private static BiasResults GetProbePoolBiasScore(VariantComparisonCase Case, CalledAllele Consensus,
float ProbePoolBiasThreshold, VariantCallingParameters variantCallingParameters, int AltCountA, int AltCountB, int DepthA, int DepthB, Genotype Genotype, bool AltChangeToRef)
{
double ProbePoolPScore = 0; //no bias;
double ProbePoolGATKBiasScore = -100; //no bias;
int NoiseLevel = Consensus.NoiseLevelApplied;
BiasResults PB = new BiasResults();
if ((AltChangeToRef) || (Case == VariantComparisonCase.AgreedOnReference))
{
PB.GATKBiasScore = ProbePoolGATKBiasScore;
PB.BiasScore = ProbePoolPScore;
return(PB);
}
if ((Case == VariantComparisonCase.OneReferenceOneAlternate) ||
(Case == VariantComparisonCase.CanNotCombine))
{
Consensus.Filters.Add(FilterType.PoolBias);
PB.GATKBiasScore = 0;
PB.BiasScore = 1;
return(PB);
}
if (Case == VariantComparisonCase.AgreedOnAlternate)
{
int[] supportByPool = new int[]
{
AltCountA, AltCountB, 0
};
int[] covByPool = new int[]
{
DepthA, DepthB, 0
};
BiasResults ProbePoolBiasResults =
StrandBiasCalculator.CalculateStrandBiasResults(
covByPool, supportByPool,
NoiseLevel, variantCallingParameters.MinimumFrequency, ProbePoolBiasThreshold, StrandBiasModel.Extended);
ProbePoolGATKBiasScore = Math.Min(0, ProbePoolBiasResults.GATKBiasScore); //just cap it at upperbound 0, dont go higher.
ProbePoolGATKBiasScore = Math.Max(-100, ProbePoolGATKBiasScore); //just cap it at lowerbound -100, dont go higher.
ProbePoolPScore = Math.Min(1, ProbePoolBiasResults.BiasScore);
if (!ProbePoolBiasResults.BiasAcceptable)
{
Consensus.Filters.Add(FilterType.PoolBias);
}
}
PB.GATKBiasScore = ProbePoolGATKBiasScore;
PB.BiasScore = ProbePoolPScore;
return(PB);
}
public void TestSBCalculationsForForcedVariants()
{
var CoverageByStrandDirection = new int[] { 70038, 65998, 0 }; //forward,reverse,stitched
var SupportByStrandDirection = new int[] { 54, 11, 0 };
BiasResults SB = StrandBiasCalculator.CalculateStrandBiasResults(
CoverageByStrandDirection, SupportByStrandDirection, 20, 0.01, 0.5, StrandBiasModel.Poisson);
Assert.Equal(SB.BiasScore, 1.0);
Assert.Equal(SB.GATKBiasScore, 0);
}
public void TestSBCalculationsForSomaticAndDiploidSettings()
{
double fwdCov = 10000;
double revCov = 10000;
double testVariantFreqA = 0.05;
double testVariantFreqB = 0.25;
double testVariantFreqC = 0.020;
double testVariantFreqD = 0.005;
var CoverageByStrandDirection = new int[] { (int)fwdCov, (int)revCov, 0 }; //forward,reverse,stitched
var EqualSupportByStrandDirectionA = new int[] { (int)(fwdCov * testVariantFreqA), (int)(revCov * testVariantFreqA), 0 };
var EqualSupportByStrandDirectionB = new int[] { (int)(fwdCov * testVariantFreqB), (int)(revCov * testVariantFreqB), 0 };
//happy path, no bias
BiasResults SB_somatic = StrandBiasCalculator.CalculateStrandBiasResults(
CoverageByStrandDirection, EqualSupportByStrandDirectionB, 20, 0.01, 0.5, StrandBiasModel.Extended);
BiasResults SB_diploid = StrandBiasCalculator.CalculateStrandBiasResults(
CoverageByStrandDirection, EqualSupportByStrandDirectionB, 20, 0.20, 0.5, StrandBiasModel.Diploid);
Assert.Equal(SB_somatic.BiasScore, 0);
Assert.Equal(SB_somatic.GATKBiasScore, double.NegativeInfinity);
Assert.Equal(SB_somatic.BiasAcceptable, true);
Assert.Equal(SB_diploid.BiasScore, 0);
Assert.Equal(SB_diploid.GATKBiasScore, double.NegativeInfinity);
Assert.Equal(SB_diploid.BiasAcceptable, true);
//bias if you are looking for a 20% variant (only one side is sufficient to call),
//but not biased in the somatic case (both show up sufficiently)
var SupportByStrandDirection_bias20 = new int[] { (int)(fwdCov * testVariantFreqA), (int)(revCov * testVariantFreqB), 0 };
SB_somatic = StrandBiasCalculator.CalculateStrandBiasResults(
CoverageByStrandDirection, SupportByStrandDirection_bias20, 20, 0.01, 0.5, StrandBiasModel.Extended);
SB_diploid = StrandBiasCalculator.CalculateStrandBiasResults(
CoverageByStrandDirection, SupportByStrandDirection_bias20, 20, 0.20, 0.5, StrandBiasModel.Diploid);
Assert.Equal(SB_somatic.BiasScore, 0);
Assert.Equal(SB_somatic.GATKBiasScore, double.NegativeInfinity);
Assert.Equal(SB_somatic.BiasAcceptable, true);
Assert.Equal(Math.Log10(SB_diploid.BiasScore), 74.3, 1); // a great big bias
Assert.Equal(SB_diploid.GATKBiasScore, 743.5, 1);
Assert.Equal(SB_diploid.BiasAcceptable, false);
//bias if you are looking for even a 1% variant or a 20% variant
var SupportByStrandDirection_bias01 = new int[] { (int)(fwdCov * testVariantFreqC), (int)(revCov * testVariantFreqD), 0 };
SB_somatic = StrandBiasCalculator.CalculateStrandBiasResults(
CoverageByStrandDirection, SupportByStrandDirection_bias01, 20, 0.01, 0.5, StrandBiasModel.Extended);
SB_diploid = StrandBiasCalculator.CalculateStrandBiasResults(
CoverageByStrandDirection, SupportByStrandDirection_bias01, 20, 0.20, 0.5, StrandBiasModel.Diploid);
Assert.Equal(SB_somatic.BiasScore, 1.000, 3);
Assert.Equal(SB_somatic.GATKBiasScore, 0.002, 3);
Assert.Equal(SB_somatic.BiasAcceptable, false);
Assert.Equal(SB_diploid.BiasScore, 1.000, 3);// a great big bias
Assert.Equal(SB_diploid.GATKBiasScore, 0.000, 3);
Assert.Equal(SB_diploid.BiasAcceptable, false);
}
