellxgene_schema/validate.py
@@ -800,6 +800,13 @@ def _validate_seurat_convertibility(self):
                     )
 
                 self.is_seurat_convertible = False
+        if self.adata.raw and self.adata.raw.X.shape[1] != self.adata.raw.var.shape[0]:
+            self.warnings.append(
+                f"This dataset cannot be converted to the .rds (Seurat v4) format. "
+                f"There is a mismatch in the number of variables in the raw matrix and the raw var key-indexed "
+                f"variables."
+            )
+            self.is_seurat_convertible = False
 
     def _validate_embedding_dict(self):
         """
diff --git a/cellxgene_schema_cli/tests/test_validate.py b/cellxgene_schema_cli/tests/test_validate.py
index 0c71f6fa6..447fe295c 100644
--- a/cellxgene_schema_cli/tests/test_validate.py
+++ b/cellxgene_schema_cli/tests/test_validate.py
@@ -54,16 +54,16 @@ def test_schema_definition(self):
             self.assertTrue("type" in self.schema_def["components"]["obs"]["columns"][i])
             if i == "curie":
                 self.assertIsInstance(
-                    self.schema_def["components"]["obs"]["columns"][i]["curie_constrains"],
+                    self.schema_def["components"]["obs"]["columns"][i]["curie_constraints"],
                     dict,
                 )
                 self.assertIsInstance(
-                    self.schema_def["components"]["obs"]["columns"][i]["curie_constrains"]["ontolgies"],
+                    self.schema_def["components"]["obs"]["columns"][i]["curie_constraints"]["ontolgies"],
                     list,
                 )
 
                 # Check that the allowed ontologies are in the ontology checker
-                for ontology_name in self.schema_def["components"]["obs"]["columns"][i]["curie_constrains"][
+                for ontology_name in self.schema_def["components"]["obs"]["columns"][i]["curie_constraints"][
                     "ontolgies"
                 ]:
                     self.assertTrue(self.OntologyChecker.is_valid_ontology(ontology_name))
@@ -281,8 +281,10 @@ def test__validate_with_h5ad_invalid_and_without_labels(self):
 
 
 class TestSeuratConvertibility(unittest.TestCase):
-    def validation_helper(self, matrix):
+    def validation_helper(self, matrix, raw=None):
         data = anndata.AnnData(X=matrix, obs=good_obs, uns=good_uns, obsm=good_obsm, var=good_var)
+        if raw:
+            data.raw = raw
         self.validator: Validator = Validator()
         self.validator._set_schema_def()
         self.validator.schema_def["max_size_for_seurat"] = 2**3 - 1  # Reduce size required to fail (faster tests)
@@ -319,3 +321,12 @@ def test_determine_seurat_convertibility(self):
         self.validator._validate_seurat_convertibility()
         self.assertTrue(len(self.validator.warnings) == 0)
         self.assertTrue(self.validator.is_seurat_convertible)
+
+        # h5ad where raw matrix variable count != length of raw var variables array is not Seurat-convertible
+        matrix = sparse.csr_matrix(np.zeros([good_obs.shape[0], good_var.shape[0]], dtype=np.float32))
+        raw = anndata.AnnData(X=matrix, var=good_var)
+        raw.var.drop('ENSSASG00005000004', axis=0, inplace=True)
+        self.validation_helper(matrix, raw)
+        self.validator._validate_seurat_convertibility()
+        self.assertTrue(len(self.validator.warnings) == 1)
+        self.assertFalse(self.validator.is_seurat_convertible)

From 5ab4e57a7ec878ed18d86e9047ab52db79cd92e3 Mon Sep 17 00:00:00 2001
From: nayib-jose-gloria <ngloria@chanzuckerberg.com>
Date: Fri, 15 Sep 2023 13:07:52 -0400
Subject: [PATCH 3/7] =?UTF-8?q?Bump=20version:=204.0.0-rc.0=20=E2=86=92=20?=
 =?UTF-8?q?4.0.0-rc.0?=
MIME-Version: 1.0
Content-Type: text/plain; charset=UTF-8
Content-Transfer-Encoding: 8bit

