Merge pull request #56 from VariantEffect/mavedb-dev

Release 2025.2.0

Author: bencap

docker-compose-dev.yml

@@ -30,7 +30,7 @@ services:
       - vrs-mapping-data-dev:/var/lib/postgresql/data
 
   seqrepo:
-    image: biocommons/seqrepo:2021-01-29
+    image: biocommons/seqrepo:2024-12-20
     volumes:
       - vrs-mapping-seqrepo-dev:/usr/local/share/seqrepo
 

settings/.env.dev

@@ -30,4 +30,4 @@ MAVEDB_API_KEY=
 # Environment variables for seqrepo
 ####################################################################################################
 
-SEQREPO_ROOT_DIR=/usr/local/share/seqrepo/2021-01-29
+SEQREPO_ROOT_DIR=/usr/local/share/seqrepo/2024-12-20

src/api/routers/map.py

@@ -6,22 +6,31 @@
 from fastapi.responses import JSONResponse
 from requests import HTTPError
 
-from dcd_mapping.align import AlignmentError, BlatNotFoundError, build_alignment_result
+from dcd_mapping.align import build_alignment_result
 from dcd_mapping.annotate import (
     _get_computed_reference_sequence,
     _get_mapped_reference_sequence,
     _set_scoreset_layer,
     annotate,
 )
-from dcd_mapping.lookup import DataLookupError
-from dcd_mapping.mavedb_data import (
+from dcd_mapping.exceptions import (
+    AlignmentError,
+    BlatNotFoundError,
+    DataLookupError,
+    MissingSequenceIdError,
+    ResourceAcquisitionError,
     ScoresetNotSupportedError,
+    UnsupportedReferenceSequenceNameSpaceError,
+    UnsupportedReferenceSequencePrefixError,
+    VrsMapError,
+)
+from dcd_mapping.mavedb_data import (
     get_raw_scoreset_metadata,
     get_scoreset_metadata,
     get_scoreset_records,
+    patch_target_sequence_type,
     with_mavedb_score_set,
 )
-from dcd_mapping.resource_utils import ResourceAcquisitionError
 from dcd_mapping.schemas import (
     ScoreAnnotation,
     ScoresetMapping,
@@ -30,7 +39,7 @@
     VrsVersion,
 )
 from dcd_mapping.transcripts import select_transcripts
-from dcd_mapping.vrs_map import VrsMapError, vrs_map
+from dcd_mapping.vrs_map import vrs_map
 
 router = APIRouter(
     prefix="/api/v1", tags=["mappings"], responses={404: {"description": "Not found"}}
@@ -48,6 +57,7 @@ async def map_scoreset(urn: str, store_path: Path | None = None) -> JSONResponse
     try:
         metadata = get_scoreset_metadata(urn, store_path)
         records = get_scoreset_records(metadata, True, store_path)
+        metadata = patch_target_sequence_type(metadata, records)
     except ScoresetNotSupportedError as e:
         return JSONResponse(
             content=ScoresetMapping(
@@ -66,6 +76,7 @@ async def map_scoreset(urn: str, store_path: Path | None = None) -> JSONResponse
                 error_message="Score set contains no variants to map",
             ).model_dump(exclude_none=True)
         )
+    total_score_records = sum(len(v) for v in records.values())
 
     try:
         alignment_results = build_alignment_result(metadata, True)
@@ -112,21 +123,38 @@ async def map_scoreset(urn: str, store_path: Path | None = None) -> JSONResponse
                 transcript=transcripts[target_gene],
                 silent=True,
             )
-    except VrsMapError as e:
+    except (
+        UnsupportedReferenceSequenceNameSpaceError,
+        VrsMapError,
+        UnsupportedReferenceSequencePrefixError,
+        MissingSequenceIdError,
+    ) as e:
         return JSONResponse(
             content=ScoresetMapping(
                 metadata=metadata, error_message=str(e).strip("'")
             ).model_dump(exclude_none=True)
         )
-    if not vrs_results or all(
-        mapping_result is None for mapping_result in vrs_results.values()
-    ):
+
+    nonetype_vrs_results = [
+        result is None
+        for target_gene in vrs_results
+        for result in vrs_results[target_gene]
+    ]
+
+    if not vrs_results or all(nonetype_vrs_results):
         return JSONResponse(
             content=ScoresetMapping(
                 metadata=metadata,
                 error_message="No variant mappings available for this score set",
             ).model_dump(exclude_none=True)
         )
+    if any(nonetype_vrs_results):
+        return JSONResponse(
+            content=ScoresetMapping(
+                metadata=metadata,
+                error_message="Some variants generated vrs results, but not all. If any variants were mapped, all should have been.",
+            ).model_dump(exclude_none=True)
+        )
 
