public void Assign_WhenIntervalsNull_ReturnNull()
{
var sequence = new SimpleSequence("AAA");
var codons = Codons.GetCodons("A", "G", -1, -1, -1, -1, sequence);
Assert.Equal("", codons.Reference);
Assert.Equal("", codons.Alternate);
}
public void Assign_SNV()
{
var sequence = new Mock <ISequence>();
sequence.SetupGet(x => x.Length).Returns(100);
sequence.Setup(x => x.Substring(21, 2)).Returns("CA");
var codons = Codons.GetCodons("A", "G", 24, 24, 8, 8, sequence.Object);
Assert.Equal("caA", codons.Reference);
Assert.Equal("caG", codons.Alternate);
}
public void Assign_SNV_SuffixLenTooBig()
{
var sequence = new Mock <ISequence>();
sequence.SetupGet(x => x.Length).Returns(89);
sequence.Setup(x => x.Substring(87, 1)).Returns("t");
var codons = Codons.GetCodons("C", "T", 89, 89, 30, 30, sequence.Object);
Assert.Equal("tC", codons.Reference);
Assert.Equal("tT", codons.Alternate);
}
public void Assign_MNV()
{
var sequence = new Mock <ISequence>();
sequence.SetupGet(x => x.Length).Returns(100);
sequence.Setup(x => x.Substring(21, 2)).Returns("CA");
sequence.Setup(x => x.Substring(28, 2)).Returns("GG");
var codons = Codons.GetCodons("GTGCT", "ACCGA", 24, 28, 8, 10, sequence.Object);
Assert.Equal("caGTGCTgg", codons.Reference);
Assert.Equal("caACCGAgg", codons.Alternate);
}
public void GetCodons_OutOfRangeIndexes_Adjusted(int cdsStart, int cdsEnd, int proteinBegin, int proteinEnd, string expectedRefCodons)
{
var sequence = new Mock <ISequence>();
sequence.SetupGet(x => x.Length).Returns(99);
sequence.Setup(x => x.Substring(0, 0)).Returns("");
sequence.Setup(x => x.Substring(0, 4)).Returns("ACGT");
sequence.Setup(x => x.Substring(4, 2)).Returns("CA");
sequence.Setup(x => x.Substring(94, 5)).Returns("GCTGA");
sequence.Setup(x => x.Substring(93, 1)).Returns("G");
var codons = Codons.GetCodons("", cdsStart, cdsEnd, proteinBegin, proteinEnd, sequence.Object);
Assert.Equal(expectedRefCodons, codons.Reference);
}
AltAminoAcids, string RefCodons, string AltCodons, string TranscriptAltAllele, string TranscriptRefAllele) AnnotateTranscript(ITranscript transcript, ISimpleVariant variant, AminoAcids aminoAcids, ISequence refSequence)
{
bool onReverseStrand = transcript.Gene.OnReverseStrand;
var start = MappedPositionUtilities.FindRegion(transcript.TranscriptRegions, variant.Start);
var end = MappedPositionUtilities.FindRegion(transcript.TranscriptRegions, variant.End);
var position = GetMappedPosition(transcript.TranscriptRegions, start.Region, start.Index, end.Region,
end.Index, variant, onReverseStrand, transcript.Translation?.CodingRegion, transcript.StartExonPhase,
variant.Type == VariantType.insertion);
var codingSequence = GetCodingSequence(transcript, refSequence);
var cdnaSequence = GetCdnaSequence(transcript, refSequence);
string transcriptAltAllele = HgvsUtilities.GetTranscriptAllele(variant.AltAllele, onReverseStrand);
var codons = Codons.GetCodons(transcriptAltAllele, position.CdsStart, position.CdsEnd, position.ProteinStart, position.ProteinEnd, codingSequence);
var aa = aminoAcids.Translate(codons.Reference, codons.Alternate);
(aa, position.ProteinStart, position.ProteinEnd) = TryTrimAminoAcidsAndUpdateProteinPositions(aa, position.ProteinStart, position.ProteinEnd);
(position.CoveredCdnaStart, position.CoveredCdnaEnd) = transcript.TranscriptRegions.GetCoveredCdnaPositions(position.CdnaStart, start.Index, position.CdnaEnd, end.Index, onReverseStrand);
(position.CoveredCdsStart, position.CoveredCdsEnd, position.CoveredProteinStart, position.CoveredProteinEnd) = MappedPositionUtilities.GetCoveredCdsAndProteinPositions(position.CoveredCdnaStart, position.CoveredCdnaEnd, transcript.StartExonPhase, transcript.Translation?.CodingRegion);
var transcriptRefAllele = GetTranscriptRefAllele(position, cdnaSequence, variant, onReverseStrand);
