LocusDepthtoBAF tool #7776
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| package org.broadinstitute.hellbender.tools.sv; | ||||||
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| import com.google.common.annotations.VisibleForTesting; | ||||||
| import htsjdk.tribble.Feature; | ||||||
| import org.apache.commons.math3.distribution.ChiSquaredDistribution; | ||||||
| import org.broadinstitute.barclay.argparser.Argument; | ||||||
| import org.broadinstitute.barclay.argparser.CommandLineProgramProperties; | ||||||
| import org.broadinstitute.barclay.argparser.ExperimentalFeature; | ||||||
| import org.broadinstitute.hellbender.cmdline.StandardArgumentDefinitions; | ||||||
| import org.broadinstitute.hellbender.cmdline.programgroups.StructuralVariantDiscoveryProgramGroup; | ||||||
| import org.broadinstitute.hellbender.engine.*; | ||||||
| import org.broadinstitute.hellbender.exceptions.UserException; | ||||||
| import org.broadinstitute.hellbender.utils.MathUtils.RunningAverage; | ||||||
| import org.broadinstitute.hellbender.utils.codecs.FeatureOutputCodec; | ||||||
| import org.broadinstitute.hellbender.utils.codecs.FeatureOutputCodecFinder; | ||||||
| import org.broadinstitute.hellbender.utils.codecs.FeatureSink; | ||||||
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| import java.util.ArrayList; | ||||||
| import java.util.Arrays; | ||||||
| import java.util.List; | ||||||
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| /** | ||||||
| * <p>Merges locus-sorted LocusDepth evidence files, and calculates the bi-allelic frequency for each | ||||||
| * sample and site, and writes these values as a BafEvidence output file.</p> | ||||||
|
There was a problem hiding this comment. Add a description of the filtering methodology |
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| * | ||||||
| * <h3>Inputs</h3> | ||||||
| * | ||||||
| * <ul> | ||||||
| * <li> | ||||||
| * One or more LocusDepth evidence files, or a file containing a list of evidence files, one per line. | ||||||
| * </li> | ||||||
| * </ul> | ||||||
| * | ||||||
| * <h3>Output</h3> | ||||||
| * | ||||||
| * <ul> | ||||||
| * <li> | ||||||
| * An output file containing merged BafEvidence from the inputs. | ||||||
| * </li> | ||||||
| * </ul> | ||||||
| * | ||||||
| * <h3>Usage example</h3> | ||||||
| * | ||||||
| * <pre> | ||||||
| * gatk LocusDepthtoBAF \ | ||||||
| * -F file1.ld.txt.gz [-F file2.ld.txt.gz ...] \ | ||||||
| * -O merged.baf.bci | ||||||
| * </pre> | ||||||
| * | ||||||
| * @author Ted Sharpe <[email protected]> | ||||||
| */ | ||||||
| @CommandLineProgramProperties( | ||||||
| summary = "Convert LocusDepth to BafEvidence", | ||||||
| oneLineSummary = "Convert LocusDepth to BafEvidence", | ||||||
| programGroup = StructuralVariantDiscoveryProgramGroup.class | ||||||
| ) | ||||||
| @ExperimentalFeature | ||||||
| public class LocusDepthtoBAF extends MultiFeatureWalker<LocusDepth> { | ||||||
| public static final String LOCUS_DEPTH_FILE_NAME = "locus-depth"; | ||||||
| public static final String SAMPLE_NAMES_NAME = "sample-names"; | ||||||
| public static final String BAF_EVIDENCE_FILE_NAME = "baf-evidence-output"; | ||||||
| public static final String MIN_TOTAL_DEPTH_NAME = "min-total-depth"; | ||||||
| public static final String MAX_STD_NAME = "max-std"; | ||||||
| public static final String MIN_HET_LIKELIHOOD = "min-het-likelihood"; | ||||||
| public static final String COMPRESSION_LEVEL_NAME = "compression-level"; | ||||||
| public static ChiSquaredDistribution chiSqDist = new ChiSquaredDistribution(null, 1.); | ||||||
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| @Argument( | ||||||
| doc = "Locus depth files to process", | ||||||
| fullName = LOCUS_DEPTH_FILE_NAME, | ||||||
| shortName = StandardArgumentDefinitions.FEATURE_SHORT_NAME ) | ||||||
| private List<FeatureInput<LocusDepth>> locusDepthFiles; | ||||||
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| @Argument(fullName = SAMPLE_NAMES_NAME, doc = "Sample names", optional = true) | ||||||
|
There was a problem hiding this comment. Can you elaborate on what this does in the doc? Is it used for subsetting? |
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| private List<String> sampleNames; | ||||||
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| @Argument( | ||||||
| doc = "BAF output file", | ||||||
| fullName = BAF_EVIDENCE_FILE_NAME, | ||||||
| shortName = StandardArgumentDefinitions.OUTPUT_SHORT_NAME ) | ||||||
| private GATKPath bafOutputFile; | ||||||
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| @Argument( | ||||||
| doc = "Maximum standard deviation across bafs at a locus (otherwise locus will be ignored)", | ||||||
| fullName = MAX_STD_NAME, optional = true ) | ||||||
| private double maxStdDev = .2; | ||||||
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| @Argument( | ||||||
| doc = "Minimum total depth at a locus (otherwise locus will be ignored)", | ||||||
| fullName = MIN_TOTAL_DEPTH_NAME, optional = true ) | ||||||
| private int minTotalDepth = 10; | ||||||
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| @Argument( | ||||||
| doc = "Minimum likelihood of site being biallelic and heterozygous", | ||||||
| fullName = MIN_HET_LIKELIHOOD, optional = true ) | ||||||
| private double minHetLikelihood = .5; | ||||||
|
There was a problem hiding this comment. I think this should be a probability instead of likelihood |
