private static void GetBinRatio(string tumorBinnedPath, string normalBinnedPath, string ratioBinnedPath,
string ploidyBedPath, NexteraManifest manifest = null)
{
PloidyInfo referencePloidy = String.IsNullOrEmpty(ploidyBedPath) ? null : PloidyInfo.LoadPloidyFromBedFile(ploidyBedPath);
double tumorMedian = (new BinCounts(tumorBinnedPath, manifest: manifest)).OnTargetMedianBinCount;
double normalMedian = (new BinCounts(normalBinnedPath, manifest: manifest)).OnTargetMedianBinCount;
double librarySizeFactor = (tumorMedian > 0 && normalMedian > 0) ? normalMedian / tumorMedian : 1;
using (GzipReader tumorReader = new GzipReader(tumorBinnedPath))
using (GzipReader normalReader = new GzipReader(normalBinnedPath))
using (GzipWriter writer = new GzipWriter(ratioBinnedPath))
{
string normalLine;
string tumorLine;
string[] normalToks;
string[] tumorToks;
double normalCount;
double tumorCount;
double ratio;
while ((normalLine = normalReader.ReadLine()) != null)
{
tumorLine = tumorReader.ReadLine();
normalToks = normalLine.Split('\t');
tumorToks = tumorLine.Split('\t');
normalCount = double.Parse(normalToks[3]);
tumorCount = double.Parse(tumorToks[3]);
// The weighted average count of a bin could be less than 1.
// Using these small counts for coverage normalization creates large ratios.
// It would be better to just drop these bins so we don't introduce too much noise into segmentation and CNV calling.
if (normalCount < 1) { continue; } // skip the bin
string chrom = normalToks[0];
int start = int.Parse(normalToks[1]);
int end = int.Parse(normalToks[2]);
// get the normal ploidy from intervalsWithPloidyByChrom
double factor = CanvasDiploidBinRatioFactor * GetPloidy(referencePloidy, chrom, start, end) / 2.0;
ratio = tumorCount / normalCount * factor * librarySizeFactor;
normalToks[3] = String.Format("{0}", ratio);
writer.WriteLine(String.Join("\t", normalToks));
}
}
}
