diff --git a/java/src/org/broadinstitute/sting/gatk/refdata/features/annotator/AnnotatorInputTableCodec.java b/java/src/org/broadinstitute/sting/gatk/refdata/features/annotator/AnnotatorInputTableCodec.java index 903133ffa..e87986a2e 100755 --- a/java/src/org/broadinstitute/sting/gatk/refdata/features/annotator/AnnotatorInputTableCodec.java +++ b/java/src/org/broadinstitute/sting/gatk/refdata/features/annotator/AnnotatorInputTableCodec.java @@ -92,13 +92,10 @@ public class AnnotatorInputTableCodec implements ReferenceDependentFeatureCodec< GenomeLoc loc; String chr = st.nextToken(); - if ( chr.indexOf(":") != -1 ) { + if ( chr.indexOf(":") != -1 ) loc = genomeLocParser.parseGenomeInterval(chr); - } else { - if ( st.countTokens() < 3 ) - throw new CodecLineParsingException("Couldn't parse GenomeLoc out of the following line because there aren't enough tokens.\nLine: " + line); + else loc = genomeLocParser.createGenomeLoc(chr, Integer.valueOf(st.nextToken()), Integer.valueOf(st.nextToken())); - } return new AnnotatorInputTableFeature(loc.getContig(), (int)loc.getStart(), (int)loc.getStop()); } diff --git a/java/src/org/broadinstitute/sting/gatk/walkers/annotator/HaplotypeScore.java b/java/src/org/broadinstitute/sting/gatk/walkers/annotator/HaplotypeScore.java index b3288d738..d539007dd 100644 --- a/java/src/org/broadinstitute/sting/gatk/walkers/annotator/HaplotypeScore.java +++ b/java/src/org/broadinstitute/sting/gatk/walkers/annotator/HaplotypeScore.java @@ -40,6 +40,7 @@ import org.broadinstitute.sting.utils.pileup.*; import java.util.*; import net.sf.samtools.SAMRecord; import org.broadinstitute.sting.utils.sam.ReadUtils; +import org.broadinstitute.sting.utils.sam.GATKSAMRecord; public class HaplotypeScore implements InfoFieldAnnotation, StandardAnnotation { private final static boolean DEBUG = false; @@ -47,6 +48,11 @@ public class HaplotypeScore implements InfoFieldAnnotation, StandardAnnotation { private final static int MAX_CONSENSUS_HAPLOTYPES_TO_CONSIDER = 20; private final static char REGEXP_WILDCARD = '.'; + public boolean useRead(PileupElement p) { + return ! ReadUtils.is454Read(p.getRead()); + //return ! (p.getRead() instanceof GATKSAMRecord && ! ((GATKSAMRecord)p.getRead()).isGoodBase(p.getOffset())) && ! ReadUtils.is454Read(p.getRead()); + } + public Map annotate(RefMetaDataTracker tracker, ReferenceContext ref, Map stratifiedContexts, VariantContext vc) { if ( !vc.isBiallelic() || !vc.isSNP() || stratifiedContexts.size() == 0 ) // size 0 means that call was made by someone else and we have no data here return null; @@ -88,15 +94,11 @@ public class HaplotypeScore implements InfoFieldAnnotation, StandardAnnotation { ArrayList haplotypeList = new ArrayList(); PriorityQueue haplotypeQueue = new PriorityQueue(100, new HaplotypeComparator()); - - for ( ExtendedPileupElement p : pileup.extendedForeachIterator() ) { - if (ReadUtils.is454Read(p.getRead())) - continue; - Haplotype haplotypeFromRead = getHaplotypeFromRead(p, contextSize); - - - haplotypeQueue.add(haplotypeFromRead); - //haplotypeList.add(haplotypeFromRead); + for ( PileupElement p : pileup ) { + if ( useRead(p) ) { + Haplotype haplotypeFromRead = getHaplotypeFromRead(p, contextSize); + haplotypeQueue.add(haplotypeFromRead); + } } // Now that priority queue has been built with all reads at context, we need to merge and find possible segregating haplotypes @@ -161,7 +163,7 @@ public class HaplotypeScore implements InfoFieldAnnotation, StandardAnnotation { return null; } - private Haplotype getHaplotypeFromRead(ExtendedPileupElement p, int contextSize) { + private Haplotype getHaplotypeFromRead(PileupElement p, int contextSize) { SAMRecord read = p.getRead(); int readOffsetFromPileup = p.getOffset(); int baseOffsetStart = readOffsetFromPileup - (contextSize - 1)/2; @@ -239,24 +241,28 @@ public class HaplotypeScore implements InfoFieldAnnotation, StandardAnnotation { // if ( DEBUG ) System.out.printf("HAP1: %s%n", haplotypes.get(1)); double[][] haplotypeScores = new double[pileup.size()][haplotypes.size()]; - for ( ExtendedPileupElement p : pileup.extendedForeachIterator() ) { - SAMRecord read = p.getRead(); - int readOffsetFromPileup = p.getOffset(); + int pileupOffset = 0; + for ( PileupElement p : pileup ) { + if ( useRead(p) ) { + SAMRecord read = p.getRead(); + int readOffsetFromPileup = p.getOffset(); - if (ReadUtils.is454Read(read)) - continue; + if (ReadUtils.is454Read(read)) + continue; - if ( DEBUG ) System.out.printf("--------------------------------------------- Read %s%n", read.getReadName()); - double m = 10000000; - for ( int i = 0; i < haplotypes.size(); i++ ) { - Haplotype haplotype = haplotypes.get(i); - int start = readOffsetFromPileup - (contextSize - 1)/2; - double score = scoreReadAgainstHaplotype(read, start, contextSize, haplotype); - haplotypeScores[p.getPileupOffset()][i] = score; - if ( DEBUG ) System.out.printf(" vs. haplotype %d = %f%n", i, score); - m = Math.min(score, m); + if ( DEBUG ) System.out.printf("--------------------------------------------- Read %s%n", read.getReadName()); + double m = 10000000; + for ( int