public static string GetHgvscAnnotation(ITranscript transcript, ISimpleVariant variant, ISequence refSequence,
int regionStart, int regionEnd)
{
// sanity check: don't try to handle odd characters, make sure this is not a reference allele,
// and make sure that we have protein coordinates
if (variant.Type == VariantType.reference || SequenceUtilities.HasNonCanonicalBase(variant.AltAllele))
{
return(null);
}
var onReverseStrand = transcript.Gene.OnReverseStrand;
var refAllele = onReverseStrand ? SequenceUtilities.GetReverseComplement(variant.RefAllele) : variant.RefAllele;
var altAllele = onReverseStrand ? SequenceUtilities.GetReverseComplement(variant.AltAllele) : variant.AltAllele;
// decide event type from HGVS nomenclature
var genomicChange = GetGenomicChange(transcript, onReverseStrand, refSequence, variant);
var variantStart = variant.Start;
var variantEnd = variant.End;
if (genomicChange == GenomicChange.Duplication)
{
(variantStart, variantEnd, refAllele, regionStart, regionEnd) = transcript.TranscriptRegions.ShiftDuplication(variantStart, altAllele, onReverseStrand);
}
var startPositionOffset = HgvsUtilities.GetCdnaPositionOffset(transcript, variantStart, regionStart);
var endPositionOffset = variantStart == variantEnd
? startPositionOffset
: HgvsUtilities.GetCdnaPositionOffset(transcript, variantEnd, regionEnd);
if (onReverseStrand)
{
var tmp = startPositionOffset;
startPositionOffset = endPositionOffset;
endPositionOffset = tmp;
}
// sanity check: make sure we have coordinates
if (startPositionOffset == null || endPositionOffset == null)
{
return(null);
}
var transcriptLen = transcript.End - transcript.Start + 1;
//_hgvs notation past the transcript
if (startPositionOffset.Position > transcriptLen || endPositionOffset.Position > transcriptLen)
{
return(null);
}
var hgvsNotation = new HgvscNotation(refAllele, altAllele, transcript.Id.WithVersion, genomicChange,
startPositionOffset, endPositionOffset, transcript.Translation != null);
// generic formatting
return(hgvsNotation.ToString());
}
private static bool IsHgvspNull(string transcriptAltAllele, int cdsStart, int cdsEnd, ISimpleVariant variant,
string hgvscNotation)
{
return(string.IsNullOrEmpty(hgvscNotation) ||
variant.Type == VariantType.reference ||
SequenceUtilities.HasNonCanonicalBase(transcriptAltAllele) ||
cdsStart == -1 ||
cdsEnd == -1);
}
/// <summary>
/// return a string representing the cDNA-level effect of this allele in HGVS format [TranscriptVariationAllele.pm:568 hgvs_transcript]
/// </summary>
public void SetAnnotation()
{
// sanity check: don't try to handle odd characters, make sure this is not a reference allele,
// and make sure that we have protein coordinates
if (_variant.IsReference || SequenceUtilities.HasNonCanonicalBase(_ta.TranscriptAlternateAllele))
{
return;
}
GetGenomicChange(_transcript, _hgvsNotation, _isGenomicDuplicate);
GetCdnaPosition(_hgvsNotation.Start);
if (_hgvsStart == _hgvsEnd)
{
_hgvsNotation.End = _hgvsNotation.Start;
}
else
{
GetCdnaPosition(_hgvsNotation.End);
}
// sanity check: make sure we have coordinates
if (_hgvsNotation.Start.Position == null || _hgvsNotation.End.Position == null)
{
return;
}
var transcriptLen = _transcript.End - _transcript.Start + 1;
//_hgvs notation past the transcript
if (_hgvsNotation.Start.Position > transcriptLen || _hgvsNotation.End.Position > transcriptLen)
{
return;
}
// make sure that start is always less than end
SwapEndpoints(_hgvsNotation);
// generic formatting
_ta.HgvsCodingSequenceName = FormatHgvsString();
}
/// <summary>
/// return a string representing the protein-level effect of this allele in HGVS format [TranscriptVariationAllele.pm:717 hgvs_protein]
/// </summary>
public void SetAnnotation()
{
// sanity check: don't try to handle odd characters, make sure this is not a reference allele,
// and make sure that we have protein coordinates
