Update GA4GH VRS from 0.8.4 to 2.0.1

gnomad/utils/annotations.py

@@ -36,56 +36,56 @@
 
 VRS_CHROM_IDS = {
     "GRCh38": {
-        "chr1": "ga4gh:SQ.Ya6Rs7DHhDeg7YaOSg1EoNi3U_nQ9SvO",
-        "chr2": "ga4gh:SQ.pnAqCRBrTsUoBghSD1yp_jXWSmlbdh4g",
-        "chr3": "ga4gh:SQ.Zu7h9AggXxhTaGVsy7h_EZSChSZGcmgX",
-        "chr4": "ga4gh:SQ.HxuclGHh0XCDuF8x6yQrpHUBL7ZntAHc",
-        "chr5": "ga4gh:SQ.aUiQCzCPZ2d0csHbMSbh2NzInhonSXwI",
-        "chr6": "ga4gh:SQ.0iKlIQk2oZLoeOG9P1riRU6hvL5Ux8TV",
-        "chr7": "ga4gh:SQ.F-LrLMe1SRpfUZHkQmvkVKFEGaoDeHul",
-        "chr8": "ga4gh:SQ.209Z7zJ-mFypBEWLk4rNC6S_OxY5p7bs",
-        "chr9": "ga4gh:SQ.KEO-4XBcm1cxeo_DIQ8_ofqGUkp4iZhI",
-        "chr10": "ga4gh:SQ.ss8r_wB0-b9r44TQTMmVTI92884QvBiB",
-        "chr11": "ga4gh:SQ.2NkFm8HK88MqeNkCgj78KidCAXgnsfV1",
-        "chr12": "ga4gh:SQ.6wlJpONE3oNb4D69ULmEXhqyDZ4vwNfl",
-        "chr13": "ga4gh:SQ._0wi-qoDrvram155UmcSC-zA5ZK4fpLT",
-        "chr14": "ga4gh:SQ.eK4D2MosgK_ivBkgi6FVPg5UXs1bYESm",
-        "chr15": "ga4gh:SQ.AsXvWL1-2i5U_buw6_niVIxD6zTbAuS6",
-        "chr16": "ga4gh:SQ.yC_0RBj3fgBlvgyAuycbzdubtLxq-rE0",
-        "chr17": "ga4gh:SQ.dLZ15tNO1Ur0IcGjwc3Sdi_0A6Yf4zm7",
-        "chr18": "ga4gh:SQ.vWwFhJ5lQDMhh-czg06YtlWqu0lvFAZV",
-        "chr19": "ga4gh:SQ.IIB53T8CNeJJdUqzn9V_JnRtQadwWCbl",
-        "chr20": "ga4gh:SQ.-A1QmD_MatoqxvgVxBLZTONHz9-c7nQo",
-        "chr21": "ga4gh:SQ.5ZUqxCmDDgN4xTRbaSjN8LwgZironmB8",
-        "chr22": "ga4gh:SQ.7B7SHsmchAR0dFcDCuSFjJAo7tX87krQ",
-        "chrX": "ga4gh:SQ.w0WZEvgJF0zf_P4yyTzjjv9oW1z61HHP",
-        "chrY": "ga4gh:SQ.8_liLu1aycC0tPQPFmUaGXJLDs5SbPZ5",
+        "chr1": "SQ.Ya6Rs7DHhDeg7YaOSg1EoNi3U_nQ9SvO",
+        "chr2": "SQ.pnAqCRBrTsUoBghSD1yp_jXWSmlbdh4g",
+        "chr3": "SQ.Zu7h9AggXxhTaGVsy7h_EZSChSZGcmgX",
+        "chr4": "SQ.HxuclGHh0XCDuF8x6yQrpHUBL7ZntAHc",
+        "chr5": "SQ.aUiQCzCPZ2d0csHbMSbh2NzInhonSXwI",
+        "chr6": "SQ.0iKlIQk2oZLoeOG9P1riRU6hvL5Ux8TV",
+        "chr7": "SQ.F-LrLMe1SRpfUZHkQmvkVKFEGaoDeHul",
+        "chr8": "SQ.209Z7zJ-mFypBEWLk4rNC6S_OxY5p7bs",
+        "chr9": "SQ.KEO-4XBcm1cxeo_DIQ8_ofqGUkp4iZhI",
+        "chr10": "SQ.ss8r_wB0-b9r44TQTMmVTI92884QvBiB",
+        "chr11": "SQ.2NkFm8HK88MqeNkCgj78KidCAXgnsfV1",
+        "chr12": "SQ.6wlJpONE3oNb4D69ULmEXhqyDZ4vwNfl",
+        "chr13": "SQ._0wi-qoDrvram155UmcSC-zA5ZK4fpLT",
+        "chr14": "SQ.eK4D2MosgK_ivBkgi6FVPg5UXs1bYESm",
+        "chr15": "SQ.AsXvWL1-2i5U_buw6_niVIxD6zTbAuS6",
+        "chr16": "SQ.yC_0RBj3fgBlvgyAuycbzdubtLxq-rE0",
+        "chr17": "SQ.dLZ15tNO1Ur0IcGjwc3Sdi_0A6Yf4zm7",
+        "chr18": "SQ.vWwFhJ5lQDMhh-czg06YtlWqu0lvFAZV",
+        "chr19": "SQ.IIB53T8CNeJJdUqzn9V_JnRtQadwWCbl",
+        "chr20": "SQ.-A1QmD_MatoqxvgVxBLZTONHz9-c7nQo",
+        "chr21": "SQ.5ZUqxCmDDgN4xTRbaSjN8LwgZironmB8",
+        "chr22": "SQ.7B7SHsmchAR0dFcDCuSFjJAo7tX87krQ",
