Implemented fully symmetric sliding window read-backed phaser
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@4104 348d0f76-0448-11de-a6fe-93d51630548a
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@ -45,6 +45,8 @@ import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
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import java.io.*;
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import java.io.*;
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import java.util.*;
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import java.util.*;
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import static org.broadinstitute.sting.utils.vcf.VCFUtils.getVCFHeadersFromRods;
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/**
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/**
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* Walks along all loci, caching a user-defined window of VariantContext sites, and then finishes phasing them when they go out of range (using downstream reads).
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* Walks along all loci, caching a user-defined window of VariantContext sites, and then finishes phasing them when they go out of range (using downstream reads).
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@ -71,31 +73,37 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
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@Argument(fullName = "variantStatsFilePrefix", shortName = "variantStats", doc = "The prefix of the VCF/phasing statistics files", required = false)
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@Argument(fullName = "variantStatsFilePrefix", shortName = "variantStats", doc = "The prefix of the VCF/phasing statistics files", required = false)
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protected String variantStatsFilePrefix = null;
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protected String variantStatsFilePrefix = null;
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private PhasingQualityStatsWriter statsWriter = null;
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private LinkedList<VariantAndReads> unphasedSiteQueue = null;
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private LinkedList<VariantAndReads> phasedSites = null; // the phased VCs to be emitted, and the alignment bases at these positions
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private LinkedList<VariantAndReads> siteQueue = null;
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private VariantAndReads prevVr = null; // the VC emitted after phasing, and the alignment bases at the position emitted
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private static PreciseNonNegativeDouble ZERO = new PreciseNonNegativeDouble(0.0);
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private static PreciseNonNegativeDouble ZERO = new PreciseNonNegativeDouble(0.0);
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private static boolean DEBUG_DETAILED = true;
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private static boolean DEBUG_DETAILED = true;
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private void initializeVcfWriter(VariantContext vc) {
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private LinkedList<String> rodNames = null;
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private PhasingQualityStatsWriter statsWriter = null;
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public void initialize() {
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rodNames = new LinkedList<String>();
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rodNames.add("variant");
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unphasedSiteQueue = new LinkedList<VariantAndReads>();
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phasedSites = new LinkedList<VariantAndReads>();
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initializeVcfWriter();
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if (variantStatsFilePrefix != null)
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statsWriter = new PhasingQualityStatsWriter(variantStatsFilePrefix);
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}
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private void initializeVcfWriter() {
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// setup the header fields
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// setup the header fields
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Set<VCFHeaderLine> hInfo = new HashSet<VCFHeaderLine>();
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Set<VCFHeaderLine> hInfo = new HashSet<VCFHeaderLine>();
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hInfo.addAll(VCFUtils.getHeaderFields(getToolkit()));
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hInfo.addAll(VCFUtils.getHeaderFields(getToolkit()));
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hInfo.add(new VCFHeaderLine("reference", getToolkit().getArguments().referenceFile.getName()));
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hInfo.add(new VCFHeaderLine("reference", getToolkit().getArguments().referenceFile.getName()));
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hInfo.add(new VCFFormatHeaderLine("PQ", 1, VCFHeaderLineType.Float, "Read-backed phasing quality"));
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hInfo.add(new VCFFormatHeaderLine("PQ", 1, VCFHeaderLineType.Float, "Read-backed phasing quality"));
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writer.writeHeader(new VCFHeader(hInfo, new TreeSet<String>(vc.getSampleNames())));
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Map<String, VCFHeader> rodNameToHeader = getVCFHeadersFromRods(getToolkit(), rodNames);
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}
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writer.writeHeader(new VCFHeader(hInfo, new TreeSet<String>(rodNameToHeader.get(rodNames.get(0)).getGenotypeSamples())));
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public void initialize() {
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siteQueue = new LinkedList<VariantAndReads>();
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prevVr = new VariantAndReads(null, null, true);
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if (variantStatsFilePrefix != null)
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statsWriter = new PhasingQualityStatsWriter(variantStatsFilePrefix);
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}
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}
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public boolean generateExtendedEvents() {
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public boolean generateExtendedEvents() {
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@ -107,7 +115,7 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
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}
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}
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/**
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/**
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* For each site of interest, cache the current site and then use the cache to phase all upstream sites
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* For each site of interest, cache the current site and then use the cache to phase all sites
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* for which "sufficient" information has already been observed.
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* for which "sufficient" information has already been observed.
