diff --git a/src/main/java/org/broadinstitute/hellbender/tools/walkers/contamination/ContaminationModel.java b/src/main/java/org/broadinstitute/hellbender/tools/walkers/contamination/ContaminationModel.java index 14f97958f97..a26ec2820da 100644 --- a/src/main/java/org/broadinstitute/hellbender/tools/walkers/contamination/ContaminationModel.java +++ b/src/main/java/org/broadinstitute/hellbender/tools/walkers/contamination/ContaminationModel.java @@ -36,6 +36,8 @@ public class ContaminationModel { public static final double UNSCRUPULOUS_HOM_REF_ALLELE_FRACTION = 0.15; public static final double UNSCRUPULOUS_HOM_REF_FRACTION_TO_REMOVE_FOR_POSSIBLE_LOH = 0.1; public static final double UNSCRUPULOUS_HOM_REF_PERCENTILE = 100 * ( 1 - UNSCRUPULOUS_HOM_REF_FRACTION_TO_REMOVE_FOR_POSSIBLE_LOH); + public static final double MINIMUM_UNSCRUPULOUS_HOM_REF_ALT_FRACTION_THRESHOLD = 0.1; + public static final double MAF_STEP_SIZE = 0.04; private final double contamination; private final double errorRate; @@ -101,12 +103,13 @@ public Pair calculateContaminationFromHoms(final List result = calculateContamination(Strategy.UNSCRUPULOUS_HOM_REF, tumorSites, 0); + return Double.isNaN(result.getLeft()) ? Pair.of(0.0, 1.0) : result; } /** @@ -134,8 +137,9 @@ private Pair calculateContamination(final Strategy strategy, fin final List candidateHomRefs = tumorSites.stream() .filter(site -> site.getAltFraction() < UNSCRUPULOUS_HOM_REF_ALLELE_FRACTION) .collect(Collectors.toList()); - final double threshold = new Percentile(UNSCRUPULOUS_HOM_REF_PERCENTILE).evaluate(candidateHomRefs.stream().mapToDouble(PileupSummary::getAltFraction).toArray()); - genotypingHoms = candidateHomRefs.stream().filter(site -> site.getAltFraction() < threshold).collect(Collectors.toList()); + final double altFractionThreshold = Math.max(MINIMUM_UNSCRUPULOUS_HOM_REF_ALT_FRACTION_THRESHOLD, + new Percentile(UNSCRUPULOUS_HOM_REF_PERCENTILE).evaluate(candidateHomRefs.stream().mapToDouble(PileupSummary::getAltFraction).toArray())); + genotypingHoms = candidateHomRefs.stream().filter(site -> site.getAltFraction() <= altFractionThreshold).collect(Collectors.toList()); } final List homs = subsetSites(tumorSites, genotypingHoms); final double tumorErrorRate = calculateErrorRate(tumorSites); diff --git a/src/test/java/org/broadinstitute/hellbender/tools/walkers/contamination/CalculateContaminationIntegrationTest.java b/src/test/java/org/broadinstitute/hellbender/tools/walkers/contamination/CalculateContaminationIntegrationTest.java index 010f54669c7..ca0abdf5e11 100644 --- a/src/test/java/org/broadinstitute/hellbender/tools/walkers/contamination/CalculateContaminationIntegrationTest.java +++ b/src/test/java/org/broadinstitute/hellbender/tools/walkers/contamination/CalculateContaminationIntegrationTest.java @@ -20,11 +20,11 @@ * Created by David Benjamin on 2/16/17. */ public class CalculateContaminationIntegrationTest extends CommandLineProgramTest { - public static final File SPIKEIN_DATA_DIRECTORY = new File(getTestDataDir(), "calculatecontamination"); - public static final File NA12891_1_PCT_NA12892_99_PCT = new