public CanvasRunner Create(bool isSomatic, CanvasCoverageMode coverageMode,
int countsPerBin, Dictionary <string, string> customParameters)
{
var settings = IsasConfigurationSettings.GetConfigSettings();
var canvasFolder = new DirectoryLocation(Isas.Framework.Utilities.Utilities.GetAssemblyFolder(typeof(CanvasRunner)));
var commandManager = new CommandManager(new ExecutableProcessor(settings, _logger, canvasFolder));
var tabixWrapper = TabixWrapperFactory.GetTabixWrapper(_logger, _workDoer, commandManager);
var bAlleleBedGraphWriter = new BAlleleBedGraphWriter(new BgzfBedGraphWriter(new RoundingBedGraphWriter(new BedGraphWriterFacade(), 4), tabixWrapper));
return(new CanvasRunner(_logger, _workDoer, _checkpointRunner, _runtimeExecutable, _runtimeCommandPrefix, isSomatic, coverageMode, countsPerBin, bAlleleBedGraphWriter, customParameters, canvasFolder.FullName));
}
public static void Evaluate(string truthSetPath, string cnvCallsPath, string excludedBed, string outputPath, EvaluateCnvOptions options)
{
double heterogeneityFraction = options.HeterogeneityFraction;
var knownCn = LoadKnownCn(truthSetPath, heterogeneityFraction);
knownCn = knownCn.SelectValues(
truthEntries => truthEntries.Where(truthEntry => truthEntry.Length >= options.MinEntrySize).ToList());
var calls = GetCnvCallsFromVcf(cnvCallsPath, options.DQscoreThreshold);
calls = calls.SelectValues(
chromosomeCalls => chromosomeCalls.Where(call => call.Length >= options.MinEntrySize).ToList());
// LoadRegionsOfInterest(options.RoiBed?.FullName);
var excludeIntervals = new Dictionary <string, List <CNInterval> >();
if (!string.IsNullOrEmpty(excludedBed))
{
var excludeIntervalsTmp = LoadIntervalsFromBed(excludedBed, false, 1.0);
List <string> keys = excludeIntervalsTmp.Keys.ToList();
foreach (string key in keys)
{
string chr = key;
if (!calls.ContainsKey(chr))
{
chr = key.Replace("chr", "");
}
if (!calls.ContainsKey(chr))
{
chr = "chr" + key;
}
if (!calls.ContainsKey(chr))
{
Console.WriteLine($"Error: Skipping exclude intervals for chromosome {key} with no truth data." +
$"Check that chromosome names are spelled correctly for exclude intervals");
continue;
}
excludeIntervals[chr] = excludeIntervalsTmp[key];
}
}
Console.WriteLine("TruthSet\t{0}", truthSetPath);
Console.WriteLine("CNVCalls\t{0}", cnvCallsPath);
bool includePassingOnly = Path.GetFileName(cnvCallsPath).ToLower().Contains("vcf");
var logger = new Logger(new[] { Console.Out }, new[] { Console.Error });
var settings = IsasConfigurationSettings.GetConfigSettings();
var output = new DirectoryLocation(outputPath);
var workerDirectory = new DirectoryLocation(Isas.Framework.Utilities.Utilities.GetAssemblyFolder(typeof(CNVChecker)));
var commandManager = new CommandManager(new ExecutableProcessor(settings, logger, workerDirectory));
WorkDoerFactory.RunWithWorkDoer(logger, settings, output, workDoer =>
{
var tabixWrapper = TabixWrapperFactory.GetTabixWrapper(logger, workDoer, commandManager);
var ploidyCorrector = new PloidyCorrector(logger, workDoer,
new PloidyEstimator(logger, workDoer, null, false, commandManager), tabixWrapper, false);
var checker = new CNVChecker(options.DQscoreThreshold, excludeIntervals, ploidyCorrector);
if (options.PloidyInfo.SexPloidyInfo != null)
{
Console.WriteLine($">>>Getting reference ploidy from provided ploidy information and PAR bed file '{options.PloidyInfo.ParBed}'");
var ploidy = checker.GetPloidy(options.PloidyInfo, output);
var referencePloidy = LoadReferencePloidy(options.PloidyInfo.SexPloidyInfo, options.PloidyInfo.ParBed);
knownCn = GetKnownCopyNumberWithReferencePloidy(referencePloidy, knownCn);
calls = GetCallsWithRefPloidy(calls, ploidy);
}
var cnvEvaluator = new CnvEvaluator(checker);
