public void VennVcf_CombineTwoPoolVariants_Qscore_DiffentNL_Test()
{
//chr3 41266161 . A G 30 PASS DP=3067 GT:GQ:AD:VF:NL:SB 0/1:30:3005,54:0.0176:35:-100.0000
CalledAllele VarA = new CalledAllele()
{
Chromosome = "chr3",
ReferencePosition = 41266161,
TotalCoverage = 3067,
Genotype = Pisces.Domain.Types.Genotype.HeterozygousAltRef,
VariantQscore = 30,
GenotypeQscore = 30,
AlleleSupport = 54,
ReferenceSupport = 3005,
NoiseLevelApplied = 35,
StrandBiasResults = new Pisces.Domain.Models.BiasResults()
{
GATKBiasScore = -100.0000
},
ReferenceAllele = "A",
AlternateAllele = "G",
Type = Pisces.Domain.Types.AlleleCategory.Snv
};
///chr3 41266161 . A . 75 PASS DP=3795 GT:GQ:AD:VF:NL:SB 0/0:75:3780:0.0040:2:-100.0000
CalledAllele VarB = new CalledAllele()
{
Chromosome = "chr3",
ReferencePosition = 41266161,
TotalCoverage = 3795,
Genotype = Pisces.Domain.Types.Genotype.HomozygousRef,
VariantQscore = 75,
GenotypeQscore = 75,
AlleleSupport = 3780,
ReferenceSupport = 3780,
NoiseLevelApplied = 2,
StrandBiasResults = new Pisces.Domain.Models.BiasResults()
{
GATKBiasScore = -100.0000
},
ReferenceAllele = "A",
AlternateAllele = ".",
Type = Pisces.Domain.Types.AlleleCategory.Reference
};
//old answer
//chr3 41266161 . A . 100.00 PASS DP=6862;cosmic=COSM1423020,COSM1423021;EVS=0|69.0|6503;phastCons GT:GQ:AD:VF:NL:SB:PB:GQX 0/0:100:6785:0.0079:35:-100:-100.0000:100
SampleAggregationParameters SampleAggregationOptions = new SampleAggregationParameters();
SampleAggregationOptions.ProbePoolBiasThreshold = 0.5f;
SampleAggregationOptions.HowToCombineQScore = SampleAggregationParameters.CombineQScoreMethod.CombinePoolsAndReCalculate;
_basicOptions.BamFilterParams.MinimumBaseCallQuality = 20;
_basicOptions.VariantCallingParams.MinimumFrequency = 0.01f;
_basicOptions.VariantCallingParams.MinimumFrequencyFilter = 0.03f;
_basicOptions.SampleAggregationParameters = SampleAggregationOptions;
string consensusOut = Path.Combine(_TestDataPath, "ConsensusOut.vcf");
VariantComparisonCase ComparisonCase = VennProcessor.GetComparisonCase(VarA, VarB);
ConsensusBuilder consensusBuilder = new ConsensusBuilder(consensusOut, _basicOptions);
AggregateAllele consensus = consensusBuilder.CombineVariants(VarA, VarB, ComparisonCase);
Console.WriteLine(consensus.ToString());
double expectedNoiseLevel = MathOperations.PtoQ(
(MathOperations.QtoP(35) + MathOperations.QtoP(2)) / (2.0)); // 5
//GT:GQ:AD:VF:NL:SB:PB:GQX 0/0:100:6785:0.0079:35:-100:-100.0000:100
Assert.NotNull(consensus);
Assert.Equal(consensus.VariantQscore, 100);
Assert.Equal(consensus.ReferenceAllele, "A");
Assert.Equal(consensus.AlternateAllele, ".");
Assert.Equal(consensus.Genotype, Pisces.Domain.Types.Genotype.HomozygousRef);
Assert.Equal(consensus.TotalCoverage, 6862);
Assert.Equal(consensus.ReferenceSupport, 6785);
Assert.Equal(consensus.AlleleSupport, 6785);
Assert.Equal(consensus.GenotypeQscore, 100);
Assert.Equal(consensus.Frequency, 0.98877877f);
Assert.Equal(consensus.NoiseLevelApplied, ((int)expectedNoiseLevel));
Assert.Equal(consensus.NoiseLevelApplied, 5);
Assert.Equal(consensus.StrandBiasResults.GATKBiasScore, -100);
Assert.Equal(consensus.PoolBiasResults.GATKBiasScore, -100.0000);
//now check, we take the min NL score if we are taking the min Q score.
// (in this case of combined alt+ref -> ref, the q score will still need to be recalculated.
//just with the MIN NL.
SampleAggregationOptions.HowToCombineQScore = SampleAggregationParameters.CombineQScoreMethod.TakeMin;
ComparisonCase = VennProcessor.GetComparisonCase(VarA, VarB);
consensus = consensusBuilder.CombineVariants(VarA, VarB, ComparisonCase);
Assert.Equal(consensus.NoiseLevelApplied, 2);
Assert.Equal(consensus.VariantQscore, 100);
//ok, now sanity check we dont barf if either input is null:
ComparisonCase = VennProcessor.GetComparisonCase(VarA, null);
consensus = consensusBuilder.CombineVariants(VarA, null, ComparisonCase);
Assert.Equal(consensus.NoiseLevelApplied, 35);
Assert.Equal(consensus.VariantQscore, 100);
ComparisonCase = VennProcessor.GetComparisonCase(null, VarB);
consensus = consensusBuilder.CombineVariants(null, VarB, ComparisonCase);
Assert.Equal(consensus.NoiseLevelApplied, 2);
Assert.Equal(consensus.VariantQscore, 100);
//ok, lets check this again, for the PoolQScores option.
//sanity check we dont barf if either input is null:
SampleAggregationOptions.HowToCombineQScore = SampleAggregationParameters.CombineQScoreMethod.CombinePoolsAndReCalculate;
ComparisonCase = VennProcessor.GetComparisonCase(VarA, null);
consensus = consensusBuilder.CombineVariants(VarA, null, ComparisonCase);
Assert.Equal(consensus.NoiseLevelApplied, 35);
Assert.Equal(consensus.VariantQscore, 100);//low freq variant -> nocall. note, qscore would be 41 if NL = 20.
ComparisonCase = VennProcessor.GetComparisonCase(null, VarB);
consensus = consensusBuilder.CombineVariants(null, VarB, ComparisonCase);
Assert.Equal(consensus.NoiseLevelApplied, 2);
Assert.Equal(consensus.VariantQscore, 100); //sold ref
}
