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handle overlapping mates in M2 isActive #5078

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Aug 3, 2018
Merged

handle overlapping mates in M2 isActive #5078

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7 changes: 7 additions & 0 deletions src/main/java/org/broadinstitute/hellbender/tools/walkers/mutect/M2ArgumentCollection.java
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Original file line number Diff line number Diff line change
Expand Up @@ -23,6 +23,7 @@ public class M2ArgumentCollection extends AssemblyBasedCallerArgumentCollection
public static final String EMISSION_LOG_SHORT_NAME = "emit-lod";
public static final String INITIAL_TUMOR_LOD_LONG_NAME = "initial-tumor-lod";
public static final String INITIAL_TUMOR_LOD_SHORT_NAME = "init-lod";
public static final String INITIAL_PCR_ERROR_QUAL = "initial-pcr-qual";
public static final String MAX_POPULATION_AF_LONG_NAME = "max-population-af";
public static final String MAX_POPULATION_AF_SHORT_NAME = "max-af";
public static final String DOWNSAMPLING_STRIDE_LONG_NAME = "downsampling-stride";
Expand Down Expand Up @@ -108,6 +109,12 @@ public double getDefaultAlleleFrequency() {
@Argument(fullName = INITIAL_TUMOR_LOD_LONG_NAME, shortName = INITIAL_TUMOR_LOD_SHORT_NAME, optional = true, doc = "LOD threshold to consider pileup active.")
public double initialTumorLod = 2.0;

/**
* PCR error rate for overlapping fragments in isActive()
*/
@Argument(fullName = INITIAL_PCR_ERROR_QUAL, optional = true, doc = "PCR error rate for overlapping fragments in isActive()")
public int initialPCRErrorQual = 40;

/**
* In tumor-only mode, we discard variants with population allele frequencies greater than this threshold.
*/
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12 changes: 8 additions & 4 deletions src/main/java/org/broadinstitute/hellbender/tools/walkers/mutect/Mutect2Engine.java
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Expand Up @@ -259,14 +259,14 @@ public ActivityProfileState isActive(final AlignmentContext context, final Refer

final ReadPileup pileup = context.getBasePileup();
final ReadPileup tumorPileup = pileup.getPileupForSample(tumorSample, header);
final List<Byte> tumorAltQuals = altQuals(tumorPileup, refBase);
final List<Byte> tumorAltQuals = altQuals(tumorPileup, refBase, MTAC.initialPCRErrorQual);
final double tumorLog10Odds = MathUtils.logToLog10(lnLikelihoodRatio(tumorPileup.size()-tumorAltQuals.size(), tumorAltQuals));

if (tumorLog10Odds < MTAC.initialTumorLod) {
return new ActivityProfileState(refInterval, 0.0);
} else if (hasNormal() && !MTAC.genotypeGermlineSites) {
final ReadPileup normalPileup = pileup.getPileupForSample(normalSample, header);
final List<Byte> normalAltQuals = altQuals(normalPileup, refBase);
final List<Byte> normalAltQuals = altQuals(normalPileup, refBase, MTAC.initialPCRErrorQual);
final int normalAltCount = normalAltQuals.size();
final double normalQualSum = normalAltQuals.stream().mapToDouble(Byte::doubleValue).sum();
if (normalAltCount > normalPileup.size() * MAX_ALT_FRACTION_IN_NORMAL && normalQualSum > MAX_NORMAL_QUAL_SUM) {
Expand Down Expand Up @@ -297,8 +297,9 @@ private static byte indelQual(final int indelLength) {
return (byte) Math.min(INDEL_START_QUAL + (indelLength - 1) * INDEL_CONTINUATION_QUAL, Byte.MAX_VALUE);
}

private static List<Byte> altQuals(final ReadPileup pileup, final byte refBase) {
private static List<Byte> altQuals(final ReadPileup pileup, final byte refBase, final int pcrErrorQual) {
final List<Byte> result = new ArrayList<>();
final int position = pileup.getLocation().getStart();

for (final PileupElement pe : pileup) {
final int indelLength = getCurrentOrFollowingIndelLength(pe);
Expand All @@ -307,7 +308,10 @@ private static List<Byte> altQuals(final ReadPileup pileup, final byte refBase)
} else if (isNextToUsefulSoftClip(pe)) {
result.add(indelQual(1));
} else if (pe.getBase() != refBase && pe.getQual() > MINIMUM_BASE_QUALITY) {
result.add(pe.getQual());
final GATKRead read = pe.getRead();
final int mateStart = read.mateIsUnmapped() ? Integer.MAX_VALUE : read.getMateStart();
final boolean overlapsMate = mateStart <= position && position < mateStart + read.getLength();
result.add(overlapsMate ? (byte) FastMath.min(pe.getQual(), pcrErrorQual/2) : pe.getQual());
}
}

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