i = 0; i < haplotypes.size(); i++ ) { + Haplotype haplotype = haplotypes.get(i); + int start = readOffsetFromPileup - (contextSize - 1)/2; + double score = scoreReadAgainstHaplotype(read, start, contextSize, haplotype); + haplotypeScores[pileupOffset][i] = score; + if ( DEBUG ) System.out.printf(" vs. haplotype %d = %f%n", i, score); + m = Math.min(score, m); + } + if ( DEBUG ) System.out.printf(" => best score was %f%n", m); } - if ( DEBUG ) System.out.printf(" => best score was %f%n", m); + pileupOffset++; // todo -- remove me } double overallScore = 0.0; diff --git a/java/src/org/broadinstitute/sting/gatk/walkers/varianteval/VariantEvalWalker.java b/java/src/org/broadinstitute/sting/gatk/walkers/varianteval/VariantEvalWalker.java index 7cfdbcafa..11398fb04 100755 --- a/java/src/org/broadinstitute/sting/gatk/walkers/varianteval/VariantEvalWalker.java +++ b/java/src/org/broadinstitute/sting/gatk/walkers/varianteval/VariantEvalWalker.java @@ -43,6 +43,7 @@ import org.broadinstitute.sting.gatk.walkers.RodWalker; import org.broadinstitute.sting.gatk.walkers.Window; import org.broadinstitute.sting.gatk.walkers.TreeReducible; import org.broadinstitute.sting.gatk.walkers.variantrecalibration.Tranche; +import org.broadinstitute.sting.gatk.walkers.variantrecalibration.VariantRecalibrator; import org.broadinstitute.sting.utils.SampleUtils; import org.broadinstitute.sting.utils.report.ReportMarshaller; import org.broadinstitute.sting.utils.report.VE2ReportFactory; @@ -307,7 +308,7 @@ public class VariantEvalWalker extends RodWalker implements Tr // we are going to build a few select names automatically from the tranches file for ( Tranche t : Tranche.readTraches(new File(TRANCHE_FILENAME)) ) { logger.info("Adding select for all variant above the pCut of : " + t); - SELECT_EXPS.add(String.format("QUAL >= %.2f", t.pCut)); + SELECT_EXPS.add(String.format(VariantRecalibrator.VQS_LOD_KEY + " >= %.2f", t.minVQSLod)); SELECT_NAMES.add(String.format("FDR-%.2f", t.fdr)); } } diff --git a/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/ApplyVariantCuts.java b/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/ApplyVariantCuts.java index d4e0153d6..1da542f5e 100755 --- a/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/ApplyVariantCuts.java +++ b/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/ApplyVariantCuts.java @@ -100,11 +100,11 @@ public class ApplyVariantCuts extends RodWalker { if( tranches.size() >= 2 ) { for( int iii = 0; iii < tranches.size() - 1; iii++ ) { Tranche t = tranches.get(iii); - hInfo.add(new VCFFilterHeaderLine(t.name, String.format("FDR tranche level at qual: " + t.pCut + " <= x < " + tranches.get(iii+1).pCut))); + hInfo.add(new VCFFilterHeaderLine(t.name, String.format("FDR tranche level at VSQ Lod: " + t.minVQSLod + " <= x < " + tranches.get(iii+1).minVQSLod))); } } if( tranches.size() >= 1 ) { - hInfo.add(new VCFFilterHeaderLine(tranches.get(0).name + "+", String.format("FDR tranche level at qual < " + tranches.get(0).pCut))); + hInfo.add(new VCFFilterHeaderLine(tranches.get(0).name + "+", String.format("FDR tranche level at VQS Lod < " + tranches.get(0).minVQSLod))); } else { throw new UserException("No tranches were found in the file or were above the FDR Filter level " + FDR_FILTER_LEVEL); } @@ -131,28 +131,31 @@ public class ApplyVariantCuts extends RodWalker { if( vc != null && !vc.getSource().equals(DbSNPHelper.STANDARD_DBSNP_TRACK_NAME) && vc.isSNP() ) { String filterString = null; if( !vc.isFiltered() ) { - final double qual = vc.getPhredScaledQual(); - - for( int i = tranches.size() - 1; i >= 0; i-- ) { - Tranche tranche = tranches.get(i); - if( qual >= tranche.pCut ) { - if (i == tranches.size() - 1) { - filterString = VCFConstants.PASSES_FILTERS_v4; - } else { - filterString = tranche.name; + try { + final double lod = vc.getAttributeAsDouble(VariantRecalibrator.VQS_LOD_KEY); + for( int i = tranches.size() - 1; i >= 0; i-- ) { + Tranche tranche = tranches.get(i); + if( lod >= tranche.minVQSLod ) { + if (i == tranches.size() - 1) { + filterString = VCFConstants.PASSES_FILTERS_v4; + } else { + filterString = tranche.name; + } + break; } - break; } - } - if( filterString == null ) { - filterString = tranches.get(0).name+"+"; - } + if( filterString == null ) { + filterString = tranches.get(0).name+"+"; + } - if ( !filterString.equals(VCFConstants.PASSES_FILTERS_v4) ) { - Set filters = new HashSet(); - filters.add(filterString); - vc = VariantContext.modifyFilters(vc, filters); + if ( !filterString.equals(VCFConstants.PASSES_FILTERS_v4) ) { + Set filters = new HashSet(); + filters.add(filterString); + vc = VariantContext.modifyFilters(vc, filters); + } + } catch ( ClassCastException e ) { + throw new UserException.MalformedFile(vc.getSource(), "Invalid value for VQS key " + VariantRecalibrator.VQS_LOD_KEY + " at variant " + vc, e); } } diff --git a/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/GenerateVariantClustersWalker.java b/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/GenerateVariantClustersWalker.java index c82c18c09..b2907e3cf 100755 --- a/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/GenerateVariantClustersWalker.java +++ b/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/GenerateVariantClustersWalker.java @@ -183,7 +183,6 @@ public class GenerateVariantClustersWalker extends RodWalker vcsHapMap = tracker.getVariantContexts(ref, "hapmap", null, context.getLocation(), false, true); @@ -201,7 +200,7 @@ public class GenerateVariantClustersWalker extends RodWalker 0.0 && variantDatum.qual > QUAL_THRESHOLD ) { + if( variantDatum.weight > 0.0 && vc.getPhredScaledQual() > QUAL_THRESHOLD ) { mapList.add( variantDatum ); } } diff --git a/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/Tranche.java b/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/Tranche.java index 1be2eb1d0..2caf27e8a 100755 --- a/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/Tranche.java +++ b/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/Tranche.java @@ -49,33 +49,35 @@ import java.util.*; public class Tranche implements Comparable { private static final int CURRENT_VERSION = 2; - public double fdr, pCut, targetTiTv, knownTiTv, novelTiTv; + public double fdr, minVQSLod, targetTiTv, knownTiTv, novelTiTv; public int numKnown,numNovel; public String name; - public Tranche(double fdr, double targetTiTv, double pCut, int numKnown, double knownTiTv, int numNovel, double novelTiTv) { - this(fdr, targetTiTv, pCut, numKnown, knownTiTv, numNovel, novelTiTv, "anonymous"); + public Tranche(double fdr, double targetTiTv, double minVQSLod, int numKnown, double knownTiTv, int numNovel, double novelTiTv) { + this(fdr, targetTiTv, minVQSLod, numKnown, knownTiTv, numNovel, novelTiTv, "anonymous"); } - public Tranche(double fdr, double targetTiTv, double pCut, int numKnown, double knownTiTv, int numNovel, double novelTiTv, String name) { + public Tranche(double fdr, double targetTiTv, double minVQSLod, int numKnown, double knownTiTv, int numNovel, double novelTiTv, String name) { this.fdr = fdr; this.targetTiTv = targetTiTv; - this.pCut = pCut; + this.minVQSLod = minVQSLod; this.novelTiTv = novelTiTv; this.numNovel = numNovel; this.knownTiTv = knownTiTv; this.numKnown = numKnown; this.name = name; -// if ( targetTiTv < 0.5 || targetTiTv > 10 ) -// throw new UserException("Target Ti/Tv ratio is unreasonable " + targetTiTv); -// -// if ( numKnown < 0 || numNovel < 0) -// throw new ReviewedStingException("Invalid tranch - no. variants is < 0 : known " + numKnown + " novel " + numNovel); + if ( fdr <= 0.0 ) + throw new UserException("Target FDR is unreasonable " + fdr); + + if ( targetTiTv < 0.5 || targetTiTv > 10 ) + throw new UserException("Target Ti/Tv ratio is unreasonable " + targetTiTv); + + if ( numKnown < 0 || numNovel < 0) + throw new ReviewedStingException("Invalid tranch - no. variants is < 0 : known " + numKnown + " novel " + numNovel); if ( name == null ) throw new ReviewedStingException("BUG -- name cannot be null"); - } public int compareTo(Tranche other) { @@ -83,8 +85,8 @@ public class Tranche implements Comparable { } public String toString() { - return String.format("Tranche fdr=%.2f minQual=%.2f known=(%d @ %.2f) novel=(%d @ %.2f) name=%s]", - fdr, pCut, numKnown, knownTiTv, numNovel, novelTiTv, name); + return String.format("Tranche fdr=%.2f minVQSLod=%.4f known=(%d @ %.2f) novel=(%d @ %.2f) name=%s]", + fdr, minVQSLod, numKnown, knownTiTv, numNovel, novelTiTv, name); } /** @@ -103,12 +105,12 @@ public class Tranche implements Comparable { stream.println("# Variant quality score tranches file"); stream.println("# Version number " + CURRENT_VERSION); - stream.println("FDRtranche,targetTiTv,numKnown,numNovel,knownTiTv,novelTiTv,pCut,filterName"); + stream.println("FDRtranche,targetTiTv,numKnown,numNovel,knownTiTv,novelTiTv,minVQSLod,filterName"); Tranche prev = null; for ( Tranche t : tranches ) { - stream.printf("%.2f,%.2f,%d,%d,%.4f,%.4f,%.2f,FDRtranche%.2fto%.2f%n", - t.fdr,t.targetTiTv,t.numKnown,t.numNovel,t.knownTiTv,t.novelTiTv, t.pCut, + stream.printf("%.2f,%.2f,%d,%d,%.4f,%.4f,%.4f,FDRtranche%.2fto%.2f%n", + t.fdr,t.targetTiTv,t.numKnown,t.numNovel,t.knownTiTv,t.novelTiTv, t.minVQSLod, (prev == null ? 0.0 : prev.fdr), t.fdr); prev = t; } @@ -117,8 +119,10 @@ public class Tranche implements Comparable { } private static double getDouble(Map bindings, String key, boolean required) { - if ( bindings.containsKey(key) ) - return Double.valueOf(bindings.get(key)); + if ( bindings.containsKey(key) ) { + String val = bindings.get(key); + return Double.valueOf(val); + } else if ( required ) { throw new UserException.MalformedFile("Malformed tranches file. Missing required key " + key); } @@ -154,6 +158,11 @@ public class Tranche implements Comparable { final String[] vals = line.split(","); if( header == null ) { header = vals; + if ( header.length == 5 ) + // old style tranches file, throw an error + throw new UserException.MalformedFile(f, "Unfortuanately, your tranches file is from a previous version of this tool and cannot be used with the latest code. Please rerun VariantRecalibrator"); + if ( header.length != 8 ) + throw new UserException.MalformedFile(f, "Expected 