refactored into new package
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@1158 348d0f76-0448-11de-a6fe-93d51630548a
This commit is contained in:
kcibul
parent
1c83b4d949
commit
6a25f0b9c5
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@ -0,0 +1,184 @@
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package org.broadinstitute.sting.playground.gatk.walkers.cancer;
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import net.sf.samtools.SAMRecord;
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import java.util.List;
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import java.util.ArrayList;
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import org.broadinstitute.sting.playground.utils.GenotypeLikelihoods;
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/**
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* Created by IntelliJ IDEA.
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* User: kcibul
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* Date: Jun 27, 2009
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* Time: 3:41:59 PM
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* To change this template use File | Settings | File Templates.
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*/
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public class LocusReadPile {
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public List<SAMRecord> reads = new ArrayList<SAMRecord>();
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public List<Integer> offsets = new ArrayList<Integer>();
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public char refBase;
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public int minQualityScore;
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public GenotypeLikelihoods likelihoods = new GenotypeLikelihoods();
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public QualitySums qualitySums = new QualitySums();
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public LocusReadPile(char refBase) {
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this(refBase, 0);
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}
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public LocusReadPile(char refBase, int minQualityScore) {
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this.refBase = refBase;
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this.minQualityScore = minQualityScore;
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}
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public void add(SAMRecord read, int offset) {
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char base = read.getReadString().charAt(offset);
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byte qual = read.getBaseQualities()[offset];
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if (base == 'N' || base == 'n') { return; }
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reads.add(read);
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offsets.add(offset);
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likelihoods.add(refBase, base, qual);
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if (qual > this.minQualityScore) qualitySums.incrementSum(base, qual);
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}
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public String getLocusBases() {
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return getLocusBases(0);
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}
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public String getLocusBases(int locusOffset) {
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StringBuilder sb = new StringBuilder();
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for(int i=0; i<reads.size(); i++) {
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SAMRecord read = reads.get(i);
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int readOffset = offsets.get(i);
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int offset = readOffset + locusOffset;
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if (offset >= 0 && offset < read.getReadString().length()) {
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char base = read.getReadString().charAt(offset);
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sb.append(base);
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}
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}
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return sb.toString();
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}
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public double getAltVsRef(char altAllele) {
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double[] tumorRefAlt = extractRefAlt(this.likelihoods, this.refBase, altAllele);
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double tumorLod = Math.log10(tumorRefAlt[1] + tumorRefAlt[2]) - tumorRefAlt[0];
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return tumorLod;
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}
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public double getRefVsAlt(char altAllele) {
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double[] refAlt = extractRefAlt(this.likelihoods, this.refBase, altAllele);
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double normalLod = refAlt[0] - Math.log10(refAlt[1] + refAlt[2]);
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return normalLod;
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}
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/**
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* Extract the LOD comparing ref:ref to ref:alt and alt:alt
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*/
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private double[] extractRefAlt(GenotypeLikelihoods gl, char ref, char altAllele) {
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double refRef = 0;
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double altRef = 0;
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double altAlt = 0;
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for(int j=0; j<10; j++) {
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String gt = gl.genotypes[j];
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double likelihood = gl.likelihoods[j];
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// the ref:mutant theory
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if ( (gt.charAt(0) == ref && gt.charAt(1) == altAllele) ||
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(gt.charAt(0) == altAllele && gt.charAt(1) == ref) ) {
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altRef += Math.pow(10, likelihood);
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}
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if ( gt.charAt(0) == altAllele && gt.charAt(1) == altAllele) {
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altAlt += Math.pow(10, likelihood);
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}
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if ( gt.charAt(0) == ref && gt.charAt(1) == ref) {
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refRef = likelihood;
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}
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}
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return new double[]{refRef, altRef, altAlt};
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}
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private GenotypeLikelihoods getLikelihood(int locusOffset) {
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GenotypeLikelihoods likelihoods = new GenotypeLikelihoods();
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for(int i=0; i<reads.size(); i++) {
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SAMRecord read = reads.get(i);
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int readOffset = offsets.get(i);
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int offset = readOffset + locusOffset;
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if (offset >= 0 && offset < read.getReadString().length()) {
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char base = read.getReadString().charAt(offset);
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byte qual = read.getBaseQualities()[offset];
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likelihoods.add(refBase, base, qual);
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}
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}
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return likelihoods;
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}
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public double[] getNormalizedProbs(int locusOffset, int qThreshold) {
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GenotypeLikelihoods likelihoods = new GenotypeLikelihoods();
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// FIXME: gaddy suggested this "correction" which evidently has a name...
