public void MergeDbSnp1KpEvsRefMinor()
{
const string vcfLine1 = "1 69428 rs140739101 T G . . RS=140739101;RSPOS=69428;dbSNPBuildID=134;SSR=0;SAO=0;VP=0x050200000a05140026000100;WGT=1;VC=SNV;S3D;NSM;REF;ASP;VLD;KGPhase3;CAF=0.981,0.01897;COMMON=1";
//vcf line is modified
const string vcfLine2 = "1 69428 rs140739101 T G 100 PASS AC=4956;AF=0.989617;AN=5008;NS=2504;DP=17611;EAS_AF=0.003;AMR_AF=0.036;AFR_AF=0.0015;EUR_AF=0.0497;SAS_AF=0.0153;AA=.|||;VT=SNP;EX_TARGET;EAS_AN=1008;EAS_AC=3;EUR_AN=1006;EUR_AC=50;AFR_AN=1322;AFR_AC=2;AMR_AN=694;AMR_AC=25;SAS_AN=978;SAS_AC=15";
const string vcfLine3 = "1 69428 rs140739101 T G . PASS BSNP=dbSNP_134;EA_AC=313,6535;AA_AC=14,3808;TAC=327,10343;MAF=4.5707,0.3663,3.0647;GTS=GG,GT,TT;EA_GTC=92,129,3203;AA_GTC=1,12,1898;GTC=93,141,5101;DP=110;GL=OR4F5;CP=1.0;CG=0.9;AA=T;CA=.;EXOME_CHIP=no;GWAS_PUBMED=.;FG=NM_001005484.1:missense;HGVS_CDNA_VAR=NM_001005484.1:c.338T>G;HGVS_PROTEIN_VAR=NM_001005484.1:p.(F113C);CDS_SIZES=NM_001005484.1:918;GS=205;PH=probably-damaging:0.999;EA_AGE=.;AA_AGE=.";
var sa = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(69428));
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItem = dbsnpReader.ExtractItem(vcfLine1)[0];
dbSnpItem.SetSupplementaryAnnotations(sa);
var oneKGenItem = _oneKGenReader.ExtractItems(vcfLine2)[0];
oneKGenItem.SetSupplementaryAnnotations(sa);
var evsReader = new EvsReader(_renamer);
var evsItem = evsReader.ExtractItems(vcfLine3)[0];
evsItem.SetSupplementaryAnnotations(sa);
sa.FinalizePositionalAnnotations();
var dbSnp = sa.SaPosition.AlleleSpecificAnnotations["G"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as DbSnpAnnotation;
Assert.NotNull(dbSnp);
Assert.Equal(new List <long> {
140739101
}, dbSnp.DbSnp);
Assert.Equal(true, sa.SaPosition.IsRefMinorAllele);
}
public void MergeConflictingEvsItems()
{
const string vcfLine1 = "1 1564952 rs112177324 T G,A . PASS BSNP=dbSNP_132;EA_AC=2,3039,4701;AA_AC=44,279,3231;TAC=46,3318,7932;MAF=39.2793,9.0884,29.7805;GTS=A1A1,A1A2,A1R,A2A2,A2R,RR;EA_GTC=0,1,1,707,1624,1538;AA_GTC=4,4,32,41,193,1503;GTC=4,5,33,748,1817,3041;DP=10;GL=MIB2;CP=0.8;CG=-0.0;AA=.;CA=.;EXOME_CHIP=no;GWAS_PUBMED=.;FG=NM_080875.2:intron,NM_080875.2:intron,NM_001170689.1:intron,NM_001170689.1:intron,NM_001170688.1:intron,NM_001170688.1:intron,NM_001170687.1:intron,NM_001170687.1:intron,NM_001170686.1:intron,NM_001170686.1:intron;HGVS_CDNA_VAR=NM_080875.2:c.2908+7del1,NM_080875.2:c.2908+6_2908+7insG,NM_001170689.1:c.2187-66del1,NM_001170689.1:c.2187-67_2187-66insG,NM_001170688.1:c.2713+7del1,NM_001170688.1:c.2713+6_2713+7insG,NM_001170687.1:c.2866+7del1,NM_001170687.1:c.2866+6_2866+7insG,NM_001170686.1:c.2896+7del1,NM_001170686.1:c.2896+6_28967insG;HGVS_PROTEIN_VAR=.,.,.,.,.,.,.,.,.,.;CDS_SIZES=NM_080875.2:3213,NM_080875.2:3213,NM_001170689.1:2262,NM_001170689.1:2262,NM_001170688.1:3018,NM_001170688.1:3018,NM_001170687.1:3171,NM_001170687.1:3171,NM_001170686.1:3201,NM_001170686.1:3201;GS=.,.,.,.,.,.,.,.,.,.;PH=.,.,.,.,.,.,.,.,.,.;EA_AGE=.;AA_AGE=.";
const string vcfLine2 = "1 1564952 rs140739101 T A . PASS BSNP=dbSNP_134;EA_AC=313,6535;AA_AC=14,3808;TAC=327,10343;MAF=4.5707,0.3663,3.0647;GTS=GG,GT,TT;EA_GTC=92,129,3203;AA_GTC=1,12,1898;GTC=93,141,5101;DP=110;GL=OR4F5;CP=1.0;CG=0.9;AA=T;CA=.;EXOME_CHIP=no;GWAS_PUBMED=.;FG=NM_001005484.1:missense;HGVS_CDNA_VAR=NM_001005484.1:c.338T>G;HGVS_PROTEIN_VAR=NM_001005484.1:p.(F113C);CDS_SIZES=NM_001005484.1:918;GS=205;PH=probably-damaging:0.999;EA_AGE=.;AA_AGE=.";
var sa1 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(1564952));
var sa2 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(1564952));
var evsReader = new EvsReader(_renamer);
var evsItems = evsReader.ExtractItems(vcfLine1);
foreach (var item in evsItems)
{
item.SetSupplementaryAnnotations(sa1);
}
evsItems.Clear();
evsItems.AddRange(evsReader.ExtractItems(vcfLine2));
foreach (var item in evsItems)
{
item?.SetSupplementaryAnnotations(sa2);
}
sa1.MergeSaCreator(sa2);
