public void Right_Identity_WhenRefSequenceNull()
{
var originalVariant = GetDeletion();
var rotatedVariant = VariantRotator.Right(originalVariant, null, null, false);
Assert.True(ReferenceEquals(originalVariant, rotatedVariant));
}
public void Right_Identity_WhenNotInsertionOrDeletion()
{
var originalVariant = new SimpleVariant(ChromosomeUtilities.Chr1, 966392, 966392, "T", "A", VariantType.SNV);
var rotated = VariantRotator.Right(originalVariant, null, _refSequence, false);
Assert.True(ReferenceEquals(originalVariant, rotated));
}
public static IAnnotatedTranscript GetAnnotatedTranscript(ITranscript transcript, IVariant leftShiftedVariant,
ISequence refSequence, IPredictionCache siftCache, IPredictionCache polyphenCache, AminoAcids aminoAcids)
{
var rightShiftedVariant = VariantRotator.Right(leftShiftedVariant, transcript, refSequence,
transcript.Gene.OnReverseStrand);
var leftAnnotation = AnnotateTranscript(transcript, leftShiftedVariant, aminoAcids, refSequence);
var rightAnnotation = ReferenceEquals(leftShiftedVariant, rightShiftedVariant)
? leftAnnotation
: AnnotateTranscript(transcript, rightShiftedVariant, aminoAcids, refSequence);
var consequences = GetConsequences(transcript, leftShiftedVariant, leftAnnotation.VariantEffect);
var hgvsCoding = HgvsCodingNomenclature.GetHgvscAnnotation(transcript, rightShiftedVariant, refSequence,
rightAnnotation.Position.RegionStartIndex, rightAnnotation.Position.RegionEndIndex);
var hgvsProtein = HgvsProteinNomenclature.GetHgvsProteinAnnotation(transcript,
rightAnnotation.RefAminoAcids, rightAnnotation.AltAminoAcids, rightAnnotation.TranscriptAltAllele,
rightAnnotation.Position, rightAnnotation.VariantEffect, rightShiftedVariant, refSequence, hgvsCoding,
leftShiftedVariant.Chromosome.UcscName == "chrM");
var predictionScores = GetPredictionScores(leftAnnotation.Position, leftAnnotation.RefAminoAcids,
leftAnnotation.AltAminoAcids, siftCache, polyphenCache, transcript.SiftIndex, transcript.PolyPhenIndex);
return(new AnnotatedTranscript(transcript, leftAnnotation.RefAminoAcids, leftAnnotation.AltAminoAcids,
leftAnnotation.RefCodons, leftAnnotation.AltCodons, leftAnnotation.Position, hgvsCoding, hgvsProtein,
predictionScores.Sift, predictionScores.PolyPhen, consequences, false));
}
public void Right_Identity_WhenNotInsertionOrDeletion()
{
var originalVariant = GetDeletion();
originalVariant.SetupGet(x => x.Type).Returns(VariantType.SNV);
var rotated = VariantRotator.Right(originalVariant.Object, null, _refSequence, false);
Assert.True(ReferenceEquals(originalVariant.Object, rotated));
}
public void Right_Identity_VariantBeforeTranscript_ForwardStrand()
{
var originalVariant = GetDeletion();
var transcript = new Mock <ITranscript>();
transcript.SetupGet(x => x.Start).Returns(966397);
transcript.SetupGet(x => x.Gene.OnReverseStrand).Returns(false);
var rotated = VariantRotator.Right(originalVariant, transcript.Object, _refSequence, transcript.Object.Gene.OnReverseStrand);
Assert.True(ReferenceEquals(originalVariant, rotated));
}
public void Right_Insertion()
{
var variant = GetInsertion();
var transcript = new Mock <ITranscript>();
transcript.SetupGet(x => x.Start).Returns(966300);
transcript.SetupGet(x => x.End).Returns(966405);
transcript.SetupGet(x => x.Gene.OnReverseStrand).Returns(false);
var rotated = VariantRotator.Right(variant, transcript.Object, _refSequence, transcript.Object.Gene.OnReverseStrand);
Assert.False(ReferenceEquals(variant, rotated));
Assert.Equal(966403, rotated.Start);
Assert.Equal("TG", rotated.AltAllele);
}
public void Right_Deletion_ReverseStrand()
{
var variant = new SimpleVariant(ChromosomeUtilities.Chr1, 966399, 966401, "TG", "", VariantType.deletion);
var transcript = new Mock <ITranscript>();
transcript.SetupGet(x => x.Start).Returns(966300);
transcript.SetupGet(x => x.End).Returns(966405);
transcript.SetupGet(x => x.Gene.OnReverseStrand).Returns(true);
var rotatedVariant = VariantRotator.Right(variant, transcript.Object, _refSequence, transcript.Object.Gene.OnReverseStrand);
Assert.False(ReferenceEquals(variant, rotatedVariant));
Assert.Equal(966393, rotatedVariant.Start);
Assert.Equal("TG", rotatedVariant.RefAllele);
}
public void Right_Deletion_ForwardStrand()
{
// chr1 966391 . ATG A 2694.00 PASS .
var variant = GetDeletion();
var transcript = new Mock <ITranscript>();
transcript.SetupGet(x => x.Start).Returns(966300);
transcript.SetupGet(x => x.End).Returns(966405);
transcript.SetupGet(x => x.Gene.OnReverseStrand).Returns(false);
var rotatedVariant = VariantRotator.Right(variant, transcript.Object, _refSequence, transcript.Object.Gene.OnReverseStrand);
Assert.False(ReferenceEquals(variant, rotatedVariant));
Assert.Equal(966400, rotatedVariant.Start);
Assert.Equal("TG", rotatedVariant.RefAllele);
}
public void Right_Identity_WithNoRotation()
{
var originalVariant = GetDeletion();
ISequence refSequence = new SimpleSequence(
new string('A', VariantRotator.MaxDownstreamLength) + "GAGAGTTAGGTA" +
new string('A', VariantRotator.MaxDownstreamLength), 965891);
var transcript = new Mock <ITranscript>();
transcript.SetupGet(x => x.Start).Returns(966300);
transcript.SetupGet(x => x.End).Returns(966405);
transcript.SetupGet(x => x.Gene.OnReverseStrand).Returns(false);
var rotated = VariantRotator.Right(originalVariant, transcript.Object, refSequence, transcript.Object.Gene.OnReverseStrand);
Assert.True(ReferenceEquals(originalVariant, rotated));
}
public static string GetNotation(string refseqAccession, ISimpleVariant variant, ISequence refSequence,
IInterval referenceInterval)
{
var rotatedVariant = VariantRotator.Right(variant, referenceInterval, refSequence, false);
var start = Math.Min(rotatedVariant.Start, rotatedVariant.End);
var end = Math.Max(rotatedVariant.Start, rotatedVariant.End);
var referenceBases = rotatedVariant.RefAllele;
var alternateBases = rotatedVariant.AltAllele;
var type = HgvsCodingNomenclature.GetGenomicChange(referenceInterval, false, refSequence, rotatedVariant);
if (type == GenomicChange.Duplication && variant.Type == VariantType.insertion)
{
referenceBases = alternateBases;
end = start;
start = end - referenceBases.Length + 1;
}
return(HgvsUtilities.FormatDnaNotation(start.ToString(), end.ToString(), refseqAccession, referenceBases, alternateBases, type, NotationType));
}
