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Multiallelic implementation of the TDT should be a pairwise list of values as per Mark Daly. Integration tests change because the count in the header is now A instead of 1.

This commit is contained in:
Eric Banks 2012-02-10 14:15:59 -05:00
parent f1990981fc
commit f52f1f659f
2 changed files with 20 additions and 27 deletions
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45
public/java/src/org/broadinstitute/sting/gatk/walkers/annotator/TransmissionDisequilibriumTest.java
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@ -9,6 +9,7 @@ import org.broadinstitute.sting.gatk.walkers.annotator.interfaces.ExperimentalAn
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.gatk.walkers.annotator.interfaces.RodRequiringAnnotation;
import org.broadinstitute.sting.utils.MathUtils; import org.broadinstitute.sting.utils.MathUtils;
import org.broadinstitute.sting.utils.codecs.vcf.VCFHeaderLineCount;
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;
import org.broadinstitute.sting.utils.exceptions.UserException; import org.broadinstitute.sting.utils.exceptions.UserException;
@ -58,41 +59,33 @@ public class TransmissionDisequilibriumTest extends InfoFieldAnnotation implemen
// return the descriptions used for the VCF INFO meta field // return the descriptions used for the VCF INFO meta field
public List<String> getKeyNames() { return Arrays.asList("TDT"); } public List<String> getKeyNames() { return Arrays.asList("TDT"); }
public List<VCFInfoHeaderLine> getDescriptions() { return Arrays.asList(new VCFInfoHeaderLine("TDT", 1, VCFHeaderLineType.Float, "Test statistic from Wittkowski transmission disequilibrium test.")); } public List<VCFInfoHeaderLine> getDescriptions() { return Arrays.asList(new VCFInfoHeaderLine("TDT", VCFHeaderLineCount.A, VCFHeaderLineType.Float, "Test statistic from Wittkowski transmission disequilibrium test.")); }
// 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 List<Double> calculateTDT( final VariantContext vc, final Set<Sample> triosToTest ) {
double nABGivenABandBB = 0.0; List<Double> pairwiseTDTs = new ArrayList<Double>(10);
double nBBGivenABandBB = 0.0; final int HomRefIndex = 0;
double nAAGivenABandAB = 0.0;
double nBBGivenABandAB = 0.0;
double nAAGivenAAandAB = 0.0;
double nABGivenAAandAB = 0.0;
// for each pair of alleles, add the likelihoods // for each pair of alleles, add the likelihoods
int numAlleles = vc.getNAlleles(); int numAltAlleles = vc.getAlternateAlleles().size();
for ( int allele1 = 0; allele1 < numAlleles; allele1++ ) { for ( int alt = 1; alt <= numAltAlleles; alt++ ) {
final int HOM1index = determineHomIndex(allele1, numAlleles); final int HetIndex = alt;
final int HomVarIndex = determineHomIndex(alt, numAltAlleles+1);
for ( int allele2 = allele1 + 1; allele2 < numAlleles; allele2++ ) { final double nABGivenABandBB = calculateNChildren(vc, triosToTest, HetIndex, HetIndex, HomVarIndex) + calculateNChildren(vc, triosToTest, HetIndex, HomVarIndex, HetIndex);
final double nBBGivenABandBB = calculateNChildren(vc, triosToTest, HomVarIndex, HetIndex, HomVarIndex) + calculateNChildren(vc, triosToTest, HomVarIndex, HomVarIndex, HetIndex);
final double nAAGivenABandAB = calculateNChildren(vc, triosToTest, HomRefIndex, HetIndex, HetIndex);
final double nBBGivenABandAB = calculateNChildren(vc, triosToTest, HomVarIndex, HetIndex, HetIndex);
final double nAAGivenAAandAB = calculateNChildren(vc, triosToTest, HomRefIndex, HomRefIndex, HetIndex) + calculateNChildren(vc, triosToTest, HomRefIndex, HetIndex, HomRefIndex);
final double nABGivenAAandAB = calculateNChildren(vc, triosToTest, HetIndex, HomRefIndex, HetIndex) + calculateNChildren(vc, triosToTest, HetIndex, HetIndex, HomRefIndex);
// TODO -- cache these for better performance final double numer = (nABGivenABandBB - nBBGivenABandBB) + 2.0 * (nAAGivenABandAB - nBBGivenABandAB) + (nAAGivenAAandAB - nABGivenAAandAB);
final int HETindex = HOM1index + (allele2 - allele1); final double denom = (nABGivenABandBB + nBBGivenABandBB) + 4.0 * (nAAGivenABandAB + nBBGivenABandAB) + (nAAGivenAAandAB + nABGivenAAandAB);
final int HOM2index = determineHomIndex(allele2, numAlleles); pairwiseTDTs.add((numer * numer) / denom);
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); return pairwiseTDTs;
final double denom = (nABGivenABandBB + nBBGivenABandBB) + 4.0 * (nAAGivenABandAB + nBBGivenABandAB) + (nAAGivenAAandAB + nABGivenAAandAB);
return (numer * numer) / denom;
} }
private double calculateNChildren( final VariantContext vc, final Set<Sample> triosToTest, final int childIdx, final int momIdx, final int dadIdx ) { private double calculateNChildren( final VariantContext vc, final Set<Sample> triosToTest, final int childIdx, final int momIdx, final int dadIdx ) {

2
public/java/test/org/broadinstitute/sting/gatk/walkers/annotator/VariantAnnotatorIntegrationTest.java
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@ -179,7 +179,7 @@ public class VariantAnnotatorIntegrationTest extends WalkerTest {
@Test @Test
public void testTDTAnnotation() { public void testTDTAnnotation() {
final String MD5 = "0aedd760e8099f0b95d53a41bdcd793e"; final String MD5 = "a78c1e950740d3c13c0258960c5fa8e1";
WalkerTestSpec spec = new WalkerTestSpec( WalkerTestSpec spec = new WalkerTestSpec(
"-T VariantAnnotator -R " + b37KGReference + " -A TransmissionDisequilibriumTest --variant:vcf " + validationDataLocation + "ug.random50000.subset300bp.chr1.family.vcf" + "-T VariantAnnotator -R " + b37KGReference + " -A TransmissionDisequilibriumTest --variant:vcf " + validationDataLocation + "ug.random50000.subset300bp.chr1.family.vcf" +
" -L " + validationDataLocation + "ug.random50000.subset300bp.chr1.family.vcf -NO_HEADER -ped " + validationDataLocation + "ug.random50000.family.ped -o %s", 1, " -L " + validationDataLocation + "ug.random50000.subset300bp.chr1.family.vcf -NO_HEADER -ped " + validationDataLocation + "ug.random50000.family.ped -o %s", 1,