+        "chrX": "SQ.w0WZEvgJF0zf_P4yyTzjjv9oW1z61HHP",
+        "chrY": "SQ.8_liLu1aycC0tPQPFmUaGXJLDs5SbPZ5",
     },
     "GRCh37": {
-        "1": "ga4gh:SQ.S_KjnFVz-FE7M0W6yoaUDgYxLPc1jyWU",
-        "2": "ga4gh:SQ.9KdcA9ZpY1Cpvxvg8bMSLYDUpsX6GDLO",
-        "3": "ga4gh:SQ.VNBualIltAyi2AI_uXcKU7M9XUOuA7MS",
-        "4": "ga4gh:SQ.iy7Zfceb5_VGtTQzJ-v5JpPbpeifHD_V",
-        "5": "ga4gh:SQ.vbjOdMfHJvTjK_nqvFvpaSKhZillW0SX",
-        "6": "ga4gh:SQ.KqaUhJMW3CDjhoVtBetdEKT1n6hM-7Ek",
-        "7": "ga4gh:SQ.IW78mgV5Cqf6M24hy52hPjyyo5tCCd86",
-        "8": "ga4gh:SQ.tTm7wmhz0G4lpt8wPspcNkAD_qiminj6",
-        "9": "ga4gh:SQ.HBckYGQ4wYG9APHLpjoQ9UUe9v7NxExt",
-        "10": "ga4gh:SQ.-BOZ8Esn8J88qDwNiSEwUr5425UXdiGX",
-        "11": "ga4gh:SQ.XXi2_O1ly-CCOi3HP5TypAw7LtC6niFG",
-        "12": "ga4gh:SQ.105bBysLoDFQHhajooTAUyUkNiZ8LJEH",
-        "13": "ga4gh:SQ.Ewb9qlgTqN6e_XQiRVYpoUfZJHXeiUfH",
-        "14": "ga4gh:SQ.5Ji6FGEKfejK1U6BMScqrdKJK8GqmIGf",
-        "15": "ga4gh:SQ.zIMZb3Ft7RdWa5XYq0PxIlezLY2ccCgt",
-        "16": "ga4gh:SQ.W6wLoIFOn4G7cjopxPxYNk2lcEqhLQFb",
-        "17": "ga4gh:SQ.AjWXsI7AkTK35XW9pgd3UbjpC3MAevlz",
-        "18": "ga4gh:SQ.BTj4BDaaHYoPhD3oY2GdwC_l0uqZ92UD",
-        "19": "ga4gh:SQ.ItRDD47aMoioDCNW_occY5fWKZBKlxCX",
-        "20": "ga4gh:SQ.iy_UbUrvECxFRX5LPTH_KPojdlT7BKsf",
-        "21": "ga4gh:SQ.LpTaNW-hwuY_yARP0rtarCnpCQLkgVCg",
-        "22": "ga4gh:SQ.XOgHwwR3Upfp5sZYk6ZKzvV25a4RBVu8",
-        "X": "ga4gh:SQ.v7noePfnNpK8ghYXEqZ9NukMXW7YeNsm",
-        "Y": "ga4gh:SQ.BT7QyW5iXaX_1PSX-msSGYsqRdMKqkj-",
+        "1": "SQ.S_KjnFVz-FE7M0W6yoaUDgYxLPc1jyWU",
+        "2": "SQ.9KdcA9ZpY1Cpvxvg8bMSLYDUpsX6GDLO",
+        "3": "SQ.VNBualIltAyi2AI_uXcKU7M9XUOuA7MS",
+        "4": "SQ.iy7Zfceb5_VGtTQzJ-v5JpPbpeifHD_V",
+        "5": "SQ.vbjOdMfHJvTjK_nqvFvpaSKhZillW0SX",
+        "6": "SQ.KqaUhJMW3CDjhoVtBetdEKT1n6hM-7Ek",
+        "7": "SQ.IW78mgV5Cqf6M24hy52hPjyyo5tCCd86",
+        "8": "SQ.tTm7wmhz0G4lpt8wPspcNkAD_qiminj6",
+        "9": "SQ.HBckYGQ4wYG9APHLpjoQ9UUe9v7NxExt",
+        "10": "SQ.-BOZ8Esn8J88qDwNiSEwUr5425UXdiGX",
+        "11": "SQ.XXi2_O1ly-CCOi3HP5TypAw7LtC6niFG",
+        "12": "SQ.105bBysLoDFQHhajooTAUyUkNiZ8LJEH",
+        "13": "SQ.Ewb9qlgTqN6e_XQiRVYpoUfZJHXeiUfH",
+        "14": "SQ.5Ji6FGEKfejK1U6BMScqrdKJK8GqmIGf",
+        "15": "SQ.zIMZb3Ft7RdWa5XYq0PxIlezLY2ccCgt",
+        "16": "SQ.W6wLoIFOn4G7cjopxPxYNk2lcEqhLQFb",
+        "17": "SQ.AjWXsI7AkTK35XW9pgd3UbjpC3MAevlz",
+        "18": "SQ.BTj4BDaaHYoPhD3oY2GdwC_l0uqZ92UD",
+        "19": "SQ.ItRDD47aMoioDCNW_occY5fWKZBKlxCX",
+        "20": "SQ.iy_UbUrvECxFRX5LPTH_KPojdlT7BKsf",
+        "21": "SQ.LpTaNW-hwuY_yARP0rtarCnpCQLkgVCg",
+        "22": "SQ.XOgHwwR3Upfp5sZYk6ZKzvV25a4RBVu8",
+        "X": "SQ.v7noePfnNpK8ghYXEqZ9NukMXW7YeNsm",
+        "Y": "SQ.BT7QyW5iXaX_1PSX-msSGYsqRdMKqkj-",
     },
 }
 
