diff --git a/src/main/java/org/broadinstitute/hellbender/tools/walkers/genotyper/AlleleSubsettingUtils.java b/src/main/java/org/broadinstitute/hellbender/tools/walkers/genotyper/AlleleSubsettingUtils.java index 660bf634393..b40d2620cba 100644 --- a/src/main/java/org/broadinstitute/hellbender/tools/walkers/genotyper/AlleleSubsettingUtils.java +++ b/src/main/java/org/broadinstitute/hellbender/tools/walkers/genotyper/AlleleSubsettingUtils.java @@ -287,18 +287,15 @@ else if ( clazz.equals(int[].class) ) { * * @param vc target variant context. * @param numAltAllelesToKeep number of alt alleles to keep. + * @param ensureReturnContainsAlt make sure the alleles returned include an alternate, even if it's not in the most likely genotype * @return the list of alleles to keep, including the reference and {@link Allele#NON_REF_ALLELE} if present * */ public static List calculateMostLikelyAlleles(final VariantContext vc, final int defaultPloidy, - final int numAltAllelesToKeep) { + final int numAltAllelesToKeep, boolean ensureReturnContainsAlt) { Utils.nonNull(vc, "vc is null"); Utils.validateArg(defaultPloidy > 0, () -> "default ploidy must be > 0 but defaultPloidy=" + defaultPloidy); Utils.validateArg(numAltAllelesToKeep > 0, () -> "numAltAllelesToKeep must be > 0, but numAltAllelesToKeep=" + numAltAllelesToKeep); - //allow PLs or GPs (as for GATK-DRAGEN), but we need some kind of genotype data - Utils.validateArg(vc.getGenotypes().stream().anyMatch(g -> g.hasPL() || g.hasExtendedAttribute(VCFConstants.GENOTYPE_POSTERIORS_KEY)), () -> "Most likely alleles cannot be calculated without likelihoods"); - //NOTE: this is used in the reblocking case when we have a hom-ref GT and real ALTs - final boolean allHomRefData = vc.getGenotypes().stream().allMatch(g -> g.hasPL() && g.getPL()[0] == 0); //PL=[0,0,0] is okay, we just don't want confident variants final boolean hasSymbolicNonRef = vc.hasAllele(Allele.NON_REF_ALLELE); final int numberOfAllelesThatArentProperAlts = hasSymbolicNonRef ? 2 : 1; @@ -308,11 +305,7 @@ public static List calculateMostLikelyAlleles(final VariantContext vc, f return vc.getAlleles(); } - final double[] likelihoodSums = calculateLikelihoodSums(vc, defaultPloidy, allHomRefData); - if (MathUtils.sum(likelihoodSums) == 0.0 && !allHomRefData) { - throw new IllegalStateException("No likelihood sum exceeded zero -- method was called for variant data " + - "with no variant information."); - } + final double[] likelihoodSums = calculateLikelihoodSums(vc, defaultPloidy, ensureReturnContainsAlt); return filterToMaxNumberOfAltAllelesBasedOnScores(numAltAllelesToKeep, vc.getAlleles(), likelihoodSums); } @@ -342,9 +335,12 @@ public static List filterToMaxNumberOfAltAllelesBasedOnScores(int numAlt * * Since GLs are log likelihoods, this quantity is thus * SUM_{samples whose likeliest genotype contains this alt allele} log(likelihood alt / likelihood hom ref) + * @param vc + * @param defaultPloidy + * @param countAllelesWithoutHomRef true if we know the input is hom-ref, but we still want to know the most likely ALT */ @VisibleForTesting - static double[] calculateLikelihoodSums(final VariantContext vc, final int defaultPloidy, final boolean allHomRefData) { + static double[] calculateLikelihoodSums(final VariantContext vc, final int defaultPloidy, final boolean countAllelesWithoutHomRef) { final double[] likelihoodSums = new double[vc.getNAlleles()]; for ( final Genotype genotype : vc.getGenotypes().iterateInSampleNameOrder() ) { final GenotypeLikelihoods gls = genotype.getLikelihoods(); @@ -352,7 +348,7 @@ static double[] calculateLikelihoodSums(final VariantContext vc, final int defau continue; } final double[] glsVector = gls.getAsVector(); - final int indexOfMostLikelyVariantGenotype = MathUtils.maxElementIndex(glsVector, allHomRefData ? 