Optimizing DiagnoseTargets
* Fixed output format to get a valid vcf * Optimzed the per sample pileup routine O(n^2) => O(n) pileup for samples * Added support to overlapping intervals * Removed expand target functionality (for now) * Removed total depth (pointless metric)
This commit is contained in:
Mauricio Carneiro
parent
1df0adf862
commit
cd842b650e
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@ -24,6 +24,7 @@
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package org.broadinstitute.sting.gatk.walkers.diagnostics.targets;
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import net.sf.picard.util.PeekableIterator;
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import org.broad.tribble.Feature;
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import org.broadinstitute.sting.commandline.*;
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import org.broadinstitute.sting.gatk.contexts.AlignmentContext;
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@ -32,8 +33,6 @@ import org.broadinstitute.sting.gatk.refdata.RefMetaDataTracker;
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import org.broadinstitute.sting.gatk.walkers.*;
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import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.AnnotatorCompatibleWalker;
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import org.broadinstitute.sting.utils.GenomeLoc;
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import org.broadinstitute.sting.utils.GenomeLocComparator;
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import org.broadinstitute.sting.utils.GenomeLocParser;
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import org.broadinstitute.sting.utils.SampleUtils;
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import org.broadinstitute.sting.utils.codecs.vcf.*;
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import org.broadinstitute.sting.utils.exceptions.UserException;
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@ -79,10 +78,7 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> implements Annotato
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private IntervalBinding<Feature> intervalTrack = null;
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@Output(doc = "File to which variants should be written", required = true)
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protected VCFWriter vcfWriter = null;
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@Argument(fullName = "expand_interval", shortName = "exp", doc = "", required = false)
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private int expandInterval = 50;
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private VCFWriter vcfWriter = null;
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@Argument(fullName = "minimum_base_quality", shortName = "mbq", doc = "", required = false)
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private int minimumBaseQuality = 20;
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@ -96,13 +92,11 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> implements Annotato
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@Argument(fullName = "maximum_coverage", shortName = "maxcov", doc = "", required = false)
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private int maximumCoverage = 700;
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private TreeSet<GenomeLoc> intervalList = null; // The list of intervals of interest (plus expanded intervals if user wants them)
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private HashMap<GenomeLoc, IntervalStatistics> intervalMap = null; // interval => statistics
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private Iterator<GenomeLoc> intervalListIterator; // An iterator to go over all the intervals provided as we traverse the genome
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private GenomeLoc currentInterval = null; // The "current" interval loaded
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private IntervalStatistics currentIntervalStatistics = null; // The "current" interval being filled with statistics
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private Set<String> samples = null; // All the samples being processed
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private GenomeLocParser parser; // just an object to allow us to create genome locs (for the expanded intervals)
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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 final Allele SYMBOLIC_ALLELE = Allele.create("<DT>", false); // avoid creating the symbolic allele multiple times
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@Override
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public void initialize() {
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@ -111,72 +105,22 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> implements Annotato
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if (intervalTrack == null)
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throw new UserException("This tool currently only works if you provide an interval track");
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parser = new GenomeLocParser(getToolkit().getMasterSequenceDictionary()); // Important to initialize the parser before creating the intervals below
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List<GenomeLoc> originalList = intervalTrack.getIntervals(getToolkit()); // The original list of targets provided by the user that will be expanded or not depending on the options provided
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intervalList = new TreeSet<GenomeLoc>(new GenomeLocComparator());
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intervalMap = new HashMap<GenomeLoc, IntervalStatistics>();
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for (GenomeLoc interval : originalList)
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intervalList.add(interval);
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//addAndExpandIntervalToMap(interval);
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intervalListIterator = new PeekableIterator<GenomeLoc>(intervalTrack.getIntervals(getToolkit()).listIterator());
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intervalListIterator = intervalList.iterator();
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// get all of the unique sample names
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samples = SampleUtils.getSAMFileSamples(getToolkit().getSAMFileHeader());
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// initialize the header
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Set<VCFHeaderLine> headerInfo = getHeaderInfo();
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vcfWriter.writeHeader(new VCFHeader(headerInfo, samples));
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}
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/**
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* Gets the header lines for the VCF writer
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*
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* @return A set of VCF header lines
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*/
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private Set<VCFHeaderLine> getHeaderInfo() {
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Set<VCFHeaderLine> headerLines = new HashSet<VCFHeaderLine>();
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// INFO fields for overall data
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headerLines.add(new VCFInfoHeaderLine("END", 1, VCFHeaderLineType.Integer, "Stop position of the interval"));
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headerLines.add(new VCFInfoHeaderLine("DP", 1, VCFHeaderLineType.Integer, "Total depth in the site. Sum of the depth of all pools"));
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headerLines.add(new VCFInfoHeaderLine("AD", 1, VCFHeaderLineType.Float, "Average depth across the interval. Sum of the depth in a lci divided by interval size."));
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headerLines.add(new VCFInfoHeaderLine("Diagnose Targets", 0, VCFHeaderLineType.Flag, "DiagnoseTargets mode"));
