fix: still return a result for protein/cdna with no mane data found (#…

…507) - Creates an enum for vrs sequence location accession status - Fix getting priority translation result in `_get_priority_translation_result` when there are multiple translation results for a given ac status
cancervariants · Sep 22, 2023 · 40e18f2 · 40e18f2
1 parent 8d7150c
commit 40e18f2
Show file tree

Hide file tree

Showing 9 changed files with 111 additions and 150 deletions.
diff --git a/tests/test_normalize.py b/tests/test_normalize.py
@@ -41,127 +41,37 @@ def dis3_p63a():
             "type": "Allele",
         },
         "molecule_context": "protein",
-        "gene_context": {
-            "id": "normalize.gene:DIS3",
-            "type": "GeneDescriptor",
-            "label": "DIS3",
-            "xrefs": ["ensembl:ENSG00000083520", "ncbigene:22894"],
-            "alternate_labels": [
-                "dis3p",
-                "RRP44",
-                "KIAA1008",
-                "2810028N01Rik",
-                "EXOSC11",
-            ],
-            "extensions": [
-                {"name": "symbol_status", "value": "approved", "type": "Extension"},
-                {
-                    "name": "approved_name",
-                    "value": "DIS3 homolog, exosome endoribonuclease and 3'-5' exoribonuclease",  # noqa: E501
-                    "type": "Extension",
-                },
-                {
-                    "name": "hgnc_locations",
-                    "value": [
-                        {
-                            "species_id": "taxonomy:9606",
-                            "interval": {
-                                "type": "CytobandInterval",
-                                "start": "q21.33",
-                                "end": "q21.33",
-                            },
-                            "_id": "ga4gh:VCL.84IPub_nKl33cWX9pNoPeGsyeVuJnyra",
-                            "type": "ChromosomeLocation",
-                            "chr": "13",
-                        }
-                    ],
-                    "type": "Extension",
-                },
-                {
-                    "type": "Extension",
-                    "name": "ensembl_locations",
-                    "value": [
-                        {
-                            "_id": "ga4gh:VSL.HZtod8n11kD7jCAbtsJLDGwLKCEhRWO1",
-                            "type": "SequenceLocation",
-                            "sequence_id": "ga4gh:SQ._0wi-qoDrvram155UmcSC-zA5ZK4fpLT",
-                            "interval": {
-                                "start": {"type": "Number", "value": 72752168},
-                                "end": {"type": "Number", "value": 72782096},
-                                "type": "SequenceInterval",
-                            },
-                        }
-                    ],
-                },
-                {
-                    "type": "Extension",
-                    "name": "ncbi_locations",
-                    "value": [
-                        {
-                            "_id": "ga4gh:VCL.84IPub_nKl33cWX9pNoPeGsyeVuJnyra",
-                            "type": "ChromosomeLocation",
-                            "species_id": "taxonomy:9606",
-                            "chr": "13",
-                            "interval": {
-                                "end": "q21.33",
-                                "start": "q21.33",
-                                "type": "CytobandInterval",
-                            },
-                        },
-                        {
-                            "_id": "ga4gh:VSL.BIRwPLT8rtyOnhd3aUXaz4xlHC4P4zA8",
-                            "type": "SequenceLocation",
-                            "sequence_id": "ga4gh:SQ._0wi-qoDrvram155UmcSC-zA5ZK4fpLT",
-                            "interval": {
-                                "start": {"type": "Number", "value": 72752168},
-                                "end": {"type": "Number", "value": 72781900},
-                                "type": "SequenceInterval",
-                            },
-                        },
-                    ],
-                },
-                {
-                    "name": "associated_with",
-                    "value": [
-                        "vega:OTTHUMG00000017070",
-                        "ccds:CCDS9447",
-                        "orphanet:470196",
-                        "ena.embl:AB023225",
-                        "ccds:CCDS45057",
-                        "omim:607533",
-                        "pubmed:11935316",
-                        "refseq:NM_014953",
-                        "uniprot:Q9Y2L1",
-                        "ccds:CCDS81772",
-                        "ucsc:uc001vix.6",
-                        "pubmed:9562621",
-                    ],
-                    "type": "Extension",
-                },
-                {
-                    "name": "previous_symbols",
-                    "value": ["KIAA1008"],
-                    "type": "Extension",
-                },
-                {
-                    "type": "Extension",
-                    "name": "hgnc_locus_type",
-                    "value": "gene with protein product",
-                },
-                {
-                    "type": "Extension",
-                    "name": "ncbi_gene_type",
-                    "value": "protein-coding",
-                },
-                {
-                    "type": "Extension",
-                    "name": "ensembl_biotype",
-                    "value": "protein_coding",
+        "gene_context": "hgnc:20604",
+        "vrs_ref_allele_seq": "P",
+    }
+    return VariationDescriptor(**params)
+
+
+@pytest.fixture(scope="module")
+def tp53_g262c():
+    """Create TP53 G262C test fixture."""
+    params = {
+        "id": "normalize.variation:TP53%20G262C",
+        "type": "VariationDescriptor",
+        "variation_id": "ga4gh:VA.M_aggPZhA47fKQbmDhajHujncmFjMtB7",
+        "variation": {
+            "_id": "ga4gh:VA.M_aggPZhA47fKQbmDhajHujncmFjMtB7",
+            "location": {
+                "_id": "ga4gh:VSL.2rV8a3PeziQSLNLBzmXMlRHX-vxYRLpS",
+                "interval": {
+                    "end": {"value": 262, "type": "Number"},
+                    "start": {"value": 261, "type": "Number"},
+                    "type": "SequenceInterval",
                 },
-            ],
-            "gene_id": "hgnc:20604",
+                "sequence_id": "ga4gh:SQ.YIlmVwD0rxIqnlvb-8WujHPbR0j3WEGI",
+                "type": "SequenceLocation",
+            },
+            "state": {"sequence": "C", "type": "LiteralSequenceExpression"},
+            "type": "Allele",
         },
-        "vrs_ref_allele_seq": "P",
+        "molecule_context": "protein",
+        "gene_context": "hgnc:11998",
+        "vrs_ref_allele_seq": "G",
     }
     return VariationDescriptor(**params)
 