1 : 0, glsVector.length); + final int indexOfMostLikelyVariantGenotype = MathUtils.maxElementIndex(glsVector, countAllelesWithoutHomRef ? 1 : 0, glsVector.length); final double GLDiffBetweenRefAndBestVariantGenotype = Math.abs(glsVector[indexOfMostLikelyVariantGenotype] - glsVector[PL_INDEX_OF_HOM_REF]); final int ploidy = genotype.getPloidy() > 0 ? genotype.getPloidy() : defaultPloidy; diff --git a/src/main/java/org/broadinstitute/hellbender/tools/walkers/genotyper/GenotypingEngine.java b/src/main/java/org/broadinstitute/hellbender/tools/walkers/genotyper/GenotypingEngine.java index bb184d693d3..bfc29e9aed7 100644 --- a/src/main/java/org/broadinstitute/hellbender/tools/walkers/genotyper/GenotypingEngine.java +++ b/src/main/java/org/broadinstitute/hellbender/tools/walkers/genotyper/GenotypingEngine.java @@ -134,7 +134,7 @@ public VariantContext calculateGenotypes(final VariantContext vc, final Genotype VariantContext reducedVC = vc; if (maxAltAlleles < vc.getAlternateAlleles().size()) { - final List allelesToKeep = AlleleSubsettingUtils.calculateMostLikelyAlleles(vc, defaultPloidy, maxAltAlleles); + final List allelesToKeep = AlleleSubsettingUtils.calculateMostLikelyAlleles(vc, defaultPloidy, maxAltAlleles, false); final GenotypesContext reducedGenotypes = allelesToKeep.size() == 1 ? GATKVariantContextUtils.subsetToRefOnly(vc, defaultPloidy) : AlleleSubsettingUtils.subsetAlleles(vc.getGenotypes(), defaultPloidy, vc.getAlleles(), allelesToKeep, gpc, GenotypeAssignmentMethod.BEST_MATCH_TO_ORIGINAL); //with no PLs in some reblocked GVCFs, no-calls are just going to cause problems, so keep 0/0 genotypes as such without trying to recall diff --git a/src/main/java/org/broadinstitute/hellbender/tools/walkers/variantutils/ReblockGVCF.java b/src/main/java/org/broadinstitute/hellbender/tools/walkers/variantutils/ReblockGVCF.java index d02d60f3618..acb953d3210 100644 --- a/src/main/java/org/broadinstitute/hellbender/tools/walkers/variantutils/ReblockGVCF.java +++ b/src/main/java/org/broadinstitute/hellbender/tools/walkers/variantutils/ReblockGVCF.java @@ -505,7 +505,8 @@ protected GenotypeBuilder changeCallToHomRefVersusNonRef(final VariantContext lo if (posteriorsKey != null && genotype.hasExtendedAttribute(posteriorsKey)) { subsetHomRefPosteriorsToRefVersusNonRef(lowQualVariant, gb); } else { - final List bestAlleles = AlleleSubsettingUtils.calculateMostLikelyAlleles(lowQualVariant, genotype.getPloidy(), 1); + //find best ALT so we can use its likelihood for NON_REF + final List bestAlleles = AlleleSubsettingUtils.calculateMostLikelyAlleles(lowQualVariant, genotype.getPloidy(), 1, true); final Allele bestAlt = bestAlleles.stream().filter(a -> !a.isReference()).findFirst().orElse(Allele.NON_REF_ALLELE); //allow span dels //we care about the best alt even though it's getting removed because NON_REF should get the best likelihoods //it shouldn't matter that we're passing in different alt alleles since the GenotypesContext only knows @@ -928,7 +929,7 @@ private static int[] getGenotypePosteriorsOtherwiseLikelihoods(final Genotype ge private void subsetHomRefPosteriorsToRefVersusNonRef(final VariantContext result, final GenotypeBuilder gb) { //TODO: bestAlleles needs to be modified for posteriors final Genotype genotype = result.getGenotype(0); - final List bestAlleles = AlleleSubsettingUtils.calculateMostLikelyAlleles(result, genotype.getPloidy(), 1); + final List bestAlleles = AlleleSubsettingUtils.calculateMostLikelyAlleles(result, genotype.getPloidy(), 1, false); final Allele bestAlt = bestAlleles.stream().filter(a -> !a.isReference()).findFirst().orElse(Allele.NON_REF_ALLELE); //allow span dels final int[] idxVector = result.getGLIndicesOfAlternateAllele(bestAlt); final int[] multiallelicPLs = getGenotypePosteriorsOtherwiseLikelihoods(genotype, posteriorsKey); diff --git a/src/test/java/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFsIntegrationTest.java b/src/test/java/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFsIntegrationTest.java index c52e2c7aab5..f56ff949e47 100644 --- a/src/test/java/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFsIntegrationTest.java +++ b/src/test/java/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFsIntegrationTest.java @@ -159,6 +159,7 @@ public Object[][] gvcfsToGenotype() { b37_reference_20_21}, //23 highly multi-allelic sites across 54 1000G exomes to test allele subsetting and QUAL calculation + //plus one 10-allele WGS variant that's all hom-ref with one GT that has unnormalized PLs from some sort of GenomicsDB corner case {getTestFile("multiallelicQualRegression.vcf "), getTestFile("multiallelicQualRegression.expected.vcf"), NO_EXTRA_ARGS, hg38Reference} diff --git a/src/test/java/org/broadinstitute/hellbender/tools/walkers/genotyper/AlleleSubsettingUtilsUnitTest.java b/src/test/java/org/broadinstitute/hellbender/tools/walkers/genotyper/AlleleSubsettingUtilsUnitTest.java index a5061033f6d..ab26f27869b 100644 --- a/src/test/java/org/broadinstitute/hellbender/tools/walkers/genotyper/AlleleSubsettingUtilsUnitTest.java +++ b/src/test/java/org/broadinstitute/hellbender/tools/walkers/genotyper/AlleleSubsettingUtilsUnitTest.java @@ -1,7 +1,6 @@ package org.broadinstitute.hellbender.tools.walkers.genotyper; import htsjdk.variant.variantcontext.*; -import htsjdk.variant.vcf.VCFConstants; import org.broadinstitute.hellbender.exceptions.UserException; import org.broadinstitute.hellbender.utils.MathUtils; import org.broadinstitute.hellbender.GATKBaseTest; @@ -288,7 +287,7 @@ public Object[][] makeUpdatePLsSACsAndADData() { public void testCalculateMostLikelyAllelesTieDoesntRemoveAllTiedAlleles(){ VariantContext vc = new VariantContextBuilder(null, "1", 100, 100, Arrays.asList(Aref, C, G)) .genotypes(Arrays.asList(new GenotypeBuilder("sample1", Arrays.asList(C,G)).PL( new double[]{5, 5, 5, 5, 0, 5}).make())).make(); - Assert.assertEquals(AlleleSubsettingUtils.calculateMostLikelyAlleles(vc, 2, 1), Arrays.asList(Aref,C)) ; + Assert.assertEquals(AlleleSubsettingUtils.calculateMostLikelyAlleles(vc, 2, 1, false), Arrays.asList(Aref,C)) ; } @DataProvider @@ -315,9 +314,9 @@ public void testThatFilteringWorksCorrectly(int numToKeep, List alleles, @Test public void testCalculateMostLikelyAllelesPreconditions(){ VariantContext vc = new VariantContextBuilder(null, "1", 100, 100, Arrays.asList(Aref, C, G)).make(); - Assert.assertThrows(IllegalArgumentException.class, () -> AlleleSubsettingUtils.calculateMostLikelyAlleles(null, 2, 2)); - Assert.assertThrows(IllegalArgumentException.class, () -> AlleleSubsettingUtils.calculateMostLikelyAlleles(vc, 0, 2)); - Assert.assertThrows(IllegalArgumentException.class, () -> AlleleSubsettingUtils.calculateMostLikelyAlleles(vc, 2, 0)); + Assert.assertThrows(IllegalArgumentException.class, () -> AlleleSubsettingUtils.calculateMostLikelyAlleles(null, 2, 