public void GenotypeIndex_is_correct_w_refMinor_allele()
{
var vcfFields1 =
"1 10628385 . C <NON_REF> . LowGQX;HighDPFRatio END=10628385;BLOCKAVG_min30p3a GT:GQX:DP:DPF 0/0:24:9:18".Split('\t');
var vcfFields2 =
"1 10628385 . C <NON_REF> . LowGQX;HighDPFRatio END=10628385;BLOCKAVG_min30p3a GT:GQX:DP:DPF 0/0:24:9:18".Split('\t');
var chromosome = new Chromosome("chr1", "1", 0);
var inforData = new InfoData(null, null, VariantType.SNV, null, null, null, null, null, false, null, null,
false, false, "", null, null);
var position1 = new Position(chromosome, 10628385, 10628385, "C", new[] { "." }, 100, null, null, null, inforData, vcfFields1, new[] { false }, false);
var position2 = new Position(chromosome, 10628385, 10628385, "C", new[] { "." }, 100, null, null, null, inforData, vcfFields2, new[] { false }, false);
var variant = new Variant(chromosome, 10628385, 10628385, "C", "<NON_REF>", VariantType.reference, null, true, false, false, null, null, new AnnotationBehavior(true, false, false, true, false, false));
var annotatedVariant = new AnnotatedVariant(variant);
annotatedVariant.SupplementaryAnnotations.Add(new AnnotatedSaDataSource(new SaDataSource("testSource", "Test", "C", false, true, "pathogenic", null), "C"));
var annotatedPosition1 = new AnnotatedPosition(position1, new IAnnotatedVariant[] { annotatedVariant });
var annotatedPosition2 = new AnnotatedPosition(position2, new IAnnotatedVariant[] { annotatedVariant });
var converter = new VcfConversion();
var observedVcf1 = converter.Convert(annotatedPosition1).Split("\t")[VcfCommon.InfoIndex];
var observedVcf2 = converter.Convert(annotatedPosition2).Split("\t")[VcfCommon.InfoIndex];
Assert.Equal("RefMinor;Test=1|pathogenic", observedVcf1);
Assert.Equal("RefMinor;Test=1|pathogenic", observedVcf2);
}
public void regulatory_region_is_added()
{
var mockedRegulatory = new Mock <IAnnotatedRegulatoryRegion>();
mockedRegulatory.SetupGet(x => x.Consequences).Returns(new List <ConsequenceTag> {
ConsequenceTag.regulatory_region_variant
});
mockedRegulatory.SetupGet(x => x.RegulatoryRegion.Id).Returns(CompactId.Convert("ENSR12345"));
var vcfFields = "chr1 101 sa123 A . . . . .".Split("\t");
var chrom = new Chromosome("chr1", "1", 0);
var inforData = new InfoData(null, null, VariantType.SNV, null, null, null, null, null, false, null, null,
false, false, "Test=abc", null, null);
var position = new Position(chrom, 101, 101, "A", new[] { "." }, 100, null, null, null, inforData, vcfFields, new[] { false }, false);
var variant = new Variant(chrom, 101, 101, "A", ".", VariantType.reference, null, false, false, false, null, null, new AnnotationBehavior(true, false, false, true, false, false));
var annotatedVariant = new AnnotatedVariant(variant);
annotatedVariant.RegulatoryRegions.Add(mockedRegulatory.Object);
IAnnotatedVariant[] annotatedVariants = { annotatedVariant };
var annotatedPosition = new AnnotatedPosition(position, annotatedVariants);
var converter = new VcfConversion();
var observedVcf = converter.Convert(annotatedPosition).Split("\t")[VcfCommon.InfoIndex];
Assert.Equal("Test=abc;CSQR=1|ENSR12345|regulatory_region_variant", observedVcf);
}
public void GenotypeIndex_is_correct_w_nonInformative_altAlleles_filtered()
{
var vcfFields1 = "chr1 101 sa123 A <*>,T . . .".Split("\t");
var vcfFields2 = "chr1 101 sa123 A <M>,T . . .".Split("\t");
var vcfFields3 = "chr1 101 sa123 A *,T . . .".Split("\t");