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*
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*
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* @param tracker the meta-data tracker
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* @param tracker the meta-data tracker
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@ -121,8 +129,6 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
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PhasingStats phaseStats = new PhasingStats();
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PhasingStats phaseStats = new PhasingStats();
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LinkedList<String> rodNames = new LinkedList<String>();
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rodNames.add("variant");
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boolean requireStartHere = true; // only see each VariantContext once
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boolean requireStartHere = true; // only see each VariantContext once
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boolean takeFirstOnly = false; // take as many entries as the VCF file has
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boolean takeFirstOnly = false; // take as many entries as the VCF file has
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for (VariantContext vc : tracker.getVariantContexts(ref, rodNames, null, context.getLocation(), requireStartHere, takeFirstOnly)) {
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for (VariantContext vc : tracker.getVariantContexts(ref, rodNames, null, context.getLocation(), requireStartHere, takeFirstOnly)) {
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@ -131,7 +137,7 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
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processVariant = false;
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processVariant = false;
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VariantAndReads vr = new VariantAndReads(vc, context, processVariant);
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VariantAndReads vr = new VariantAndReads(vc, context, processVariant);
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siteQueue.add(vr);
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unphasedSiteQueue.add(vr);
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int numReads = 0;
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int numReads = 0;
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if (context.hasBasePileup()) {
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if (context.hasBasePileup()) {
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@ -143,50 +149,101 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
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PhasingStats addInPhaseStats = new PhasingStats(numReads, 1);
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PhasingStats addInPhaseStats = new PhasingStats(numReads, 1);
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phaseStats.addIn(addInPhaseStats);
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phaseStats.addIn(addInPhaseStats);
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}
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}
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List<VariantContext> phasedList = processQueue(ref.getLocus(), phaseStats);
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List<VariantContext> phasedList = processQueue(phaseStats, false);
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return new PhasingStatsAndOutput(phaseStats, phasedList);
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return new PhasingStatsAndOutput(phaseStats, phasedList);
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}
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}
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private List<VariantContext> processQueue(GenomeLoc loc, PhasingStats phaseStats) {
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private List<VariantContext> processQueue(PhasingStats phaseStats, boolean processAll) {
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List<VariantContext> vcList = new LinkedList<VariantContext>();
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GenomeLoc lastLocus = null;
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if (!processAll && !unphasedSiteQueue.isEmpty())
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lastLocus = VariantContextUtils.getLocation(unphasedSiteQueue.peekLast().variant);
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while (!siteQueue.isEmpty()) {
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List<VariantContext> oldPhasedList = new LinkedList<VariantContext>();
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if (loc != null) {
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while (!unphasedSiteQueue.isEmpty()) {
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VariantContext vc = siteQueue.peek().variant;
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if (!processAll) { // otherwise, phase until the end of unphasedSiteQueue
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if (isInWindowRange(loc, VariantContextUtils.getLocation(vc))) {
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VariantContext nextToPhaseVc = unphasedSiteQueue.peek().variant;
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// loc is still not far enough ahead of vc (since we ASSUME that the VCF is ordered by <contig,locus>)
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if (isInWindowRange(lastLocus, VariantContextUtils.getLocation(nextToPhaseVc))) {
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/* lastLocus is still not far enough ahead of nextToPhaseVc to have all phasing information for nextToPhaseVc
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(note that we ASSUME that the VCF is ordered by <contig,locus>) */
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break;
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break;
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}
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}
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// Already saw all variant positions within cacheWindow distance ahead of vc (on its contig)
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// Already saw all variant positions within cacheWindow distance ahead of vc (on its contig)
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}
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}
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VariantContext phasedVc = finalizePhasingAndRemove(phaseStats);
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vcList.add(phasedVc);
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// Update phasedSites before it's used in finalizePhasing:
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oldPhasedList.addAll(discardIrrelevantPhasedSites());
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VariantAndReads phasedVr = finalizePhasing(unphasedSiteQueue.remove(), phaseStats);
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phasedSites.add(phasedVr);
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}
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}
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// Update phasedSites after finalizePhasing is done:
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oldPhasedList.addAll(discardIrrelevantPhasedSites());
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return oldPhasedList;
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}
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private List<VariantContext> discardIrrelevantPhasedSites() {
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List<VariantContext> vcList = new LinkedList<VariantContext>();
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VariantContext nextToPhaseVc = null;
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if (!unphasedSiteQueue.isEmpty())
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nextToPhaseVc = unphasedSiteQueue.peek().variant;
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while (!phasedSites.isEmpty()) {
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VariantAndReads phasedVr = phasedSites.peek();
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VariantContext phasedVc = phasedVr.variant;
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if (nextToPhaseVc != null && phasedVr.processVariant &&
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(isInWindowRange(phasedVc, nextToPhaseVc) // nextToPhaseVc is still not far enough ahead of phasedVc to exclude phasedVc from calculations
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// since ALWAYS want the previous site to be included for phasing nextToPhaseVc:
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|| (phasedSites.size() == 1 && VariantContextUtils.getLocation(phasedVc).onSameContig(VariantContextUtils.getLocation(nextToPhaseVc))))) {
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break;
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}
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vcList.add(phasedSites.remove().variant);
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}
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return vcList;
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return vcList;
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}
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}
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/* Finalize phasing of vc (head of siteQueue) using all VariantContext objects in the siteQueue that are
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/* Finalize phasing of vc (head of unphasedSiteQueue) using all VariantContext objects in
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within cacheWindow distance ahead of vc (on its contig).
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phasedSites and all in unphasedSiteQueue that are within cacheWindow distance ahead of vc (on its contig).
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ASSUMES:
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1. siteQueue is NOT empty.
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ASSUMES: All VariantContexts in unphasedSiteQueue are in positions downstream of vc (head of queue).
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2. All VariantContexts in siteQueue are in positions downstream of vc (head of queue).
