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Generalized the TDT for multi-allelic events

This commit is contained in:
Eric Banks 2012-02-03 12:23:21 -05:00
parent f596377e73
commit 3abfbcbcf2
1 changed files with 39 additions and 15 deletions
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54
public/java/src/org/broadinstitute/sting/gatk/walkers/annotator/TransmissionDisequilibriumTest.java
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@ -7,6 +7,7 @@ import org.broadinstitute.sting.gatk.samples.Sample;
import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.AnnotatorCompatibleWalker; import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.AnnotatorCompatibleWalker;
import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.ExperimentalAnnotation; import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.ExperimentalAnnotation;
import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.InfoFieldAnnotation; import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.InfoFieldAnnotation;
import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.RodRequiringAnnotation;
import org.broadinstitute.sting.utils.MathUtils; import org.broadinstitute.sting.utils.MathUtils;
import org.broadinstitute.sting.utils.codecs.vcf.VCFHeaderLineType; import org.broadinstitute.sting.utils.codecs.vcf.VCFHeaderLineType;
import org.broadinstitute.sting.utils.codecs.vcf.VCFInfoHeaderLine; import org.broadinstitute.sting.utils.codecs.vcf.VCFInfoHeaderLine;
@ -17,16 +18,13 @@ import java.util.*;
/** /**
* Created by IntelliJ IDEA. * Created by IntelliJ IDEA.
* User: rpoplin, lfran * User: rpoplin, lfran, ebanks
* Date: 11/14/11 * Date: 11/14/11
*/ */
public class TransmissionDisequilibriumTest extends InfoFieldAnnotation implements ExperimentalAnnotation { public class TransmissionDisequilibriumTest extends InfoFieldAnnotation implements ExperimentalAnnotation, RodRequiringAnnotation {
private Set<Sample> trios = null; private Set<Sample> trios = null;
private final static int REF = 0;
private final static int HET = 1;
private final static int HOM = 2;
private final static int MIN_NUM_VALID_TRIOS = 5; // don't calculate this population-level statistic if there are less than X trios with full genotype likelihood information private final static int MIN_NUM_VALID_TRIOS = 5; // don't calculate this population-level statistic if there are less than X trios with full genotype likelihood information
public Map<String, Object> annotate(RefMetaDataTracker tracker, AnnotatorCompatibleWalker walker, ReferenceContext ref, Map<String, AlignmentContext> stratifiedContexts, VariantContext vc) { public Map<String, Object> annotate(RefMetaDataTracker tracker, AnnotatorCompatibleWalker walker, ReferenceContext ref, Map<String, AlignmentContext> stratifiedContexts, VariantContext vc) {
@ -38,10 +36,10 @@ public class TransmissionDisequilibriumTest extends InfoFieldAnnotation implemen
} }
} }
final Map<String,Object> toRet = new HashMap<String,Object>(1); final Map<String, Object> toRet = new HashMap<String, Object>(1);
final HashSet<Sample> triosToTest = new HashSet<Sample>(); final HashSet<Sample> triosToTest = new HashSet<Sample>();
for( final Sample child : trios) { for( final Sample child : trios ) {
final boolean hasAppropriateGenotypes = vc.hasGenotype(child.getID()) && vc.getGenotype(child.getID()).hasLikelihoods() && final boolean hasAppropriateGenotypes = vc.hasGenotype(child.getID()) && vc.getGenotype(child.getID()).hasLikelihoods() &&
vc.hasGenotype(child.getPaternalID()) && vc.getGenotype(child.getPaternalID()).hasLikelihoods() && vc.hasGenotype(child.getPaternalID()) && vc.getGenotype(child.getPaternalID()).hasLikelihoods() &&
vc.hasGenotype(child.getMaternalID()) && vc.getGenotype(child.getMaternalID()).hasLikelihoods(); vc.hasGenotype(child.getMaternalID()) && vc.getGenotype(child.getMaternalID()).hasLikelihoods();
@ -65,28 +63,54 @@ public class TransmissionDisequilibriumTest extends InfoFieldAnnotation implemen
// Following derivation in http://en.wikipedia.org/wiki/Transmission_disequilibrium_test#A_modified_version_of_the_TDT // Following derivation in http://en.wikipedia.org/wiki/Transmission_disequilibrium_test#A_modified_version_of_the_TDT
private double calculateTDT( final VariantContext vc, final Set<Sample> triosToTest ) { private double calculateTDT( final VariantContext vc, final Set<Sample> triosToTest ) {
