diff --git a/v03_pipeline/lib/annotations/sv.py b/v03_pipeline/lib/annotations/sv.py index 278c045eb..868232a2f 100644 --- a/v03_pipeline/lib/annotations/sv.py +++ b/v03_pipeline/lib/annotations/sv.py @@ -180,6 +180,7 @@ def gnomad_svs( gnomad_svs_ht: hl.Table, **_: Any, ) -> hl.Expression: + gnomad_svs_ht = gnomad_svs_ht.drop('locus', 'alleles') return gnomad_svs_ht.annotate( ID=gnomad_svs_ht.KEY, )[ht['info.GNOMAD_V4.1_TRUTH_VID']] diff --git a/v03_pipeline/lib/reference_datasets/gnomad_svs.py b/v03_pipeline/lib/reference_datasets/gnomad_svs.py index 5743de3c4..114a45f3b 100644 --- a/v03_pipeline/lib/reference_datasets/gnomad_svs.py +++ b/v03_pipeline/lib/reference_datasets/gnomad_svs.py @@ -14,5 +14,4 @@ def get_ht(path: str, reference_genome: ReferenceGenome) -> hl.Table: N_HET=ht.info.N_HET, N_HOMREF=ht.info.N_HOMREF, ) - ht = ht.key_by('KEY') - return ht.drop('locus', 'alleles') + return ht.key_by('KEY') diff --git a/v03_pipeline/lib/reference_datasets/gnomad_svs_test.py b/v03_pipeline/lib/reference_datasets/gnomad_svs_test.py new file mode 100644 index 000000000..ff24aa3d1 --- /dev/null +++ b/v03_pipeline/lib/reference_datasets/gnomad_svs_test.py @@ -0,0 +1,93 @@ +import unittest +from unittest.mock import patch + +import hail as hl + +from v03_pipeline.lib.model import ReferenceGenome +from v03_pipeline.lib.reference_datasets.reference_dataset import ReferenceDataset + +TEST_GNOMAD_SVS_RAW_HT = ( + 'v03_pipeline/var/test/reference_datasets/raw/gnomad_svs_from_vcf.ht' +) + + +class GnomadSVsTest(unittest.TestCase): + @patch('v03_pipeline.lib.reference_datasets.gnomad_svs.vcf_to_ht') + def test_gnomad_svs(self, mock_vcf_to_ht): + mock_vcf_to_ht.return_value = hl.read_table(TEST_GNOMAD_SVS_RAW_HT) + ht = ReferenceDataset.gnomad_svs.get_ht(ReferenceGenome.GRCh38) + self.assertEqual( + ht.collect(), + [ + hl.Struct( + KEY='gnomAD-SV_v3_BND_chr1_1a45f73a', + locus=hl.Locus( + contig='chr1', + position=10434, + reference_genome=ReferenceGenome.GRCh38, + ), + alleles=['N', ''], + AF=0.11413399875164032, + AC=8474, + AN=74246, + N_HET=8426, + N_HOMREF=28673, + ), + hl.Struct( + KEY='gnomAD-SV_v3_BND_chr1_3fa36917', + locus=hl.Locus( + contig='chr1', + position=10440, + reference_genome=ReferenceGenome.GRCh38, + ), + alleles=['N', ''], + AF=0.004201000090688467, + AC=466, + AN=110936, + N_HET=466, + N_HOMREF=55002, + ), + hl.Struct( + KEY='gnomAD-SV_v3_BND_chr1_7bbf34b5', + locus=hl.Locus( + contig='chr1', + position=10464, + reference_genome=ReferenceGenome.GRCh38, + ), + alleles=['N', ''], + AF=0.03698499873280525, + AC=3119, + AN=84332, + N_HET=3115, + N_HOMREF=39049, + ), + hl.Struct( + KEY='gnomAD-SV_v3_BND_chr1_933a2971', + locus=hl.Locus( + contig='chr1', + position=10450, + reference_genome=ReferenceGenome.GRCh38, + ), + alleles=['N', ''], + AF=0.3238990008831024, + AC=21766, + AN=67200, + N_HET=21616, + N_HOMREF=11909, + ), + hl.Struct( + KEY='gnomAD-SV_v3_DUP_chr1_01c2781c', + locus=hl.Locus( + contig='chr1', + position=10000, + reference_genome=ReferenceGenome.GRCh38, + ), + alleles=['N', ''], + AF=0.0019970000721514225, + AC=139, + AN=69594, + N_HET=139, + N_HOMREF=34658, + ), + ], + ) diff --git a/v03_pipeline/lib/reference_datasets/reference_dataset.py b/v03_pipeline/lib/reference_datasets/reference_dataset.py index a8482c578..d2adab683 100644 --- a/v03_pipeline/lib/reference_datasets/reference_dataset.py +++ b/v03_pipeline/lib/reference_datasets/reference_dataset.py @@ -104,6 +104,12 @@ def version(self, reference_genome: ReferenceGenome) -> str: ) return version + def dataset_types( + self, + reference_genome: ReferenceGenome, + ) -> frozenset[DatasetType]: + return CONFIG[self][reference_genome][DATASET_TYPES] + @property def enums(self) -> dict | None: return CONFIG[self].get(ENUMS) @@ -143,11 +149,9 @@ def get_ht( if enum_selects: ht = ht.transmute(**enum_selects) ht = filter_contigs(ht, reference_genome) - # Reference Datasets are DatasetType agnostic, but these - # methods (in theory) support SV/GCNV. SNV_INDEL - # is passed as a proxy for non-SV/GCNV. - validate_allele_type(ht, DatasetType.SNV_INDEL) - validate_no_duplicate_variants(ht, reference_genome, DatasetType.SNV_INDEL) + for dataset_type in self.dataset_types(reference_genome): + validate_allele_type(ht, dataset_type) + validate_no_duplicate_variants(ht, reference_genome, dataset_type) # NB: we do not filter with "filter" here # ReferenceDatasets are DatasetType agnostic and that # filter is only used at annotation time. diff --git a/v03_pipeline/migrations/annotations/0004_add_gnomad_svs.py b/v03_pipeline/migrations/annotations/0004_add_gnomad_svs.py new file mode 100644 index 000000000..3cb3a4c98 --- /dev/null +++ b/v03_pipeline/migrations/annotations/0004_add_gnomad_svs.py @@ -0,0 +1,52 @@ +import hail as hl + +from v03_pipeline.lib.annotations import sv +from v03_pipeline.lib.migration.base_migration import BaseMigration +from v03_pipeline.lib.model import DatasetType, ReferenceGenome +from v03_pipeline.lib.reference_datasets.reference_dataset import ReferenceDataset + +# This vcf was generated with the gatk command: +# +# gatk SVConcordance --verbosity DEBUG --evaluation /var/seqr/phase4.seqr.gnomad_v4_tmp.vcf.gz +# --truth /var/seqr/gnomad.v4.1.sv.sites.modified.vcf.bgz +# --sequence-dictionary gs://gcp-public-data--broad-references/hg38/v0/Homo_sapiens_assembly38.dict +# +# Followed by: +# bcftools annotate --rename-annots /var/seqr/remap /var/seqr/phase4.seqr.gnomad_v4_tmp.vcf.gz | bgzip > /var/seqr/phase4.seqr.gnomad_v4.vcf.gz +# +# where remap contains "INFO/TRUTH_VID GNOMAD_V4.1_TRUTH_VID" +PHASE_4_CALLSET_WITH_GNOMAD_V4 = 'gs://seqr-loading-temp/phase4.seqr.gnomad_v4.vcf.gz' + + +class AddGnomadSVs(BaseMigration): + reference_genome_dataset_types: frozenset[ + tuple[ReferenceGenome, DatasetType] + ] = frozenset( + ((ReferenceGenome.GRCh38, DatasetType.SV),), + ) + + @staticmethod + def migrate(ht: hl.Table, **_) -> hl.Table: + mapping_ht = ( + hl.import_vcf( + PHASE_4_CALLSET_WITH_GNOMAD_V4, + reference_genome=ReferenceGenome.GRCh38.value, + force_bgz=True, + ) + .key_rows_by('rsid') + .rows() + ) + ht = ht.annotate( + **{ + 'info.GNOMAD_V4.1_TRUTH_VID': mapping_ht[ht.key].info[ + 'GNOMAD_V4.1_TRUTH_VID' + ], + }, + ) + gnomad_svs_ht = ReferenceDataset.gnomad_svs.get_ht(ReferenceGenome.GRCh38) + ht = ht.annotate(gnomad_svs=sv.gnomad_svs(ht, gnomad_svs_ht)) + ht = ht.drop('info.GNOMAD_V4.1_TRUTH_VID') + return ht.annotate_globals( + versions=ht.globals.versions.annotate(gnomad_svs='1.0'), + enums=ht.globals.enums.annotate(gnomad_svs=hl.Struct()), + ) diff --git a/v03_pipeline/var/test/reference_datasets/GRCh38/gnomad_svs/1.0.ht/.README.txt.crc b/v03_pipeline/var/test/reference_datasets/GRCh38/gnomad_svs/1.0.ht/.README.txt.crc index c743d6946..0bc2c6163 100644 Binary files a/v03_pipeline/var/test/reference_datasets/GRCh38/gnomad_svs/1.0.ht/.README.txt.crc and b/v03_pipeline/var/test/reference_datasets/GRCh38/gnomad_svs/1.0.ht/.README.txt.crc differ diff --git a/v03_pipeline/var/test/reference_datasets/GRCh38/gnomad_svs/1.0.ht/.metadata.json.gz.crc b/v03_pipeline/var/test/reference_datasets/GRCh38/gnomad_svs/1.0.ht/.metadata.json.gz.crc index f1c831b07..79a393e98 100644 Binary files a/v03_pipeline/var/test/reference_datasets/GRCh38/gnomad_svs/1.0.ht/.metadata.json.gz.crc and b/v03_pipeline/var/test/reference_datasets/GRCh38/gnomad_svs/1.0.ht/.metadata.json.gz.crc differ diff --git a/v03_pipeline/var/test/reference_datasets/GRCh38/gnomad_svs/1.0.ht/README.txt b/v03_pipeline/var/test/reference_datasets/GRCh38/gnomad_svs/1.0.ht/README.txt index 50aa6a3d3..967ef021c 100644 --- a/v03_pipeline/var/test/reference_datasets/GRCh38/gnomad_svs/1.0.ht/README.txt +++ b/v03_pipeline/var/test/reference_datasets/GRCh38/gnomad_svs/1.0.ht/README.txt @@ -1,3 +1,3 @@ This folder comprises a Hail (www.hail.is) native Table or MatrixTable. 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