public static IGenotypeCalculator CreateGenotypeCalculator(PloidyModel ploidyModel, float minimumFrequencyFilter,
int minEmitDepth, DiploidThresholdingParameters snvParameters, DiploidThresholdingParameters indelParameters,
int minGQscore, int maxGQscore, float targetLODVariantFrequency,
float minimumEmitFrequency = 0,
string refName = null, bool?isMale = null)
{
if (ploidyModel == PloidyModel.Somatic || refName == "chrM")
{
return(new SomaticGenotypeCalculator(minimumFrequencyFilter, minEmitDepth, minGQscore, maxGQscore,
minimumEmitFrequency, targetLODVariantFrequency));
}
if (isMale == null)
{
return(new DiploidGenotypeCalculator(snvParameters, indelParameters, minEmitDepth, minGQscore, maxGQscore));
}
if (isMale.Value && (refName == "chrY" || refName == "chrX"))
{
return(new HaploidGenotyeCalculator(minEmitDepth, minGQscore, maxGQscore, snvParameters.MinorVF, snvParameters.MajorVF));
}
if (!isMale.Value && refName == "chrY")
{
Common.IO.Utility.Logger.WriteWarningToLog("chrY exists in Female samples");
return(new HaploidGenotyeCalculator(minEmitDepth, minGQscore, maxGQscore, snvParameters.MinorVF, snvParameters.MajorVF));
}
return(new DiploidGenotypeCalculator(snvParameters, snvParameters, minEmitDepth, minGQscore, maxGQscore));
}
public DiploidGenotypeCalculator(DiploidThresholdingParameters parameters, int minCalledVariantDepth, int minGQscore, int maxGQscore)
{
_diploidThresholdingParameters = parameters;
MinGQScore = minGQscore;
MaxGQScore = maxGQscore;
MinDepthToGenotype = minCalledVariantDepth;
}
public DiploidGenotypeCalculator(DiploidThresholdingParameters snvParameters, DiploidThresholdingParameters indelParameters,
int minCalledVariantDepth, int minGQscore, int maxGQscore)
{
_diploidSnvThresholdingParameters = snvParameters;
_diploidIndelThresholdingParameters = indelParameters;
MinGQScore = minGQscore;
MaxGQScore = maxGQscore;
MinDepthToGenotype = minCalledVariantDepth;
MinVarFrequency = _diploidSnvThresholdingParameters.MinorVF;
}
public DiploidGenotypeCalculator()
{
var defaultParams = new VariantCallingParameters();
_diploidSnvThresholdingParameters = defaultParams.DiploidSNVThresholdingParameters;
_diploidIndelThresholdingParameters = defaultParams.DiploidINDELThresholdingParameters;
MinGQScore = defaultParams.MinimumGenotypeQScore;
MaxGQScore = defaultParams.MaximumGenotypeQScore;
MinDepthToGenotype = defaultParams.MinimumCoverage;
MinVarFrequency = _diploidSnvThresholdingParameters.MinorVF;
}
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);
}
public static IGenotypeCalculator CreateGenotypeCalculator(PloidyModel ploidyModel, float minCalledVariantFreq,
int minCalledVariantDepth, DiploidThresholdingParameters parameters, int minGQscore, int maxGQscore)
{
return((ploidyModel == PloidyModel.Somatic)
? (IGenotypeCalculator) new SomaticGenotypeCalculator(minCalledVariantFreq, minCalledVariantDepth, minGQscore, maxGQscore)
: new DiploidGenotypeCalculator(parameters, minCalledVariantDepth, minGQscore, maxGQscore));
}