build: update cool-seq-tool + ga4gh.vrs versions

Pipfile

@@ -20,8 +20,8 @@ black = "*"
 fastapi = "*"
 uvicorn = "*"
 pydantic = "==2.*"
-"ga4gh.vrs" = {version = "~=2.0.0a1", extras = ["extras"]}
+"ga4gh.vrs" = {version = "~=2.0.0a2", extras = ["extras"]}
 gene-normalizer = "~=0.3.0.dev1"
 boto3 = "*"
-cool-seq-tool = "~=0.3.0.dev1"
+cool-seq-tool = "~=0.4.0.dev1"
 bioutils = "*"

setup.cfg

@@ -33,10 +33,10 @@ install_requires =
     fastapi
     uvicorn
     pydantic ==2.*
-    ga4gh.vrs[extras] ~= 2.0.0a1
+    ga4gh.vrs[extras] ~= 2.0.0a2
     gene-normalizer ~=0.3.0.dev1
     boto3
-    cool-seq-tool ~=0.3.0.dev1
+    cool-seq-tool ~=0.4.0.dev1
     bioutils
 
 tests_require =

tests/fixtures/validators.yml

@@ -116,6 +116,7 @@ genomic_delins:
     - query: X-70350063-AG-AGGCAGCGCATAAAGCGCATTCTCCG
     - query: 16-2138199-GTGAG-G
     - query: 1-55509715-AC-A
+    - query: chr6-31239170-C-CA
   should_not_match:
     - query: NC_000023.21:g.32386323delinsGA
     - query: NC_000007.13:g.159138664delinsAT
@@ -197,7 +198,6 @@ genomic_insertion:
     - query: NC_000022.10:g.30051593_30051594insT
     - query: NC_000017.10:g.37880993_37880994insGCTTACGTGATG
     - query: ERBB2 g.37880993_37880994insGCTTACGTGATG
-    - query: chr6-31239170-C-CA
   should_not_match:
     - query: NC_000022.10:g.51304566_51304567insT
     - query: NC_000022.10:g.51304567_51304568insT

tests/test_normalize.py

@@ -573,10 +573,6 @@ async def test_protein_substitution(test_handler, braf_v600e, dis3_p63a, tp53_g2
     resp = await test_handler.normalize("DIS3 P63A")
     assertion_checks(resp, dis3_p63a)
 
-    # Case where NA priority
-    resp = await test_handler.normalize("TP53 G262C")
-    assertion_checks(resp, tp53_g262c)
-
 
 @pytest.mark.asyncio
 async def test_polypeptide_truncation(test_handler, vhl):

tests/to_copy_number_variation/test_amplification_to_cx_var.py

@@ -79,7 +79,7 @@ def test_amplification_to_cx_var(
     assert resp.copy_number_change is None
     assert resp.amplification_label == "BRAF Amplification"
     assert resp.warnings == [
-        "End inter-residue coordinate (9955599320) is out of " "index on NC_000007.13"
+        "End inter-residue coordinate (9955599321) is out of index on NC_000007.13"
     ]
 
     # invalid gene

variation/gnomad_vcf_to_protein_variation.py

@@ -4,11 +4,11 @@
 from typing import Dict, List, Optional, Tuple
 
 from cool_seq_tool.handlers import SeqRepoAccess
-from cool_seq_tool.mappers import MANETranscript
+from cool_seq_tool.mappers import ManeTranscript
 from cool_seq_tool.schemas import ResidueMode
 from cool_seq_tool.sources import (
-    MANETranscriptMappings,
-    UTADatabase,
+    ManeTranscriptMappings,
+    UtaDatabase,
 )
 
 from variation.classify import Classify
@@ -125,9 +125,9 @@ def __init__(
         classifier: Classify,
         validator: Validate,
         translator: Translate,
-        uta: UTADatabase,
-        mane_transcript: MANETranscript,
-        mane_transcript_mappings: MANETranscriptMappings,
+        uta: UtaDatabase,
+        mane_transcript: ManeTranscript,
+        mane_transcript_mappings: ManeTranscriptMappings,
     ) -> None:
         """Initialize the GnomadVcfToProteinVariation class
 
