public void MissingRefAllele()
{
JsonUtilities.AlleleEquals(
"chr1 15274 . A . 279.00 PASS SNVSB=-39.1;SNVHPOL=2 GT:GQ:GQX:DP:DPF:AD 1/2:58:55:20:1:0,5,15",
Resources.MiniSuppAnnot("chr1_15274_15275.nsa"),
"{\"refAllele\":\"A\",\"begin\":15274,\"chromosome\":\"chr1\",\"end\":15274,\"globalMinorAllele\":\"G\",\"gmaf\":0.3472,\"isReferenceMinorAllele\":true,\"variantType\":\"SNV\",\"vid\":\"1:15274:A\"}");
}
public void MantaDelWithoutSymbolicAllele()
{
JsonUtilities.AlleleEquals(
"1 1530648 MantaDEL:116:0:0:0:3:1 GAGACAGAGAGAAACAGAGACAGAGACAGAGAGGCAGACAGAGAGAGAGACAGACAGAGAGCAGAACAGGGAGAGACAAAGAGACAGAGAGAGAGAGAGACACAGAGAGAGAGAGATAGAGAGAGGCAGACAGAGACAGAGAGACAGACAGACACAGAGCAGAACAGGGAGAGACAGAGAGAGAGAGACAGAGAGAGGCAGAC GA . MinSomaticScore END=1530850;SVTYPE=DEL;SVLEN=-202;CIGAR=1M202D;CIPOS=0,3;HOMLEN=3;HOMSEQ=AGA;SOMATIC;SOMATICSCORE=17 PR:SR 13,0:25,3 24,0:33,10",
null,
"{\"altAllele\":\"-\",\"refAllele\":\"GACAGAGAGAAACAGAGACAGAGACAGAGAGGCAGACAGAGAGAGAGACAGACAGAGAGCAGAACAGGGAGAGACAAAGAGACAGAGAGAGAGAGAGACACAGAGAGAGAGAGATAGAGAGAGGCAGACAGAGACAGAGAGACAGACAGACACAGAGCAGAACAGGGAGAGACAGAGAGAGAGAGACAGAGAGAGGCAGAC\",\"begin\":1530650,\"chromosome\":\"1\",\"end\":1530850,\"variantType\":\"deletion\",\"vid\":\"1:1530650:1530850\"}");
}
public void BadClivarRef()
{
JsonUtilities.AlleleEquals(
"11 109157259 . T . . PASS RefMinor;GMAF=T|0.01877 GT:GQX:DP:DPF:AD 0/0:69:24:3:24",
Resources.MiniSuppAnnot("chr11_109157259_109157260.nsa"),
"{\"refAllele\":\"T\",\"begin\":109157259,\"chromosome\":\"11\",\"end\":109157259,\"globalMinorAllele\":\"T\",\"gmaf\":0.01877,\"isReferenceMinorAllele\":true,\"variantType\":\"SNV\",\"vid\":\"11:109157259:T\"}");
}
public void RefAlleleDash()
{
JsonUtilities.AlleleEquals(
"17 46107 . A G 153 LowGQX SNVSB=-20.1;SNVHPOL=4;CSQ=G|ENSG00000262836|ENST00000576171|Transcript|upstream_gene_variant||||||||4729|||||||YES|||||||| GT:GQ:GQX:DP:DPF:AD 1/1:18:18:7:0:0,7",
Resources.MiniSuppAnnot("chr17_77263_77265.nsa"),
"{\"altAllele\":\"G\",\"refAllele\":\"A\",\"begin\":46107,\"chromosome\":\"17\",\"end\":46107,\"variantType\":\"SNV\",\"vid\":\"17:46107:G\"}");
}
public void BreakEndBeginOutput()
{
JsonUtilities.AlleleEquals(
"1 28722335 MantaBND:4051:0:2:0:0:0:0 T [3:115024109[T . PASS SVTYPE=BND;MATEID=MantaBND:4051:0:2:0:0:0:1;IMPRECISE;CIPOS=-209,210;SOMATIC;SOMATICSCORE=42;BND_DEPTH=23;MATE_BND_DEPTH=24 PR 25,0 71,10",
null,
"{\"altAllele\":\"[3:115024109[T\",\"refAllele\":\"T\",\"begin\":28722335,\"chromosome\":\"1\",\"end\":28722335,\"variantType\":\"translocation_breakend\",\"vid\":\"1:28722335:-:3:115024109:+\"}");
}
public void VariantTypeMissing()
{
JsonUtilities.AlleleEquals(
"1 17224554 Canvas:GAIN:1:17224555:17275816 N <CNV> 31 PASS SVTYPE=CNV;END=17275816 RC:BC:CN:MCC . 151:42:5:4",
null,