---
 cellxgene_schema_cli/cellxgene_schema/__init__.py | 2 +-
 cellxgene_schema_cli/setup.py                     | 2 +-
 2 files changed, 2 insertions(+), 2 deletions(-)

diff --git a/cellxgene_schema_cli/cellxgene_schema/__init__.py b/cellxgene_schema_cli/cellxgene_schema/__init__.py
index cb467ae1d..14c14eb36 100644
--- a/cellxgene_schema_cli/cellxgene_schema/__init__.py
+++ b/cellxgene_schema_cli/cellxgene_schema/__init__.py
@@ -1 +1 @@
-__version__ = "4.0.0-rc.0"
+__version__ = "__version__ = "4.0.0-rc.0""
diff --git a/cellxgene_schema_cli/setup.py b/cellxgene_schema_cli/setup.py
index e51d24064..95f2c1573 100644
--- a/cellxgene_schema_cli/setup.py
+++ b/cellxgene_schema_cli/setup.py
@@ -5,7 +5,7 @@
 
 setup(
     name="cellxgene-schema",
-    version="4.0.0-rc.0",
+    version="version="4.0.0-rc.0"",
     url="https://github.com/chanzuckerberg/single-cell-curation",
     license="MIT",
     author="Chan Zuckerberg Initiative",

From 2b85dc8a02dab19b21a964cfb97edcb30b57dfef Mon Sep 17 00:00:00 2001
From: nayib-jose-gloria <ngloria@chanzuckerberg.com>
Date: Fri, 15 Sep 2023 13:08:46 -0400
Subject: [PATCH 4/7] add tests + simplify suffix write-labels + validation now
 that its not allowed

---
 .../schema_definitions/schema_definition.yaml |   2 -
 .../cellxgene_schema/validate.py              |  47 +-----
 .../cellxgene_schema/write_labels.py          |  24 +--
 .../tests/test_schema_compliance.py           | 138 +++++++++++++++---
 cellxgene_schema_cli/tests/test_validate.py   |  40 +++--
 5 files changed, 150 insertions(+), 101 deletions(-)

diff --git a/cellxgene_schema_cli/cellxgene_schema/schema_definitions/schema_definition.yaml b/cellxgene_schema_cli/cellxgene_schema/schema_definitions/schema_definition.yaml
index bd5cac351..caf2ae618 100644
--- a/cellxgene_schema_cli/cellxgene_schema/schema_definitions/schema_definition.yaml
+++ b/cellxgene_schema_cli/cellxgene_schema/schema_definitions/schema_definition.yaml
@@ -554,8 +554,6 @@ components:
                             - "nucleus"
             tissue_type:
                 type: categorical
-                error_message_suffix: >-
-                    Only 'cell culture', 'organoid', or 'tissue' are allowed.
                 enum:
                     - "cell culture"
                     - "organoid"
diff --git a/cellxgene_schema_cli/cellxgene_schema/validate.py b/cellxgene_schema_cli/cellxgene_schema/validate.py
index 964c1982c..c3a3720d8 100644
--- a/cellxgene_schema_cli/cellxgene_schema/validate.py
+++ b/cellxgene_schema_cli/cellxgene_schema/validate.py
@@ -43,35 +43,6 @@ def __init__(self, ignore_labels=False):
         # Matrix (e.g., X, raw.X, ...) number non-zero cache
         self.number_non_zero = dict()
 
