public void OneAlleleFreqMissing()
{
var sa = new SupplementaryAnnotationPosition(825069);
var saCreator = new SupplementaryPositionCreator(sa);
var dbSnp = new DbSnpAnnotation
{
DbSnp = new List <long> {
4475692
}
};
var oneKg = new OneKGenAnnotation
{
OneKgAllAn = 5008,
OneKgAllAc = 3392
};
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, "C", dbSnp);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.OneKg, "C", oneKg);
var saReader = new MockSupplementaryAnnotationReader(sa);
VcfUtilities.FieldContains(saReader,
"chr1 825069 rs4475692 G A,C 362.00 LowGQX;HighDPFRatio SNVSB=-36.9;SNVHPOL=3 GT:GQ:GQX:DP:DPF:AD 1/2:4:0:52:38:8,11,33",
"AF1000G=.,0.677316", VcfCommon.InfoIndex);
}
public void UpstreamGeneVariant()
{
var sa = new SupplementaryAnnotationPosition(46107)
{
IsRefMinorAllele = true,
GlobalMajorAllele = "G",
GlobalMajorAlleleFrequency = "0.9029",
GlobalMinorAllele = "A",
GlobalMinorAlleleFrequency = "0.0971"
};
var saReader = new MockSupplementaryAnnotationReader(sa);
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000576171_chr17_Ensembl84"), saReader,
"17 46107 . A . 153 LowGQX SNVSB=-20.1;SNVHPOL=4;GMAF=G|0.9988;RefMinor;CSQT=A||ENST00000576171|upstream_gene_variant GT:GQ:GQX:DP:DPF:AD 1/1:18:18:7:0:0,7");
Assert.NotNull(annotatedVariant);
Assert.Contains("\"isReferenceMinorAllele\":true", annotatedVariant.ToString());
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.FirstOrDefault();
Assert.NotNull(altAllele);
const string expectedJsonLine = "{\"refAllele\":\"A\",\"begin\":46107,\"chromosome\":\"17\",\"end\":46107,\"globalMinorAllele\":\"A\",\"gmaf\":0.0971,\"isReferenceMinorAllele\":true,\"variantType\":\"SNV\",\"vid\":\"17:46107:A\",\"transcripts\":{\"ensembl\":[{\"transcript\":\"ENST00000576171.1\",\"bioType\":\"lincRNA\",\"geneId\":\"ENSG00000273172\",\"hgnc\":\"AC108004.2\",\"consequence\":[\"upstream_gene_variant\"],\"isCanonical\":true}]}}";
// ReSharper disable once PossibleNullReferenceException
Assert.Equal(expectedJsonLine, altAllele.ToString());
}
public void IntergenicVariant()
{
var sa = new SupplementaryAnnotationPosition(47960)
{
IsRefMinorAllele = true,
GlobalMajorAllele = "A",
GlobalMajorAlleleFrequency = "0.9239"
};
var saReader = new MockSupplementaryAnnotationReader(sa);
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000518655_chr1_Ensembl84"), saReader,
"chr1 47960 . T . 1242.00 PASS SNVSB=-87.0;SNVHPOL=3");
Assert.NotNull(annotatedVariant);
Assert.Contains("\"isReferenceMinorAllele\":true", annotatedVariant.ToString());
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.FirstOrDefault();
Assert.NotNull(altAllele);
// intergenic variant are not exposed in the JSON file
AssertUtilities.CheckEnsemblTranscriptCount(0, altAllele);
AssertUtilities.CheckRefSeqTranscriptCount(0, altAllele);
}
public void MultiVariantEntry()
{
var reader = new ClinVarXmlReader(new FileInfo(Resources.TopPath("RCV000007484.xml")), _reader, _sequence);
foreach (var clinVarItem in reader)
{
switch (clinVarItem.Start)
{
case 8045031:
Assert.Equal("G", clinVarItem.ReferenceAllele);
Assert.Equal("A", clinVarItem.AltAllele);
break;
case 8021911:
Assert.Equal("GTGCTGGACGGTGTCCCT", clinVarItem.AltAllele);
var sa = new SupplementaryAnnotationPosition(clinVarItem.Start);
var saCreator = new SupplementaryPositionCreator(sa);
