Outputting missing intervals in DiagnoseTargets
Problem ------ Diagnose Targets identifies holes in the coverage of a targetted experiment, but it only reports them doesn't list the actual missing loci Solution ------ This commit implements an optional intervals file output listing the exact loci that did not pass filters Itemized changes -------------- * Cache callable statuses (to avoid recalculation) * Add functionality to output missing intervals * Implement new tool to qualify the missing intervals (QualifyMissingIntervals) by gc content, size, type of missing coverage and origin (coding sequence, intron, ...)
This commit is contained in:
Mauricio Carneiro
parent
1466396a31
commit
3dbb86b052
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@ -120,7 +120,7 @@ abstract class AbstractStratification {
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*
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* @return the callable status(es) for the whole object
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*/
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public abstract Iterable<CallableStatus> callableStatuses();
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public abstract List<CallableStatus> callableStatuses();
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/**
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@ -65,6 +65,8 @@ import org.broadinstitute.variant.variantcontext.*;
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import org.broadinstitute.variant.variantcontext.writer.VariantContextWriter;
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import org.broadinstitute.variant.vcf.*;
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import java.io.FileWriter;
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import java.io.IOException;
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import java.util.*;
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/**
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@ -122,13 +124,12 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> {
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@ArgumentCollection
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private ThresHolder thresholds = new ThresHolder();
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private Map<GenomeLoc, IntervalStratification> intervalMap = null; // maps each interval => statistics
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private Map<GenomeLoc, IntervalStratification> intervalMap = null; // maps each interval => statistics
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private PeekableIterator<GenomeLoc> intervalListIterator; // an iterator to go over all the intervals provided as we traverse the genome
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private Set<String> samples = null; // all the samples being processed
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private static final Allele SYMBOLIC_ALLELE = Allele.create("<DT>", false); // avoid creating the symbolic allele multiple times
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private static final Allele UNCOVERED_ALLELE = Allele.create("A", true); // avoid creating the 'fake' ref allele for uncovered intervals multiple times
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private static final int INITIAL_HASH_SIZE = 500000;
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private static final int INITIAL_HASH_SIZE = 50; // enough room for potential overlapping intervals plus recently finished intervals
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@Override
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public void initialize() {
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@ -149,7 +150,7 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> {
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}
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@Override
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public Long map(RefMetaDataTracker tracker, ReferenceContext ref, AlignmentContext context) {
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public Long map(final RefMetaDataTracker tracker, final ReferenceContext ref, final AlignmentContext context) {
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GenomeLoc refLocus = ref.getLocus();
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// process and remove any intervals in the map that are don't overlap the current locus anymore
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@ -187,7 +188,7 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> {
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* @param result number of loci processed by the walker
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*/
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@Override
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public void onTraversalDone(Long result) {
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public void onTraversalDone(final Long result) {
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for (GenomeLoc interval : intervalMap.keySet())
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outputStatsToVCF(intervalMap.get(interval), UNCOVERED_ALLELE);
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@ -197,6 +198,14 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> {
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intervalListIterator.next();
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interval = intervalListIterator.peek();
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}
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if (thresholds.missingTargets != null) {
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try {
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thresholds.missingTargets.close();
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} catch (IOException e) {
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e.printStackTrace();
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}
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}
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}
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/**
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@ -210,7 +219,11 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> {
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final List<GenomeLoc> toRemove = new LinkedList<GenomeLoc>();
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for (GenomeLoc key : intervalMap.keySet()) {
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if (key.isBefore(refLocus)) {
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outputStatsToVCF(intervalMap.get(key), Allele.create(refBase, true));
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final IntervalStratification intervalStats = intervalMap.get(key);
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outputStatsToVCF(intervalStats, Allele.create(refBase, true));
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if (hasMissingLoci(intervalStats)) {
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outputMissingInterval(intervalStats);
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}
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toRemove.add(key);
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}
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}
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@ -224,7 +237,7 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> {
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*
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* @param refLocus the current reference locus
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*/
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private void addNewOverlappingIntervals(GenomeLoc refLocus) {
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private void addNewOverlappingIntervals(final GenomeLoc refLocus) {
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GenomeLoc interval = intervalListIterator.peek();
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while (interval != null && !interval.isPast(refLocus)) {
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intervalMap.put(interval, createIntervalStatistic(interval));
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@ -239,10 +252,9 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> {
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* @param stats The statistics of the interval
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* @param refAllele the reference allele
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*/
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private void outputStatsToVCF(IntervalStratification stats, Allele refAllele) {
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private void outputStatsToVCF(final IntervalStratification stats, final Allele refAllele) {
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GenomeLoc interval = stats.getInterval();
