/// <summary>
/// Determines if the modification falls on a variant amino acid
/// </summary>
/// <param name="protein"></param>
/// <param name=""></param>
/// <returns></returns>
public static bool IsSequenceVariantModification(SequenceVariation appliedVariant, int variantProteinIndex)
{
return(appliedVariant != null && appliedVariant.Includes(variantProteinIndex));
}
/// <summary>
/// Applies a single variant to a protein sequence
/// </summary>
/// <param name="variantGettingApplied"></param>
/// <returns></returns>
internal static Protein ApplySingleVariant(SequenceVariation variantGettingApplied, Protein protein, string individual)
{
string seqBefore = protein.BaseSequence.Substring(0, variantGettingApplied.OneBasedBeginPosition - 1);
string seqVariant = variantGettingApplied.VariantSequence;
int afterIdx = variantGettingApplied.OneBasedBeginPosition + variantGettingApplied.OriginalSequence.Length - 1;
SequenceVariation variantAfterApplication = new SequenceVariation(
variantGettingApplied.OneBasedBeginPosition,
variantGettingApplied.OneBasedBeginPosition + variantGettingApplied.VariantSequence.Length - 1,
variantGettingApplied.OriginalSequence,
variantGettingApplied.VariantSequence,
variantGettingApplied.Description.Description,
variantGettingApplied.OneBasedModifications.ToDictionary(kv => kv.Key, kv => kv.Value));
// check to see if there is incomplete indel overlap, which would lead to weird variant sequences
// complete overlap is okay, since it will be overwritten; this can happen if there are two alternate alleles,
// e.g. reference sequence is wrong at that point
bool intersectsAppliedRegionIncompletely = protein.AppliedSequenceVariations.Any(x => variantGettingApplied.Intersects(x) && !variantGettingApplied.Includes(x));
IEnumerable <SequenceVariation> appliedVariations = new[] { variantAfterApplication };
string seqAfter = null;
if (intersectsAppliedRegionIncompletely)
{
// use original protein sequence for the remaining sequence
seqAfter = protein.BaseSequence.Length - afterIdx <= 0 ? "" : protein.NonVariantProtein.BaseSequence.Substring(afterIdx);
}
else
{
// use this variant protein sequence for the remaining sequence
seqAfter = protein.BaseSequence.Length - afterIdx <= 0 ? "" : protein.BaseSequence.Substring(afterIdx);
appliedVariations = appliedVariations
.Concat(protein.AppliedSequenceVariations.Where(x => !variantGettingApplied.Includes(x)))
.ToList();
}
string variantSequence = (seqBefore + seqVariant + seqAfter).Split('*')[0]; // there may be a stop gained
// adjust indices
List <ProteolysisProduct> adjustedProteolysisProducts = AdjustProteolysisProductIndices(variantGettingApplied, variantSequence, protein, protein.ProteolysisProducts);
Dictionary <int, List <Modification> > adjustedModifications = AdjustModificationIndices(variantGettingApplied, variantSequence, protein);
List <SequenceVariation> adjustedAppliedVariations = AdjustSequenceVariationIndices(variantGettingApplied, variantSequence, appliedVariations);
return(new Protein(variantSequence, protein, adjustedAppliedVariations, adjustedProteolysisProducts, adjustedModifications, individual));
}