var vcfFields4 = "chr1 101 sa123 A <NON_REF>,T . . .".Split("\t");
var vcfFields5 = "chr1 101 sa123 A T,<*> . . .".Split("\t");
var vcfFields6 = "chr1 101 sa123 A T,<M> . . .".Split("\t");
var vcfFields7 = "chr1 101 sa123 A T,* . . .".Split("\t");
var vcfFields8 = "chr1 101 sa123 A T,<NON_REF> . . .".Split("\t");
var chrom = new Chromosome("chr1", "1", 0);
var inforData = new InfoData(null, null, VariantType.SNV, null, null, null, null, null, false, null, null,
false, false, "", null, null);
var position1 = new Position(chrom, 101, 101, "A", new[] { "<*>", "T" }, 100, null, null, null, inforData, vcfFields1, new[] { false }, false);
var position2 = new Position(chrom, 101, 101, "A", new[] { "<M>", "T" }, 100, null, null, null, inforData, vcfFields2, new[] { false }, false);
var position3 = new Position(chrom, 101, 101, "A", new[] { "*", "T" }, 100, null, null, null, inforData, vcfFields3, new[] { false }, false);
var position4 = new Position(chrom, 101, 101, "A", new[] { "<NON_REF>", "T" }, 100, null, null, null, inforData, vcfFields4, new[] { false }, false);
var position5 = new Position(chrom, 101, 101, "A", new[] { "T", "<*>" }, 100, null, null, null, inforData, vcfFields5, new[] { false }, false);
var position6 = new Position(chrom, 101, 101, "A", new[] { "T", "<M>" }, 100, null, null, null, inforData, vcfFields6, new[] { false }, false);
var position7 = new Position(chrom, 101, 101, "A", new[] { "T", "*" }, 100, null, null, null, inforData, vcfFields7, new[] { false }, false);
var position8 = new Position(chrom, 101, 101, "A", new[] { "T", "<NON_REF>" }, 100, null, null, null, inforData, vcfFields8, new[] { false }, false);
var variant = new Variant(chrom, 101, 101, "A", "T", VariantType.SNV, null, false, false, false, null, null, new AnnotationBehavior(true, false, false, true, false, false));
var annotatedVariant = new AnnotatedVariant(variant);
annotatedVariant.SupplementaryAnnotations.Add(new AnnotatedSaDataSource(new SaDataSource("testSource", "Test", "T", false, true, "pathogenic", null), "T"));
IAnnotatedVariant[] annotatedVariants = { annotatedVariant };
var annotatedPosition1 = new AnnotatedPosition(position1, annotatedVariants);
var annotatedPosition2 = new AnnotatedPosition(position2, annotatedVariants);
var annotatedPosition3 = new AnnotatedPosition(position3, annotatedVariants);
var annotatedPosition4 = new AnnotatedPosition(position4, annotatedVariants);
var annotatedPosition5 = new AnnotatedPosition(position5, annotatedVariants);
var annotatedPosition6 = new AnnotatedPosition(position6, annotatedVariants);
var annotatedPosition7 = new AnnotatedPosition(position7, annotatedVariants);
var annotatedPosition8 = new AnnotatedPosition(position8, annotatedVariants);
var converter = new VcfConversion();
var observedVcf1 = converter.Convert(annotatedPosition1).Split("\t")[VcfCommon.InfoIndex];
var observedVcf2 = converter.Convert(annotatedPosition2).Split("\t")[VcfCommon.InfoIndex];
var observedVcf3 = converter.Convert(annotatedPosition3).Split("\t")[VcfCommon.InfoIndex];
var observedVcf4 = converter.Convert(annotatedPosition4).Split("\t")[VcfCommon.InfoIndex];
var observedVcf5 = converter.Convert(annotatedPosition5).Split("\t")[VcfCommon.InfoIndex];
var observedVcf6 = converter.Convert(annotatedPosition6).Split("\t")[VcfCommon.InfoIndex];
var observedVcf7 = converter.Convert(annotatedPosition7).Split("\t")[VcfCommon.InfoIndex];
