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Merge pull request #25 from broadinstitute/md_hmm_fail_GSA-751 

Md hmm fail gsa 751
This commit is contained in:
delangel 2013-02-09 16:43:50 -08:00
parent b7593aeadc b4417dff5b
commit f8e2153c71
15 changed files with 844 additions and 684 deletions
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60
protected/java/src/org/broadinstitute/sting/gatk/walkers/annotator/HaplotypeScore.java
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@ -91,8 +91,6 @@ public class HaplotypeScore extends InfoFieldAnnotation implements StandardAnnot
final Map<String, PerReadAlleleLikelihoodMap> stratifiedPerReadAlleleLikelihoodMap) {
if (vc.isSNP() && stratifiedContexts != null)
return annotatePileup(ref, stratifiedContexts, vc);
else if (stratifiedPerReadAlleleLikelihoodMap != null && vc.isVariant())
return annotateWithLikelihoods(stratifiedPerReadAlleleLikelihoodMap, vc);
else
return null;
}
@ -133,31 +131,6 @@ public class HaplotypeScore extends InfoFieldAnnotation implements StandardAnnot
return map;
}
private Map<String, Object> annotateWithLikelihoods(final Map<String, PerReadAlleleLikelihoodMap> stratifiedPerReadAlleleLikelihoodMap,
final VariantContext vc) {
final MathUtils.RunningAverage scoreRA = new MathUtils.RunningAverage();
for (final Genotype genotype : vc.getGenotypes()) {
final PerReadAlleleLikelihoodMap perReadAlleleLikelihoodMap = stratifiedPerReadAlleleLikelihoodMap.get(genotype.getSampleName());
if (perReadAlleleLikelihoodMap == null)
continue;
Double d = scoreIndelsAgainstHaplotypes(perReadAlleleLikelihoodMap);
if (d == null)
continue;
scoreRA.add(d); // Taking the simple average of all sample's score since the score can be negative and the RMS doesn't make sense
}
// if (scoreRA.observationCount() == 0)
// return null;
// annotate the score in the info field
final Map<String, Object> map = new HashMap<String, Object>();
map.put(getKeyNames().get(0), String.format("%.4f", scoreRA.mean()));
return map;
}
private static class HaplotypeComparator implements Comparator<Haplotype>, Serializable {
public int compare(Haplotype a, Haplotype b) {
@ -412,39 +385,6 @@ public class HaplotypeScore extends InfoFieldAnnotation implements StandardAnnot
return mismatches - expected;
}
private Double scoreIndelsAgainstHaplotypes(final PerReadAlleleLikelihoodMap perReadAlleleLikelihoodMap) {
final ArrayList<double[]> haplotypeScores = new ArrayList<double[]>();
if (perReadAlleleLikelihoodMap.isEmpty())
return null;
for (Map<Allele,Double> el : perReadAlleleLikelihoodMap.getLikelihoodMapValues()) {
// retrieve likelihood information corresponding to this read
// Score all the reads in the pileup, even the filtered ones
final double[] scores = new double[el.size()];
int i = 0;
for (Map.Entry<Allele, Double> a : el.entrySet()) {
scores[i++] = -a.getValue();
if (DEBUG) {
System.out.printf(" vs. haplotype %d = %f%n", i - 1, scores[i - 1]);
}
}
haplotypeScores.add(scores);
}
// indel likelihoods are strict log-probs, not phred scored
double overallScore = 0.0;
for (final double[] readHaplotypeScores : haplotypeScores) {
overallScore += MathUtils.arrayMin(readHaplotypeScores);
}
return overallScore;
}
public List<String> getKeyNames() {
return Arrays.asList("HaplotypeScore");
}

18
protected/java/src/org/broadinstitute/sting/gatk/walkers/haplotypecaller/LikelihoodCalculationEngine.java
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@ -72,13 +72,10 @@ public class LikelihoodCalculationEngine {
switch (hmmType) {
case EXACT:
pairHMM = new ExactPairHMM();
pairHMM = new Log10PairHMM(true);
break;
case ORIGINAL:
pairHMM = new OriginalPairHMM();
break;
case CACHING:
pairHMM = new CachingPairHMM();
pairHMM = new Log10PairHMM(false);
break;
case LOGLESS_CACHING:
pairHMM = new LoglessCachingPairHMM();
@ -150,7 +147,7 @@ public class LikelihoodCalculationEngine {
for( int jjj = 0; jjj < numHaplotypes; jjj++ ) {
final Haplotype haplotype = haplotypes.get(jjj);
final int haplotypeStart = ( previousHaplotypeSeen == null ? 0 : computeFirstDifferingPosition(haplotype.getBases(), previousHaplotypeSeen.getBases()) );
final int haplotypeStart = ( previousHaplotypeSeen == null ? 0 : PairHMM.findFirstPositionWhereHaplotypesDiffer(haplotype.getBases(), previousHaplotypeSeen.getBases()) );
previousHaplotypeSeen = haplotype;
perReadAlleleLikelihoodMap.add(read, alleleVersions.get(haplotype),
@ -161,15 +158,6 @@ public class LikelihoodCalculationEngine {
return perReadAlleleLikelihoodMap;
}
private static int computeFirstDifferingPosition( final byte[] b1, final byte[] b2 ) {
for( int iii = 0; iii < b1.length && iii < b2.length; iii++ ) {
if( b1[iii] != b2[iii] ) {
return iii;
}
}
return Math.min(b1.length, b2.length);
}
@Requires({"alleleOrdering.size() > 0"})
@Ensures({"result.length == result[0].length", "result.length == alleleOrdering.size()"})
public static double[][] computeDiploidHaplotypeLikelihoods( final String sample,

