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Fix to quality score calculation for sites with spanning deletions (#…
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…6859)

* fix off-by one error that was causing the qual calculation to miss probability assigned to homozygous star allele genotypes
* make sure we output all sites if forceOutput it true, even if low-qual 
* updates to handle the case where the only alleles are ref and star
* add update expected results option to GenotypeGVCFsIntegrationTest
* update integration test files
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@cwhelan @mwalker174
cwhelan authored and mwalker174 committed Nov 3, 2020
1 parent 24273bc commit 1218956
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Showing 60 changed files with 1,758 additions and 1,794 deletions.
2 changes: 1 addition & 1 deletion src/main/java/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFs.java
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Expand Up @@ -282,7 +282,7 @@ public void apply(final Locatable loc, List<VariantContext> variants, ReadsConte

if (regenotypedVC != null) {
final SimpleInterval variantStart = new SimpleInterval(regenotypedVC.getContig(), regenotypedVC.getStart(), regenotypedVC.getStart());
if ((inForceOutputIntervals || !GATKVariantContextUtils.isSpanningDeletionOnly(regenotypedVC)) &&
if ((forceOutput || !GATKVariantContextUtils.isSpanningDeletionOnly(regenotypedVC)) &&
(!onlyOutputCallsStartingInIntervals || intervals.stream().anyMatch(interval -> interval.contains (variantStart)))) {
vcfWriter.add(regenotypedVC);
}
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1 change: 1 addition & 0 deletions src/main/java/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFsEngine.java
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Expand Up @@ -400,6 +400,7 @@ public VariantContextWriter setupVCFWriter(Set<VCFHeaderLine> defaultToolVCFHead
if ( dbsnp.dbsnp != null ) {
VCFStandardHeaderLines.addStandardInfoLines(headerLines, true, VCFConstants.DBSNP_KEY);
}
headerLines.add(GATKVCFHeaderLines.getFilterLine(GATKVCFConstants.LOW_QUAL_FILTER_NAME));

final Set<String> sampleNameSet = samples.asSetOfSamples();
outputHeader = new VCFHeader(headerLines, new TreeSet<>(sampleNameSet));
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6 changes: 3 additions & 3 deletions ...g/broadinstitute/hellbender/tools/walkers/genotyper/afcalc/AlleleFrequencyCalculator.java
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Expand Up @@ -86,7 +86,7 @@ private static int[] genotypeIndicesWithOnlyRefAndSpanDel(final int ploidy, fina
} else {
final int spanDelIndex = alleles.indexOf(Allele.SPAN_DEL);
// allele counts are in the GenotypeLikelihoodCalculator format of {ref index, ref count, span del index, span del count}
return new IndexRange(0, ploidy).mapToInteger(n -> glCalc.alleleCountsToIndex(new int[]{0, ploidy - n, spanDelIndex, n}));
return new IndexRange(0, ploidy + 1).mapToInteger(n -> glCalc.alleleCountsToIndex(new int[]{0, ploidy - n, spanDelIndex, n}));
}
}

Expand Down Expand Up @@ -162,7 +162,7 @@ public AFCalculationResult calculate(final VariantContext vc, final int defaultP
}

// if the VC is biallelic the allele-specific qual equals the variant qual
if (numAlleles == 2) {
if (numAlleles == 2 && !spanningDeletionPresent) {
continue;
}

Expand All @@ -183,7 +183,7 @@ public AFCalculationResult calculate(final VariantContext vc, final int defaultP
}

// for biallelic the allele-specific qual equals the variant qual, and we short-circuited the calculation above
if (numAlleles == 2) {
if (numAlleles == 2 && !spanningDeletionPresent) {
log10POfZeroCountsByAllele[1] = log10PNoVariant;
}