-    @staticmethod
-    def _curie_remove_suffix(term_id: str, suffix_def: dict) -> Tuple[str, str]:
-        """
-        Remove suffix from a curie term id, if none present return it unmodified
-
-        :param str term_id: the curie term id to validate
-        :param dict{str: list[str], ...} suffix_def: dictionary whose keys are ontology term ids and values
-        are list of allowed suffixes
-
-        :rtype Tuple[str, str]
-        :return the term_id with suffixed stripped, and the suffix
-        """
-
-        id_suffix = ""
-
-        for ontology_name, suffixes in suffix_def.items():
-            for suffix in suffixes:
-                suffix = suffix.replace("(", r"\(")
-                suffix = suffix.replace(")", r"\)")
-                search_results = re.search(r"%s$" % suffix, term_id)
-                if search_results:
-                    stripped_term_id = re.sub(r"%s$" % suffix, "", term_id)
-                    if ONTOLOGY_CHECKER.is_valid_term_id(ontology_name, stripped_term_id):
-                        id_suffix = search_results.group(0)
-
-                        return stripped_term_id, id_suffix
-
-        return term_id, id_suffix
-
     def _validate_encoding_version(self):
         import h5py
 
@@ -228,7 +199,7 @@ def _validate_curie(self, term_id: str, column_name: str, curie_constraints: dic
 
         # If there are forbidden terms
         if "forbidden" in curie_constraints and term_id in curie_constraints["forbidden"]:
-            self.errors.append(f"'{term_id}' in '{column_name}' is not allowed'.")
+            self.errors.append(f"'{term_id}' in '{column_name}' is not allowed.")
             return
 
         # If NA is found in allowed ontologies, it means only exceptions should be found. If no exceptions were found
@@ -237,10 +208,6 @@ def _validate_curie(self, term_id: str, column_name: str, curie_constraints: dic
             self.errors.append(f"'{term_id}' in '{column_name}' is not a valid value of '{column_name}'.")
             return
 
-        # Check if there are any allowed suffixes and remove them if needed
-        if "suffixes" in curie_constraints:
-            term_id, suffix = self._curie_remove_suffix(term_id, curie_constraints["suffixes"])
-
         # Check that term id belongs to allowed ontologies
         self._validate_curie_ontology(term_id, column_name, curie_constraints["ontologies"])
 
@@ -436,15 +403,9 @@ def _validate_column(self, column: pd.Series, column_name: str, df_name: str, co
                 self.errors.append(f"Column '{column_name}' in dataframe '{df_name}' must not contain NaN values.")
                 return
 
-            if "curie_constraints" not in column_def:
-                raise ValueError(f"Corrupt schema definition, no 'curie_constraints' were found for '{column_name}'")
-            if "ontologies" not in column_def["curie_constraints"]:
-                raise ValueError(
-                    f"allowed 'ontologies' must be specified under 'curie constraints' for '{column_name}'"
-                )
-
-            for term_id in column.drop_duplicates():
-                self._validate_curie(term_id, column_name, column_def["curie_constraints"])
+            if "curie_constraints" in column_def:
+                for term_id in column.drop_duplicates():
+                    self._validate_curie(term_id, column_name, column_def["curie_constraints"])
 
         # Add error suffix to errors found here
         if "error_message_suffix" in column_def:
diff --git a/cellxgene_schema_cli/cellxgene_schema/write_labels.py b/cellxgene_schema_cli/cellxgene_schema/write_labels.py
index f558c3b22..380bd6534 100644
--- a/cellxgene_schema_cli/cellxgene_schema/write_labels.py
+++ b/cellxgene_schema_cli/cellxgene_schema/write_labels.py
@@ -122,31 +122,21 @@ def _get_mapping_dict_curie(self, ids: List[str], curie_constraints: dict) -> Di
         mapping_dict = {}
         allowed_ontologies = curie_constraints["ontologies"]
 