     annotated_vrs_results = {}
     try:
@@ -144,15 +172,27 @@ async def map_scoreset(urn: str, store_path: Path | None = None) -> JSONResponse
                 metadata=metadata, error_message=str(e).strip("'")
             ).model_dump(exclude_none=True)
         )
-    if not annotated_vrs_results or all(
-        mapping_result is None for mapping_result in annotated_vrs_results.values()
-    ):
+
+    nonetype_annotated_vrs_results = [
+        result is None
+        for target_gene in annotated_vrs_results
+        for result in annotated_vrs_results[target_gene]
+    ]
+
+    if not annotated_vrs_results or all(nonetype_annotated_vrs_results):
         return JSONResponse(
             content=ScoresetMapping(
                 metadata=metadata,
                 error_message="No annotated variant mappings available for this score set",
             ).model_dump(exclude_none=True)
         )
+    if any(nonetype_annotated_vrs_results):
+        return JSONResponse(
+            content=ScoresetMapping(
+                metadata=metadata,
+                error_message="Some variants generated annotated vrs results, but not all. If any variants were annotated, all should have been.",
+            ).model_dump(exclude_none=True)
+        )
 
     try:
         raw_metadata = get_raw_scoreset_metadata(urn, store_path)
@@ -233,6 +273,14 @@ async def map_scoreset(urn: str, store_path: Path | None = None) -> JSONResponse
             ).model_dump(exclude_none=True)
         )
 
+    if len(mapped_scores) != total_score_records:
+        return JSONResponse(
+            content=ScoresetMapping(
+                metadata=metadata,
+                error_message=f"Mismatch between number of mapped scores ({len(mapped_scores)}) and total score records ({total_score_records}). This is unexpected and indicates an issue with the mapping process.",
+            ).model_dump(exclude_none=True)
+        )
+
     return JSONResponse(
         content=ScoresetMapping(
             metadata=raw_metadata,

src/dcd_mapping/align.py

@@ -12,12 +12,15 @@
 from Bio.SearchIO._model import Hit, QueryResult
 from cool_seq_tool.schemas import Strand
 
-from dcd_mapping.lookup import get_chromosome_identifier, get_gene_location
-from dcd_mapping.mavedb_data import LOCAL_STORE_PATH, ScoresetNotSupportedError
-from dcd_mapping.resource_utils import (
+from dcd_mapping.exceptions import (
+    AlignmentError,
+    BlatNotFoundError,
     ResourceAcquisitionError,
-    http_download,
+    ScoresetNotSupportedError,
 )
+from dcd_mapping.lookup import get_chromosome_identifier, get_gene_location
+from dcd_mapping.mavedb_data import LOCAL_STORE_PATH
+from dcd_mapping.resource_utils import http_download
 from dcd_mapping.schemas import (
     AlignmentResult,
     GeneLocation,
@@ -32,14 +35,6 @@
 _logger = logging.getLogger(__name__)
 
 
-class AlignmentError(Exception):
-    """Raise when errors encountered during alignment."""
-
-
-class BlatNotFoundError(AlignmentError):
-    """Raise when BLAT binary appears to be missing."""
-
-
 def _write_query_file(file: Path, lines: list[str]) -> None:
     """Write lines to query file. This method is broken out to enable easy mocking while
     testing.
@@ -363,6 +358,11 @@ def align(
                     msg = f"BLAT result {target_label} matches multiple target gene names in scoreset {scoreset_metadata.urn}"
         target_gene = scoreset_metadata.target_genes[target_label]
         alignment_results[target_label] = _get_best_match(blat_result, target_gene)
+    # confirm that there is an alignment result for each target gene
+    for target_gene in scoreset_metadata.target_genes:
+        if target_gene not in alignment_results:
+            msg = f"No BLAT result found for target gene {target_gene} in scoreset {scoreset_metadata.urn}"
+            raise AlignmentError(msg)
     return alignment_results
 