13
protected/java/src/org/broadinstitute/sting/gatk/walkers/indels/PairHMMIndelErrorModel.java
View File

@ -48,14 +48,12 @@ package org.broadinstitute.sting.gatk.walkers.indels;
import com.google.java.contract.Ensures;
import org.broadinstitute.sting.gatk.contexts.ReferenceContext;
import org.broadinstitute.sting.utils.genotyper.PerReadAlleleLikelihoodMap;
import org.broadinstitute.sting.utils.Haplotype;
import org.broadinstitute.sting.utils.MathUtils;
import org.broadinstitute.sting.utils.clipping.ReadClipper;
import org.broadinstitute.sting.utils.exceptions.UserException;
import org.broadinstitute.sting.utils.pairhmm.ExactPairHMM;
//import org.broadinstitute.sting.utils.pairhmm.LoglessCachingPairHMM;
import org.broadinstitute.sting.utils.pairhmm.OriginalPairHMM;
import org.broadinstitute.sting.utils.genotyper.PerReadAlleleLikelihoodMap;
import org.broadinstitute.sting.utils.pairhmm.Log10PairHMM;
import org.broadinstitute.sting.utils.pairhmm.PairHMM;
import org.broadinstitute.sting.utils.pileup.PileupElement;
import org.broadinstitute.sting.utils.pileup.ReadBackedPileup;
@ -68,6 +66,8 @@ import java.util.Arrays;
import java.util.LinkedHashMap;
import java.util.Map;
//import org.broadinstitute.sting.utils.pairhmm.LoglessCachingPairHMM;
public class PairHMMIndelErrorModel {
public static final int BASE_QUAL_THRESHOLD = 20;
@ -116,12 +116,11 @@ public class PairHMMIndelErrorModel {
switch (hmmType) {
case EXACT:
pairHMM = new ExactPairHMM();
pairHMM = new Log10PairHMM(true);
break;
case ORIGINAL:
pairHMM = new OriginalPairHMM();
pairHMM = new Log10PairHMM(false);
break;
case CACHING:
case LOGLESS_CACHING: //TODO: still not tested so please do not use yet
//pairHMM = new LoglessCachingPairHMM(); //TODO - add it back when the figure out how to use the protected LoglessCachingPairHMM class
throw new UserException.BadArgumentValue("pairHMM"," this option (LOGLESS_CACHING in UG) is still under development");