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*/
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*/
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private VariantAndReads finalizePhasing(VariantAndReads vr, PhasingStats phaseStats) {
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private VariantContext finalizePhasingAndRemove(PhasingStats phaseStats) {
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VariantAndReads vr = siteQueue.remove(); // remove vr from head of queue
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VariantContext vc = vr.variant;
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if (!vr.processVariant)
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if (!vr.processVariant)
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return vc; // return vc as is
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return vr; // return vr as is
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boolean hasPreviousSite = previousIsRelevantTo(vc);
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VariantContext vc = vr.variant;
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logger.debug("Will phase vc = " + VariantContextUtils.getLocation(vc));
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logger.debug("Will phase vc = " + VariantContextUtils.getLocation(vc));
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LinkedList<VariantAndReads> windowVaList = new LinkedList<VariantAndReads>();
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// Find the previous VariantContext (that was processed and phased):
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VariantAndReads prevVr = null;
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Iterator<VariantAndReads> backwardsIt = phasedSites.descendingIterator();
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while (backwardsIt.hasNext()) {
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VariantAndReads backVr = backwardsIt.next();
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if (backVr.processVariant) {
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prevVr = backVr;
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break;
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}
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}
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boolean hasPreviousSite = (prevVr != null);
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LinkedList<VariantAndReads> windowVaList = null;
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if (hasPreviousSite) {
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if (hasPreviousSite) {
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windowVaList.add(prevVr); // need to add one position for phasing context
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windowVaList = new LinkedList<VariantAndReads>();
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windowVaList.add(vr); // add position to be phased
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for (VariantAndReads nextVr : siteQueue) {
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// Include previously phased sites in the phasing computation:
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for (VariantAndReads phasedVr : phasedSites) {
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if (phasedVr.processVariant)
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windowVaList.add(phasedVr);
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}
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// Add position to be phased:
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windowVaList.add(vr);
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// Include as of yet unphased sites in the phasing computation:
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for (VariantAndReads nextVr : unphasedSiteQueue) {
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if (!isInWindowRange(vc, nextVr.variant)) //nextVr too far ahead of the range used for phasing vc
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if (!isInWindowRange(vc, nextVr.variant)) //nextVr too far ahead of the range used for phasing vc
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break;
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break;
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if (nextVr.processVariant) // include in the phasing computation
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if (nextVr.processVariant) // include in the phasing computation
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@ -201,7 +258,6 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
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logger.debug("");
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logger.debug("");
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Map<String, Genotype> sampGenotypes = vc.getGenotypes();
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Map<String, Genotype> sampGenotypes = vc.getGenotypes();
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VariantContext prevVc = prevVr.variant;
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Map<String, Genotype> phasedGtMap = new TreeMap<String, Genotype>();
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Map<String, Genotype> phasedGtMap = new TreeMap<String, Genotype>();
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// Perform per-sample phasing:
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// Perform per-sample phasing:
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@ -215,115 +271,154 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
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Biallele biall = new Biallele(gt);
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Biallele biall = new Biallele(gt);
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HashMap<String, Object> gtAttribs = new HashMap<String, Object>(gt.getAttributes());
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HashMap<String, Object> gtAttribs = new HashMap<String, Object>(gt.getAttributes());
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if (hasPreviousSite && gt.isHet() && prevVc.getGenotype(samp).isHet()) { //otherwise, can trivially phase