clinVarItem.SetSupplementaryAnnotations(saCreator);
Assert.Equal("iGTGCTGGACGGTGTCCCT", clinVarItem.SaAltAllele);
break;
default:
throw new InvalidDataException($"Unexpected clinvar item start point : {clinVarItem.Start}");
}
}
}
public void EvsOutputTest()
{
var sa = new SupplementaryAnnotationPosition(115256529);
var dbSnp = new DbSnpAnnotation
{
DbSnp = new List <long> {
121913237
}
};
var evs = new EvsAnnotation
{
EvsAll = "0.0001",
EvsCoverage = "102",
NumEvsSamples = "3456"
};
var saCreator = new SupplementaryPositionCreator(sa);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.Evs, "C", evs);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, "C", dbSnp);
var saReader = new MockSupplementaryAnnotationReader(sa);
VcfUtilities.FieldContains(saReader,
"chr1\t115256529\t.\tT\tC\t1000\tPASS\t.\tGT\t0/1", "EVS=0.0001|102|3456", VcfCommon.InfoIndex);
}
public void AlleleFrequency1KgOutputTest()
{
var sa = new SupplementaryAnnotationPosition(115256529);
var oneKg = new OneKGenAnnotation
{
OneKgAllAn = 5008,
OneKgAllAc = 2130,
OneKgAmrAn = 694,
OneKgAmrAc = 250
};
var dbSnp = new DbSnpAnnotation
{
DbSnp = new List <long> {
11554290
}
};
var saCreator = new SupplementaryPositionCreator(sa);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.OneKg, "C", oneKg);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, "C", dbSnp);
var saReader = new MockSupplementaryAnnotationReader(sa);
VcfUtilities.FieldContains(saReader,
"chr1\t115256529\t.\tT\tC\t1000\tPASS\t.\tGT\t0/1", "AF1000G=0.425319", VcfCommon.InfoIndex);
}
public void CosmicOutputTest()
{
var sa = new SupplementaryAnnotationPosition(115256529);
var saCreator = new SupplementaryPositionCreator(sa);
var altAllele = "C";
var cosmicItem1 = new CosmicItem("chr1", 115256529, "COSM1000", "T", altAllele, "TP53",
new HashSet <CosmicItem.CosmicStudy> {
new CosmicItem.CosmicStudy("", "carcinoma", "oesophagus")
}, 1,
altAllele);
var cosmicItem2 = new CosmicItem("chr1", 115256529, "COSM1001", "T", altAllele, "TP53",
new HashSet <CosmicItem.CosmicStudy> {
new CosmicItem.CosmicStudy("01", "carcinoma", "large_intestine")
}, 1,
altAllele);
cosmicItem1.AddCosmicToSa(saCreator);
cosmicItem2.AddCosmicToSa(saCreator);
var saReader = new MockSupplementaryAnnotationReader(sa);
VcfUtilities.FieldContains(saReader,
"chr1\t115256529\t.\tT\tC\t1000\tPASS\t.\tGT\t0/1", "cosmic=1|COSM1000", VcfCommon.InfoIndex);
}
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;
}
/// <summary>
/// reads the supplementary annotation from disk
/// </summary>
private static SupplementaryAnnotationPosition Read(ExtendedBinaryReader reader, int referencePos)
{
var sa = new SupplementaryAnnotationPosition(referencePos);
SupplementaryAnnotationPosition.Read(reader, sa);
return(sa);
}
public void AllSuppAnnotOutputTest()
{
const string altAllele = "C";
var sa = new SupplementaryAnnotationPosition(115256529);
var oneKg = new OneKGenAnnotation
{
OneKgAllAn = 5008,
OneKgAllAc = 2130,
OneKgAmrAn = 694,
OneKgAmrAc = 250
};
var dbSnp = new DbSnpAnnotation
{
DbSnp = new List <long> {
11554290
}
};
var saCreator = new SupplementaryPositionCreator(sa);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.OneKg, "C", oneKg);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, "C", dbSnp);