@@ -934,7 +844,7 @@ def gnomad_vcf_genomic_delins3():
 
 
 @pytest.mark.asyncio
-async def test_protein_substitution(test_handler, braf_v600e, dis3_p63a):
+async def test_protein_substitution(test_handler, braf_v600e, dis3_p63a, tp53_g262c):
     """Test that protein substitutions normalize correctly."""
     resp = await test_handler.normalize("     BRAF      V600E    ")
     assertion_checks(resp.variation_descriptor, braf_v600e, "BRAF      V600E")
@@ -966,6 +876,11 @@ async def test_protein_substitution(test_handler, braf_v600e, dis3_p63a):
     resp = await test_handler.normalize("DIS3 P63A")
     assertion_checks(resp.variation_descriptor, dis3_p63a, "DIS3 P63A")
 
+    # Case where NA priority
+    q = "TP53 G262C"
+    resp = await test_handler.normalize(q)
+    assertion_checks(resp.variation_descriptor, tp53_g262c, q)
+
 
 @pytest.mark.asyncio
 async def test_polypeptide_truncation(test_handler, vhl):
@@ -1563,7 +1478,6 @@ async def test_valid_queries(test_handler):
     assert await test_handler.normalize("CCND1 Y44D")
 
     resp = await test_handler.normalize("NC_000002.12:g.73448098_73448100delCTC")
-    assert resp
     assert resp.variation_descriptor.variation.state.sequence == "CTC"
     assert (
         resp.variation_descriptor.variation.id
@@ -1582,6 +1496,11 @@ async def test_valid_queries(test_handler):
         resp = await test_handler.normalize(q)
         assert resp.variation_descriptor, q
 
+    # Test where Mane data not found
+    resp = await test_handler.normalize("ALK p.A1280V")
+    assert resp.variation_descriptor.variation
+    assert resp.warnings == ["Unable to find MANE representation"]
+
 