if (_variant.IsReference || !_ta.HasValidCdsEnd || !_ta.HasValidCdsEnd ||
SequenceUtilities.HasNonCanonicalBase(_ta.TranscriptAlternateAllele))
{
return;
}
// check if this is a stop retained variant
if (_variantEffect.IsStopRetained())
{
_ta.HgvsProteinSequenceName = $"{_ta.HgvsCodingSequenceName}(p.=)";
return;
}
// clip the alleles
AminoAcids.RemovePrefixAndSuffix(_hgvsNotation);
// set the protein change
_hgvsNotation.Type = GetGeneralProteinChange();
if (_hgvsNotation.Type != ProteinChange.None)
{
_hgvsNotation.Type = GetSpecificProteinChange();
// convert ref & alt peptides taking into account HGVS rules
GetHgvsPeptides(_ta);
}
// no protein change - return transcript nomenclature with flag for neutral protein consequence
if (_hgvsNotation.Type == ProteinChange.None)
{
_ta.HgvsProteinSequenceName = $"{_ta.HgvsCodingSequenceName}(p.=)";
return;
}
// string formatting
_ta.HgvsProteinSequenceName = GetHgvsProteinFormat(_ta);
}
public void HasNonCanonicalBase(string bases, bool expectedResult)
{
var observedResult = SequenceUtilities.HasNonCanonicalBase(bases);
Assert.Equal(expectedResult, observedResult);
}
public void NonCanonical(string bases)
{
Assert.True(SequenceUtilities.HasNonCanonicalBase(bases));
}
public static string GetHgvscAnnotation(ITranscript transcript, ISimpleVariant variant, ISequence refSequence,
int regionStart, int regionEnd, string transcriptRef, string transcriptAlt)
{
// sanity check: don't try to handle odd characters, make sure this is not a reference allele,
// and make sure that we have protein coordinates
if (variant.Type == VariantType.reference || SequenceUtilities.HasNonCanonicalBase(variant.AltAllele))
{
return(null);
}
// do not report HGVSc notation when variant lands inside gap region
if (regionStart > -1 && regionEnd > -1)
{
var startRegion = transcript.TranscriptRegions[regionStart];
var endRegion = transcript.TranscriptRegions[regionEnd];
if (startRegion.Id == endRegion.Id && startRegion.Type == TranscriptRegionType.Gap &&
endRegion.Type == TranscriptRegionType.Gap)
{
return(null);
}
}
bool onReverseStrand = transcript.Gene.OnReverseStrand;
string refAllele = string.IsNullOrEmpty(transcriptRef)? onReverseStrand ? SequenceUtilities.GetReverseComplement(variant.RefAllele) : variant.RefAllele
: transcriptRef;
string altAllele = string.IsNullOrEmpty(transcriptAlt)
? onReverseStrand ? SequenceUtilities.GetReverseComplement(variant.AltAllele) : variant.AltAllele
: transcriptAlt;
// decide event type from HGVS nomenclature
var genomicChange = GetGenomicChange(transcript, onReverseStrand, refSequence, variant);
int variantStart = variant.Start;
int variantEnd = variant.End;
if (genomicChange == GenomicChange.Duplication)
{
(variantStart, variantEnd, refAllele, regionStart, regionEnd) = transcript.TranscriptRegions.ShiftDuplication(variantStart, altAllele, onReverseStrand);
}
var startPositionOffset = HgvsUtilities.GetCdnaPositionOffset(transcript, variantStart, regionStart, true);
var endPositionOffset = variantStart == variantEnd
? startPositionOffset
: HgvsUtilities.GetCdnaPositionOffset(transcript, variantEnd, regionEnd, false);
if (onReverseStrand)
{
var tmp = startPositionOffset;
startPositionOffset = endPositionOffset;
endPositionOffset = tmp;
}
if (startPositionOffset == null && variant.Type == VariantType.insertion)
{
startPositionOffset = new PositionOffset(endPositionOffset.Position + 1, endPositionOffset.Offset, $"{endPositionOffset.Position + 1}", endPositionOffset.HasStopCodonNotation);
}
// sanity check: make sure we have coordinates
if (startPositionOffset == null || endPositionOffset == null)
{
return(null);
}
var hgvsNotation = new HgvscNotation(refAllele, altAllele, transcript.Id.WithVersion, genomicChange,
startPositionOffset, endPositionOffset, transcript.Translation != null);
// generic formatting
return(hgvsNotation.ToString());
}
