private static string GetHgvsFrameshiftNotation(ISequence refSequence, int cdsBegin, int cdsEnd,
string transcriptAltAllele, ITranscript transcript, bool isMitochondrial, string proteinId, int start,
int end)
{
var peptideSeq = transcript.Translation.PeptideSeq;
var altPeptideSeq = HgvsUtilities.GetAltPeptideSequence(refSequence, cdsBegin, cdsEnd, transcriptAltAllele, transcript, isMitochondrial);
if (start > end)
{
Swap.Int(ref start, ref end);
}
var frameshiftedParameters = HgvsUtilities.GetChangesAfterFrameshift(start, peptideSeq, altPeptideSeq);
start = frameshiftedParameters.Item1;
var refAminoAcid = frameshiftedParameters.Item2;
var altAminoAcid = frameshiftedParameters.Item3;
var refAbbreviation = AminoAcids.ConvertAminoAcidToAbbreviation(refAminoAcid);
if (altAminoAcid == AminoAcids.StopCodonChar)
{
return(HgvspNotation.GetSubstitutionNotation(proteinId, start, refAbbreviation, "Ter"));
}
var altAbbreviation = AminoAcids.ConvertAminoAcidToAbbreviation(altAminoAcid);
var countToStop = HgvsUtilities.GetNumAminoAcidsUntilStopCodon(altPeptideSeq, peptideSeq, start - 1, true);
return(HgvspNotation.GetFrameshiftNotation(proteinId, start, refAbbreviation, altAbbreviation, countToStop));
}
public static string GetHgvsProteinAnnotation(
ITranscript transcript,
string refAminoAcids,
string altAminoAcids,
string transcriptAltAllele,
IMappedPosition position,
VariantEffect variantEffect,
ISimpleVariant variant,
ISequence refSequence,
string hgvscNotation,
bool isMitochondrial)
{
if (IsHgvspNull(transcriptAltAllele, position.CdsStart, position.CdsEnd, variant, hgvscNotation))
{
return(null);
}
var peptideSeq = transcript.Translation.PeptideSeq;
// Amino acid seq should never go past the stop codon
refAminoAcids = !refAminoAcids.EndsWith(AminoAcids.StopCodon) && refAminoAcids.Contains(AminoAcids.StopCodon)
? refAminoAcids.OptimizedSplit(AminoAcids.StopCodon[0])[0] + AminoAcids.StopCodon
: refAminoAcids;
int proteinStart = position.ProteinStart;
HgvsUtilities.ShiftAndRotateAlleles(ref proteinStart, ref refAminoAcids, ref altAminoAcids, peptideSeq);
var end = proteinStart + refAminoAcids.Length - 1;
var refAbbreviation = AminoAcids.GetAbbreviations(refAminoAcids);
var altAbbreviation = AminoAcids.GetAbbreviations(altAminoAcids);
var proteinId = transcript.Translation.ProteinId.WithVersion;
var proteinChange = GetProteinChange(proteinStart, refAminoAcids, altAminoAcids, peptideSeq, variantEffect);
// ReSharper disable once SwitchStatementMissingSomeCases
switch (proteinChange)
{
case ProteinChange.Substitution:
return(HgvspNotation.GetSubstitutionNotation(proteinId, proteinStart, refAbbreviation, altAbbreviation));
case ProteinChange.Unknown:
return(HgvspNotation.GetUnknownNotation(proteinId, proteinStart, end, refAbbreviation, altAbbreviation));
case ProteinChange.Deletion:
return(HgvspNotation.GetDeletionNotation(proteinId, proteinStart, end, refAbbreviation, variantEffect.IsStopGained()));
case ProteinChange.Duplication:
proteinStart -= altAminoAcids.Length;
return(HgvspNotation.GetDuplicationNotation(proteinId, proteinStart, end, altAbbreviation));
case ProteinChange.Frameshift:
return(GetHgvsFrameshiftNotation(refSequence, position.CdsStart, position.CdsEnd, transcriptAltAllele,
transcript, isMitochondrial, proteinId, proteinStart, end));
case ProteinChange.None:
return(HgvspNotation.GetSilentNotation(hgvscNotation, proteinStart, refAbbreviation, variantEffect.IsStopRetained()));
case ProteinChange.DelIns:
return(HgvspNotation.GetDelInsNotation(proteinId, proteinStart, end, refAbbreviation, altAbbreviation));
case ProteinChange.Insertion:
Swap.Int(ref proteinStart, ref end);
return(HgvspNotation.GetInsertionNotation(proteinId, proteinStart, end, altAbbreviation, peptideSeq));
case ProteinChange.Extension:
var altPeptideSequence = HgvsUtilities.GetAltPeptideSequence(refSequence, position.CdsStart, position.CdsEnd,
transcriptAltAllele, transcript, isMitochondrial);
altAbbreviation = proteinStart <= altPeptideSequence.Length ? AminoAcids.ConvertAminoAcidToAbbreviation(altPeptideSequence[proteinStart - 1]): "Ter";
var countToStop = HgvsUtilities.GetNumAminoAcidsUntilStopCodon(altPeptideSequence, peptideSeq, proteinStart - 1, false);
return(HgvspNotation.GetExtensionNotation(proteinId, proteinStart, refAbbreviation, altAbbreviation, countToStop));
case ProteinChange.StartLost:
return(HgvspNotation.GetStartLostNotation(proteinId, proteinStart, end, refAbbreviation));
}
return(null);
}