var observedVcf8 = converter.Convert(annotatedPosition8).Split("\t")[VcfCommon.InfoIndex];
Assert.Equal("Test=2|pathogenic", observedVcf1);
Assert.Equal("Test=2|pathogenic", observedVcf2);
Assert.Equal("Test=2|pathogenic", observedVcf3);
Assert.Equal("Test=2|pathogenic", observedVcf4);
Assert.Equal("Test=1|pathogenic", observedVcf5);
Assert.Equal("Test=1|pathogenic", observedVcf6);
Assert.Equal("Test=1|pathogenic", observedVcf7);
Assert.Equal("Test=1|pathogenic", observedVcf8);
}
public void MissingRefBlockEntry()
{
const string vcfLine = "1 10005 . C . . LowGQX END=10034;BLOCKAVG_min30p3a GT:GQX:DP:DPF 0/0:3:1:0";
var vcfVariant = VcfUtilities.GetVcfVariant(vcfLine);
var annotatedVariant = DataUtilities.GetVariant(DataUtilities.EmptyCachePrefix, vcfLine);
var vcf = new VcfConversion();
var observedVcfLine = vcf.Convert(vcfVariant, annotatedVariant);
Assert.Equal(vcfLine, observedVcfLine);
}
public void Only_canonical_transcripts_are_reported_in_vcf()
{
var mockedTranscript1 = new Mock <IAnnotatedTranscript>();
mockedTranscript1.Setup(x => x.Transcript.IsCanonical).Returns(true);
mockedTranscript1.Setup(x => x.Transcript.Id).Returns(CompactId.Convert("ENST12345", 1));
mockedTranscript1.Setup(x => x.Transcript.Gene.Symbol).Returns("testGene1");
mockedTranscript1.SetupGet(x => x.Consequences)
.Returns(new List <ConsequenceTag> {
ConsequenceTag.five_prime_UTR_variant
});
var mockedTranscript2 = new Mock <IAnnotatedTranscript>();
mockedTranscript2.Setup(x => x.Transcript.IsCanonical).Returns(false);
mockedTranscript2.Setup(x => x.Transcript.Id).Returns(CompactId.Convert("ENST23456", 2));
mockedTranscript2.Setup(x => x.Transcript.Gene.Symbol).Returns("testGene2");
mockedTranscript2.SetupGet(x => x.Consequences)
.Returns(new List <ConsequenceTag> {
ConsequenceTag.missense_variant
});
var mockedTranscript3 = new Mock <IAnnotatedTranscript>();
mockedTranscript3.Setup(x => x.Transcript.IsCanonical).Returns(true);
mockedTranscript3.Setup(x => x.Transcript.Id).Returns(CompactId.Convert("NM_1234", 3));
mockedTranscript3.Setup(x => x.Transcript.Gene.Symbol).Returns("testGene3");
mockedTranscript3.SetupGet(x => x.Consequences)
.Returns(new List <ConsequenceTag> {
ConsequenceTag.missense_variant, ConsequenceTag.splice_region_variant
});
var vcfFields = "chr1 101 sa123 A T . . .".Split("\t");
var chrom = new Chromosome("chr1", "1", 0);
var inforData = new InfoData(null, null, VariantType.SNV, null, null, null, null, null, false, null, null,
false, false, "", null, null);
var position = new Position(chrom, 101, 101, "A", new[] { "T" }, 100, null, null, null, inforData, vcfFields, new[] { false }, false);
var variant = new Variant(chrom, 101, 101, "A", "T", VariantType.SNV, null, false, false, false, null, null, new AnnotationBehavior(true, false, false, true, false, false));
var annotatedVariant = new AnnotatedVariant(variant);
annotatedVariant.EnsemblTranscripts.Add(mockedTranscript1.Object);
annotatedVariant.EnsemblTranscripts.Add(mockedTranscript2.Object);
annotatedVariant.RefSeqTranscripts.Add(mockedTranscript3.Object);
IAnnotatedVariant[] annotatedVariants = { annotatedVariant };
var annotatedPosition = new AnnotatedPosition(position, annotatedVariants);
var converter = new VcfConversion();
var observedVcf = converter.Convert(annotatedPosition).Split("\t")[VcfCommon.InfoIndex];