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//likelihoods.add(refBase, refBase, (byte) 20);
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for(int i=0; i<reads.size(); i++) {
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SAMRecord read = reads.get(i);
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int readOffset = offsets.get(i);
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int offset = readOffset + locusOffset;
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if (offset >= 0 && offset < read.getReadString().length()) {
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char base = read.getReadString().charAt(offset);
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byte qual = read.getBaseQualities()[offset];
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if (qual >= qThreshold) {
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likelihoods.add(refBase, base, qual);
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// if (locusOffset == -43) System.out.println("\tUSING " + base + " " + qual);
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} else {
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// if (locusOffset == -43) System.out.println("\tDropping " + base + " " + qual);
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}
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}
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}
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double[] logLikelihood = likelihoods.likelihoods;
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double[] nonLogLikelihood = new double[10];
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double sum = 0;
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for(int i=0; i<10; i++) {
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nonLogLikelihood[i] = Math.pow(10, logLikelihood[i]);
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sum += nonLogLikelihood[i];
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}
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double[] normalizedProbs = new double[10];
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for(int i=0; i<10; i++) {
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normalizedProbs[i] = nonLogLikelihood[i] / sum;
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}
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//quick sanity check
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// sum=0;
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// for(int i=0; i<10; i++) {
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// sum += normalizedProbs[i];
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// }
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// System.out.println("normalized probs = " + sum);
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return normalizedProbs;
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}
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}
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@ -0,0 +1,58 @@
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package org.broadinstitute.sting.playground.gatk.walkers.cancer;
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/**
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* Created by IntelliJ IDEA.
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* User: kcibul
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* Date: Jun 27, 2009
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* Time: 3:43:29 PM
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* To change this template use File | Settings | File Templates.
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*/
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public class QualitySums {
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private int a = 0;
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private int c = 0;
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private int g = 0;
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private int t = 0;
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private int aCounts = 0;
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private int cCounts = 0;
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private int gCounts = 0;
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private int tCounts = 0;
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public int getQualitySum(final char base) {
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if (base == 'a' || base == 'A') { return a; }
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if (base == 'c' || base == 'C') { return c; }
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if (base == 'g' || base == 'G') { return g; }
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if (base == 't' || base == 'T') { return t; }
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throw new RuntimeException("Unknown base: " + base);
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}
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public int getCounts(final char base) {
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if (base == 'a' || base == 'A') { return aCounts; }
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if (base == 'c' || base == 'C') { return cCounts; }
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if (base == 'g' || base == 'G') { return gCounts; }
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if (base == 't' || base == 'T') { return tCounts; }
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throw new RuntimeException("Unknown base: " + base);
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}
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public void incrementSum(final char base, final byte qual) {
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if (base == 'a' || base == 'A') { a += qual; aCounts++;}
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else if (base == 'c' || base == 'C') { c += qual; cCounts++;}
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else if (base == 'g' || base == 'G') { g += qual; gCounts++; }
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else if (base == 't' || base == 'T') { t += qual; tCounts++; }
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else throw new RuntimeException("Unknown base: " + base);
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}
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public int getOtherQualities(final char base) {
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int total = a + c + g + t;
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if (base == 'a' || base == 'A') { return total-a; }
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else if (base == 'c' || base == 'C') { return total-c; }
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else if (base == 'g' || base == 'G') { return total-g; }
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else if (base == 't' || base == 'T') { return total-t; }
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else throw new RuntimeException("Unknown base: " + base);
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}
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public void reset() {
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a = 0; c = 0; g = 0; t = 0;
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aCounts = 0; cCounts = 0; gCounts = 0; tCounts = 0;
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}
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}
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@ -1,4 +1,4 @@
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package org.broadinstitute.sting.playground.gatk.walkers;
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package org.broadinstitute.sting.playground.gatk.walkers.cancer;
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import org.broadinstitute.sting.gatk.LocusContext;
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import org.broadinstitute.sting.gatk.refdata.ReferenceOrderedDatum;
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@ -1,4 +1,4 @@
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package org.broadinstitute.sting.playground.gatk.walkers;
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package org.broadinstitute.sting.playground.gatk.walkers.cancer;
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import net.sf.picard.reference.ReferenceSequence;
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import net.sf.samtools.Cigar;
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@ -27,42 +27,6 @@ public class SomaticMutationWalker extends LocusWalker<Integer, Integer> {
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StrandImbalance,
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Misalignment
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}
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protected static class QualitySums {
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private int a = 0;
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private int c = 0;
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private int g = 0;
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private int t = 0;
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public int get(final char base) {
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if (base == 'a' || base == 'A') { return a; }
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if (base == 'c' || base == 'C') { return c; }
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if (base == 'g' || base == 'G') { return g; }
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if (base == 't' || base == 'T') { return t; }