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31 changes: 24 additions & 7 deletions src/test/java/org/broadinstitute/hellbender/tools/walkers/GenotypeGVCFsIntegrationTest.java
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Expand Up @@ -44,6 +44,12 @@

public class GenotypeGVCFsIntegrationTest extends CommandLineProgramTest {

// If true, update the expected outputs in tests that assert an exact match vs. prior output,
// instead of actually running the tests. Can be used with "./gradlew test -Dtest.single=GenotypeGVCFsIntegrationTest"
// to update all of the exact-match tests at once. After you do this, you should look at the
// diffs in the new expected outputs in git to confirm that they are consistent with expectations.
public static final boolean UPDATE_EXACT_MATCH_EXPECTED_OUTPUTS = false;

private static final List<String> NO_EXTRA_ARGS = Collections.emptyList();
private static final String BASE_PAIR_EXPECTED = "gvcf.basepairResolution.gatk3.7_30_ga4f720357.output.vcf";
private static final String b38_reference_20_21 = largeFileTestDir + "Homo_sapiens_assembly38.20.21.fasta";
Expand Down Expand Up @@ -163,6 +169,14 @@ public Object[][] GVCFsWithNewMQFormat() {
};
}

/*
* Make sure that someone didn't leave the UPDATE_EXACT_MATCH_EXPECTED_OUTPUTS toggle turned on
*/
@Test
public void assertThatExpectedOutputUpdateToggleIsDisabled() {
Assert.assertFalse(UPDATE_EXACT_MATCH_EXPECTED_OUTPUTS, "The toggle to update expected outputs should not be left enabled");
}

/*
This test is useful for testing changes in GATK4 versus different versions of GATK3.
To use, set GATK3_PATH to point to a particular version of gatk, then enable this test and run.
Expand Down Expand Up @@ -354,25 +368,28 @@ private void runGenotypeGVCFSAndAssertSomething(File input, File expected, List<
}

private void runGenotypeGVCFSAndAssertSomething(String input, File expected, List<String> additionalArguments, BiConsumer<VariantContext, VariantContext> assertion, String reference) throws IOException {
final File output = createTempFile("genotypegvcf", ".vcf");
final File output = UPDATE_EXACT_MATCH_EXPECTED_OUTPUTS ? expected : createTempFile("genotypegvcf", ".vcf");

final ArgumentsBuilder args = new ArgumentsBuilder();
args.addReference(new File(reference))
.add("V", input)
.addFlag(RMSMappingQuality.RMS_MAPPING_QUALITY_OLD_BEHAVIOR_OVERRIDE_ARGUMENT)
.add(StandardArgumentDefinitions.ADD_OUTPUT_VCF_COMMANDLINE, false)
.addOutput(output);

additionalArguments.forEach(args::addRaw);

Utils.resetRandomGenerator();
runCommandLine(args);

final List<VariantContext> expectedVC = VariantContextTestUtils.getVariantContexts(expected);
final List<VariantContext> actualVC = VariantContextTestUtils.getVariantContexts(output);
try {
assertForEachElementInLists(actualVC, expectedVC, assertion);
} catch (final AssertionError error) {
throw error;
if (! UPDATE_EXACT_MATCH_EXPECTED_OUTPUTS) {
final List<VariantContext> expectedVC = VariantContextTestUtils.getVariantContexts(expected);
final List<VariantContext> actualVC = VariantContextTestUtils.getVariantContexts(output);
try {
assertForEachElementInLists(actualVC, expectedVC, assertion);
} catch (final AssertionError error) {
throw error;
}
}
}