var evs =
sa1.SaPosition.AlleleSpecificAnnotations["A"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Evs)] as
EvsAnnotation;
Assert.NotNull(evs);
Assert.True(evs.HasConflicts);
}
public void NumEvsSamplesTest()
{
const string vcfLine = "1 1564952 rs112177324 TG TGG,T . PASS BSNP=dbSNP_132;EA_AC=2,3039,4701;AA_AC=44,279,3231;TAC=46,3318,7932;MAF=39.2793,9.0884,29.7805;GTS=A1A1,A1A2,A1R,A2A2,A2R,RR;EA_GTC=0,1,1,707,1624,1538;AA_GTC=4,4,32,41,193,1503;GTC=4,5,33,748,1817,3041;DP=10;GL=MIB2;CP=0.8;CG=-0.0;AA=.;CA=.;EXOME_CHIP=no;GWAS_PUBMED=.;FG=NM_080875.2:intron,NM_080875.2:intron,NM_001170689.1:intron,NM_001170689.1:intron,NM_001170688.1:intron,NM_001170688.1:intron,NM_001170687.1:intron,NM_001170687.1:intron,NM_001170686.1:intron,NM_001170686.1:intron;HGVS_CDNA_VAR=NM_080875.2:c.2908+7del1,NM_080875.2:c.2908+6_2908+7insG,NM_001170689.1:c.2187-66del1,NM_001170689.1:c.2187-67_2187-66insG,NM_001170688.1:c.2713+7del1,NM_001170688.1:c.2713+6_2713+7insG,NM_001170687.1:c.2866+7del1,NM_001170687.1:c.2866+6_2866+7insG,NM_001170686.1:c.2896+7del1,NM_001170686.1:c.2896+6_28967insG;HGVS_PROTEIN_VAR=.,.,.,.,.,.,.,.,.,.;CDS_SIZES=NM_080875.2:3213,NM_080875.2:3213,NM_001170689.1:2262,NM_001170689.1:2262,NM_001170688.1:3018,NM_001170688.1:3018,NM_001170687.1:3171,NM_001170687.1:3171,NM_001170686.1:3201,NM_001170686.1:3201;GS=.,.,.,.,.,.,.,.,.,.;PH=.,.,.,.,.,.,.,.,.,.;EA_AGE=.;AA_AGE=.";
var evsReader = new EvsReader(_renamer);
var evsItemsList = evsReader.ExtractItems(vcfLine);
var sa = new SupplementaryAnnotationPosition(1564953);
var saCreator = new SupplementaryPositionCreator(sa);
var additionalItems = new List <SupplementaryDataItem>();
foreach (var evsItem in evsItemsList)
{
additionalItems.Add(evsItem.SetSupplementaryAnnotations(saCreator));
}
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(saCreator);
}
var evs =
sa.AlleleSpecificAnnotations["iG"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Evs)] as EvsAnnotation;
Assert.NotNull(evs);
Assert.Equal("5648", evs.NumEvsSamples);//GTC=4,5,33,748,1817,3041;
}
public void Merge1KgEvsExac()
{
const string vcfLine1 =
"1 13382 rs191719684 C G . PASS DBSNP=dbSNP_135;EA_AC=0,8600;AA_AC=17,4389;TAC=17,12989;MAF=0.0,0.3858,0.1307;GTS=GG,GC,CC;EA_GTC=0,0,4300;AA_GTC=0,17,2186;GTC=0,17,6486;DP=54;GL=SAMD11;CP=0.0;CG=1.5;AA=C;CA=.;EXOME_CHIP=no;GWAS_PUBMED=.;FG=NM_152486.2:intron;HGVS_CDNA_VAR=NM_152486.2:c.-30C>G;HGVS_PROTEIN_VAR=.;CDS_SIZES=NM_152486.2:2046;GS=.;PH=.;EA_AGE=.;AA_AGE=24.3+/-50.5";
const string vcfLine2 =
"1 13382 . C G 320.40 VQSRTrancheSNP99.60to99.80 AC=3;AC_AFR=0;AC_AMR=0;AC_Adj=1;AC_EAS=0;AC_FIN=0;AC_Het=1;AC_Hom=0;AC_NFE=0;AC_OTH=0;AC_SAS=1;AF=1.079e-04;AN=27810;AN_AFR=460;AN_AMR=82;AN_Adj=5728;AN_EAS=148;AN_FIN=4;AN_NFE=1400;AN_OTH=60;AN_SAS=3574;BaseQRankSum=-8.880e-01;ClippingRankSum=0.493;DP=86138;FS=0.000;GQ_MEAN=11.35;GQ_STDDEV=12.58;Het_AFR=0;Het_AMR=0;Het_EAS=0;Het_FIN=0;Het_NFE=0;Het_OTH=0;Het_SAS=1;Hom_AFR=0;Hom_AMR=0;Hom_EAS=0;Hom_FIN=0;Hom_NFE=0;Hom_OTH=0;Hom_SAS=0;InbreedingCoeff=-0.0832;MQ=34.49;MQ0=0;MQRankSum=-6.910e-01;NCC=72140;QD=20.03;ReadPosRankSum=-2.073e+00;VQSLOD=-4.106e+00;culprit=MQ;DP_HIST=9135|1821|1658|665|130|135|199|110|41|8|2|1|0|0|0|0|0|0|0|0,1|0|1|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0;GQ_HIST=1432|8682|140|118|2625|254|121|17|3|1|10|24|364|94|9|11|0|0|0|0,0|1|0|0|0|0|0|0|1|0|0|0|0|0|0|0|0|0|0|0;DOUBLETON_DIST=.;AC_MALE=1;AC_FEMALE=0;AN_MALE=3866;AN_FEMALE=1862;AC_CONSANGUINEOUS=0;AN_CONSANGUINEOUS=684;Hom_CONSANGUINEOUS=0";
const string vcfLine3 =
"1 13382 rs538606945 C G 100 PASS AC=1;AF=0.000199681;AN=5008;NS=2504;DP=28817;EAS_AF=0;AMR_AF=0;AFR_AF=0;EUR_AF=0;SAS_AF=0.001;AA=c|||;VT=SNP";
var sa1 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(13382));
var evsReader = new EvsReader(_renamer);
var evsItem = evsReader.ExtractItems(vcfLine1)[0];
evsItem.SetSupplementaryAnnotations(sa1);
var sa2 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(13382));
