public static TypeOfUpdateNeeded ProcessLocus(VcfConsumerAppOptions options, RecalibrationResults results,
List <CalledAllele> incomingAlleles, out List <CalledAllele> outGoingAlleles)
{
// Use somatic call for chrM
if (GenotypeCreator.GetPloidyForThisChr(
options.VariantCallingParams.PloidyModel,
options.VariantCallingParams.IsMale,
incomingAlleles.First().Chromosome) != PloidyModel.DiploidByAdaptiveGT)
{
return(GetTypeOfUpdate((AdaptiveGtOptions)options, incomingAlleles, TypeOfUpdateNeeded.NoChangeNeeded,
out outGoingAlleles));
}
var orderedAlleles = GetTopTwoAlleles(incomingAlleles);
if (orderedAlleles.Count == 1)
{
var alleles = ProcessSingleVariantLocus(incomingAlleles[0], results);
return(GetTypeOfUpdate((AdaptiveGtOptions)options, alleles, TypeOfUpdateNeeded.Modify, out outGoingAlleles));
}
else
{
var alleles = ProcessMultiAllelicLocus(orderedAlleles, results);
return(GetTypeOfUpdate((AdaptiveGtOptions)options, alleles, TypeOfUpdateNeeded.Modify, out outGoingAlleles));
}
}
public void ChrYMaleTests()
{
var diploidPars = new DiploidThresholdingParameters(new float[] { 0.2f, 0.7f, 0.8f });
var genotypeCaculator = GenotypeCreator.CreateGenotypeCalculator(PloidyModel.Diploid, 0.05f, 30, diploidPars, diploidPars, 0, 100, 0.05f, 0.02f, "chrY", true);
Assert.True(genotypeCaculator is HaploidGenotyeCalculator);
}
public CallableNeighborhood(VcfNeighborhood vcfNeighborhood, VariantCallingParameters variantCallingParams, ChrReference chrReference = null)
{
//housekeeping
_nbhdGTcalculator = GenotypeCreator.CreateGenotypeCalculator(variantCallingParams.PloidyModel, variantCallingParams.MinimumFrequencyFilter,
variantCallingParams.MinimumCoverage,
variantCallingParams.DiploidSNVThresholdingParameters,
variantCallingParams.DiploidINDELThresholdingParameters,
variantCallingParams.AdaptiveGenotypingParameters,
variantCallingParams.MinimumGenotypeQScore, variantCallingParams.MaximumGenotypeQScore, variantCallingParams.TargetLODFrequency);
_vcfNeighborhood = vcfNeighborhood;
_acceptedPhasedVariants = new List <CalledAllele>();
_rejectedPhasedVariants = new List <CalledAllele>();
UsedRefCountsLookup = new Dictionary <int, SuckedUpRefRecord>();
MaxQScore = variantCallingParams.MaximumVariantQScore;
//prep vcf nbhd for use, so we know the final range of loci in play
vcfNeighborhood.OrderVariantSitesByFirstTrueStartPosition();
vcfNeighborhood.SetRangeOfInterest();
//set reference bases here, then let go of the chr
if ((chrReference == null) || (chrReference.Sequence == null)) //be gentle if they did not include a ref genome
{
NbhdReferenceSequenceSubstring = new String('R', vcfNeighborhood.LastPositionOfInterestWithLookAhead - vcfNeighborhood.FirstPositionOfInterest);
}
else
{
NbhdReferenceSequenceSubstring = chrReference.Sequence.Substring(vcfNeighborhood.FirstPositionOfInterest - 1, vcfNeighborhood.LastPositionOfInterestWithLookAhead - vcfNeighborhood.FirstPositionOfInterest);
}
}
public void ChrYUnknownGenderTests_thresholding()
{
var diploidPars = new DiploidThresholdingParameters(new float[] { 0.2f, 0.7f, 0.8f });
var genotypeCaculator = GenotypeCreator.CreateGenotypeCalculator(PloidyModel.DiploidByThresholding, 0.05f, 30, diploidPars, diploidPars, null, 0, 100, 0.05f, 0.02f, "chrY");
Assert.True(genotypeCaculator is DiploidThresholdingGenotyper);
Assert.Equal(PloidyModel.DiploidByThresholding, GenotypeCreator.GetPloidyForThisChr(PloidyModel.DiploidByThresholding, 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"));
}
public void ChrMGenotypeCalculatorTests()
{