var cosmicItem1 = new CosmicItem("chr1", 115256529, "COSM1000", "T", altAllele, "TP53",
new HashSet <CosmicItem.CosmicStudy> {
new CosmicItem.CosmicStudy("", "carcinoma", "oesophagus")
}, 1,
altAllele);
var cosmicItem2 = new CosmicItem("chr1", 115256529, "COSM1001", "T", altAllele, "TP53",
new HashSet <CosmicItem.CosmicStudy> {
new CosmicItem.CosmicStudy("01", "carcinoma", "large_intestine")
}, 1,
altAllele);
cosmicItem1.AddCosmicToSa(saCreator);
cosmicItem2.AddCosmicToSa(saCreator);
var clinvarItem1 = new ClinVarItem(null, 0, null, altAllele, null, "RCV001",
null, null, new List <string> {
"ORPHA2462"
}, null, null, "other");
sa.ClinVarItems.Add(clinvarItem1);
var saReader = new MockSupplementaryAnnotationReader(sa);
var infoColumn = VcfUtilities.GetVcfColumn(saReader,
"chr1\t115256529\t.\tT\tC\t1000\tPASS\t.\tGT\t0/1", VcfCommon.InfoIndex);
Assert.Contains("AF1000G=0.425319", infoColumn);
Assert.Contains("cosmic=1|COSM1000,1|COSM1001", infoColumn);
Assert.Contains("clinvar=1|other", infoColumn);
}
public void RwDbsnpGlobalAlleles()
{
//NIR-1262
var randomPath = Path.Combine(Path.GetTempPath(), Path.GetRandomFileName());
// create our expected data source versions
var dbSnpVersion = new DataSourceVersion("dbSNP", "147", DateTime.Parse("2016-07-26").Ticks);
var expectedDataSourceVersions = new List <DataSourceVersion> {
dbSnpVersion
};
const string vcfLine1 =
"2 141724543 rs112783784 A C,T . . RS=112783784;RSPOS=141724543;dbSNPBuildID=132;SSR=0;SAO=0;VP=0x050100080015140136000100;WGT=1;VC=SNV;SLO;INT;OTH;ASP;VLD;GNO;KGPhase1;KGPhase3;CAF=0.04113,0.9105,0.04832;COMMON=1";
const string vcfLine2 =
"2 141724543 rs4300776 A C . . RS=4300776;RSPOS=141724543;dbSNPBuildID=111;SSR=0;SAO=0;VP=0x050100080015000102000100;WGT=1;VC=SNV;SLO;INT;OTH;ASP;GNO;CAF=0.04113,0.9105;COMMON=1";
var sa = new SupplementaryAnnotationPosition(141724543);
var saCreator = new SupplementaryPositionCreator(sa);
var dbsnpReader = new DbSnpReader(_renamer);
foreach (var dbSnpItem in dbsnpReader.ExtractItem(vcfLine1))
{
dbSnpItem.SetSupplementaryAnnotations(saCreator);
}
foreach (var dbSnpItem in dbsnpReader.ExtractItem(vcfLine2))
{
dbSnpItem.SetSupplementaryAnnotations(saCreator);
}
// write the supplementary annotation file
using (var writer = new SupplementaryAnnotationWriter(randomPath, "chr1", expectedDataSourceVersions))
{
saCreator.FinalizePositionalAnnotations();
writer.Write(saCreator, sa.ReferencePosition);
}
using (var reader = new SupplementaryAnnotationReader(randomPath))
{
// extract the three annotations
var observedAnnotation = reader.GetAnnotation(141724543) as SupplementaryAnnotationPosition;
Assert.NotNull(observedAnnotation);
Assert.Equal("C", observedAnnotation.GlobalMajorAllele);
Assert.Equal("0.9105", observedAnnotation.GlobalMajorAlleleFrequency);
Assert.Equal("T", observedAnnotation.GlobalMinorAllele);
Assert.Equal("0.04832", observedAnnotation.GlobalMinorAlleleFrequency);
}
File.Delete(randomPath);
File.Delete(randomPath + ".idx");
}
public void ReadWriteCustomAnnotation()
{
var randomPath = GetRandomPath(true);
// 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 customFile = new FileInfo(Resources.TopPath("customCosmic.vcf"));
var customReader = new CustomAnnotationReader(customFile, _renamer);
// all items from this file should be of type cosmic.
