public void MergeDbSnpItems()
{
const string vcfLine1 = "1 10228 rs143255646 TA T . . RS=143255646;RSPOS=10229;dbSNPBuildID=134;SSR=0;SAO=0;VP=0x050000020005000002000200;WGT=1;VC=DIV;R5;ASP";
const string vcfLine2 = "1 10228 rs200462216 TAACCCCTAACCCTAACCCTAAACCCTA T . . RS=200462216;RSPOS=10229;dbSNPBuildID=137;SSR=0;SAO=0;VP=0x050000020005000002000200;WGT=1;VC=DIV;R5;ASP";
var sa = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(10229));
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItem1 = dbsnpReader.ExtractItem(vcfLine1)[0];
var dbSnpItem2 = dbsnpReader.ExtractItem(vcfLine2)[0];
var additionalItems = new List <SupplementaryDataItem>
{
dbSnpItem1.SetSupplementaryAnnotations(sa),
dbSnpItem2.SetSupplementaryAnnotations(sa)
};
//sa.Clear();
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa);
}
var dbSnp1 =
sa.SaPosition.AlleleSpecificAnnotations["1"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as
DbSnpAnnotation;
Assert.NotNull(dbSnp1);
var dbSnp27 =
sa.SaPosition.AlleleSpecificAnnotations["27"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as
DbSnpAnnotation;
Assert.NotNull(dbSnp27);
Assert.Equal(dbSnp1.DbSnp, new List <long> {
143255646
});
Assert.Equal(dbSnp27.DbSnp, new List <long> {
200462216
});
}
public void NoMinorAllele()
{
const string vcfLine =
"17 828 rs62053745 T C . . RS=62053745;RSPOS=828;dbSNPBuildID=129;SSR=0;SAO=0;VP=0x050100080005140136000100;WGT=1;VC=SNV;SLO;INT;ASP;VLD;GNO;KGPhase1;KGPhase3;CAF=.,0.7424;COMMON=1";
var dbsnpReader = new DbSnpReader(null, _refChromDict);
var dbSnpEntry = dbsnpReader.ExtractItem(vcfLine)[0];
Assert.Equal("C", dbSnpEntry.AlternateAllele);
Assert.Equal(0.7424, dbSnpEntry.AltAlleleFreq);
Assert.Equal(double.MinValue, dbSnpEntry.RefAlleleFreq);
}
public void MergeDbSnpCosmic1Kg()
{
const string vcfLine1 = "1 10228 rs143255646 TA T . . RS=143255646;RSPOS=10229;dbSNPBuildID=134;SSR=0;SAO=0;VP=0x050000020005000002000200;WGT=1;VC=DIV;R5;ASP";
const string vcfLine2 = "1 10228 . TA T 100 PASS AC=2130;AF=0.425319;AN=5008;NS=2504;DP=103152;EAS_AF=0.3363;AMR_AF=0.3602;AFR_AF=0.4909;EUR_AF=0.4056;SAS_AF=0.4949;AA=|||unknown(NO_COVERAGE)";
var sa = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(10229));
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItem1 = dbsnpReader.ExtractItem(vcfLine1)[0];
var additionalItems = new List <SupplementaryDataItem>
{
dbSnpItem1.SetSupplementaryAnnotations(sa)
};
var cosmicItem1 = new CosmicItem("1", 10229, "COSM1000", "TA", "T", "TP53",
new HashSet <CosmicItem.CosmicStudy> {
new CosmicItem.CosmicStudy(null, "carcinoma", "oesophagus")
}, null);
additionalItems.Add(cosmicItem1.SetSupplementaryAnnotations(sa));
var oneKGenItem = _oneKGenReader.ExtractItems(vcfLine2)[0];
additionalItems.Add(oneKGenItem.SetSupplementaryAnnotations(sa));
//sa.Clear();
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa);
}
var asa = sa.SaPosition.AlleleSpecificAnnotations["1"];
var dbSnp = asa.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as DbSnpAnnotation;
var oneKg = asa.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)] as OneKGenAnnotation;
Assert.NotNull(oneKg);
var oneKgAc = oneKg.OneKgAllAc;
var oneKgAn = oneKg.OneKgAllAn;
Assert.NotNull(oneKgAc);
Assert.NotNull(oneKgAn);
Assert.NotNull(dbSnp);
Assert.NotNull(oneKg);
Assert.Equal(dbSnp.DbSnp, new List <long> {
143255646
});
Assert.Equal("0.425319", (oneKgAc.Value / (double)oneKgAn.Value).ToString(JsonCommon.FrequencyRoundingFormat));
Assert.True(sa.SaPosition.ContainsCosmicId("COSM1000"));
}
public void MissingDbsnpId()
{
const string vcfLine =
"X 21505833 rs12395602 G A,C,T . . RS=12395602;RSPOS=21505833;dbSNPBuildID=120;SSR=0;SAO=0;VP=0x05010008000505051f000101;WGT=1;VC=SNV;SLO;INT;ASP;VLD;G5;HD;GNO;KGPhase1";
var dbsnpReader = new DbSnpReader(null, _refChromDict);
var dbSnpEntries = dbsnpReader.ExtractItem(vcfLine);
Assert.Equal(3, dbSnpEntries.Count);
Assert.Equal("A", dbSnpEntries[0].AlternateAllele);
Assert.Equal(12395602, dbSnpEntries[0].RsId);
Assert.Equal("C", dbSnpEntries[1].AlternateAllele);
Assert.Equal(12395602, dbSnpEntries[1].RsId);
Assert.Equal("T", dbSnpEntries[2].AlternateAllele);
Assert.Equal(12395602, dbSnpEntries[2].RsId);
}
public void MergeDbSnp1KpEvs()
{
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=.|||;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);
var asa = sa.SaPosition.AlleleSpecificAnnotations["G"];
var dbSnp = asa.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as DbSnpAnnotation;
var oneKg = asa.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)] as OneKGenAnnotation;
var evs = asa.Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Evs)] as EvsAnnotation;
Assert.NotNull(dbSnp);
Assert.NotNull(oneKg);
Assert.NotNull(evs);
var oneKgAc = oneKg.OneKgEurAc;
var oneKgAn = oneKg.OneKgEurAn;
Assert.NotNull(oneKgAc);
Assert.NotNull(oneKgAn);
Assert.Equal(new List <long> {
140739101
}, dbSnp.DbSnp);
Assert.Equal("0.049702", (oneKgAc.Value / (double)oneKgAn.Value).ToString(JsonCommon.FrequencyRoundingFormat));
Assert.Equal("0.045707", evs.EvsEur);
Assert.False(sa.SaPosition.IsRefMinorAllele);
}
public void MissingDbsnpId()
{
const string vcfLine =
"X 21505833 rs12395602 G A,C,T . . RS=12395602;RSPOS=21505833;dbSNPBuildID=120;SSR=0;SAO=0;VP=0x05010008000505051f000101;WGT=1;VC=SNV;SLO;INT;ASP;VLD;G5;HD;GNO;KGPhase1";
var sequenceProvider = ParserTestUtils.GetSequenceProvider(21505833, "G", 'G', ChromosomeUtilities.RefNameToChromosome);
var dbsnpReader = new DbSnpReader(null, sequenceProvider);
var dbSnpEntries = dbsnpReader.ExtractItem(vcfLine).ToList();
Assert.Equal(3, dbSnpEntries.Count);
Assert.Equal("A", dbSnpEntries[0].AltAllele);
Assert.Equal(12395602, dbSnpEntries[0].RsId);
Assert.Equal("C", dbSnpEntries[1].AltAllele);
Assert.Equal(12395602, dbSnpEntries[1].RsId);
Assert.Equal("T", dbSnpEntries[2].AltAllele);
Assert.Equal(12395602, dbSnpEntries[2].RsId);
}
public void RefGlobalMajor()
{
// NIR-942
const string vcfLine =
"1 1242707 rs2274262 A G,T . . RS=2274262;RSPOS=1242707;RV;dbSNPBuildID=100;SSR=0;SAO=0;VP=0x0501004a000507013e000100;WGT=1;VC=SNV;SLO;U5;INT;R5;ASP;VLD;G5A;G5;GNO;KGPhase1;KGPhase3;CAF=0.4,0.4,0.2;COMMON=1";
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpEntry = dbsnpReader.ExtractItem(vcfLine)[0];
var sa = new SupplementaryAnnotationPosition(1242707);
var saCreator = new SupplementaryPositionCreator(sa);
dbSnpEntry.SetSupplementaryAnnotations(saCreator);
saCreator.FinalizePositionalAnnotations();
Assert.Equal("A", sa.GlobalMajorAllele);
Assert.Equal("G", sa.GlobalMinorAllele);
}
public void DisregardZeroFreq()
{
const string vcfLine =
"1 241369 rs11490246 C T . . RS=11490246;RSPOS=241369;dbSNPBuildID=120;SSR=0;SAO=0;VP=0x050100000005000126000100;WGT=1;VC=SNV;SLO;ASP;GNO;KGPhase3;CAF=0,1;COMMON=0";
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpEntry = dbsnpReader.ExtractItem(vcfLine)[0];
var sa = new SupplementaryAnnotationPosition(828);
var saCreator = new SupplementaryPositionCreator(sa);
dbSnpEntry.SetSupplementaryAnnotations(saCreator);
saCreator.FinalizePositionalAnnotations();
Assert.Equal("T", sa.GlobalMajorAllele);
Assert.Equal("1", sa.GlobalMajorAlleleFrequency);
Assert.Null(sa.GlobalMinorAllele);
Assert.Null(sa.GlobalMinorAlleleFrequency);
}
public void MissingDbsnpId()
{
// refactorSA. Annotation for C is missing in the database. have to debug that.
const string vcfLine =
"X 21505833 rs12395602 G A,C,T . . RS=12395602;RSPOS=21505833;dbSNPBuildID=120;SSR=0;SAO=0;VP=0x05010008000505051f000101;WGT=1;VC=SNV;SLO;INT;ASP;VLD;G5;HD;GNO;KGPhase1";
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpEntries = dbsnpReader.ExtractItem(vcfLine);
var sa = new SupplementaryAnnotationPosition(21505833);
var saCreator = new SupplementaryPositionCreator(sa);
foreach (var dbSnpEntry in dbSnpEntries)
{
dbSnpEntry.SetSupplementaryAnnotations(saCreator);
}
saCreator.FinalizePositionalAnnotations();
var dbSnpA =
sa.AlleleSpecificAnnotations["A"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as
DbSnpAnnotation;
Assert.NotNull(dbSnpA);
var dbSnpC =
sa.AlleleSpecificAnnotations["C"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as
DbSnpAnnotation;
Assert.NotNull(dbSnpC);
var dbSnpT =
sa.AlleleSpecificAnnotations["T"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as
DbSnpAnnotation;
Assert.NotNull(dbSnpT);
Assert.Equal(12395602, dbSnpA.DbSnp[0]);
Assert.Equal(12395602, dbSnpC.DbSnp[0]);
Assert.Equal(12395602, dbSnpT.DbSnp[0]);
}
public void NoMinorAllele1()
{
const string vcfLine =
"17 828 rs62053745 T C . . RS=62053745;RSPOS=828;dbSNPBuildID=129;SSR=0;SAO=0;VP=0x050100080005140136000100;WGT=1;VC=SNV;SLO;INT;ASP;VLD;GNO;KGPhase1;KGPhase3;CAF=0.7424,.;COMMON=1";
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpEntry = dbsnpReader.ExtractItem(vcfLine)[0];
var sa = new SupplementaryAnnotationPosition(828);
var saCreator = new SupplementaryPositionCreator(sa);
dbSnpEntry.SetSupplementaryAnnotations(saCreator);
saCreator.FinalizePositionalAnnotations();
Assert.Equal("T", sa.GlobalMajorAllele);
Assert.Equal("0.7424", sa.GlobalMajorAlleleFrequency);
Assert.Null(sa.GlobalMinorAllele);
Assert.Null(sa.GlobalMinorAlleleFrequency);
}
public void MergeDbSnpCosmic()
{
const string vcfLine1 = "1 10228 rs143255646 TA T . . RS=143255646;RSPOS=10229;dbSNPBuildID=134;SSR=0;SAO=0;VP=0x050000020005000002000200;WGT=1;VC=DIV;R5;ASP";
var sa = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(10229));
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItem1 = dbsnpReader.ExtractItem(vcfLine1)[0];
var additionalItems = new List <SupplementaryDataItem>
{
dbSnpItem1.SetSupplementaryAnnotations(sa)
};
var cosmicItem1 = new CosmicItem("1", 10229, "COSM1000", "TA", "T", "TP53",
new HashSet <CosmicItem.CosmicStudy> {
new CosmicItem.CosmicStudy(null, "carcinoma", "oesophagus")
}, null);
var cosmicItem2 = new CosmicItem("1", 10229, "COSM1000", "TA", "T", "TP53",
new HashSet <CosmicItem.CosmicStudy> {
new CosmicItem.CosmicStudy("01", "carcinoma", "large_intestine")
}, null);
additionalItems.Add(cosmicItem1.SetSupplementaryAnnotations(sa));
additionalItems.Add(cosmicItem2.SetSupplementaryAnnotations(sa));
//sa.Clear();
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa);
}
var dbSnpAnnotation =
sa.SaPosition.AlleleSpecificAnnotations["1"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as
DbSnpAnnotation;
Assert.NotNull(dbSnpAnnotation);
Assert.Equal(dbSnpAnnotation.DbSnp, new List <long> {
143255646
});
Assert.True(sa.SaPosition.ContainsCosmicId("COSM1000"));
}
public void ReadWriteDbSnpCosmic()
{
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 cosmicVersion = new DataSourceVersion("COSMIC", "GRCh37_v71", DateTime.Parse("2014-10-21").Ticks);
var expectedDataSourceVersions = new List <DataSourceVersion> {
dbSnpVersion, cosmicVersion
};
// create our expected supplementary annotations
const string vcfLine1 = "1 10228 rs143255646 TA T . . RS=143255646;RSPOS=10229;dbSNPBuildID=134;SSR=0;SAO=0;VP=0x050000020005000002000200;WGT=1;VC=DIV;R5;ASP";
var sa = new SupplementaryAnnotationPosition(10229);
var saCreator = new SupplementaryPositionCreator(sa);
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItem1 = dbsnpReader.ExtractItem(vcfLine1)[0];
var additionalItems = new List <SupplementaryDataItem>
{
dbSnpItem1.SetSupplementaryAnnotations(saCreator)
};
var cosmicItem1 = new CosmicItem("1", 10229, "COSM1000", "TA", "T", "TP53",
new HashSet <CosmicItem.CosmicStudy> {
new CosmicItem.CosmicStudy("", "carcinoma", "oesophagus")
}, null);
var cosmicItem2 = new CosmicItem("1", 10229, "COSM1000", "TA", "T", "TP53",
new HashSet <CosmicItem.CosmicStudy> {
new CosmicItem.CosmicStudy("01", "carcinoma", "large_intestine")
}, null);
additionalItems.Add(cosmicItem1.SetSupplementaryAnnotations(saCreator));
additionalItems.Add(cosmicItem2.SetSupplementaryAnnotations(saCreator));
//sa.Clear();
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(saCreator);
}
Assert.Equal(1, sa.CosmicItems.Count);
// the preceeding code has been unit tested in MergeDbSnpCosmic()
// 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))
{
// extract the three annotations
var observedAnnotation1 = reader.GetAnnotation(10229) as SupplementaryAnnotationPosition;
Assert.NotNull(observedAnnotation1);
var expDbSnp =
sa.AlleleSpecificAnnotations["1"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as
DbSnpAnnotation;
Assert.NotNull(expDbSnp);
var obsDbSnp =
observedAnnotation1.AlleleSpecificAnnotations["1"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as
DbSnpAnnotation;
Assert.NotNull(obsDbSnp);
Assert.Equal(expDbSnp.DbSnp, obsDbSnp.DbSnp);
Assert.True(observedAnnotation1.ContainsCosmicId(sa.CosmicItems[0].ID));
Assert.Equal(1, observedAnnotation1.CosmicItems.Count);
}
File.Delete(randomPath);
File.Delete(randomPath + ".idx");
}
public void ReadWriteExacDbsnp()
{
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 cosmicVersion = new DataSourceVersion("COSMIC", "GRCh37_v71", DateTime.Parse("2014-10-21").Ticks);
var expectedDataSourceVersions = new List <DataSourceVersion> {
dbSnpVersion, cosmicVersion
};
// create our expected supplementary annotations
const string vcfLine1 = "2 48010488 rs1042821 G A . . RS=1042821;RSPOS=48010488;RV;dbSNPBuildID=86;SSR=0;SAO=1;VP=0x050168420a05150136100100;GENEINFO=MSH6:2956;WGT=1;VC=SNV;PM;PMC;SLO;NSM;REF;U5;R5;ASP;VLD;G5;GNO;KGPhase1;KGPhase3;LSD;CAF=0.7991,0.2009;COMMON=1";
const string vcfLine2 =
"2 48010488 rs1042821 G A,C 14068898.15 PASS AC=21019,1;AC_AFR=1700,0;AC_AMR=1015,1;AC_Adj=19510,1;AC_EAS=1973,0;AC_FIN=743,0;AC_Het=15722,1,0;AC_Hom=1894,0;AC_NFE=10593,0;AC_OTH=147,0;AC_SAS=3339,0;AF=0.178,8.487e-06;AN=117830;AN_AFR=6388;AN_AMR=9014;AN_Adj=91130;AN_EAS=6792;AN_FIN=5078;AN_NFE=48404;AN_OTH=664;AN_SAS=14790;BaseQRankSum=-4.850e-01;ClippingRankSum=-1.400e-01;DB;DP=1206681;FS=0.000;GQ_MEAN=129.86;GQ_STDDEV=221.88;Het_AFR=1322,0,0;Het_AMR=931,1,0;Het_EAS=1511,0,0;Het_FIN=665,0,0;Het_NFE=8585,0,0;Het_OTH=111,0,0;Het_SAS=2597,0,0;Hom_AFR=189,0;Hom_AMR=42,0;Hom_EAS=231,0;Hom_FIN=39,0;Hom_NFE=1004,0;Hom_OTH=18,0;Hom_SAS=371,0;InbreedingCoeff=0.0376;MQ=60.00;MQ0=0;MQRankSum=0.00;NCC=3737;POSITIVE_TRAIN_SITE;QD=17.46;ReadPosRankSum=0.181;VQSLOD=5.87;culprit=MQ;DP_HIST=3051|9435|11318|5521|9711|11342|4131|1270|615|404|328|266|264|262|196|186|126|115|97|277,133|968|2180|3402|3564|2815|1772|954|551|389|321|263|261|261|196|186|126|115|97|277,0|0|0|1|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0;GQ_HIST=949|2966|347|492|15135|1435|1335|854|421|526|590|416|13672|1951|445|462|255|174|211|16279,24|79|81|124|135|96|110|118|97|180|228|137|182|191|126|171|180|151|192|16229,0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|1";
var sa = new SupplementaryAnnotationPosition(48010488);
var saCreator = new SupplementaryPositionCreator(sa);
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItem1 = dbsnpReader.ExtractItem(vcfLine1)[0];
dbSnpItem1.SetSupplementaryAnnotations(saCreator);
var exacReader = new ExacReader(_renamer);
foreach (var exacItem in exacReader.ExtractItems(vcfLine2))
{
exacItem.SetSupplementaryAnnotations(saCreator);
}
// write the supplementary annotation file
using (var writer = new SupplementaryAnnotationWriter(randomPath, "chr2", expectedDataSourceVersions))
{
writer.Write(saCreator, sa.ReferencePosition);
}
// read the supplementary annotation file
using (var reader = new SupplementaryAnnotationReader(randomPath))
{
// extract the three annotations
var observedAnnotation1 = reader.GetAnnotation(48010488) as SupplementaryAnnotationPosition;
Assert.NotNull(observedAnnotation1);
var expDbSnpA =
sa.AlleleSpecificAnnotations["A"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as DbSnpAnnotation;
var obsDbSnpA =
observedAnnotation1.AlleleSpecificAnnotations["A"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as DbSnpAnnotation;
Assert.NotNull(expDbSnpA);
Assert.NotNull(obsDbSnpA);
// we want to make sure we are reading the values we have written
Assert.Equal(expDbSnpA.DbSnp, obsDbSnpA.DbSnp);
var expExacA =
sa.AlleleSpecificAnnotations["A"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Exac)] as ExacAnnotation;
var obsExacA =
observedAnnotation1.AlleleSpecificAnnotations["A"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Exac)] as ExacAnnotation;
Assert.NotNull(expExacA);
Assert.NotNull(obsExacA);
Assert.Equal(expExacA.ExacAllAn, obsExacA.ExacAllAn);
Assert.Equal(expExacA.ExacCoverage, obsExacA.ExacCoverage);
Assert.Equal(Convert.ToDouble(expExacA.ExacAllAc), Convert.ToDouble(obsExacA.ExacAllAc));
Assert.Equal(Convert.ToDouble(expExacA.ExacAfrAc), Convert.ToDouble(obsExacA.ExacAfrAc));
Assert.Equal(Convert.ToDouble(expExacA.ExacAmrAc), Convert.ToDouble(obsExacA.ExacAmrAc));
Assert.Equal(Convert.ToDouble(expExacA.ExacEasAc), Convert.ToDouble(obsExacA.ExacEasAc));
Assert.Equal(Convert.ToDouble(expExacA.ExacFinAc), Convert.ToDouble(obsExacA.ExacFinAc));
Assert.Equal(Convert.ToDouble(expExacA.ExacNfeAc), Convert.ToDouble(obsExacA.ExacNfeAc));
Assert.Equal(Convert.ToDouble(expExacA.ExacOthAc), Convert.ToDouble(obsExacA.ExacOthAc));
Assert.Equal(Convert.ToDouble(expExacA.ExacSasAc), Convert.ToDouble(obsExacA.ExacSasAc));
var expExacC =
sa.AlleleSpecificAnnotations["C"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Exac)] as ExacAnnotation;
var obsExacC =
observedAnnotation1.AlleleSpecificAnnotations["C"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Exac)] as ExacAnnotation;
Assert.NotNull(expExacC);
Assert.NotNull(obsExacC);
Assert.Equal(expExacC.ExacCoverage, obsExacC.ExacCoverage);
Assert.Equal(Convert.ToDouble(expExacC.ExacAllAc), Convert.ToDouble(obsExacC.ExacAllAc));
Assert.Equal(Convert.ToDouble(expExacC.ExacAfrAc), Convert.ToDouble(obsExacC.ExacAfrAc));
Assert.Equal(Convert.ToDouble(expExacC.ExacAmrAc), Convert.ToDouble(obsExacC.ExacAmrAc));
Assert.Equal(Convert.ToDouble(expExacC.ExacEasAc), Convert.ToDouble(obsExacC.ExacEasAc));
Assert.Equal(Convert.ToDouble(expExacC.ExacFinAc), Convert.ToDouble(obsExacC.ExacFinAc));
Assert.Equal(Convert.ToDouble(expExacC.ExacNfeAc), Convert.ToDouble(obsExacC.ExacNfeAc));
Assert.Equal(Convert.ToDouble(expExacC.ExacOthAc), Convert.ToDouble(obsExacC.ExacOthAc));
Assert.Equal(Convert.ToDouble(expExacC.ExacSasAc), Convert.ToDouble(obsExacC.ExacSasAc));
}
File.Delete(randomPath);
File.Delete(randomPath + ".idx");
}
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);
}