var exacReader = new ExacReader(_renamer);
var exacItem = exacReader.ExtractItems(vcfLine2)[0];
exacItem.SetSupplementaryAnnotations(sa2);
var sa3 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(13382));
var onekReader = new OneKGenReader(_renamer);
var onekItem = onekReader.ExtractItems(vcfLine3)[0];
onekItem.SetSupplementaryAnnotations(sa3);
sa1.MergeSaCreator(sa2);
sa1.MergeSaCreator(sa3);
var asa = sa1.SaPosition.AlleleSpecificAnnotations["G"];
var exac = asa.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Exac)] as ExacAnnotation;
var oneKg = asa.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)] as OneKGenAnnotation;
var evs = asa.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Evs)] as EvsAnnotation;
Assert.NotNull(exac);
Assert.NotNull(oneKg);
Assert.NotNull(evs);
var oneKgAc = oneKg.OneKgAllAc;
var oneKgAn = oneKg.OneKgAllAn;
var exacAllAc = exac.ExacAllAc;
var exacAllAn = exac.ExacAllAn;
Assert.NotNull(oneKgAc);
Assert.NotNull(oneKgAn);
Assert.NotNull(exacAllAc);
Assert.NotNull(exacAllAn);
Assert.Equal("0.0002", (oneKgAc.Value / (double)oneKgAn.Value).ToString(JsonCommon.FrequencyRoundingFormat));
Assert.Equal("0.001307", evs.EvsAll);
Assert.Equal("0.000175", (exacAllAc.Value / (double)exacAllAn.Value).ToString(JsonCommon.FrequencyRoundingFormat));
}
public void EvsDepthFieldTest()
{
const string vcfLine = "1 69428 rs140739101 T G . PASS BSNP=dbSNP_134;EA_AC=313,6535;AA_AC=14,3808;TAC=327,10343;MAF=4.5707,0.3663,3.0647;GTS=GG,GT,TT;EA_GTC=92,129,3203;AA_GTC=1,12,1898;GTC=93,141,5101;DP=110;GL=OR4F5;CP=1.0;CG=0.9;AA=T;CA=.;EXOME_CHIP=no;GWAS_PUBMED=.;FG=NM_001005484.1:missense;HGVS_CDNA_VAR=NM_001005484.1:c.338T>G;HGVS_PROTEIN_VAR=NM_001005484.1:p.(F113C);CDS_SIZES=NM_001005484.1:918;GS=205;PH=probably-damaging:0.999;EA_AGE=.;AA_AGE=.";
var fileInfo = new StreamReader(new MemoryStream());
var evsReader = new EvsReader(fileInfo, _refChromDict);
var evs = evsReader.ExtractItems(vcfLine)[0];
Assert.NotNull(evs);
const string expectedRes = "\"sampleCount\":5335,\"coverage\":110,\"allAf\":0.030647,\"afrAf\":0.003663,\"eurAf\":0.045707";
Assert.Equal(expectedRes, evs.GetJsonString());
}
private void CreateEvsTsv(string fileName)
{
if (string.IsNullOrEmpty(fileName))
{
return;
}
var benchMark = new Benchmark();
var version = DataSourceVersionReader.GetSourceVersion(fileName);
using (var writer = new EvsTsvWriter(version, _outputDirectory, _genomeAssembly, new ReferenceSequenceProvider(FileUtilities.GetReadStream(_compressedReferencePath))))
{
var evsReader = new EvsReader(GZipUtilities.GetAppropriateStreamReader(fileName), _refNamesDictionary);
TsvWriterUtilities.WriteSortedItems(evsReader.GetEvsItems(), writer);
}
var timeSpan = Benchmark.ToHumanReadable(benchMark.GetElapsedTime());
TsvWriterUtilities.WriteCompleteInfo("EVS", version.Version, timeSpan);
}
public void EvsDepthFieldTest()
{
const string vcfLine = "1 69428 rs140739101 T G . PASS BSNP=dbSNP_134;EA_AC=313,6535;AA_AC=14,3808;TAC=327,10343;MAF=4.5707,0.3663,3.0647;GTS=GG,GT,TT;EA_GTC=92,129,3203;AA_GTC=1,12,1898;GTC=93,141,5101;DP=110;GL=OR4F5;CP=1.0;CG=0.9;AA=T;CA=.;EXOME_CHIP=no;GWAS_PUBMED=.;FG=NM_001005484.1:missense;HGVS_CDNA_VAR=NM_001005484.1:c.338T>G;HGVS_PROTEIN_VAR=NM_001005484.1:p.(F113C);CDS_SIZES=NM_001005484.1:918;GS=205;PH=probably-damaging:0.999;EA_AGE=.;AA_AGE=.";
var evsReader = new EvsReader(_renamer);
var evsItem = evsReader.ExtractItems(vcfLine)[0];
var sa = new SupplementaryAnnotationPosition(69428);
var saCreator = new SupplementaryPositionCreator(sa);
evsItem.SetSupplementaryAnnotations(saCreator);
var evs =
sa.AlleleSpecificAnnotations["G"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Evs)] as EvsAnnotation;
Assert.NotNull(evs);
Assert.Equal("110", evs.EvsCoverage);
}
public void NumEvsSamplesTest()
{