File(SPIKEIN_DATA_DIRECTORY, "NA12891_0.01_NA12892_0.99.table"); - public static final File NA12891_3_PCT_NA12892_97_PCT = new File(SPIKEIN_DATA_DIRECTORY, "NA12891_0.03_NA12892_0.97.table"); - public static final File NA12891_5_PCT_NA12892_95_PCT = new File(SPIKEIN_DATA_DIRECTORY, "NA12891_0.05_NA12892_0.95.table"); - public static final File NA12891_8_PCT_NA12892_92_PCT = new File(SPIKEIN_DATA_DIRECTORY, "NA12891_0.08_NA12892_0.92.table"); + public static final File CONTAMINATION_TEST_DATA_DIRECTORY = new File(getTestDataDir(), "calculatecontamination"); + public static final File NA12891_1_PCT_NA12892_99_PCT = new File(CONTAMINATION_TEST_DATA_DIRECTORY, "NA12891_0.01_NA12892_0.99.table"); + public static final File NA12891_3_PCT_NA12892_97_PCT = new File(CONTAMINATION_TEST_DATA_DIRECTORY, "NA12891_0.03_NA12892_0.97.table"); + public static final File NA12891_5_PCT_NA12892_95_PCT = new File(CONTAMINATION_TEST_DATA_DIRECTORY, "NA12891_0.05_NA12892_0.95.table"); + public static final File NA12891_8_PCT_NA12892_92_PCT = new File(CONTAMINATION_TEST_DATA_DIRECTORY, "NA12891_0.08_NA12892_0.92.table"); public static final double BASELINE_CONTAMINATION_OF_NA12892 = 0.001; @DataProvider(name = "includeHomAlts") @@ -152,4 +152,21 @@ public void testMatchedNormal() { final double calculatedContamination = ContaminationRecord.readFromFile(contaminationTable).get(0).getContamination(); Assert.assertEquals(calculatedContamination, contamination, 0.01); } + + @Test + public void testSmallGenePanelWithNoHomAlts() { + final File inputPileups = new File(CONTAMINATION_TEST_DATA_DIRECTORY, "small_gene_panel.pileups"); + final File contaminationTable = createTempFile("contamination", ".table"); + + final String[] args = { + "-I", inputPileups.getAbsolutePath(), + "-O", contaminationTable.getAbsolutePath(), + }; + runCommandLine(args); + + final double calculatedContamination = ContaminationRecord.readFromFile(contaminationTable).get(0).getContamination(); + + Assert.assertFalse(Double.isNaN(calculatedContamination)); + Assert.assertTrue(calculatedContamination < 0.2); + } } \ No newline at end of file diff --git a/src/test/resources/org/broadinstitute/hellbender/tools/calculatecontamination/small_gene_panel.pileups b/src/test/resources/org/broadinstitute/hellbender/tools/calculatecontamination/small_gene_panel.pileups new file mode 100644 index 00000000000..c3d553d0c37 --- /dev/null +++ b/src/test/resources/org/broadinstitute/hellbender/tools/calculatecontamination/small_gene_panel.pileups @@ -0,0 +1,1934 @@ +#SAMPLE=NGS170303-13DF +contig position ref_count alt_count other_alt_count allele_frequency +chr1 985826 1 0 0 0.0112655 +chr1 985900 3 0 0 0.0147823 +chr1 985999 1 0 0 0.0140709 +chr1 986010 1 0 0 0.0111126 +chr1 1021408 1 0 0 0.0157902 +chr1 1222267 2 0 0 0.17354 +chr1 1229114 1 0 0 0.0364279 +chr1 1247555 1 0 0 0.0155276 +chr1 1247588 1 0 0 0.0277505 +chr1 1277735 1 0 0 0.0243823 +chr1 1336006 1 0 0 0.035275 +chr1 2518410 1 0 0 0.0214516 +chr1 3311101 1 0 0 0.0609517 +chr1 3679775 0 4 0 0.188212 +chr1 3679783 5 0 0 0.0126403 +chr1 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