-        # Remove any suffixes if any
-        # original_ids will have untouched ids which will be used for mapping
-        # id_suffixes will save suffixes if any, these will be used to append to labels
-        # ids will have the ids without suffixes
-        original_ids = ids.copy()
-        id_suffixes = [""] * len(ids)
-
-        if "suffixes" in curie_constraints:
-            for i in range(len(ids)):
-                ids[i], id_suffixes[i] = Validator._curie_remove_suffix(ids[i], curie_constraints["suffixes"])
-
-        for original_id, id, id_suffix in zip(original_ids, ids, id_suffixes):
+        # Map term_ids to their human-readable ontology labels
+        for term_id in ids:
             # If there are exceptions the label should be the same as the id
-            if "exceptions" in curie_constraints and original_id in curie_constraints["exceptions"]:
-                mapping_dict[original_id] = original_id
+            if "exceptions" in curie_constraints and term_id in curie_constraints["exceptions"]:
+                mapping_dict[term_id] = term_id
                 continue
 
             for ontology_name in allowed_ontologies:
                 if ontology_name == "NA":
                     continue
-                if ONTOLOGY_CHECKER.is_valid_term_id(ontology_name, id):
-                    mapping_dict[original_id] = ONTOLOGY_CHECKER.get_term_label(ontology_name, id) + id_suffix
+                if ONTOLOGY_CHECKER.is_valid_term_id(ontology_name, term_id):
+                    mapping_dict[term_id] = ONTOLOGY_CHECKER.get_term_label(ontology_name, term_id)
 
         # Check that all ids got a mapping. All ids should be found if adata was validated
-        for id in original_ids:
+        for id in ids:
             if id not in mapping_dict:
                 raise ValueError(f"Add labels error: Unable to get label for '{id}'")
 
diff --git a/cellxgene_schema_cli/tests/test_schema_compliance.py b/cellxgene_schema_cli/tests/test_schema_compliance.py
index 56af22d6c..2e67f307a 100644
--- a/cellxgene_schema_cli/tests/test_schema_compliance.py
+++ b/cellxgene_schema_cli/tests/test_schema_compliance.py
@@ -281,16 +281,31 @@ def test_assay_ontology_term_id(self):
 
     def test_cell_type_ontology_term_id(self):
         """
-        cell_type_ontology_term_id categorical with str categories. This MUST be a CL term.
+        cell_type_ontology_term_id categorical with str categories. This MUST be a CL term, and must NOT match forbidden
+        columns defined in schema
         """
 
         # Not a valid term
-        self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "cell_type_ontology_term_id"] = "EFO:0000001"
-        self.validator.validate_adata()
-        self.assertEqual(
-            self.validator.errors,
-            ["ERROR: 'EFO:0000001' in 'cell_type_ontology_term_id' is not a valid " "ontology term id of 'CL'."],
-        )
+        with self.subTest(forbidden_term="EFO:0000001"):
+            self.validator.adata.obs.loc[
+                self.validator.adata.obs.index[0], "cell_type_ontology_term_id"
+            ] = "EFO:0000001"
+            self.validator.validate_adata()
+            self.assertEqual(
+                self.validator.errors,
+                ["ERROR: 'EFO:0000001' in 'cell_type_ontology_term_id' is not a valid " "ontology term id of 'CL'."],
+            )
+
+        for term in self.validator.schema_def["components"]["obs"]["columns"]["cell_type_ontology_term_id"][
+            "curie_constraints"
+        ]["forbidden"]:
+            with self.subTest(forbidden_term=term):
+                self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "cell_type_ontology_term_id"] = term
+                self.validator.validate_adata()
+                self.assertEqual(
+                    self.validator.errors,
+                    [f"ERROR: '{term}' in 'cell_type_ontology_term_id' is not allowed."],
+                )
 