2, false)); + Assert.assertThrows(IllegalArgumentException.class, () -> AlleleSubsettingUtils.calculateMostLikelyAlleles(vc, 0, 2, false)); + Assert.assertThrows(IllegalArgumentException.class, () -> AlleleSubsettingUtils.calculateMostLikelyAlleles(vc, 2, 0, false)); } @Test diff --git a/src/test/java/org/broadinstitute/hellbender/tools/walkers/haplotypecaller/HaplotypeCallerIntegrationTest.java b/src/test/java/org/broadinstitute/hellbender/tools/walkers/haplotypecaller/HaplotypeCallerIntegrationTest.java index 4f8175e6748..8d75c7d5c16 100644 --- a/src/test/java/org/broadinstitute/hellbender/tools/walkers/haplotypecaller/HaplotypeCallerIntegrationTest.java +++ b/src/test/java/org/broadinstitute/hellbender/tools/walkers/haplotypecaller/HaplotypeCallerIntegrationTest.java @@ -1404,7 +1404,7 @@ public void testMaxAlternateAlleles(final String bam, final String reference, fi final Map> expectedSubsettedAllelesByLocus = new HashMap<>(); for ( final VariantContext vc : callsNoMaxAlternateAlleles ) { if ( getNumAltAllelesExcludingNonRef(vc) > maxAlternateAlleles ) { - final List mostLikelyAlleles = AlleleSubsettingUtils.calculateMostLikelyAlleles(vc, HomoSapiensConstants.DEFAULT_PLOIDY, maxAlternateAlleles); + final List mostLikelyAlleles = AlleleSubsettingUtils.calculateMostLikelyAlleles(vc, HomoSapiensConstants.DEFAULT_PLOIDY, maxAlternateAlleles, false); expectedSubsettedAllelesByLocus.put(new SimpleInterval(vc), mostLikelyAlleles); } } diff --git a/src/test/resources/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFs/multiallelicQualRegression.vcf b/src/test/resources/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFs/multiallelicQualRegression.vcf index 319814ca3e3..79b4848bd53 100644 --- a/src/test/resources/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFs/multiallelicQualRegression.vcf +++ b/src/test/resources/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFs/multiallelicQualRegression.vcf @@ -55,3375 +55,12 @@ ##INFO= ##INFO= ##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= -##contig= 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./.:.:0:39:.:.:0,0,872,0,872,872,0,872,872,872,0,872,872,872,872,0,872,872,872,872,872,0,872,872,872,872,872,872,0,872,872,872,872,872,872,872,0,872,872,872,872,872,872,872,872,0,872,872,872,872,872,872,872,872,872,0,872,872,872,872,872,872,872,872,872,872:.:42 ./.:20,0,0,0,0,0,0,0,0,0,0:60:.:0|1:931134_C_CA:0,60,1243,60,1243,1243,60,1243,1243,1243,60,1243,1243,1243,1243,60,1243,1243,1243,1243,1243,60,1243,1243,1243,1243,1243,1243,60,1243,1243,1243,1243,1243,1243,1243,60,1243,1243,1243,1243,1243,1243,1243,1243,60,1243,1243,1243,1243,1243,1243,1243,1243,1243,60,1243,1243,1243,1243,1243,1243,1243,1243,1243,1243:0,20,0,0:20 ./.:.:0:24:.:.:0,0,331,0,331,331,0,331,331,331,0,331,331,331,331,0,331,331,331,331,331,0,331,331,331,331,331,331,0,331,331,331,331,331,331,331,0,331,331,331,331,331,331,331,331,0,331,331,331,331,331,331,331,331,331,0,331,331,331,331,331,331,331,331,331,331:.:28 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./.:.:0:33:.:.:0,0,567,0,567,567,0,567,567,567,0,567,567,567,567,0,567,567,567,567,567,0,567,567,567,567,567,567,0,567,567,567,567,567,567,567,0,567,567,567,567,567,567,567,567,0,567,567,567,567,567,567,567,567,567,0,567,567,567,567,567,567,567,567,567,567:.:39 ./.:.:0:46:.:.:0,0,773,0,773,773,0,773,773,773,0,773,773,773,773,0,773,773,773,773,773,0,773,773,773,773,773,773,0,773,773,773,773,773,773,773,0,773,773,773,773,773,773,773,773,0,773,773,773,773,773,773,773,773,773,0,773,773,773,773,773,773,773,773,773,773:.:57 ./.:19,0,0,0,0,0,0,0,0,0,0:22:.:0|1:931130_T_TCCCCAGGC:0,57,3236,57,3236,3236,57,3236,3236,3236,57,3236,3236,3236,3236,57,3236,3236,3236,3236,3236,57,3236,3236,3236,3236,3236,3236,22,3201,3201,3201,3201,3201,3201,3198,57,3236,3236,3236,3236,3236,3236,3201,3236,57,3236,3236,3236,3236,3236,3236,3201,3236,3236,57,3236,3236,3236,3236,3236,3236,3201,3236,3236,3236:0,19,0,0:19 ./.:.:0:31:.:.:0,0,477,0,477,477,0,477,477,477,0,477,477,477,477,0,477,477,477,477,477,0,477,477,477,477,477,477,0,477,477,477,477,477,477,477,0,477,477,477,477,477,477,477,477,0,477,477,477,477,477,477,477,477,477,0,477,477,477,477,477,477,477,477,477,477:.:33 ./.:.:0:29:.:.:0,0,503,0,503,503,0,503,503,503,0,503,503,503,503,0,503,503,503,503,503,0,503,503,503,503,503,503,0,503,503,503,503,503,503,503,0,503,503,503,503,503,503,503,503,0,503,503,503,503,503,503,503,503,503,0,503,503,503,503,503,503,503,503,503,503:.:34 ./.:18,0,0,0,0,0,0,0,0,0,0:54:.:.:.:0,54,747,54,779,1031,54,747,779,747,54,747,779,747,747,54,747,779,747,747,747,54,747,779,747,747,747,747,54,747,779,747,747,747,747,747,54,747,779,747,747,747,747,747,747,54,747,779,747,747,747,747,747,747,747,54,747,779,747,747,747,747,747,747,747,747:0,18,0,0:18 ./.:19,0,0,0,0,0,0,0,0,0,0:56:.:.:.:0,56,751,56,751,751,56,751,751,751,56,751,751,751,751,56,751,751,751,751,751,56,751,751,751,751,751,751,56,751,751,751,751,751,751,751,56,751,751,751,751,751,751,751,751,56,751,751,751,751,751,751,751,751,751,56,751,751,751,751,751,751,751,751,751,751:2,17,0,0:19 chr1 3836468 . GTTTT GTTTTT,GTTTTTTT,G,GTTT,GTT,GT,GTTTTTT, . . AS_QUALapprox=|286|166|103|29|87|28|403|0;AS_RAW_BaseQRankSum=|-0.700,1|0.000,1,1.300,1|-0.800,1|-2.300,1|0.000,1,0.600,1|0.800,1|0.600,1,1.000,1|;AS_RAW_MQ=172286.000|86400.000|24825.000|14400.000|21600.000|14400.000|14400.000|49587.000|0.000;AS_RAW_MQRankSum=|0.000,1|-1.100,1,-0.700,1|1.100,1|1.200,1|1.500,1,1.600,1|0.000,1|-0.900,1,-0.800,1|;AS_RAW_ReadPosRankSum=|0.300,1|-2.700,1,0.600,1|-1.000,1|-1.000,1|-0.600,1,-0.200,1|0.500,1|-0.800,1,-0.300,1|;AS_SB_TABLE=53,5|20,2|9,0|3,1|4,2|4,0|3,1|20,1|0,0;AS_VarDP=58|24|9|4|6|4|4|21|0;BaseQRankSum=0;DP=2100;MQRankSum=0;QUALapprox=1141;RAW_GT_COUNT=0,8,3;RAW_MQandDP=1647249,550;ReadPosRankSum=-0.23;VarDP=145 GT:AD:GQ:PL:SB:DP 0/1:11,22,0,0,0,0,0,0,0:99:239,0,174,338,219,636,338,219,636,636,338,219,636,636,636,338,219,636,636,636,636,338,219,636,636,636,636,636,338,219,636,636,636,636,636,636,338,219,636,636,636,636,636,636,636:11,0,29,4:44 0/0:.:50:.:.:27 0/0:.:10:.:.:30 0/0:.:10:.:.:28 0/0:.:0:.:.:3 0/0:.:60:.:.:27 0/0:.:30:.:.:59 0/2:3,0,7,0,0,0,0,0,0:59:132,142,223,0,80,59,142,223,80,223,142,223,80,223,223,142,223,80,223,223,223,142,223,80,223,223,223,223,142,223,80,223,223,223,223,223,142,223,80,223,223,223,223,223,223:3,0,7,0:10 0/0:.:60:.:.:33 0/0:.:60:.:.:31 .:.:.:.:.:. 0/0:.:60:.:.:27 0/0:.:60:.:.:30 0/0:.:40:.:.:51 0/0:.:60:.:.:29 0/0:.:60:.:.:31 0/3:8,0,0,4,0,0,0,0,0:99:103,160,534,160,534,534,0,437,437,670,160,534,534,437,534,160,534,534,437,534,534,160,534,534,437,534,534,534,160,534,534,437,534,534,534,534,160,534,534,437,534,534,534,534,534:8,0,5,1:14 0/0:.:60:.:.:30 0/0:.:60:.:.:32 0/0:.:60:.:.:37 0/0:.:40:.:.:49 0/0:.:60:.:.:36 0/2:2,0,2,0,0,0,0,0,0:34:34,42,113,0,71,65,42,113,71,113,42,113,71,113,113,42,113,71,113,113,113,42,113,71,113,113,113,113,42,113,71,113,113,113,113,113,42,113,71,113,113,113,113,113,113:0,2,2,0:4 0/4:10,0,0,0,4,0,0,0,0:19:19,48,195,48,195,195,48,195,195,195,0,147,147,147,135,48,195,195,195,147,195,48,195,195,195,147,195,195,48,195,195,195,147,195,195,195,48,195,195,195,147,195,195,195,195:9,1,2,2:14 0/0:.:30:.:.:58 0/0:.:60:.:.:32 0/5:11,0,0,0,0,2,0,0,0:20:20,54,305,54,305,305,54,305,305,305,54,305,305,305,305,0,251,251,251,251,245,54,305,305,305,305,251,305,54,305,305,305,305,251,305,305,54,305,305,305,305,251,305,305,305:11,0,2,0:13 0/0:.:60:.:.:26 0/0:.:60:.:.:26 0/0:.:60:.:.:32 .:.:.:.:.:. 