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throw new RuntimeException("Unknown base: " + base);
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}
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public void incrementSum(final char base, final byte qual) {
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if (base == 'a' || base == 'A') { a += qual; }
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else if (base == 'c' || base == 'C') { c += qual; }
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else if (base == 'g' || base == 'G') { g += qual; }
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else if (base == 't' || base == 'T') { t += qual; }
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else throw new RuntimeException("Unknown base: " + base);
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}
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public int getOtherQualities(final char base) {
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int total = a + c + g + t;
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if (base == 'a' || base == 'A') { return total-a; }
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else if (base == 'c' || base == 'C') { return total-c; }
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else if (base == 'g' || base == 'G') { return total-g; }
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else if (base == 't' || base == 'T') { return total-t; }
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else throw new RuntimeException("Unknown base: " + base);
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}
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public void reset() {
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a = 0; c = 0; g = 0; t = 0;
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}
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}
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@Argument(fullName = "tumor_sample_name", shortName = "s1", required = true, doc="Name of the tumor sample")
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public String tumorSampleName;
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@ -103,168 +67,6 @@ public class SomaticMutationWalker extends LocusWalker<Integer, Integer> {
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public static int MIN_QSCORE = 13;
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private static class LocusReadPile {
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private char refBase;
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public List<SAMRecord> reads = new ArrayList<SAMRecord>();
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public List<Integer> offsets = new ArrayList<Integer>();
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public GenotypeLikelihoods likelihoods = new GenotypeLikelihoods();
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public QualitySums qualitySums = new QualitySums();
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public LocusReadPile(char refBase) {
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this.refBase = refBase;
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}
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public void add(SAMRecord read, int offset) {
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char base = read.getReadString().charAt(offset);
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byte qual = read.getBaseQualities()[offset];
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if (base == 'N' || base == 'n') { return; }
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reads.add(read);
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offsets.add(offset);
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likelihoods.add(refBase, base, qual);
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if (qual > MIN_QSCORE) qualitySums.incrementSum(base, qual);
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}
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public String getLocusBases() {
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return getLocusBases(0);
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}
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public String getLocusBases(int locusOffset) {
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StringBuilder sb = new StringBuilder();
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for(int i=0; i<reads.size(); i++) {
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SAMRecord read = reads.get(i);
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int readOffset = offsets.get(i);
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int offset = readOffset + locusOffset;
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if (offset >= 0 && offset < read.getReadString().length()) {
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char base = read.getReadString().charAt(offset);
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sb.append(base);
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}
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}
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return sb.toString();
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}
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public double getAltVsRef(char altAllele) {
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double[] tumorRefAlt = extractRefAlt(this.likelihoods, this.refBase, altAllele);
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double tumorLod = Math.log10(tumorRefAlt[1] + tumorRefAlt[2]) - tumorRefAlt[0];
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return tumorLod;
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}
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public double getRefVsAlt(char altAllele) {
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double[] refAlt = extractRefAlt(this.likelihoods, this.refBase, altAllele);
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double normalLod = refAlt[0] - Math.log10(refAlt[1] + refAlt[2]);
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return normalLod;
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}
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/**
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* Extract the LOD comparing ref:ref to ref:alt and alt:alt
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*/
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private double[] extractRefAlt(GenotypeLikelihoods gl, char ref, char altAllele) {
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double refRef = 0;
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double altRef = 0;
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double altAlt = 0;
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for(int j=0; j<10; j++) {
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String gt = gl.genotypes[j];
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double likelihood = gl.likelihoods[j];
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// the ref:mutant theory
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if ( (gt.charAt(0) == ref && gt.charAt(1) == altAllele) ||
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(gt.charAt(0) == altAllele && gt.charAt(1) == ref) ) {
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altRef += Math.pow(10, likelihood);
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}
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if ( gt.charAt(0) == altAllele && gt.charAt(1) == altAllele) {
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altAlt += Math.pow(10, likelihood);
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}
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if ( gt.charAt(0) == ref && gt.charAt(1) == ref) {
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refRef = likelihood;
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}
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}
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return new double[]{refRef, altRef, altAlt};
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}
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private GenotypeLikelihoods getLikelihood(int locusOffset) {
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GenotypeLikelihoods likelihoods = new GenotypeLikelihoods();
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for(int i=0; i<reads.size(); i++) {
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SAMRecord read = reads.get(i);
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int readOffset = offsets.get(i);
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int offset = readOffset + locusOffset;
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if (offset >= 0 && offset < read.getReadString().length()) {
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char base = read.getReadString().charAt(offset);
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byte qual = read.getBaseQualities()[offset];
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likelihoods.add(refBase, base, qual);
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}
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}
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return likelihoods;
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}
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public double[] getNormalizedProbs(int locusOffset, int qThreshold) {
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GenotypeLikelihoods likelihoods = new GenotypeLikelihoods();
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// FIXME: gaddy suggested this "correction" which evidently has a name...