     def test_development_stage_ontology_term_id_human(self):
         """
@@ -377,7 +392,7 @@ def test_development_stage_ontology_term_id_all_species(self):
         self.assertEqual(
             self.validator.errors,
             [
-                "ERROR: 'UBERON:0000071' in 'development_stage_ontology_term_id' is not allowed'. When "
+                "ERROR: 'UBERON:0000071' in 'development_stage_ontology_term_id' is not allowed. When "
                 "'organism_ontology_term_id' is not 'NCBITaxon:10090' "
                 "nor 'NCBITaxon:9606', 'development_stage_ontology_term_id' MUST be a child term id of "
                 "'UBERON:0000105' excluding 'UBERON:0000071', or unknown.",
@@ -506,23 +521,54 @@ def test_tissue_ontology_term_id_base(self):
 
     def test_tissue_ontology_term_id_cell_culture(self):
         """
-        Cell Culture - must not accept suffixes like "(cell culture)"
+        Cell Culture - must be a valid CL term other than forbidden columns in schema definition. Can NOT include
+        suffixes.
         """
-
-        self.validator.adata.obs.loc[
-            self.validator.adata.obs.index[0], "tissue_ontology_term_id"
-        ] = "CL:0000057 (cell culture)"
         self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "tissue_type"] = "cell culture"
-        self.validator.validate_adata()
-        self.assertEqual(
-            self.validator.errors,
-            [
-                "ERROR: 'CL:0000057 (cell culture)' in 'tissue_ontology_term_id' is not a valid ontology term id of "
-                "'CL'. When 'tissue_type' is 'cell culture', 'tissue_ontology_term_id' MUST be a CL term "
-                "and it can not be 'CL:0000255' (eukaryotic cell), 'CL:0000257' (Eumycetozoan cell), "
-                "nor 'CL:0000548' (animal cell)."
-            ],
-        )
+
+        with self.subTest(case="error, suffix in term ID"):
+            self.validator.adata.obs.loc[
+                self.validator.adata.obs.index[0], "tissue_ontology_term_id"
+            ] = "CL:0000057 (cell culture)"
+            self.validator.validate_adata()
+            self.assertEqual(
+                self.validator.errors,
+                [
+                    "ERROR: 'CL:0000057 (cell culture)' in 'tissue_ontology_term_id' is not a valid ontology term id "
+                    "of 'CL'. When 'tissue_type' is 'cell culture', 'tissue_ontology_term_id' MUST be a CL term "
+                    "and it can not be 'CL:0000255' (eukaryotic cell), 'CL:0000257' (Eumycetozoan cell), "
+                    "nor 'CL:0000548' (animal cell)."
+                ],
+            )
+
+        with self.subTest(case="error, not a CL term"):
+            self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "tissue_ontology_term_id"] = "EFO:0000001"
+            self.validator.validate_adata()
+            self.assertEqual(
+                self.validator.errors,
+                [
+                    "ERROR: 'EFO:0000001' in 'tissue_ontology_term_id' is not a valid ontology term id of "
+                    "'CL'. When 'tissue_type' is 'cell culture', 'tissue_ontology_term_id' MUST be a CL term "
+                    "and it can not be 'CL:0000255' (eukaryotic cell), 'CL:0000257' (Eumycetozoan cell), "
+                    "nor 'CL:0000548' (animal cell)."
+                ],
+            )
+
+        for term in self.validator.schema_def["components"]["obs"]["columns"]["cell_type_ontology_term_id"][
+            "curie_constraints"
+        ]["forbidden"]:
+            with self.subTest(case="error", forbidden_term=term):
+                self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "tissue_ontology_term_id"] = term
+                self.validator.validate_adata()
+                self.assertEqual(
+                    self.validator.errors,
+                    [
+                        f"ERROR: '{term}' in 'tissue_ontology_term_id' is not allowed. When 'tissue_type' is "
+                        f"'cell culture', 'tissue_ontology_term_id' MUST be a CL term "
+                        "and it can not be 'CL:0000255' (eukaryotic cell), 'CL:0000257' (Eumycetozoan cell), "
+                        "nor 'CL:0000548' (animal cell)."
+                    ],
+                )
 
     def test_tissue_ontology_term_id_organoid(self):
         """
@@ -544,6 +590,52 @@ def test_tissue_ontology_term_id_organoid(self):
             ],
         )
 