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| @Argument( | ||||||
| doc = "Output compression level", | ||||||
| fullName = COMPRESSION_LEVEL_NAME, | ||||||
| minValue = 0, maxValue = 9, optional = true ) | ||||||
| private int compressionLevel = 4; | ||||||
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| private FeatureSink<BafEvidence> writer; | ||||||
| private final List<BafEvidence> sameLocusBuffer = new ArrayList<>(); | ||||||
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| @Override | ||||||
| @SuppressWarnings("unchecked") | ||||||
| public void onTraversalStart() { | ||||||
| super.onTraversalStart(); | ||||||
| final FeatureOutputCodec<? extends Feature, ? extends FeatureSink<? extends Feature>> codec = | ||||||
| FeatureOutputCodecFinder.find(bafOutputFile); | ||||||
| if ( !codec.getFeatureType().isAssignableFrom(BafEvidence.class) ) { | ||||||
| throw new UserException("We're intending to write BafEvidence, but the feature type " + | ||||||
| "associated with the output file expects features of type " + | ||||||
| codec.getFeatureType().getSimpleName()); | ||||||
| } | ||||||
| writer = (FeatureSink<BafEvidence>)codec.makeSink(bafOutputFile, | ||||||
| getBestAvailableSequenceDictionary(), | ||||||
| sampleNames, compressionLevel); | ||||||
| } | ||||||
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| @Override | ||||||
| public void apply( LocusDepth locusDepth, Object header, | ||||||
| ReadsContext readsContext, ReferenceContext referenceContext ) { | ||||||
| final double baf = calcBAF(locusDepth); | ||||||
| if ( baf > 0. ) { | ||||||
| final BafEvidence bafEvidence = | ||||||
| new BafEvidence(locusDepth.getSample(), locusDepth.getContig(), | ||||||
| locusDepth.getStart(), baf); | ||||||
| if ( !sameLocus(bafEvidence) ) { | ||||||
| processBuffer(); | ||||||
| } | ||||||
| sameLocusBuffer.add(bafEvidence); | ||||||
| } | ||||||
| } | ||||||
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| @Override | ||||||
| public Object onTraversalSuccess() { | ||||||
| super.onTraversalSuccess(); | ||||||
| if ( !sameLocusBuffer.isEmpty() ) { | ||||||
| processBuffer(); | ||||||
| } | ||||||
| writer.close(); | ||||||
| return null; | ||||||
| } | ||||||
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| @VisibleForTesting double calcBAF( final LocusDepth locusDepth ) { | ||||||
| final int totalDepth = locusDepth.getTotalDepth(); | ||||||
| if ( totalDepth < minTotalDepth ) { | ||||||
| return 0.; | ||||||
| } | ||||||
| double expectRefAlt = totalDepth / 2.; | ||||||
|
There was a problem hiding this comment.
Suggested change
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| final double refDiff = locusDepth.getRefDepth() - expectRefAlt; | ||||||
| final double altDiff = locusDepth.getAltDepth() - expectRefAlt; | ||||||
| double chiSq = (refDiff * refDiff + altDiff * altDiff) / expectRefAlt; | ||||||
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There was a problem hiding this comment.
Suggested change
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| double fitProb = 1. - chiSqDist.cumulativeProbability(chiSq); | ||||||
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There was a problem hiding this comment. Add comment that this is a Pearson chi-squared test There was a problem hiding this comment.
Suggested change
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| if ( fitProb < minHetLikelihood ) { | ||||||
| return 0.; | ||||||
| } | ||||||
| return (double)locusDepth.getAltDepth() / totalDepth; | ||||||
|
There was a problem hiding this comment.
Suggested change
I can never remember if casts get applied before division |
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| } | ||||||
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| private boolean sameLocus( final BafEvidence bafEvidence ) { | ||||||
| if ( sameLocusBuffer.isEmpty() ) { | ||||||
| return true; | ||||||
| } | ||||||
| final BafEvidence curLocus = sameLocusBuffer.get(0); | ||||||
| return curLocus.getContig().equals(bafEvidence.getContig()) && | ||||||
| curLocus.getStart() == bafEvidence.getStart(); | ||||||
| } | ||||||
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| private void processBuffer() { | ||||||
| int nBafs = sameLocusBuffer.size(); | ||||||
| if ( nBafs == 1 ) { | ||||||
| writer.write(new BafEvidence(sameLocusBuffer.get(0), .5)); | ||||||
| } else { | ||||||
| final RunningAverage ra = new RunningAverage(); | ||||||
| for ( final BafEvidence bafEvidence : sameLocusBuffer ) { | ||||||
| ra.add(bafEvidence.getValue()); | ||||||
| } | ||||||
| final double stddev = ra.stddev(); | ||||||
| if ( stddev <= maxStdDev ) { | ||||||
| final double[] vals = new double[nBafs]; | ||||||
| for ( int idx = 0; idx != nBafs; ++idx ) { | ||||||
| vals[idx] = sameLocusBuffer.get(idx).getValue(); | ||||||
| } | ||||||
| Arrays.sort(vals); | ||||||
| int midIdx = nBafs / 2; | ||||||
| double median = | ||||||
| (nBafs & 1) != 0 ? vals[midIdx] : (vals[midIdx] + vals[midIdx - 1])/2.; | ||||||
| final double adj = .5 - median; | ||||||
| for ( final BafEvidence bafEvidence : sameLocusBuffer ) { | ||||||
| writer.write(new BafEvidence(bafEvidence, bafEvidence.getValue()+adj)); | ||||||
| } | ||||||
| } | ||||||
| } | ||||||
| sameLocusBuffer.clear(); | ||||||
| } | ||||||
| } | ||||||
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Can you please add a quick unit test for this?