const string vcfLine = "1 1564952 rs112177324 TG TGG,T . PASS BSNP=dbSNP_132;EA_AC=2,3039,4701;AA_AC=44,279,3231;TAC=46,3318,7932;MAF=39.2793,9.0884,29.7805;GTS=A1A1,A1A2,A1R,A2A2,A2R,RR;EA_GTC=0,1,1,707,1624,1538;AA_GTC=4,4,32,41,193,1503;GTC=4,5,33,748,1817,3041;DP=10;GL=MIB2;CP=0.8;CG=-0.0;AA=.;CA=.;EXOME_CHIP=no;GWAS_PUBMED=.;FG=NM_080875.2:intron,NM_080875.2:intron,NM_001170689.1:intron,NM_001170689.1:intron,NM_001170688.1:intron,NM_001170688.1:intron,NM_001170687.1:intron,NM_001170687.1:intron,NM_001170686.1:intron,NM_001170686.1:intron;HGVS_CDNA_VAR=NM_080875.2:c.2908+7del1,NM_080875.2:c.2908+6_2908+7insG,NM_001170689.1:c.2187-66del1,NM_001170689.1:c.2187-67_2187-66insG,NM_001170688.1:c.2713+7del1,NM_001170688.1:c.2713+6_2713+7insG,NM_001170687.1:c.2866+7del1,NM_001170687.1:c.2866+6_2866+7insG,NM_001170686.1:c.2896+7del1,NM_001170686.1:c.2896+6_28967insG;HGVS_PROTEIN_VAR=.,.,.,.,.,.,.,.,.,.;CDS_SIZES=NM_080875.2:3213,NM_080875.2:3213,NM_001170689.1:2262,NM_001170689.1:2262,NM_001170688.1:3018,NM_001170688.1:3018,NM_001170687.1:3171,NM_001170687.1:3171,NM_001170686.1:3201,NM_001170686.1:3201;GS=.,.,.,.,.,.,.,.,.,.;PH=.,.,.,.,.,.,.,.,.,.;EA_AGE=.;AA_AGE=.";
var fileInfo = new StreamReader(new MemoryStream());
var evsReader = new EvsReader(fileInfo, _refChromDict);
var evs = evsReader.ExtractItems(vcfLine);
Assert.NotNull(evs);
Assert.Equal(2, evs.Count);
const string expectedRes1 = "\"sampleCount\":5648,\"coverage\":10,\"allAf\":0.004072,\"afrAf\":0.012380,\"eurAf\":0.000258";
Assert.Equal(expectedRes1, evs[0].GetJsonString());
Assert.Equal("TGG", evs[0].AlternateAllele);
const string expectedRes2 = "\"sampleCount\":5648,\"coverage\":10,\"allAf\":0.293732,\"afrAf\":0.078503,\"eurAf\":0.392534";
Assert.Equal(expectedRes2, evs[1].GetJsonString());
Assert.Equal("T", evs[1].AlternateAllele);
}
public void MultiAlleleMergeDbSnp1KpEvsSaRw()
{
// create our expected data source versions
var dbSnpVersion = new DataSourceVersion("dbSNP", "142", DateTime.Parse("2015-01-02").Ticks);
var oneKGenVersion = new DataSourceVersion("1000 Genomes Project", "phase3_shapeit2_mvncall_integrated_v5.", DateTime.Parse("2013-05-02").Ticks);
var evsDataSource = new DataSourceVersion("EVS", "V2", DateTime.Parse("2013-11-13").Ticks);
var expectedDataSourceVersions = new List <DataSourceVersion> {
dbSnpVersion, oneKGenVersion, evsDataSource
};
// create our expected supplementary annotations
const string vcfLine1 = "1 1564952 rs112177324 TG T . . RS=112177324;RSPOS=1564953;dbSNPBuildID=132;SSR=0;SAO=0;VP=0x05010008000514013e000200;WGT=1;VC=DIV;SLO;INT;ASP;VLD;GNO;KGPhase1;KGPhase3;CAF=0.8468,0.1506;COMMON=1";
const string vcfLine2 = "1 1564952 rs112177324 TG TGG,T 100 PASS AC=13,754;AF=0.00259585,0.150559;AN=5008;NS=2504;DP=8657;EAS_AF=0,0.0933;AMR_AF=0.0014,0.2046;AFR_AF=0.0091,0.0182;EUR_AF=0,0.3588;SAS_AF=0,0.136";
const string vcfLine3 = "1 1564952 rs112177324 TG TGG,T . PASS BSNP=dbSNP_132;EA_AC=2,3039,4701;AA_AC=44,279,3231;TAC=46,3318,7932;MAF=39.2793,9.0884,29.7805;GTS=A1A1,A1A2,A1R,A2A2,A2R,RR;EA_GTC=0,1,1,707,1624,1538;AA_GTC=4,4,32,41,193,1503;GTC=4,5,33,748,1817,3041;DP=10;GL=MIB2;CP=0.8;CG=-0.0;AA=.;CA=.;EXOME_CHIP=no;GWAS_PUBMED=.;FG=NM_080875.2:intron,NM_080875.2:intron,NM_001170689.1:intron,NM_001170689.1:intron,NM_001170688.1:intron,NM_001170688.1:intron,NM_001170687.1:intron,NM_001170687.1:intron,NM_001170686.1:intron,NM_001170686.1:intron;HGVS_CDNA_VAR=NM_080875.2:c.2908+7del1,NM_080875.2:c.2908+6_2908+7insG,NM_001170689.1:c.2187-66del1,NM_001170689.1:c.2187-67_2187-66insG,NM_001170688.1:c.2713+7del1,NM_001170688.1:c.2713+6_2713+7insG,NM_001170687.1:c.2866+7del1,NM_001170687.1:c.2866+6_2866+7insG,NM_001170686.1:c.2896+7del1,NM_001170686.1:c.2896+6_28967insG;HGVS_PROTEIN_VAR=.,.,.,.,.,.,.,.,.,.;CDS_SIZES=NM_080875.2:3213,NM_080875.2:3213,NM_001170689.1:2262,NM_001170689.1:2262,NM_001170688.1:3018,NM_001170688.1:3018,NM_001170687.1:3171,NM_001170687.1:3171,NM_001170686.1:3201,NM_001170686.1:3201;GS=.,.,.,.,.,.,.,.,.,.;PH=.,.,.,.,.,.,.,.,.,.;EA_AGE=.;AA_AGE=.";
var sa = new SupplementaryAnnotationPosition(1564953);