0/0:.:60:.:.:29 6/7:1,0,0,0,0,0,4,6,0:47:141,222,534,222,534,534,222,534,534,534,222,534,534,534,534,222,534,534,534,534,534,113,472,472,472,472,472,742,47,137,137,137,137,137,0,82,222,534,534,534,534,534,472,137,534:0,1,9,1:11 0/0:.:10:.:.:40 0/0:.:60:.:.:41 0/0:.:60:.:.:30 0/7:2,0,0,0,0,0,0,9,0:10:186,193,234,193,234,234,193,234,234,234,193,234,234,234,234,193,234,234,234,234,234,193,234,234,234,234,234,234,0,41,41,41,41,41,41,10,193,234,234,234,234,234,234,41,234:1,1,8,1:11 0/0:.:20:.:.:43 4/7:0,0,0,0,2,0,0,6,0:30:153,176,228,176,228,228,176,228,228,228,143,196,196,196,229,176,228,228,228,196,228,176,228,228,228,196,228,228,30,54,54,54,0,54,54,41,176,228,228,228,196,228,228,54,228:0,0,8,0:8 0/0:.:10:.:.:28 0/0:.:60:.:.:29 .:.:.:.:.:. 0/0:.:60:.:.:30 0/5:10,0,0,0,0,2,0,0,0:67:67,155,689,155,689,689,155,689,689,689,155,689,689,689,689,0,279,279,279,279,163,155,689,689,689,689,279,689,155,689,689,689,689,279,689,689,155,689,689,689,689,279,689,689,689:10,0,3,1:14 0/0:.:30:.:.:34 0/0:.:50:.:.:23 0/0:.:50:.:.:37 0/0:.:60:.:.:29 0/0:.:30:.:.:34 0/0:.:20:.:.:43 .:.:.:.:.:. 0/0:.:60:.:.:31 0/0:.:60:.:.:39 0/0:.:60:.:.:28 0/0:.:60:.:.:36 0/0:.:60:.:.:38 0/0:.:30:.:.:36 0/0:.:50:.:.:31 0/0:.:50:.:.:29 .:.:.:.:.:. 0/0:.:60:.:.:33 .:.:.:.:.:. 1/1:0,2,0,0,0,0,0,0,0:8:47,8,0,47,8,47,47,8,47,47,47,8,47,47,47,47,8,47,47,47,47,47,8,47,47,47,47,47,47,8,47,47,47,47,47,47,47,8,47,47,47,47,47,47,47:0,0,2,0:2 0/0:.:10:.:.:15 .:.:.:.:.:. chr1 11055120 . CTTT CTTTT,C,CT,CTT,CTTTTT,CTTTTTT,CTTTTTTT, . . 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AACACAC AACACACAC,AACAC,A,AAC,CACACAC,AACACACACAC,ACACACAC,AAACACACAC, . . AS_QUALapprox=|830|949|6317|1836|1976|978|1304|736|724;AS_RAW_BaseQRankSum=|-2.600,1,-0.400,1,0.000,1,0.200,1,0.600,2|-0.600,1,0.000,2,0.200,1,0.600,1,0.900,1|-0.400,1,-0.300,2,-0.200,1,0.100,1,0.400,1,0.600,2,0.700,1,0.900,1,1.000,1,1.800,1|0.000,1,0.200,1,0.600,2,0.900,2|0.000,1,0.200,1,0.600,3,0.900,1|0.000,1,0.200,1,0.600,2,0.900,1|0.000,1,0.200,1,0.600,2,0.900,1|0.000,1,0.200,1,0.600,2,0.900,1|0.000,1,0.200,1,0.600,2,0.900,1;AS_RAW_MQ=879551.000|13361.000|21200.000|350230.000|87817.000|17789.000|8800.000|0.000|0.000|90052.000;AS_RAW_MQRankSum=|-3.300,1,-1.300,1,-0.300,1,0.000,1,0.300,1,1.300,1|-1.300,1,-1.100,1,-0.400,1,-0.300,1,0.100,1,1.300,1|-3.200,1,-1.600,1,-1.100,1,-0.400,2,-0.300,1,-0.200,1,0.200,1,0.300,2,0.800,1,0.900,1|-3.500,1,-1.300,1,-1.100,1,-0.300,1,0.300,1,1.300,1|-1.300,1,-1.100,1,-0.300,1,0.000,1,0.300,1,1.300,1|-1.300,1,-1.100,1,-0.300,1,0.300,1,1.300,1|-1.300,1,-1.100,1,-0.300,1,0.300,1,1.300,1|-1.300,1,-1.100,1,-0.300,1,0.300,1,1.300,1|-1.300,1,-1.100,1,-0.300,1,0.300,1,1.300,1;AS_RAW_ReadPosRankSum=|-1.700,1,-1.400,1,0.300,1,0.600,2,1.900,1|-1.400,1,-0.600,1,0.300,2,0.600,1,1.200,1|-1.800,1,-1.700,1,-1.500,1,-0.600,1,-0.400,2,0.400,1,0.600,2,1.000,1,1.500,1,2.200,1|-1.700,1,-1.400,1,-0.600,1,-0.500,1,0.300,1,0.600,1|-1.700,1,-1.400,1,-0.600,1,0.300,1,0.600,1,1.400,1|-1.700,1,-1.400,1,-0.600,1,0.300,1,0.600,1|-1.700,1,-1.400,1,-0.600,1,0.300,1,0.600,1|-1.700,1,-1.400,1,-0.600,1,0.300,1,0.600,1|-1.700,1,-1.400,1,-0.600,1,0.300,1,0.600,1;AS_SB_TABLE=47,212|3,2|1,6|13,103|5,21|2,4|0,3|0,0|0,0|5,22;AS_VarDP=256|11|10|143|26|3|5|1|0|0;BaseQRankSum=0.475;DP=3280;MQRankSum=-0.22;QUALapprox=9035;RAW_GT_COUNT=0,14,10;RAW_MQandDP=4464534,1328;ReadPosRankSum=0.644;VarDP=533 