+    def test_tissue_ontology_term_id_child_of_anatomical_entity(self):
+        """
+        Tissue ontology term ID must be a CHILD TERM of 'UBERON:0001062' (anatomical entity) if tissue_type is
+        organoid or tissue.
+        """
+        self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "tissue_ontology_term_id"] = "UBERON:0001062"
+        with self.subTest(tissue_type="tissue"):
+            self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "tissue_type"] = "tissue"
+            self.validator.validate_adata()
+            self.assertEqual(
+                self.validator.errors,
+                [
+                    "ERROR: 'UBERON:0001062' in 'tissue_ontology_term_id' is not a child term id of "
+                    "'[['UBERON:0001062']]'. When 'tissue_type' is 'tissue' or 'organoid', 'tissue_ontology_term_id' "
+                    "MUST be a child term id of 'UBERON:0001062' (anatomical entity)."
+                ],
+            )
+
+        with self.subTest(tissue_type="organoid"):
+            self.validator.adata.obs.tissue_type = self.validator.adata.obs.tissue_type.cat.add_categories(["organoid"])
+            self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "tissue_type"] = "organoid"
+            self.validator.validate_adata()
+            self.assertEqual(
+                self.validator.errors,
+                [
+                    "ERROR: 'UBERON:0001062' in 'tissue_ontology_term_id' is not a child term id of "
+                    "'[['UBERON:0001062']]'. When 'tissue_type' is 'tissue' or 'organoid', 'tissue_ontology_term_id' "
+                    "MUST be a child term id of 'UBERON:0001062' (anatomical entity)."
+                ],
+            )
+
+    def test_tissue_type(self):
+        """
+        tissue_type must be one of 'cell culture', 'tissue', or 'organoid'
+        """
+        self.validator.adata.obs.tissue_type = self.validator.adata.obs.tissue_type.cat.add_categories(["organ"])
+        self.validator.adata.obs.loc[self.validator.adata.obs.index[0], "tissue_type"] = "organ"
+        self.validator.validate_adata()
+        self.assertEqual(
+            self.validator.errors,
+            [
+                "ERROR: Column 'tissue_type' in dataframe 'obs' contains invalid values "
+                "'['organ']'. Values must be one of ['cell culture', 'organoid', 'tissue']"
+            ],
+        )
+
     def test_sex_ontology_term_id(self):
         """
         sex_ontology_term_id categorical with str categories.
diff --git a/cellxgene_schema_cli/tests/test_validate.py b/cellxgene_schema_cli/tests/test_validate.py
index 447fe295c..36df2231e 100644
--- a/cellxgene_schema_cli/tests/test_validate.py
+++ b/cellxgene_schema_cli/tests/test_validate.py
@@ -52,21 +52,29 @@ def test_schema_definition(self):
         # Check that any columns in obs that are "curie" have "curie_constraints" and "ontologies" under the constraints
         for i in self.schema_def["components"]["obs"]["columns"]:
             self.assertTrue("type" in self.schema_def["components"]["obs"]["columns"][i])
-            if i == "curie":
-                self.assertIsInstance(
-                    self.schema_def["components"]["obs"]["columns"][i]["curie_constraints"],
-                    dict,
-                )
-                self.assertIsInstance(
-                    self.schema_def["components"]["obs"]["columns"][i]["curie_constraints"]["ontolgies"],
-                    list,
-                )
-
-                # Check that the allowed ontologies are in the ontology checker
-                for ontology_name in self.schema_def["components"]["obs"]["columns"][i]["curie_constraints"][
-                    "ontolgies"
-                ]:
-                    self.assertTrue(self.OntologyChecker.is_valid_ontology(ontology_name))
+            if self.schema_def["components"]["obs"]["columns"][i]["type"] == "curie":
+                if "curie_constraints" in self.schema_def["components"]["obs"]["columns"][i]:
+                    self.assertIsInstance(
+                        self.schema_def["components"]["obs"]["columns"][i]["curie_constraints"],
+                        dict,
+                    )
+                    self.assertIsInstance(
+                        self.schema_def["components"]["obs"]["columns"][i]["curie_constraints"]["ontologies"],
+                        list,
+                    )
+
+                    # Check that the allowed ontologies are in the ontology checker or 'NA' (special case)
+                    for ontology_name in self.schema_def["components"]["obs"]["columns"][i]["curie_constraints"][
+                        "ontologies"
+                    ]:
+                        if ontology_name != "NA":
+                            self.assertTrue(self.OntologyChecker.is_valid_ontology(ontology_name))
+                else:
+                    # if no curie_constraints in top-level for type curie, assert that 'dependencies' list exists
+                    self.assertIsInstance(
+                        self.schema_def["components"]["obs"]["columns"][i]["dependencies"],
+                        list,
+                    )
 
