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package org.broadinstitute.gatk.tools.walkers.validation.validationsiteselector;
import org.broadinstitute.gatk.utils.commandline.*;
import org.broadinstitute.gatk.engine.CommandLineGATK;
import org.broadinstitute.gatk.engine.contexts.AlignmentContext;
import org.broadinstitute.gatk.engine.contexts.ReferenceContext;
import org.broadinstitute.gatk.engine.refdata.RefMetaDataTracker;
import org.broadinstitute.gatk.engine.walkers.RodWalker;
import org.broadinstitute.gatk.utils.GenomeLocParser;
import org.broadinstitute.gatk.utils.SampleUtils;
import org.broadinstitute.gatk.utils.help.HelpConstants;
import org.broadinstitute.gatk.utils.variant.GATKVariantContextUtils;
import htsjdk.variant.vcf.VCFHeader;
import htsjdk.variant.vcf.VCFHeaderLine;
import org.broadinstitute.gatk.utils.variant.GATKVCFUtils;
import org.broadinstitute.gatk.utils.help.DocumentedGATKFeature;
import htsjdk.variant.variantcontext.VariantContext;
import htsjdk.variant.variantcontext.writer.VariantContextWriter;
import java.io.File;
import java.util.*;
/**
* Randomly selects VCF records according to specified options.
*
* <p>
* ValidationSiteSelectorWalker is intended for use in experiments where we sample data randomly from a set of variants, for example
* in order to choose sites for a follow-up validation study.
*
* Sites are selected randomly but within certain restrictions. There are two main sources of restrictions
* a) Sample restrictions. A user can specify a set of samples, and we will only consider sites which are polymorphic within such given sample subset.
* These sample restrictions can be given as a set of individual samples, a text file (each line containing a sample name), or a regular expression.
* A user can additionally specify whether samples will be considered based on their genotypes (a non-reference genotype means that such sample is polymorphic in that variant,
* and hence that variant will be considered for inclusion in set), or based on their PLs.
* b) A user can additionally specify a sampling method based on allele frequency. Two sampling methods are currently supported.
* 1. Uniform sampling will just sample uniformly from variants polymorphic in selected samples.
* 2. Sampling based on Allele Frequency spectrum will ensure that output sites have the same AF distribution as the input set.
*
* User can additionally restrict output to a particular type of variant (SNP, Indel, etc.)
*
* <h3>Input</h3>
* <p>
* One or more variant sets to choose from.
* </p>
*
* <h3>Output</h3>
* <p>
* A sites-only VCF with the desired number of randomly selected sites.
* </p>
*
* <h3>Examples</h3>
* <pre>
* java -Xmx2g -jar GenomeAnalysisTK.jar \
* -R ref.fasta \
* -T ValidationSiteSelectorWalker \
* --variant input1.vcf \
* --variant input2.vcf \
* -sn NA12878 \
* -o output.vcf \
* --numValidationSites 200 \
* -sampleMode POLY_BASED_ON_GT \
* -freqMode KEEP_AF_SPECTRUM
*
* java -Xmx2g -jar GenomeAnalysisTK.jar \
* -R ref.fasta \
* -T ValidationSiteSelectorWalker \
* --variant:foo input1.vcf \
* --variant:bar input2.vcf \
* --numValidationSites 200 \
* -sf samples.txt \
* -o output.vcf \
* -sampleMode POLY_BASED_ON_GT \
* -freqMode UNIFORM
* -selectType INDEL
* </pre>
*
*/
@DocumentedGATKFeature( groupName = HelpConstants.DOCS_CAT_VALIDATION, extraDocs = {CommandLineGATK.class} )
public class ValidationSiteSelector extends RodWalker<Integer, Integer> {
public enum AF_COMPUTATION_MODE {
KEEP_AF_SPECTRUM,
UNIFORM
}
public enum SAMPLE_SELECTION_MODE {
NONE,
POLY_BASED_ON_GT,
POLY_BASED_ON_GL
}
/**
* The input VCF file
*/
@Input(fullName="variant", shortName = "V", doc="Input VCF file, can be specified multiple times", required=true)
public List<RodBinding<VariantContext>> variants;
/**
* The output VCF file
*/
@Output(doc="File to which variants should be written")
protected VariantContextWriter vcfWriter = null;
/**
* Sample name(s) to subset the input VCF to, prior to selecting variants. -sn A -sn B subsets to samples A and B.