if (checker.DQscoreThreshold.HasValue && !Path.GetFileName(cnvCallsPath).ToLower().Contains("vcf"))
{
throw new ArgumentException("CNV.vcf must be in a vcf format when --dqscore option is used");
}
cnvEvaluator.ComputeAccuracy(knownCn, cnvCallsPath, outputPath, includePassingOnly, options, calls);
if (includePassingOnly)
{
cnvEvaluator.ComputeAccuracy(knownCn, cnvCallsPath, outputPath, false, options, calls);
}
ComputeCallability(logger, calls, options, output);
Console.WriteLine(">>>Done - results written to {0}", outputPath);
});
}
private static int Run(string[] args)
{
Utilities.LogCommandLine(args);
string outDir = null;
var segmentFiles = new List <string>();
var variantFrequencyFiles = new List <string>();
var sampleTypesString = new List <string>();
string ploidyBedPath = null;
string referenceFolder = null;
var sampleNames = new List <string>();
bool needHelp = false;
int? qScoreThresholdOption = null;
int? dqScoreThresholdOption = null;
string commonCnvsBedPath = null;
string parameterconfigPath = Path.Combine(Isas.Framework.Utilities.Utilities.GetAssemblyFolder(typeof(Program)), "PedigreeCallerParameters.json");
var p = new OptionSet()
{
{ "i|infile=", "file containing bins, their counts, and assigned segments (obtained from CanvasPartition.exe)", v => segmentFiles.Add(v) },
{ "v|varfile=", "file containing variant frequencies (obtained from CanvasSNV.exe)", v => variantFrequencyFiles.Add(v) },
{ "t|sampleType=", "sample types", v => sampleTypesString.Add(v) },
{ "o|outdir=", "name of output directory", v => outDir = v },
{ "r|reference=", "reference genome folder that contains GenomeSize.xml", v => referenceFolder = v },
{ "n|sampleName=", "sample name for output VCF header (optional)", v => sampleNames.Add(v) },
{ "p|ploidyBed=", "bed file specifying reference ploidy (e.g. for sex chromosomes) (optional)", v => ploidyBedPath = v },
{ "h|help", "show this message and exit", v => needHelp = v != null },
{ "q|qscore=", $"quality filter threshold (default {CanvasPedigreeCaller.DefaultQualityFilterThreshold})", v => qScoreThresholdOption = int.Parse(v) },
{ "commoncnvs=", "bed file with common CNVs (always include these intervals into segmentation results)", v => commonCnvsBedPath = v },
{ "d|dqscore=", $"de novo quality filter threshold (default {CanvasPedigreeCaller.DefaultDeNovoQualityFilterThreshold})", v => dqScoreThresholdOption = int.Parse(v) },
{ "c|config=", $"parameter configuration path (default {parameterconfigPath})", v => parameterconfigPath = v }
};
var extraArgs = p.Parse(args);
if (extraArgs.Count > 0)
{
Console.WriteLine("* Error: I don't understand the argument '{0}'", extraArgs[0]);
needHelp = true;
}
if (needHelp)
{
ShowHelp(p);
return(0);
}
if (!segmentFiles.Any() || !variantFrequencyFiles.Any() || string.IsNullOrEmpty(referenceFolder) || string.IsNullOrEmpty(outDir))
{
ShowHelp(p);
return(0);
}
foreach (string segmentFile in segmentFiles)
{
if (File.Exists(segmentFile))
{
continue;
}
Console.WriteLine($"CanvasPedigreeCaller.exe: File {segmentFile} does not exist! Exiting.");
return(1);
}
foreach (string variantFrequencyFile in variantFrequencyFiles)
{
if (File.Exists(variantFrequencyFile))
{
continue;
}
Console.WriteLine($"CanvasPedigreeCaller.exe: File {variantFrequencyFile} does not exist! Exiting.");
return(1);
}
var sampleTypesEnum = sampleTypesString.Select(GetSampleType).ToList();
if (!File.Exists(Path.Combine(referenceFolder, "GenomeSize.xml")))
{
Console.WriteLine($"CanvasPedigreeCaller.exe: File {Path.Combine(referenceFolder, "GenomeSize.xml")} does not exist! Exiting.");
return(1);
}
if (!File.Exists(parameterconfigPath))
{
Console.WriteLine($"CanvasPedigreeCaller.exe: File {parameterconfigPath} does not exist! Exiting.");
return(1);
}
if (commonCnvsBedPath != null)
