public int CallVariants(string variantFrequencyFile, string inFile, string outFile, string ploidyVcfPath, string referenceFolder, string sampleName,
string truthDataPath)
{
if (!string.IsNullOrEmpty(truthDataPath))
{
_cnOracle = new CopyNumberOracle();
_cnOracle.LoadKnownCN(truthDataPath);
}
_segments = Segments.ReadSegments(_logger, new FileLocation(inFile));
_allSegments = _segments.AllSegments.ToList();
TempFolder = Path.GetDirectoryName(inFile);
if (_allSegments.Count == 0)
{
Console.WriteLine("CanvasDiploidCaller: No segments loaded; no CNV calls will be made.");
CanvasSegmentWriter.WriteSegments(outFile, _allSegments, _model?.DiploidCoverage, referenceFolder,
sampleName, null, null, QualityFilterThreshold, false, null, null);
return(0);
}
PloidyInfo ploidy = null;
if (!string.IsNullOrEmpty(ploidyVcfPath))
{
ploidy = PloidyInfo.LoadPloidyFromVcfFileNoSampleId(ploidyVcfPath);
}
// load MAF
var allelesByChromosome = CanvasIO.ReadFrequenciesWrapper(_logger, new FileLocation(variantFrequencyFile), _segments.IntervalsByChromosome);
_segments.AddAlleles(allelesByChromosome);
MeanCoverage = allelesByChromosome.SelectMany(x => x.Value).SelectMany(y => y.TotalCoverage).Average();
AggregateVariantCoverage(ref _allSegments);
// Create new models for different copy number states
InitializePloidies();
// Compute statistics on the copy number two regions
float[] diploidCounts = AggregateCounts(ref _allSegments);
_diploidCoverage = Utilities.Mean(diploidCounts);
_coverageWeightingFactor = CoverageWeighting / _diploidCoverage;
// new coverage model
_model = new CoverageModel {
DiploidCoverage = _diploidCoverage
};
List <SegmentInfo> segments = new List <SegmentInfo>();
foreach (CanvasSegment segment in _allSegments)
{
SegmentInfo info = new SegmentInfo {
Segment = segment
};
List <double> mafs = new List <double>();
foreach (float value in segment.Balleles.Frequencies)
{
mafs.Add(value > 0.5 ? 1 - value : value);
}
if (mafs.Count > 0)
{
info.Maf = Utilities.Median(mafs);
}
else
{
info.Maf = -1;
}
info.Coverage = Utilities.Median(segment.Counts);
info.Weight = _allSegments.Count > 100 ? segment.Length : segment.BinCount;
segments.Add(info);
}
AssignPloidyCallsDistance(_model);
CanvasSegment.AssignQualityScores(_allSegments, CanvasSegment.QScoreMethod.LogisticGermline, _germlineScoreParameters);
// Merge neighboring segments that got the same copy number call.
// merging segments requires quality scores so we do it after quality scores have been assigned
var mergedSegments = CanvasSegment.MergeSegments(_allSegments);
// recalculating qscores after merging segments improves performance!
CanvasSegment.AssignQualityScores(mergedSegments, CanvasSegment.QScoreMethod.LogisticGermline, _germlineScoreParameters);
CanvasSegment.SetFilterForSegments(QualityFilterThreshold, mergedSegments, CanvasFilter.SegmentSizeCutoff);
List <string> extraHeaders = new List <string>();
var coverageOutputPath = SingleSampleCallset.GetCoverageAndVariantFrequencyOutputPath(outFile);
CanvasSegment.WriteCoveragePlotData(mergedSegments, _model.DiploidCoverage, ploidy, coverageOutputPath, referenceFolder);
if (_cnOracle != null)
{
GenerateReportVersusKnownCopyNumber();
}
if (!string.IsNullOrEmpty(ploidy?.HeaderLine))
{
extraHeaders.Add(ploidy.HeaderLine);
}
CanvasSegmentWriter.WriteSegments(outFile, mergedSegments, _model.DiploidCoverage, referenceFolder, sampleName,
extraHeaders, ploidy, QualityFilterThreshold, false, null, null);
return(0);
}