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if (hasPreviousSite && gt.isHet()) {
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logger.debug("NON-TRIVIALLY CARE about TOP vs. BOTTOM for: ");
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VariantContext prevVc = prevVr.variant;
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logger.debug("\n" + biall);
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Genotype prevGenotype = prevVc.getGenotype(samp);
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if (prevGenotype.isHet()) { //otherwise, can trivially phase
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logger.debug("NON-TRIVIALLY CARE about TOP vs. BOTTOM for: ");
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logger.debug("\n" + biall);
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List<VariantAndReads> sampleWindowVaList = new LinkedList<VariantAndReads>();
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List<VariantAndReads> sampleWindowVaList = new LinkedList<VariantAndReads>();
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for (VariantAndReads phaseInfoVr : windowVaList) {
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int phasingSiteIndex = -1;
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VariantContext phaseInfoVc = phaseInfoVr.variant;
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int currentIndex = 0;
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Genotype phaseInfoGt = phaseInfoVc.getGenotype(samp);
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for (VariantAndReads phaseInfoVr : windowVaList) {
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if (phaseInfoGt.isHet()) { // otherwise, of no value to phasing
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VariantContext phaseInfoVc = phaseInfoVr.variant;
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sampleWindowVaList.add(phaseInfoVr);
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Genotype phaseInfoGt = phaseInfoVc.getGenotype(samp);
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logger.debug("STARTING TO PHASE USING POS = " + VariantContextUtils.getLocation(phaseInfoVc));
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if (phaseInfoGt.isHet()) { // otherwise, of no value to phasing
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sampleWindowVaList.add(phaseInfoVr);
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if (phasingSiteIndex == -1) {
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if (phaseInfoVr == vr)
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phasingSiteIndex = currentIndex;
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else
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currentIndex++;
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}
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logger.debug("STARTING TO PHASE USING POS = " + VariantContextUtils.getLocation(phaseInfoVc));
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}
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}
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}
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}
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if (logger.isDebugEnabled() && (phasingSiteIndex == -1 || phasingSiteIndex == 0))
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if (sampleWindowVaList.size() > maxPhaseSites) {
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throw new StingException("Internal error: could NOT find vr and/or prevVr!");
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logger.warn("Trying to phase sample " + samp + " at locus " + VariantContextUtils.getLocation(vc) + " within a window of " + cacheWindow + " bases yields " + sampleWindowVaList.size() + " heterozygous sites to phase -- REDUCING to first " + maxPhaseSites + " sites!");
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sampleWindowVaList = sampleWindowVaList.subList(0, maxPhaseSites);
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}
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/* Will map a phase and its "complement" to a single representative phase,
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if (sampleWindowVaList.size() > maxPhaseSites) {
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and marginalizeTable() marginalizes to the first 2 positions [i.e., the previous position and the current position]:
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logger.warn("Trying to phase sample " + samp + " at locus " + VariantContextUtils.getLocation(vc) + " within a window of " + cacheWindow + " bases yields " + sampleWindowVaList.size() + " heterozygous sites to phase -- REDUCING to " + maxPhaseSites + " sites:\n" + toString(sampleWindowVaList));
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*/
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HaplotypeTableCreator tabCreator = new BiallelicComplementHaplotypeTableCreator(sampleWindowVaList, samp, 2);
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PhasingTable sampleHaps = tabCreator.getNewTable();
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// Assemble the "sub-reads" from the heterozygous positions for this sample:
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int prevSiteIndex = phasingSiteIndex - 1;
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LinkedList<ReadBasesAtPosition> allPositions = new LinkedList<ReadBasesAtPosition>();
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int numToUse = maxPhaseSites - 2; // since always keep prevVr and vr
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for (VariantAndReads phaseInfoVr : sampleWindowVaList) {
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int halfToUse = new Double(Math.floor(numToUse / 2.0)).intValue();
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ReadBasesAtPosition readBases = phaseInfoVr.sampleReadBases.get(samp);
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allPositions.add(readBases);
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}
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HashMap<String, Read> allReads = convertReadBasesAtPositionToReads(allPositions);