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// FORMAT fields for each genotype
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headerLines.add(new VCFFormatHeaderLine("DP", 1, VCFHeaderLineType.Integer, "Total depth in the site. Sum of the depth of all pools"));
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headerLines.add(new VCFFormatHeaderLine("AD", 1, VCFHeaderLineType.Float, "Average depth across the interval. Sum of the depth in a lci divided by interval size."));
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// FILTER fields
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for (CallableStatus stat : CallableStatus.values()) {
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headerLines.add(new VCFHeaderLine(stat.name(), stat.description));
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}
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return headerLines;
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samples = SampleUtils.getSAMFileSamples(getToolkit().getSAMFileHeader()); // get all of the unique sample names for the VCF Header
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vcfWriter.writeHeader(new VCFHeader(getHeaderInfo(), samples)); // initialize the VCF header
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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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GenomeLoc refLocus = ref.getLocus();
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while (currentInterval == null || currentInterval.isBefore(refLocus)) { // do this for first time and while currentInterval is behind current locus
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if (!intervalListIterator.hasNext())
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return 0L;
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if (currentInterval != null)
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processIntervalStats(currentInterval, Allele.create(ref.getBase(), true));
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removePastIntervals(refLocus, ref.getBase()); // process and remove any intervals in the map that are don't overlap the current locus anymore
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addNewOverlappingIntervals(refLocus); // add all new intervals that may overlap this reference locus
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currentInterval = intervalListIterator.next();
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addAndExpandIntervalToMap(currentInterval);
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currentIntervalStatistics = intervalMap.get(currentInterval);
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}
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if (currentInterval.isPast(refLocus)) // skip if we are behind the current interval
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return 0L;
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currentIntervalStatistics.addLocus(context); // Add current locus to stats
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for (IntervalStatistics intervalStatistics : intervalMap.values())
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intervalStatistics.addLocus(context); // Add current locus to stats
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return 1L;
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}
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@ -198,10 +142,15 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> implements Annotato
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return sum + value;
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}
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/**
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* Process all remaining intervals
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*
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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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for (GenomeLoc interval : intervalMap.keySet())
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processIntervalStats(interval, Allele.create("<DT>", true));
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for (GenomeLoc interval : intervalMap.keySet())
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processIntervalStats(intervalMap.get(interval), Allele.create("A"));
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}
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@Override
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@ -219,82 +168,111 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> implements Annotato
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@Override
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public boolean alwaysAppendDbsnpId() {return false;}
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private GenomeLoc createIntervalBefore(GenomeLoc interval) {
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int start = Math.max(interval.getStart() - expandInterval, 0);
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int stop = Math.max(interval.getStart() - 1, 0);
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return parser.createGenomeLoc(interval.getContig(), interval.getContigIndex(), start, stop);
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}
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/**
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* Removes all intervals that are behind the current reference locus from the intervalMap
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*
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* @param refLocus the current reference locus
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* @param refBase the reference allele
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*/
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private void removePastIntervals(GenomeLoc refLocus, byte refBase) {
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List<GenomeLoc> toRemove = new LinkedList<GenomeLoc>();
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for (GenomeLoc interval : intervalMap.keySet())
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if (interval.isBefore(refLocus)) {
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processIntervalStats(intervalMap.get(interval), Allele.create(refBase, true));
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toRemove.add(interval);
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}
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private GenomeLoc createIntervalAfter(GenomeLoc interval) {
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int contigLimit = getToolkit().getSAMFileHeader().getSequenceDictionary().getSequence(interval.getContigIndex()).getSequenceLength();
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int start = Math.min(interval.getStop() + 1, contigLimit);
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int stop = Math.min(interval.getStop() + expandInterval, contigLimit);
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return parser.createGenomeLoc(interval.getContig(), interval.getContigIndex(), start, stop);
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for (GenomeLoc interval : toRemove)
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intervalMap.remove(interval);
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GenomeLoc interval = intervalListIterator.peek(); // clean up all intervals that we might have skipped because there was no data
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while(interval != null && interval.isBefore(refLocus)) {
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interval = intervalListIterator.next();
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processIntervalStats(createIntervalStatistic(interval), Allele.create(refBase, true));
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interval = intervalListIterator.peek();
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}
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}
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/**
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* Takes an interval and commits it to memory.