 @pytest.mark.asyncio
 async def test_no_matches(test_handler):

diff --git a/variation/normalize.py b/variation/normalize.py
@@ -5,6 +5,7 @@
 
 from cool_seq_tool.data_sources import SeqRepoAccess, TranscriptMappings, UTADatabase
 from ga4gh.vrsatile.pydantic.vrs_models import CopyChange
+from ga4gh.vrsatile.pydantic.vrsatile_models import MoleculeContext
 from gene.query import QueryHandler as GeneQueryHandler
 
 from variation.classify import Classify
@@ -19,6 +20,7 @@
 from variation.schemas.translation_response_schema import (
     AC_PRIORITY_LABELS,
     TranslationResult,
+    VrsSeqLocAcStatus,
 )
 from variation.to_vrsatile import ToVRSATILE
 from variation.tokenize import Tokenize
@@ -65,7 +67,7 @@ def __init__(
 
     @staticmethod
     def _get_priority_translation_result(
-        translations: List[TranslationResult], ac_status: str
+        translations: List[TranslationResult], ac_status: VrsSeqLocAcStatus
     ) -> Optional[TranslationResult]:
         """Get prioritized translation result. Tries to find translation results with
         the same `vrs_seq_loc_ac_status` as `ac_status`. If more than one translation
@@ -87,6 +89,10 @@ def _get_priority_translation_result(
         # Different `og_ac`'s can lead to different translation results.
         # We must be consistent in what we return in /normalize
         if len_preferred_translations > 1:
+            preferred_translations.sort(
+                key=lambda t: (t.og_ac.split(".")[0], int(t.og_ac.split(".")[1])),
+                reverse=True,
+            )
             og_ac_preferred_match = (
                 [t for t in preferred_translations if t.og_ac == t.vrs_seq_loc_ac]
                 or [None]
@@ -99,10 +105,6 @@ def _get_priority_translation_result(
             if og_ac_preferred_match:
                 translation_result = og_ac_preferred_match
             else:
-                preferred_translations.sort(
-                    key=lambda t: (t.og_ac.split(".")[0], int(t.og_ac.split(".")[1])),
-                    reverse=True,
-                )
                 translation_result = preferred_translations[0]
         elif len_preferred_translations == 1:
             translation_result = preferred_translations[0]
@@ -251,6 +253,16 @@ async def normalize(
                         translations, ac_status
                     )
                     if translation_result:
+                        if (
+                            translation_result.vrs_seq_loc_ac_status
+                            == VrsSeqLocAcStatus.NA
+                        ):
+                            molecule_context = (
+                                translation_result.validation_result.classification.molecule_context
+                            )
+                            if molecule_context != MoleculeContext.GENOMIC:
+                                # Only supports protein/cDNA at the moment
+                                warnings.append("Unable to find MANE representation")
                         break
 
                 # Get variation descriptor information

diff --git a/variation/schemas/translation_response_schema.py b/variation/schemas/translation_response_schema.py
@@ -1,4 +1,5 @@
 """Module for Translation Response Schema."""
+from enum import Enum
 from typing import Dict, Optional
 
 from cool_seq_tool.schemas import TranscriptPriorityLabel
@@ -7,21 +8,31 @@
 from variation.schemas.validation_response_schema import ValidationResult
 
 
+class VrsSeqLocAcStatus(str, Enum):
+    """Create enum for VRS SequenceLocation accession status.
+    Order when defining matters.
+        First has highest priority, last has lowest priority
+    Once issue-191 is resolved in cool-seq-tool, we should use the
+    TranscriptPriorityLabel enum
+    """
+
+    MANE_SELECT = TranscriptPriorityLabel.MANESelect.value
+    MANE_PLUS_CLINICAL = TranscriptPriorityLabel.MANEPlusClinical.value
+    LONGEST_COMPATIBLE_REMAINING = (
+        TranscriptPriorityLabel.LongestCompatibleRemaining.value
+    )
+    GRCH38 = "GRCh38"  # will change to lowercase in cool-seq-tool issue-191
+    NA = "na"
+
+
+AC_PRIORITY_LABELS = [m for m in VrsSeqLocAcStatus.__members__.values()]
+
+
 class TranslationResult(BaseModel):
     """Translation Result"""
 