203
protected/java/src/org/broadinstitute/sting/utils/pairhmm/CachingPairHMM.java
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@ -1,203 +0,0 @@
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package org.broadinstitute.sting.utils.pairhmm;
import org.broadinstitute.sting.utils.MathUtils;
import org.broadinstitute.sting.utils.QualityUtils;
import java.util.Arrays;
/**
* Created with IntelliJ IDEA.
* User: rpoplin, carneiro
* Date: 10/16/12
*/
public class CachingPairHMM extends OriginalPairHMM {
double[][] constantMatrix = null; // The cache in the CachingPairHMM
double[][] distanceMatrix = null; // The cache in the CachingPairHMM
protected static final double [] firstRowConstantMatrix = {
QualityUtils.qualToProbLog10((byte) (DEFAULT_GOP + DEFAULT_GOP)),
QualityUtils.qualToProbLog10(DEFAULT_GCP),
QualityUtils.qualToErrorProbLog10(DEFAULT_GOP),
QualityUtils.qualToErrorProbLog10(DEFAULT_GCP),
0.0,
0.0
};
@Override
public void initialize( final int READ_MAX_LENGTH, final int HAPLOTYPE_MAX_LENGTH ) {
super.initialize(READ_MAX_LENGTH, HAPLOTYPE_MAX_LENGTH);
// M, X, and Y arrays are of size read and haplotype + 1 because of an extra column for initial conditions and + 1 to consider the final base in a non-global alignment
final int X_METRIC_LENGTH = READ_MAX_LENGTH + 2;
final int Y_METRIC_LENGTH = HAPLOTYPE_MAX_LENGTH + 2;
constantMatrix = new double[X_METRIC_LENGTH][6];
distanceMatrix = new double[X_METRIC_LENGTH][Y_METRIC_LENGTH];
// fill in the first row
for( int jjj = 2; jjj < Y_METRIC_LENGTH; jjj++ ) {
updateCell(1, jjj, 0.0, firstRowConstantMatrix, matchMetricArray, XMetricArray, YMetricArray);
}
}
@Override
public double computeReadLikelihoodGivenHaplotypeLog10( final byte[] haplotypeBases,
final byte[] readBases,
final byte[] readQuals,
final byte[] insertionGOP,
final byte[] deletionGOP,
final byte[] overallGCP,
final int hapStartIndex,
final boolean recacheReadValues ) {
if( recacheReadValues ) {
initializeConstants( insertionGOP, deletionGOP, overallGCP );
}
initializeDistanceMatrix( haplotypeBases, readBases, readQuals, hapStartIndex );
// M, X, and Y arrays are of size read and haplotype + 1 because of an extra column for initial conditions and + 1 to consider the final base in a non-global alignment
final int X_METRIC_LENGTH = readBases.length + 2;
final int Y_METRIC_LENGTH = haplotypeBases.length + 2;
for (int i = 2; i < X_METRIC_LENGTH; i++) {
for (int j = hapStartIndex+1; j < Y_METRIC_LENGTH; j++) {
updateCell(i, j, distanceMatrix[i][j], constantMatrix[i], matchMetricArray, XMetricArray, YMetricArray);
}
}
// final probability is the log10 sum of the last element in all three state arrays
final int endI = X_METRIC_LENGTH - 1;
final int endJ = Y_METRIC_LENGTH - 1;
return MathUtils.approximateLog10SumLog10(matchMetricArray[endI][endJ], XMetricArray[endI][endJ], YMetricArray[endI][endJ]);
}
/**
* Initializes the matrix that holds all the constants related to the editing
* distance between the read and the haplotype.
*
* @param haplotypeBases the bases of the haplotype
* @param readBases the bases of the read
* @param readQuals the base quality scores of the read
* @param startIndex where to start updating the distanceMatrix (in case this read is similar to the previous read)
*/
public void initializeDistanceMatrix( final byte[] haplotypeBases,
final byte[] readBases,
final byte[] readQuals,
final int startIndex ) {
// initialize the pBaseReadLog10 matrix for all combinations of read x haplotype bases
// Abusing the fact that java initializes arrays with 0.0, so no need to fill in rows and columns below 2.
for (int i = 0; i < readBases.length; i++) {
final byte x = readBases[i];
final byte qual = readQuals[i];
for (int j = startIndex; j < haplotypeBases.length; j++) {
final byte y = haplotypeBases[j];
distanceMatrix[i+2][j+2] = ( x == y || x == (byte) 'N' || y == (byte) 'N' ?
QualityUtils.qualToProbLog10(qual) : QualityUtils.qualToErrorProbLog10(qual) );
}
}
}
/**
* Initializes the matrix that holds all the constants related to quality scores.
*
* @param insertionGOP insertion quality scores of the read
* @param deletionGOP deletion quality scores of the read
* @param overallGCP overall gap continuation penalty
*/
public void initializeConstants( final byte[] insertionGOP,
final byte[] deletionGOP,
final byte[] overallGCP ) {
final int l = insertionGOP.length;
constantMatrix[1] = firstRowConstantMatrix;
for (int i = 0; i < l; i++) {
final int qualIndexGOP = Math.min(insertionGOP[i] + deletionGOP[i], Byte.MAX_VALUE);
constantMatrix[i+2][0] = QualityUtils.qualToProbLog10((byte) qualIndexGOP);
constantMatrix[i+2][1] = QualityUtils.qualToProbLog10(overallGCP[i]);
constantMatrix[i+2][2] = QualityUtils.qualToErrorProbLog10(insertionGOP[i]);
constantMatrix[i+2][3] = QualityUtils.qualToErrorProbLog10(overallGCP[i]);
constantMatrix[i+2][4] = QualityUtils.qualToErrorProbLog10(deletionGOP[i]);
constantMatrix[i+2][5] = QualityUtils.qualToErrorProbLog10(overallGCP[i]);
}
constantMatrix[l+1][4] = 0.0;
constantMatrix[l+1][5] = 0.0;
}
/**
* Updates a cell in the HMM matrix
*
* The read and haplotype indices are offset by one because the state arrays have an extra column to hold the
* initial conditions
* @param indI row index in the matrices to update
* @param indJ column index in the matrices to update
* @param prior the likelihood editing distance matrix for the read x haplotype
* @param constants an array with the six constants relevant to this location
* @param matchMetricArray the matches likelihood matrix
* @param XMetricArray the insertions likelihood matrix
* @param YMetricArray the deletions likelihood matrix
*/
private void updateCell( final int indI, final int indJ, final double prior, final double[] constants,
final double[][] matchMetricArray, final double[][] XMetricArray, final double[][] YMetricArray ) {
matchMetricArray[indI][indJ] = prior +
MathUtils.approximateLog10SumLog10( matchMetricArray[indI - 1][indJ - 1] + constants[0],
XMetricArray[indI - 1][indJ - 1] + constants[1],
YMetricArray[indI - 1][indJ - 1] + constants[1] );
XMetricArray[indI][indJ] = MathUtils.approximateLog10SumLog10( matchMetricArray[indI - 1][indJ] + constants[2],
XMetricArray[indI - 1][indJ] + constants[3]);
YMetricArray[indI][indJ] = MathUtils.approximateLog10SumLog10( matchMetricArray[indI][indJ - 1] + constants[4],
YMetricArray[indI][indJ - 1] + constants[5]);
}
}

116
protected/java/src/org/broadinstitute/sting/utils/pairhmm/LoglessCachingPairHMM.java
View File