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//likelihoods.add(refBase, refBase, (byte) 20);
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for(int i=0; i<reads.size(); i++) {
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SAMRecord read = reads.get(i);
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int readOffset = offsets.get(i);
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int offset = readOffset + locusOffset;
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if (offset >= 0 && offset < read.getReadString().length()) {
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char base = read.getReadString().charAt(offset);
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byte qual = read.getBaseQualities()[offset];
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if (qual >= qThreshold) {
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likelihoods.add(refBase, base, qual);
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// if (locusOffset == -43) System.out.println("\tUSING " + base + " " + qual);
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} else {
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// if (locusOffset == -43) System.out.println("\tDropping " + base + " " + qual);
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}
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}
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}
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double[] logLikelihood = likelihoods.likelihoods;
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double[] nonLogLikelihood = new double[10];
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double sum = 0;
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for(int i=0; i<10; i++) {
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nonLogLikelihood[i] = Math.pow(10, logLikelihood[i]);
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sum += nonLogLikelihood[i];
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}
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double[] normalizedProbs = new double[10];
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for(int i=0; i<10; i++) {
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normalizedProbs[i] = nonLogLikelihood[i] / sum;
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}
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//quick sanity check
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// sum=0;
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// for(int i=0; i<10; i++) {
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// sum += normalizedProbs[i];
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// }
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// System.out.println("normalized probs = " + sum);
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return normalizedProbs;
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}
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}
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public Integer map(RefMetaDataTracker tracker, char ref, LocusContext context) {
|
||||
Map<Character, Integer> midp = new HashMap<Character, Integer>();
|
||||
midp.put('A', Integer.MAX_VALUE);
|
||||
|
|
@ -291,8 +93,8 @@ public class SomaticMutationWalker extends LocusWalker<Integer, Integer> {
|
|||
|
||||
List<SAMRecord> reads = context.getReads();
|
||||
|
||||
LocusReadPile tumorReadPile = new LocusReadPile(upRef);
|
||||
LocusReadPile normalReadPile = new LocusReadPile(upRef);
|
||||
LocusReadPile tumorReadPile = new LocusReadPile(upRef,MIN_QSCORE);
|
||||
LocusReadPile normalReadPile = new LocusReadPile(upRef,MIN_QSCORE);
|
||||
|
||||
for ( int i = 0; i < reads.size(); i++ )
|
||||
{
|
||||
|
|
@ -350,8 +152,8 @@ public class SomaticMutationWalker extends LocusWalker<Integer, Integer> {
|
|||
// (i) either an adjusted quality score sum in the tumor for the mutant base must be
|
||||
// at least 100 or the LOD score for mutant:ref + mutant:mutant vs ref:ref must
|
||||
// be at least 6.3;
|
||||
int mutantSum = tumorReadPile.qualitySums.get(altAllele);
|
||||
int refSum = tumorReadPile.qualitySums.get(upRef);
|
||||
int mutantSum = tumorReadPile.qualitySums.getQualitySum(altAllele);
|
||||
int refSum = tumorReadPile.qualitySums.getQualitySum(upRef);
|
||||
|
||||
if (tumorReadPile.getAltVsRef(altAllele) >= TUMOR_LOD_THRESHOLD
|
||||
// ||
|
||||
|
|
@ -365,7 +167,10 @@ public class SomaticMutationWalker extends LocusWalker<Integer, Integer> {
|
|||
// (ii) the quality score sum for the mutant base in the normal must be < 50 and the
|
||||
// LOD score for ref:ref vs mutant:ref + mutant:mutant must be at least 2.3.