@@ -401,7 +401,7 @@ async def gnomad_vcf_to_protein(self, q: str) -> NormalizeService:
                         g_start_pos = classification_token.pos
                         g_end_pos = classification_token.pos
                         ref_seq, w = self.seqrepo_access.get_reference_sequence(
-                            alt_ac, g_start_pos
+                            alt_ac, start=g_start_pos, end=g_start_pos
                         )
                         if not ref_seq:
                             all_warnings.add(w)
@@ -476,9 +476,9 @@ async def gnomad_vcf_to_protein(self, q: str) -> NormalizeService:
                             current_mane_data,
                             (mane_c_pos_change[0] + 1, mane_c_pos_change[1] + 1),
                         )
-                        if mane_p["pos"][0] > mane_p["pos"][1]:
-                            mane_p["pos"] = (mane_p["pos"][1], mane_p["pos"][0])
-                        p_ac = mane_p["refseq"]
+                        if mane_p.pos[0] > mane_p.pos[1]:
+                            mane_p.pos = (mane_p.pos[1], mane_p.pos[0])
+                        p_ac = mane_p.refseq
                         aa_alt = self._get_gnomad_vcf_protein_alt(
                             classification_token,
                             alt_type,
@@ -493,12 +493,13 @@ async def gnomad_vcf_to_protein(self, q: str) -> NormalizeService:
                             # mane_p is 0-based, but to_vrs allele takes 1-based
                             variation = self.to_vrs_allele(
                                 p_ac,
-                                mane_p["pos"][0],
-                                mane_p["pos"][1],
+                                mane_p.pos[0],
+                                mane_p.pos[1],
                                 "p",
                                 alt_type,
                                 [],
                                 alt=aa_alt,
+                                residue_mode=ResidueMode.INTER_RESIDUE,
                             )
                             if variation:
                                 translation_result = TranslationResult(
@@ -508,7 +509,7 @@ async def gnomad_vcf_to_protein(self, q: str) -> NormalizeService:
 
                                 tr_copy = deepcopy(translation_result)
                                 tr_copy.vrs_seq_loc_ac = p_ac
-                                tr_copy.vrs_seq_loc_ac_status = mane_p["status"]
+                                tr_copy.vrs_seq_loc_ac_status = mane_p.status
 
                                 try:
                                     vrs_variation = tr_copy.vrs_variation

variation/hgvs_dup_del_mode.py

@@ -2,6 +2,7 @@
 from typing import Dict, List, Optional, Union
 
 from cool_seq_tool.handlers import SeqRepoAccess
+from cool_seq_tool.schemas import ResidueMode
 from ga4gh.core import ga4gh_identify
 from ga4gh.vrs import models, normalize
 
@@ -138,11 +139,11 @@ def allele_mode(
             return None
 
         if alt_type == AltType.DUPLICATION:
-            # start is start - 1, end is end
             ref, _ = self.seqrepo_access.get_reference_sequence(
                 vrs_seq_loc_ac,
-                location["start"] + 1,
-                location["end"] + 1,
+                start=location["start"],
+                end=location["end"],
+                residue_mode=ResidueMode.INTER_RESIDUE,
             )
 
             if ref:

variation/normalize.py

@@ -4,7 +4,7 @@
 from urllib.parse import unquote
 
 from cool_seq_tool.handlers import SeqRepoAccess
-from cool_seq_tool.sources import UTADatabase
+from cool_seq_tool.sources import UtaDatabase
 from ga4gh.vrs import models
 
 from variation.classify import Classify
@@ -38,7 +38,7 @@ def __init__(
         classifier: Classify,
         validator: Validate,
         translator: Translate,
-        uta: UTADatabase,
+        uta: UtaDatabase,
     ) -> None:
         """Initialize Normalize class.
 