Assert.Equal("CSQT=1|testGene1|ENST12345.1|5_prime_UTR_variant,1|testGene3|NM_1234.3|missense_variant&splice_region_variant", observedVcf);
}
public static string GetVcfColumn(ISupplementaryAnnotationReader saReader, string vcfLine,
int vcfColumn)
{
var vcfVariant = GetVcfVariant(vcfLine);
var annotationSource = ResourceUtilities.GetAnnotationSource(DataUtilities.EmptyCachePrefix, saReader);
UnifiedJson.NeedsVariantComma = false;
var annotatedVariant = annotationSource?.Annotate(vcfVariant);
Assert.NotNull(annotatedVariant);
var vcf = new VcfConversion();
return(vcf.Convert(vcfVariant, annotatedVariant).Split('\t')[vcfColumn]);
}
public void Original_dbsnp_nonrsid_get_kept()
{
var vcfFields = "chr1 101 sa123 A T . . .".Split("\t");
var chrom = new Chromosome("chr1", "1", 0);
var inforData = new InfoData(null, null, VariantType.SNV, null, null, null, null, null, false, null, null,
false, false, "", null, null);
var position = new Position(chrom, 101, 101, "A", new[] { "T" }, 100, null, null, null, inforData, vcfFields, new[] { false }, false);
var variant = new Variant(chrom, 101, 101, "A", "T", VariantType.SNV, null, false, false, false, null, null, new AnnotationBehavior(true, false, false, true, false, false));
var annotatedVariant = new AnnotatedVariant(variant);
IAnnotatedVariant[] annotatedVariants = { annotatedVariant };
var annotatedPosition = new AnnotatedPosition(position, annotatedVariants);
var converter = new VcfConversion();
var observedVcf = converter.Convert(annotatedPosition).Split("\t")[VcfCommon.IdIndex];
Assert.Equal("sa123", observedVcf);
}
public void original_updated_info_is_added_to_info_field()
{
var vcfFields = "chr1 101 sa123 A . . . . .".Split("\t");
var chrom = new Chromosome("chr1", "1", 0);
var inforData = new InfoData(null, null, VariantType.SNV, null, null, null, null, null, false, null, null,
false, false, "Test=abc", null, null);
var position = new Position(chrom, 101, 101, "A", new[] { "." }, 100, null, null, null, inforData, vcfFields, new[] { false }, false);
var variant = new Variant(chrom, 101, 101, "A", ".", VariantType.reference, null, true, false, false, null, null, new AnnotationBehavior(true, false, false, true, false, false));
var annotatedVariant = new AnnotatedVariant(variant);
IAnnotatedVariant[] annotatedVariants = { annotatedVariant };
var annotatedPosition = new AnnotatedPosition(position, annotatedVariants);
var converter = new VcfConversion();
var observedVcf = converter.Convert(annotatedPosition).Split("\t")[VcfCommon.InfoIndex];
Assert.Equal("Test=abc;RefMinor", observedVcf);
}
public void Original_dbsnp_nonrsid_merged_with_rsid_from_dbsnp()
{
var vcfFields = "chr1 101 sa123 A T . . .".Split("\t");
var chrom = new Chromosome("chr1", "1", 0);
var inforData = new InfoData(null, null, VariantType.SNV, null, null, null, null, null, false, null, null,
false, false, "", null, null);
var position = new Position(chrom, 101, 101, "A", new[] { "T" }, 100, null, null, null, inforData, vcfFields, new[] { false }, false);
var variant = new Variant(chrom, 101, 101, "A", "T", VariantType.SNV, null, false, false, false, null, null, new AnnotationBehavior(true, false, false, true, false, false));
var annotatedVariant = new AnnotatedVariant(variant);
annotatedVariant.SupplementaryAnnotations.Add(new AnnotatedSaDataSource(new SaDataSource("dbsnp", "", "T", true, false, "rs456", null), "T"));