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logger.debug("Number of reads at sites: " + allReads.size());
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int numUsedReads = 0;
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// Update the phasing table based on each of the sub-reads for this sample:
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int numOnLeft = prevSiteIndex;
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for (Map.Entry<String, Read> nameToReads : allReads.entrySet()) {
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int numOnRight = sampleWindowVaList.size() - (phasingSiteIndex + 1);
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Read rd = nameToReads.getValue();
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if (rd.numNonNulls() <= 1) // can't possibly provide any phasing information, so save time
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continue;
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numUsedReads++;
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int useOnLeft, useOnRight;
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if (DEBUG_DETAILED)
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if (numOnLeft <= numOnRight) {
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logger.debug("rd = " + rd + "\tname = " + nameToReads.getKey() + (rd.isGapped() ? "\tGAPPED" : ""));
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useOnLeft = Math.min(halfToUse, numOnLeft);
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useOnRight = Math.min(numToUse - useOnLeft, numOnRight);
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for (PhasingTable.PhasingTableEntry pte : sampleHaps) {
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}
|
||||||
PhasingScore score = rd.matchHaplotypeClassScore(pte.getHaplotypeClass());
|
else { // numOnRight < numOnLeft
|
||||||
pte.getScore().integrateReadScore(score);
|
useOnRight = Math.min(halfToUse, numOnRight);
|
||||||
|
useOnLeft = Math.min(numToUse - useOnRight, numOnLeft);
|
||||||
if (DEBUG_DETAILED)
|
}
|
||||||
logger.debug("score(" + rd + ", " + pte.getHaplotypeClass() + ") = " + score);
|
int startIndex = prevSiteIndex - useOnLeft;
|
||||||
|
int stopIndex = phasingSiteIndex + useOnRight + 1; // put the index 1 past the desired index to keep
|
||||||
|
phasingSiteIndex -= startIndex;
|
||||||
|
sampleWindowVaList = sampleWindowVaList.subList(startIndex, stopIndex);
|
||||||
|
logger.warn("REDUCED to " + sampleWindowVaList.size() + " sites:\n" + toString(sampleWindowVaList));
|
||||||
}
|
}
|
||||||
|
|
||||||
|
PhaseResult pr = phaseSample(samp, sampleWindowVaList, phasingSiteIndex);
|
||||||
|
genotypesArePhased = (pr.phaseQuality >= phaseQualityThresh);
|
||||||
|
if (genotypesArePhased) {
|
||||||
|
Biallele prevBiall = new Biallele(prevGenotype);
|
||||||
|
|
||||||
|
logger.debug("CHOSEN PHASE FOR PREVIOUS:\n" + prevBiall + "\n");
|
||||||
|
logger.debug("CHOSE PHASE:\n" + biall + "\n\n");
|
||||||
|
|
||||||
|
ensurePhasing(biall, prevBiall, pr.haplotype);
|
||||||
|
gtAttribs.put("PQ", pr.phaseQuality);
|
||||||
|
}
|
||||||
|
|
||||||
|
if (statsWriter != null)
|
||||||
|
statsWriter.addStat(samp, VariantContextUtils.getLocation(vc), distance(prevVc, vc), pr.phaseQuality);
|
||||||
|
|
||||||
|
PhaseCounts sampPhaseCounts = samplePhaseStats.get(samp);
|
||||||
|
if (sampPhaseCounts == null) {
|
||||||
|
sampPhaseCounts = new PhaseCounts();
|
||||||
|
samplePhaseStats.put(samp, sampPhaseCounts);
|
||||||
|
}
|
||||||
|
sampPhaseCounts.numTestedSites++;
|
||||||
|
if (genotypesArePhased)
|
||||||
|
sampPhaseCounts.numPhased++;
|
||||||
}
|
}
|
||||||
logger.debug("\nPhasing table [AFTER CALCULATION]:\n" + sampleHaps + "\n");
|
|
||||||
logger.debug("numUsedReads = " + numUsedReads);
|
|
||||||
|
|
||||||
// Marginalize each haplotype to its first 2 positions:
|
|
||||||
sampleHaps = HaplotypeTableCreator.marginalizeTable(sampleHaps);
|
|
||||||
logger.debug("\nPhasing table [AFTER MAPPING]:\n" + sampleHaps + "\n");
|
|
||||||
|
|
||||||
// Determine the phase at this position:
|
|
||||||
sampleHaps.normalizeScores();
|
|
||||||
logger.debug("\nPhasing table [AFTER NORMALIZATION]:\n" + sampleHaps + "\n");
|
|
||||||
|
|
||||||
PhasingTable.PhasingTableEntry maxEntry = sampleHaps.maxEntry();
|
|
||||||
double posteriorProb = maxEntry.getScore().getValue();
|
|
||||||
|
|
||||||
// convert posteriorProb to PHRED scale, but do NOT cap the quality as in QualityUtils.probToQual(posteriorProb):
|
|
||||||
PreciseNonNegativeDouble sumErrorProbs = new PreciseNonNegativeDouble(ZERO);
|
|
||||||
for (PhasingTable.PhasingTableEntry pte : sampleHaps) {
|
|
||||||
if (pte != maxEntry)
|
|
||||||
sumErrorProbs.plusEqual(pte.getScore());
|
|
||||||
}
|
|
||||||
double phaseQuality = -10.0 * (sumErrorProbs.getLog10Value());
|
|
||||||
|
|
||||||
logger.debug("MAX hap:\t" + maxEntry.getHaplotypeClass() + "\tposteriorProb:\t" + posteriorProb + "\tphaseQuality:\t" + phaseQuality);
|
|
||||||
|
|
||||||
if (statsWriter != null)
|
|
||||||
statsWriter.addStat(samp, distance(prevVc, vc), phaseQuality);
|
|
||||||
|
|
||||||
genotypesArePhased = (phaseQuality >= phaseQualityThresh);
|
|
||||||
if (genotypesArePhased) {
|
|
||||||
Biallele prevBiall = new Biallele(prevVc.getGenotype(samp));
|
|
||||||
ensurePhasing(biall, prevBiall, maxEntry.getHaplotypeClass().getRepresentative());
|
|
||||||
gtAttribs.put("PQ", phaseQuality);
|
|
||||||
|
|
||||||
logger.debug("CHOSE PHASE:\n" + biall + "\n\n");
|
|
||||||
}
|
|
||||||
|
|
||||||
PhaseCounts sampPhaseCounts = samplePhaseStats.get(samp);
|
|
||||||
if (sampPhaseCounts == null) {
|
|
||||||
sampPhaseCounts = new PhaseCounts();
|
|
||||||
samplePhaseStats.put(samp, sampPhaseCounts);
|
|
||||||
}
|
|
||||||
sampPhaseCounts.numTestedSites++;
|
|
||||||
sampPhaseCounts.numPhased += (genotypesArePhased ? 1 : 0);
|
|
||||||
}
|
}
|
||||||
|
|
||||||
List<Allele> phasedAll = biall.getAllelesAsList();
|
List<Allele> phasedAll = biall.getAllelesAsList();
|
||||||
Genotype phasedGt = new Genotype(gt.getSampleName(), phasedAll, gt.getNegLog10PError(), gt.getFilters(), gtAttribs, genotypesArePhased);
|
Genotype phasedGt = new Genotype(gt.getSampleName(), phasedAll, gt.getNegLog10PError(), gt.getFilters(), gtAttribs, genotypesArePhased);