@ -46,20 +46,25 @@
package org.broadinstitute.sting.utils.pairhmm;
import com.google.java.contract.Ensures;
import com.google.java.contract.Requires;
import org.broadinstitute.sting.utils.QualityUtils;
import java.util.Arrays;
/**
* Created with IntelliJ IDEA.
* User: rpoplin, carneiro
* Date: 10/16/12
*/
public class LoglessCachingPairHMM extends CachingPairHMM {
public class LoglessCachingPairHMM extends PairHMM {
protected static final double SCALE_FACTOR_LOG10 = 300.0;
double[][] constantMatrix = null; // The cache
double[][] distanceMatrix = null; // The cache
boolean constantsAreInitialized = false;
/**
* Cached data structure that describes the first row's edge condition in the HMM
*/
protected static final double [] firstRowConstantMatrix = {
QualityUtils.qualToProb((byte) (DEFAULT_GOP + DEFAULT_GOP)),
QualityUtils.qualToProb(DEFAULT_GCP),
@ -69,63 +74,48 @@ public class LoglessCachingPairHMM extends CachingPairHMM {
1.0
};
/**
* {@inheritDoc}
*/
@Override
public void initialize( final int READ_MAX_LENGTH, final int HAPLOTYPE_MAX_LENGTH ) {
public void initialize( final int readMaxLength, final int haplotypeMaxLength) {
super.initialize(readMaxLength, haplotypeMaxLength);
// M, X, and Y arrays are of size read and haplotype + 1 because of an extra column for initial conditions and + 1 to consider the final base in a non-global alignment
final int X_METRIC_LENGTH = READ_MAX_LENGTH + 2;
final int Y_METRIC_LENGTH = HAPLOTYPE_MAX_LENGTH + 2;
matchMetricArray = new double[X_METRIC_LENGTH][Y_METRIC_LENGTH];
XMetricArray = new double[X_METRIC_LENGTH][Y_METRIC_LENGTH];
YMetricArray = new double[X_METRIC_LENGTH][Y_METRIC_LENGTH];
for( int iii=0; iii < X_METRIC_LENGTH; iii++ ) {
Arrays.fill(matchMetricArray[iii], 0.0);
Arrays.fill(XMetricArray[iii], 0.0);
Arrays.fill(YMetricArray[iii], 0.0);
}
// the initial condition
matchMetricArray[1][1] = Math.pow(10.0, SCALE_FACTOR_LOG10); // Math.log10(1.0);
constantMatrix = new double[X_METRIC_LENGTH][6];
distanceMatrix = new double[X_METRIC_LENGTH][Y_METRIC_LENGTH];
// fill in the first row
for( int jjj = 2; jjj < Y_METRIC_LENGTH; jjj++ ) {
updateCell(1, jjj, 1.0, firstRowConstantMatrix, matchMetricArray, XMetricArray, YMetricArray);
}
constantMatrix = new double[X_METRIC_MAX_LENGTH][6];
distanceMatrix = new double[X_METRIC_MAX_LENGTH][Y_METRIC_MAX_LENGTH];
}
/**
* {@inheritDoc}
*/
@Override
public double computeReadLikelihoodGivenHaplotypeLog10( final byte[] haplotypeBases,
final byte[] readBases,
final byte[] readQuals,
final byte[] insertionGOP,
final byte[] deletionGOP,
final byte[] overallGCP,
final int hapStartIndex,
final boolean recacheReadValues ) {
if( recacheReadValues ) {
initializeConstants( insertionGOP, deletionGOP, overallGCP );
}
public double subComputeReadLikelihoodGivenHaplotypeLog10( final byte[] haplotypeBases,
final byte[] readBases,
final byte[] readQuals,
final byte[] insertionGOP,
final byte[] deletionGOP,
final byte[] overallGCP,
final int hapStartIndex,
final boolean recacheReadValues ) {
if ( ! constantsAreInitialized || recacheReadValues )
initializeConstants( haplotypeBases.length, readBases.length, insertionGOP, deletionGOP, overallGCP );
initializeDistanceMatrix( haplotypeBases, readBases, readQuals, hapStartIndex );
// M, X, and Y arrays are of size read and haplotype + 1 because of an extra column for initial conditions and + 1 to consider the final base in a non-global alignment
final int X_METRIC_LENGTH = readBases.length + 2;
final int Y_METRIC_LENGTH = haplotypeBases.length + 2;
// NOTE NOTE NOTE -- because of caching we need to only operate over X and Y according to this
// read and haplotype lengths, not the max lengths
final int readXMetricLength = readBases.length + 2;
final int hapYMetricLength = haplotypeBases.length + 2;
for (int i = 2; i < X_METRIC_LENGTH; i++) {
for (int j = hapStartIndex+1; j < Y_METRIC_LENGTH; j++) {
for (int i = 2; i < readXMetricLength; i++) {
// +1 here is because hapStartIndex is 0-based, but our matrices are 1 based
for (int j = hapStartIndex+1; j < hapYMetricLength; j++) {
updateCell(i, j, distanceMatrix[i][j], constantMatrix[i], matchMetricArray, XMetricArray, YMetricArray);
}
}
// final probability is the log10 sum of the last element in all three state arrays
final int endI = X_METRIC_LENGTH - 1;
final int endJ = Y_METRIC_LENGTH - 1;
final int endI = readXMetricLength - 1;
final int endJ = hapYMetricLength - 1;
return Math.log10( matchMetricArray[endI][endJ] + XMetricArray[endI][endJ] + YMetricArray[endI][endJ] ) - SCALE_FACTOR_LOG10;
}
@ -160,13 +150,32 @@ public class LoglessCachingPairHMM extends CachingPairHMM {
/**
* Initializes the matrix that holds all the constants related to quality scores.
*
* @param haplotypeSize the number of bases in the haplotype we are testing
* @param readSize the number of bases in the read we are testing
* @param insertionGOP insertion quality scores of the read
* @param deletionGOP deletion quality scores of the read
* @param overallGCP overall gap continuation penalty
*/
public void initializeConstants( final byte[] insertionGOP,
final byte[] deletionGOP,
final byte[] overallGCP ) {
@Requires({
"haplotypeSize > 0",
"readSize > 0",
"insertionGOP != null && insertionGOP.length == readSize",
"deletionGOP != null && deletionGOP.length == readSize",
"overallGCP != null && overallGCP.length == readSize"
})
@Ensures("constantsAreInitialized")
private void initializeConstants( final int haplotypeSize,
final int readSize,
final byte[] insertionGOP,
final byte[] deletionGOP,
final byte[] overallGCP ) {
// the initial condition -- must be here because it needs that actual read and haplotypes, not the maximum in init
matchMetricArray[1][1] = Math.pow(10.0, SCALE_FACTOR_LOG10) / getNPotentialXStarts(haplotypeSize, readSize);
// fill in the first row
for( int jjj = 2; jjj < Y_METRIC_MAX_LENGTH; jjj++ ) {
updateCell(1, jjj, 1.0, firstRowConstantMatrix, matchMetricArray, XMetricArray, YMetricArray);
}
final int l = insertionGOP.length;
constantMatrix[1] = firstRowConstantMatrix;
@ -181,6 +190,9 @@ public class LoglessCachingPairHMM extends CachingPairHMM {
}
constantMatrix[l+1][4] = 1.0;
constantMatrix[l+1][5] = 1.0;
// note that we initialized the constants
constantsAreInitialized = true;
}
/**