var saCreator = new SupplementaryPositionCreator(sa);
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItem = dbsnpReader.ExtractItem(vcfLine1)[0];
var additionalItems = new List <SupplementaryDataItem>
{
dbSnpItem.SetSupplementaryAnnotations(saCreator)
};
var oneKGenReader = new OneKGenReader(_renamer);
var oneKGenItem = oneKGenReader.ExtractItems(vcfLine2)[0];
additionalItems.Add(oneKGenItem.SetSupplementaryAnnotations(saCreator));
var evsReader = new EvsReader(_renamer);
var evsItemsList = evsReader.ExtractItems(vcfLine3);
foreach (var evsItem in evsItemsList)
{
additionalItems.Add(evsItem.SetSupplementaryAnnotations(saCreator));
}
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(saCreator);
}
// write the supplementary annotation file
var randomPath = Path.Combine(Path.GetTempPath(), Path.GetRandomFileName());
using (var writer = new SupplementaryAnnotationWriter(randomPath, "chr1", expectedDataSourceVersions))
{
writer.Write(saCreator, sa.ReferencePosition);
}
// read the supplementary annotation file
using (var reader = new SupplementaryAnnotationReader(randomPath))
{
var observedDataSourceVersions = reader.Header.DataSourceVersions;
// check the data source versions
Assert.Equal(observedDataSourceVersions.Count, 3);
var observedDataSourceVersion = observedDataSourceVersions[0];
Assert.Equal(dbSnpVersion.Name, observedDataSourceVersion.Name);
Assert.Equal(dbSnpVersion.Version, observedDataSourceVersion.Version);
Assert.Equal(dbSnpVersion.ReleaseDateTicks, observedDataSourceVersion.ReleaseDateTicks);
// checking the global alleles
Assert.Null(sa.GlobalMajorAllele);
Assert.Null(sa.GlobalMajorAlleleFrequency);
Assert.Null(sa.GlobalMinorAllele);
Assert.Null(sa.GlobalMinorAlleleFrequency);
// extract the three annotations
var observedAnnotation = reader.GetAnnotation(1564953) as SupplementaryAnnotationPosition;
Assert.NotNull(observedAnnotation);
var expectedInsOneKgAllAc = ((OneKGenAnnotation)sa.AlleleSpecificAnnotations["iG"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)]).OneKgAllAc;
var expectedDelHasOneKg = sa.AlleleSpecificAnnotations["1"].HasDataSource(DataSourceCommon.DataSource.OneKg);
var expectedInsEvsAfr = ((EvsAnnotation)sa.AlleleSpecificAnnotations["iG"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Evs)]).EvsAfr;
var expectedInsHasDbSnp = sa.AlleleSpecificAnnotations["iG"].HasDataSource(DataSourceCommon.DataSource.DbSnp);
var obsAsaIns = observedAnnotation.AlleleSpecificAnnotations["iG"];
var obsAsaDel = observedAnnotation.AlleleSpecificAnnotations["1"];
Assert.Equal(expectedInsOneKgAllAc, ((OneKGenAnnotation)obsAsaIns.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)]).OneKgAllAc);
Assert.Equal(expectedDelHasOneKg, obsAsaDel.HasDataSource(DataSourceCommon.DataSource.OneKg));
Assert.Equal(expectedInsEvsAfr, ((EvsAnnotation)obsAsaIns.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Evs)]).EvsAfr);
Assert.Equal(expectedInsHasDbSnp, obsAsaIns.HasDataSource(DataSourceCommon.DataSource.DbSnp));
}
File.Delete(randomPath);
File.Delete(randomPath + ".idx");
}
public void ReadAndWriteDbSnp1KgEvs()
{
var randomPath = Path.Combine(Path.GetTempPath(), Path.GetRandomFileName());
// create our expected data source versions
var dbSnpVersion = new DataSourceVersion("dbSNP", "142", DateTime.Parse("2015-01-02").Ticks);
var oneKGenVersion = new DataSourceVersion("1000 Genomes Project", "phase3_shapeit2_mvncall_integrated_v5.", DateTime.Parse("2013-05-02").Ticks);
var evsDataSource = new DataSourceVersion("EVS", "V2", DateTime.Parse("2013-11-13").Ticks);
var expectedDataSourceVersions = new List <DataSourceVersion> {
dbSnpVersion, oneKGenVersion, evsDataSource
};
// create our expected supplementary annotations
const string vcfLine1 = "1 69428 rs140739101 T G . . RS=140739101;RSPOS=69428;dbSNPBuildID=134;SSR=0;SAO=0;VP=0x050200000a05140026000100;WGT=1;VC=SNV;S3D;NSM;REF;ASP;VLD;KGPhase3;CAF=0.981,0.01897;COMMON=1";