8 elements in header line " + line); } else { if ( header.length != vals.length ) throw new UserException.MalformedFile(f, "Line had too few/many fields. Header = " + header.length + " vals " + vals.length + " line " + line); @@ -162,11 +171,11 @@ public class Tranche implements Comparable { for ( int i = 0; i < vals.length; i++ ) bindings.put(header[i], vals[i]); tranches.add(new Tranche(getDouble(bindings,"FDRtranche", true), getDouble(bindings,"targetTiTv", false), - getDouble(bindings,"pCut", true), + getDouble(bindings,"minVQSLod", true), getInteger(bindings,"numKnown", false), getDouble(bindings,"knownTiTv", false), getInteger(bindings,"numNovel", true), - Math.max(getDouble(bindings,"novelTiTv", false), getDouble(bindings,"novelTITV", false)), + getDouble(bindings,"novelTiTv", true), bindings.get("filterName"))); } } diff --git a/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantDatum.java b/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantDatum.java index dc2ba54da..f49cd4b7a 100755 --- a/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantDatum.java +++ b/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantDatum.java @@ -36,10 +36,10 @@ public class VariantDatum implements Comparable { public double[] annotations; public boolean isTransition; public boolean isKnown; - public double qual; + public double lod; public double weight; public int compareTo(VariantDatum other) { - return Double.compare(this.qual, other.qual); + return Double.compare(this.lod, other.lod); } } diff --git a/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantGaussianMixtureModel.java b/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantGaussianMixtureModel.java index 6600470aa..3254e4184 100755 --- a/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantGaussianMixtureModel.java +++ b/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantGaussianMixtureModel.java @@ -444,7 +444,7 @@ public final class VariantGaussianMixtureModel extends VariantOptimizationModel } public final double evaluateVariant( GenomeLocParser genomeLocParser, final VariantContext vc ) { - final double[] pVarInCluster = new double[maxGaussians]; + final double[] log10pVarInCluster = new double[maxGaussians]; final double[] annotations = new double[dataManager.numAnnotations]; for( int jjj = 0; jjj < dataManager.numAnnotations; jjj++ ) { @@ -452,14 +452,7 @@ public final class VariantGaussianMixtureModel extends VariantOptimizationModel annotations[jjj] = (value - dataManager.meanVector[jjj]) / dataManager.varianceVector[jjj]; } - evaluateGaussiansForSingleVariant( annotations, pVarInCluster ); - - double sum = 0.0; - for( int kkk = 0; kkk < maxGaussians; kkk++ ) { - sum += pVarInCluster[kkk]; - } - - return sum; + return evaluateGaussiansForSingleVariant( annotations, log10pVarInCluster ); } // --------------------------------------------------------------------------------------------------------- @@ -474,7 +467,7 @@ public final class VariantGaussianMixtureModel extends VariantOptimizationModel public final static List findTranches( final VariantDatum[] data, final double[] FDRtranches, double targetTiTv, File debugFile ) { logger.info(String.format("Finding tranches for %d variants with %d FDRs and a target TiTv of %.2f", data.length, FDRtranches.length, targetTiTv)); - List tranchesData = sortVariantsbyQual(data); + List tranchesData = sortVariantsbyLod(data); double[] runningTiTv = calculateRunningTiTv(tranchesData); if ( debugFile != null) { writeTranchesDebuggingInfo(debugFile, tranchesData, runningTiTv); } @@ -502,14 +495,14 @@ public final class VariantGaussianMixtureModel extends VariantOptimizationModel out.println("Qual isTransition runningTiTv"); for ( int i = 0; i < runningTiTv.length; i++ ) { VariantDatum d = tranchesData.get(i); - out.printf("%.4f %d %.4f%n", d.qual, d.isTransition ? 1 : 0, runningTiTv[i]); + out.printf("%.4f %d %.4f%n", d.lod, d.isTransition ? 1 : 0, runningTiTv[i]); } } catch (FileNotFoundException e) { throw new UserException.CouldNotCreateOutputFile(f, e); } } - private final static List sortVariantsbyQual(final VariantDatum[] data) { + private final static List sortVariantsbyLod(final VariantDatum[] data) { List sorted = new ArrayList(Arrays.asList(data)); Collections.sort(sorted); return sorted; @@ -555,10 +548,10 @@ public final class VariantGaussianMixtureModel extends VariantOptimizationModel public final static Tranche trancheOfVariants( final List data, int minI, double fdr, double targetTiTv ) { int numKnown = 0, numNovel = 0, knownTi = 0, knownTv = 0, novelTi = 0, novelTv = 0; - double qualThreshold = data.get(minI).qual; + double minLod = data.get(minI).lod; VariantDatum last = null; for ( VariantDatum datum : data ) { - if ( datum.qual >= qualThreshold ) { + if ( datum.lod >= minLod ) { //if( ! datum.isKnown ) System.out.println(datum.pos); if ( datum.isKnown ) { numKnown++; @@ -575,7 +568,7 @@ public final class VariantGaussianMixtureModel extends VariantOptimizationModel double knownTiTv = knownTi / Math.max(1.0 * knownTv, 1.0); double novelTiTv = novelTi / Math.max(1.0 * novelTv, 1.0); - return new Tranche(fdr, targetTiTv, qualThreshold, numKnown, knownTiTv, numNovel, novelTiTv); + return new Tranche(fdr, targetTiTv, minLod, numKnown, knownTiTv, numNovel, novelTiTv); } public final static double fdrToTiTv(double desiredFDR, double targetTiTv) { @@ -666,8 +659,7 @@ public final class VariantGaussianMixtureModel extends VariantOptimizationModel return likelihood / sumWeight; } - - private void evaluateGaussiansForSingleVariant( final double[] annotations, final double[] pVarInCluster ) { + private double evaluateGaussiansForSingleVariant( final double[] annotations, final double[] log10pVarInCluster ) { final int numAnnotations = annotations.length; @@ -689,10 +681,12 @@ public final class VariantGaussianMixtureModel extends VariantOptimizationModel final double denomLog10 = CONSTANT_GAUSSIAN_DENOM_LOG10 + sqrtDeterminantLog10[kkk]; final double evalGaussianPDFLog10 = (( -0.5 * sum ) / Math.log(10.0)) - denomLog10; - final double pVar1 = Math.pow(10.0, pClusterLog10[kkk] + evalGaussianPDFLog10); - pVarInCluster[kkk] = pVar1; + //final double pVar1 = Math.pow(10.0, pClusterLog10[kkk] + evalGaussianPDFLog10); + final double pVar1 = pClusterLog10[kkk] + evalGaussianPDFLog10; + log10pVarInCluster[kkk] = pVar1; } + return MathUtils.log10sumLog10(log10pVarInCluster); } diff --git a/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantRecalibrator.java b/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantRecalibrator.java index 958b98be8..0f9125690 100755 --- a/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantRecalibrator.java +++ b/java/src/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantRecalibrator.java @@ -40,6 +40,7 @@ import org.broadinstitute.sting.utils.*; import org.broadinstitute.sting.utils.collections.ExpandingArrayList; import org.broadinstitute.sting.utils.collections.NestedHashMap; import org.broadinstitute.sting.utils.exceptions.UserException; +import org.broadinstitute.sting.utils.exceptions.ReviewedStingException; import org.broadinstitute.sting.utils.vcf.VCFUtils; import java.io.File; @@ -57,6 +58,8 @@ import java.util.*; */ public class VariantRecalibrator extends RodWalker, ExpandingArrayList> { + public static final String VQS_LOD_KEY = "VQSLOD"; + public static final double SMALLEST_LOG10_PVAR = -1e6; ///////////////////////////// // Inputs @@ -115,13 +118,9 @@ public class VariantRecalibrator extends RodWalker inputNames = new HashSet(); private NestedHashMap priorCache = new NestedHashMap(); private boolean trustACField = false; - private double maxQualObserved = 0.0; private PrintStream tranchesStream = null; - private static double round2(double num) { - double result = num * 100.0; + private static double round4(double num) { + double result = num * 10000.0; result = Math.round(result); - result = result / 100.0; + result = result / 10000.0; return result; } @@ -196,8 +194,7 @@ public class VariantRecalibrator extends RodWalker hInfo = new HashSet(); final TreeSet samples = new TreeSet(); hInfo.addAll(VCFUtils.getHeaderFields(getToolkit(), inputNames)); - hInfo.add(new VCFInfoHeaderLine("OQ", 1, VCFHeaderLineType.Float, "The original variant quality score")); - hInfo.add(new VCFInfoHeaderLine("LOD", 1, VCFHeaderLineType.Float, "The log odds ratio calculated by the VR algorithm which was turned into the phred scaled recalibrated quality score")); + hInfo.add(new VCFInfoHeaderLine(VQS_LOD_KEY, 1, VCFHeaderLineType.Float, "log10-scaled probability of variant being true under the trained gaussian mixture model")); samples.addAll(SampleUtils.getUniqueSamplesFromRods(getToolkit(), inputNames)); final VCFHeader vcfHeader = new VCFHeader(hInfo, samples); @@ -288,19 +285,20 @@ public class VariantRecalibrator extends RodWalker maxQualObserved ) { - maxQualObserved = variantDatum.qual; + final double log10pVar = theModel.evaluateVariant( ref.getGenomeLocParser(),vc ); + final double lod = priorLodFactor + log10pVar; + + if ( lod == Double.NEGATIVE_INFINITY ) { + throw new ReviewedStingException("Negative infinity detected during summation at " + vc); } + variantDatum.pos = vc.getStart(); + variantDatum.lod = round4(lod); + mapList.add( variantDatum ); final Map attrs = new HashMap(vc.getAttributes()); - attrs.put("OQ", String.format("%.2f", vc.getPhredScaledQual())); - attrs.put("LOD", String.format("%.4f", lod)); - VariantContext newVC = VariantContext.modifyPErrorFiltersAndAttributes(vc, variantDatum.qual / 10.0, new HashSet(), attrs); + attrs.put(VariantRecalibrator.VQS_LOD_KEY, String.format("%.4f", lod)); + VariantContext newVC = VariantContext.modifyPErrorFiltersAndAttributes(vc, vc.getNegLog10PError(), new HashSet(), attrs); vcfWriter.add( newVC, ref.getBase() ); } diff --git a/java/src/org/broadinstitute/sting/playground/gatk/walkers/genotyper/UnifiedGenotyperEngine.java b/java/src/org/broadinstitute/sting/playground/gatk/walkers/genotyper/UnifiedGenotyperEngine.java index 5d74d5201..a398bbc4a 100755 --- a/java/src/org/broadinstitute/sting/playground/gatk/walkers/genotyper/UnifiedGenotyperEngine.java +++ b/java/src/org/broadinstitute/sting/playground/gatk/walkers/genotyper/UnifiedGenotyperEngine.java @@ -233,7 +233,7 @@ public class UnifiedGenotyperEngine { // the overall lod //double overallLog10PofNull = log10AlleleFrequencyPosteriors.get()[0]; - double overallLog10PofF = MathUtils.log10sum(log10AlleleFrequencyPosteriors.get(), 1); + double overallLog10PofF = MathUtils.log10sumLog10(log10AlleleFrequencyPosteriors.get(), 1); if ( DEBUG_SLOD ) System.out.println("overallLog10PofF=" + overallLog10PofF); // the forward lod @@ -243,7 +243,7 @@ public class UnifiedGenotyperEngine { afcm.get().getLog10PNonRef(tracker, refContext, GLs, log10AlleleFrequencyPriors, log10AlleleFrequencyPosteriors.get()); //double[] normalizedLog10Posteriors = MathUtils.normalizeFromLog10(log10AlleleFrequencyPosteriors.get(), true); double forwardLog10PofNull = log10AlleleFrequencyPosteriors.get()[0]; - double forwardLog10PofF = MathUtils.log10sum(log10AlleleFrequencyPosteriors.get(), 1); + double forwardLog10PofF = MathUtils.log10sumLog10(log10AlleleFrequencyPosteriors.get(), 1); if ( DEBUG_SLOD ) System.out.println("forwardLog10PofNull=" + forwardLog10PofNull + ", forwardLog10PofF=" + forwardLog10PofF); // the reverse lod @@ -253,7 +253,7 @@ public class UnifiedGenotyperEngine { afcm.get().getLog10PNonRef(tracker, refContext, GLs, log10AlleleFrequencyPriors, log10AlleleFrequencyPosteriors.get()); //normalizedLog10Posteriors = MathUtils.normalizeFromLog10(log10AlleleFrequencyPosteriors.get(), true); double reverseLog10PofNull = log10AlleleFrequencyPosteriors.get()[0]; - double reverseLog10PofF = MathUtils.log10sum(log10AlleleFrequencyPosteriors.get(), 1); + double reverseLog10PofF = MathUtils.log10sumLog10(log10AlleleFrequencyPosteriors.get(), 1); if ( DEBUG_SLOD ) System.out.println("reverseLog10PofNull=" + reverseLog10PofNull + ", reverseLog10PofF=" + reverseLog10PofF); double forwardLod = forwardLog10PofF + reverseLog10PofNull - overallLog10PofF; diff --git a/java/src/org/broadinstitute/sting/utils/MathUtils.java b/java/src/org/broadinstitute/sting/utils/MathUtils.java index 77efeecc3..f7d7a434a 100755 --- a/java/src/org/broadinstitute/sting/utils/MathUtils.java +++ b/java/src/org/broadinstitute/sting/utils/MathUtils.java @@ -58,7 +58,7 @@ public class MathUtils { return s; } - public static double log10sum(double[] log10p, int start) { + public static double log10sumLog10(double[] log10p, int start) { double sum = 0.0; double maxValue = Utils.findMaxEntry(log10p); @@ -76,9 +76,14 @@ public class MathUtils { } public static double sumLog10(double[] log10values) { - double s = 0.0; - for ( double v : log10values) s += Math.pow(10.0, v); - return s; + return Math.pow(10.0, log10sumLog10(log10values)); +// double s = 0.0; +// for ( double v : log10values) s += Math.pow(10.0, v); +// return s; + } + + public static double log10sumLog10(double[] log10values) { + return log10sumLog10(log10values, 0); } public static boolean wellFormedDouble(double val) { diff --git a/java/src/org/broadinstitute/sting/utils/pileup/AbstractReadBackedPileup.java b/java/src/org/broadinstitute/sting/utils/pileup/AbstractReadBackedPileup.java index 95f1e3073..6ee64cabb 100644 --- a/java/src/org/broadinstitute/sting/utils/pileup/AbstractReadBackedPileup.java +++ b/java/src/org/broadinstitute/sting/utils/pileup/AbstractReadBackedPileup.java @@ -652,19 +652,6 @@ public abstract class AbstractReadBackedPileup extendedForeachIterator() { - ArrayList x = new ArrayList(size()); - int i = 0; - for ( PileupElement pile : this ) { - x.add(new ExtendedPileupElement(pile.getRead(), pile.getOffset(), i++, this)); - } - - return new IterableIterator(x.iterator()); - } - /** * Simple useful routine to count the number of deletion bases in this pileup * diff --git a/java/src/org/broadinstitute/sting/utils/pileup/ExtendedPileupElement.java b/java/src/org/broadinstitute/sting/utils/pileup/ExtendedPileupElement.java deleted file mode 100755 index a2ada94c5..000000000 --- a/java/src/org/broadinstitute/sting/utils/pileup/ExtendedPileupElement.java +++ /dev/null @@ -1,29 +0,0 @@ -package org.broadinstitute.sting.utils.pileup; - -import net.sf.samtools.SAMRecord; - -/** - * Created by IntelliJ IDEA. - * User: depristo - * Date: Apr 14, 2009 - * Time: 8:54:05 AM - * To change this template use File | Settings | File Templates. - */ -public class ExtendedPileupElement extends PileupElement { - private int pileupOffset = 0; - private ReadBackedPileup pileup = null; - - public ExtendedPileupElement( SAMRecord read, int readOffset, int pileupOffset, ReadBackedPileup pileup ) { - super(read, readOffset); - this.pileupOffset = pileupOffset; - this.pileup = pileup; - } - - public int getPileupOffset() { - return pileupOffset; - } - - public ReadBackedPileup getPileup() { - return pileup; - } -} \ No newline at end of file diff --git a/java/src/org/broadinstitute/sting/utils/pileup/ReadBackedPileup.java b/java/src/org/broadinstitute/sting/utils/pileup/ReadBackedPileup.java index 9454adfd7..ff6b2c122 100644 --- a/java/src/org/broadinstitute/sting/utils/pileup/ReadBackedPileup.java +++ b/java/src/org/broadinstitute/sting/utils/pileup/ReadBackedPileup.java @@ -141,9 +141,6 @@ public interface ReadBackedPileup extends Iterable { */ public ReadBackedPileup getPileupForSample(String sampleName); - // todo -- delete or make private - public IterableIterator extendedForeachIterator(); - /** * Simple useful routine to count the number of deletion bases in this pileup * diff --git a/java/test/org/broadinstitute/sting/gatk/walkers/varianteval/VariantEvalIntegrationTest.java b/java/test/org/broadinstitute/sting/gatk/walkers/varianteval/VariantEvalIntegrationTest.java index 9f84a3e65..912907721 100755 --- a/java/test/org/broadinstitute/sting/gatk/walkers/varianteval/VariantEvalIntegrationTest.java +++ b/java/test/org/broadinstitute/sting/gatk/walkers/varianteval/VariantEvalIntegrationTest.java @@ -143,8 +143,8 @@ public class VariantEvalIntegrationTest extends WalkerTest { @Test public void testTranches() { - String extraArgs = "-T VariantEval -R "+ hg18Reference +" -B:eval,vcf " + validationDataLocation + "GA2.WEx.cleaned.ug.snpfiltered.indelfiltered.optimized.vcf -o %s -E TiTvVariantEvaluator -L chr1 -noStandard -reportType CSV -tf " + testDir + "tranches.4.txt"; - WalkerTestSpec spec = new WalkerTestSpec(extraArgs,1,Arrays.asList("85b6621c64cc8f9a3b68cea644edf216")); + String extraArgs = "-T VariantEval -R "+ hg18Reference +" -B:eval,vcf " + validationDataLocation + "GA2.WEx.cleaned.ug.snpfiltered.indelfiltered.optimized.vcf -o %s -E TiTvVariantEvaluator -L chr1 -noStandard -reportType CSV -tf " + testDir + "tranches.6.txt"; + WalkerTestSpec spec = new WalkerTestSpec(extraArgs,1,Arrays.asList("1002c7a71e6c14f87398d924ac1d92af")); executeTestParallel("testTranches",spec); //executeTest("testACDiscordanceAtAC1EvalAC2Comp",spec); } diff --git a/java/test/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantGaussianMixtureModelUnitTest.java b/java/test/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantGaussianMixtureModelUnitTest.java index b0933735c..50d1484f9 100644 --- a/java/test/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantGaussianMixtureModelUnitTest.java +++ b/java/test/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantGaussianMixtureModelUnitTest.java @@ -59,7 +59,7 @@ public final class VariantGaussianMixtureModelUnitTest extends BaseTest { VariantDatum[] variantData1 = new VariantDatum[N_VARIANTS]; private final File QUAL_DATA = new File(testDir + "tranches.raw.dat"); - private final double[] FDRS = new double[]{0.1, 1, 10, 100}; + private final double[] FDRS = new double[]{0.1, 1, 2, 10}; private final double TARGET_TITV = 2.8; private final File EXPECTED_TRANCHES_NEW = new File(testDir + "tranches.6.txt"); private final File EXPECTED_TRANCHES_OLD = new File(testDir + "tranches.4.txt"); @@ -68,12 +68,13 @@ public final class VariantGaussianMixtureModelUnitTest extends BaseTest { List vd = new ArrayList(); try { for ( String line : new XReadLines(QUAL_DATA, true) ) { - String[] parts = line.split(" "); + String[] parts = line.split("\t"); + // QUAL,TRANSITION,ID,LOD,FILTER if ( ! parts[0].equals("QUAL") ) { VariantDatum datum = new VariantDatum(); - datum.qual = Double.valueOf(parts[0]); + datum.lod = Double.valueOf(parts[3]); datum.isTransition = parts[1].equals("1"); - datum.isKnown = parts[2].equals("1"); + datum.isKnown = ! parts[2].equals("."); vd.add(datum); } } @@ -94,7 +95,7 @@ public final class VariantGaussianMixtureModelUnitTest extends BaseTest { read(EXPECTED_TRANCHES_NEW); } - @Test + @Test(expectedExceptions = {UserException.MalformedFile.class}) public final void readOldFormat() { read(EXPECTED_TRANCHES_OLD); } @@ -103,13 +104,6 @@ public final class VariantGaussianMixtureModelUnitTest extends BaseTest { return Tranche.readTraches(f); } - @Test - public final void testNewAndOldAretheSame() { - List newFormat = read(EXPECTED_TRANCHES_NEW); - List oldFormat = read(EXPECTED_TRANCHES_OLD); - assertTranchesAreTheSame(newFormat, oldFormat, false, true); - } - private static void assertTranchesAreTheSame(List newFormat, List oldFormat, boolean completeP, boolean includeName) { Assert.assertEquals(oldFormat.size(), newFormat.size()); for ( int i = 0; i < newFormat.size(); i++ ) { @@ -136,15 +130,15 @@ public final class VariantGaussianMixtureModelUnitTest extends BaseTest { assertTranchesAreTheSame(read(EXPECTED_TRANCHES_NEW), tranches, true, false); } -// @Test(expectedExceptions = {UserException.class}) -// public final void testBadFDR() { -// List vd = readData(); -// VariantGaussianMixtureModel.findTranches(vd.toArray(new VariantDatum[0]), new double[]{-1}, TARGET_TITV); -// } -// -// @Test(expectedExceptions = {UserException.class}) -// public final void testBadTargetTiTv() { -// List vd = readData(); -// VariantGaussianMixtureModel.findTranches(vd.toArray(new VariantDatum[0]), FDRS, 0.1); -// } + @Test(expectedExceptions = {UserException.class}) + public final void testBadFDR() { + List vd = readData(); + VariantGaussianMixtureModel.findTranches(vd.toArray(new VariantDatum[0]), new double[]{-1}, TARGET_TITV); + } + + @Test(expectedExceptions = {UserException.class}) + public final void testBadTargetTiTv() { + List