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 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 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 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 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 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 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 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 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 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));
}
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 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 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 MultiAlleleTest()
{
var sa = new SupplementaryAnnotationPosition(4634317);
var oneKg1 = new OneKGenAnnotation
{
AncestralAllele = "C",
OneKgAllAn = 5008,
OneKgAllAc = 2049
};
var oneKg2 = new OneKGenAnnotation
{
AncestralAllele = "C",
OneKgAllAn = 5008,
OneKgAllAc = 1200
};
var dbSnp = new DbSnpAnnotation
{
DbSnp = new List <long> {
11078537
}
};
var saCreator = new SupplementaryPositionCreator(sa);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, "A", dbSnp);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.DbSnp, "T", dbSnp);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.OneKg, "A", oneKg1);
saCreator.AddExternalDataToAsa(DataSourceCommon.DataSource.OneKg, "T", oneKg2);
var saReader = new MockSupplementaryAnnotationReader(sa);
VcfUtilities.FieldContains(saReader,
"17\t4634317\trs11078537\tC\tA,T\t256\tPASS\t.\tGT\t0/1", "AF1000G=0.409145,0.239617", VcfCommon.InfoIndex);
}