     def test_validate_ontology_good(self):
         self.validator._validate_curie("CL:0000066", self.column_name, self.curie_constraints)
@@ -325,7 +333,7 @@ def test_determine_seurat_convertibility(self):
         # h5ad where raw matrix variable count != length of raw var variables array is not Seurat-convertible
         matrix = sparse.csr_matrix(np.zeros([good_obs.shape[0], good_var.shape[0]], dtype=np.float32))
         raw = anndata.AnnData(X=matrix, var=good_var)
-        raw.var.drop('ENSSASG00005000004', axis=0, inplace=True)
+        raw.var.drop("ENSSASG00005000004", axis=0, inplace=True)
         self.validation_helper(matrix, raw)
         self.validator._validate_seurat_convertibility()
         self.assertTrue(len(self.validator.warnings) == 1)

From d696720c52ea8406923c73cdd8b3126bbe497ee4 Mon Sep 17 00:00:00 2001
From: nayib-jose-gloria <ngloria@chanzuckerberg.com>
Date: Fri, 15 Sep 2023 13:09:48 -0400
Subject: [PATCH 5/7] =?UTF-8?q?Bump=20version:=204.0.0-rc.0=20=E2=86=92=20?=
 =?UTF-8?q?4.0.0-rc.1?=
MIME-Version: 1.0
Content-Type: text/plain; charset=UTF-8
Content-Transfer-Encoding: 8bit

---
 .bumpversion.cfg                                  | 2 +-
 cellxgene_schema_cli/cellxgene_schema/__init__.py | 2 +-
 cellxgene_schema_cli/setup.py                     | 2 +-
 3 files changed, 3 insertions(+), 3 deletions(-)

diff --git a/.bumpversion.cfg b/.bumpversion.cfg
index 5a2e12934..d391347f1 100644
--- a/.bumpversion.cfg
+++ b/.bumpversion.cfg
@@ -1,5 +1,5 @@
 [bumpversion]
-current_version = 4.0.0-rc.0
+current_version = 4.0.0-rc.1
 commit = True
 parse = (?P<major>\d+)\.(?P<minor>\d+)\.(?P<patch>\d+)(?:-(?P<prerel>rc)\.(?P<prerelversion>\d+))?
 serialize = 
diff --git a/cellxgene_schema_cli/cellxgene_schema/__init__.py b/cellxgene_schema_cli/cellxgene_schema/__init__.py
index 14c14eb36..abb8475c3 100644
--- a/cellxgene_schema_cli/cellxgene_schema/__init__.py
+++ b/cellxgene_schema_cli/cellxgene_schema/__init__.py
@@ -1 +1 @@
-__version__ = "__version__ = "4.0.0-rc.0""
+__version__ = "__version__ = "4.0.0-rc.1""
diff --git a/cellxgene_schema_cli/setup.py b/cellxgene_schema_cli/setup.py
index 95f2c1573..db2a3135e 100644
--- a/cellxgene_schema_cli/setup.py
+++ b/cellxgene_schema_cli/setup.py
@@ -5,7 +5,7 @@
 
 setup(
     name="cellxgene-schema",
-    version="version="4.0.0-rc.0"",
+    version="version="4.0.0-rc.1"",
     url="https://github.com/chanzuckerberg/single-cell-curation",
     license="MIT",
     author="Chan Zuckerberg Initiative",