 

src/dcd_mapping/annotate.py

@@ -140,7 +140,7 @@ def _get_vrs_ref_allele_seq(
     metadata: TargetGene,
     urn: str,
     tx_select_results: TxSelectResult | None,
-) -> Extension:
+) -> Extension | None:
     """Create `vrs_ref_allele_seq` property."""
     start, end = _offset_allele_ref_seq(urn, allele.location.start, allele.location.end)
     if (
@@ -161,8 +161,12 @@ def _get_vrs_ref_allele_seq(
         seq = f"ga4gh:{allele.location.sequenceReference.refgetAccession}"  # type: ignore
         sr = get_seqrepo()
         ref = sr.get_sequence(seq, start, end)
-        if ref is None:
-            raise ValueError
+
+    if not ref:
+        msg = f"Could not retrieve reference sequence for allele {allele.id} in urn {urn} with start {start} and end {end}"
+        _logger.warning(msg)
+        return None
+
     return Extension(type="Extension", name="vrs_ref_allele_seq", value=ref)
 
 
@@ -256,23 +260,28 @@ def _annotate_allele_mapping(
     post_mapped: Allele = mapped_score.post_mapped
 
     # get vrs_ref_allele_seq for pre-mapped variants
-    pre_mapped.extensions = [
-        _get_vrs_ref_allele_seq(pre_mapped, metadata, urn, tx_results)
-    ]
+    ref_allele_seq_extension = _get_vrs_ref_allele_seq(
+        pre_mapped, metadata, urn, tx_results
+    )
+    if ref_allele_seq_extension is not None:
+        pre_mapped.extensions = [ref_allele_seq_extension]
 
     if post_mapped:
         # Determine reference sequence
         if mapped_score.annotation_layer == AnnotationLayer.GENOMIC:
             sequence_id = f"ga4gh:{mapped_score.post_mapped.location.sequenceReference.refgetAccession}"
             accession = get_chromosome_identifier_from_vrs_id(sequence_id)
             if accession is None:
-                raise ValueError
-            if accession.startswith("refseq:"):
+                accession = None
+                mapped_score.error_message = "Could not determine accession for this annotation. No allele expression is available."
+            elif accession.startswith("refseq:"):
                 accession = accession[7:]
         else:
             if tx_results is None or isinstance(tx_results, TxSelectError):
-                raise ValueError  # impossible by definition
-            accession = tx_results.np
+                accession = None
+                mapped_score.error_message = "Could not determine accession for this annotation. No allele expression is available."
+            else:
+                accession = tx_results.np
 
         sr = get_seqrepo()
         loc = mapped_score.post_mapped.location
@@ -281,8 +290,9 @@ def _annotate_allele_mapping(
         post_mapped.extensions = [
             Extension(type="Extension", name="vrs_ref_allele_seq", value=ref)
         ]
-        hgvs_string, syntax = _get_hgvs_string(post_mapped, accession)
-        post_mapped.expressions = [Expression(syntax=syntax, value=hgvs_string)]
+        if accession:
+            hgvs_string, syntax = _get_hgvs_string(post_mapped, accession)
+            post_mapped.expressions = [Expression(syntax=syntax, value=hgvs_string)]
 
     if vrs_version == VrsVersion.V_1_3:
         pre_mapped = _allele_to_vod(pre_mapped)
@@ -295,9 +305,7 @@ def _annotate_allele_mapping(
         mavedb_id=mapped_score.accession_id,
         score=float(mapped_score.score) if mapped_score.score else None,
         annotation_layer=mapped_score.annotation_layer,
-        error_message=mapped_score.error_message
-        if mapped_score.error_message
-        else None,  # TODO might not need if statement here
+        error_message=mapped_score.error_message,
     )
 