47
protected/java/test/org/broadinstitute/sting/gatk/walkers/genotyper/BiasedDownsamplingIntegrationTest.java
View File

@ -102,7 +102,7 @@ public class BiasedDownsamplingIntegrationTest extends WalkerTest {
WalkerTestSpec spec = new WalkerTestSpec(
baseCommand2 + " -I " + ArtificalBAMLocation + bam1 + " -I " + ArtificalBAMLocation + bam2 + " -o %s ", 1,
Arrays.asList("e5fe7246526916af104a6f3e5dd67297"));
Arrays.asList("e2e5a8dd313f8d7e382e7d49dfac59a2"));
executeTest("test contamination on Artificial Contamination (flat) on " + bam1 + " and " + bam2 + " with default downsampling.", spec);
}
@ -115,47 +115,47 @@ public class BiasedDownsamplingIntegrationTest extends WalkerTest {
@Test
public void testFlatContaminationCase1() {
testFlatContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.05, "e5fe7246526916af104a6f3e5dd67297");
testFlatContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.05, "e2e5a8dd313f8d7e382e7d49dfac59a2");
}
@Test
public void testFlatContaminationCase2() {
testFlatContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.1, "ff490f52dc47ed54c5b9bffae73e819d");
testFlatContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.1, "549737002f98775fea8f46e7ea174dde");
}
@Test
public void testFlatContaminationCase3() {
testFlatContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.2, "5efd81caff20fa39da4446ef854d81cc");
testFlatContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.2, "529d82c2a33fcc303a5dc55de2d56979");
}
@Test
public void testFlatContaminationCase4() {
testFlatContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.2.NA11918.reduced.bam", 0.1, "48e6da2d78caa693a177e38b6d35c63f");
testFlatContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.2.NA11918.reduced.bam", 0.1, "b5689972fbb7d230a372ee5f0da1c6d7");
}
@Test
public void testFlatContaminationCase5() {
testFlatContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.2.NA11918.reduced.bam", 0.2, "02dd71427c2ead3c4444d00ad211a79d");
testFlatContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.2.NA11918.reduced.bam", 0.2, "9dceee2e921b53fbc1ce137a7e0b7b74");
}
@Test
public void testFlatContaminationCase6() {
testFlatContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.2.NA11918.reduced.bam", 0.3, "b4271277813dc9146cb247d4495ee843");
testFlatContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.2.NA11918.reduced.bam", 0.3, "d6a74061033503af80dcaea065bfa075");
}
@Test
public void testFlatContaminationCase7() {
testFlatContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.1, "acdf3c236a9d05885d4be890a39aa48d");
testFlatContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.1, "7d1b5efab58a1b8f9d99fcf5af82f15a");
}
@Test
public void testFlatContaminationCase8() {
testFlatContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.2, "8f16a8bd41a18e14e17710f3f1baaaf5");
testFlatContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.2, "a7f8d5c79626aff59d7f426f79d8816e");
}
@Test
public void testFlatContaminationCase9() {
testFlatContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.3, "06110b035fd3f1e87ea4f27b7500096d");
testFlatContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.3, "fcf482398b7c908e3e2d1e4d5da6377b");
}
private void testPerSampleContamination(String bam1, String bam2, String persampleFile, final String md5) {
@ -167,42 +167,42 @@ public class BiasedDownsamplingIntegrationTest extends WalkerTest {
@Test
public void testPerSampleContaminationCase1() {
testPerSampleContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.1.txt", "4510dd668891ad378cd8b6f8da1dc35d");
testPerSampleContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.1.txt", "e00278527a294833259e9e411728e395");
}
@Test
public void testPerSampleContaminationCase2() {
testPerSampleContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.2.txt", "d8a0d0024574da7249d682e145f1c286");
testPerSampleContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.2.txt", "a443e793f0b0e2ffce1b751634d706e2");
}
@Test
public void testPerSampleContaminationCase3() {
testPerSampleContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.3.txt", "2014464dbbaa62279fb79791a1a7ff6a");
testPerSampleContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.3.txt", "e11d83a7815ce757afbcf7689568cb25");
}
@Test
public void testPerSampleContaminationCase4() {
testPerSampleContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.4.txt", "26382eda9dddb910fc7e2bdf3b83f42e");
testPerSampleContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.4.txt", "615042eeeffe042bd1c86279d34f80b6");
}
@Test
public void testPerSampleContaminationCase5() {
testPerSampleContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.1.txt", "ca54f5c4f249d5e461b407696f3851d2");
testPerSampleContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.1.txt", "9bc99fc79ca34744bf26cb19ee4ef44d");
}
@Test
public void testPerSampleContaminationCase6() {
testPerSampleContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.2.txt", "37c8cc33faec5324de6e007180186823");
testPerSampleContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.2.txt", "143626fe5fce765d6c997a64f058a813");
}
@Test
public void testPerSampleContaminationCase7() {
testPerSampleContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.3.txt", "57fa162f9d3487605997cdf6d11448b6");
testPerSampleContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.3.txt", "f2593674cef894eda4e0be9cf3158f57");
}
@Test
public void testPerSampleContaminationCase8() {
testPerSampleContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.4.txt", "4ee1bbf61c5e5c018cc78d521e3ed334");
testPerSampleContamination("NA11918.with.2.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", ArtificalBAMLocation + "contamination.case.4.txt", "fb7ce0740767ae3896b3e552026da1e4");
}
@ -218,7 +218,7 @@ public class BiasedDownsamplingIntegrationTest extends WalkerTest {
final String baseCommand = "-T HaplotypeCaller -R " + b36KGReference + " --no_cmdline_in_header --dbsnp " + b36dbSNP129;
WalkerTestSpec spec = new WalkerTestSpec(
baseCommand + " -I " + validationDataLocation + "NA12878.1kg.p2.chr1_10mb_11_mb.SLX.bam -o %s -L 1:10,000,000-10,010,000 -contamination 0.20", 1,
Arrays.asList("c23c69b3c5a337a818f963c87940b041"));
Arrays.asList("1b2d71f72b49e36325a3cb7aeab37270"));
executeTest("HC calling with contamination_percentage_to_filter 0.20", spec);
}
@ -244,17 +244,20 @@ public class BiasedDownsamplingIntegrationTest extends WalkerTest {
executeTest("HC test contamination on Artificial Contamination (flat) on " + bam1 + " and " + bam2 + " downsampling " + downsampling.toString(), spec);
}
@Test
// TODO -- Yossi will fix with JIRA GSA-765
@Test(enabled = false)
public void testHCFlatContaminationCase1() {
testHCFlatContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.05, "9fc24de333e8cba3f6b41ad8cc1362d8");
}
@Test
// TODO -- Yossi will fix with JIRA GSA-765
@Test(enabled = false)
public void testHCFlatContaminationCase2() {
testHCFlatContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.1, "57b5291ec216bf071b3c80b70f0f69bb");
}
@Test
// TODO -- Yossi will fix with JIRA GSA-765
@Test(enabled = false)
public void testHCFlatContaminationCase3() {
testHCFlatContamination("NA11918.with.1.NA12842.reduced.bam", "NA12842.with.1.NA11918.reduced.bam", 0.2, "c875633954a299c9f082159b5b24aa57");
}