IAnnotatedVariant[] annotatedVariants = { annotatedVariant };
var annotatedPosition = new AnnotatedPosition(position, annotatedVariants);
var converter = new VcfConversion();
var observedVcf = converter.Convert(annotatedPosition).Split("\t")[VcfCommon.IdIndex];
Assert.Equal("sa123;rs456", observedVcf);
}
public void OneKGAnnotation_is_handled()
{
var vcfFields = "chr1 101 sa123 A T . . .".Split("\t");
var chrom = new Chromosome("chr1", "1", 0);
var inforData = new InfoData(null, null, VariantType.SNV, null, null, null, null, null, false, null, null,
false, false, "", null, null);
var position = new Position(chrom, 101, 101, "A", new[] { "T" }, 100, null, null, null, inforData, vcfFields, new[] { false }, false);
var variant = new Variant(chrom, 101, 101, "A", "T", VariantType.SNV, null, false, false, false, null, null, new AnnotationBehavior(true, false, false, true, false, false));
var annotatedVariant = new AnnotatedVariant(variant);
annotatedVariant.SupplementaryAnnotations.Add(new AnnotatedSaDataSource(new SaDataSource("oneKg", "AF1000G", "T", true, false, "0.000599;t", null), "T"));
IAnnotatedVariant[] annotatedVariants = { annotatedVariant };
var annotatedPosition = new AnnotatedPosition(position, annotatedVariants);
var converter = new VcfConversion();
var observedVcf = converter.Convert(annotatedPosition).Split("\t")[VcfCommon.InfoIndex];
Assert.Equal("AA=t;AF1000G=0.000599", observedVcf);
}
public void Gmaf_outputed()
{
var vcfFields = "chr1 101 sa123 A T . . .".Split("\t");
var chrom = new Chromosome("chr1", "1", 0);
var inforData = new InfoData(null, null, VariantType.SNV, null, null, null, null, null, false, null, null,
false, false, "", null, null);
var position = new Position(chrom, 101, 101, "A", new[] { "T" }, 100, null, null, null, inforData, vcfFields, new[] { false }, false);
var variant = new Variant(chrom, 101, 101, "A", "T", VariantType.SNV, null, false, false, false, null, null, new AnnotationBehavior(true, false, false, true, false, false));
var annotatedVariant = new AnnotatedVariant(variant);
annotatedVariant.SupplementaryAnnotations.Add(new AnnotatedSaDataSource(new SaDataSource("globalAllele", "GMAF", "N", false, false, "G|0.002", null), "N"));
IAnnotatedVariant[] annotatedVariants = { annotatedVariant };
var annotatedPosition = new AnnotatedPosition(position, annotatedVariants);
var converter = new VcfConversion();
var observedVcf = converter.Convert(annotatedPosition).Split("\t")[VcfCommon.InfoIndex];
Assert.Equal("GMAF=G|0.002", observedVcf);
}
public void Only_allele_specific_entry_for_annotation_not_matched_by_allele_is_output()
{
var vcfFields = "chr1 101 sa123 A T . . .".Split("\t");
var chrom = new Chromosome("chr1", "1", 0);
var inforData = new InfoData(null, null, VariantType.SNV, null, null, null, null, null, false, null, null,
false, false, "", null, null);
var position = new Position(chrom, 101, 101, "A", new[] { "T" }, 100, null, null, null, inforData, vcfFields, new[] { false }, false);
var variant = new Variant(chrom, 101, 101, "A", "T", VariantType.SNV, null, false, false, false, null, null, new AnnotationBehavior(true, false, false, true, false, false));
var annotatedVariant = new AnnotatedVariant(variant);
annotatedVariant.SupplementaryAnnotations.Add(new AnnotatedSaDataSource(new SaDataSource("testSource", "Test", "T", false, true, "pathogenic", null), "T"));