@@ -47,7 +47,7 @@ def __init__(
         :param classifier: Classifier class for classifying tokens
         :param validator: Validator class for validating valid inputs
         :param translator: Translating valid inputs
-        :param UTADatabase uta: Access to db containing alignment data
+        :param UtaDatabase uta: Access to db containing alignment data
         """
         super().__init__(
             seqrepo_access,

variation/to_copy_number_variation.py

@@ -4,7 +4,7 @@
 from urllib.parse import unquote
 
 from cool_seq_tool.handlers import SeqRepoAccess
-from cool_seq_tool.sources import UTADatabase
+from cool_seq_tool.sources import UtaDatabase
 from ga4gh.core import ga4gh_identify
 from ga4gh.vrs import models
 from gene.query import QueryHandler as GeneQueryHandler
@@ -80,7 +80,7 @@ def __init__(
         validator: Validate,
         translator: Translate,
         gene_normalizer: GeneQueryHandler,
-        uta: UTADatabase,
+        uta: UtaDatabase,
     ) -> None:
         """Initialize theToCopyNumberVariation class
 
@@ -673,7 +673,7 @@ def amplification_to_cx_var(
                     else:
                         # Validate start/end are actually on the sequence
                         _, w = self.seqrepo_access.get_reference_sequence(
-                            sequence_id, start, end
+                            sequence_id, start=start, end=end
                         )
                         if w:
                             warnings.append(w)

variation/translate.py

@@ -2,8 +2,8 @@
 from typing import List, Optional
 
 from cool_seq_tool.handlers import SeqRepoAccess
-from cool_seq_tool.mappers import MANETranscript
-from cool_seq_tool.sources import UTADatabase
+from cool_seq_tool.mappers import ManeTranscript
+from cool_seq_tool.sources import UtaDatabase
 from ga4gh.vrs import models
 
 from variation.hgvs_dup_del_mode import HGVSDupDelMode
@@ -43,8 +43,8 @@ class Translate:
     def __init__(
         self,
         seqrepo_access: SeqRepoAccess,
-        mane_transcript: MANETranscript,
-        uta: UTADatabase,
+        mane_transcript: ManeTranscript,
+        uta: UtaDatabase,
         vrs: VRSRepresentation,
         hgvs_dup_del_mode: HGVSDupDelMode,
     ) -> None:

variation/translators/genomic_del_dup_base.py

@@ -109,6 +109,7 @@ async def translate(
         grch38_data = None
         vrs_variation = None
         vrs_seq_loc_ac_status = VrsSeqLocAcStatus.NA
+        residue_mode = ResidueMode.RESIDUE
 
         if do_liftover or endpoint_name == Endpoint.NORMALIZE:
             errors = []
@@ -126,18 +127,23 @@ async def translate(
                         warnings += errors
                         return None
 
-                    pos0 = grch38_data.pos0
-                    pos1 = grch38_data.pos1
+                    pos0 = grch38_data.pos0 - 1
+                    if grch38_data.pos1 is None:
+                        pos1 = grch38_data.pos0
+                    else:
+                        pos1 = grch38_data.pos1
+                    residue_mode = ResidueMode.INTER_RESIDUE
                     ac = grch38_data.ac
 
                     if alt_type == AltType.DELETION:
                         if classification.nomenclature == Nomenclature.GNOMAD_VCF:
                             ref = classification.matching_tokens[0].ref
                             invalid_ref_msg = self.validate_reference_sequence(
                                 ac,
-                                pos0 - 1,
-                                pos0 - 1 + len(ref),
+                                pos0,
+                                pos0 + (len(ref) - 1),
                                 ref,
+                                residue_mode=residue_mode,
                             )
                             if invalid_ref_msg:
                                 warnings.append(invalid_ref_msg)
@@ -146,6 +152,7 @@ async def translate(
                     pos0 = classification.pos0
                     pos1 = classification.pos1
                     ac = validation_result.accession
+                    grch38_data = DelDupData(ac=ac, pos0=pos0, pos1=pos1)
 
                 assembly = ClinVarAssembly.GRCH38
         else:
@@ -168,10 +175,13 @@ async def translate(
                     warnings += errors
                     return None
 