8
protected/java/test/org/broadinstitute/sting/gatk/walkers/genotyper/UnifiedGenotyperGeneralPloidyIntegrationTest.java
View File

@ -106,22 +106,22 @@ public class UnifiedGenotyperGeneralPloidyIntegrationTest extends WalkerTest {
@Test(enabled = true)
public void testBOTH_GGA_Pools() {
PC_LSV_Test(String.format(" -maxAltAlleles 2 -ploidy 24 -gt_mode GENOTYPE_GIVEN_ALLELES -out_mode EMIT_ALL_SITES -alleles %s",LSV_ALLELES),"LSV_BOTH_GGA","BOTH","d1c113a17e36762d27eb27fd12528e52");
PC_LSV_Test(String.format(" -maxAltAlleles 2 -ploidy 24 -gt_mode GENOTYPE_GIVEN_ALLELES -out_mode EMIT_ALL_SITES -alleles %s",LSV_ALLELES),"LSV_BOTH_GGA","BOTH","71f16e19b7d52e8edee46f4121e59f54");
}
@Test(enabled = true)
public void testINDEL_GGA_Pools() {
PC_LSV_Test(String.format(" -maxAltAlleles 1 -ploidy 24 -gt_mode GENOTYPE_GIVEN_ALLELES -out_mode EMIT_ALL_SITES -alleles %s",LSV_ALLELES),"LSV_INDEL_GGA","INDEL","ab043eed87fadbe5761a55a4912b19ac");
PC_LSV_Test(String.format(" -maxAltAlleles 1 -ploidy 24 -gt_mode GENOTYPE_GIVEN_ALLELES -out_mode EMIT_ALL_SITES -alleles %s",LSV_ALLELES),"LSV_INDEL_GGA","INDEL","3f7d763c654f1d708323f369ea4a099b");
}
@Test(enabled = true)
public void testINDEL_maxAltAlleles2_ploidy3_Pools_noRef() {
PC_LSV_Test_NoRef(" -maxAltAlleles 2 -ploidy 3","LSV_INDEL_DISC_NOREF_p3","INDEL","95d48e0680019d5406ff9adb8f2ff3ca");
PC_LSV_Test_NoRef(" -maxAltAlleles 2 -ploidy 3","LSV_INDEL_DISC_NOREF_p3","INDEL","ae70e023e2b5f70d99bde2458f0a1f58");
}
@Test(enabled = true)
public void testINDEL_maxAltAlleles2_ploidy1_Pools_noRef() {
PC_LSV_Test_NoRef(" -maxAltAlleles 2 -ploidy 1","LSV_INDEL_DISC_NOREF_p1","INDEL","8a4ddd64c4e9c42b4a8622582fcfa9c9");
PC_LSV_Test_NoRef(" -maxAltAlleles 2 -ploidy 1","LSV_INDEL_DISC_NOREF_p1","INDEL","fed2c8fc5100a388e9773bb98bf98750");
}
@Test(enabled = true)

43
protected/java/test/org/broadinstitute/sting/gatk/walkers/genotyper/UnifiedGenotyperIntegrationTest.java
View File