"{\"altAllele\":\"CNV\",\"refAllele\":\"N\",\"begin\":17224555,\"chromosome\":\"1\",\"end\":17275816,\"variantType\":\"copy_number_variation\",\"vid\":\"1:17224555:17275816:5\"}");
}
public void FullSvDeletionSupport()
{
JsonUtilities.AlleleEquals(
"chr1 964001 . A <DEL> . PASS SVTYPE=DEL;SVLEN=-7;IMPRECISE;CIPOS=-170,170;CIEND=-175,175 GT:GQX:DP:DPF 0/0:99:34:2",
Resources.MiniSuppAnnot("chr1_964001_964008.nsa"),
"{\"altAllele\":\"deletion\",\"refAllele\":\"A\",\"begin\":964002,\"chromosome\":\"chr1\",\"end\":964008,\"variantType\":\"deletion\",\"vid\":\"1:964002:964008\"}");
}
public void AddExonTest()
{
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000427857_chr1_Ensembl84"), null,
"1 803780 Canvas:GAIN:1:803781:821943 N <CNV> 2 q10;CLT10kb SVTYPE=CNV;END=821943 RC:BC:CN 174:2:4");
Assert.NotNull(annotatedVariant);
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"CNV\",\"refAllele\":\"N\",\"begin\":803781,\"chromosome\":\"1\",\"end\":821943,\"variantType\":\"copy_number_variation\",\"vid\":\"1:803781:821943:4\",\"overlappingGenes\":[\"FAM41C\"],\"transcripts\":{\"ensembl\":[{\"transcript\":\"ENST00000427857.1\",\"bioType\":\"lincRNA\",\"exons\":\"1-3/3\",\"introns\":\"1-2/2\",\"geneId\":\"ENSG00000230368\",\"hgnc\":\"FAM41C\",\"consequence\":[\"transcript_amplification\",\"copy_number_increase\"]}]}}");
}
public void SvDelMissingTranscript()
{
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000594233_chr1_Ensembl84"), null,
"1 823854 MantaDEL:60:0:0:0:2:4 AGGGAGAGAAAGGGAAAGAAGGAAAGAAACAAGGAAGCAGGGAGGGAGAGAAAGAGGAAGGGAG A 49 MaxDepth;MaxMQ0Frac END=823917;SVTYPE=DEL;SVLEN=-63;CIGAR=1M63D;CSQT=1|AL645608.2|ENST00000594233| GT:GQ:PR:SR 0/1:49:21,0:35,8");
Assert.NotNull(annotatedVariant);
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"-\",\"refAllele\":\"GGGAGAGAAAGGGAAAGAAGGAAAGAAACAAGGAAGCAGGGAGGGAGAGAAAGAGGAAGGGAG\",\"begin\":823855,\"chromosome\":\"1\",\"end\":823917,\"variantType\":\"deletion\",\"vid\":\"1:823855:823917\",\"transcripts\":{\"ensembl\":[{\"transcript\":\"ENST00000594233.1\",\"bioType\":\"protein_coding\",\"geneId\":\"ENSG00000269308\",\"hgnc\":\"AL645608.2\",\"consequence\":[\"downstream_gene_variant\"],\"isCanonical\":true,\"proteinId\":\"ENSP00000470877.1\"}]}}");
}
public void CnvIgnoreFlankingGenes()
{
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000427857_chr1_Ensembl84"), null,
"1 816800 Canvas:GAIN:1:816801:821943 N <CNV> 2 q10;CLT10kb SVTYPE=CNV;END=821943 RC:BC:CN 174:2:4");
Assert.NotNull(annotatedVariant);
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"CNV\",\"refAllele\":\"N\",\"begin\":816801,\"chromosome\":\"1\",\"end\":821943,\"variantType\":\"copy_number_variation\",\"vid\":\"1:816801:821943:4\"}");
}
public void AlleleSpecificDbsnpId()
{