GT:AD:GQ:PL:SB:DP 0/1:26,9,0,0,0,0,0,0,0,0:36:36,0,1006,236,1081,1900,236,1081,1900,1900,236,1081,1900,1900,1900,236,1081,1900,1900,1900,1900,236,1081,1900,1900,1900,1900,1900,236,1081,1900,1900,1900,1900,1900,1900,236,1081,1900,1900,1900,1900,1900,1900,1900,236,1081,1900,1900,1900,1900,1900,1900,1900,1900:4,6,17,7:51 0/0:.:10:.:.:26 0/0:.:20:.:.:31 0/0:.:0:.:.:26 0/0:.:10:.:.:7 0/2:9,0,3,0,0,0,0,0,0,0:9:9,96,1297,0,1147,1124,96,1297,1147,1297,96,1297,1147,1297,1297,96,1297,1147,1297,1297,1297,96,1297,1147,1297,1297,1297,1297,96,1297,1147,1297,1297,1297,1297,1297,96,1297,1147,1297,1297,1297,1297,1297,1297,96,1297,1147,1297,1297,1297,1297,1297,1297,1297:1,8,0,4:13 0/0:.:60:.:.:69 3/4:0,0,0,7,11,0,0,0,0,0:99:676,559,526,559,526,526,254,258,258,220,156,154,154,0,103,559,526,526,258,154,526,559,526,526,258,154,526,526,559,526,526,258,154,526,526,526,559,526,526,258,154,526,526,526,526,559,526,526,258,154,526,526,526,526,526:0,0,4,14:18 0/3:7,0,0,9,0,0,0,0,0,0:99:575,480,731,480,731,731,0,301,301,465,480,731,731,301,731,480,731,731,301,731,731,480,731,731,301,731,731,731,480,731,731,301,731,731,731,731,480,731,731,301,731,731,731,731,731,480,731,731,301,731,731,731,731,731,731:2,5,0,11:18 3/4:0,0,0,7,5,0,0,0,0,0:91:584,462,445,462,445,445,169,171,171,193,124,137,137,0,91,462,445,445,171,137,445,462,445,445,171,137,445,445,462,445,445,171,137,445,445,445,462,445,445,171,137,445,445,445,445,462,445,445,171,137,445,445,445,445,445:0,0,3,11:14 0/0:.:60:.:.:67 0/3:7,0,0,2,0,0,0,0,0,0:99:220,146,534,146,534,534,0,389,389,364,146,534,534,389,534,146,534,534,389,534,534,146,534,534,389,534,534,534,146,534,534,389,534,534,534,534,146,534,534,389,534,534,534,534,534,146,534,534,389,534,534,534,534,534,534:0,7,0,3:10 0/0:.:20:.:.:21 0/0:.:0:.:.:25 0/0:.:30:.:.:35 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0/3:12,0,0,7,0,0,0,0,0,0:99:238,274,759,274,759,759,0,486,486,462,274,759,759,486,759,274,759,759,486,759,759,274,759,759,486,759,759,759,274,759,759,486,759,759,759,759,274,759,759,486,759,759,759,759,759,274,759,759,486,759,759,759,759,759,759:2,10,1,6:19 0/0:.:50:.:.:65 0/0:.:50:.:.:59 0/0:.:40:.:.:49 0/0:.:60:.:.:62 0/5:11,0,0,0,0,1,0,0,0,0:71:71,202,1661,202,1661,1661,202,1661,1661,1661,202,1661,1661,1661,1661,0,587,587,587,587,745,202,1661,1661,1661,1661,587,1661,202,1661,1661,1661,1661,587,1661,1661,202,1661,1661,1661,1661,587,1661,1661,1661,202,1661,1661,1661,1661,587,1661,1661,1661,1661:2,9,3,7:21 0/0:.:60:.:.:57 0/0:.:50:.:.:38 0/0:.:60:.:.:67 0/3:3,0,0,7,0,0,0,0,0,0:99:213,286,1226,286,1226,1226,0,942,942,1038,286,1226,1226,942,1226,286,1226,1226,942,1226,1226,286,1226,1226,942,1226,1226,1226,286,1226,1226,942,1226,1226,1226,1226,286,1226,1226,942,1226,1226,1226,1226,1226,286,1226,1226,942,1226,1226,1226,1226,1226,1226:0,3,1,7:11 0/0:.:60:.:.:83 0/0:.:40:.:.:60 0/0:.:60:.:.:56 0/3:28,0,0,13,0,0,0,0,0,0:99:463,547,1661,547,1661,1661,0,1114,1114,1074,547,1661,1661,1114,1661,547,1661,1661,1114,1661,1661,547,1661,1661,1114,1661,1661,1661,547,1661,1661,1114,1661,1661,1661,1661,547,1661,1661,1114,1661,1661,1661,1661,1661,547,1661,1661,1114,1661,1661,1661,1661,1661,1661:4,24,1,12:41 0/0:.:60:.:.:55 3/7:10,0,0,8,0,0,0,1,0,0:99:741,901,1620,901,1620,1620,418,974,974,1141,901,1620,1620,974,1620,901,1620,1620,974,1620,1620,901,1620,1620,974,1620,1620,1620,161,773,773,0,773,773,773,904,901,1620,1620,974,1620,1620,1620,773,1620,901,1620,1620,974,1620,1620,1620,773,1620,1620:0,10,0,11:21 