var customItems = customReader.ToList();
var sa = new SupplementaryAnnotationPosition(69224);
var saCreator = new SupplementaryPositionCreator(sa);
foreach (var customItem in customItems)
{
// NOTE that the two custom items are for different position, but for the purpose of our test, this is not an issue.
customItem.SetSupplementaryAnnotations(saCreator);
}
// the above code was unit tested in MergeDbSnpClinVar()
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(69224);
Assert.NotNull(observedAnnotation1);
for (var i = 0; i < sa.CustomItems.Count; i++)
{
Assert.Equal(sa.CustomItems[i].Id, observedAnnotation1.CustomItems[i].Id);
Assert.Equal(sa.CustomItems[i].AnnotationType, observedAnnotation1.CustomItems[i].AnnotationType);
Assert.Equal(sa.CustomItems[i].IsAlleleSpecific, observedAnnotation1.CustomItems[i].IsAlleleSpecific);
Assert.True(sa.CustomItems[i].StringFields.SequenceEqual(observedAnnotation1.CustomItems[i].StringFields));
if (sa.CustomItems[i].BooleanFields.Count > 0)
{
Assert.True(sa.CustomItems[i].BooleanFields.SequenceEqual(observedAnnotation1.CustomItems[i].BooleanFields));
}
}
}
}
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");
}
/// <summary>
/// constructor
/// </summary>
public SaReadWriteTests(ChromosomeRenamerFixture fixture)
{
_renamer = fixture.Renamer;
_sequence = fixture.Sequence;
_reader = fixture.Reader;
// create our expected data source versions
_expectedDataSourceVersion = new DataSourceVersion("ClinVar", "13.5", DateTime.Parse("2015-01-19").Ticks);
_expectedDataSourceVersions = new List <DataSourceVersion> {
_expectedDataSourceVersion
};
// create our expected supplementary annotations
var dbSnp1 = new DbSnpAnnotation
{
DbSnp = new List <long> {
1
}
};
_expectedAnnotation1 = new SupplementaryAnnotationPosition(100);
new SupplementaryPositionCreator(_expectedAnnotation1).AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, AltAllele, dbSnp1);
var dbSnp2 = new DbSnpAnnotation
{
DbSnp = new List <long> {
2
}
};
_expectedAnnotation2 = new SupplementaryAnnotationPosition(101);
new SupplementaryPositionCreator(_expectedAnnotation2).AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, AltAllele, dbSnp2);
var dbSnp3 = new DbSnpAnnotation
{
DbSnp = new List <long> {
3
}
};
_expectedAnnotation3 = new SupplementaryAnnotationPosition(102);
new SupplementaryPositionCreator(_expectedAnnotation3).AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, AltAllele, dbSnp3);
_expectedInterval = new SupplementaryInterval(1, 1000, "chr1", null, VariantType.copy_number_variation, null, _renamer);
_randomPath = Path.Combine(Path.GetTempPath(), Path.GetRandomFileName());
// write the supplementary annotation file
WriteSupplementaryAnnotationFile(_randomPath);
}
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 ClinVarOutputTest()
{
var sa = new SupplementaryAnnotationPosition(115256529);
var clinvarItem1 = new ClinVarItem(null, 0, null, "C", null, "RCV001",
null, null, new List <string> {
"ORPHA2462"
}, null, null, "other");
sa.ClinVarItems.Add(clinvarItem1);
var saReader = new MockSupplementaryAnnotationReader(sa);
VcfUtilities.FieldContains(saReader,
"chr1\t115256529\t.\tT\tC\t1000\tPASS\t.\tGT\t0/1", "clinvar=1|other", VcfCommon.InfoIndex);
}
public void NullVcfFieldTest()
{
var sa = new SupplementaryAnnotationPosition(9580071);