@@ -2672,9 +2672,13 @@ def add_gks_vrs(
         "state": {"type": "LiteralSequenceExpression", "sequence": vrs_state_sequence},
     }
 
-    location_id = ga4gh_core._internal.identifiers.ga4gh_identify(
-        ga4gh_vrs.models.SequenceLocation(**vrs_dict_out["location"])
+    seq_ref = ga4gh_vrs.models.SequenceReference(refgetAccession=vrs_chrom_id)
+    seq_loc = ga4gh_vrs.models.SequenceLocation(
+        sequenceReference=seq_ref,
+        start=vrs_start_value,
+        end=vrs_end_value,
     )
+    location_id = ga4gh_core.ga4gh_identify(seq_loc)
 
     vrs_dict_out["location"]["_id"] = location_id
 
@@ -2860,9 +2864,7 @@ def _create_group_dicts(
         ancillaryResults["grpMaxFAF95"] = {
             "frequency": input_struct.grpMaxFAF95.grpmax_gen_anc,
             "confidenceInterval": 0.95,
-            "groupId": (
-                f"{gnomad_id}.{input_struct.grpMaxFAF95.grpmax_gen_anc.upper()}"
-            ),
+            "groupId": f"{gnomad_id}.{input_struct.grpMaxFAF95.grpmax_gen_anc.upper()}",
         }
 
     # Add joint group max FAF if it exists.

requirements.txt

@@ -1,5 +1,5 @@
 annoy
-ga4gh.vrs[extras]==0.8.4
+ga4gh.vrs[extras]==2.0.1
 hail
 hdbscan
 ipywidgets

tests/utils/test_annotations.py

@@ -2,10 +2,14 @@
 
 from typing import Dict, List
 
+import ga4gh.core as ga4gh_core
+import ga4gh.vrs as ga4gh_vrs
 import hail as hl
 import pytest
 
 from gnomad.utils.annotations import (
+    VRS_CHROM_IDS,
+    add_gks_vrs,
     annotate_downsamplings,
     fill_missing_key_combinations,
     get_copy_state_by_sex,
@@ -1088,6 +1092,110 @@ def test_merge_histograms_sum_with_negatives_error(self, sample_ht):
             ht.select(result_hist=result_hist).collect()
 