const string vcfLine2 = "1 69428 rs140739101 T G 100 PASS AC=95;AF=0.0189696;AN=5008;NS=2504;DP=17611;EAS_AF=0.003;AMR_AF=0.036;AFR_AF=0.0015;EUR_AF=0.0497;SAS_AF=0.0153;AA=.|||";
const string vcfLine3 = "1 69428 rs140739101 T G . PASS BSNP=dbSNP_134;EA_AC=313,6535;AA_AC=14,3808;TAC=327,10343;MAF=4.5707,0.3663,3.0647;GTS=GG,GT,TT;EA_GTC=92,129,3203;AA_GTC=1,12,1898;GTC=93,141,5101;DP=110;GL=OR4F5;CP=1.0;CG=0.9;AA=T;CA=.;EXOME_CHIP=no;GWAS_PUBMED=.;FG=NM_001005484.1:missense;HGVS_CDNA_VAR=NM_001005484.1:c.338T>G;HGVS_PROTEIN_VAR=NM_001005484.1:p.(F113C);CDS_SIZES=NM_001005484.1:918;GS=205;PH=probably-damaging:0.999;EA_AGE=.;AA_AGE=.";
const string altAllele = "G";
var sa = new SupplementaryAnnotationPosition(69428);
var saCreator = new SupplementaryPositionCreator(sa);
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItem = dbsnpReader.ExtractItem(vcfLine1)[0];
dbSnpItem.SetSupplementaryAnnotations(saCreator);
var oneKGenReader = new OneKGenReader(_renamer);
var oneKGenItem = oneKGenReader.ExtractItems(vcfLine2)[0];
oneKGenItem.SetSupplementaryAnnotations(saCreator);
var evsReader = new EvsReader(_renamer);
var evsItem = evsReader.ExtractItems(vcfLine3)[0];
evsItem.SetSupplementaryAnnotations(saCreator);
// the preceeding code has been unit tested in MergeDbSnp1kpEvs()
// write the supplementary annotation file
using (var writer = new SupplementaryAnnotationWriter(randomPath, "chr1", expectedDataSourceVersions))
{
writer.Write(saCreator, sa.ReferencePosition);
}
// read the supplementary annotation file
using (var reader = new SupplementaryAnnotationReader(randomPath))
{
var observedDataSourceVersions = reader.Header.DataSourceVersions;
// check the data source versions
Assert.Equal(observedDataSourceVersions.Count, 3);
var observedDataSourceVersion = observedDataSourceVersions[0];
Assert.Equal(dbSnpVersion.Name, observedDataSourceVersion.Name);
Assert.Equal(dbSnpVersion.Version, observedDataSourceVersion.Version);
Assert.Equal(dbSnpVersion.ReleaseDateTicks, observedDataSourceVersion.ReleaseDateTicks);
// extract the three annotations
var observedAnnotation1 = reader.GetAnnotation(69428) as SupplementaryAnnotationPosition;
Assert.NotNull(observedAnnotation1);
var expDbSnp =
sa.AlleleSpecificAnnotations[altAllele].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)]
as DbSnpAnnotation;
Assert.NotNull(expDbSnp);
var expOneKg =
sa.AlleleSpecificAnnotations[altAllele].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)]
as OneKGenAnnotation;
Assert.NotNull(expOneKg);
var expEvs =
sa.AlleleSpecificAnnotations[altAllele].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Evs)]
as EvsAnnotation;
Assert.NotNull(expEvs);
var obsDbSnp = observedAnnotation1.AlleleSpecificAnnotations[altAllele].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)]
as DbSnpAnnotation;
Assert.NotNull(obsDbSnp);
var obsOneKg = observedAnnotation1.AlleleSpecificAnnotations[altAllele].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)]
as OneKGenAnnotation;
Assert.NotNull(obsOneKg);
var obsEvs = observedAnnotation1.AlleleSpecificAnnotations[altAllele].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Evs)]
as EvsAnnotation;
Assert.NotNull(obsEvs);
Assert.Equal(expDbSnp.DbSnp, obsDbSnp.DbSnp);
Assert.Equal(expEvs.EvsAll, obsEvs.EvsAll);
Assert.Equal(expOneKg.OneKgAllAc, obsOneKg.OneKgAllAc);
Assert.Equal(expEvs.EvsCoverage, obsEvs.EvsCoverage);
Assert.Equal(expEvs.NumEvsSamples, obsEvs.NumEvsSamples);
}
File.Delete(randomPath);
File.Delete(randomPath + ".idx");
}
public void MultiAlleleMergeDbSnp1KpEvs()
{
const string vcfLine1 = "1 1564952 rs112177324 TG T . . RS=112177324;RSPOS=1564953;dbSNPBuildID=132;SSR=0;SAO=0;VP=0x05010008000514013e000200;WGT=1;VC=DIV;SLO;INT;ASP;VLD;GNO;KGPhase1;KGPhase3;CAF=0.8468,0.1506;COMMON=1";
const string vcfLine2 = "1 1564952 rs112177324 TG TGG,T 100 PASS AC=13,754;AF=0.00259585,0.150559;AN=5008;NS=2504;DP=8657;EAS_AF=0,0.0933;AMR_AF=0.0014,0.2046;AFR_AF=0.0091,0.0182;EUR_AF=0,0.3588;SAS_AF=0,0.136";