{
if (!File.Exists(commonCnvsBedPath))
{
Console.WriteLine($"CanvasPedigreeCaller.exe: File {commonCnvsBedPath} does not exist! Exiting.");
return(1);
}
}
var parameterconfigFile = new FileLocation(parameterconfigPath);
var callerParameters = Deserialize <PedigreeCallerParameters>(parameterconfigFile);
int qScoreThreshold = CanvasPedigreeCaller.DefaultQualityFilterThreshold;
if (qScoreThresholdOption != null)
{
qScoreThreshold = qScoreThresholdOption.Value;
Console.WriteLine($"CanvasPedigreeCaller.exe: Using user-supplied quality score threshold {qScoreThresholdOption}.");
}
if (qScoreThreshold < 0 || qScoreThreshold >= callerParameters.MaxQscore)
{
throw new IlluminaException($"Quality score threshold must be >= 0 and < {callerParameters.MaxQscore}");
}
int dqScoreThreshold = CanvasPedigreeCaller.DefaultDeNovoQualityFilterThreshold;
if (dqScoreThresholdOption != null)
{
dqScoreThreshold = dqScoreThresholdOption.Value;
Console.WriteLine($"CanvasPedigreeCaller.exe: Using user-supplied de novo quality score threshold {qScoreThresholdOption}.");
}
if (dqScoreThreshold < 0 || dqScoreThreshold >= callerParameters.MaxQscore)
{
throw new IlluminaException($"De novo quality score threshold must be >= 0 and < {callerParameters.MaxQscore}");
}
var logger = new Logger(new[] { Console.Out }, new[] { Console.Error });
var settings = IsasConfigurationSettings.GetConfigSettings();
var outputDirectory = new DirectoryLocation(outDir);
var workerDirectory = new DirectoryLocation(Isas.Framework.Utilities.Utilities.GetAssemblyFolder(typeof(CanvasPedigreeCaller)));
var commandManager = new CommandManager(new ExecutableProcessor(settings, logger, workerDirectory));
var result = -1;
var pedigreeCallerWorkDirectory = outputDirectory.GetDirectoryLocation("CanvasPedigreeCaller");
WorkDoerFactory.RunWithWorkDoer(logger, settings, pedigreeCallerWorkDirectory, workDoer =>
{
var copyNumberLikelihoodCalculator = new CopyNumberLikelihoodCalculator(callerParameters.MaximumCopyNumber);
var variantCaller = callerParameters.DefaultCaller == CallerType.VariantCaller ?
(IVariantCaller) new VariantCaller(copyNumberLikelihoodCalculator, callerParameters, qScoreThreshold) :
new HaplotypeVariantCaller(copyNumberLikelihoodCalculator, callerParameters, qScoreThreshold);
var copyNumberModelFactory = new HaplotypeCopyNumberModelFactory();
var referenceGenome = new ReferenceGenomeFactory().GetReferenceGenome(new DirectoryLocation(referenceFolder));
var genomeMetadata = referenceGenome.GenomeMetadata;
var coverageBigWigWriterFactory =
new CoverageVisualizationWriterFactory(logger, workDoer, commandManager, genomeMetadata);
var roundingBedGraphWriter = new RoundingBedGraphWriter(new BedGraphWriterFacade(), 4);
var coverageBigWigWriter = coverageBigWigWriterFactory.CreateBinCoverageBigWigWriter(roundingBedGraphWriter);
var segmentCoverageBedGraphWriter = coverageBigWigWriterFactory.CreateSegmentBedGraphWriter(roundingBedGraphWriter);
var tabixWrapper = TabixWrapperFactory.GetTabixWrapper(logger, workDoer, commandManager);
var bgzfBedGraphWriter = new BgzfBedGraphWriter(new BedGraphWriterFacade(), tabixWrapper);
var copyNumberBedGraphWriter = new CopyNumberBedGraphWriter(bgzfBedGraphWriter, new CopyNumberBedGraphCalculator());
var caller = new CanvasPedigreeCaller(logger, qScoreThreshold, dqScoreThreshold, callerParameters, copyNumberLikelihoodCalculator, variantCaller, coverageBigWigWriter, copyNumberModelFactory, copyNumberBedGraphWriter, segmentCoverageBedGraphWriter);
var outVcf = outputDirectory.GetFileLocation("CNV.vcf.gz");
result = caller.CallVariants(variantFrequencyFiles, segmentFiles, outVcf, ploidyBedPath, referenceFolder, sampleNames, commonCnvsBedPath, sampleTypesEnum);
});
return(result);
}