 
@@ -311,23 +319,32 @@ def _annotate_haplotype_mapping(
     """Perform annotations and, if necessary, create VRS 1.3 equivalents for haplotype mappings."""
     pre_mapped: Haplotype = mapped_score.pre_mapped  # type: ignore
     post_mapped: Haplotype = mapped_score.post_mapped  # type: ignore
+
     # get vrs_ref_allele_seq for pre-mapped variants
     for allele in pre_mapped.members:
-        allele.extensions = [_get_vrs_ref_allele_seq(allele, metadata, urn, tx_results)]
+        ref_allele_seq_extension = _get_vrs_ref_allele_seq(
+            allele, metadata, urn, tx_results
+        )
+        if ref_allele_seq_extension is not None:
+            allele.extensions = [ref_allele_seq_extension]
 
     if post_mapped:
         # Determine reference sequence
         if mapped_score.annotation_layer == AnnotationLayer.GENOMIC:
             sequence_id = f"ga4gh:{post_mapped.members[0].location.sequenceReference.refgetAccession}"
             accession = get_chromosome_identifier_from_vrs_id(sequence_id)
             if accession is None:
-                raise ValueError
-            if accession.startswith("refseq:"):
+                accession = None
+                mapped_score.error_message = "Could not determine accession for this annotation. No allele expression is available."
+            elif accession.startswith("refseq:"):
                 accession = accession[7:]
         else:
             if tx_results is None or isinstance(tx_results, TxSelectError):
-                raise ValueError  # impossible by definition
-            accession = tx_results.np
+                # impossible by definition
+                accession = None
+                mapped_score.error_message = "Could not determine accession for this annotation. No allele expression is available."
+            else:
+                accession = tx_results.np
 
         sr = get_seqrepo()
         for allele in post_mapped.members:
@@ -337,8 +354,9 @@ def _annotate_haplotype_mapping(
             allele.extensions = [
                 Extension(type="Extension", name="vrs_ref_allele_seq", value=ref)
             ]
-            hgvs, syntax = _get_hgvs_string(allele, accession)
-            allele.expressions = [Expression(syntax=syntax, value=hgvs)]
+            if accession:
+                hgvs, syntax = _get_hgvs_string(allele, accession)
+                allele.expressions = [Expression(syntax=syntax, value=hgvs)]
 
     if vrs_version == VrsVersion.V_1_3:
         pre_mapped = _haplotype_to_haplotype_1_3(pre_mapped)
@@ -351,9 +369,7 @@ def _annotate_haplotype_mapping(
         mavedb_id=mapped_score.accession_id,
         score=float(mapped_score.score) if mapped_score.score is not None else None,
         annotation_layer=mapped_score.annotation_layer,
-        error_message=mapped_score.error_message
-        if mapped_score.error_message
-        else None,  # TODO might not need if statement here
+        error_message=mapped_score.error_message,
     )
 
 
@@ -388,6 +404,7 @@ def annotate(
                 ScoreAnnotationWithLayer(
                     mavedb_id=mapped_score.accession_id,
                     score=float(mapped_score.score) if mapped_score.score else None,
+                    vrs_version=vrs_version,
                     error_message=mapped_score.error_message,
                 )
             )
@@ -410,8 +427,16 @@ def annotate(
                 )
             )
         else:
-            # TODO how to combine this error message with other potential error messages?
-            ValueError("inconsistent variant structure")
+            score_annotations.append(
+                ScoreAnnotationWithLayer(
+                    pre_mapped=mapped_score.pre_mapped,
+                    post_mapped=mapped_score.post_mapped,
+                    vrs_version=vrs_version,
+                    mavedb_id=mapped_score.accession_id,
+                    score=float(mapped_score.score) if mapped_score.score else None,
+                    error_message=f"Multiple issues with annotation: Inconsistent variant structure (Allele and Haplotype mix).{' ' + mapped_score.error_message if mapped_score.error_message else ''}",
+                )
+            )
 
     return score_annotations
 
@@ -519,11 +544,6 @@ def _set_scoreset_layer(
     expressions. If genomic expressions are available, that's what we'd like to use.
     This function tells us how to filter the final annotation objects.
     """
-    if urn.startswith("urn:mavedb:00000097"):
-        _logger.debug(
-            "Manually selecting protein annotation for scores from urn:mavedb:00000097"
-        )
-        return AnnotationLayer.PROTEIN
     for mapping in mappings:
         if mapping.annotation_layer == AnnotationLayer.GENOMIC:
             return AnnotationLayer.GENOMIC