private void AssignMcc(CanvasSegment canvasSegment, ICopyNumberModel copyNumberModel,
PhasedGenotype gtStates, int copyNumber)
{
const int diploidCopyNumber = 2;
if (copyNumber > diploidCopyNumber)
{
canvasSegment.MajorChromosomeCount =
Math.Max(gtStates.CopyNumberA, gtStates.CopyNumberB);
int?selectedGtState = _genotypes[copyNumber].IndexOf(gtStates);
canvasSegment.MajorChromosomeCountScore = GetGtLogLikelihoodScore(canvasSegment.Balleles, _genotypes[copyNumber], ref selectedGtState, copyNumberModel);
}
else
{
// variant caller does not attempt to call LOH, for DELs CN=MCC
if (copyNumber == diploidCopyNumber)
{
canvasSegment.MajorChromosomeCount = null;
}
else
{
canvasSegment.MajorChromosomeCount = copyNumber;
}
canvasSegment.MajorChromosomeCountScore = null;
}
}
private double GetProbandLogLikelihood(ICopyNumberModel copyNumberModel, int childCopyNumber, PhasedGenotype parent1GtStates, PhasedGenotype parent2GtStates, bool isInheritedCnv, CanvasSegment canvasSegment,
double bestLogLikelihood, ref PhasedGenotype bestGtState)
{
foreach (var childGtState in _genotypes[childCopyNumber])
{
double currentChildLogLikelihood;
if (IsGtPedigreeConsistent(parent1GtStates, childGtState) &&
IsGtPedigreeConsistent(parent2GtStates, childGtState) &&
isInheritedCnv)
{
currentChildLogLikelihood = copyNumberModel.GetGenotypeLogLikelihood(canvasSegment.Balleles, childGtState);
}
else
{
continue;
}
if (currentChildLogLikelihood > bestLogLikelihood)
{
bestLogLikelihood = currentChildLogLikelihood;
bestGtState = childGtState;
}
}
return(bestLogLikelihood);
}
private static double GetCurrentGtLogLikelihood(ICopyNumberModel copyNumberModel, CanvasSegment canvasSegment, PhasedGenotype gtStates)
{
return(copyNumberModel.GetGenotypeLogLikelihood(canvasSegment.Balleles, gtStates));
}
internal static double GetGtLogLikelihoodScore(Balleles gtObservedCounts, List <PhasedGenotype> gtModelCounts, ref int?selectedGtState, ICopyNumberModel copyNumberModel)
{
const int maxGQscore = 60;
var gtLogLikelihoods = Enumerable.Repeat(Double.NegativeInfinity, gtModelCounts.Count).ToList();
var gtModelCounter = -1;
foreach (var gtModelCount in gtModelCounts)
{
gtModelCounter++;
// As we don't estimate allele CN but only MCC, focus on upper-triangle
if (gtModelCount.CopyNumberA < gtModelCount.CopyNumberB)
{
continue;
}
gtLogLikelihoods[gtModelCounter] = copyNumberModel.GetGenotypeLogLikelihood(gtObservedCounts, gtModelCount);
}
var maxLogLikelihood = gtLogLikelihoods.Max();
if (!selectedGtState.HasValue)
{
selectedGtState = gtLogLikelihoods.IndexOf(maxLogLikelihood);
}
double normalizationConstant = gtLogLikelihoods.Sum(ll => Math.Exp(ll - maxLogLikelihood));
double gqscore = -10.0 * Math.Log10((normalizationConstant - 1) / normalizationConstant);
if (Double.IsInfinity(gqscore) | gqscore > maxGQscore)
{
gqscore = maxGQscore;
}
return(Double.IsNaN(gqscore) || Double.IsInfinity(gqscore) ? 0 : gqscore);
}
