public void MultiAlleleProteinAlteringVariant()
{
// GGGACTGGA|protein_altering_variant|MODIFIER||91544|Transcript|NM_183008.2|protein_coding|16/16||NM_183008.2:c.1501_1533delinsTCCAGTCCC|NP_892120.2:p.Pro501_Pro509delinsSer|1774-1806|1501-1533|501-511|PSPGPGPGPSP/SSP|CCCAGTCCCGGTCCCGGTCCCGGCCCCAGTCCC/TCCAGTCCC|||-1|||YES||NP_892120.2|rseq_mrna_match&rseq_ens_match_cds||||||||
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("NM_183008_chr1_RefSeq84"),
"chr1\t26608819\t.\tAGGGACTGGGGCCGGGACCGGGACCGGGACTGGG\tAGGGACTGGG,AGGGACTGGA\t60\tPASS\tCIGAR=1M24D9M,9M25D1I;RU=.,.;REFREP=3,.;IDREP=2,.;GMAF=A|0.3934;cosmic=COSM3749046;CSQT=1|CEP85|NM_022778.3|downstream_gene_variant,2|CEP85|NM_022778.3|downstream_gene_variant,1|SH3BGRL3|NM_031286.3|downstream_gene_variant,2|SH3BGRL3|NM_031286.3|downstream_gene_variant,1|UBXN11|NM_183008.2|inframe_deletion,2|UBXN11|NM_183008.2|\tGT:GQ:GQX:DPI:AD\t1/2:143:119:23:0,3,3");
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(2, annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.ElementAt(1);
Assert.NotNull(altAllele);
AssertUtilities.CheckRefSeqTranscriptCount(1, altAllele);
var transcript = altAllele.RefSeqTranscripts.FirstOrDefault();
Assert.NotNull(transcript);
// ReSharper disable once PossibleNullReferenceException
var observedConsequence = string.Join("&", transcript.Consequence);
const string expectedConsequence = "protein_altering_variant";
Assert.Equal(expectedConsequence, observedConsequence);
}
public void GatkGenomeVcf()
{
const bool isGatkGenomeVcf = true;
var vcfVariant = VcfUtilities.GetVcfVariant("1 10360 . C <NON_REF> . PASS END=10362 GT:DP:GQ:MIN_DP:PL 0/0:198:99:196:0,120,1800", isGatkGenomeVcf);
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000483270_chr1_Ensembl84"), vcfVariant);
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(0, annotatedVariant);
}
public void DuplicatedTranscripts()
{
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000483270_chr1_Ensembl84"),
"1 15910881 MantaBND:17185:0:1:0:9:0:0 G [2:86827867[G . MinSomaticScore SVTYPE=BND;MATEID=MantaBND:17185:0:1:0:9:0:1;CIPOS=0,7;HOMLEN=7;HOMSEQ=TGATCCG;SOMATIC;SOMATICSCORE=19;BND_DEPTH=26;MATE_BND_DEPTH=21 PR:SR 30,0:20,0 64,2:173,8");
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(1, annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.First();
AssertUtilities.CheckEnsemblTranscriptCount(1, altAllele);
}
public void ReferenceNoCallsOverlapTranscript(bool enableRefNoCall, bool limitToTranscript, int numberOfAnnotatedAlleles)
{
var annotationSource = ResourceUtilities.GetAnnotationSource(Resources.CacheGRCh37("ENST00000483270_chr1_Ensembl84"), null) as NirvanaAnnotationSource;
if (enableRefNoCall)
{
annotationSource?.EnableReferenceNoCalls(limitToTranscript);
}
var annotatedVariant = DataUtilities.GetVariant(annotationSource,
"1 15886104 . C . . LowQ END=15890000 . .");
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(numberOfAnnotatedAlleles, annotatedVariant);
}
public void InsertionAtRegFeatureStart()
{
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENSR00001625040_chr11_Ensembl84_reg"),
"11\t121973583\t.\tC\tCA\t.\tRepeat;QSI_ref SOMATIC;QSI=29;TQSI=1;NT=hom;QSI_NT=29;TQSI_NT=1;SGT=hom->het;RU=A;RC=9;IC=10;IHP=10 DP:DP2:TAR:TIR:TOR:DP50:FDP50:SUBDP50\t52:52:0,0:49,49:3,3:54.96:0.00:0.00\t131:131:34,34:77,77:19,19:130.89:1.24:0.00");
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(1, annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.First();
Assert.NotNull(altAllele);
AssertUtilities.CheckRegulatoryCount(0, altAllele);
}
public void FuzzyInsertion()
{
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh38("ENST00000471857_chr2_Ensembl84"), null,