|
||||||
phasedGtMap.put(samp, phasedGt);
|
phasedGtMap.put(samp, phasedGt);
|
||||||
}
|
}
|
||||||
|
|
||||||
VariantContext phasedVc = new VariantContext(vc.getName(), vc.getChr(), vc.getStart(), vc.getEnd(), vc.getAlleles(), phasedGtMap, vc.getNegLog10PError(), vc.getFilters(), vc.getAttributes());
|
|
||||||
prevVr.variant = phasedVc;
|
|
||||||
prevVr.sampleReadBases = vr.sampleReadBases;
|
|
||||||
|
|
||||||
phaseStats.addIn(new PhasingStats(samplePhaseStats));
|
phaseStats.addIn(new PhasingStats(samplePhaseStats));
|
||||||
|
|
||||||
return phasedVc;
|
VariantContext phasedVc = new VariantContext(vc.getName(), vc.getChr(), vc.getStart(), vc.getEnd(), vc.getAlleles(), phasedGtMap, vc.getNegLog10PError(), vc.getFilters(), vc.getAttributes());
|
||||||
|
return new VariantAndReads(phasedVc, vr.sampleReadBases, vr.processVariant);
|
||||||
|
}
|
||||||
|
|
||||||
|
private PhaseResult phaseSample(String sample, List<VariantAndReads> variantList, int phasingSiteIndex) {
|
||||||
|
/* Will map a phase and its "complement" to a single representative phase,
|
||||||
|
and marginalizeTable() marginalizes to 2 positions [starting at the previous position, and then the current position]:
|
||||||
|
*/
|
||||||
|
HaplotypeTableCreator tabCreator = new BiallelicComplementHaplotypeTableCreator(variantList, sample, phasingSiteIndex - 1, 2);
|
||||||
|
PhasingTable sampleHaps = tabCreator.getNewTable();
|
||||||
|
|
||||||
|
// Assemble the "sub-reads" from the heterozygous positions for this sample:
|
||||||
|
LinkedList<ReadBasesAtPosition> allPositions = new LinkedList<ReadBasesAtPosition>();
|
||||||
|
for (VariantAndReads phaseInfoVr : variantList) {
|
||||||
|
ReadBasesAtPosition readBases = phaseInfoVr.sampleReadBases.get(sample);
|
||||||
|
allPositions.add(readBases);
|
||||||
|
}
|
||||||
|
HashMap<String, Read> allReads = convertReadBasesAtPositionToReads(allPositions);
|
||||||
|
logger.debug("Number of reads at sites: " + allReads.size());
|
||||||
|
int numUsedReads = 0;
|
||||||
|
|
||||||
|
// Update the phasing table based on each of the sub-reads for this sample:
|
||||||
|
for (Map.Entry<String, Read> nameToReads : allReads.entrySet()) {
|
||||||
|
Read rd = nameToReads.getValue();
|
||||||
|
if (rd.numNonNulls() <= 1) // can't possibly provide any phasing information, so save time
|
||||||
|
continue;
|
||||||
|
|
||||||
|
numUsedReads++;
|
||||||
|
if (DEBUG_DETAILED)
|
||||||
|
logger.debug("rd = " + rd + "\tname = " + nameToReads.getKey() + (rd.isGapped() ? "\tGAPPED" : ""));
|
||||||
|
|
||||||
|
for (PhasingTable.PhasingTableEntry pte : sampleHaps) {
|
||||||
|
PhasingScore score = rd.matchHaplotypeClassScore(pte.getHaplotypeClass());
|
||||||
|
pte.getScore().integrateReadScore(score);
|
||||||
|
|
||||||
|
if (DEBUG_DETAILED)
|
||||||
|
logger.debug("score(" + rd + ", " + pte.getHaplotypeClass() + ") = " + score);
|
||||||
|
}
|
||||||
|
}
|
||||||
|
logger.debug("\nPhasing table [AFTER CALCULATION]:\n" + sampleHaps + "\n");
|
||||||
|
logger.debug("numUsedReads = " + numUsedReads);
|
||||||
|
|
||||||
|
// Marginalize each haplotype to its first 2 positions:
|
||||||
|
sampleHaps = HaplotypeTableCreator.marginalizeTable(sampleHaps);
|
||||||
|
logger.debug("\nPhasing table [AFTER MAPPING]:\n" + sampleHaps + "\n");
|
||||||
|
|
||||||
|
// Determine the phase at this position:
|
||||||
|
sampleHaps.normalizeScores();
|
||||||
|
logger.debug("\nPhasing table [AFTER NORMALIZATION]:\n" + sampleHaps + "\n");
|
||||||
|
|
||||||
|
PhasingTable.PhasingTableEntry maxEntry = sampleHaps.maxEntry();
|
||||||
|
double posteriorProb = maxEntry.getScore().getValue();
|
||||||
|
|
||||||
|
// convert posteriorProb to PHRED scale, but do NOT cap the quality as in QualityUtils.probToQual(posteriorProb):
|
||||||
|
PreciseNonNegativeDouble sumErrorProbs = new PreciseNonNegativeDouble(ZERO);
|
||||||
|
for (PhasingTable.PhasingTableEntry pte : sampleHaps) {
|
||||||
|
if (pte != maxEntry)
|
||||||
|
sumErrorProbs.plusEqual(pte.getScore());
|
||||||
|
}
|
||||||
|
double phaseQuality = -10.0 * (sumErrorProbs.getLog10Value());
|
||||||
|
|
||||||
|
logger.debug("MAX hap:\t" + maxEntry.getHaplotypeClass() + "\tposteriorProb:\t" + posteriorProb + "\tphaseQuality:\t" + phaseQuality);
|
||||||
|
|
||||||
|
return new PhaseResult(maxEntry.getHaplotypeClass().getRepresentative(), phaseQuality);
|
||||||
}
|
}
|
||||||
|
|
||||||
/*
|
/*
|
||||||
|
|
@ -343,11 +438,6 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
|
||||||
curBiall.swapAlleles();
|
curBiall.swapAlleles();
|
||||||
}
|
}
|
||||||
|
|
||||||
private boolean previousIsRelevantTo(VariantContext vc) {
|
|
||||||
VariantContext prevVc = prevVr.variant;
|
|
||||||
return (prevVc != null && VariantContextUtils.getLocation(prevVc).onSameContig(VariantContextUtils.getLocation(vc)));
|
|
||||||
}
|
|
||||||
|
|
||||||
private boolean isInWindowRange(VariantContext vc1, VariantContext vc2) {
|
private boolean isInWindowRange(VariantContext vc1, VariantContext vc2) {
|
||||||
GenomeLoc loc1 = VariantContextUtils.getLocation(vc1);
|
GenomeLoc loc1 = VariantContextUtils.getLocation(vc1);
|
||||||
GenomeLoc loc2 = VariantContextUtils.getLocation(vc2);
|
GenomeLoc loc2 = VariantContextUtils.getLocation(vc2);
|
||||||
|
|
@ -369,9 +459,6 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
|
||||||
}
|
}
|
||||||
|
|
||||||
private void writeVCF(VariantContext vc) {
|
private void writeVCF(VariantContext vc) {
|
||||||
if (writer == null)
|
|
||||||
initializeVcfWriter(vc);
|
|
||||||
|
|
||||||
byte refBase;
|
byte refBase;
|
||||||
if (!vc.isIndel()) {
|
if (!vc.isIndel()) {
|
||||||
Allele varAllele = vc.getReference();
|
Allele varAllele = vc.getReference();
|
||||||
|
|
@ -393,12 +480,12 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
|
||||||
}
|
}
|
||||||
|
|
||||||
/**
|
/**
|
||||||
* Phase anything left in the cached siteQueue, and report the number of reads and VariantContexts processed.
|
* Phase anything left in the cached unphasedSiteQueue, and report the number of reads and VariantContexts processed.
|
||||||
*
|
*
|
||||||
* @param result the number of reads and VariantContexts seen.
|
* @param result the number of reads and VariantContexts seen.