|
||||
double normalLod = normalReadPile.getRefVsAlt(altAllele);
|
||||
if ( normalReadPile.qualitySums.get(altAllele) > 50 || normalLod < NORMAL_LOD_THRESHOLD) {
|
||||
QualitySums normQs = normalReadPile.qualitySums;
|
||||
|
||||
if ( (normQs.getCounts(altAllele) >= 2 && normQs.getQualitySum(altAllele) > 20)
|
||||
|| normalLod < NORMAL_LOD_THRESHOLD) {
|
||||
continue;
|
||||
}
|
||||
|
||||
|
|
@ -402,14 +207,14 @@ public class SomaticMutationWalker extends LocusWalker<Integer, Integer> {
|
|||
// at least 100 or the LOD score for mutant:ref + mutant:mutant vs ref:ref must
|
||||
// be at least 6.3;
|
||||
double tumorLod = t2.getAltVsRef(altAllele);
|
||||
if (mode.equals("full") && t2.qualitySums.get(altAllele) < MIN_MUTANT_SUM && tumorLod < TUMOR_LOD_THRESHOLD) {
|
||||
if (mode.equals("full") && t2.qualitySums.getQualitySum(altAllele) < MIN_MUTANT_SUM && tumorLod < TUMOR_LOD_THRESHOLD) {
|
||||
if (OUTPUT_FAILURES) {
|
||||
|
||||
String msg = "FAILED due to MAX MM QSCORE TEST." +
|
||||
" LOD was " + tumorReadPile.getAltVsRef(altAllele) +
|
||||
" LOD is now " + t2.getAltVsRef(altAllele) +
|
||||
" QSUM was " + tumorReadPile.qualitySums.get(altAllele) +
|
||||
" QSUM is now " + t2.qualitySums.get(altAllele);
|
||||
" QSUM was " + tumorReadPile.qualitySums.getQualitySum(altAllele) +
|
||||
" QSUM is now " + t2.qualitySums.getQualitySum(altAllele);
|
||||
|
||||
out.println(
|
||||
context.getContig() + "\t" +
|
||||
|
|
@ -458,11 +263,11 @@ public class SomaticMutationWalker extends LocusWalker<Integer, Integer> {
|
|||
String msg =
|
||||
(failedMidpointCheck?"__FAILED-MPCHECK":"") +
|
||||
"TScore:" + tumorLod +
|
||||
"__TRefSum: " + tumorReadPile.qualitySums.get(upRef) +
|
||||
"__TAltSum: " + tumorReadPile.qualitySums.get(altAllele) +
|
||||
"__TRefSum: " + tumorReadPile.qualitySums.getQualitySum(upRef) +
|
||||
"__TAltSum: " + tumorReadPile.qualitySums.getQualitySum(altAllele) +
|
||||
"__NScore:" + normalLod +
|
||||
"__NRefSum: " + normalReadPile.qualitySums.get(upRef) +
|
||||
"__NAltSum: " + normalReadPile.qualitySums.get(altAllele) +
|
||||
"__NRefSum: " + normalReadPile.qualitySums.getQualitySum(upRef) +
|
||||
"__NAltSum: " + normalReadPile.qualitySums.getQualitySum(altAllele) +
|
||||
"__maxSkewLod_" + failureReason.second + "_" +
|
||||
"__MIDP: " + midp.get(altAllele);
|
||||
|
||||
|
|
@ -528,7 +333,7 @@ public class SomaticMutationWalker extends LocusWalker<Integer, Integer> {
|
|||
if (read.getReadNegativeStrandFlag()) { seenOnNegative = true; } else { seenOnPositive = true; }
|
||||
}
|
||||
if (!seenOnPositive || !seenOnNegative) {
|
||||
// return MutantFailureReason.StrandImbalance;
|
||||
return new Pair<MutantFailureReason, Double>(MutantFailureReason.StrandImbalance, 0d);
|
||||
}
|
||||
|
||||
|
||||
Loading…
Reference in New Issue