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* It will expand it if so told by the -exp command line argument
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* Adds all intervals that overlap the current reference locus to the intervalMap
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*
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* @param interval The new interval to process
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* @param refLocus the current reference locus
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*/
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private void addAndExpandIntervalToMap(GenomeLoc interval) {
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if (expandInterval > 0) {
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GenomeLoc before = createIntervalBefore(interval);
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GenomeLoc after = createIntervalAfter(interval);
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intervalList.add(before);
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intervalList.add(after);
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intervalMap.put(before, new IntervalStatistics(samples, before, minimumCoverage, maximumCoverage, minimumMappingQuality, minimumBaseQuality));
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intervalMap.put(after, new IntervalStatistics(samples, after, minimumCoverage, maximumCoverage, minimumMappingQuality, minimumBaseQuality));
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private void addNewOverlappingIntervals(GenomeLoc refLocus) {
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GenomeLoc interval = intervalListIterator.peek();
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while (interval != null && !interval.isPast(refLocus)) {
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System.out.println("LOCUS : " + refLocus + " -- " + interval);
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intervalMap.put(interval, createIntervalStatistic(interval));
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intervalListIterator.next(); // discard the interval (we've already added it to the map)
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interval = intervalListIterator.peek();
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}
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if (!intervalList.contains(interval))
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intervalList.add(interval);
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intervalMap.put(interval, new IntervalStatistics(samples, interval, minimumCoverage, maximumCoverage, minimumMappingQuality, minimumBaseQuality));
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}
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/**
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* Takes the interval, finds it in the stash, prints it to the VCF, and removes it
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*
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* @param interval The interval in memory that you want to write out and clear
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* @param allele the allele
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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 processIntervalStats(GenomeLoc interval, Allele allele) {
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IntervalStatistics stats = intervalMap.get(interval);
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private void processIntervalStats(IntervalStatistics stats, Allele refAllele) {
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GenomeLoc interval = stats.getInterval();
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List<Allele> alleles = new ArrayList<Allele>();
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Map<String, Object> attributes = new HashMap<String, Object>();
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ArrayList<Genotype> genotypes = new ArrayList<Genotype>();
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alleles.add(allele);
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VariantContextBuilder vcb = new VariantContextBuilder("DiagnoseTargets", interval.getContig(), interval.getStart(), interval.getStop(), alleles);
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alleles.add(refAllele);
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alleles.add(SYMBOLIC_ALLELE);
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VariantContextBuilder vcb = new VariantContextBuilder("DiagnoseTargets", interval.getContig(), interval.getStart(), interval.getStart(), alleles);
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vcb = vcb.log10PError(VariantContext.NO_LOG10_PERROR); // QUAL field makes no sense in our VCF
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vcb.filters(statusesToStrings(stats.callableStatuses()));
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attributes.put(VCFConstants.END_KEY, interval.getStop());
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attributes.put(VCFConstants.DEPTH_KEY, stats.totalCoverage());
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attributes.put("AV", stats.averageCoverage());
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attributes.put(VCFConstants.DEPTH_KEY, stats.averageCoverage());
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vcb = vcb.attributes(attributes);
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for (String sample : samples) {
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Map<String, Object> infos = new HashMap<String, Object>();
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infos.put("DP", stats.getSample(sample).totalCoverage());
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infos.put("AV", stats.getSample(sample).averageCoverage());
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infos.put(VCFConstants.DEPTH_KEY, stats.getSample(sample).averageCoverage());
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Set<String> filters = new HashSet<String>();
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filters.addAll(statusesToStrings(stats.getSample(sample).getCallableStatuses()));
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genotypes.add(new Genotype(sample, alleles, VariantContext.NO_LOG10_PERROR, filters, infos, false));
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genotypes.add(new Genotype(sample, null, VariantContext.NO_LOG10_PERROR, filters, infos, false));
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}
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vcb = vcb.genotypes(genotypes);
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vcfWriter.add(vcb.make());
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intervalMap.remove(interval);
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}
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/**
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* Gets the header lines for the VCF writer
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*
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* @return A set of VCF header lines