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final List<Allele> alleles = new ArrayList<Allele>();
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final Map<String, Object> attributes = new HashMap<String, Object>();
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final ArrayList<Genotype> genotypes = new ArrayList<Genotype>();
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@ -274,6 +286,55 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> {
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vcfWriter.add(vcb.make());
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}
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private boolean hasMissingStatuses(AbstractStratification stats) {
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return !stats.callableStatuses().isEmpty();
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}
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private boolean hasMissingLoci(final IntervalStratification stats) {
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return thresholds.missingTargets != null && hasMissingStatuses(stats);
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}
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private void outputMissingInterval(final IntervalStratification stats) {
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final GenomeLoc interval = stats.getInterval();
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final boolean missing[] = new boolean[interval.size()];
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Arrays.fill(missing, true);
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for (AbstractStratification sample : stats.getElements()) {
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if (hasMissingStatuses(sample)) {
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int pos = 0;
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for (AbstractStratification locus : sample.getElements()) {
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if (locus.callableStatuses().isEmpty()) {
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missing[pos] = false;
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}
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pos++;
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}
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}
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}
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int start = -1;
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boolean insideMissing = false;
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for (int i = 0; i < missing.length; i++) {
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if (missing[i] && !insideMissing) {
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start = interval.getStart() + i;
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insideMissing = true;
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} else if (!missing[i] && insideMissing) {
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final int stop = interval.getStart() + i - 1;
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outputMissingInterval(interval.getContig(), start, stop);
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insideMissing = false;
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}
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}
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if (insideMissing) {
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outputMissingInterval(interval.getContig(), start, interval.getStop());
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}
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}
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private void outputMissingInterval(final String contig, final int start, final int stop){
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final FileWriter out = thresholds.missingTargets;
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try {
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out.write(String.format("%s:%d-%d\n", contig, start, stop));
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} catch (IOException e) {
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e.printStackTrace();
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}
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}
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/**
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* Function that process a set of statuses into strings
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*
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@ -56,6 +56,7 @@ import java.util.*;
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final class IntervalStratification extends AbstractStratification {
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private final Map<String, AbstractStratification> samples;
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private final GenomeLoc interval;
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private List<CallableStatus> callableStatuses;
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public IntervalStratification(Set<String> samples, GenomeLoc interval, ThresHolder thresholds) {
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super(thresholds);
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@ -113,7 +114,13 @@ final class IntervalStratification extends AbstractStratification {
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* {@inheritDoc}
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*/
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@Override
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public Iterable<CallableStatus> callableStatuses() {
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public List<CallableStatus> callableStatuses() {
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if (callableStatuses == null)
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callableStatuses = calculateStatus();
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return callableStatuses;
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}
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private List<CallableStatus> calculateStatus() {
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final List<CallableStatus> output = new LinkedList<CallableStatus>();
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// check if any of the votes pass the threshold
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@ -117,7 +117,7 @@ final class SampleStratification extends AbstractStratification {
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* {@inheritDoc}
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*/
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@Override
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public Iterable<CallableStatus> callableStatuses() {
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public List<CallableStatus> callableStatuses() {
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final List<CallableStatus> output = new LinkedList<CallableStatus>();
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// get the sample statuses of all the Loci Metrics
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@ -47,7 +47,9 @@
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package org.broadinstitute.sting.gatk.walkers.diagnostics.diagnosetargets;
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import org.broadinstitute.sting.commandline.Argument;
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import org.broadinstitute.sting.commandline.Output;
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import java.io.FileWriter;
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import java.util.LinkedList;
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import java.util.List;
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@ -114,6 +116,9 @@ final class ThresHolder {
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@Argument(fullName = "quality_status_threshold", shortName = "stQ", doc = "The proportion of the loci needed for calling POOR_QUALITY", required = false)
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public double qualityStatusThreshold = 0.50;
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@Output(fullName = "missing_intervals", shortName = "missing", doc ="Produces a file with the intervals that don't pass filters", required = false)
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public FileWriter missingTargets = null;
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public final List<Metric> locusMetricList = new LinkedList<Metric>();
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public final List<Metric> sampleMetricList = new LinkedList<Metric>();
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public final List<Metric> intervalMetricList = new LinkedList<Metric>();
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