@ -76,7 +76,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
public void testMultiSamplePilot1() {
WalkerTest.WalkerTestSpec spec = new WalkerTest.WalkerTestSpec(
baseCommand + " -I " + validationDataLocation + "low_coverage_CEU.chr1.10k-11k.bam -o %s -L 1:10,022,000-10,025,000", 1,
Arrays.asList("847605f4efafef89529fe0e496315edd"));
Arrays.asList("2f15ef1ead56d875a3f1d53772f52b3a"));
executeTest("test MultiSample Pilot1", spec);
}
@ -100,7 +100,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
public void testSingleSamplePilot2() {
WalkerTest.WalkerTestSpec spec = new WalkerTest.WalkerTestSpec(
baseCommand + " -I " + validationDataLocation + "NA12878.1kg.p2.chr1_10mb_11_mb.SLX.bam -o %s -L 1:10,000,000-10,100,000", 1,
Arrays.asList("dff4412a074940d26994f9552476b209"));
Arrays.asList("33ab66c2f062cfa1f7fcc077165f778c"));
executeTest("test SingleSample Pilot2", spec);
}
@ -108,7 +108,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
public void testMultipleSNPAlleles() {
WalkerTest.WalkerTestSpec spec = new WalkerTest.WalkerTestSpec(
"-T UnifiedGenotyper -R " + b37KGReference + " --no_cmdline_in_header -glm BOTH --dbsnp " + b37dbSNP129 + " -I " + privateTestDir + "multiallelic.snps.bam -o %s -L " + privateTestDir + "multiallelic.snps.intervals", 1,
Arrays.asList("35479a79e1ce7c15493bd77e58cadcaa"));
Arrays.asList("9fac00485419878749b03706ae6b852f"));
executeTest("test Multiple SNP alleles", spec);
}
@ -124,7 +124,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
public void testReverseTrim() {
WalkerTest.WalkerTestSpec spec = new WalkerTest.WalkerTestSpec(
"-T UnifiedGenotyper -R " + b37KGReference + " --no_cmdline_in_header -glm INDEL -I " + validationDataLocation + "CEUTrio.HiSeq.b37.chr20.10_11mb.bam -o %s -L 20:10289124 -L 20:10090289", 1,
Arrays.asList("1e61de694b51d7c0f26da5179ee6bb0c"));
Arrays.asList("eb9604b77a7d6baab60c81ac3db5e47b"));
executeTest("test reverse trim", spec);
}
@ -132,7 +132,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
public void testMismatchedPLs() {
WalkerTest.WalkerTestSpec spec = new WalkerTest.WalkerTestSpec(
"-T UnifiedGenotyper -R " + b37KGReference + " --no_cmdline_in_header -glm INDEL -I " + privateTestDir + "mismatchedPLs.bam -o %s -L 1:24020341", 1,
Arrays.asList("935ee705ffe8cc6bf1d9efcceea271c8"));
Arrays.asList("0636c9ad2a83713c8d2cb08154043222"));
executeTest("test mismatched PLs", spec);
}
@ -142,7 +142,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
//
// --------------------------------------------------------------------------------------------------------------
private final static String COMPRESSED_OUTPUT_MD5 = "e6e33f0ebabab027eabed51fe9a08da9";
private final static String COMPRESSED_OUTPUT_MD5 = "d5a7326fdcf6d441b73c381912ad3a2a";
@Test
public void testCompressedOutput() {
@ -268,12 +268,12 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
// --------------------------------------------------------------------------------------------------------------
@Test
public void testHeterozyosity1() {
testHeterozosity( 0.01, "bdc8760d7ae1e01c0510b12c1e6fcfa3" );
testHeterozosity( 0.01, "ffc1f83a045dc09360e11de7a8efd159" );
}
@Test
public void testHeterozyosity2() {
testHeterozosity( 1.0 / 1850, "f508f06a47305e11e62776615cb14fe3" );
testHeterozosity( 1.0 / 1850, "5426a98df9f5fd70aef295d889c4e4f1" );
}
private void testHeterozosity(final double arg, final String md5) {
@ -297,7 +297,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
" -o %s" +
" -L 1:10,000,000-10,100,000",
1,
Arrays.asList("13d91059f58fb50a07a6a34b9438a45b"));
Arrays.asList("68961b19a29ae224059c33ef41cdcb58"));
executeTest(String.format("test multiple technologies"), spec);
}
@ -316,7 +316,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
" -L 1:10,000,000-10,100,000" +
" -baq CALCULATE_AS_NECESSARY",
1,
Arrays.asList("07d8b77a5f6697f3a47a4f1efb0dcf50"));
Arrays.asList("9fcb234f7573209dec4dae86db091efd"));
executeTest(String.format("test calling with BAQ"), spec);
}
@ -335,7 +335,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
" -o %s" +
" -L 1:10,000,000-10,500,000",
1,
Arrays.asList("0f026d2e568172cf32813cc54ea7ba23"));
Arrays.asList("1cb469b9cc8e6c70430021540bf1af8b"));
executeTest(String.format("test indel caller in SLX"), spec);
}
@ -350,7 +350,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
" -minIndelCnt 1" +
" -L 1:10,000,000-10,100,000",
1,
Arrays.asList("e7ad858e9d6617534761918561f3ed4c"));
Arrays.asList("c7e59f9ab718df4c604626a0f51af606"));
executeTest(String.format("test indel caller in SLX with low min allele count"), spec);
}
@ -363,7 +363,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
" -o %s" +
" -L 1:10,000,000-10,500,000",
1,
Arrays.asList("8231ae37b52b927db9fc1e5c221b0ba0"));
Arrays.asList("4bebbe4ed4a7554285a3b4bb7311101c"));
executeTest(String.format("test indel calling, multiple technologies"), spec);
}
@ -373,7 +373,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
WalkerTest.WalkerTestSpec spec = new WalkerTest.WalkerTestSpec(
baseCommandIndels + " --genotyping_mode GENOTYPE_GIVEN_ALLELES -alleles " + privateTestDir + "indelAllelesForUG.vcf -I " + validationDataLocation +
"pilot2_daughters.chr20.10k-11k.bam -o %s -L 20:10,000,000-10,100,000", 1,
Arrays.asList("9430fe36789a791fcff6162f768ae563"));
Arrays.asList("86880ec78755ae91cb5bb34a0631a32c"));
executeTest("test MultiSample Pilot2 indels with alleles passed in", spec);
}
@ -383,21 +383,22 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
baseCommandIndels + " --output_mode EMIT_ALL_SITES --genotyping_mode GENOTYPE_GIVEN_ALLELES -alleles "
+ privateTestDir + "indelAllelesForUG.vcf -I " + validationDataLocation +
"pilot2_daughters.chr20.10k-11k.bam -o %s -L 20:10,000,000-10,100,000", 1,
Arrays.asList("8d8dbf483526b0b309f5728619a74a86"));
Arrays.asList("2584d5e3ade1b548f1fe9cdcafbe1b28"));
executeTest("test MultiSample Pilot2 indels with alleles passed in and emitting all sites", spec);
}
@Test
public void testMultiSampleIndels1() {
// since we're going to test the MD5s with GGA only do one here
WalkerTest.WalkerTestSpec spec1 = new WalkerTest.WalkerTestSpec(
baseCommandIndels + " -I " + validationDataLocation + "low_coverage_CEU.chr1.10k-11k.bam -o %s -L 1:10450700-10551000", 1,
Arrays.asList("a47810de2f6ef8087f4644064a0814bc"));
Arrays.asList(""));
List<File> result = executeTest("test MultiSample Pilot1 CEU indels", spec1).getFirst();
WalkerTest.WalkerTestSpec spec2 = new WalkerTest.WalkerTestSpec(
baseCommandIndels + " --genotyping_mode GENOTYPE_GIVEN_ALLELES -alleles " + result.get(0).getAbsolutePath() + " -I " + validationDataLocation +
"low_coverage_CEU.chr1.10k-11k.bam -o %s -L 1:10450700-10551000", 1,
Arrays.asList("53b8d2b0fa63c5d1019855e8e0db28f0"));
Arrays.asList("08b3a85be00c8f6a4fefd3c671463ecf"));
executeTest("test MultiSample Pilot1 CEU indels using GENOTYPE_GIVEN_ALLELES", spec2);
}
@ -419,7 +420,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
" -o %s" +
" -L 20:10,000,000-10,100,000",
1,
Arrays.asList("1e0d2c15546c3b0959b00ffb75488b56"));
Arrays.asList("8a7966e4b67334bca6083670c5a16b67"));
executeTest(String.format("test UG with base indel quality scores"), spec);
}
@ -453,7 +454,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
public void testMinIndelFraction0() {
WalkerTest.WalkerTestSpec spec = new WalkerTest.WalkerTestSpec(
assessMinIndelFraction + " -minIndelFrac 0.0", 1,
Arrays.asList("db3026c49a3de7a5cb9a3d77635d0706"));
Arrays.asList("556c214366e82e4682e753ce93307a4e"));
executeTest("test minIndelFraction 0.0", spec);
}
@ -461,7 +462,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
public void testMinIndelFraction25() {
WalkerTest.WalkerTestSpec spec = new WalkerTest.WalkerTestSpec(
assessMinIndelFraction + " -minIndelFrac 0.25", 1,
Arrays.asList("7ab8e5ee15ab98d6756b0eea0f4d3798"));
Arrays.asList("1df02b805d9dfbd532fa3632875a989d"));
executeTest("test minIndelFraction 0.25", spec);
}
@ -508,7 +509,7 @@ public class UnifiedGenotyperIntegrationTest extends WalkerTest {
@Test
public void testReducedBamINDELs() {
testReducedCalling("INDEL", "a85c110fcac9574a54c7daccb1e2d5ae");
testReducedCalling("INDEL", "acde5694a74f867256a54a26cbebbf21");
}