"chr2\t90221381\tMantaINS:49750:2:2:0:6:0\tC\t<INS>\t282\tPASS\tEND=90221390;SVTYPE=INS;LEFT_SVINSSEQ=CCGTGGCCACTCAGTTTTAGCGTCTCTGCTCTATTTGGACATTTTGCAGTTCT;RIGHT_SVINSSEQ=GATGTTGCAACTTATTACGGTCAACGGACTTACAATGCCCCTGA;DQ=0\tGT:FT:GQ:PL:PR:SR\t0/1:PASS:107:157,0,975:1,0:19,7\t0/1:PASS:175:225,0,730:1,0:14,7\t0/0:PASS:112:0,62,899:1,0:14,0");
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(1, annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.First();
Assert.NotNull(altAllele);
AssertUtilities.CheckEnsemblTranscriptCount(1, altAllele);
}
public void CdnaPositionShouldNotBeReported()
{
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("NM_005101_chr1_RefSeq84"), null,
"1 948846 . T TA . . .");
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(1, annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.First();
Assert.NotNull(altAllele);
AssertUtilities.CheckRefSeqTranscriptCount(1, altAllele);
Assert.Null(altAllele.RefSeqTranscripts.First().ComplementaryDnaPosition);
}
public void DisableMitochondrialAnnotation()
{
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000387314_chrM_Ensembl84"), null,
"MT 589 . C A . PASS . . .");
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(1, annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.First();
Assert.NotNull(altAllele);
AssertUtilities.CheckEnsemblTranscriptCount(0, altAllele);
Assert.DoesNotContain("ENST00000387314", altAllele.ToString());
}
public void MissingCosmicId()
{
var annotatedVariant = DataUtilities.GetVariant(DataUtilities.EmptyCachePrefix, Resources.MiniSuppAnnot("chr1_26608814_26608815.nsa"),
"1 26608811 . TCCAGGACAGGGACTGGGGCCGGGACCGGGACC TCCGGGACC,TCCAGGACA 139 LowGQXHetAltDel CIGAR=1M24D8M,9M24");
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(2, annotatedVariant);
var altAllele = JsonUtilities.GetAllele(annotatedVariant);
var altAllele2 = JsonUtilities.GetAllele(annotatedVariant, 1);
Assert.Contains(
"\"cosmic\":[{\"id\":\"COSM4143711\",\"refAllele\":\"A\",\"altAllele\":\"G\",\"gene\":\"UBXN11\",\"sampleCount\":22,\"studies\":[{\"histology\":\"carcinoma\",\"primarySite\":\"upper aerodigestive tract\"},{\"id\":589,\"histology\":\"other\",\"primarySite\":\"thyroid\"}]}]",
altAllele);
Assert.DoesNotContain("\"cosmic\":", altAllele2);
}
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 VepMissingRegulatoryFeature()
{
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENSR00000554042_chr1_Ensembl84_reg"),
"1 225615945 . T C . PASS SOMATIC;QSS=78;TQSS=1;NT=ref;QSS_NT=78;TQSS_NT=1;SGT=TT->CT;DP=159;MQ=60.00;MQ0=0;ALTPOS=44;ALTMAP=26;ReadPosRankSum=-0.92;SNVSB=0.00;PNOISE=0.00;PNOISE2=0.00;VQSR=9.59 DP:FDP:SDP:SUBDP:AU:CU:GU:TU 48:0:0:0:0,0:1,1:1,1:46,46 111:6:0:0:0,0:29,33:1,2:75,76");
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(1, annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.First();
Assert.NotNull(altAllele);
AssertUtilities.CheckRegulatoryCount(1, altAllele);
var regulatoryRegion = altAllele.RegulatoryRegions.FirstOrDefault();
Assert.NotNull(regulatoryRegion);
Assert.Equal("ENSR00000554042", regulatoryRegion.ID);
}
public void IntronNumbers()
{
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000380060_chrX_Ensembl84"),
"chrX 17705850 rs397759640;rs5901624 C CT 1815.96 PASS . . .");
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(1, annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.First();
Assert.NotNull(altAllele);
AssertUtilities.CheckEnsemblTranscriptCount(1, altAllele);
var transcript = altAllele.EnsemblTranscripts.FirstOrDefault();
Assert.NotNull(transcript);
Assert.Equal("1/7", transcript.Introns);
AssertUtilities.CheckJsonContains("\"introns\":\"1/7\"", annotatedVariant);
}
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);
}