var genotypeCaculator = GenotypeCreator.CreateGenotypeCalculator(PloidyModel.DiploidByThresholding, 0.05f, 30, null, null, null, 0, 100, 0.05f, 0.02f, "chrM");
Assert.True(genotypeCaculator is SomaticGenotyper);
Assert.Equal(0.02f, genotypeCaculator.MinVarFrequency);
genotypeCaculator.SetMinFreqFilter(0.05f);
Assert.Equal(0.05f, genotypeCaculator.MinVarFrequencyFilter);
genotypeCaculator.SetMinFreqFilter(0.01f);
Assert.Equal(0.02f, genotypeCaculator.MinVarFrequencyFilter);
}
public void ChrXMaleGenotypeCalculatorTests()
{
var diploidPars = new DiploidThresholdingParameters(new float[] { 0.2f, 0.7f, 0.8f });
var genotypeCaculator = GenotypeCreator.CreateGenotypeCalculator(PloidyModel.DiploidByThresholding, 0.05f, 30, diploidPars, diploidPars, null, 0, 100, 0.05f, 0.02f, "chrX", true);
Assert.True(genotypeCaculator is HaploidGenotyper);
Assert.Equal(0.2f, genotypeCaculator.MinVarFrequency);
genotypeCaculator.SetMinFreqFilter(0.05f);
Assert.Equal(0.2f, genotypeCaculator.MinVarFrequencyFilter);
genotypeCaculator.SetMinFreqFilter(0.3f);
Assert.Equal(0.3f, genotypeCaculator.MinVarFrequencyFilter);
}
public VcfNeighborhood(VariantCallingParameters variantCallingParams, string refName, VariantSite vs1, VariantSite vs2, string interveningRef)
{
_nbhdGTcalculator = GenotypeCreator.CreateGenotypeCalculator(variantCallingParams.PloidyModel, variantCallingParams.MinimumFrequencyFilter,
variantCallingParams.MinimumCoverage,
variantCallingParams.DiploidThresholdingParameters,
variantCallingParams.MinimumGenotpyeQScore, variantCallingParams.MaximumGenotpyeQScore);
VcfVariantSites = new List <VariantSite>();
_referenceName = refName;
_acceptedPhasedVariants = new List <CalledAllele>();
_rejectedPhasedVariants = new List <CalledAllele>();
UsedRefCountsLookup = new Dictionary <int, int>();
AddVariantSite(vs1, vs1.VcfReferenceAllele.Substring(0, 1));
AddVariantSite(vs2, interveningRef);
SetID();
}
protected virtual IAlleleCaller CreateVariantCaller(ChrReference chrReference, ChrIntervalSet intervalSet)
{
var coverageCalculator = CreateCoverageCalculator();
var genotypeCalculator = GenotypeCreator.CreateGenotypeCalculator(
_options.PloidyModel, _options.FilteredVariantFrequency, _options.MinimumDepth, _options.DiploidThresholdingParameters, _options.MinimumGenotypeQScore, _options.MaximumGenotypeQScore);
return(new AlleleCaller(new VariantCallerConfig
{
IncludeReferenceCalls = _options.OutputgVCFFiles,
MinVariantQscore = _options.MinimumVariantQScore,
MaxVariantQscore = _options.MaximumVariantQScore,
MinGenotypeQscore = _options.MinimumGenotypeQScore,
MaxGenotypeQscore = _options.MaximumGenotypeQScore,
VariantQscoreFilterThreshold = _options.FilteredVariantQScore,
MinCoverage = _options.MinimumDepth,
MinFrequency = _options.MinimumFrequency,
EstimatedBaseCallQuality = GetEstimatedBaseCallQuality(),
StrandBiasModel = _options.StrandBiasModel,
StrandBiasFilterThreshold = _options.StrandBiasAcceptanceCriteria,
FilterSingleStrandVariants = _options.FilterOutVariantsPresentOnlyOneStrand,
GenotypeCalculator = genotypeCalculator,
VariantFreqFilter = _options.FilteredVariantFrequency,
LowGTqFilter = _options.LowGenotypeQualityFilter,
IndelRepeatFilter = _options.IndelRepeatFilter,
LowDepthFilter = _options.LowDepthFilter,
ChrReference = chrReference,
RMxNFilterSettings = new RMxNFilterSettings
{
RMxNFilterMaxLengthRepeat = _options.RMxNFilterMaxLengthRepeat,
RMxNFilterMinRepetitions = _options.RMxNFilterMinRepetitions,
RMxNFilterFrequencyLimit = _options.RMxNFilterFrequencyLimit
},