From 8203af30ac70fd7e7e9c744297edd2bff5588868 Mon Sep 17 00:00:00 2001
From: nayib-jose-gloria <ngloria@chanzuckerberg.com>
Date: Fri, 15 Sep 2023 13:14:17 -0400
Subject: [PATCH 6/7] fix versions

---
 cellxgene_schema_cli/cellxgene_schema/__init__.py | 2 +-
 cellxgene_schema_cli/setup.py                     | 2 +-
 2 files changed, 2 insertions(+), 2 deletions(-)

diff --git a/cellxgene_schema_cli/cellxgene_schema/__init__.py b/cellxgene_schema_cli/cellxgene_schema/__init__.py
index abb8475c3..6ecb6d70d 100644
--- a/cellxgene_schema_cli/cellxgene_schema/__init__.py
+++ b/cellxgene_schema_cli/cellxgene_schema/__init__.py
@@ -1 +1 @@
-__version__ = "__version__ = "4.0.0-rc.1""
+__version__ = "4.0.0-rc.1"
diff --git a/cellxgene_schema_cli/setup.py b/cellxgene_schema_cli/setup.py
index db2a3135e..91937e0d2 100644
--- a/cellxgene_schema_cli/setup.py
+++ b/cellxgene_schema_cli/setup.py
@@ -5,7 +5,7 @@
 
 setup(
     name="cellxgene-schema",
-    version="version="4.0.0-rc.1"",
+    version="4.0.0-rc.1",
     url="https://github.com/chanzuckerberg/single-cell-curation",
     license="MIT",
     author="Chan Zuckerberg Initiative",

From fb5384ec642d267bb650fe51ac91280ea10c9f25 Mon Sep 17 00:00:00 2001
From: nayib-jose-gloria <ngloria@chanzuckerberg.com>
Date: Mon, 18 Sep 2023 10:47:00 -0400
Subject: [PATCH 7/7] lint fix

---
 cellxgene_schema_cli/cellxgene_schema/validate.py | 10 +---------
 1 file changed, 1 insertion(+), 9 deletions(-)

diff --git a/cellxgene_schema_cli/cellxgene_schema/validate.py b/cellxgene_schema_cli/cellxgene_schema/validate.py
index b2c21ae57..1e9030c29 100644
--- a/cellxgene_schema_cli/cellxgene_schema/validate.py
+++ b/cellxgene_schema_cli/cellxgene_schema/validate.py
@@ -1,9 +1,8 @@
 import logging
 import math
 import os
-import re
 from datetime import datetime
-from typing import Dict, List, Optional, Tuple, Union
+from typing import Dict, List, Optional, Union
 
 import anndata
 import numpy as np
@@ -761,13 +760,6 @@ def _validate_seurat_convertibility(self):
                     )
 
                 self.is_seurat_convertible = False
-        if self.adata.raw and self.adata.raw.X.shape[1] != self.adata.raw.var.shape[0]:
-            self.warnings.append(
-                f"This dataset cannot be converted to the .rds (Seurat v4) format. "
-                f"There is a mismatch in the number of variables in the raw matrix and the raw var key-indexed "
-                f"variables."
-            )
-            self.is_seurat_convertible = False
 
         if self.adata.raw and self.adata.raw.X.shape[1] != self.adata.raw.var.shape[0]:
             self.warnings.append(