Support for EXPERIMENT sampling-based genotype likelihoods
git-svn-id: file:///humgen/gsa-scr1/gsa-engineering/svn_contents/trunk@3044 348d0f76-0448-11de-a6fe-93d51630548a
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depristo
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@ -12,8 +12,14 @@ import org.broadinstitute.sting.gatk.contexts.variantcontext.Allele;
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import java.util.*;
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public class DiploidGenotypeCalculationModel extends JointEstimateGenotypeCalculationModel {
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/**
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* Should we enable the experimental genotype likelihood calculations?
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*/
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protected boolean useExptGenotypeLikelihoods = false;
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protected DiploidGenotypeCalculationModel() {}
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protected DiploidGenotypeCalculationModel(boolean useExptGenotypeLikelihoods) {
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this.useExptGenotypeLikelihoods = useExptGenotypeLikelihoods;
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}
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// the GenotypeLikelihoods map
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private HashMap<String, GenotypeLikelihoods> GLs = new HashMap<String, GenotypeLikelihoods>();
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@ -21,7 +27,9 @@ public class DiploidGenotypeCalculationModel extends JointEstimateGenotypeCalcul
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private enum GenotypeType { REF, HET, HOM }
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protected void initialize(char ref, Map<String, StratifiedAlignmentContext> contexts, StratifiedAlignmentContext.StratifiedContextType contextType) {
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protected void initialize(char ref,
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Map<String, StratifiedAlignmentContext> contexts,
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StratifiedAlignmentContext.StratifiedContextType contextType) {
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// initialize the GenotypeLikelihoods
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GLs.clear();
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AFMatrixMap.clear();
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@ -40,7 +48,13 @@ public class DiploidGenotypeCalculationModel extends JointEstimateGenotypeCalcul
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ReadBackedPileup pileup = context.getContext(contextType).getBasePileup();
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// create the GenotypeLikelihoods object
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GenotypeLikelihoods GL = new GenotypeLikelihoods(baseModel, priors, defaultPlatform);
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GenotypeLikelihoods GL;
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if ( useExptGenotypeLikelihoods ) {
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GL = new SamplingGenotypeLikelihoods(baseModel, priors, defaultPlatform);
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} else {
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GL = new GenotypeLikelihoods(baseModel, priors, defaultPlatform);
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}
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GL.add(pileup, true);
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GLs.put(sample, GL);
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@ -19,6 +19,7 @@ public abstract class GenotypeCalculationModel implements Cloneable {
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public enum Model {
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JOINT_ESTIMATE,
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JOINT_ESTIMATE_EXPT_GL,
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POOLED,
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INDELS
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}
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@ -65,7 +65,9 @@ public class GenotypeCalculationModelFactory {
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GenotypeCalculationModel gcm;
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switch ( UAC.genotypeModel ) {
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case JOINT_ESTIMATE:
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gcm = new DiploidGenotypeCalculationModel();
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case JOINT_ESTIMATE_EXPT_GL:
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boolean useExptGenotypeLikelihoods = UAC.genotypeModel == JOINT_ESTIMATE_EXPT_GL;
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gcm = new DiploidGenotypeCalculationModel(useExptGenotypeLikelihoods);
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break;
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case POOLED:
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gcm = new PooledCalculationModel();
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@ -0,0 +1,169 @@
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package org.broadinstitute.sting.gatk.walkers.genotyper;
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import net.sf.samtools.SAMRecord;
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import org.broadinstitute.sting.utils.*;
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import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
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import org.broadinstitute.sting.utils.pileup.PileupElement;
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import org.broadinstitute.sting.utils.genotype.DiploidGenotype;
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import static java.lang.Math.log10;
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import static java.lang.Math.pow;
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import java.util.Arrays;
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import java.util.Comparator;
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public class SamplingGenotypeLikelihoods extends GenotypeLikelihoods {
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/**
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* Create a new GenotypeLikelhoods object with flat priors for each diploid genotype
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*
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* @param m base model
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*/
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public SamplingGenotypeLikelihoods(BaseMismatchModel m) {
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super(m);
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enableCacheFlag = false;
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}
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/**
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* Create a new GenotypeLikelhoods object with flat priors for each diploid genotype
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*
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* @param m base model
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* @param pl default platform
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*/
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public SamplingGenotypeLikelihoods(BaseMismatchModel m, EmpiricalSubstitutionProbabilities.SequencerPlatform pl) {
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super(m, pl);
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enableCacheFlag = false;
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}
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/**
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* Create a new GenotypeLikelhoods object with given priors for each diploid genotype
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*
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* @param m base model
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* @param priors priors
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*/
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public SamplingGenotypeLikelihoods(BaseMismatchModel m, DiploidGenotypePriors priors) {
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super(m, priors);
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enableCacheFlag = false;
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}
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/**
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* Create a new GenotypeLikelhoods object with given priors for each diploid genotype
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*
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* @param m base model
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* @param priors priors
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* @param pl default platform