NoiseModel = _options.NoiseModel
}, intervalSet,
CreateVariantCollapser(chrReference.Name, coverageCalculator),
coverageCalculator));
}
protected virtual IAlleleCaller CreateVariantCaller(ChrReference chrReference, ChrIntervalSet intervalSet, IAlignmentSource alignmentSource, HashSet <Tuple <string, int, string, string> > forceGtAlleles = null)
{
var coverageCalculator = CreateCoverageCalculator(alignmentSource);
var genotypeCalculator = GenotypeCreator.CreateGenotypeCalculator(
_options.VariantCallingParameters.PloidyModel, _options.VariantCallingParameters.MinimumFrequencyFilter,
_options.VariantCallingParameters.MinimumCoverage,
_options.VariantCallingParameters.DiploidSNVThresholdingParameters,
_options.VariantCallingParameters.DiploidINDELThresholdingParameters,
_options.VariantCallingParameters.AdaptiveGenotypingParameters,
_options.VariantCallingParameters.MinimumGenotypeQScore,
_options.VariantCallingParameters.MaximumGenotypeQScore,
_options.VariantCallingParameters.TargetLODFrequency,
_options.VariantCallingParameters.MinimumFrequency,
chrReference.Name, _options.VariantCallingParameters.IsMale);
genotypeCalculator.SetMinFreqFilter(_options.VariantCallingParameters.MinimumFrequencyFilter);
var locusProcessor = _options.VariantCallingParameters.PloidyModel == PloidyModel.DiploidByThresholding
? (ILocusProcessor) new DiploidLocusProcessor()
: new SomaticLocusProcessor();
var variantCallerConfig = new VariantCallerConfig
{
IncludeReferenceCalls = _options.VcfWritingParameters.OutputGvcfFile,
MinVariantQscore = _options.VariantCallingParameters.MinimumVariantQScore,
MaxVariantQscore = _options.VariantCallingParameters.MaximumVariantQScore,
MinGenotypeQscore = _options.VariantCallingParameters.MinimumGenotypeQScore,
MaxGenotypeQscore = _options.VariantCallingParameters.MaximumGenotypeQScore,
VariantQscoreFilterThreshold = _options.VariantCallingParameters.MinimumVariantQScoreFilter,
NoCallFilterThreshold = _options.VariantCallingParameters.NoCallFilterThreshold,
AmpliconBiasFilterThreshold = _options.VariantCallingParameters.AmpliconBiasFilterThreshold,
MinCoverage = _options.VariantCallingParameters.MinimumCoverage,
MinFrequency = genotypeCalculator.MinVarFrequency,
NoiseLevelUsedForQScoring = _options.VariantCallingParameters.NoiseLevelUsedForQScoring,
StrandBiasModel = _options.VariantCallingParameters.StrandBiasModel,
StrandBiasFilterThreshold = _options.VariantCallingParameters.StrandBiasAcceptanceCriteria,
FilterSingleStrandVariants = _options.VariantCallingParameters.FilterOutVariantsPresentOnlyOneStrand,
GenotypeCalculator = genotypeCalculator,
VariantFreqFilter = genotypeCalculator.MinVarFrequencyFilter,
LowGTqFilter = _options.VariantCallingParameters.LowGenotypeQualityFilter,
IndelRepeatFilter = _options.VariantCallingParameters.IndelRepeatFilter,
LowDepthFilter = _options.VariantCallingParameters.LowDepthFilter,
ChrReference = chrReference,
RMxNFilterSettings = new RMxNFilterSettings
{
RMxNFilterMaxLengthRepeat = _options.VariantCallingParameters.RMxNFilterMaxLengthRepeat,
RMxNFilterMinRepetitions = _options.VariantCallingParameters.RMxNFilterMinRepetitions,
RMxNFilterFrequencyLimit = _options.VariantCallingParameters.RMxNFilterFrequencyLimit
},
NoiseModel = _options.VariantCallingParameters.NoiseModel,
LocusProcessor = locusProcessor
};
var alleleCaller = new AlleleCaller(variantCallerConfig, intervalSet,
CreateVariantCollapser(chrReference.Name, coverageCalculator),
coverageCalculator);
alleleCaller.AddForcedGtAlleles(forceGtAlleles);
return(alleleCaller);
}