|
||||||
*/
|
*/
|
||||||
public void onTraversalDone(PhasingStats result) {
|
public void onTraversalDone(PhasingStats result) {
|
||||||
List<VariantContext> finalList = processQueue(null, result);
|
List<VariantContext> finalList = processQueue(result, true);
|
||||||
writeVarContList(finalList);
|
writeVarContList(finalList);
|
||||||
if (statsWriter != null)
|
if (statsWriter != null)
|
||||||
statsWriter.close();
|
statsWriter.close();
|
||||||
|
|
@ -532,6 +619,12 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
|
||||||
public HashMap<String, ReadBasesAtPosition> sampleReadBases;
|
public HashMap<String, ReadBasesAtPosition> sampleReadBases;
|
||||||
public boolean processVariant;
|
public boolean processVariant;
|
||||||
|
|
||||||
|
public VariantAndReads(VariantContext variant, HashMap<String, ReadBasesAtPosition> sampleReadBases, boolean processVariant) {
|
||||||
|
this.variant = variant;
|
||||||
|
this.sampleReadBases = sampleReadBases;
|
||||||
|
this.processVariant = processVariant;
|
||||||
|
}
|
||||||
|
|
||||||
public VariantAndReads(VariantContext variant, AlignmentContext alignment, boolean processVariant) {
|
public VariantAndReads(VariantContext variant, AlignmentContext alignment, boolean processVariant) {
|
||||||
this.variant = variant;
|
this.variant = variant;
|
||||||
this.sampleReadBases = new HashMap<String, ReadBasesAtPosition>();
|
this.sampleReadBases = new HashMap<String, ReadBasesAtPosition>();
|
||||||
|
|
@ -560,6 +653,20 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
|
||||||
}
|
}
|
||||||
}
|
}
|
||||||
|
|
||||||
|
private static String toString(List<VariantAndReads> vrList) {
|
||||||
|
boolean first = true;
|
||||||
|
StringBuilder sb = new StringBuilder();
|
||||||
|
for (VariantAndReads vr : vrList) {
|
||||||
|
if (first)
|
||||||
|
first = false;
|
||||||
|
else
|
||||||
|
sb.append(" -- ");
|
||||||
|
|
||||||
|
sb.append(VariantContextUtils.getLocation(vr.variant));
|
||||||
|
}
|
||||||
|
return sb.toString();
|
||||||
|
}
|
||||||
|
|
||||||
private static class ReadBase {
|
private static class ReadBase {
|
||||||
public String readName;
|
public String readName;
|
||||||
public byte base;
|
public byte base;
|
||||||
|
|
@ -599,19 +706,14 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
|
||||||
//
|
//
|
||||||
private static abstract class HaplotypeTableCreator {
|
private static abstract class HaplotypeTableCreator {
|
||||||
protected Genotype[] genotypes;
|
protected Genotype[] genotypes;
|
||||||
protected Biallele[] bialleles;
|
|
||||||
|
|
||||||
public HaplotypeTableCreator(List<VariantAndReads> vaList, String sample) {
|
public HaplotypeTableCreator(List<VariantAndReads> vaList, String sample) {
|
||||||
this.genotypes = new Genotype[vaList.size()];
|
this.genotypes = new Genotype[vaList.size()];
|
||||||
this.bialleles = new Biallele[vaList.size()];
|
|
||||||
|
|
||||||
int index = 0;
|
int index = 0;
|
||||||
for (VariantAndReads phaseInfoVr : vaList) {
|
for (VariantAndReads phaseInfoVr : vaList) {
|
||||||
VariantContext phaseInfoVc = phaseInfoVr.variant;
|
VariantContext phaseInfoVc = phaseInfoVr.variant;
|
||||||
Genotype phaseInfoGt = phaseInfoVc.getGenotype(sample);
|
Genotype phaseInfoGt = phaseInfoVc.getGenotype(sample);
|
||||||
genotypes[index] = phaseInfoGt;
|
genotypes[index++] = phaseInfoGt;
|
||||||
bialleles[index] = new Biallele(phaseInfoGt);
|
|
||||||
index++;
|
|
||||||
}
|
}
|
||||||
}
|
}
|
||||||
|
|
||||||
|
|
@ -643,7 +745,7 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
|
||||||
Haplotype rep = pte.getHaplotypeClass().getRepresentative();
|
Haplotype rep = pte.getHaplotypeClass().getRepresentative();
|
||||||
PreciseNonNegativeDouble score = hapMap.get(rep);
|
PreciseNonNegativeDouble score = hapMap.get(rep);
|
||||||
if (score == null) {
|
if (score == null) {
|
||||||
score = new PreciseNonNegativeDouble(0.0);
|
score = new PreciseNonNegativeDouble(ZERO);
|
||||||
hapMap.put(rep, score);
|
hapMap.put(rep, score);
|
||||||
}
|
}
|
||||||
score.plusEqual(pte.getScore());
|
score.plusEqual(pte.getScore());
|
||||||
|
|
@ -663,10 +765,18 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
|
||||||
}
|
}
|
||||||
|
|
||||||
private static class BiallelicComplementHaplotypeTableCreator extends HaplotypeTableCreator {
|
private static class BiallelicComplementHaplotypeTableCreator extends HaplotypeTableCreator {
|
||||||
|
private Biallele[] bialleles;
|
||||||
|
private int startIndex;
|
||||||
private int marginalizeLength;
|
private int marginalizeLength;
|
||||||
|
|
||||||
public BiallelicComplementHaplotypeTableCreator(List<VariantAndReads> vaList, String sample, int marginalizeLength) {
|
public BiallelicComplementHaplotypeTableCreator(List<VariantAndReads> vaList, String sample, int startIndex, int marginalizeLength) {
|
||||||
super(vaList, sample);
|
super(vaList, sample);
|
||||||
|
|
||||||
|
this.bialleles = new Biallele[genotypes.length];
|
||||||
|
for (int i = 0; i < genotypes.length; i++)
|
||||||
|
bialleles[i] = new Biallele(genotypes[i]);
|
||||||
|
|
||||||
|
this.startIndex = startIndex;
|
||||||
this.marginalizeLength = marginalizeLength;
|
this.marginalizeLength = marginalizeLength;
|
||||||
}
|
}
|
||||||
|
|
||||||
|
|
@ -675,15 +785,18 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
|
||||||
|
|
||||||
PhasingTable table = new PhasingTable();
|
PhasingTable table = new PhasingTable();
|
||||||
for (Haplotype hap : getAllHaplotypes()) {
|
for (Haplotype hap : getAllHaplotypes()) {
|
||||||
if (bialleles[0].matchesTopBase(hap.getBase(0))) {
|
if (bialleles[startIndex].matchesTopBase(hap.getBase(startIndex))) {
|
||||||
/* hap is the "representative" haplotype [arbitrarily defined to be
|
/* hap is the "representative" haplotype [DEFINED here to be
|
||||||
the one with the top base at the 0th position]
|
the one with the top base at the startIndex position.
