private Genotype CalculateHaploidGenotype(IEnumerable <CalledAllele> alleles,
int minDepthToGenotype, out List <CalledAllele> allelesToPrune)
{
allelesToPrune = new List <CalledAllele>();
var singleGTForLoci = Genotype.HemizygousNoCall;
var orderedVariants = GenotypeCalculatorUtilities.FilterAndOrderAllelesByFrequency(alleles, allelesToPrune, _minorVF);
var referenceFrequency = GenotypeCalculatorUtilities.GetReferenceFrequency(alleles, _minorVF);
var refExists = (referenceFrequency >= _minorVF);
var depthIssue = GenotypeCalculatorUtilities.CheckForDepthIssue(alleles, minDepthToGenotype);
bool refCall = ((orderedVariants.Count == 0) || (orderedVariants[0].Frequency < _minorVF));
if (!depthIssue && refCall && refExists && referenceFrequency > _majorVF)
{
singleGTForLoci = Genotype.HemizygousRef;
}
if (!depthIssue && !refCall && !refExists && orderedVariants[0].Frequency > _majorVF)
{
singleGTForLoci = Genotype.HemizygousAlt;
}
//if (!diploidModelFail)
allelesToPrune = GenotypeCalculatorUtilities.GetAllelesToPruneBasedOnGTCall(singleGTForLoci, orderedVariants, allelesToPrune);
return(singleGTForLoci);
}
private static Genotype CalculateDiploidGenotype(IEnumerable <CalledAllele> alleles,
int minDepthToGenotype, DiploidThresholdingParameters snvThresholdingParameters,
DiploidThresholdingParameters indelThresholdingParameters,
out List <CalledAllele> allelesToPrune)
{
allelesToPrune = new List <CalledAllele>();
var singleGTForLoci = Genotype.RefLikeNoCall;
var orderedVariants = GenotypeCalculatorUtilities.FilterAndOrderAllelesByFrequency(alleles, allelesToPrune, snvThresholdingParameters.MinorVF);
var referenceFrequency = GenotypeCalculatorUtilities.GetReferenceFrequency(alleles, snvThresholdingParameters.MinorVF);
var refExists = (referenceFrequency >= snvThresholdingParameters.MinorVF);
var depthIssue = GenotypeCalculatorUtilities.CheckForDepthIssue(alleles, minDepthToGenotype);
var diploidModelFail = false; // as in {30%,30%,30%} not {49%,49%,2%},ie, diploid model FAIL.
bool refCall = ((orderedVariants.Count == 0) || (orderedVariants[0].Frequency < snvThresholdingParameters.MinorVF));
var parameters = snvThresholdingParameters;
//do we apply SNP threshholds or indel thresholds?
if (!refCall)
{
var dominantVariant = orderedVariants.Last();
if (dominantVariant.Type != AlleleCategory.Snv)
{
parameters = indelThresholdingParameters;
}
}
if (depthIssue)
{
if (refCall)
{
singleGTForLoci = Genotype.RefLikeNoCall;
}
else
{
singleGTForLoci = Genotype.AltLikeNoCall;
}
}
else
{
//obvious reference call
if (refCall)
{
if (!refExists)
{
singleGTForLoci = Genotype.RefLikeNoCall; //there might have been an upstream deletion
}
else
{
var firstAllele = alleles.First();
//we see too much of something else (unknown) for a clean ref call.
if ((firstAllele.Type == AlleleCategory.Reference) && ((1 - firstAllele.Frequency) > parameters.MinorVF))
{
singleGTForLoci = Genotype.RefAndNoCall;
}
else
{
singleGTForLoci = Genotype.HomozygousRef; // being explicit for readability
}
}
}//else, types of alt calls...
else if ((orderedVariants[0].Frequency >= parameters.MinorVF) && (orderedVariants[0].Frequency <= parameters.MajorVF))
{
if (orderedVariants.Count == 1)
{
if (refExists)
{
singleGTForLoci = Genotype.HeterozygousAltRef;
}
else
{
singleGTForLoci = Genotype.AltAndNoCall;
}
}
else
{
//is this 0/1, 1/2, or 0/1/2 or 1/2/3/...
diploidModelFail = CheckForTriAllelicIssue(refExists, referenceFrequency, orderedVariants, parameters.SumVFforMultiAllelicSite);
if (diploidModelFail)
{
SetMultiAllelicFilter(alleles);
if (refExists)
{
singleGTForLoci = Genotype.AltLikeNoCall;
}
else
{
singleGTForLoci = Genotype.Alt12LikeNoCall;
}
}
else if (refExists)
{
singleGTForLoci = Genotype.HeterozygousAltRef;
}
else
{
singleGTForLoci = Genotype.HeterozygousAlt1Alt2;
}
}
}
else if (orderedVariants[0].Frequency > parameters.MajorVF)
{
singleGTForLoci = Genotype.HomozygousAlt;
}
}
//if (!diploidModelFail)
allelesToPrune = GenotypeCalculatorUtilities.GetAllelesToPruneBasedOnGTCall(singleGTForLoci, orderedVariants, allelesToPrune);
//tjd +
//incase of DiploidModelFail, we *used* to show all alleles we detected, but then we were worried about down stream processors.
//So now we will will prune in this case, too.
// we still will flag this DiploidModelFail site as a no call. But no longer report everything we found
//tjd -
return(singleGTForLoci);
}