 
+class TestVRSFunctions:
+    """Test the VRS-related functions."""
+
+    def test_vrs_identifier_generation(self):
+        """Test that GA4GH identifiers are generated correctly."""
+        # Test that we can import and access VRS modules
+        assert hasattr(ga4gh_core, "__version__")
+        assert hasattr(ga4gh_vrs, "models")
+        assert hasattr(ga4gh_vrs.models, "SequenceLocation")
+
+        # Test that VRS 2.0.1+ API is available
+        assert hasattr(
+            ga4gh_core, "ga4gh_identify"
+        ), "VRS 2.0.1+ ga4gh_identify function not found"
+
+        # Test that we can create a VRS object using the 2.0.1+ API
+        seq_loc = ga4gh_vrs.models.SequenceLocation(
+            sequenceReference="ga4gh:SQ.test",
+            start=1,
+            end=2,
+        )
+        assert seq_loc is not None
+
+    def test_vrs_error_handling(self):
+        """Test that VRS functions handle errors gracefully."""
+        # Test with invalid locus (should raise appropriate error)
+        with pytest.raises((AttributeError, TypeError)):
+            # This should fail because we're not providing proper Hail locus objects
+            add_gks_vrs("invalid_locus", "invalid_vrs")
+
+    def test_add_gks_vrs_actual_api_call(self):
+        """Test that add_gks_vrs actually calls the VRS 2.0.1 API with real data."""
+        # Create a real Hail locus and VRS struct that would come from actual data
+        locus = hl.locus("chr1", 100, reference_genome="GRCh38")
+
+        # Create a VRS struct that mimics what would be in actual gnomAD data
+        vrs_struct = hl.struct(
+            VRS_Allele_IDs=["test_ref_id", "ga4gh:VA.test_var_id"],
+            VRS_Starts=[99, 99],  # 0-based coordinates
+            VRS_Ends=[100, 100],
+            VRS_States=["A", "T"],  # ref, alt
+        )
+
+        # Evaluate to get actual Python objects
+        locus_py = hl.eval(locus)
+        vrs_py = hl.eval(vrs_struct)
+
+        result = add_gks_vrs(locus_py, vrs_py)
+
+        # Verify the result has the expected VRS structure
+        assert isinstance(result, dict)
+        assert result["type"] == "Allele"
+        assert "location" in result
+        assert result["location"]["type"] == "SequenceLocation"
+        assert "_id" in result["location"]  # This comes from ga4gh_identify() call
+        assert "state" in result
+        assert result["state"]["type"] == "LiteralSequenceExpression"
+        assert result["state"]["sequence"] == "T"
+
+        # Verify the chromosome ID matches our VRS_CHROM_IDS mapping
+        expected_chr1_id = VRS_CHROM_IDS["GRCh38"]["chr1"]
+        assert result["location"]["sequence_id"] == expected_chr1_id
+        assert expected_chr1_id == "SQ.Ya6Rs7DHhDeg7YaOSg1EoNi3U_nQ9SvO"
+
+        # Verify the location ID was generated by the VRS API
+        location_id = result["location"]["_id"]
+        assert isinstance(location_id, str)
+        assert location_id.startswith("ga4gh:")  # VRS identifiers start with ga4gh:
+
+    def test_add_gks_vrs_grch37_chromosome_mapping(self):
+        """Test that VRS chromosome mapping works correctly for GRCh37."""
+        # Test GRCh37 (note different chromosome naming: "1" vs "chr1")
+        locus_grch37 = hl.locus("1", 100, reference_genome="GRCh37")
+        vrs_struct = hl.struct(
+            VRS_Allele_IDs=["test_ref_id", "ga4gh:VA.test_var_id"],
+            VRS_Starts=[99, 99],
+            VRS_Ends=[100, 100],
+            VRS_States=["A", "T"],
+        )
+
+        locus_py = hl.eval(locus_grch37)
+        vrs_py = hl.eval(vrs_struct)
+
+        result = add_gks_vrs(locus_py, vrs_py)
+
+        # Verify GRCh37 chromosome 1 mapping
+        expected_chr1_grch37_id = VRS_CHROM_IDS["GRCh37"]["1"]
+        assert result["location"]["sequence_id"] == expected_chr1_grch37_id
+        assert expected_chr1_grch37_id == "SQ.S_KjnFVz-FE7M0W6yoaUDgYxLPc1jyWU"
+
+        # Verify the API was called and generated a proper identifier
+        location_id = result["location"]["_id"]
+        assert isinstance(location_id, str)
+        assert location_id.startswith("ga4gh:")
+
+    def test_vrs_version_compatibility(self):
+        """Test that VRS 2.0.1+ is properly installed."""
+        # Test that VRS 2.0.1+ API is available
+        assert hasattr(ga4gh_core, "ga4gh_identify"), "VRS 2.0.1+ is required"
+
+        # The function should work with VRS 2.0.1+
+        assert callable(add_gks_vrs)
+
+
 class TestAnnotateDownsamplings:
     """Test the annotate_downsamplings function."""