annotatedVariant.SupplementaryAnnotations.Add(new AnnotatedSaDataSource(new SaDataSource("testSource", "Test", "G", false, true, "benign", null), "T"));
IAnnotatedVariant[] annotatedVariants = { annotatedVariant };
var annotatedPosition = new AnnotatedPosition(position, annotatedVariants);
var converter = new VcfConversion();
var observedVcf = converter.Convert(annotatedPosition).Split("\t")[VcfCommon.InfoIndex];
Assert.Equal("Test=1|pathogenic", observedVcf);
}
public void AlleleMissingPhylop()
{
const string vcfLine = "1 4004037 . CG CA,TG 0 LowDP;LowGQ DP=0 GT:GQ:AD:VF:NL:SB:GQX ./.:0:0:0.000:20:-100.0000:0";
var vcfVariant = VcfUtilities.GetVcfVariant(vcfLine);
var annotatedVariant = DataUtilities.GetVariant(DataUtilities.EmptyCachePrefix, vcfLine);
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(2, annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.First();
DataUtilities.SetConservationScore(altAllele, "-0.344");
var vcf = new VcfConversion();
var observedVcfLine = vcf.Convert(vcfVariant, annotatedVariant);
Assert.Contains("phyloP=-0.344,.", observedVcfLine);
}
public void MixedAlleleRefMinor()
{
var vcfLine = "1 7965489 . C . . PASS RefMinor;phyloP=0.178 GT:GQX:DP:DPF 0/0:180:61:2";
var vcfVariant = VcfUtilities.GetVcfVariant(vcfLine);
var annotatedVariant = DataUtilities.GetVariant(DataUtilities.EmptyCachePrefix, Resources.MiniSuppAnnot("chr1_7965489_7965490.nsa"), vcfLine);
Assert.NotNull(annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.First();
Assert.NotNull(altAllele);
DataUtilities.SetConservationScore(altAllele, "0.178");
var vcf = new VcfConversion();
var observedInfoField = vcf.Convert(vcfVariant, annotatedVariant).Split('\t')[VcfCommon.InfoIndex];
Assert.Equal("phyloP=0.178", observedInfoField);
}
public void AlleleSpecificPhylop()
{
const string vcfLine = "1 4004037 . CG CA,TG 0 LowDP;LowGQ DP=0 GT:GQ:AD:VF:NL:SB:GQX ./.:0:0:0.000:20:-100.0000:0";
var vcfVariant = VcfUtilities.GetVcfVariant(vcfLine);
var annotatedVariant = DataUtilities.GetVariant(DataUtilities.EmptyCachePrefix, vcfLine);
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(2, annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.ElementAt(0);
DataUtilities.SetConservationScore(altAllele, "-0.344");
var altAllele2 = annotatedVariant.AnnotatedAlternateAlleles.ElementAt(1);
DataUtilities.SetConservationScore(altAllele2, "0.135");
var vcf = new VcfConversion();
var observedVcfLine = vcf.Convert(vcfVariant, annotatedVariant).Split('\t')[VcfCommon.InfoIndex];
Assert.Contains("phyloP=-0.344,0.135", observedVcfLine);
}
public void NoPhylopScores()
{
const string vcfLine = "1 103188976 rs35710136 CTCTA ATATA,CTCTC 41 PASS SNVSB=0.0;SNVHPOL=3;AA=.,a;GMAF=A|0.09465,A|0.4898;AF1000G=.,0.510184;phyloP=-0.094 GT:GQ:GQX:DP:DPF:AD 1/2:63:16:12:1:0,7,5";
var vcfVariant = VcfUtilities.GetVcfVariant(vcfLine);
var annotatedVariant = DataUtilities.GetVariant(DataUtilities.EmptyCachePrefix, vcfLine);
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(2, annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.First();
DataUtilities.SetConservationScore(altAllele, null);
var altAllele2 = annotatedVariant.AnnotatedAlternateAlleles.ElementAt(1);
DataUtilities.SetConservationScore(altAllele2, null);
var vcf = new VcfConversion();
var observedVcfLine = vcf.Convert(vcfVariant, annotatedVariant).Split('\t')[VcfCommon.InfoIndex];
Assert.DoesNotContain("phyloP", observedVcfLine);
}