|
||||||
|
NOTE that it is CRITICAL that this definition be consistent with the representative sub-haplotypes defined below!]
|
||||||
*/
|
*/
|
||||||
ArrayList<Haplotype> hapList = new ArrayList<Haplotype>();
|
ArrayList<Haplotype> hapList = new ArrayList<Haplotype>();
|
||||||
hapList.add(hap);
|
hapList.add(hap);
|
||||||
hapList.add(complement(hap));
|
hapList.add(complement(hap));
|
||||||
|
|
||||||
Haplotype rep = hap.subHaplotype(0, Math.min(marginalizeLength, hap.size())); // only want first marginalizeLength positions
|
// want marginalizeLength positions starting at startIndex:
|
||||||
|
Haplotype rep = hap.subHaplotype(startIndex, startIndex + marginalizeLength);
|
||||||
|
|
||||||
HaplotypeClass hapClass = new HaplotypeClass(hapList, rep);
|
HaplotypeClass hapClass = new HaplotypeClass(hapList, rep);
|
||||||
table.addEntry(hapClass, hapClassPrior);
|
table.addEntry(hapClass, hapClassPrior);
|
||||||
}
|
}
|
||||||
|
|
@ -787,6 +900,16 @@ public class ReadBackedPhasingWalker extends LocusWalker<PhasingStatsAndOutput,
|
||||||
}
|
}
|
||||||
}
|
}
|
||||||
}
|
}
|
||||||
|
|
||||||
|
private static class PhaseResult {
|
||||||
|
public Haplotype haplotype;
|
||||||
|
public double phaseQuality;
|
||||||
|
|
||||||
|
public PhaseResult(Haplotype haplotype, double phaseQuality) {
|
||||||
|
this.haplotype = haplotype;
|
||||||
|
this.phaseQuality = phaseQuality;
|
||||||
|
}
|
||||||
|
}
|
||||||
}
|
}
|
||||||
|
|
||||||
|
|
||||||
|
|
@ -903,7 +1026,7 @@ class Haplotype extends BaseArray implements Cloneable {
|
||||||
|
|
||||||
// Returns a new Haplotype containing the portion of this Haplotype between the specified fromIndex, inclusive, and toIndex, exclusive.
|
// Returns a new Haplotype containing the portion of this Haplotype between the specified fromIndex, inclusive, and toIndex, exclusive.
|
||||||
public Haplotype subHaplotype(int fromIndex, int toIndex) {
|
public Haplotype subHaplotype(int fromIndex, int toIndex) {
|
||||||
return new Haplotype(Arrays.copyOfRange(bases, fromIndex, toIndex));
|
return new Haplotype(Arrays.copyOfRange(bases, fromIndex, Math.min(toIndex, size())));
|
||||||
}
|
}
|
||||||
}
|
}
|
||||||
|
|
||||||
|
|
@ -1114,10 +1237,10 @@ class PhasingQualityStatsWriter {
|
||||||
this.variantStatsFilePrefix = variantStatsFilePrefix;
|
this.variantStatsFilePrefix = variantStatsFilePrefix;
|
||||||
}
|
}
|
||||||
|
|
||||||
public void addStat(String sample, int distanceFromPrevious, double phasingQuality) {
|
public void addStat(String sample, GenomeLoc locus, int distanceFromPrevious, double phasingQuality) {
|
||||||
BufferedWriter sampWriter = sampleToStatsWriter.get(sample);
|
BufferedWriter sampWriter = sampleToStatsWriter.get(sample);
|
||||||
if (sampWriter == null) {
|
if (sampWriter == null) {
|
||||||
String fileName = variantStatsFilePrefix + "." + sample + ".distance_PQ.txt";
|
String fileName = variantStatsFilePrefix + "." + sample + ".locus_distance_PQ.txt";
|
||||||
|
|
||||||
FileOutputStream output;
|
FileOutputStream output;
|
||||||
try {
|
try {
|
||||||
|
|
@ -1129,7 +1252,7 @@ class PhasingQualityStatsWriter {
|
||||||
sampleToStatsWriter.put(sample, sampWriter);
|
sampleToStatsWriter.put(sample, sampWriter);
|
||||||
}
|
}
|
||||||
try {
|
try {
|
||||||
sampWriter.write(distanceFromPrevious + "\t" + phasingQuality + "\n");
|
sampWriter.write(locus + "\t" + distanceFromPrevious + "\t" + phasingQuality + "\n");
|
||||||
sampWriter.flush();
|
sampWriter.flush();
|
||||||
} catch (IOException e) {
|
} catch (IOException e) {
|
||||||
throw new RuntimeException("Unable to write to per-sample phasing quality stats file", e);
|
throw new RuntimeException("Unable to write to per-sample phasing quality stats file", e);
|
||||||
|
|
|
||||||
Loading…
Reference in New Issue