*/
@Argument(fullName="sample_name", shortName="sn", doc="Include genotypes from this sample. Can be specified multiple times", required=false)
public Set<String> sampleNames = new HashSet<String>(0);
/**
* Sample regexps to subset the input VCF to, prior to selecting variants. -sn NA12* subsets to all samples with prefix NA12
*/
@Argument(fullName="sample_expressions", shortName="se", doc="Regular expression to select many samples from the ROD tracks provided. Can be specified multiple times", required=false)
public Set<String> sampleExpressions ;
/**
* File containing a list of sample names to subset the input vcf to. Equivalent to specifying the contents of the file separately with -sn
*/
@Input(fullName="sample_file", shortName="sf", doc="File containing a list of samples (one per line) to include. Can be specified multiple times", required=false)
public Set<File> sampleFiles;
/**
* A mode for selecting sites based on sample-level data. See the wiki documentation for more information.
*/
@Argument(fullName="sampleMode", shortName="sampleMode", doc="Sample selection mode", required=false)
private SAMPLE_SELECTION_MODE sampleMode = SAMPLE_SELECTION_MODE.NONE;
/**
* An P[nonref] threshold for SAMPLE_SELECTION_MODE=POLY_BASED_ON_GL. See the wiki documentation for more information.
*/
@Argument(shortName="samplePNonref",fullName="samplePNonref", doc="GL-based selection mode only: the probability" +
" that a site is non-reference in the samples for which to include the site",required=false)
private double samplePNonref = 0.99;
/**
* The number of sites in your validation set
*/
@Argument(fullName="numValidationSites", shortName="numSites", doc="Number of output validation sites", required=true)
private int numValidationSites;
/**
* Do not exclude filtered sites (e.g. not PASS or .) from consideration for validation
*/
@Argument(fullName="includeFilteredSites", shortName="ifs", doc="If true, will include filtered sites in set to choose variants from", required=false)
private boolean INCLUDE_FILTERED_SITES = false;
/**
* Argument for the frequency selection mode. (AC/AF/AN) are taken from VCF info field, not recalculated. Typically specified for sites-only VCFs that still have AC/AF/AN information.
*/
@Argument(fullName="ignoreGenotypes", shortName="ignoreGenotypes", doc="If true, will ignore genotypes in VCF, will take AC,AF from annotations and will make no sample selection", required=false)
private boolean IGNORE_GENOTYPES = false;
/**
* Argument for the frequency selection mode. Allows reference (non-polymorphic) sites to be included in the validation set.
*/
@Argument(fullName="ignorePolymorphicStatus", shortName="ignorePolymorphicStatus", doc="If true, will ignore polymorphic status in VCF, and will take VCF record directly without pre-selection", required=false)
private boolean IGNORE_POLYMORPHIC = false;
@Hidden
@Argument(fullName="numFrequencyBins", shortName="numBins", doc="Number of frequency bins if we're to match AF distribution", required=false)
private int numFrequencyBins = 20;
/**
* This argument selects allele frequency selection mode. See the wiki for more information.
*/
@Argument(fullName="frequencySelectionMode", shortName="freqMode", doc="Allele Frequency selection mode", required=false)
private AF_COMPUTATION_MODE freqMode = AF_COMPUTATION_MODE.KEEP_AF_SPECTRUM;
/**
* This argument selects particular kinds of variants (i.e. SNP, INDEL) out of a list. If left unspecified, all types are considered.
