protected override void ProgramExecution()
{
if (!Console.IsOutputRedirected)
{
Console.WriteLine("Running Nirvana on {0}:", GetFileName());
}
var outputVcfPath = ConfigurationSettings.OutputFileName + ".vcf.gz";
var outputGvcfPath = ConfigurationSettings.OutputFileName + ".genome.vcf.gz";
var outputVariantsPath = ConfigurationSettings.OutputFileName + ".json.gz";
using (var reader = GetVcfReader())
{
var booleanArguments = SetAnnotationFlags(reader.IsRcrsMitochondrion);
var annotator = GetAnnotator(reader.SampleNames, booleanArguments);
if (annotator == null)
{
throw new InvalidOperationException("Unable to perform annotation because no annotation sources could be created");
}
using (var jsonStreamWriter = GetJsonStreamWriter(outputVariantsPath))
using (var jsonWriter = GetJsonWriter(jsonStreamWriter, Date.GetTimeStamp, annotator, reader))
using (var vcfWriter = ConfigurationSettings.Vcf ? new LiteVcfWriter(outputVcfPath, reader.HeaderLines, annotator.GetDataVersion(), annotator.GetDataSourceVersions()) : null)
using (var gvcfWriter = ConfigurationSettings.Gvcf ? new LiteVcfWriter(outputGvcfPath, reader.HeaderLines, annotator.GetDataVersion(), annotator.GetDataSourceVersions()) : null)
{
string vcfLine = null;
var checker = new SortedVcfChecker();
try
{
while (true)
{
vcfLine = reader.ReadLine();
if (vcfLine == null)
{
break;
}
var fields = vcfLine.Split('\t');
if (fields.Length < VcfCommon.MinNumColumns)
{
continue;
}
var variant = new VcfVariant(fields, vcfLine, reader.IsGatkGenomeVcf);
checker.CheckVcfOrder(variant.ReferenceName);
var annotatedVariant = annotator.Annotate(variant);
var vcfOutput = GetVcfString(variant, annotatedVariant);
WriteOutput(vcfOutput, annotatedVariant, vcfWriter, gvcfWriter, jsonWriter);
}
WriteOmim(annotator, jsonWriter);
}
catch (Exception e)
{
// embed the vcf line
e.Data["VcfLine"] = vcfLine;
throw;
}
}
annotator.FinalizeMetrics();
}
}
private ExitCodes ProgramExecution()
{
var sequenceProvider = ProviderUtilities.GetSequenceProvider(_refSequencePath);
var transcriptAnnotationProvider = ProviderUtilities.GetTranscriptAnnotationProvider(_inputCachePrefix, sequenceProvider);
var saProvider = ProviderUtilities.GetSaProvider(SupplementaryAnnotationDirectories);
var conservationProvider = ProviderUtilities.GetConservationProvider(SupplementaryAnnotationDirectories);
var refMinorProvider = ProviderUtilities.GetRefMinorProvider(SupplementaryAnnotationDirectories);
var geneAnnotationProvider = ProviderUtilities.GetGeneAnnotationProvider(SupplementaryAnnotationDirectories);
var plugins = PluginUtilities.LoadPlugins(_pluginDirectory);
var annotator = ProviderUtilities.GetAnnotator(transcriptAnnotationProvider, sequenceProvider, saProvider, conservationProvider, geneAnnotationProvider, plugins);
var recomposer = _disableRecomposition ? new NullRecomposer() : Recomposer.Create(sequenceProvider, _inputCachePrefix);
var logger = _outputFileName == "-" ? (ILogger) new NullLogger() : new ConsoleLogger();
var metrics = new PerformanceMetrics(logger);
var dataSourceVersions = GetDataSourceVersions(plugins, transcriptAnnotationProvider, saProvider,
geneAnnotationProvider, conservationProvider);
var vepDataVersion = transcriptAnnotationProvider.VepVersion + "." + CacheConstants.DataVersion + "." + SaDataBaseCommon.DataVersion;
var jasixFileName = _outputFileName + ".json.gz" + JasixCommons.FileExt;
using (var outputWriter = ReadWriteUtilities.GetOutputWriter(_outputFileName))
using (var vcfReader = ReadWriteUtilities.GetVcfReader(_vcfPath, sequenceProvider.RefNameToChromosome, refMinorProvider, _reportAllSvOverlappingTranscripts, recomposer))
using (var jsonWriter = new JsonWriter(outputWriter, _annotatorVersionTag, Date.CurrentTimeStamp, vepDataVersion, dataSourceVersions, sequenceProvider.GenomeAssembly.ToString(), vcfReader.GetSampleNames()))
using (var vcfWriter = _vcf ? new LiteVcfWriter(ReadWriteUtilities.GetVcfOutputWriter(_outputFileName), vcfReader.GetHeaderLines(), _annotatorVersionTag, vepDataVersion, dataSourceVersions) : null)
using (var gvcfWriter = _gvcf ? new LiteVcfWriter(ReadWriteUtilities.GetGvcfOutputWriter(_outputFileName), vcfReader.GetHeaderLines(), _annotatorVersionTag, vepDataVersion, dataSourceVersions) : null)
using (var jasixIndexCreator = new OnTheFlyIndexCreator(FileUtilities.GetCreateStream(jasixFileName)))
{
if (!(outputWriter is BgzipTextWriter bgzipTextWriter))
{
throw new NullReferenceException("Unable to create the bgzip text writer.");
}
try
{
jasixIndexCreator.SetHeader(jsonWriter.Header);
if (vcfReader.IsRcrsMitochondrion && annotator.GenomeAssembly == GenomeAssembly.GRCh37 ||
annotator.GenomeAssembly == GenomeAssembly.GRCh38 ||
_forceMitochondrialAnnotation)
{
annotator.EnableMitochondrialAnnotation();
}
int previousChromIndex = -1;
IPosition position;
var sortedVcfChecker = new SortedVcfChecker();
while ((position = vcfReader.GetNextPosition()) != null)
{
sortedVcfChecker.CheckVcfOrder(position.Chromosome.UcscName);
previousChromIndex = UpdatePerformanceMetrics(previousChromIndex, position.Chromosome, metrics);
var annotatedPosition = annotator.Annotate(position);
string json = annotatedPosition.GetJsonString();
if (json != null)
{
WriteOutput(annotatedPosition, bgzipTextWriter.Position, jasixIndexCreator, jsonWriter, vcfWriter, gvcfWriter, json);
}
else
{
gvcfWriter?.Write(string.Join("\t", position.VcfFields));
}
metrics.Increment();
}
WriteGeneAnnotations(annotator.GetAnnotatedGenes(), jsonWriter);
}
catch (Exception e)
{
e.Data[ExitCodeUtilities.VcfLine] = vcfReader.VcfLine;
throw;
}
}
metrics.ShowAnnotationTime();
return(ExitCodes.Success);
}