private static Genotype CalculateDiploidGenotypeFromBinomialModel(
IEnumerable <CalledAllele> alleles,
int minDepthToGenotype,
AdaptiveGenotypingParameters adaptiveGenotypingParameters,
out List <CalledAllele> allelesToPrune)
{
allelesToPrune = new List <CalledAllele>();
float minVariantFrequency = GetMinVarFrequency(alleles.First().TotalCoverage,
adaptiveGenotypingParameters.SnvModel, adaptiveGenotypingParameters.SnvPrior);
double referenceFrequency = GetReferenceFrequency(alleles);
bool depthIssue = GenotypeCalculatorUtilities.CheckForDepthIssue(alleles, minDepthToGenotype);
bool refExists = referenceFrequency > minVariantFrequency;
List <CalledAllele> orderedVariants = GenotypeCalculatorUtilities.FilterAndOrderAllelesByFrequency(alleles,
allelesToPrune, minVariantFrequency);
bool refCall = orderedVariants.Count == 0;
//assume its ref call
var preliminaryGenotype = SimplifiedDiploidGenotype.HomozygousRef;
//this is order by descending - so most frequent is first.
if (!refCall)
{
//do we apply SNP threshholds or indel thresholds?
var dominantVariant = orderedVariants[0];
var(model, priors) = adaptiveGenotypingParameters.GetModelsAndPriors(dominantVariant);
preliminaryGenotype = AdaptiveGenotyperCalculator.GetSimplifiedGenotype(dominantVariant, model, priors);
minVariantFrequency = GetMinVarFrequency(dominantVariant.TotalCoverage, model, priors);
}
var finalGTForLoci = GenotypeCalculatorUtilities.ConvertSimpleGenotypeToComplexGenotype(alleles, orderedVariants,
referenceFrequency, refExists, depthIssue, refCall, minVariantFrequency,
adaptiveGenotypingParameters.SumVFforMultiAllelicSite, preliminaryGenotype);
allelesToPrune = GenotypeCalculatorUtilities.GetAllelesToPruneBasedOnGTCall(finalGTForLoci, orderedVariants, allelesToPrune);
return(finalGTForLoci);
}
public List <CalledAllele> SetGenotypes(IEnumerable <CalledAllele> alleles)
{
var singleGTForLoci = CalculateDiploidGenotypeFromBinomialModel(alleles, MinDepthToGenotype,
_adaptiveGenotypingParameters, out var allelesToPrune);
int phaseSetIndex = 1; //reserve -1 for unset, and 0 for reference, and 1 and 2 for alts
foreach (var allele in alleles)
{
allele.Genotype = singleGTForLoci;
if (allele.TotalCoverage == 0)
{
allele.GenotypeQscore = MinGQScore;
allele.GenotypePosteriors = new float[] {
_adaptiveGenotypingParameters.MaxGenotypePosteriors,
_adaptiveGenotypingParameters.MaxGenotypePosteriors,
_adaptiveGenotypingParameters.MaxGenotypePosteriors
};
}
else
{
var(model, prior) = _adaptiveGenotypingParameters.GetModelsAndPriors(allele);
MixtureModelResult adaptiveGTResult = AdaptiveGenotyperCalculator.GetGenotypeAndQScore(allele,
model, prior);
allele.GenotypeQscore = Math.Max(Math.Min(adaptiveGTResult.QScore, MaxGQScore), MinGQScore);
allele.GenotypePosteriors = adaptiveGTResult.GenotypePosteriors;
}
if (allele.IsRefType)
{
allele.PhaseSetIndex = 0;
}
else
{
allele.PhaseSetIndex = phaseSetIndex;
phaseSetIndex++;
}
}
// Calculate GP for multiallelic variant based on multinomial distribution
if (alleles.First().Genotype == Genotype.HeterozygousAlt1Alt2)
{
CalledAllele allele1 = alleles.First(), allele2 = alleles.ElementAt(1);
var(model1, _) = _adaptiveGenotypingParameters.GetModelsAndPriors(allele1);
var(model2, _) = _adaptiveGenotypingParameters.GetModelsAndPriors(allele2);
var mixtureModelResult = AdaptiveGenotyperCalculator.GetMultiAllelicQScores(allele1, allele2,
new List <double[]> {
model1, model2
});
foreach (CalledAllele allele in alleles)
{
allele.GenotypeQscore = Math.Max(Math.Min(mixtureModelResult.QScore, MaxGQScore), MinGQScore);
allele.GenotypePosteriors = mixtureModelResult.GenotypePosteriors;
}
}
return(allelesToPrune);
}