var dbSnp = new DbSnpAnnotation
{
DbSnp = null
};
var saCreator = new SupplementaryPositionCreator(sa);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, "T", dbSnp);
var saReader = new MockSupplementaryAnnotationReader(sa);
var idColumn = VcfUtilities.GetVcfColumn(saReader,
"chr12\t9580071\t.\tA\tC,T\t394.00\tPASS\t.\tGT\t0/1", VcfCommon.IdIndex);
Assert.NotNull(idColumn);
}
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 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 DbSnpOutputTest()
{
var sa = new SupplementaryAnnotationPosition(115256529);
var dbSnp = new DbSnpAnnotation
{
DbSnp = new List <long> {
11554290
}
};
var saCreator = new SupplementaryPositionCreator(sa);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, "C", dbSnp);
var saReader = new MockSupplementaryAnnotationReader(sa);
VcfUtilities.FieldContains(saReader,
"chr1\t115256529\t.\tT\tC\t1000\tPASS\t.\tGT\t0/1", "rs11554290", VcfCommon.IdIndex);
}
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 MultipleDbSnpIds()
{
var sa = new SupplementaryAnnotationPosition(115256529);
var dbSnp = new DbSnpAnnotation
{
DbSnp = new List <long> {
111, 222, 333
}
};
var saCreator = new SupplementaryPositionCreator(sa);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, "C", dbSnp);
var saReader = new MockSupplementaryAnnotationReader(sa);
VcfUtilities.FieldContains(saReader,
"chr1\t115256529\tMantaFluff\tT\tC\t1000\tPASS\t.\tGT\t0/1", "MantaFluff;rs111;rs222;rs333",
VcfCommon.IdIndex);
}
public void MultipleDbSnpIds()
{
var sa = new SupplementaryAnnotationPosition(115256529);
var dbSnp = new DbSnpAnnotation
{
DbSnp = new List <long> {
111, 222, 333
}
};
var saCreator = new SupplementaryPositionCreator(sa);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, "C", dbSnp);
var saReader = new MockSupplementaryAnnotationReader(sa);
var annotatedVariant = DataUtilities.GetVariant(DataUtilities.EmptyCachePrefix, saReader, "chr1 115256529 . T C 1000 PASS . GT 0/1");
Assert.NotNull(annotatedVariant);
Assert.Contains("\"dbsnp\":[\"rs111\",\"rs222\",\"rs333\"]", annotatedVariant.ToString());
}
public void SynonymousVariant()
{
var sa = new SupplementaryAnnotationPosition(115258746)
{
IsRefMinorAllele = true,
GlobalMajorAllele = "G",
GlobalMajorAlleleFrequency = "0.8239"
};
var saReader = new MockSupplementaryAnnotationReader(sa);
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000369535_chr1_Ensembl84"), saReader,
"chr1 115258746 . A . 265.00 PASS SNVSB=-31.9;SNVHPOL=2 GT:GQ:GQX:DP:DPF:AD 0/1:254:40:56:1:26,30");
Assert.NotNull(annotatedVariant);
Assert.Contains("\"isReferenceMinorAllele\":true", annotatedVariant.ToString());
var transcriptAllele = annotatedVariant.AnnotatedAlternateAlleles.FirstOrDefault()?.EnsemblTranscripts.FirstOrDefault();
Assert.NotNull(transcriptAllele);
// ReSharper disable once PossibleNullReferenceException
Assert.Equal("synonymous_variant", string.Join("&", transcriptAllele.Consequence));
}
public void IndelWithNoLeadingBase()
{
var cosmicReader = new MergedCosmicReader();
const string vcfLine1 = "3 10188320 COSM14426 GGTACTGAC A . . GENE=VHL;STRAND=+;CDS=c.463G>A;AA=p.?;CNT=2";
const string vcfLine2 = "3 10188320 COSM18152 G A . . GENE=VHL;STRAND=+;CDS=c.463G>A;AA=p.V155M;CNT=7";
var sa = new SupplementaryAnnotationPosition(10188320);