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*/
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private static Set<VCFHeaderLine> getHeaderInfo() {
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Set<VCFHeaderLine> headerLines = new HashSet<VCFHeaderLine>();
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// INFO fields for overall data
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headerLines.add(new VCFInfoHeaderLine(VCFConstants.END_KEY, 1, VCFHeaderLineType.Integer, "Stop position of the interval"));
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headerLines.add(new VCFInfoHeaderLine(VCFConstants.DEPTH_KEY, 1, VCFHeaderLineType.Float, "Average depth across the interval. Sum of the depth in a lci divided by interval size."));
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headerLines.add(new VCFInfoHeaderLine("Diagnose Targets", 0, VCFHeaderLineType.Flag, "DiagnoseTargets mode"));
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// FORMAT fields for each genotype
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headerLines.add(new VCFFormatHeaderLine(VCFConstants.DEPTH_KEY, 1, VCFHeaderLineType.Float, "Average depth across the interval. Sum of the depth in a lci divided by interval size."));
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// FILTER fields
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for (CallableStatus stat : CallableStatus.values())
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headerLines.add(new VCFHeaderLine(stat.name(), stat.description));
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return headerLines;
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}
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private static Set<String> statusesToStrings(Set<CallableStatus> statuses) {
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Set<String> output = new HashSet<String>(statuses.size());
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@ -303,4 +281,8 @@ public class DiagnoseTargets extends LocusWalker<Long, Long> implements Annotato
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return output;
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}
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private IntervalStatistics createIntervalStatistic(GenomeLoc interval) {
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return new IntervalStatistics(samples, interval, minimumCoverage, maximumCoverage, minimumMappingQuality, minimumBaseQuality);
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}
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}
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@ -26,6 +26,7 @@ package org.broadinstitute.sting.gatk.walkers.diagnostics.targets;
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import org.broadinstitute.sting.gatk.contexts.AlignmentContext;
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import org.broadinstitute.sting.utils.GenomeLoc;
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import org.broadinstitute.sting.utils.exceptions.ReviewedStingException;
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import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
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import java.util.HashMap;
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@ -52,18 +53,28 @@ public class IntervalStatistics {
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return samples.get(sample);
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}
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public GenomeLoc getInterval() {
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return interval;
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}
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public void addLocus(AlignmentContext context) {
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ReadBackedPileup pileup = context.getBasePileup();
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for (String sample : samples.keySet())
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getSample(sample).addLocus(context.getLocation(), pileup.getPileupForSample(sample));
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Map<String, ReadBackedPileup> samplePileups = pileup.getPileupsForSamples(samples.keySet());
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for (Map.Entry<String, ReadBackedPileup> entry : samplePileups.entrySet()) {
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String sample = entry.getKey();
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ReadBackedPileup samplePileup = entry.getValue();
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SampleStatistics sampleStatistics = samples.get(sample);
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if (sampleStatistics == null)
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throw new ReviewedStingException(String.format("Trying to add locus statistics to a sample (%s) that doesn't exist in the Interval.", sample));
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sampleStatistics.addLocus(context.getLocation(), samplePileup);
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}
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}
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public long totalCoverage() {
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if (preComputedTotalCoverage < 0)
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calculateTotalCoverage();
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return preComputedTotalCoverage;
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}
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public double averageCoverage() {
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if (preComputedTotalCoverage < 0)
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@ -677,11 +677,11 @@ public abstract class AbstractReadBackedPileup<RBP extends AbstractReadBackedPil
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PileupElementTracker<PE> filteredElements = tracker.getElements(sampleNames);
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return filteredElements != null ? (RBP) createNewPileup(loc, filteredElements) : null;
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} else {
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HashSet<String> hashSampleNames = new HashSet<String>(sampleNames); // to speed up the "contains" access in the for loop
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HashSet<String> hashSampleNames = new HashSet<String>(sampleNames); // to speed up the "contains" access in the for loop
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UnifiedPileupElementTracker<PE> filteredTracker = new UnifiedPileupElementTracker<PE>();
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for (PE p : pileupElementTracker) {
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GATKSAMRecord read = p.getRead();
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if (sampleNames != null) { // still checking on sampleNames because hashSampleNames will never be null. And empty means something else.