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4 changes: 2 additions & 2 deletions src/test/resources/large/gvcfs/combined.gatk3.7_30_ga4f720357.expected.vcf
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4 changes: 2 additions & 2 deletions src/test/resources/large/gvcfs/gatk3.7_30_ga4f720357.24_sample.21.expected.vcf
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2 changes: 1 addition & 1 deletion ...stitute/hellbender/tools/haplotypecaller/expected.testGVCFMode.gatk4.alleleSpecific.g.vcf
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Expand Up @@ -916,7 +916,7 @@
20 10068151 . A <NON_REF> . . END=10068155 GT:DP:GQ:MIN_DP:PL 0/0:29:63:28:0,63,945
20 10068156 . A <NON_REF> . . END=10068157 GT:DP:GQ:MIN_DP:PL 0/0:27:57:27:0,57,855
20 10068158 . GTGTATATATATA G,<NON_REF> 97.60 . AS_RAW_BaseQRankSum=|-0.9,1|NaN;AS_RAW_MQ=5282.00|8882.00|0.00;AS_RAW_MQRankSum=|0.3,1|NaN;AS_RAW_ReadPosRankSum=|0.5,1|NaN;AS_SB_TABLE=0,3|2,2|0,0;BaseQRankSum=-0.842;DP=28;ExcessHet=3.0103;MLEAC=1,0;MLEAF=0.500,0.00;MQRankSum=0.328;RAW_MQandDP=89764,28;ReadPosRankSum=0.524 GT:AD:DP:GQ:PL:SB 0/1:3,4,0:7:57:105,0,57,114,69,183:0,3,2,2
20 10068160 . GTATATATATATGTA G,*,<NON_REF> 88.01 . AS_RAW_BaseQRankSum=|||;AS_RAW_MQ=0.00|1682.00|8882.00|0.00;AS_RAW_MQRankSum=|||;AS_RAW_ReadPosRankSum=|||;AS_SB_TABLE=0,0|0,2|2,2|0,0;DP=32;ExcessHet=3.0103;MLEAC=1,1,0;MLEAF=0.500,0.500,0.00;RAW_MQandDP=101405,32 GT:AD:DP:GQ:PL:SB 1/2:0,2,4,0:6:53:706,158,131,98,0,53,489,171,104,458:0,0,2,4
20 10068160 . GTATATATATATGTA G,*,<NON_REF> 56.01 . AS_RAW_BaseQRankSum=|||;AS_RAW_MQ=0.00|1682.00|8882.00|0.00;AS_RAW_MQRankSum=|||;AS_RAW_ReadPosRankSum=|||;AS_SB_TABLE=0,0|0,2|2,2|0,0;DP=32;ExcessHet=3.0103;MLEAC=1,1,0;MLEAF=0.500,0.500,0.00;RAW_MQandDP=101405,32 GT:AD:DP:GQ:PL:SB 1/2:0,2,4,0:6:53:706,158,131,98,0,53,489,171,104,458:0,0,2,4
20 10068175 . T <NON_REF> . . END=10068175 GT:DP:GQ:MIN_DP:PL 0/0:20:18:20:0,18,270
20 10068176 . A <NON_REF> . . END=10068180 GT:DP:GQ:MIN_DP:PL 0/0:19:24:17:0,24,360
20 10068181 . T <NON_REF> . . END=10068185 GT:DP:GQ:MIN_DP:PL 0/0:16:27:16:0,27,405
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2 changes: 1 addition & 1 deletion ...ces/org/broadinstitute/hellbender/tools/haplotypecaller/expected.testGVCFMode.gatk4.g.vcf
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Expand Up @@ -909,7 +909,7 @@
20 10068151 . A <NON_REF> . . END=10068155 GT:DP:GQ:MIN_DP:PL 0/0:29:63:28:0,63,945
20 10068156 . A <NON_REF> . . END=10068157 GT:DP:GQ:MIN_DP:PL 0/0:27:57:27:0,57,855
20 10068158 . GTGTATATATATA G,<NON_REF> 97.60 . BaseQRankSum=-0.842;DP=28;ExcessHet=3.0103;MLEAC=1,0;MLEAF=0.500,0.00;MQRankSum=0.328;RAW_MQandDP=89764,28;ReadPosRankSum=0.524 GT:AD:DP:GQ:PL:SB 0/1:3,4,0:7:57:105,0,57,114,69,183:0,3,2,2
20 10068160 . GTATATATATATGTA G,*,<NON_REF> 88.01 . DP=32;ExcessHet=3.0103;MLEAC=1,1,0;MLEAF=0.500,0.500,0.00;RAW_MQandDP=101405,32 GT:AD:DP:GQ:PL:SB 1/2:0,2,4,0:6:53:706,158,131,98,0,53,489,171,104,458:0,0,2,4