var saCreator = new SupplementaryPositionCreator(sa);
foreach (var cosmicItem in cosmicReader.ExtractCosmicItems(vcfLine1))
{
cosmicItem.SetSupplementaryAnnotations(saCreator);
}
Assert.Equal("9A", sa.CosmicItems[0].SaAltAllele);
foreach (var cosmicItem in cosmicReader.ExtractCosmicItems(vcfLine2))
{
cosmicItem.SetSupplementaryAnnotations(saCreator);
}
Assert.Equal("A", sa.CosmicItems[1].SaAltAllele);
}
public void SpliceVariants()
{
var sa = new SupplementaryAnnotationPosition(889158)
{
IsRefMinorAllele = true,
GlobalMajorAllele = "G",
GlobalMajorAlleleFrequency = "0.8239"
};
var saReader = new MockSupplementaryAnnotationReader(sa);
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000327044_chr1_Ensembl84"), saReader,
"chr1 889158 . C . 1243.00 PASS SNVSB=-130.5;SNVHPOL=3;CSQ=C|ENSG00000188976|ENST00000327044|Transcript|splice_region_variant&intron_variant|||||||CCDS3.1|ENST00000327044.6:c.888+4C>G|||YES|||ENSP00000317992|||8/18|NOC2L||||| GT:GQ:GQX:DP:DPF:AD 1/1:313:26:105:9:0,105");
Assert.NotNull(annotatedVariant);
Assert.Contains("\"isReferenceMinorAllele\":true", annotatedVariant.ToString());
var transcriptAllele = annotatedVariant.AnnotatedAlternateAlleles.FirstOrDefault()?.EnsemblTranscripts.FirstOrDefault();
Assert.NotNull(transcriptAllele);
// ReSharper disable once PossibleNullReferenceException
Assert.Equal("splice_region_variant&intron_variant", string.Join("&", transcriptAllele.Consequence));
}
public void StartLost()
{
var sa = new SupplementaryAnnotationPosition(1558792)
{
IsRefMinorAllele = true,
GlobalMajorAllele = "C",
GlobalMajorAlleleFrequency = "0.9239"
};
var saReader = new MockSupplementaryAnnotationReader(sa);
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000487053_chr1_Ensembl84"), saReader,
"chr1 1558792 . T . 1242.00 PASS SNVSB=-87.0;SNVHPOL=3;CSQ=C|ENSG00000197530|ENST00000487053|Transcript|initiator_codon_variant&NMD_transcript_variant|353|2|1|M/T|aTg/aCg|||ENST00000487053.1:c.2T>C|ENSP00000424615.1:p.Met1?|deleterious(0)||benign(0.036)||ENSP00000424615||3/21||MIB2|||||");
Assert.NotNull(annotatedVariant);
Assert.Contains("\"isReferenceMinorAllele\":true", annotatedVariant.ToString());
var transcriptAllele = annotatedVariant.AnnotatedAlternateAlleles.FirstOrDefault()?.EnsemblTranscripts.FirstOrDefault();
Assert.NotNull(transcriptAllele);
// ReSharper disable once PossibleNullReferenceException
Assert.Equal("start_lost&NMD_transcript_variant", string.Join("&", transcriptAllele.Consequence));
}
public void IntronVariant()
{
var sa = new SupplementaryAnnotationPosition(13302)
{
IsRefMinorAllele = true,
GlobalMajorAllele = "T",
GlobalMajorAlleleFrequency = "0.9239"
};
var saReader = new MockSupplementaryAnnotationReader(sa);
var annotatedVariant = DataUtilities.GetVariant(Resources.CacheGRCh37("ENST00000518655_chr1_Ensembl84"), saReader,
"chr1 13302 . C . 1242.00 PASS SNVSB=-87.0;SNVHPOL=3");
Assert.NotNull(annotatedVariant);
Assert.Contains("\"isReferenceMinorAllele\":true", annotatedVariant.ToString());
var transcriptAllele = annotatedVariant.AnnotatedAlternateAlleles.FirstOrDefault()?.EnsemblTranscripts.FirstOrDefault();
Assert.NotNull(transcriptAllele);
// ReSharper disable once PossibleNullReferenceException
Assert.Equal("intron_variant&non_coding_transcript_variant", string.Join("&", transcriptAllele.Consequence));
}