var annotatedVariant = DataUtilities.GetVariant(DataUtilities.EmptyCachePrefix, Resources.MiniSuppAnnot("chr17_3124877_3124878.nsa"),
"17 3124877 rs182093170 T A,C 87 LowGQX SNVSB=-11.7;SNVHPOL=2;phyloP=0.058 GT:GQ:GQX:DP:DPF:AD 1/2:7:5:5:1:0,1,4");
Assert.NotNull(annotatedVariant);
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"A\",\"refAllele\":\"T\",\"begin\":3124877,\"chromosome\":\"17\",\"dbsnp\":[\"rs182093170\"],\"end\":3124877,\"variantType\":\"SNV\",\"vid\":\"17:3124877:A\"}");
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"C\",\"refAllele\":\"T\",\"begin\":3124877,\"chromosome\":\"17\",\"end\":3124877,\"variantType\":\"SNV\",\"vid\":\"17:3124877:C\"}",
1);
}
public void MissingRegulatoryFeatureJson()
{
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENSR00000669067_chr1_Ensembl84_reg"), null,
"1 16833395 . G A,T . LowQscore SOMATIC;QSS=268;TQSS=2;NT=conflict;QSS_NT=0;TQSS_NT=2;SGT=GT->AT;DP=431;MQ=53.95;MQ0=60;ALTPOS=41;ALTMAP=25;ReadPosRankSum=0.74;SNVSB=0.00;PNOISE=0.00;PNOISE2=0.00;VQSR=0.00;CSQ=A|regulatory_region_variant|MODIFIER|||RegulatoryFeature|ENSR00000669067|,T|regulatory_region_variant|MODIFIER|||RegulatoryFeature|ENSR00000669067| DP:FDP:SDP:SUBDP:AU:CU:GU:TU 130:1:0:0:17,18:0,0:27,27:85,111 236:3:0:0:52,54:1,1:27,27:153,191");
Assert.NotNull(annotatedVariant);
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"A\",\"refAllele\":\"G\",\"begin\":16833395,\"chromosome\":\"1\",\"end\":16833395,\"variantType\":\"SNV\",\"vid\":\"1:16833395:A\",\"regulatoryRegions\":[{\"id\":\"ENSR00000669067\",\"type\":\"promoter_flanking_region\",\"consequence\":[\"regulatory_region_variant\"]}]}");
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"T\",\"refAllele\":\"G\",\"begin\":16833395,\"chromosome\":\"1\",\"end\":16833395,\"variantType\":\"SNV\",\"vid\":\"1:16833395:T\",\"regulatoryRegions\":[{\"id\":\"ENSR00000669067\",\"type\":\"promoter_flanking_region\",\"consequence\":[\"regulatory_region_variant\"]}]}",
1);
}
public void Extra1000GenomeValues()
{
var annotatedVariant = DataUtilities.GetVariant(DataUtilities.EmptyCachePrefix, Resources.MiniSuppAnnot("chr17_7432913_7432914.nsa"),
"17 7432913 rs34130898 A AATT,ATTATT 100 PASS .");
Assert.NotNull(annotatedVariant);
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"ATT\",\"refAllele\":\"-\",\"begin\":7432914,\"chromosome\":\"17\",\"dbsnp\":[\"rs34130898\",\"rs397969947\"],\"end\":7432913,\"variantType\":\"insertion\",\"vid\":\"17:7432914:7432913:ATT\",\"oneKgAll\":0.357827,\"oneKgAfr\":0.303328,\"oneKgAmr\":0.396254,\"oneKgEas\":0.392857,\"oneKgEur\":0.422465,\"oneKgSas\":0.301636,\"oneKgAllAn\":5008,\"oneKgAfrAn\":1322,\"oneKgAmrAn\":694,\"oneKgEasAn\":1008,\"oneKgEurAn\":1006,\"oneKgSasAn\":978,\"oneKgAllAc\":1792,\"oneKgAfrAc\":401,\"oneKgAmrAc\":275,\"oneKgEasAc\":396,\"oneKgEurAc\":425,\"oneKgSasAc\":295}");