20 10068160 . GTATATATATATGTA G,*,<NON_REF> 56.01 . DP=32;ExcessHet=3.0103;MLEAC=1,1,0;MLEAF=0.500,0.500,0.00;RAW_MQandDP=101405,32 GT:AD:DP:GQ:PL:SB 1/2:0,2,4,0:6:53:706,158,131,98,0,53,489,171,104,458:0,0,2,4
20 10068175 . T <NON_REF> . . END=10068175 GT:DP:GQ:MIN_DP:PL 0/0:20:18:20:0,18,270
20 10068176 . A <NON_REF> . . END=10068180 GT:DP:GQ:MIN_DP:PL 0/0:19:24:17:0,24,360
20 10068181 . T <NON_REF> . . END=10068185 GT:DP:GQ:MIN_DP:PL 0/0:16:27:16:0,27,405
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2 changes: 1 addition & 1 deletion ...broadinstitute/hellbender/tools/haplotypecaller/expected.testLinkedDebruijnMode.gatk4.vcf
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Expand Up @@ -177,7 +177,7 @@
20 10067264 . G A 2937.06 . AC=2;AF=1.00;AN=2;DP=73;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=59.37;QD=29.53;SOR=0.776 GT:AD:DP:GQ:PL 1/1:0,73:73:99:2951,219,0
20 10067722 . A C 2161.06 . AC=2;AF=1.00;AN=2;DP=59;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=60.00;QD=32.63;SOR=0.846 GT:AD:DP:GQ:PL 1/1:0,54:54:99:2175,163,0
20 10068158 . GTGTATATATATA G 97.60 . AC=1;AF=0.500;AN=2;BaseQRankSum=-0.842;DP=28;ExcessHet=3.0103;FS=3.680;MLEAC=1;MLEAF=0.500;MQ=56.62;MQRankSum=0.328;QD=13.94;ReadPosRankSum=0.524;SOR=0.061 GT:AD:DP:GQ:PL 0/1:3,4:7:57:105,0,57
20 10068160 . GTATATATATATGTA G,* 88.01 . AC=1,1;AF=0.500,0.500;AN=2;DP=32;ExcessHet=3.0103;FS=0.000;MLEAC=1,1;MLEAF=0.500,0.500;MQ=56.29;QD=14.67;SOR=1.329 GT:AD:DP:GQ:PL 1/2:0,2,4:6:53:706,158,131,98,0,53
20 10068160 . GTATATATATATGTA G,* 56.01 . AC=1,1;AF=0.500,0.500;AN=2;DP=32;ExcessHet=3.0103;FS=0.000;MLEAC=1,1;MLEAF=0.500,0.500;MQ=56.29;QD=9.33;SOR=1.329 GT:AD:DP:GQ:PL 1/2:0,2,4:6:53:706,158,131,98,0,53
20 10068981 . G A 2528.06 . AC=2;AF=1.00;AN=2;DP=65;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=60.00;QD=30.36;SOR=0.941 GT:AD:DP:GQ:PL 1/1:0,61:61:99:2542,184,0
20 10070602 . T C 2706.06 . AC=2;AF=1.00;AN=2;DP=76;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=58.78;QD=28.13;SOR=0.749 GT:AD:DP:GQ:PL 1/1:0,72:72:99:2720,216,0
20 10070936 . T A 3646.06 . AC=2;AF=1.00;AN=2;DP=86;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=58.96;QD=27.97;SOR=0.846 GT:AD:DP:GQ:PL 1/1:0,82:82:99:3660,247,0
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2 changes: 1 addition & 1 deletion .../broadinstitute/hellbender/tools/haplotypecaller/expected.testVCFMode.gatk4.nonstrict.vcf
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Expand Up @@ -177,7 +177,7 @@
20 10067264 . G A 2937.06 . AC=2;AF=1.00;AN=2;DP=73;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=59.37;QD=33.11;SOR=0.776 GT:AD:DP:GQ:PL 1/1:0,73:73:99:2951,219,0
20 10067722 . A C 2161.06 . AC=2;AF=1.00;AN=2;DP=59;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=60.00;QD=30.20;SOR=0.846 GT:AD:DP:GQ:PL 1/1:0,54:54:99:2175,163,0
