public void AnnotationCarryover()
{
var saReader = ResourceUtilities.GetSupplementaryAnnotationReader(Resources.MiniSuppAnnot("chr2_90472571_90472592.nsa"));
var annotationSource = ResourceUtilities.GetAnnotationSource(DataUtilities.EmptyCachePrefix, saReader);
annotationSource?.EnableReferenceNoCalls(false);
var annotatedVariant = DataUtilities.GetVariant(annotationSource,
"2 90472571 . AAAAAAAAAAAAAAAAAAGTCC AGTCT 177 PASS CIGAR=1M21D4I;RU=.;REFREP=.;IDREP=. GT:GQ:GQX:DPI:AD 0/1:220:177:46:40,7");
Assert.NotNull(annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.First();
Assert.NotNull(altAllele);
Assert.False(altAllele.IsReferenceMinor);
Assert.Equal("indel", altAllele.VariantType);
Assert.Equal("2:90472572:90472592:GTCT", altAllele.VariantId);
annotatedVariant = DataUtilities.GetVariant(annotationSource,
"2 90472592 . C . . PASS RefMinor GT:GQX:DP:DPF:AD 0:96:33:15:33");
Assert.NotNull(annotatedVariant);
altAllele = annotatedVariant.AnnotatedAlternateAlleles.FirstOrDefault();
Assert.NotNull(altAllele);
Assert.True(altAllele.IsReferenceMinor);
Assert.Equal("SNV", altAllele.VariantType);
}
public void OverlappingTranscripts()
{
var annotationSource = ResourceUtilities.GetAnnotationSource(Resources.CacheGRCh37("chr1_89500_911300_Ensembl84_pos"), null) as NirvanaAnnotationSource;
annotationSource?.EnableReportAllSvOverlappingTranscripts();
var annotatedVariant = DataUtilities.GetVariant(annotationSource,
"chr1\t900000\t.\tG\t<DEL>\t.\tPASS\tEND=911300;SVTYPE=DEL");
Assert.NotNull(annotatedVariant);
var overlappingTranscriptIds =
JsonUtilities.GetOverlappingTranscriptIds(annotatedVariant.AnnotatedAlternateAlleles.First());
var expectedTranscripts = new List <string>
{
"ENST00000338591",
"ENST00000379410",
"ENST00000379409",
"ENST00000379407",
"ENST00000480267",
"ENST00000491024",
"ENST00000433179",
"ENST00000341290",
"ENST00000479361"
};
Assert.True(expectedTranscripts.OrderBy(t => t).SequenceEqual(overlappingTranscriptIds.OrderBy(t => t)));
Assert.Contains("{\"transcript\":\"ENST00000338591\",\"hgnc\":\"KLHL17\",\"isCanonical\":true,\"partialOverlap\":true}", annotatedVariant.ToString());
Assert.Contains("{\"transcript\":\"ENST00000379409\",\"hgnc\":\"PLEKHN1\"}", annotatedVariant.ToString());
}
public void NotNonCanonicalSpliceSurrReverse()
{
var annotationSource = ResourceUtilities.GetAnnotationSource(Resources.CacheGRCh37("ENST00000467459_chr1_Ensembl84"), null) as NirvanaAnnotationSource;
annotationSource?.AddPlugin(new VariantAnnotation.Loftee.Loftee());
var annotatedVariant = DataUtilities.GetVariant(annotationSource, "chr1 45797933 . G A\t.\tPASS\t.\t.\t.");
Assert.NotNull(annotatedVariant);
Assert.DoesNotContain("loftee", annotatedVariant.ToString());
}
public void NonCanonicalSpliceSurr()
{
var annotationSource = ResourceUtilities.GetAnnotationSource(Resources.CacheGRCh37("ENST00000366872_chr1_Ensembl84"), null) as NirvanaAnnotationSource;
annotationSource?.AddPlugin(new VariantAnnotation.Loftee.Loftee());
var annotatedVariant = DataUtilities.GetVariant(annotationSource, "chr1 223722780 . G A\t.\tPASS\t.\t.\t.");
Assert.NotNull(annotatedVariant);
Assert.Contains("loftee", annotatedVariant.ToString());
Assert.Contains("non_can_splice_surr", annotatedVariant.ToString());
}
public void NonCanonicalSpliceReverseStrand()
{
var annotationSource = ResourceUtilities.GetAnnotationSource(Resources.CacheGRCh37("ENST00000378156_chr1_Ensembl84"), null) as NirvanaAnnotationSource;
annotationSource?.AddPlugin(new VariantAnnotation.Loftee.Loftee());
var annotatedVariant = DataUtilities.GetVariant(annotationSource, "chr1\t5935162\t.\tA\tT\t.\tPASS\t.\t.\t.");
Assert.NotNull(annotatedVariant);
Assert.Contains("loftee", annotatedVariant.ToString());
Assert.Contains("non_can_splice", annotatedVariant.ToString());
}
public void SingleExon()
{
var annotationSource = ResourceUtilities.GetAnnotationSource(Resources.CacheGRCh37("ENST00000600779_chr1_Ensembl84"), null) as NirvanaAnnotationSource;
annotationSource?.AddPlugin(new VariantAnnotation.Loftee.Loftee());
var annotatedVariant = DataUtilities.GetVariant(annotationSource, "chr1\t2258668\t.\tGACACAGAAAC\tG\t.\tPASS\t.\t.\t.");
Assert.NotNull(annotatedVariant);
Assert.Contains("loftee", annotatedVariant.ToString());
Assert.Contains("single_exon", annotatedVariant.ToString());
}
public void NagnagSiteForwardStrand()
{
var annotationSource = ResourceUtilities.GetAnnotationSource(Resources.CacheGRCh37("ENST00000370165_chr1_Ensembl84"), null) as NirvanaAnnotationSource;