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"TTATT\",\"refAllele\":\"-\",\"begin\":7432914,\"chromosome\":\"17\",\"end\":7432913,\"variantType\":\"insertion\",\"vid\":\"17:7432914:7432913:TTATT\"}",
1);
}
public void Uncleared1000GenomeValues()
{
var annotatedVariant = DataUtilities.GetVariant(DataUtilities.EmptyCachePrefix, Resources.MiniSuppAnnot("chr1_8383550_8383560.nsa"),
"1 8383550 . CAAAAAAAAA C,CAAAAAAAAAAAAA 100 PASS .");
Assert.NotNull(annotatedVariant);
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"-\",\"refAllele\":\"AAAAAAAAA\",\"begin\":8383551,\"chromosome\":\"1\",\"dbsnp\":[\"rs34956825\",\"rs774024202\",\"rs796237312\"],\"end\":8383559,\"variantType\":\"deletion\",\"vid\":\"1:8383551:8383559\",\"oneKgAll\":0.921526,\"oneKgAfr\":0.847958,\"oneKgAmr\":0.903458,\"oneKgEas\":0.985119,\"oneKgEur\":0.914513,\"oneKgSas\":0.97546,\"oneKgAllAn\":5008,\"oneKgAfrAn\":1322,\"oneKgAmrAn\":694,\"oneKgEasAn\":1008,\"oneKgEurAn\":1006,\"oneKgSasAn\":978,\"oneKgAllAc\":4615,\"oneKgAfrAc\":1121,\"oneKgAmrAc\":627,\"oneKgEasAc\":993,\"oneKgEurAc\":920,\"oneKgSasAc\":954}");
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"AAAA\",\"refAllele\":\"-\",\"begin\":8383560,\"chromosome\":\"1\",\"end\":8383559,\"variantType\":\"insertion\",\"vid\":\"1:8383560:8383559:AAAA\"}",
1);
}
public void DuplicateDbSnpJson()
{
var annotatedVariant = DataUtilities.GetVariant(DataUtilities.EmptyCachePrefix, Resources.MiniSuppAnnot("chr1_8121167_8121168.nsa"),
"1 8121167 . C CAAT,CAATAAT . . .");
Assert.NotNull(annotatedVariant);
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"AAT\",\"refAllele\":\"-\",\"begin\":8121168,\"chromosome\":\"1\",\"dbsnp\":[\"rs34500567\",\"rs59792241\"],\"end\":8121167,\"variantType\":\"insertion\",\"vid\":\"1:8121168:8121167:AAT\"}");
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"AATAAT\",\"refAllele\":\"-\",\"begin\":8121168,\"chromosome\":\"1\",\"end\":8121167,\"variantType\":\"insertion\",\"vid\":\"1:8121168:8121167:AATAAT\"}",
1);
}
public void CarryOverDbsnp()
{
var annotatedVariant = DataUtilities.GetVariant(DataUtilities.EmptyCachePrefix, Resources.MiniSuppAnnot("chr2_118565152_118565155.nsa"),
"2 118565152 . AGC AGT,CGC 50 PASS SNVSB=-8.7;SNVHPOL=5;CSQ=AGT|upstream_gene_variant|MODIFIER|AC009312.1|ENSG00000238207|Transcript|ENST00000457110|antisense|||||||||||3402|-1|Clone_based_vega_gene||YES|||||||||,CGC|upstream_gene_variant|MODIFIER|AC009312.1|ENSG00000238207|Transcript|ENST00000457110|antisense|||||||||||3402|-1|Clone_based_vega_gene||YES||||||||| GT:GQ:GQX:DP:DPF:AD 1/2:83:21:12:2:0,8,4");
Assert.NotNull(annotatedVariant);
JsonUtilities.AlleleContains(annotatedVariant,