const string vcfLine3 = "1 1564952 rs112177324 TG TGG,T . PASS BSNP=dbSNP_132;EA_AC=2,3039,4701;AA_AC=44,279,3231;TAC=46,3318,7932;MAF=39.2793,9.0884,29.7805;GTS=A1A1,A1A2,A1R,A2A2,A2R,RR;EA_GTC=0,1,1,707,1624,1538;AA_GTC=4,4,32,41,193,1503;GTC=4,5,33,748,1817,3041;DP=10;GL=MIB2;CP=0.8;CG=-0.0;AA=.;CA=.;EXOME_CHIP=no;GWAS_PUBMED=.;FG=NM_080875.2:intron,NM_080875.2:intron,NM_001170689.1:intron,NM_001170689.1:intron,NM_001170688.1:intron,NM_001170688.1:intron,NM_001170687.1:intron,NM_001170687.1:intron,NM_001170686.1:intron,NM_001170686.1:intron;HGVS_CDNA_VAR=NM_080875.2:c.2908+7del1,NM_080875.2:c.2908+6_2908+7insG,NM_001170689.1:c.2187-66del1,NM_001170689.1:c.2187-67_2187-66insG,NM_001170688.1:c.2713+7del1,NM_001170688.1:c.2713+6_2713+7insG,NM_001170687.1:c.2866+7del1,NM_001170687.1:c.2866+6_2866+7insG,NM_001170686.1:c.2896+7del1,NM_001170686.1:c.2896+6_28967insG;HGVS_PROTEIN_VAR=.,.,.,.,.,.,.,.,.,.;CDS_SIZES=NM_080875.2:3213,NM_080875.2:3213,NM_001170689.1:2262,NM_001170689.1:2262,NM_001170688.1:3018,NM_001170688.1:3018,NM_001170687.1:3171,NM_001170687.1:3171,NM_001170686.1:3201,NM_001170686.1:3201;GS=.,.,.,.,.,.,.,.,.,.;PH=.,.,.,.,.,.,.,.,.,.;EA_AGE=.;AA_AGE=.";
var sa = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(1564952));
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItem = dbsnpReader.ExtractItem(vcfLine1)[0];
var additionalItems = new List <SupplementaryDataItem>
{
dbSnpItem.SetSupplementaryAnnotations(sa)
};
foreach (var oneKitem in _oneKGenReader.ExtractItems(vcfLine2))
{
additionalItems.Add(oneKitem.SetSupplementaryAnnotations(sa));
}
var evsReader = new EvsReader(_renamer);
var evsItemsList = evsReader.ExtractItems(vcfLine3);
foreach (var evsItem in evsItemsList)
{
additionalItems.Add(evsItem.SetSupplementaryAnnotations(sa));
}
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa);
}
var asa1 = sa.SaPosition.AlleleSpecificAnnotations["1"];
var dbSnp1 = asa1.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as DbSnpAnnotation;
var oneKg1 = asa1.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)] as OneKGenAnnotation;
var evs1 = asa1.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Evs)] as EvsAnnotation;
Assert.NotNull(dbSnp1);
Assert.NotNull(oneKg1);
Assert.NotNull(evs1);
var asaiG = sa.SaPosition.AlleleSpecificAnnotations["iG"];
var oneKgiG = asaiG.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)] as OneKGenAnnotation;
var evsiG = asaiG.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Evs)] as EvsAnnotation;
Assert.NotNull(oneKgiG);
Assert.NotNull(evsiG);
Assert.Equal(new List <long> {
112177324
}, dbSnp1.DbSnp);
var oneKggAc = oneKgiG.OneKgAllAc;
var oneKggAn = oneKgiG.OneKgAllAn;
var oneKg1Ac = oneKg1.OneKgAllAc;
var oneKg1An = oneKg1.OneKgAllAn;
Assert.NotNull(oneKggAc);
Assert.NotNull(oneKggAn);
Assert.NotNull(oneKg1Ac);
Assert.NotNull(oneKg1An);
Assert.Equal("0.002596", (oneKggAc.Value / (double)oneKggAn.Value).ToString(JsonCommon.FrequencyRoundingFormat));
Assert.Equal("0.150559", (oneKg1Ac.Value / (double)oneKg1An.Value).ToString(JsonCommon.FrequencyRoundingFormat));
Assert.Equal("0.012380", evsiG.EvsAfr);
Assert.Equal("0.000258", evsiG.EvsEur);
Assert.Equal("0.004072", evsiG.EvsAll);
Assert.Equal("0.078503", evs1.EvsAfr);
Assert.Equal("0.392534", evs1.EvsEur);
Assert.Equal("0.293732", evs1.EvsAll);
}
// constructor
public CreateSupplementaryDatabase(
string compressedReferencePath,
string nsdBaseFileName,
string dbSnpFileName = null,
string cosmicVcfFile = null,
string cosmicTsvFile = null,
string clinVarFileName = null,
string oneKGenomeAfFileName = null,
string evsFileName = null,
string exacFileName = null,
List <string> customFiles = null,
string dgvFileName = null,
string oneKSvFileName = null,
string clinGenFileName = null,
string chrWhiteList = null)
{
_nsdBaseFileName = nsdBaseFileName;
_dataSources = new List <DataSourceVersion>();
_iSupplementaryDataItemList = new List <IEnumerator <SupplementaryDataItem> >();
_supplementaryIntervalList = new List <SupplementaryInterval>();
Console.WriteLine("Creating supplementary annotation files... Data version: {0}, schema version: {1}", SupplementaryAnnotationCommon.DataVersion, SupplementaryAnnotationCommon.SchemaVersion);
_compressedSequence = new CompressedSequence();
var compressedSequenceReader = new CompressedSequenceReader(FileUtilities.GetReadStream(compressedReferencePath), _compressedSequence);
_renamer = _compressedSequence.Renamer;
_dataFileManager = new DataFileManager(compressedSequenceReader, _compressedSequence);
if (!string.IsNullOrEmpty(chrWhiteList))
{
Console.WriteLine("Creating SA for the following chromosomes only:");
foreach (var refSeq in chrWhiteList.Split(','))
{
InputFileParserUtilities.ChromosomeWhiteList.Add(_renamer.GetEnsemblReferenceName(refSeq));
Console.Write(refSeq + ",");
}
Console.WriteLine();
}
else
{
InputFileParserUtilities.ChromosomeWhiteList = null;
}
if (dbSnpFileName != null)
{
AddSourceVersion(dbSnpFileName);
var dbSnpReader = new DbSnpReader(new FileInfo(dbSnpFileName), _renamer);
var dbSnpEnumerator = dbSnpReader.GetEnumerator();
_iSupplementaryDataItemList.Add(dbSnpEnumerator);
}
if (cosmicVcfFile != null && cosmicTsvFile != null)
{
AddSourceVersion(cosmicVcfFile);
var cosmicReader = new MergedCosmicReader(cosmicVcfFile, cosmicTsvFile, _renamer);
var cosmicEnumerator = cosmicReader.GetEnumerator();
_iSupplementaryDataItemList.Add(cosmicEnumerator);
}
if (oneKGenomeAfFileName != null)
{
AddSourceVersion(oneKGenomeAfFileName);
var oneKGenReader = new OneKGenReader(new FileInfo(oneKGenomeAfFileName), _renamer);
var oneKGenEnumerator = oneKGenReader.GetEnumerator();
_iSupplementaryDataItemList.Add(oneKGenEnumerator);
}
if (oneKSvFileName != null)
{
if (oneKGenomeAfFileName == null)
{
AddSourceVersion(oneKSvFileName);
}
var oneKGenSvReader = new OneKGenSvReader(new FileInfo(oneKSvFileName), _renamer);
var oneKGenSvEnumerator = oneKGenSvReader.GetEnumerator();
_iSupplementaryDataItemList.Add(oneKGenSvEnumerator);
}
if (evsFileName != null)
{
AddSourceVersion(evsFileName);
var evsReader = new EvsReader(new FileInfo(evsFileName), _renamer);
var evsEnumerator = evsReader.GetEnumerator();
_iSupplementaryDataItemList.Add(evsEnumerator);
}
if (exacFileName != null)
{
AddSourceVersion(exacFileName);
var exacReader = new ExacReader(new FileInfo(exacFileName), _renamer);
var exacEnumerator = exacReader.GetEnumerator();
_iSupplementaryDataItemList.Add(exacEnumerator);
}
if (clinVarFileName != null)
{
AddSourceVersion(clinVarFileName);
var clinVarReader = new ClinVarXmlReader(new FileInfo(clinVarFileName), compressedSequenceReader, _compressedSequence);
var clinVarList = clinVarReader.ToList();
clinVarList.Sort();
Console.WriteLine($"{clinVarList.Count} clinvar items read form XML file");
IEnumerator <ClinVarItem> clinVarEnumerator = clinVarList.GetEnumerator();
_iSupplementaryDataItemList.Add(clinVarEnumerator);
}
if (dgvFileName != null)
{
AddSourceVersion(dgvFileName);
var dgvReader = new DgvReader(new FileInfo(dgvFileName), _renamer);
var dgvEnumerator = dgvReader.GetEnumerator();
_iSupplementaryDataItemList.Add(dgvEnumerator);
}
if (clinGenFileName != null)
{
AddSourceVersion(clinGenFileName);
var clinGenReader = new ClinGenReader(new FileInfo(clinGenFileName), _renamer);
var clinGenEnumerator = clinGenReader.GetEnumerator();
_iSupplementaryDataItemList.Add(clinGenEnumerator);
}
if (customFiles != null)
{
foreach (var customFile in customFiles)
{
AddSourceVersion(customFile);
var customReader = new CustomAnnotationReader(new FileInfo(customFile), _renamer);
var customEnumerator = customReader.GetEnumerator();
_iSupplementaryDataItemList.Add(customEnumerator);
}
}
// initializing the IEnumerators in the list
foreach (var iDataEnumerator in _iSupplementaryDataItemList)
{
if (!iDataEnumerator.MoveNext())
{
_iSupplementaryDataItemList.Remove(iDataEnumerator);
}
}
_additionalItemsList = new List <SupplementaryDataItem>();
}
