Release 1.40.0.1613+master

Illumina · Apr 8, 2019 · 5d187fc · 5d187fc
2 parents 6571108 + 01584bb
commit 5d187fc
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Showing 9 changed files with 41 additions and 11 deletions.
diff --git a/Src/Canvas/CanvasPedigreeCaller/CanvasPedigreeCaller.cs b/Src/Canvas/CanvasPedigreeCaller/CanvasPedigreeCaller.cs
@@ -358,7 +358,7 @@ private double GetSegmentSetLogLikelihood(ISampleMap<OverlappingSegmentsRegion>
             }
             foreach (var canvasSegment in canvasSegments)
             {
-                var copyNumbersLikelihoods = _copyNumberLikelihoodCalculator.GetCopyNumbersLikelihoods(canvasSegment, samplesInfo, copyNumberModel);
+                var copyNumbersLikelihoods = _copyNumberLikelihoodCalculator.GetCopyNumbersLikelihoods(canvasSegment, samplesInfo, copyNumberModel, _callerParameters.NumberOfTrimmedBins);
                 var (_, likelihoods) = GetCopyNumbersNoPedigreeInfo(canvasSegment, copyNumbersLikelihoods);
                 segmentSetLogLikelihood += likelihoods.MaximalLogLikelihood;
             }

diff --git a/Src/Canvas/CanvasPedigreeCaller/CopyNumberLikelihoodCalculator.cs b/Src/Canvas/CanvasPedigreeCaller/CopyNumberLikelihoodCalculator.cs
@@ -20,9 +20,8 @@ public CopyNumberLikelihoodCalculator(int maximumCopyNumber)
         /// Use likelihoods as only median point estimator is used
         /// </summary>
         public ISampleMap<Dictionary<Genotype, double>> GetCopyNumbersLikelihoods(ISampleMap<CanvasSegment> canvasSegments, ISampleMap<SampleMetrics> samplesInfo,
-            ISampleMap<ICopyNumberModel> copyNumberModel)
+            ISampleMap<ICopyNumberModel> copyNumberModel, int numberOfTrimmedBins)
         {
-            const int bins2Remove = 5;
             var genotypes = Enumerable.Range(0, _maximumCopyNumber).Select(Genotype.Create).ToList();
             const double maxCoverageMultiplier = 3.0;
             var singleSampleLikelihoods = new SampleMap<Dictionary<Genotype, double>>();
@@ -33,10 +32,27 @@ public ISampleMap<Dictionary<Genotype, double>> GetCopyNumbersLikelihoods(ISampl
 
                 foreach (var genotypeCopyNumber in genotypes)
                 {
+                    double cvg = Math.Min(canvasSegments[sampleId].TruncatedMedianCount(numberOfTrimmedBins),
+                                samplesInfo[sampleId].MeanCoverage * maxCoverageMultiplier);
+                    // In case we run into out-of-range trouble again (CANV-694), print details
+                    {
+                        int intcvg = Convert.ToInt32(cvg);
+                        int coverageBound = copyNumberModel[sampleId].GetCoverageBound();
+                        double truncatedDepth = canvasSegments[sampleId].TruncatedMedianCount(numberOfTrimmedBins);
+                        double meanTimesThree = samplesInfo[sampleId].MeanCoverage * maxCoverageMultiplier;
+                        int maxAllowedCN = copyNumberModel[sampleId].GetMaxCopyNumber();
+                        if ( intcvg >= coverageBound || genotypeCopyNumber.TotalCopyNumber > maxAllowedCN)
+                        {
+                            throw new ArgumentException(
+                                $"Tried to look up bad depth or CN for {sampleId}: depth {intcvg} CN {genotypeCopyNumber.TotalCopyNumber}" +
+                                $" where max handled values are {coverageBound} and {maxAllowedCN} respectively;" +
+                                $" original depth was {truncatedDepth}, mean * 3 was {meanTimesThree};" +
+                                $" segment {canvasSegments[sampleId].Chr}:{canvasSegments[sampleId].Begin}-{canvasSegments[sampleId].End}");
+
+                        }
+                    }
                     double currentLikelihood =
-                        copyNumberModel[sampleId].GetTotalCopyNumberLikelihoods(
-                            Math.Min(canvasSegments[sampleId].TruncatedMedianCount(bins2Remove),
-                                samplesInfo[sampleId].MeanCoverage * maxCoverageMultiplier), genotypeCopyNumber);
+                        copyNumberModel[sampleId].GetTotalCopyNumberLikelihoods(cvg, genotypeCopyNumber);
                     currentLikelihood = Double.IsNaN(currentLikelihood) || Double.IsInfinity(currentLikelihood)
                         ? 0
                         : currentLikelihood;

diff --git a/Src/Canvas/CanvasPedigreeCaller/HaplotypeCopyNumberModel.cs b/Src/Canvas/CanvasPedigreeCaller/HaplotypeCopyNumberModel.cs
@@ -29,6 +29,18 @@ public HaplotypeCopyNumberModel(List<List<double>> cnDistribution, Tuple<List<do
                 _logFactorial.Add(Math.Log(i) + _logFactorial.Last());
         }
 
