// var poissonDist = new MathNet.Numerics.Distributions.Poisson(errorRate * coverage);
public static double AssignRawPoissonQScore(int callCount, int coverage, int estimatedBaseCallQuality)
// ReSharper restore InconsistentNaming
{
double errorRate = MathOperations.QtoP(estimatedBaseCallQuality);
double callCountMinusOne = callCount - 1;
double callCountDouble = callCount;
var lambda = errorRate * coverage;
var poissonDist = new MathNet.Numerics.Distributions.Poisson(lambda);
var pValue = 1 - poissonDist.CumulativeDistribution(callCountMinusOne);
if (pValue > 0)
{
return(MathOperations.PtoQ(pValue));
}
else
{
//Approximation to get around precision issues.
double A = poissonDist.ProbabilityLn((int)callCountMinusOne);
double correction = (callCountDouble - lambda) / callCountDouble;
var qScore = -10.0 * (A - Math.Log(2.0 * correction)) / Math.Log(10.0);
return(qScore);
}
}
public static double AssignPValue(int observedCallCount, int coverage, int estimatedBaseCallQuality)
{
double errorRate = MathOperations.QtoP(estimatedBaseCallQuality);
if (observedCallCount == 0)
{
return(1.0);
}
return(1 - Poisson.Cdf(observedCallCount - 1.0, coverage * errorRate));
}
public static int Compute(CalledAllele allele, float targetLimitOfDetectionVF, int minGTQScore, int maxGTQScore)
{
double rawQ = allele.VariantQscore;
if ((allele.TotalCoverage == 0) || (allele.IsNocall))
{
return(minGTQScore);
}
if ((allele.Genotype == Genotype.HomozygousRef) || (allele.Genotype == Genotype.HomozygousAlt))
{
//a homozygous somatic call GT is a fairly strong statement. It implies
//A) we found the allele for sure (the VariantQscore)
var p1 = MathOperations.QtoP(allele.VariantQscore);
//and
//B) the chance that we missed any alternate calls is very small.
// this would be the chance false negative given VF=min freq, and coverage is as given.
//these are explictly typed, to prevent any win/linux diffs sneaking in
// in float -> double conversions inside downstream arguments
float nonAlleleObservationsF = (1f - allele.Frequency) * allele.TotalCoverage;
float expectedNonAllelObservationsF = targetLimitOfDetectionVF * allele.TotalCoverage;
//This takes care of the cases:
//A) we dont have enough depth to ever observe any non-ref variant. If, if depth is 10, we would never see a 5% variant anyway.
//B) if we see 6% not reference > 5% min safe var call freqeuncy, we are pretty worried about calling this as a 0/0 GT
if (nonAlleleObservationsF >= expectedNonAllelObservationsF)
{
return(minGTQScore);
}
//var p2 = poissonDist.CumulativeDistribution(nonRefObservations); <- this method does badly for values lower than the mean
var p2 = Poisson.Cdf(nonAlleleObservationsF, expectedNonAllelObservationsF);
rawQ = MathOperations.PtoQ(p1 + p2);
}
var qScore = Math.Min(maxGTQScore, rawQ);
qScore = Math.Max(qScore, minGTQScore);
return((int)Math.Round(qScore));
}