vd = readData(); + VariantGaussianMixtureModel.findTranches(vd.toArray(new VariantDatum[0]), FDRS, 0.1); + } } diff --git a/java/test/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantRecalibrationWalkersIntegrationTest.java b/java/test/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantRecalibrationWalkersIntegrationTest.java index 30d44a77e..0024149bb 100755 --- a/java/test/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantRecalibrationWalkersIntegrationTest.java +++ b/java/test/org/broadinstitute/sting/gatk/walkers/variantrecalibration/VariantRecalibrationWalkersIntegrationTest.java @@ -30,15 +30,15 @@ public class VariantRecalibrationWalkersIntegrationTest extends WalkerTest { VRTest yriTrio = new VRTest("yri.trio.gatk_glftrio.intersection.annotated.filtered.chr1.vcf", "ab2629d67e378fd3aceb8318f0fbfe04", // in vcf - "4dd95e9d8e5d21a6ab73de67d9663492", // tranches - "4e893672230fca625f70b0491f3b36cb", // recalVCF - "371b0e2796982485ae050e46892f6660"); // cut VCF + "d8f0a92aa42989d332d3c65f61352978", // tranches + "3370e51f6e5035f2472c66762d13c821", // recalVCF + "4801e6cfaeadc81c5c1f9bf5948e2a1c"); // cut VCF VRTest lowPass = new VRTest("lowpass.N3.chr1.raw.vcf", "725489156426e4ddd8d623ab3d4b1023", // in vcf - "dfc07132f592a811d0d6c25a4cb67a09", // tranches - "d52e4f511c9c00f8c21dffea81c47103", // recalVCF - "39716b2f03b50e88855d7975dd1b9b3e"); // cut VCF + "3a7067247146f4a77bb4fd7bc36f94c4", // tranches + "9a525c6838bff695321fc7ac0e458f9c", // recalVCF + "41e0a16af150244454ee68948ced00fb"); // cut VCF @DataProvider(name = "VRTest") public Object[][] createData1() { @@ -64,7 +64,7 @@ public class VariantRecalibrationWalkersIntegrationTest extends WalkerTest { executeTest("testGenerateVariantClusters-"+params.inVCF, spec).getFirst(); } - @Test(dataProvider = "VRTest", dependsOnMethods = {"testGenerateVariantClusters"}, enabled = true) + @Test(dataProvider = "VRTest", enabled = true) public void testVariantRecalibrator(VRTest params) { //System.out.printf("PARAMS FOR %s is %s%n", vcf, clusterFile); WalkerTest.WalkerTestSpec spec = new WalkerTest.WalkerTestSpec( @@ -85,7 +85,7 @@ public class VariantRecalibrationWalkersIntegrationTest extends WalkerTest { executeTest("testVariantRecalibrator-"+params.inVCF, spec).getFirst(); } - @Test(dataProvider = "VRTest", dependsOnMethods = {"testVariantRecalibrator"}, enabled = true) + @Test(dataProvider = "VRTest", enabled = true) public void testApplyVariantCuts(VRTest params) { WalkerTest.WalkerTestSpec spec = new WalkerTest.WalkerTestSpec( "-R " + b36KGReference + diff --git a/testdata/tranches.6.txt b/testdata/tranches.6.txt index 3849718f4..983c444b4 100644 --- a/testdata/tranches.6.txt +++ b/testdata/tranches.6.txt @@ -1,7 +1,7 @@ -# comment 1 -# comment 2 -FDRtranche,targetTiTv,numKnown,numNovel,knownTiTv,novelTiTv,pCut,filterName -0.10,2.8000,15791,893,3.3086,2.8000,1.1800,FDRtranche0.00to0.10 -1.00,2.8000,15824,903,3.3047,2.7782,1.0600,FDRtranche0.10to1.00 -10.00,2.8000,16037,984,3.2937,2.5269,0.3800,FDRtranche1.00to10.00 -100.00,2.8000,16578,1602,3.2291,1.6091,0.0000,FDRtranche10.00to100.00 +# Variant quality score tranches file +# Version number 2 +FDRtranche,targetTiTv,numKnown,numNovel,knownTiTv,novelTiTv,minVQSLod,filterName +0.10,2.80,15839,897,3.3052,2.8008,-3.8485,FDRtranche0.00to0.10 +1.00,2.80,15844,900,3.3043,2.7815,-3.8652,FDRtranche0.10to1.00 +2.00,2.80,15847,902,3.3051,2.7583,-3.8826,FDRtranche1.00to2.00 +10.00,2.80,16153,1039,3.2744,2.5704,-5.1058,FDRtranche2.00to10.00 diff --git a/testdata/tranches.raw.dat b/testdata/tranches.raw.dat index f03c9142f..7090c21b1 100644 --- a/testdata/tranches.raw.dat +++ b/testdata/tranches.raw.dat @@ -1,18180 +1,18181 @@ -27.18 1 1 -38.05 1 1 -95.21 0 0 -2318.43 1 1 -3291.07 1 1 -10982.18 1 1 -93.97999999999999 0 1 -136.49 1 1 -357.08 1 1 -1040.28 1 1 -10.36 1 1 -144.53 1 1 -174.42000000000002 1 1 -6277.560000000001 1 1 -3.84 1 1 -282.35 1 1 -10.969999999999999 0 1 -28.0 1 1 -25.77 0 0 -0.0 1 0 -144.87 1 1 -481.99 1 1 -408.35 0 1 -135.64 1 1 -6985.76 1 1 -18141.9 0 1 -50.58 1 1 -579.84 1 1 -2239.79 1 1 -22.21 1 1 -0.01 0 0 -94.77000000000001 0 0 -777.52 1 1 -2262.98 1 1 -4786.78 1 1 -4741.75 1 1 -108.75 1 1 -0.0 0 0 -6671.39 1 1 -43.92 1 1 -1492.61 0 1 -4.18 0 0 -13542.69 1 1 -2546.2 1 1 -7842.200000000001 1 1 -1566.0899999999997 1 1 -10399.15 1 1 -206.39 1 1 -0.75 1 1 -2290.01 1 1 -1042.12 0 1 -12237.45 1 1 -320.03 1 1 -0.31 1 1 -0.34 0 0 -4602.88 1 1 -879.04 0 1 -1252.93 1 1 -3196.03 1 1 -4426.74 1 1 -7.41 0 1 -14099.130000000001 1 1 -675.72 1 1 -2696.66 1 1 -6265.45 0 1 -10982.01 1 1 -18533.79 1 1 -16636.49 1 1 -4326.87 0 1 -2.23 1 1 -11538.34 1 1 -3025.89 1 1 -8736.99 1 1 -13163.66 1 1 -13189.3 1 1 -388.07000000000005 1 1 -12010.88 0 1 -1308.1099999999997 1 1 -15433.34 1 1 -352.01 0 1 -0.1 1 0 -33.3 0 1 -5671.859999999999 1 1 -11941.26 1 1 -1.18 1 0 -797.28 1 1 -12631.39 1 1 -1038.78 1 1 -5106.88 1 1 -505.39 1 1 -4631.23 1 1 -9012.07 1 1 -13209.87 1 1 -2256.27 0 1 -549.5 1 1 -2756.13 0 1 -14.07 0 1 -11.79 1 1 -4367.95 1 1 -1105.85 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