annotationSource?.AddPlugin(new VariantAnnotation.Loftee.Loftee());
var annotatedVariant = DataUtilities.GetVariant(annotationSource, "chr1\t100316589\t.\tA\tG\t.\tPASS\t.\t.\t.");
Assert.NotNull(annotatedVariant);
Assert.Contains("loftee", annotatedVariant.ToString());
Assert.Contains("nagnag_site", annotatedVariant.ToString());
Assert.Contains("bioType", annotatedVariant.ToString());
}
public void MitochondriaStopGained()
{
var annotationSource = ResourceUtilities.GetAnnotationSource(Resources.CacheGRCh37("ENST00000362079_chrM_Ensembl84"), null);
annotationSource.EnableMitochondrialAnnotation();
var annotatedVariant = DataUtilities.GetVariant(annotationSource, "chrM\t9378\t.\tG\tA\t3070.00\tPASS\t.");
Assert.NotNull(annotatedVariant);
var transcriptAllele = DataUtilities.GetTranscript(annotatedVariant, "ENST00000362079", "A");
Assert.NotNull(transcriptAllele);
Assert.Equal("stop_gained", string.Join("&", transcriptAllele.Consequence));
}
public void ReferenceNoCallsOverlapTranscript(bool enableRefNoCall, bool limitToTranscript, int numberOfAnnotatedAlleles)
{
var annotationSource = ResourceUtilities.GetAnnotationSource(Resources.CacheGRCh37("ENST00000483270_chr1_Ensembl84"), null) as NirvanaAnnotationSource;
if (enableRefNoCall)
{
annotationSource?.EnableReferenceNoCalls(limitToTranscript);
}
var annotatedVariant = DataUtilities.GetVariant(annotationSource,
"1 15886104 . C . . LowQ END=15890000 . .");
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(numberOfAnnotatedAlleles, annotatedVariant);
}
public void BasicCustomIntervalOutput()
{
var customIntervalProvider = new MockCustomIntervalProvider(ResourceUtilities.GetReadStream(Resources.CustomIntervals("chr1_IcslIntervals_69090_69091.nci")), _renamer);
var annotationSource = ResourceUtilities.GetAnnotationSource(DataUtilities.EmptyCachePrefix, null, null, customIntervalProvider);
var annotatedVariant = DataUtilities.GetVariant(annotationSource,
"chr1 69092 . T C . LowGQX;HighDPFRatio END=10244;BLOCKAVG_min30p3a GT:GQX:DP:DPF .:.:0:1");
Assert.NotNull(annotatedVariant);
const string expectedJson = "{\"altAllele\":\"C\",\"refAllele\":\"T\",\"begin\":69092,\"chromosome\":\"chr1\",\"end\":69092,\"variantType\":\"SNV\",\"vid\":\"1:69092:C\",\"IcslIntervals\":[{\"Start\":69091,\"End\":70008,\"gene\":\"OR4F5\",\"assesment\":\"Some_evidence_of_constraint\",\"score\":0.0,\"exacScore\":3.60208899915}]}";
var observedJson = JsonUtilities.GetFirstAlleleJson(annotatedVariant);
Assert.Equal(expectedJson, observedJson);
}
public void LofteeEndTruncation(bool enableLoftee, bool containLoftee)
{
var annotationSource = ResourceUtilities.GetAnnotationSource(Resources.CacheGRCh37("ENST00000369356_chr1_Ensembl84"), null) as NirvanaAnnotationSource;
if (enableLoftee)
{
annotationSource?.AddPlugin(new VariantAnnotation.Loftee.Loftee());
}
var annotatedVariant = DataUtilities.GetVariant(annotationSource, "chr1\t144852390\t.\tC\tT . LowQ . . .");
Assert.NotNull(annotatedVariant);
Assert.Equal(containLoftee, annotatedVariant.ToString().Contains("loftee"));
Assert.Equal(containLoftee, annotatedVariant.ToString().Contains("end_trunc"));
}
public void AddVariantToJsonOutputTests()
{
var customIntervals = new List <ICustomInterval>
{
new VariantAnnotation.DataStructures.CustomInterval("chr1", 118165685, 118165692, "Test", null, null)
};
var customIntervalProvider = new MockCustomIntervalProvider(customIntervals, _renamer);
var annotationSource = ResourceUtilities.GetAnnotationSource(Resources.CacheGRCh37("ENST00000006101_chr17_Ensembl84"), null, null, customIntervalProvider);
var annotatedVariant = DataUtilities.GetVariant(annotationSource,
"chr1 118165691 rs1630312 C T 156.00 PASS . GT:GQ:GQX:DP:DPF:AD 0/1:169:155:27:0:13,14");
var observedResult = annotatedVariant.ToString();
Assert.Contains("Start", observedResult);
Assert.Contains("Test", observedResult);
Assert.DoesNotContain("customIntervals", observedResult);
}
public void EnableMitochondrialAnnotation()
{
var annotationSource = ResourceUtilities.GetAnnotationSource(Resources.CacheGRCh37("ENST00000387314_chrM_Ensembl84"), null);
annotationSource.EnableMitochondrialAnnotation();
var annotatedVariant = DataUtilities.GetVariant(annotationSource, "MT 589 . C A . PASS . . .");
Assert.NotNull(annotatedVariant);
AssertUtilities.CheckAlleleCount(1, annotatedVariant);
var altAllele = annotatedVariant.AnnotatedAlternateAlleles.First();
Assert.NotNull(altAllele);
AssertUtilities.CheckEnsemblTranscriptCount(1, altAllele);
Assert.Contains("ENST00000387314", altAllele.ToString());
}