     vrs_variation: Optional[Dict]
     vrs_seq_loc_ac: Optional[StrictStr]
-    vrs_seq_loc_ac_status: StrictStr = "na"
+    vrs_seq_loc_ac_status: VrsSeqLocAcStatus = VrsSeqLocAcStatus.NA
     og_ac: Optional[StrictStr]
     validation_result: ValidationResult
-
-
-# Define accession priority. First has highest priority, last has lowest priority
-AC_PRIORITY_LABELS = [
-    TranscriptPriorityLabel.MANESelect.value,
-    TranscriptPriorityLabel.MANEPlusClinical.value,
-    TranscriptPriorityLabel.LongestCompatibleRemaining.value,
-    "GRCh38",
-    "na",
-]
diff --git a/variation/translators/genomic_del_dup_base.py b/variation/translators/genomic_del_dup_base.py
@@ -16,7 +16,10 @@
 from variation.schemas.normalize_response_schema import HGVSDupDelModeOption
 from variation.schemas.service_schema import ClinVarAssembly
 from variation.schemas.token_response_schema import AltType
-from variation.schemas.translation_response_schema import TranslationResult
+from variation.schemas.translation_response_schema import (
+    TranslationResult,
+    VrsSeqLocAcStatus,
+)
 from variation.schemas.validation_response_schema import ValidationResult
 from variation.translators.translator import Translator
 from variation.utils import get_assembly
@@ -107,7 +110,7 @@ async def translate(
 
         grch38_data = None
         vrs_variation = None
-        vrs_seq_loc_ac_status = "na"
+        vrs_seq_loc_ac_status = VrsSeqLocAcStatus.NA
 
         if do_liftover or endpoint_name == Endpoint.NORMALIZE:
             errors = []

diff --git a/variation/translators/genomic_delins.py b/variation/translators/genomic_delins.py
@@ -12,7 +12,10 @@
 )
 from variation.schemas.normalize_response_schema import HGVSDupDelModeOption
 from variation.schemas.token_response_schema import AltType
-from variation.schemas.translation_response_schema import TranslationResult
+from variation.schemas.translation_response_schema import (
+    TranslationResult,
+    VrsSeqLocAcStatus,
+)
 from variation.schemas.validation_response_schema import ValidationResult
 from variation.translators.translator import Translator
 
@@ -54,7 +57,7 @@ async def translate(
         classification: GenomicDelInsClassification = validation_result.classification
         vrs_allele = None
         vrs_seq_loc_ac = None
-        vrs_seq_loc_ac_status = "na"
+        vrs_seq_loc_ac_status = VrsSeqLocAcStatus.NA
 
         if endpoint_name == Endpoint.NORMALIZE:
             gene = (

diff --git a/variation/translators/genomic_insertion.py b/variation/translators/genomic_insertion.py
@@ -12,7 +12,10 @@
 )
 from variation.schemas.normalize_response_schema import HGVSDupDelModeOption
 from variation.schemas.token_response_schema import AltType
-from variation.schemas.translation_response_schema import TranslationResult
+from variation.schemas.translation_response_schema import (
+    TranslationResult,
+    VrsSeqLocAcStatus,
+)
 from variation.schemas.validation_response_schema import ValidationResult
 from variation.translators.translator import Translator
 
@@ -57,7 +60,7 @@ async def translate(
         )
         vrs_allele = None
         vrs_seq_loc_ac = None
-        vrs_seq_loc_ac_status = "na"
+        vrs_seq_loc_ac_status = VrsSeqLocAcStatus.NA
 
         if endpoint_name == Endpoint.NORMALIZE:
             gene = (

diff --git a/variation/translators/genomic_reference_agree.py b/variation/translators/genomic_reference_agree.py
@@ -12,7 +12,10 @@
 )
 from variation.schemas.normalize_response_schema import HGVSDupDelModeOption
 from variation.schemas.token_response_schema import AltType
-from variation.schemas.translation_response_schema import TranslationResult
+from variation.schemas.translation_response_schema import (
+    TranslationResult,
+    VrsSeqLocAcStatus,
+)
 from variation.schemas.validation_response_schema import ValidationResult
 from variation.translators.translator import Translator
 
@@ -56,7 +59,7 @@ async def translate(
         )
         vrs_allele = None
         vrs_seq_loc_ac = None
-        vrs_seq_loc_ac_status = "na"
+        vrs_seq_loc_ac_status = VrsSeqLocAcStatus.NA
 
         if endpoint_name == Endpoint.NORMALIZE:
             gene = (