"{\"altAllele\":\"T\",\"refAllele\":\"C\",\"begin\":118565154,\"chromosome\":\"2\",\"dbsnp\":[\"rs62192625\",\"rs77494680\"],\"end\":118565154,\"globalMinorAllele\":\"T\",\"gmaf\":0.3464,\"variantType\":\"SNV\",\"vid\":\"2:118565154:T");
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"C\",\"refAllele\":\"A\",\"begin\":118565152,\"chromosome\":\"2\",\"dbsnp\":[\"rs754609911\"],\"end\":118565152,\"variantType\":\"SNV\",\"vid\":\"2:118565152:C\"}",
1);
}
public void OutputSenecaCnvRelevantField()
{
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000546909_chr14_Ensembl84"), null,
"14 19431000 14_19462000 G <CNV> . PASS SVTYPE=CNV;END=19462000;CN=0;CNscore=13.41;LOH=0;ensembl_gene_id=ENSG00000257990,ENSG00000257558");
Assert.NotNull(annotatedVariant);
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"CNV\",\"refAllele\":\"G\",\"begin\":19431001,\"chromosome\":\"14\",\"end\":19462000,\"variantType\":\"copy_number_variation\",\"vid\":\"14:19431001:19462000:?\",\"overlappingGenes\":[\"RP11-536C10.15\"]}");
var observedCopyNumber = Convert.ToInt32(annotatedVariant.CopyNumber);
Assert.Equal(0, observedCopyNumber);
Assert.Contains("\"copyNumber\":0", annotatedVariant.ToString());
}
public void OutputCanvasCnvRelevantField()
{
var vcfLine = "1 9314201 Canvas:GAIN:1:9314202:9404148 N <CNV> 36 PASS SVTYPE=CNV;END=9404148;ensembl_gene_id=ENSG00000049239,ENSG00000252841,ENSG00000171621 RC:BC:CN:MCC . 151:108:6:4";
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000377403_chr1_Ensembl84"), null, vcfLine);
Assert.NotNull(annotatedVariant);
JsonUtilities.AlleleEquals(annotatedVariant,
"{\"altAllele\":\"CNV\",\"refAllele\":\"N\",\"begin\":9314202,\"chromosome\":\"1\",\"end\":9404148,\"variantType\":\"copy_number_variation\",\"vid\":\"1:9314202:9404148:6\",\"overlappingGenes\":[\"H6PD\"],\"transcripts\":{\"ensembl\":[{\"transcript\":\"ENST00000377403.2\",\"bioType\":\"protein_coding\",\"exons\":\"4-5/5\",\"introns\":\"3-4/4\",\"geneId\":\"ENSG00000049239\",\"hgnc\":\"H6PD\",\"consequence\":[\"copy_number_increase\"],\"isCanonical\":true,\"proteinId\":\"ENSP00000366620.1\"}]}}");
var cols = vcfLine.Split('\t');
var extractor = new SampleFieldExtractor(cols);
var samples = extractor.ExtractSamples();
Assert.Equal(2, samples.Count);
var sample = samples[1];
var observedCn = sample?.CopyNumber;
Assert.Equal("6", observedCn);
}
public void MissingClinvarIdRefAllele()
{
JsonUtilities.AlleleEquals("1 8021910 . GGTGCTGGACGGTGTCCCT T 362 PASS CIGAR=1M18D",
Resources.MiniSuppAnnot("chr1_8021910_8021911.nsa"),
"{\"altAllele\":\"-\",\"refAllele\":\"GGTGCTGGACGGTGTCCC\",\"begin\":8021910,\"chromosome\":\"1\",\"dbsnp\":[\"rs767770365\"],\"end\":8021927,\"variantType\":\"deletion\",\"vid\":\"1:8021910:8021927\"}");
}