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if (sampleNames != null) { // still checking on sampleNames because hashSampleNames will never be null. And empty means something else.
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if (read.getReadGroup() != null && hashSampleNames.contains(read.getReadGroup().getSample()))
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filteredTracker.add(p);
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} else {
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@ -693,6 +693,38 @@ public abstract class AbstractReadBackedPileup<RBP extends AbstractReadBackedPil
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}
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}
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@Override
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public Map<String, ReadBackedPileup> getPileupsForSamples(Collection<String> sampleNames) {
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Map<String, ReadBackedPileup> result = new HashMap<String, ReadBackedPileup>();
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if (pileupElementTracker instanceof PerSamplePileupElementTracker) {
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PerSamplePileupElementTracker<PE> tracker = (PerSamplePileupElementTracker<PE>) pileupElementTracker;
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for (String sample : sampleNames) {
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PileupElementTracker<PE> filteredElements = tracker.getElements(sampleNames);
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if (filteredElements != null)
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result.put(sample, createNewPileup(loc, filteredElements));
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}
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} else {
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Map<String, UnifiedPileupElementTracker<PE>> trackerMap = new HashMap<String, UnifiedPileupElementTracker<PE>>();
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for (String sample : sampleNames) { // initialize pileups for each sample
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UnifiedPileupElementTracker<PE> filteredTracker = new UnifiedPileupElementTracker<PE>();
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trackerMap.put(sample, filteredTracker);
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}
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for (PE p : pileupElementTracker) { // go through all pileup elements only once and add them to the respective sample's pileup
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GATKSAMRecord read = p.getRead();
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if (read.getReadGroup() != null) {
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String sample = read.getReadGroup().getSample();
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UnifiedPileupElementTracker<PE> tracker = trackerMap.get(sample);
|
||||
if (tracker != null) // we only add the pileup the requested samples. Completely ignore the rest
|
||||
tracker.add(p);
|
||||
}
|
||||
}
|
||||
for (Map.Entry<String, UnifiedPileupElementTracker<PE>> entry : trackerMap.entrySet()) // create the RBP for each sample
|
||||
result.put(entry.getKey(), createNewPileup(loc, entry.getValue()));
|
||||
}
|
||||
return result;
|
||||
}
|
||||
|
||||
|
||||
@Override
|
||||
public RBP getPileupForSample(String sampleName) {
|
||||
|
|
|
|||
|
|
@ -32,6 +32,7 @@ import org.broadinstitute.sting.utils.sam.GATKSAMRecord;
|
|||
import java.util.Collection;
|
||||
import java.util.HashSet;
|
||||
import java.util.List;
|
||||
import java.util.Map;
|
||||
|
||||
/**
|
||||
* A data retrieval interface for accessing parts of the pileup.
|
||||
|
|
@ -159,6 +160,16 @@ public interface ReadBackedPileup extends Iterable<PileupElement>, HasGenomeLoca
|
|||
*/
|
||||
public ReadBackedPileup getPileupForSamples(Collection<String> sampleNames);
|
||||
|
||||
/**
|
||||
* Gets the particular subset of this pileup for each given sample name.
|
||||
*
|
||||
* Same as calling getPileupForSample for all samples, but in O(n) instead of O(n^2).
|
||||
*
|
||||
* @param sampleNames Name of the sample to use.
|
||||
* @return A subset of this pileup containing only reads with the given sample.
|
||||
*/
|
||||
public Map<String, ReadBackedPileup> getPileupsForSamples(Collection<String> sampleNames);
|
||||
|
||||
|
||||
/**
|
||||
* Gets the particular subset of this pileup with the given sample name.
|
||||
|
|
|
|||
Loading…
Reference in New Issue