/// <summary>
/// Gets proteins with applied variants from this protein
/// </summary>
public List <ProteinWithAppliedVariants> GetVariantProteins()
{
List <SequenceVariation> uniqueEffects = SequenceVariations
.GroupBy(v => v.OriginalSequence + v.OneBasedBeginPosition.ToString() + v.VariantSequence).Select(x => x.First())
.Where(v => v.Description.Split('\t').Length >= 10) // likely a VCF line (should probably do more rigorous testing, eventually)
.OrderByDescending(v => v.OneBasedBeginPosition) // apply variants at the end of the protein sequence first
.ToList();
ProteinWithAppliedVariants variantProtein = new ProteinWithAppliedVariants(BaseSequence, this, null, null);
return(variantProtein.ApplyVariants(variantProtein, uniqueEffects));
}
/// <summary>
/// Gets proteins with applied variants from this protein
/// </summary>
public List <ProteinWithAppliedVariants> GetVariantProteins()
{
if (SequenceVariations.Count() > 0)
{
int i = 0;
int asdf = SequenceVariations.Select(v => v.Description.Split(new[] { @"\t" }, StringSplitOptions.None).Length).Max();
}
List <SequenceVariation> uniqueEffects = SequenceVariations
.GroupBy(v => v.SimpleString())
.Select(x => x.First())
.Where(v => v.Description.Split(new[] { @"\t" }, StringSplitOptions.None).Length >= 10) // likely a VCF line (should probably do more rigorous testing, eventually)
.OrderByDescending(v => v.OneBasedBeginPosition) // apply variants at the end of the protein sequence first
.ToList();
ProteinWithAppliedVariants variantProtein = new ProteinWithAppliedVariants(BaseSequence, this, null, ProteolysisProducts, OneBasedPossibleLocalizedModifications, null);
return(variantProtein.ApplyVariants(variantProtein, uniqueEffects));
}
/// <summary>
/// Applies variant changes to protein sequence
/// </summary>
/// <param name="protein"></param>
/// <param name="uniqueEffectsToApply"></param>
/// <returns></returns>
internal List <ProteinWithAppliedVariants> ApplyVariants(ProteinWithAppliedVariants protein, List <SequenceVariation> uniqueEffectsToApply)
{
// If there aren't any variants to apply, just return the base protein
if (uniqueEffectsToApply.Count == 0)
{
return(new List <ProteinWithAppliedVariants> {
protein
});
}
bool referenceAdded = false;
List <ProteinWithAppliedVariants> proteins = new List <ProteinWithAppliedVariants>();
foreach (SequenceVariation variant in uniqueEffectsToApply)
{
// Parse description into
string[] vcfFields = variant.Description.Split(new[] { @"\t" }, StringSplitOptions.None);
if (vcfFields.Length < 10)
{
continue;
}
string referenceAlleleString = vcfFields[3];
string alternateAlleleString = vcfFields[4];
string info = vcfFields[7];
string format = vcfFields[8];
string[] genotypes = Enumerable.Range(9, vcfFields.Length - 9).Select(i => vcfFields[i]).ToArray();
// loop through genotypes for this variant (e.g. tumor and normal)
for (int i = 0; i < genotypes.Length; i++)
{
if (Individual != null && Individual != i.ToString())
{
continue;
}
var genotypeFields = GenotypeDictionary(format.Trim(), genotypes[i].Trim());
// parse genotype
string[] gt = null;
if (genotypeFields.TryGetValue("GT", out string gtString))
{
gt = gtString.Split('/');
}
if (gt == null)
{
continue;
}
// parse allele depth (might be null, technically, but shouldn't be in most use cases)
string[] ad = null;
if (genotypeFields.TryGetValue("AD", out string adString))
{
ad = adString.Split(',');
}
// reference allele
if (gt.Contains("0") && !referenceAdded)
{
proteins.Add(new ProteinWithAppliedVariants(BaseSequence, Protein, AppliedSequenceVariations, ProteolysisProducts, OneBasedPossibleLocalizedModifications, i.ToString()));
referenceAdded = true; // only add the reference allele once
}
// alternate allele
// TODO: recursively apply variants to create haplotypes and be wary of combinitorial explosion
if (!gt.All(x => x == "0"))
{
// 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 = AppliedSequenceVariations.Any(x => variant.Intersects(x) && !variant.Includes(x));
string seqBefore = BaseSequence.Substring(0, variant.OneBasedBeginPosition - 1);
string seqVariant = variant.VariantSequence;
List <ProteolysisProduct> adjustedProteolysisProducts = AdjustProteolysisProductIndices(variant, ProteolysisProducts);
Dictionary <int, List <Modification> > adjustedModifications = AdjustModificationIndices(variant, OneBasedPossibleLocalizedModifications);
int afterIdx = variant.OneBasedBeginPosition + variant.OriginalSequence.Length - 1;
if (intersectsAppliedRegionIncompletely)
{
// use original protein sequence for the remaining sequence
string seqAfter = Protein.BaseSequence.Length - afterIdx <= 0 ? "" : Protein.BaseSequence.Substring(afterIdx);
proteins.Add(new ProteinWithAppliedVariants(seqBefore + seqVariant + seqAfter, Protein, new[] { variant }, adjustedProteolysisProducts, adjustedModifications, i.ToString()));
}
else
{
List <SequenceVariation> variations = AppliedSequenceVariations
.Where(x => !variant.Includes(x))
.Concat(new[] { variant })
.ToList();
// use this variant protein sequence for the remaining sequence
string seqAfter = BaseSequence.Length - afterIdx <= 0 ? "" : BaseSequence.Substring(afterIdx);
proteins.Add(new ProteinWithAppliedVariants(seqBefore + seqVariant + seqAfter, Protein, variations, adjustedProteolysisProducts, adjustedModifications, i.ToString()));
}
}
}
}
return(proteins);
}