*/
@Argument(fullName="selectTypeToInclude", shortName="selectType", doc="Select only a certain type of variants from the input file. Valid types are INDEL, SNP, MIXED, MNP, SYMBOLIC, NO_VARIATION. Can be specified multiple times", required=false)
private List<VariantContext.Type> TYPES_TO_INCLUDE = new ArrayList<VariantContext.Type>();
private TreeSet<String> samples = new TreeSet<String>();
SampleSelector sampleSelector = null;
FrequencyModeSelector frequencyModeSelector = null;
private ArrayList<VariantContext.Type> selectedTypes = new ArrayList<VariantContext.Type>();
public void initialize() {
// Get list of samples to include in the output
Map<String, VCFHeader> vcfRods = GATKVCFUtils.getVCFHeadersFromRods(getToolkit());
TreeSet<String> vcfSamples = new TreeSet<String>(SampleUtils.getSampleList(vcfRods, GATKVariantContextUtils.GenotypeMergeType.REQUIRE_UNIQUE));
Collection<String> samplesFromFile = SampleUtils.getSamplesFromFiles(sampleFiles);
Collection<String> samplesFromExpressions = SampleUtils.matchSamplesExpressions(vcfSamples, sampleExpressions);
// first, add any requested samples
samples.addAll(samplesFromFile);
samples.addAll(samplesFromExpressions);
samples.addAll(sampleNames);
// if none were requested, we want all of them
if ( samples.isEmpty() ) {
samples.addAll(vcfSamples);
}
sampleSelector = getSampleSelectorObject(sampleMode, samples);
// initialize frequency mode selector
frequencyModeSelector = getFrequencyModeSelectorObject(freqMode, getToolkit().getGenomeLocParser());
// if user specified types to include, add these, otherwise, add all possible variant context types to list of vc types to include
if (TYPES_TO_INCLUDE.isEmpty()) {
for (VariantContext.Type t : VariantContext.Type.values())
selectedTypes.add(t);
}
else {
for (VariantContext.Type t : TYPES_TO_INCLUDE)
selectedTypes.add(t);
}
Set<VCFHeaderLine> headerLines = new HashSet<VCFHeaderLine>();
headerLines.add(new VCFHeaderLine("source", "ValidationSiteSelector"));
vcfWriter.writeHeader(new VCFHeader(headerLines));
}
@Override
public Integer map(RefMetaDataTracker tracker, ReferenceContext ref, AlignmentContext context) {
if ( tracker == null )
return 0;
Collection<VariantContext> vcs = tracker.getValues(variants, context.getLocation());
if ( vcs == null || vcs.size() == 0) {
return 0;
}
for (VariantContext vc : vcs) {
if (!selectedTypes.contains(vc.getType()))
continue;
// skip if site isn't polymorphic and if user didn't request to ignore polymorphic status
if (!vc.isPolymorphicInSamples() && !IGNORE_POLYMORPHIC)
continue;
if (!INCLUDE_FILTERED_SITES && vc.filtersWereApplied() && vc.isFiltered())
continue;
// does this site pass the criteria for the samples we are interested in?
boolean passesSampleSelectionCriteria;
if (samples.isEmpty())
passesSampleSelectionCriteria = true;
else
passesSampleSelectionCriteria = sampleSelector.selectSiteInSamples(vc);
frequencyModeSelector.logCurrentSiteData(vc,passesSampleSelectionCriteria,IGNORE_GENOTYPES,IGNORE_POLYMORPHIC);
}
return 1;
}
@Override
public Integer reduceInit() { return 0; }
@Override
public Integer reduce(Integer value, Integer sum) { return value + sum; }
public void onTraversalDone(Integer result) {
logger.info("Outputting validation sites...");
ArrayList<VariantContext> selectedSites = frequencyModeSelector.selectValidationSites(numValidationSites);
for (VariantContext vc : selectedSites) {
vcfWriter.add(vc);
}
logger.info(result + " records processed.");
}
private SampleSelector getSampleSelectorObject(SAMPLE_SELECTION_MODE sampleMode, TreeSet<String> samples) {
SampleSelector sm;
switch ( sampleMode ) {
case POLY_BASED_ON_GL:
sm = new GLBasedSampleSelector(samples, Math.log10(1.0-samplePNonref));
break;
case POLY_BASED_ON_GT:
sm = new GTBasedSampleSelector(samples);
break;
case NONE:
sm = new NullSampleSelector(samples);
break;
default:
throw new IllegalArgumentException("Unsupported Sample Selection Mode: " + sampleMode);
}
return sm;
}
private FrequencyModeSelector getFrequencyModeSelectorObject (AF_COMPUTATION_MODE freqMode, GenomeLocParser parser) {
FrequencyModeSelector fm;
switch (freqMode) {
case KEEP_AF_SPECTRUM:
fm = new KeepAFSpectrumFrequencySelector(numFrequencyBins, parser);
break;
case UNIFORM:
fm = new UniformSamplingFrequencySelector(parser);
break;
default: throw new IllegalArgumentException("Unexpected Frequency Selection Mode: "+ freqMode);
}
return fm;
}
}