+        public int GetCoverageBound()
+        {
+            // _maxAlleleCounts is twice the first value for which _cnDistribution is undefined
+            // see HaplotypeCopyNumberModelFactory::CreateModel() for details
+            return _maxAlleleCounts / 2;
+        }
+
+        public int GetMaxCopyNumber()
+        {
+            return _cnDistribution.Count - 1;
+        }
+
         public double GetTotalCopyNumberLikelihoods(double segmentMedianBinCoverage, Genotype totalCopyNumberGenotype)
         {
             return _cnDistribution.Select(x => x[Convert.ToInt32(segmentMedianBinCoverage)]).ElementAt(totalCopyNumberGenotype.TotalCopyNumber);

diff --git a/Src/Canvas/CanvasPedigreeCaller/HaplotypeVariantCaller.cs b/Src/Canvas/CanvasPedigreeCaller/HaplotypeVariantCaller.cs
@@ -27,7 +27,7 @@ public HaplotypeVariantCaller(CopyNumberLikelihoodCalculator copyNumberLikelihoo
         public void CallVariant(ISampleMap<CanvasSegment> canvasSegments, ISampleMap<SampleMetrics> samplesInfo,
             ISampleMap<ICopyNumberModel> copyNumberModel, PedigreeInfo pedigreeInfo)
         {
-            var coverageLikelihoods = _copyNumberLikelihoodCalculator.GetCopyNumbersLikelihoods(canvasSegments, samplesInfo, copyNumberModel);
+            var coverageLikelihoods = _copyNumberLikelihoodCalculator.GetCopyNumbersLikelihoods(canvasSegments, samplesInfo, copyNumberModel, _callerParameters.NumberOfTrimmedBins);
             // if number and properties of SNPs in the segment are above threshold, calculate likelihood from SNPs and merge with
             // coverage likelihood to form merged likelihoods
             int nBalleles = canvasSegments.Values.First().Balleles.Size();

diff --git a/Src/Canvas/CanvasPedigreeCaller/ICopyNumberModel.cs b/Src/Canvas/CanvasPedigreeCaller/ICopyNumberModel.cs
@@ -6,6 +6,8 @@ public interface ICopyNumberModel
     {
         double GetGenotypeLogLikelihood(Balleles segmentAlleleReadCounts, PhasedGenotype phasedGenotype);
         double GetTotalCopyNumberLikelihoods(double segmentMedianBinCoverage, Genotype totalCopyNumberGenotype);
+        int GetCoverageBound();
+        int GetMaxCopyNumber();
     }
 
     public interface ICopyNumberModelFactory

diff --git a/Src/Canvas/CanvasPedigreeCaller/PedigreeCallerParameters.cs b/Src/Canvas/CanvasPedigreeCaller/PedigreeCallerParameters.cs
@@ -20,7 +20,7 @@ public class PedigreeCallerParameters
         public int MaxNumOffspringGenotypes { get; set; } = 500;
         public double DeNovoRate { get; set; } = 0.00001;
         public int MinimumCallSize { get; set; } = 2000;
-        public int NumberOfTrimmedBins { get; set; } = 2;
+        public int NumberOfTrimmedBins { get; set; } = 5;
         public int MaxCoreNumber { get; set; } = 30;
         [JsonProperty("DefaultCaller")]
         [JsonConverter(typeof(StringEnumConverter))]

diff --git a/Src/Canvas/CanvasPedigreeCaller/PedigreeCallerParameters.json b/Src/Canvas/CanvasPedigreeCaller/PedigreeCallerParameters.json
@@ -9,7 +9,7 @@
   "MaxNumOffspringGenotypes": 500,
   "DeNovoRate": 0.00001,
   "MinimumCallSize": 2000,
-  "NumberOfTrimmedBins": 2,
+  "NumberOfTrimmedBins": 5,
   "MaxCoreNumber": 30,
   "DefaultCaller": "VariantCaller"
 }
diff --git a/Src/Canvas/CanvasPedigreeCaller/VariantCaller.cs b/Src/Canvas/CanvasPedigreeCaller/VariantCaller.cs
@@ -128,7 +128,7 @@ private static int GetCnState(ISampleMap<CanvasSegment> canvasSegmentsSet, Sampl
         public void CallVariant(ISampleMap<CanvasSegment> canvasSegments, ISampleMap<SampleMetrics> samplesInfo,
             ISampleMap<ICopyNumberModel> copyNumberModel, PedigreeInfo pedigreeInfo)
         {
-            var singleSampleLikelihoods = _copyNumberLikelihoodCalculator.GetCopyNumbersLikelihoods(canvasSegments, samplesInfo, copyNumberModel);
+            var singleSampleLikelihoods = _copyNumberLikelihoodCalculator.GetCopyNumbersLikelihoods(canvasSegments, samplesInfo, copyNumberModel, _callerParameters.NumberOfTrimmedBins);
 
             (var pedigreeCopyNumbers, var pedigreeLikelihoods) = GetPedigreeCopyNumbers(pedigreeInfo, singleSampleLikelihoods);
 

diff --git a/version.txt b/version.txt
@@ -1,2 +1,2 @@
-version: 1.39.0
+version: 1.40.0
 configuration: Release