SequenceChange coveredAa;
// only generate the covered version of ref & alt alleles when CDS start/end is -1
if (position.CdsStart == -1 || position.CdsEnd == -1)
{
coveredAa = GetCoveredAa(aminoAcids, transcriptAltAllele, position.CoveredCdsStart, position.CoveredCdsEnd, position.CoveredProteinStart, position.CoveredProteinEnd, codingSequence);
(coveredAa, position.CoveredProteinStart, position.CoveredProteinEnd) = TryTrimAminoAcidsAndUpdateProteinPositions(coveredAa, position.CoveredProteinStart, position.CoveredProteinEnd);
}
else
{
coveredAa = aa;
position.CoveredProteinStart = position.ProteinStart;
position.CoveredProteinEnd = position.ProteinEnd;
}
var positionalEffect = GetPositionalEffect(transcript, variant, position, aa.Reference, aa.Alternate,
position.CoveredCdnaStart, position.CoveredCdnaEnd, position.CoveredCdsStart, position.CoveredCdsEnd);
var variantEffect = new VariantEffect(positionalEffect, variant, transcript, aa.Reference, aa.Alternate,
codons.Reference, codons.Alternate, position.ProteinStart, coveredAa.Reference, coveredAa.Alternate);
return(variantEffect, position, aa.Reference, aa.Alternate, codons.Reference, codons.Alternate, transcriptAltAllele, transcriptRefAllele);
}
AltAminoAcids, string RefCodons, string AltCodons, string TranscriptAltAllele) AnnotateTranscript(ITranscript transcript, ISimpleVariant variant, AminoAcids aminoAcids,
ISequence refSequence)
{
var onReverseStrand = transcript.Gene.OnReverseStrand;
var start = MappedPositionUtilities.FindRegion(transcript.TranscriptRegions, variant.Start);
var end = MappedPositionUtilities.FindRegion(transcript.TranscriptRegions, variant.End);
var position = GetMappedPosition(transcript.TranscriptRegions, start.Region, start.Index, end.Region,
end.Index, variant, onReverseStrand, transcript.Translation?.CodingRegion, transcript.StartExonPhase,
variant.Type == VariantType.insertion);
var transcriptRefAllele = HgvsUtilities.GetTranscriptAllele(variant.RefAllele, onReverseStrand);
var transcriptAltAllele = HgvsUtilities.GetTranscriptAllele(variant.AltAllele, onReverseStrand);
var codingSequence = transcript.Translation == null
? null
: new CodingSequence(refSequence, transcript.Translation.CodingRegion, transcript.TranscriptRegions,
transcript.Gene.OnReverseStrand, transcript.StartExonPhase);
var codons = Codons.GetCodons(transcriptRefAllele, transcriptAltAllele, position.CdsStart, position.CdsEnd,
position.ProteinStart, position.ProteinEnd, codingSequence);
var coveredCdna = transcript.TranscriptRegions.GetCoveredCdnaPositions(position.CdnaStart, start.Index,
position.CdnaEnd, end.Index, onReverseStrand);
var coveredCds = MappedPositionUtilities.GetCoveredCdsPositions(coveredCdna.Start, coveredCdna.End,
transcript.StartExonPhase, transcript.Translation?.CodingRegion);
var aa = aminoAcids.Translate(codons.Reference, codons.Alternate);
var positionalEffect = GetPositionalEffect(transcript, variant, position, aa.Reference, aa.Alternate,
coveredCdna.Start, coveredCdna.End, coveredCds.Start, coveredCds.End);
var variantEffect = new VariantEffect(positionalEffect, variant, transcript, aa.Reference, aa.Alternate,
codons.Reference, codons.Alternate, position.ProteinStart);
return(variantEffect, position, aa.Reference, aa.Alternate, codons.Reference, codons.Alternate,
transcriptAltAllele);
}
private static SequenceChange GetCoveredAa(AminoAcids aminoAcids, string transcriptAltAllele, int coveredCdsStart, int coveredCdsEnd, int coveredProteinStart, int coveredProteinEnd, ISequence codingSequence)
{
var codonsChange = Codons.GetCodons(transcriptAltAllele, coveredCdsStart, coveredCdsEnd, coveredProteinStart, coveredProteinEnd, codingSequence);
return(aminoAcids.Translate(codonsChange.Reference, codonsChange.Alternate));
}