20 10068158 . GTGTATATATATA G 97.60 . AC=1;AF=0.500;AN=2;BaseQRankSum=-0.842;DP=28;ExcessHet=3.0103;FS=3.680;MLEAC=1;MLEAF=0.500;MQ=56.62;MQRankSum=0.328;QD=13.94;ReadPosRankSum=0.524;SOR=0.061 GT:AD:DP:GQ:PL 0/1:3,4:7:57:105,0,57
20 10068160 . GTATATATATATGTA G,* 88.01 . AC=1,1;AF=0.500,0.500;AN=2;DP=32;ExcessHet=3.0103;FS=0.000;MLEAC=1,1;MLEAF=0.500,0.500;MQ=56.29;QD=14.67;SOR=1.329 GT:AD:DP:GQ:PL 1/2:0,2,4:6:53:706,158,131,98,0,53
20 10068160 . GTATATATATATGTA G,* 56.01 . AC=1,1;AF=0.500,0.500;AN=2;DP=32;ExcessHet=3.0103;FS=0.000;MLEAC=1,1;MLEAF=0.500,0.500;MQ=56.29;QD=9.33;SOR=1.329 GT:AD:DP:GQ:PL 1/2:0,2,4:6:53:706,158,131,98,0,53
20 10068981 . G A 2518.06 . AC=2;AF=1.00;AN=2;DP=65;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=60.00;QD=30.49;SOR=0.941 GT:AD:DP:GQ:PL 1/1:0,61:61:99:2532,184,0
20 10070602 . T C 2706.06 . AC=2;AF=1.00;AN=2;DP=76;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=58.78;QD=31.67;SOR=0.749 GT:AD:DP:GQ:PL 1/1:0,72:72:99:2720,216,0
20 10070936 . T A 3646.06 . AC=2;AF=1.00;AN=2;DP=86;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=58.96;QD=29.53;SOR=0.846 GT:AD:DP:GQ:PL 1/1:0,82:82:99:3660,247,0
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2 changes: 1 addition & 1 deletion ...ources/org/broadinstitute/hellbender/tools/haplotypecaller/expected.testVCFMode.gatk4.vcf
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Expand Up @@ -177,7 +177,7 @@
20 10067264 . G A 2937.06 . AC=2;AF=1.00;AN=2;DP=73;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=59.37;QD=33.11;SOR=0.776 GT:AD:DP:GQ:PL 1/1:0,73:73:99:2951,219,0
20 10067722 . A C 2161.06 . AC=2;AF=1.00;AN=2;DP=59;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=60.00;QD=30.20;SOR=0.846 GT:AD:DP:GQ:PL 1/1:0,54:54:99:2175,163,0
20 10068158 . GTGTATATATATA G 97.60 . AC=1;AF=0.500;AN=2;BaseQRankSum=-0.842;DP=28;ExcessHet=3.0103;FS=3.680;MLEAC=1;MLEAF=0.500;MQ=56.62;MQRankSum=0.328;QD=13.94;ReadPosRankSum=0.524;SOR=0.061 GT:AD:DP:GQ:PL 0/1:3,4:7:57:105,0,57
20 10068160 . GTATATATATATGTA G,* 88.01 . AC=1,1;AF=0.500,0.500;AN=2;DP=32;ExcessHet=3.0103;FS=0.000;MLEAC=1,1;MLEAF=0.500,0.500;MQ=56.29;QD=14.67;SOR=1.329 GT:AD:DP:GQ:PL 1/2:0,2,4:6:53:706,158,131,98,0,53
20 10068160 . GTATATATATATGTA G,* 56.01 . AC=1,1;AF=0.500,0.500;AN=2;DP=32;ExcessHet=3.0103;FS=0.000;MLEAC=1,1;MLEAF=0.500,0.500;MQ=56.29;QD=9.33;SOR=1.329 GT:AD:DP:GQ:PL 1/2:0,2,4:6:53:706,158,131,98,0,53
20 10068981 . G A 2518.06 . AC=2;AF=1.00;AN=2;DP=65;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=60.00;QD=30.49;SOR=0.941 GT:AD:DP:GQ:PL 1/1:0,61:61:99:2532,184,0
20 10070602 . T C 2706.06 . AC=2;AF=1.00;AN=2;DP=76;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=58.78;QD=31.67;SOR=0.749 GT:AD:DP:GQ:PL 1/1:0,72:72:99:2720,216,0
20 10070936 . T A 3646.06 . AC=2;AF=1.00;AN=2;DP=86;ExcessHet=3.0103;FS=0.000;MLEAC=2;MLEAF=1.00;MQ=58.96;QD=29.53;SOR=0.846 GT:AD:DP:GQ:PL 1/1:0,82:82:99:3660,247,0
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