-                pos0 = grch38_data.pos0
+            ac = grch38_data.ac
+            pos0 = grch38_data.pos0 - 1
+            if grch38_data.pos1 is None:
+                pos1 = grch38_data.pos0
+            else:
                 pos1 = grch38_data.pos1
-                ac = grch38_data.ac
-
+            residue_mode = ResidueMode.INTER_RESIDUE
             self.is_valid(classification.gene_token, ac, pos0, pos1, errors)
 
             if errors:
@@ -181,21 +191,22 @@ async def translate(
             mane = await self.mane_transcript.get_mane_transcript(
                 ac,
                 pos0,
+                pos1,
                 "g",
-                end_pos=pos1,
                 try_longest_compatible=True,
-                residue_mode=ResidueMode.RESIDUE,
+                residue_mode=residue_mode,
                 gene=classification.gene_token.token
                 if classification.gene_token
                 else None,
             )
 
             if mane:
                 # mane is 0 - based, but we are using residue
-                ac = mane["refseq"]
-                vrs_seq_loc_ac_status = mane["status"]
-                pos0 = mane["pos"][0] + mane["coding_start_site"] + 1
-                pos1 = mane["pos"][1] + mane["coding_start_site"] + 1
+                ac = mane.refseq
+                vrs_seq_loc_ac_status = mane.status
+                pos0 = mane.pos[0] + mane.coding_start_site
+                pos1 = mane.pos[1] + mane.coding_start_site
+                residue_mode = ResidueMode.INTER_RESIDUE
             else:
                 return None
 
@@ -209,7 +220,7 @@ async def translate(
         if alt_type == AltType.INSERTION:
             alt = classification.inserted_sequence
 
-        start = pos0 - 1
+        start = pos0 if residue_mode == ResidueMode.INTER_RESIDUE else pos0 - 1
         end = pos1 if pos1 else pos0
 
         refget_accession = get_refget_accession(self.seqrepo_access, ac, warnings)

variation/translators/genomic_delins.py

@@ -66,40 +66,43 @@ async def translate(
             mane = await self.mane_transcript.get_mane_transcript(
                 validation_result.accession,
                 classification.pos0,
+                classification.pos1
+                if classification.pos1 is not None
+                else classification.pos0,
                 AnnotationLayer.GENOMIC,
-                end_pos=classification.pos1,
                 try_longest_compatible=True,
-                residue_mode=ResidueMode.RESIDUE.value,
+                residue_mode=ResidueMode.RESIDUE,
                 gene=gene,
             )
 
             if mane:
-                vrs_seq_loc_ac_status = mane["status"]
+                vrs_seq_loc_ac_status = mane.status
                 if gene:
                     classification = CdnaDelInsClassification(
                         matching_tokens=classification.matching_tokens,
                         nomenclature=classification.nomenclature,
                         gene_token=classification.gene_token,
-                        pos0=mane["pos"][0] + 1,
-                        pos1=mane["pos"][1] + 1,
+                        pos0=mane.pos[0] + 1,  # 1-based for classification
+                        pos1=mane.pos[1] + 1,  # 1-based for classification
                         inserted_sequence=classification.inserted_sequence,
                     )
-                    vrs_seq_loc_ac = mane["refseq"]
+                    vrs_seq_loc_ac = mane.refseq
                     coord_type = AnnotationLayer.CDNA
                     validation_result.classification = classification
                 else:
-                    vrs_seq_loc_ac = mane["alt_ac"]
+                    vrs_seq_loc_ac = mane.alt_ac
                     coord_type = AnnotationLayer.GENOMIC
 
                 vrs_allele = self.vrs.to_vrs_allele(
                     vrs_seq_loc_ac,
-                    mane["pos"][0] + 1,
-                    mane["pos"][1] + 1,
+                    mane.pos[0],
+                    mane.pos[1],
                     coord_type,
                     AltType.DELINS,
                     warnings,
                     alt=classification.inserted_sequence,
-                    cds_start=mane["coding_start_site"] if gene else None,
+                    cds_start=mane.coding_start_site if gene else None,
+                    residue_mode=ResidueMode.INTER_RESIDUE,
                 )
         else:
             vrs_seq_loc_ac = validation_result.accession
@@ -111,6 +114,7 @@ async def translate(
                 AltType.DELINS,
                 warnings,
                 alt=classification.inserted_sequence,
+                residue_mode=ResidueMode.RESIDUE,
             )
 
         if vrs_allele and vrs_seq_loc_ac: