public void DuplicateDbsnp()
{
// NIR-853: can't reproduce the problem at dbSnp parsing and merging.
const string vcfLine1 =
"1 8121167 rs34500567 C CAAT,CAATAATAAAATAATAATAATAAT,CAATAAT,CAAT . . RS=34500567;RSPOS=8121167;dbSNPBuildID=126;SSR=0;SAO=0;VP=0x050000000005000002000200;WGT=1;VC=DIV;ASP;CAF=0.9726,.,.,.,.,0.9726;COMMON=1";
const string vcfLine2 =
"1 8121167 rs566669620 C CAATAATAAAAT . . RS=566669620;RSPOS=8121175;dbSNPBuildID=142;SSR=0;SAO=0;VP=0x050000000005040024000200;WGT=1;VC=DIV;ASP;VLD;KGPhase3;CAF=0.9726,0.0007987;COMMON=1";
const string vcfLine3 =
"1 8121167 rs59792241 C CAAT,CAATAATAAAATAATAATAATAAT,CAATAAT,CAAT . . RS=59792241;RSPOS=8121205;dbSNPBuildID=137;SSR=0;SAO=0;VP=0x050000000005000002000200;WGT=1;VC=DIV;ASP;CAF=0.9726,.,.,.,.,0.9726;COMMON=1";
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItems1 = dbsnpReader.ExtractItem(vcfLine1);
var dbSnpItems2 = dbsnpReader.ExtractItem(vcfLine2);
var dbSnpItems3 = dbsnpReader.ExtractItem(vcfLine3);
var sa1 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(8121168));
var sa2 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(8121168));
var sa3 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(8121168));
var additionalItems = dbSnpItems1.Select(dbSnpItem => dbSnpItem.SetSupplementaryAnnotations(sa1)).ToList();
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa1);
}
additionalItems.Clear();
additionalItems.AddRange(dbSnpItems2.Select(dbSnpItem => dbSnpItem.SetSupplementaryAnnotations(sa2)));
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa2);
}
additionalItems.Clear();
foreach (var dbSnpItem in dbSnpItems3)
{
additionalItems.Add(dbSnpItem.SetSupplementaryAnnotations(sa3));
}
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa3);
}
sa1.MergeSaCreator(sa2);
sa1.MergeSaCreator(sa3);
var dbSnp =
sa1.SaPosition.AlleleSpecificAnnotations["iAAT"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as
DbSnpAnnotation;
Assert.NotNull(dbSnp);
Assert.Equal(2, dbSnp.DbSnp.Count);
Assert.Equal(34500567, dbSnp.DbSnp[0]);
Assert.Equal(59792241, dbSnp.DbSnp[1]);
}
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 MergeConflictingExacItems()
{
const string vcfLine1 = "1 13528 . C G,T 1771.54 VQSRTrancheSNP99.60to99.80 AC=21,11;AC_AFR=12,0;AC_AMR=1,0;AC_Adj=13,9;AC_EAS=0,0;AC_FIN=0,0;AC_Het=13,9,0;AC_Hom=0,0;AC_NFE=0,2;AC_OTH=0,0;AC_SAS=0,7;AF=6.036e-04,3.162e-04;AN=34792;AN_AFR=390;AN_AMR=116;AN_Adj=10426;AN_EAS=150;AN_FIN=8;AN_NFE=2614;AN_OTH=116;AN_SAS=7032;BaseQRankSum=1.23;ClippingRankSum=0.056;DP=144988;FS=0.000;GQ_MEAN=14.54;GQ_STDDEV=16.53;Het_AFR=12,0,0;Het_AMR=1,0,0;Het_EAS=0,0,0;Het_FIN=0,0,0;Het_NFE=0,2,0;Het_OTH=0,0,0;Het_SAS=0,7,0;Hom_AFR=0,0;Hom_AMR=0,0;Hom_EAS=0,0;Hom_FIN=0,0;Hom_NFE=0,0;Hom_OTH=0,0;Hom_SAS=0,0;InbreedingCoeff=0.0557;MQ=31.08;MQ0=0;MQRankSum=-5.410e-01;NCC=67387;QD=1.91;ReadPosRankSum=0.206;VQSLOD=-2.705e+00;culprit=MQ;DP_HIST=10573|1503|705|1265|2477|613|167|52|18|11|8|3|0|0|1|0|0|0|0|0,2|6|2|1|4|0|3|1|0|0|2|0|0|0|0|0|0|0|0|0,1|0|0|0|1|1|3|0|1|1|1|0|0|0|1|0|0|0|0|0;GQ_HIST=342|11195|83|56|3154|517|367|60|12|4|5|7|1373|180|15|16|1|0|1|8,0|0|1|0|1|0|3|1|0|1|2|0|1|2|0|1|1|0|1|6,0|1|0|0|1|1|0|0|1|0|0|1|1|1|1|0|0|0|0|2";
const string vcfLine2 =
"1 13528 . C T 334.33 VQSRTrancheSNP99.60to99.80 AC=2;AC_AFR=0;AC_AMR=0;AC_Adj=2;AC_EAS=0;AC_FIN=0;AC_Het=2;AC_Hom=0;AC_NFE=0;AC_OTH=0;AC_SAS=2;AF=5.957e-05;AN=33576;AN_AFR=392;AN_AMR=114;AN_Adj=10200;AN_EAS=146;AN_FIN=6;AN_NFE=2556;AN_OTH=110;AN_SAS=6876;BaseQRankSum=-1.988e+00;ClippingRankSum=0.525;DP=142450;FS=2.634;GQ_MEAN=14.30;GQ_STDDEV=15.90;Het_AFR=0;Het_AMR=0;Het_EAS=0;Het_FIN=0;Het_NFE=0;Het_OTH=0;Het_SAS=2;Hom_AFR=0;Hom_AMR=0;Hom_EAS=0;Hom_FIN=0;Hom_NFE=0;Hom_OTH=0;Hom_SAS=0;InbreedingCoeff=-0.0753;MQ=31.78;MQ0=0;MQRankSum=0.578;NCC=68350;QD=5.31;ReadPosRankSum=-5.730e-01;VQSLOD=-3.582e+00;culprit=MQ;DP_HIST=10108|1417|742|1238|2324|682|184|56|20|11|4|2|0|0|0|0|0|0|0|0,0|0|0|1|0|0|0|0|0|1|0|0|0|0|0|0|0|0|0|0;GQ_HIST=335|10726|91|50|3215|542|410|67|10|3|1|6|1138|163|14|15|0|0|0|2,0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|0|2;DOUBLETON_DIST=0.028857408061;AC_MALE=1;AC_FEMALE=1;AN_MALE=7294;AN_FEMALE=2906;AC_CONSANGUINEOUS=0;AN_CONSANGUINEOUS=1360;Hom_CONSANGUINEOUS=0;";
var sa1 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(13528));
var sa2 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(13528));
var exacReader = new ExacReader(_renamer);
var exacItems = exacReader.ExtractItems(vcfLine1);
foreach (var item in exacItems)
{
item.SetSupplementaryAnnotations(sa1);
}
exacItems.Clear();
exacItems.AddRange(exacReader.ExtractItems(vcfLine2));
foreach (var item in exacItems)
{
item?.SetSupplementaryAnnotations(sa2);
}
sa1.MergeSaCreator(sa2);
var exac =
sa1.SaPosition.AlleleSpecificAnnotations["T"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.Exac)] as
ExacAnnotation;
Assert.NotNull(exac);
Assert.True(exac.HasConflicts);
}
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 MergeDbSnp1Kg()
{
//NIR-1262
const string vcfLine =
"1 825069 rs4475692 G A,C . . RS=4475692;RSPOS=825069;dbSNPBuildID=111;SSR=0;SAO=0;VP=0x050100000005170126000100;WGT=1;VC=SNV;SLO;ASP;VLD;G5A;G5;GNO;KGPhase3;CAF=0.3227,.,0.6773;COMMON=1";
const string vcfLine1Kg =
"1 825069 rs4475692 G C 100 PASS AC=3392;AF=0.677316;AN=5008;NS=2504;DP=22495;EAS_AF=0.754;AMR_AF=0.5692;AFR_AF=0.6127;EUR_AF=0.7286;SAS_AF=0.7096;AA=g|||;VT=SNP;EAS_AN=1008;EAS_AC=760;EUR_AN=1006;EUR_AC=733;AFR_AN=1322;AFR_AC=810;AMR_AN=694;AMR_AC=395;SAS_AN=978;SAS_AC=694\tGT";
var dbsnpReader = new DbSnpReader(_renamer);
var sa = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(825069));
foreach (var dbSnpEntry in dbsnpReader.ExtractItem(vcfLine))
{
dbSnpEntry.SetSupplementaryAnnotations(sa);
}
var sa1 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(825069));
var onekgReader = new OneKGenReader(_renamer);
foreach (var onekgItem in onekgReader.ExtractItems(vcfLine1Kg))
{
onekgItem.SetSupplementaryAnnotations(sa1);
}
sa.MergeSaCreator(sa1);
sa.FinalizePositionalAnnotations();
Assert.Equal("C", sa.SaPosition.GlobalMajorAllele);
Assert.Equal("G", sa.SaPosition.GlobalMinorAllele);
}
public void DeletionAndSnvMerge()
{
// NIR-906
const string vcfLine1 =
"2 193187631 rs774176075 TGTTG T . . RS=774176075;RSPOS=193187632;dbSNPBuildID=144;SSR=0;SAO=0;VP=0x050000000005000002000200;WGT=1;VC=DIV;ASP";
const string vcfLine2 = "2 193187632 rs2592266 G T . . RS=2592266;RSPOS=193187632;dbSNPBuildID=100;SSR=0;SAO=0;VP=0x050000000005150026000100;WGT=1;VC=SNV;ASP;VLD;G5;KGPhase3;CAF=0.01937,0.9806;COMMON=1";
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpEntry1 = dbsnpReader.ExtractItem(vcfLine1)[0];
var dbSnpEntry2 = dbsnpReader.ExtractItem(vcfLine2)[0];
var sa = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(193187632));
var additionalEntry = dbSnpEntry1.SetSupplementaryAnnotations(sa);
additionalEntry.SetSupplementaryAnnotations(sa);
var sa2 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(193187632));
dbSnpEntry2.SetSupplementaryAnnotations(sa2);
sa.MergeSaCreator(sa2);
sa.FinalizePositionalAnnotations();
Assert.Equal("T", sa.SaPosition.GlobalMajorAllele);
Assert.Equal("0.9806", sa.SaPosition.GlobalMajorAlleleFrequency);
Assert.Equal("G", sa.SaPosition.GlobalMinorAllele);
Assert.Equal("0.01937", sa.SaPosition.GlobalMinorAlleleFrequency);
}
public void MergeSnvAndDeletion()
{
// NIR-906
const string vcfLine1 =
"1 862389 rs6693546 A G . . RS=6693546;RSPOS=862389;dbSNPBuildID=116;SSR=0;SAO=0;VP=0x05010008000515013e000100;WGT=1;VC=SNV;SLO;INT;ASP;VLD;G5;GNO;KGPhase1;KGPhase3;CAF=0.3171,0.6829;COMMON=1";
const string vcfLine2 = "1 862388 rs534606253 GA G . . RS=534606253;RSPOS=862389;dbSNPBuildID=142;SSR=0;SAO=0;VP=0x050000080005040024000200;WGT=1;VC=DIV;INT;ASP;VLD;KGPhase3;CAF=0.996,0.003994;COMMON=1";
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpEntry1 = dbsnpReader.ExtractItem(vcfLine1)[0];
var dbSnpEntry2 = dbsnpReader.ExtractItem(vcfLine2)[0];
var sa = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(862389));
dbSnpEntry1.SetSupplementaryAnnotations(sa);
var sa2 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(862389));
var additionalEntry = dbSnpEntry2.SetSupplementaryAnnotations(sa2);
additionalEntry.SetSupplementaryAnnotations(sa2);
sa.MergeSaCreator(sa2);
sa.FinalizePositionalAnnotations();
Assert.Equal("G", sa.SaPosition.GlobalMajorAllele);
Assert.Equal("0.6829", sa.SaPosition.GlobalMajorAlleleFrequency);
Assert.Equal("A", sa.SaPosition.GlobalMinorAllele);
Assert.Equal("0.3171", sa.SaPosition.GlobalMinorAlleleFrequency);
}
public void MultipleDbsnpMerge()
{
// NIR-778, 805. The second dbSNP id is missing from the SA database.
const string vcfLine1 =
"17 3616153 rs34081014 C G . . RS=34081014;RSPOS=3616153;dbSNPBuildID=126;SSR=0;SAO=0;VP=0x050000000005140136000100;WGT=1;VC=SNV;ASP;VLD;GNO;KGPhase1;KGPhase3;CAF=0.9297,0.07029;COMMON=1";
const string vcfLine2 =
"17 3616152 rs71362546 GCTG GCTT,GGTG . . RS=71362546;RSPOS=3616153;dbSNPBuildID=130;SSR=0;SAO=0;VP=0x050100000005000102000810;WGT=1;VC=MNV;SLO;ASP;GNO;NOC";
var sa1 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(3616153));
var sa2 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(3616153));
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItem1 = dbsnpReader.ExtractItem(vcfLine1)[0];
var dbSnpItems = dbsnpReader.ExtractItem(vcfLine2);
dbSnpItem1.SetSupplementaryAnnotations(sa1);
var additionalItems = dbSnpItems.Select(dbSnpItem => dbSnpItem.SetSupplementaryAnnotations(sa1)).ToList();
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa2);
}
sa1.MergeSaCreator(sa2);
var dbSnp =
sa1.SaPosition.AlleleSpecificAnnotations["G"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as
DbSnpAnnotation;
Assert.NotNull(dbSnp);
Assert.Equal(dbSnp.DbSnp, new List <long> {
34081014, 71362546
});
}
public void MergeConflictingOneKitems1()
{
const string vcfLine1 =
"1 20505705 rs35377696 C CTCTG,CTG,CTGTG 100 PASS AC=46,1513,152;AF=0.0091853,0.302117,0.0303514;AN=5008;NS=2504;DP=23578;EAS_AF=0,0.2718,0.0268;AMR_AF=0.0086,0.2939,0.0072;AFR_AF=0.0303,0.2693,0.0756;EUR_AF=0,0.3032,0.001;SAS_AF=0,0.3824,0.0194";
const string vcfLine2 =
"1 20505705 . C CTG 100 PASS AC=4;AF=0.000798722;AN=5008;NS=2504;DP=23578;EAS_AF=0.002;AMR_AF=0;AFR_AF=0.0008;EUR_AF=0.001;SAS_AF=0";
//var sa1 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(20505706);
//var sa2 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(20505706);
var sa1 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(20505706));
var sa2 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(20505706));
var additionalItems = _oneKGenReader.ExtractItems(vcfLine1).Select(oneKitem => oneKitem.SetSupplementaryAnnotations(sa1)).ToList();
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa1);
}
additionalItems.Clear();
additionalItems.AddRange(_oneKGenReader.ExtractItems(vcfLine2).Select(oneKitem => oneKitem.SetSupplementaryAnnotations(sa2)));
foreach (var item in additionalItems)
{
item?.SetSupplementaryAnnotations(sa2);
}
sa1.MergeSaCreator(sa2);
Assert.True(sa1.SaPosition.AlleleSpecificAnnotations["iTG"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)].HasConflicts);
// Assert.Null(sa1.AlleleSpecificAnnotations["iTG"].OneKgAll);
}
public void BadRefMinor2()
{
// NIR-1368
const string vcfLine1 =
"X 1389061 . A C 100 PASS AC=3235;AF=0.645966;AN=5008;NS=2504;DP=13425;AMR_AF=0.7262;AFR_AF=0.2504;EUR_AF=0.8827;SAS_AF=0.7955;EAS_AF=0.7282;AA=a|||;VT=SNP";
const string vcfLine2 =
"X 1389061 . A C,T 100 PASS AC=2120,1771;AF=0.423323,0.353634;AN=5008;NS=2504;DP=13425;AMR_AF=0.4625,0.2997;AFR_AF=0.087,0.5998;EUR_AF=0.6551,0.2306;SAS_AF=0.5859,0.2157;EAS_AF=0.4484,0.3244;AA=a|||;VT=SNP;MULTI_ALLELIC";
var sa1 = new SupplementaryPositionCreator();
var sa2 = new SupplementaryPositionCreator();
foreach (var oneKitem in _oneKGenReader.ExtractItems(vcfLine1))
{
oneKitem.SetSupplementaryAnnotations(sa1);
}
foreach (var oneKitem in _oneKGenReader.ExtractItems(vcfLine2))
{
oneKitem.SetSupplementaryAnnotations(sa2);
}
sa1.MergeSaCreator(sa2);
Assert.False(sa1.IsRefMinor());
}
public void MergeDbSnpClinVar()
{
const string vcfLine = "1 225592188 rs387906416 TAGAAGA CTTCTAG . . RS=387906416;RSPOS=225592188;RV;dbSNPBuildID=137;SSR=0;SAO=1;VP=0x050060000605000002110800;GENEINFO=LBR:3930;WGT=1;VC=MNV;PM;NSN;REF;ASP;LSD;OM";
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItems = dbsnpReader.ExtractItem(vcfLine);
var sa = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(225592188));
foreach (var dbSnpItem in dbSnpItems)
{
dbSnpItem.SetSupplementaryAnnotations(sa);
}
var xmlReader = new ClinVarXmlReader(new FileInfo(Resources.TopPath("RCV000087262.xml")), _reader, _sequence);
foreach (var clinVarItem in xmlReader)
{
var sa1 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(225592188));
clinVarItem.SetSupplementaryAnnotations(sa1);
sa.MergeSaCreator(sa1);
}
Assert.Equal(1, sa.SaPosition.ClinVarItems.Count);
foreach (var clinVarEntry in sa.SaPosition.ClinVarItems)
{
Assert.Equal(clinVarEntry.ID, "RCV000087262.3");
Assert.Equal(clinVarEntry.MedGenIDs.First(), "C0030779");
Assert.Equal(clinVarEntry.Phenotypes.First(), "Pelger-Huët anomaly");
}
}
public void MergeConflictingOneKitemsSnv()
{
const string vcfLine1 =
"X 129354240 rs1160681 C A 100 PASS AC=1996;AF=0.528742;AN=3775;NS=2504;DP=10421;AMR_AF=0.353;AFR_AF=0.5953;EUR_AF=0.3052;SAS_AF=0.3896;EAS_AF=0.2738;AA=C|||;VT=SNP";
const string vcfLine2 =
"X 129354240 . C A,G 100 PASS AC=1981,15;AF=0.524768,0.00397351;AN=3775;NS=2504;DP=10421;AMR_AF=0.353,0;AFR_AF=0.584,0.0113;EUR_AF=0.3052,0;SAS_AF=0.3896,0;EAS_AF=0.2738,0;AA=C|||;VT=SNP;MULTI_ALLELIC";
var sa1 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(129354240));
var sa2 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(129354240));
var oneKitem1 = _oneKGenReader.ExtractItems(vcfLine1)[0];
oneKitem1.SetSupplementaryAnnotations(sa1);
foreach (var oneKitem in _oneKGenReader.ExtractItems(vcfLine2))
{
oneKitem.SetSupplementaryAnnotations(sa2);
}
sa1.MergeSaCreator(sa2);
var oneKg =
sa1.SaPosition.AlleleSpecificAnnotations["A"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)] as
OneKGenAnnotation;
Assert.NotNull(oneKg);
Assert.True(oneKg.HasConflicts);
}
public void ReadWriteClinVar()
{
//test to make sure that we write a ClinVar entry and read back the same thing.
var xmlReader = new ClinVarXmlReader(new FileInfo(@"Resources\RCV000152657.xml"), _reader, _sequence);
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 clinVarVersion = new DataSourceVersion("ClinVar", "13.5", DateTime.Parse("2015-01-19").Ticks);
var expectedDataSourceVersions = new List <DataSourceVersion> {
dbSnpVersion, clinVarVersion
};
var sa = new SupplementaryAnnotationPosition(10183457);
var saCreator = new SupplementaryPositionCreator(sa);
foreach (var clinVarItem in xmlReader)
{
clinVarItem.SetSupplementaryAnnotations(saCreator);
saCreator.MergeSaCreator(saCreator);
}
using (var writer = new SupplementaryAnnotationWriter(randomPath, "chr9", expectedDataSourceVersions))
{
writer.Write(saCreator, sa.ReferencePosition);
}
// read the supplementary annotation file
using (var reader = new SupplementaryAnnotationReader(randomPath))
{
var observedAnnotation = reader.GetAnnotation(10183457) as SupplementaryAnnotationPosition;
Assert.NotNull(observedAnnotation);
for (var i = 0; i < sa.ClinVarItems.Count; i++)
{
Assert.Equal(sa.ClinVarItems[i].ID, observedAnnotation.ClinVarItems[i].ID);
Assert.Equal(sa.ClinVarItems[i].Significance, observedAnnotation.ClinVarItems[i].Significance);
Assert.Equal(sa.ClinVarItems[i].LastUpdatedDate, observedAnnotation.ClinVarItems[i].LastUpdatedDate);
Assert.True(sa.ClinVarItems[i].Phenotypes.SequenceEqual(observedAnnotation.ClinVarItems[i].Phenotypes));
Assert.True(sa.ClinVarItems[i].MedGenIDs.SequenceEqual(observedAnnotation.ClinVarItems[i].MedGenIDs));
Assert.True(sa.ClinVarItems[i].OrphanetIDs.SequenceEqual(observedAnnotation.ClinVarItems[i].OrphanetIDs));
Assert.Equal(sa.ClinVarItems[i].AlleleOrigins, observedAnnotation.ClinVarItems[i].AlleleOrigins);
Assert.True(sa.ClinVarItems[i].OmimIDs.SequenceEqual(observedAnnotation.ClinVarItems[i].OmimIDs));
Assert.True(sa.ClinVarItems[i].PubmedIds.SequenceEqual(observedAnnotation.ClinVarItems[i].PubmedIds));
}
}
File.Delete(randomPath);
File.Delete(randomPath + ".idx");
}
public void Utf8ClinVar()
{
// NIR-900
var xmlReader = new ClinVarXmlReader(new FileInfo(Resources.TopPath("RCV000087262.xml")), _reader, _sequence);
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 clinVarVersion = new DataSourceVersion("ClinVar", "13.5", DateTime.Parse("2015-01-19").Ticks);
var expectedDataSourceVersions = new List <DataSourceVersion> {
dbSnpVersion, clinVarVersion
};
// This is the case where Nirvana throws an error: Too many bytes in what should have been a 7 bit encoded Int32.
var sa = new SupplementaryAnnotationPosition(225592188);
var saCreator = new SupplementaryPositionCreator(sa);
foreach (var clinVarItem in xmlReader)
{
clinVarItem.SetSupplementaryAnnotations(saCreator);
saCreator.MergeSaCreator(saCreator);
}
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(225592188) as SupplementaryAnnotationPosition;
Assert.NotNull(observedAnnotation1);
for (var i = 0; i < sa.ClinVarItems.Count; i++)
{
Assert.Equal(sa.ClinVarItems[i].Phenotypes, observedAnnotation1.ClinVarItems[i].Phenotypes);
}
}
File.Delete(randomPath);
File.Delete(randomPath + ".idx");
}
public void NonConflictingOneKitems1()
{
// NIR-1147
const string vcfLine1 = "X 5331877 rs71800267 AAC AACAC,A 100 PASS AC=159,562;AF=0.0421192,0.148874;AN=3775;NS=2504;OLD_VARIANT=X:5331899:CAC/CACAC/C;DP=9474;AMR_AF=0.0014,0.0908;AFR_AF=0.025,0.2769;EUR_AF=0.0109,0.0835;SAS_AF=0.0481,0.0307;EAS_AF=0.0665,0.0188;VT=INDEL;MULTI_ALLELIC";
const string vcfLine2 = "X 5331877 . AACACACACAC A 100 PASS AC= 101;AF=0.026755;AN=3775;NS=2504;DP=9474;AMR_AF=0.0086;AFR_AF=0.0711;EUR_AF=0.001;SAS_AF=0;EAS_AF=0;VT=INDEL";
var sa1 = new SupplementaryPositionCreator();
var sa2 = new SupplementaryPositionCreator();
var oneKitem1 = _oneKGenReader.ExtractItems(vcfLine1)[1];
var additionalItems = new List <SupplementaryDataItem>
{
oneKitem1.SetSupplementaryAnnotations(sa1)
};
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa1);
}
additionalItems.Clear();
additionalItems.AddRange(_oneKGenReader.ExtractItems(vcfLine2).Select(oneKitem => oneKitem.SetSupplementaryAnnotations(sa2)));
foreach (var item in additionalItems)
{
item?.SetSupplementaryAnnotations(sa2);
}
sa1.MergeSaCreator(sa2);
// in some cases, the merge happens using setSupplementaryAnnotation(). this unit test checks if that path is ok
var oneKg2 =
sa1.SaPosition.AlleleSpecificAnnotations["2"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)] as
OneKGenAnnotation;
Assert.NotNull(oneKg2);
var oneKg10 =
sa1.SaPosition.AlleleSpecificAnnotations["10"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)] as
OneKGenAnnotation;
Assert.NotNull(oneKg10);
Assert.False(oneKg2.HasConflicts);
Assert.NotNull(oneKg2.OneKgAllAc);
Assert.False(oneKg10.HasConflicts);
}
public void MergeMultipleDbSnpItems()
{
const string vcfLine1 =
"1 1469597 rs3118506 GCG GC,GG . . RS=3118506;RSPOS=1469598;RV;dbSNPBuildID=103;SSR=0;SAO=0;VP=0x050000800005000002000110;WGT=1;VC=SNV;U3;ASP;NOC";
const string vcfLine2 =
"1 1469598 rs368645009 CG C . . RS=368645009;RSPOS=1469599;RV;dbSNPBuildID=138;SSR=0;SAO=0;VP=0x050000800005000002000200;WGT=1;VC=DIV;U3;ASP";
var sa1 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(1469599));
var sa2 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(1469599));
var dbsnpReader = new DbSnpReader(_renamer);
var dbSnpItems = dbsnpReader.ExtractItem(vcfLine1);
var dbSnpItem2 = dbsnpReader.ExtractItem(vcfLine2)[0];
var additionalItems = dbSnpItems.Select(dbSnpItem => dbSnpItem.SetSupplementaryAnnotations(sa1)).ToList();
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa1);
}
additionalItems.Clear();
additionalItems.Add(dbSnpItem2.SetSupplementaryAnnotations(sa2));
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa2);
}
sa1.MergeSaCreator(sa2);
var expectedDbSnp = new List <long> {
3118506, 368645009
};
var dbSnp =
sa1.SaPosition.AlleleSpecificAnnotations["1"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.DbSnp)] as
DbSnpAnnotation;
Assert.NotNull(dbSnp);
Assert.Equal(expectedDbSnp, dbSnp.DbSnp);
}
public void MultiEntryMixedVariant()
{
var sa1 = new SupplementaryPositionCreator();
var oneKItem1 = _oneKGenReader.ExtractItems(VcfLine5)[0];
var oneKItem2 = _oneKGenReader.ExtractItems(VcfLine6)[0];
oneKItem1.SetSupplementaryAnnotations(sa1);
// additional items are ignored since they cannot be SNVs
var sa2 = new SupplementaryPositionCreator();
oneKItem2.SetSupplementaryAnnotations(sa2);
sa1.MergeSaCreator(sa2);
sa1.FinalizePositionalAnnotations();
Assert.True(sa1.IsRefMinor());
}
public void RefMinorNonSnv()
{
// NIR-903
const string vcfLine1 =
"X 1619046 . C A 100 PASS AC=2620;AF=0.53163;AN=5008;NS=2504;DP=15896;AMR_AF=0.6412;AFR_AF=0.1415;EUR_AF=0.6153;SAS_AF=0.5419;EAS_AF=0.8323;AA=c|||;VT=SNP";
const string vcfLine2 =
"X 1619046 . C AG 100 PASS AC=2163,730;AF=0.431909;AN=5008;NS=2504;DP=15896;AMR_AF=0.428;AFR_AF=0.1422;EUR_AF=0.4036;SAS_AF=0.4622;EAS_AF=0.8135;AA=c|||;VT=SNP;MULTI_ALLELIC";
var oneKItem1 = _oneKGenReader.ExtractItems(vcfLine1)[0];
var oneKItem2 = _oneKGenReader.ExtractItems(vcfLine2)[0];
var sa1 = new SupplementaryPositionCreator();
var sa2 = new SupplementaryPositionCreator();
oneKItem1.SetSupplementaryAnnotations(sa1);
oneKItem2.SetSupplementaryAnnotations(sa2);
sa1.MergeSaCreator(sa2);
Assert.False(sa1.IsRefMinor());
}
public void BadRefMinor()
{
// NIR-903
const string vcfLine1 =
"X 1619046 . C A 100 PASS AC=2620;AF=0.523163;AN=5008;NS=2504;DP=15896;AMR_AF=0.6412;AFR_AF=0.1415;EUR_AF=0.6153;SAS_AF=0.5419;EAS_AF=0.8323;AA=c|||;VT=SNP";
const string vcfLine2 =
"X 1619046 . C A,G 100 PASS AC=2163,730;AF=0.431909,0.145767;AN=5008;NS=2504;DP=15896;AMR_AF=0.428,0.3372;AFR_AF=0.1422,0.0159;EUR_AF=0.4036,0.3419;SAS_AF=0.4622,0.1299;EAS_AF=0.8135,0.004;AA=c|||;VT=SNP;MULTI_ALLELIC";
var sa1 = new SupplementaryPositionCreator();
var sa2 = new SupplementaryPositionCreator();
foreach (var oneKitem in _oneKGenReader.ExtractItems(vcfLine1))
{
oneKitem.SetSupplementaryAnnotations(sa1);
}
foreach (var oneKitem in _oneKGenReader.ExtractItems(vcfLine2))
{
oneKitem.SetSupplementaryAnnotations(sa2);
}
sa1.MergeSaCreator(sa2);
Assert.False(sa1.IsRefMinor());
var oneKgG =
sa1.SaPosition.AlleleSpecificAnnotations["G"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)]
as OneKGenAnnotation;
var oneKgA =
sa1.SaPosition.AlleleSpecificAnnotations["A"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)]
as OneKGenAnnotation;
Assert.NotNull(oneKgG);
Assert.NotNull(oneKgA);
// all onek entries should also be cleared
Assert.True(oneKgA.HasConflicts);
Assert.False(oneKgG.HasConflicts);
Assert.Equal("0.145767", GetAlleleFrequency(oneKgG.OneKgAllAn, oneKgG.OneKgAllAc));
}
public void MergeConflictingOneKitems()
{
const string vcfLine1 =
"1 11408760 rs112877363 CTATG C 100 PASS AC=6;AF=0.00119808;AN=5008;NS=2504;DP=23213;EAS_AF=0;AMR_AF=0;AFR_AF=0.0045;EUR_AF=0;SAS_AF=0";
const string vcfLine2 =
"1 11408760 rs59160279 CTATG CTATGTATG,C 100 PASS AC=174,763;AF=0.0347444,0.152356;AN=5008;NS=2504;DP=23213;EAS_AF=0.0069,0.0615;AMR_AF=0.0259,0.062;AFR_AF=0.0749,0.4213;EUR_AF=0.0378,0.0239;SAS_AF=0.0123,0.0787";
var sa1 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(11408761));
var sa2 = new SupplementaryPositionCreator(new SupplementaryAnnotationPosition(11408761));
var oneKitem1 = _oneKGenReader.ExtractItems(vcfLine1)[0];
var additionalItems = new List <SupplementaryDataItem>
{
oneKitem1.SetSupplementaryAnnotations(sa1)
};
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa1);
}
additionalItems.Clear();
additionalItems.AddRange(_oneKGenReader.ExtractItems(vcfLine2).Select(oneKitem => oneKitem.SetSupplementaryAnnotations(sa2)));
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa2);
}
sa1.MergeSaCreator(sa2);
var oneKg =
sa1.SaPosition.AlleleSpecificAnnotations["4"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)] as
OneKGenAnnotation;
Assert.NotNull(oneKg);
// For conflicting entries, we clear all fields
Assert.True(oneKg.HasConflicts);
}
public void DiscardConflictingOneKitems()
{
// NIR-1147
const string vcfLine1 = "22 17996285 rs35048606 A ATCTC 100 PASS AC=12;AF=0.00239617;AN=5008;NS=2504;DP=19702;EAS_AF=0.0119;AMR_AF=0;AFR_AF=0;EUR_AF=0;SAS_AF=0;VT=INDEL";
const string vcfLine2 = "22 17996285 rs35048606;rs5746424 A ATCTC,C 100 PASS AC=3444,1141;AF=0.6877,0.227835;AN=5008;NS=2504;DP=19702;EAS_AF=0.497,0.4544;AMR_AF=0.6354,0.2205;AFR_AF=0.798,0.1815;EUR_AF=0.7068,0.1233;SAS_AF=0.7526,0.1697;VT=SNP,INDEL;MULTI_ALLELIC";
var sa1 = new SupplementaryPositionCreator();
var sa2 = new SupplementaryPositionCreator();
var oneKitem1 = _oneKGenReader.ExtractItems(vcfLine1)[0];
var additionalItems = new List <SupplementaryDataItem>
{
oneKitem1.SetSupplementaryAnnotations(sa1)
};
foreach (var item in additionalItems)
{
item.SetSupplementaryAnnotations(sa1);
}
additionalItems.Clear();
additionalItems.AddRange(_oneKGenReader.ExtractItems(vcfLine2).Select(oneKitem => oneKitem.SetSupplementaryAnnotations(sa2)));
foreach (var item in additionalItems)
{
item?.SetSupplementaryAnnotations(sa2);
}
sa1.MergeSaCreator(sa2);
var oneKg =
sa1.SaPosition.AlleleSpecificAnnotations["iTCTC"].Annotations[DataSourceCommon.GetIndex(DataSourceCommon.DataSource.OneKg)] as
OneKGenAnnotation;
Assert.NotNull(oneKg);
// in some cases, the merge happens using setSupplementaryAnnotation(). this unit test checks if that path is ok
Assert.True(oneKg.HasConflicts);
}
public void CreateDatabase()
{
var unsorted = 0;
_creationBench = new Benchmark();
_prevSaCreator = null;
// loading ref sequence
var saCreator = GetNextSupplementaryAnnotation();
while (saCreator != null)
{
if (!_currentRefName.Equals(saCreator.RefSeqName)) //sanity check
{
throw new Exception("Error: currentRef != sa ref");
}
if (_saWriter == null) //check for empty writer
{
Console.WriteLine("Supplementary annotationa writer was not initialized");
return;
}
// this SA is not the first one in current contig
if (_prevSaCreator != null)
{
if (saCreator.ReferencePosition == _prevSaCreator.ReferencePosition)
{
_prevSaCreator.MergeSaCreator(saCreator);
}
else
{
if (_prevSaCreator.RefSeqName == saCreator.RefSeqName && _prevSaCreator.ReferencePosition > saCreator.ReferencePosition)
{
Console.WriteLine("Unsorted records:{0}, {1}, {2}, {3}", _prevSaCreator.RefSeqName,
_prevSaCreator.ReferencePosition, saCreator.RefSeqName, saCreator.ReferencePosition);
unsorted++;
}
if (!_prevSaCreator.IsEmpty())
{
_saWriter.Write(_prevSaCreator, _prevSaCreator.ReferencePosition);
_numSaWritten++;
}
_prevSaCreator = saCreator;
}
}
else
{
_prevSaCreator = saCreator;
}
saCreator = GetNextSupplementaryAnnotation();
}
// do not forgot to write the last item
CloseCurrentSaWriter();
Console.WriteLine("");
Console.WriteLine("unsorted records: {0}", unsorted);
}