public static IGenotypeCalculator CreateGenotypeCalculator(PloidyModel ploidyModel, float minimumFrequencyFilter,
int minEmitDepth, DiploidThresholdingParameters snvParameters, DiploidThresholdingParameters indelParameters,
AdaptiveGenotypingParameters adaptiveGenotypingParameters,
int minGQscore, int maxGQscore, float targetLODVariantFrequency,
float minimumEmitFrequency = 0,
string refName = null, bool?isMale = null)
{
var ploidyModelForThisChr = GetPloidyForThisChr(ploidyModel, isMale, refName);
switch (ploidyModelForThisChr)
{
case PloidyModel.Haploid:
return(new HaploidGenotyper(minEmitDepth, minGQscore, maxGQscore, snvParameters.MinorVF, snvParameters.MajorVF));
case PloidyModel.DiploidByAdaptiveGT:
return(new DiploidAdaptiveGenotyper(minEmitDepth, minGQscore, maxGQscore, adaptiveGenotypingParameters));
case PloidyModel.DiploidByThresholding:
return(new DiploidThresholdingGenotyper(snvParameters, snvParameters, minEmitDepth, minGQscore, maxGQscore));
case PloidyModel.Somatic:
default:
return(new SomaticGenotyper(minimumFrequencyFilter, minEmitDepth, minGQscore, maxGQscore,
minimumEmitFrequency, targetLODVariantFrequency));
}
}
public DiploidAdaptiveGenotyper(int minCalledVariantDepth, int minGQscore, int maxGQscore,
AdaptiveGenotypingParameters adaptiveGenotypingParameters)
{
MinDepthToGenotype = minCalledVariantDepth;
MinGQScore = minGQscore;
MaxGQScore = maxGQscore;
_adaptiveGenotypingParameters = adaptiveGenotypingParameters;
}
public DiploidAdaptiveGenotyper()
{
var defaultParams = new VariantCallingParameters();
_adaptiveGenotypingParameters = new AdaptiveGenotypingParameters();
MinGQScore = defaultParams.MinimumGenotypeQScore;
MaxGQScore = defaultParams.MaximumGenotypeQScore;
MinDepthToGenotype = defaultParams.MinimumCoverage;
}
public void ChrYUnknownGenderTests_adaptive()
{
var adaptiveGTparams = new AdaptiveGenotypingParameters();
var diploidPars = new DiploidThresholdingParameters(new float[] { 0.2f, 0.7f, 0.8f });
var genotypeCaculator = GenotypeCreator.CreateGenotypeCalculator(PloidyModel.DiploidByAdaptiveGT, 0.05f, 30, diploidPars, diploidPars, adaptiveGTparams, 0, 100, 0.05f, 0.02f, "chrY");
Assert.True(genotypeCaculator is DiploidAdaptiveGenotyper);
Assert.Equal(PloidyModel.DiploidByAdaptiveGT, GenotypeCreator.GetPloidyForThisChr(PloidyModel.DiploidByAdaptiveGT, null, "chrY"));
}
public void ChrMMaleTests_adaptive()
{
var adaptiveGTparams = new AdaptiveGenotypingParameters();
var diploidPars = new DiploidThresholdingParameters(new float[] { 0.2f, 0.7f, 0.8f });
var genotypeCaculator = GenotypeCreator.CreateGenotypeCalculator(PloidyModel.DiploidByAdaptiveGT, 0.05f, 30, diploidPars, diploidPars, adaptiveGTparams,
0, 100, 0.05f, 0.02f, "chrM", true);
Assert.True(genotypeCaculator is SomaticGenotyper);
Assert.Equal(PloidyModel.Somatic, GenotypeCreator.GetPloidyForThisChr(PloidyModel.DiploidByAdaptiveGT, true, "chrM"));
}
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);
}
private static AdaptiveGenotypingParameters UpdateAdaptiveGenotypingParameters(AdaptiveGenotypingParameters parameters, string inputModelFilePath)
{
if (File.Exists(inputModelFilePath))
{
var newModels = MixtureModel.ReadModelsFile(inputModelFilePath);
parameters.SnvModel = newModels[0].Means;
parameters.SnvPrior = newModels[0].Priors;
parameters.IndelModel = newModels[1].Means;
parameters.IndelPrior = newModels[1].Priors;
}
else
{
throw new ArgumentException("No AdaptiveGT model file found at " + inputModelFilePath);
}
return(parameters);
}