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*/
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public SamplingGenotypeLikelihoods(BaseMismatchModel m, DiploidGenotypePriors priors, EmpiricalSubstitutionProbabilities.SequencerPlatform pl) {
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super(m, priors, pl);
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enableCacheFlag = false;
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}
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/**
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* Cloning of the object
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* @return clone
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* @throws CloneNotSupportedException
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*/
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protected Object clone() throws CloneNotSupportedException {
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return super.clone();
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}
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/**
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* Updates likelihoods and posteriors to reflect the additional observations contained within the
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* read-based pileup up by calling add(observedBase, qualityScore) for each base / qual in the
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* pileup
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*
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* @param pileup read pileup
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* @param ignoreBadBases should we ignore bad bases
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* @return the number of good bases found in the pileup
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*/
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public int add(ReadBackedPileup pileup, boolean ignoreBadBases) {
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// we're actually going to be happy with our homozygous theories
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int n = super.add(pileup, ignoreBadBases);
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// Now, loop over the heterygous theories and do our fancy sampling calculation
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FourBaseProbabilities[] probs = fourBaseProbVector(n, pileup, ignoreBadBases);
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for ( DiploidGenotype g : DiploidGenotype.values() ) {
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if ( g.isHet() ) {
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//System.out.printf("DEBUG: computing best k for %s at %s%n", g, pileup.getLocation());
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double likelihood = calculateSamplingHetGenotypeLikelihood(probs, g, n);
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//System.out.printf("DEBUG: L was %.2f%n", likelihood);
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if ( likelihood != 1 ) {
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log10Likelihoods[g.ordinal()] = likelihood;
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log10Posteriors[g.ordinal()] = likelihood + priors.getPrior(g);
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}
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}
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}
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return n;
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}
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public int add(char observedBase, byte qualityScore, SAMRecord read, int offset) {
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throw new UnsupportedOperationException("BUG: Sampling genotype likelihoods does not support sequential addition of bases; use add(ReadBackedPileup) instead");
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}
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private double calculateSamplingHetGenotypeLikelihood(FourBaseProbabilities[] probs, DiploidGenotype g, int goodBaseDepth) {
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double bestLog10L = 1;
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//int bestK = -1;
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for ( int k = 0; k < goodBaseDepth; k++ ) {
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// for every possible sampling depth of the A allele
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double log10BinomialSampling = Math.log10(MathUtils.binomialProbabilityLog(k, goodBaseDepth, 0.5));
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double log10Het = mostLikelyKBases(probs, k, BaseUtils.simpleBaseToBaseIndex(g.base1), BaseUtils.simpleBaseToBaseIndex(g.base2));
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double log10L = log10BinomialSampling + log10Het;
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//System.out.printf(" DEBUG: computing best k = %d, bin = %.2f, het = %.2f, log10L = %.2f%n", k, log10BinomialSampling, log10Het, log10L);
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if ( log10L > bestLog10L || bestLog10L == 1 ) {
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bestLog10L = log10L;
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//bestK = k;
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}
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}
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//System.out.printf(" DEBUG: best k = %d with log10L of %.2f%n", bestK, bestLog10L);
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return bestLog10L;
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}
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FourBaseProbabilities[] fourBaseProbVector(int n, ReadBackedPileup pileup, boolean ignoreBadBases) {
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FourBaseProbabilities[] probs = new FourBaseProbabilities[n];
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int i = 0;
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for ( PileupElement p : pileup ) {
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char observedBase = (char)p.getBase();
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byte qualityScore = p.getQual();
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SAMRecord read = p.getRead();
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int offset = p.getOffset();
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if ( ! ignoreBadBases || ! badBase(observedBase) ) {
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FourBaseProbabilities fbl = fourBaseLikelihoods.computeLog10Likelihoods(observedBase, qualityScore, read, offset);
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if ( fbl != null ) {
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probs[i++] = fbl;
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}
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}
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}
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return probs;
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}
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class FourBaseComparator implements Comparator<FourBaseProbabilities> {
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int index = 0;
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public FourBaseComparator(int i) { index = i; }
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public int compare(FourBaseProbabilities a, FourBaseProbabilities b) {
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return -1 * Double.compare(a.getLog10Likelihood(index), b.getLog10Likelihood(index));
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}
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}
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protected static final double log103 = log10(3.0);
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double mostLikelyKBases(FourBaseProbabilities[] probs, int k, int base1, int base2) {
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if ( k == 0 ) // optimization -- if k > 1, we've already sorted the vector
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Arrays.sort(probs, new FourBaseComparator(base1));
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double log10L = 0;
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for ( int i = 0; i < probs.length; i++ ) {
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int base = i < k ? base1 : base2;
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log10L += probs[i].getLog10Likelihood(base) - log103;
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//System.out.printf("%3d %d %.2f %.2f %.2f%n", i, base, probs[i].getLog10Likelihood(base), probs[i].getLog10Likelihood(base1), probs[i].getLog10Likelihood(base2));
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}
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return log10L;
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}
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}
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