- VCF Datasources now have to match the alt and ref alleles to be con…

…dsidered a hit.
broadinstitute · May 22, 2018 · 5d0bbf2 · 5d0bbf2
1 parent 742d6e6
commit 5d0bbf2
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diff --git a/...org/broadinstitute/hellbender/tools/funcotator/dataSources/vcf/VcfFuncotationFactory.java b/...org/broadinstitute/hellbender/tools/funcotator/dataSources/vcf/VcfFuncotationFactory.java
@@ -149,10 +149,9 @@ protected List<Funcotation> createFuncotationsOnVariant(final VariantContext var
                         // By this point we know the feature type is correct, so we cast it:
                         final VariantContext variantFeature = (VariantContext) feature;
 
-                        //TODO: Add a test that tests alt allele position hit, but misses on the alt allele.
                         // Now we create one funcotation for each Alternate allele:
                         for ( final Allele altAllele : alternateAlleles ) {
-                            if (!variantFeature.hasAlternateAllele(altAllele)) {
+                            if (!(variantFeature.hasAlternateAllele(altAllele) && variantFeature.getReference().equals(variant.getReference()))) {
                                 continue;
                             }
                             // Add all Info keys/values to a copy of our default map:

diff --git a/src/test/java/org/broadinstitute/hellbender/tools/funcotator/FuncotatorIntegrationTest.java b/src/test/java/org/broadinstitute/hellbender/tools/funcotator/FuncotatorIntegrationTest.java
@@ -52,6 +52,7 @@ public class FuncotatorIntegrationTest extends CommandLineProgramTest {
     private static final String PIK3CA_VCF_HG38 = toolsTestDir + "funcotator/hg38_trio.pik3ca.vcf";
     private static final String PIK3CA_VCF_HG19_SNPS = toolsTestDir + "funcotator/PIK3CA_SNPS_3.vcf";
     private static final String PIK3CA_VCF_HG19_INDELS = toolsTestDir + "funcotator/PIK3CA_INDELS_3.vcf";
+    private static final String PIK3CA_VCF_HG19_ALTS = toolsTestDir + "funcotator/PIK3CA_3_miss_clinvar_alt_only.vcf";
     private static final String DS_PIK3CA_DIR = largeFileTestDir + "funcotator/small_ds/";
 
     static {
@@ -503,4 +504,45 @@ public void testVcfMafConcordanceForProteinChange(final String inputVcf, final S
             Assert.assertEquals(mafProteinChanges, vcfProteinChanges, "Failed matching " + annotationToCheck);
         }
     }
+
+    @Test
+    public void testVcfDatasourceAccountsForAltAlleles() {
+        final FuncotatorArgumentDefinitions.OutputFormatType vcfOutputFormatType = FuncotatorArgumentDefinitions.OutputFormatType.VCF;
+        final File vcfOutputFile = getOutputFile(vcfOutputFormatType);
+
+        final ArgumentsBuilder argumentsVcf = new ArgumentsBuilder();
+
+        argumentsVcf.addVCF(new File(PIK3CA_VCF_HG19_ALTS));
+        argumentsVcf.addOutput(vcfOutputFile);
+        argumentsVcf.addReference(new File(FuncotatorTestConstants.HG19_3_REFERENCE_FILE_NAME));
+        argumentsVcf.addArgument(FuncotatorArgumentDefinitions.DATA_SOURCES_PATH_LONG_NAME, DS_PIK3CA_DIR);
+        argumentsVcf.addArgument(FuncotatorArgumentDefinitions.REFERENCE_VERSION_LONG_NAME, FuncotatorTestConstants.REFERENCE_VERSION_HG19);
+        argumentsVcf.addArgument(FuncotatorArgumentDefinitions.OUTPUT_FORMAT_LONG_NAME, vcfOutputFormatType.toString());
+        argumentsVcf.addBooleanArgument(FuncotatorArgumentDefinitions.IGNORE_FILTERED_VARIANTS_LONG_NAME, false);
+
+        // We need this argument since we are testing on a subset of b37
+        argumentsVcf.addBooleanArgument(FuncotatorArgumentDefinitions.ALLOW_HG19_GENCODE_B37_CONTIG_MATCHING_OVERRIDE_LONG_NAME, true);
+        runCommandLine(argumentsVcf);
+
+        final Pair<VCFHeader, List<VariantContext>> vcfInfo = VariantContextTestUtils.readEntireVCFIntoMemory(vcfOutputFile.getAbsolutePath());
+        final List<VariantContext> variantContexts = vcfInfo.getRight();
+        final VCFHeader vcfHeader = vcfInfo.getLeft();
+        final VCFInfoHeaderLine funcotationHeaderLine = vcfHeader.getInfoHeaderLine(VcfOutputRenderer.FUNCOTATOR_VCF_FIELD_NAME);
+        final String[] funcotationKeys = extractFuncotatorKeysFromHeaderDescription(funcotationHeaderLine.getDescription());
+
+        // The first variant context should have clinvar annotations, since it hit on the alt allele.  None of the rest.
+        final String funcotationInfoFieldWithClinVarHit = variantContexts.get(0).getAttributeAsString(VcfOutputRenderer.FUNCOTATOR_VCF_FIELD_NAME, null);
+        Assert.assertEquals(FuncotatorUtils.getFuncotationMapFromVcfFuncotationField(funcotationKeys, funcotationInfoFieldWithClinVarHit).get("dummy_ClinVar_VCF_CLNDISDB"),
+            FuncotatorUtils.sanitizeFuncotationForVcf("MedGen:C0027672,SNOMED_CT:699346009"));
+
+        // The rest should not have any clinvar hits.
+        final List<String> clinvarAnnotations = new ArrayList();
+        final List<String> clinvarAnnotationsTruth = new ArrayList();
+        for (int i = 1; i < variantContexts.size(); i++) {
+            final String infoField = variantContexts.get(i).getAttributeAsString(VcfOutputRenderer.FUNCOTATOR_VCF_FIELD_NAME, null);
+            clinvarAnnotations.add(FuncotatorUtils.getFuncotationMapFromVcfFuncotationField(funcotationKeys, infoField).get("dummy_ClinVar_VCF_CLNDISDB"));
+            clinvarAnnotationsTruth.add(FuncotatorUtils.sanitizeFuncotationForVcf(""));
+        }
+        Assert.assertEquals(clinvarAnnotations, clinvarAnnotationsTruth);
+    }
 }
diff --git a/...sources/org/broadinstitute/hellbender/tools/funcotator/PIK3CA_3_miss_clinvar_alt_only.vcf b/...sources/org/broadinstitute/hellbender/tools/funcotator/PIK3CA_3_miss_clinvar_alt_only.vcf
@@ -0,0 +1,10 @@
+##fileformat=VCFv4.1
+##fileDate=201708028
+##source=FuncotatorTestsV0.1
+##reference=file:///Users/jonn/Development/references/Homo_sapiens_assembly19.fasta
+#CHROM	POS	ID	REF	ALT	QUAL	FILTER	INFO
+3	178866587	.	G	A	40	.	.
+3	178866587	.	G	T	40	.	.
+3	178866586	.	A	ACGA	40	.	.
+3	178866586	.	AG	A	40	.	.
+3	178866587	.	G	GAG	40	.	.