final double nABGivenABandBB = calculateNChildren(vc, triosToTest, HET, HET, HOM) + calculateNChildren(vc, triosToTest, HET, HOM, HET); double nABGivenABandBB = 0.0;
final double nBBGivenABandBB = calculateNChildren(vc, triosToTest, HOM, HET, HOM) + calculateNChildren(vc, triosToTest, HOM, HOM, HET); double nBBGivenABandBB = 0.0;
final double nAAGivenABandAB = calculateNChildren(vc, triosToTest, REF, HET, HET); double nAAGivenABandAB = 0.0;
final double nBBGivenABandAB = calculateNChildren(vc, triosToTest, HOM, HET, HET); double nBBGivenABandAB = 0.0;
final double nAAGivenAAandAB = calculateNChildren(vc, triosToTest, REF, REF, HET) + calculateNChildren(vc, triosToTest, REF, HET, REF); double nAAGivenAAandAB = 0.0;
final double nABGivenAAandAB = calculateNChildren(vc, triosToTest, HET, REF, HET) + calculateNChildren(vc, triosToTest, HET, HET, REF); double nABGivenAAandAB = 0.0;
// for each pair of alleles, add the likelihoods
int numAlleles = vc.getNAlleles();
for ( int allele1 = 0; allele1 < numAlleles; allele1++ ) {
for ( int allele2 = allele1 + 1; allele2 < numAlleles; allele2++ ) {
// TODO -- cache these for better performance
final int HOM1index = determineHomIndex(allele1, numAlleles);
final int HETindex = HOM1index + (allele2 - allele1);
final int HOM2index = determineHomIndex(allele2, numAlleles);
nABGivenABandBB += calculateNChildren(vc, triosToTest, HETindex, HETindex, HOM2index) + calculateNChildren(vc, triosToTest, HETindex, HOM2index, HETindex);
nBBGivenABandBB += calculateNChildren(vc, triosToTest, HOM2index, HETindex, HOM2index) + calculateNChildren(vc, triosToTest, HOM2index, HOM2index, HETindex);
nAAGivenABandAB += calculateNChildren(vc, triosToTest, HOM1index, HETindex, HETindex);
nBBGivenABandAB += calculateNChildren(vc, triosToTest, HOM2index, HETindex, HETindex);
nAAGivenAAandAB += calculateNChildren(vc, triosToTest, HOM1index, HOM1index, HETindex) + calculateNChildren(vc, triosToTest, HOM1index, HETindex, HOM1index);
nABGivenAAandAB += calculateNChildren(vc, triosToTest, HETindex, HOM1index, HETindex) + calculateNChildren(vc, triosToTest, HETindex, HETindex, HOM1index);
}
}
final double numer = (nABGivenABandBB - nBBGivenABandBB) + 2.0 * (nAAGivenABandAB - nBBGivenABandAB) + (nAAGivenAAandAB - nABGivenAAandAB); final double numer = (nABGivenABandBB - nBBGivenABandBB) + 2.0 * (nAAGivenABandAB - nBBGivenABandAB) + (nAAGivenAAandAB - nABGivenAAandAB);
final double denom = (nABGivenABandBB + nBBGivenABandBB) + 4.0 * (nAAGivenABandAB + nBBGivenABandAB) + (nAAGivenAAandAB + nABGivenAAandAB); final double denom = (nABGivenABandBB + nBBGivenABandBB) + 4.0 * (nAAGivenABandAB + nBBGivenABandAB) + (nAAGivenAAandAB + nABGivenAAandAB);
return (numer * numer) / denom; return (numer * numer) / denom;
} }
private double calculateNChildren( final VariantContext vc, final Set<Sample> triosToTest, final int childIdx, final int parent1Idx, final int parent2Idx ) { private double calculateNChildren( final VariantContext vc, final Set<Sample> triosToTest, final int childIdx, final int momIdx, final int dadIdx ) {
final double likelihoodVector[] = new double[triosToTest.size()]; final double likelihoodVector[] = new double[triosToTest.size()];
int iii = 0; int iii = 0;
for( final Sample child : triosToTest ) { for( final Sample child : triosToTest ) {
final double[] momGL = vc.getGenotype(child.getMaternalID()).getLikelihoods().getAsVector(); final double[] momGL = vc.getGenotype(child.getMaternalID()).getLikelihoods().getAsVector();
final double[] dadGL = vc.getGenotype(child.getPaternalID()).getLikelihoods().getAsVector(); final double[] dadGL = vc.getGenotype(child.getPaternalID()).getLikelihoods().getAsVector();
final double[] childGL = vc.getGenotype(child.getID()).getLikelihoods().getAsVector(); final double[] childGL = vc.getGenotype(child.getID()).getLikelihoods().getAsVector();
likelihoodVector[iii++] = momGL[parent1Idx] + dadGL[parent2Idx] + childGL[childIdx]; likelihoodVector[iii++] = momGL[momIdx] + dadGL[dadIdx] + childGL[childIdx];
} }
return MathUtils.sumLog10(likelihoodVector); return MathUtils.sumLog10(likelihoodVector);
} }
private static int determineHomIndex(final int alleleIndex, int numAlleles) {
int result = 0;
for ( int i = 0; i < alleleIndex; i++ )
result += numAlleles--;
return result;
}
} }