0/4:39,0,0,0,7,0,0,0,0,0:99:146,221,1589,221,1589,1589,221,1589,1589,1589,0,1378,1378,1378,1349,221,1589,1589,1589,1378,1589,221,1589,1589,1589,1378,1589,1589,221,1589,1589,1589,1378,1589,1589,1589,221,1589,1589,1589,1378,1589,1589,1589,1589,221,1589,1589,1589,1378,1589,1589,1589,1589,1589:7,32,0,11:50 0/0:.:20:.:.:48 3/2:1,0,3,9,0,0,0,0,0,0:88:549,435,488,330,333,307,88,171,0,321,435,488,333,171,488,435,488,333,171,488,488,435,488,333,171,488,488,488,435,488,333,171,488,488,488,488,435,488,333,171,488,488,488,488,488,435,488,333,171,488,488,488,488,488,488:0,1,2,16:19 0/0:.:60:.:.:60 0/0:.:50:.:.:23 0/0:.:60:.:.:28 0/0:.:60:.:.:73 0/8:8,0,0,0,0,0,0,0,0,0:12:12,142,1567,142,1567,1567,142,1567,1567,1567,142,1567,1567,1567,1567,142,1567,1567,1567,1567,1567,142,1567,1567,1567,1567,1567,1567,142,1567,1567,1567,1567,1567,1567,1567,0,1281,1281,1281,1281,1281,1281,1281,1237,142,1567,1567,1567,1567,1567,1567,1567,1281,1567:1,7,0,1:9 3/2:3,0,4,9,0,0,0,0,0,0:43:486,415,521,327,363,340,43,174,0,238,415,521,363,174,521,415,521,363,174,521,521,415,521,363,174,521,521,521,415,521,363,174,521,521,521,521,415,521,363,174,521,521,521,521,521,415,521,363,174,521,521,521,521,521,521:1,2,2,14:19 0/0:.:40:.:.:68 3/3:0,0,0,11,0,0,0,0,0,0:36:478,478,478,478,478,478,36,36,36,0,478,478,478,36,478,478,478,478,36,478,478,478,478,478,36,478,478,478,478,478,478,36,478,478,478,478,478,478,478,36,478,478,478,478,478,478,478,478,36,478,478,478,478,478,478:0,0,0,11:11 0/0:.:40:.:.:62 0/0:.:50:.:.:33 0/0:.:40:.:.:55 0/0:.:60:.:.:58 0/3:42,0,0,6,0,0,0,0,0,0:99:196,255,1702,255,1702,1702,0,1455,1455,1421,255,1702,1702,1455,1702,255,1702,1702,1455,1702,1702,255,1702,1702,1455,1702,1702,1702,255,1702,1702,1455,1702,1702,1702,1702,255,1702,1702,1455,1702,1702,1702,1702,1702,255,1702,1702,1455,1702,1702,1702,1702,1702,1702:12,30,1,9:52 0/0:.:10:.:.:18 0/0:.:60:.:.:58 0/0:.:60:.:.:59 0/0:.:60:.:.:47 3/5:0,0,0,4,0,0,0,0,0,0:99:420,485,1364,485,1364,1364,245,1124,1124,1229,485,1364,1364,1124,1364,175,244,244,0,244,569,485,1364,1364,1124,1364,244,1364,485,1364,1364,1124,1364,244,1364,1364,485,1364,1364,1124,1364,244,1364,1364,1364,485,1364,1364,1124,1364,244,1364,1364,1364,1364:0,0,0,4:4 0/0:.:20:.:.:52 0/3:24,0,0,7,0,0,0,0,0,0:99:129,246,1575,246,1575,1575,0,911,911,873,246,1575,1575,911,1575,246,1575,1575,911,1575,1575,246,1575,1575,911,1575,1575,1575,246,1575,1575,911,1575,1575,1575,1575,246,1575,1575,911,1575,1575,1575,1575,1575,246,1575,1575,911,1575,1575,1575,1575,1575,1575:3,21,1,6:31 0/0:.:50:.:.:44 3/4:0,0,0,6,3,0,0,0,0,0:78:371,303,290,303,290,290,83,94,94,78,129,129,129,0,101,303,290,290,94,129,290,303,290,290,94,129,290,290,303,290,290,94,129,290,290,290,303,290,290,94,129,290,290,290,290,303,290,290,94,129,290,290,290,290,290:0,0,0,9:9 .:.:.:.:.:. 0/3:15,0,0,14,0,0,0,0,0,0:99:503,548,1352,548,1352,1352,0,804,804,758,548,1352,1352,804,1352,548,1352,1352,804,1352,1352,548,1352,1352,804,1352,1352,1352,548,1352,1352,804,1352,1352,1352,1352,548,1352,1352,804,1352,1352,1352,1352,1352,548,1352,1352,804,1352,1352,1352,1352,1352,1352:1,14,2,12:29 diff --git a/src/test/resources/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFs/multiallelicQualRegression.vcf.idx b/src/test/resources/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFs/multiallelicQualRegression.vcf.idx index 90f10b9024e..e29984d6567 100644 Binary files a/src/test/resources/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFs/multiallelicQualRegression.vcf.idx and b/src/test/resources/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFs/multiallelicQualRegression.vcf.idx differ