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));
}
}
private static List <CalledAllele> ProcessMultiAllelicLocus(List <CalledAllele> orderedVariants,
RecalibrationResults results)
{
RecalibrationResult resultForVariant = GetModelFromType(orderedVariants[0], results);
MixtureModelResult mixtureModelResult = GetModelResult(orderedVariants[0], resultForVariant);
switch (mixtureModelResult.GenotypeCategory)
{
case SimplifiedDiploidGenotype.HomozygousRef:
case SimplifiedDiploidGenotype.HomozygousAlt:
var allele = UpdateGenotypeAndQScore(orderedVariants[0], mixtureModelResult);
return(new List <CalledAllele> {
allele
});
case SimplifiedDiploidGenotype.HeterozygousAltRef:
orderedVariants[0].Genotype = Genotype.HeterozygousAlt1Alt2;
orderedVariants[1].Genotype = Genotype.HeterozygousAlt1Alt2;
orderedVariants = UpdateMultiAllelicQScores(orderedVariants, results);
return(orderedVariants);
default:
throw new ArgumentException("Invalid model results");
}
}
private static List <CalledAllele> ProcessSingleVariantLocus(CalledAllele allele,
RecalibrationResults results)
{
RecalibrationResult resultForVariant = GetModelFromType(allele, results);
return(new List <CalledAllele> {
UpdateVariant(allele, resultForVariant)
});
}
private static RecalibrationResult GetModelFromType(CalledAllele allele, RecalibrationResults results)
{
var variantType = VariantReader.GetVariantType(allele);
RecalibrationResult resultForVariant;
if (variantType == VariantType.NoVariant || variantType == VariantType.Snv)
{
resultForVariant = results.SnvResults;
}
else if (variantType == VariantType.Indel)
{
resultForVariant = results.IndelResults;
}
else
{
throw new ArgumentException("Variant type unrecognized.");
}
return(resultForVariant);
}
public void Recalibrate()
{
// Read in VCF
Logger.WriteToLog("Reading in vcf for variant frequencies.");
List <RecalibratedVariantsCollection> variants = VariantReader.GetVariantFrequencies(_options.VcfPath);
// Fit new models or load models from file
List <MixtureModel> models;
if (_options.ModelFile == null)
{
models = GetNewModels(_options.VcfPath, _options.OutputDirectory, variants);
}
else
{
models = ApplyModels(_options.VcfPath, _options.ModelFile, variants);
}
RecalibrationResults recalibrationResults = SummarizeModels(models, variants);
AdaptiveGtWriter.RewriteVcf(_options.VcfPath, _options.OutputDirectory, _options, recalibrationResults);
}
private static List <CalledAllele> UpdateMultiAllelicQScores(List <CalledAllele> variantList, RecalibrationResults results)
{
// Determine model types
RecalibrationResult model1 = GetModelFromType(variantList[0], results);
RecalibrationResult model2 = GetModelFromType(variantList[1], results);
// Calculate posteriors based on multinomial distribution
int dp = variantList[0].TotalCoverage;
int[] ad = new int[3];
ad[2] = variantList[0].AlleleSupport; //temp[1];
ad[1] = variantList[1].AlleleSupport; //temp[0];
ad[0] = dp - ad[1] - ad[2];
if (ad[0] < 0)
{
ad[0] = 0;
dp = ad[1] + ad[2];
}
var mixtureModelResult = MixtureModel.GetMultinomialQScores(ad, dp,
new List <double[]> {
model1.Means, model2.Means
});
// Update variant genotypes fields
variantList[0].GenotypePosteriors = mixtureModelResult.GenotypePosteriors;
variantList[1].GenotypePosteriors = mixtureModelResult.GenotypePosteriors;
variantList[0].GenotypeQscore = mixtureModelResult.QScore;
variantList[1].GenotypeQscore = mixtureModelResult.QScore;
return(variantList);
}
public static void RewriteVcf(string vcfIn, string outDir, AdaptiveGtOptions options, RecalibrationResults results)
{
Logger.WriteToLog("Rewriting VCF.");
string vcfFileName = Path.GetFileName(vcfIn);
if (vcfFileName.Contains("genome."))
{
vcfFileName = vcfFileName.Replace("genome", "recal");
}
else
{
vcfFileName = vcfFileName.Replace(".vcf", ".recal.vcf");
}
string vcfOut = Path.Combine(outDir, vcfFileName);
if (File.Exists(vcfOut))
{
File.Delete(vcfOut);
}
VcfUpdater <RecalibrationResults> .UpdateVcfLociByLoci(vcfOut, options, false, results, LocusProcessor.ProcessLocus,
(List <string> vcfLine) => TypeOfUpdateNeeded.Modify, GetAdaptiveGtWriter);
Logger.WriteToLog("filtering complete.");
}