26
protected/java/test/org/broadinstitute/sting/gatk/walkers/haplotypecaller/HaplotypeCallerIntegrationTest.java
View File

@ -68,12 +68,12 @@ public class HaplotypeCallerIntegrationTest extends WalkerTest {
@Test
public void testHaplotypeCallerMultiSample() {
HCTest(CEUTRIO_BAM, "", "e623c11a2d0e533a4b7fc7e51a7d7d6f");
HCTest(CEUTRIO_BAM, "", "042b76d4ba0c8f76e2e9cadd1c20d90d");
}
@Test
public void testHaplotypeCallerSingleSample() {
HCTest(NA12878_BAM, "", "fe373ccdd2c40c1bed8d7d3cd61cc9c1");
HCTest(NA12878_BAM, "", "1b39ac32c9cbba26ed60c6b06be81359");
}
@Test(enabled = false)
@ -84,7 +84,7 @@ public class HaplotypeCallerIntegrationTest extends WalkerTest {
@Test
public void testHaplotypeCallerMultiSampleGGA() {
HCTest(CEUTRIO_BAM, "--max_alternate_alleles 3 -gt_mode GENOTYPE_GIVEN_ALLELES -out_mode EMIT_ALL_SITES -alleles " + validationDataLocation + "combined.phase1.chr20.raw.indels.sites.vcf",
"21a0eae5dbed776ebae471f5e83fca3d");
"86ceec507e70d542decdae1d20ed6f82");
}
private void HCTestComplexGGA(String bam, String args, String md5) {
@ -96,13 +96,13 @@ public class HaplotypeCallerIntegrationTest extends WalkerTest {
@Test
public void testHaplotypeCallerMultiSampleGGAComplex() {
HCTestComplexGGA(NA12878_CHR20_BAM, "-L 20:119673-119823 -L 20:121408-121538",
"75e1df0dcf3728fd2b6e4735c4cc88ce");
"76d4c4a112cf60080adf74c3e116d1fb");
}
@Test
@Test(enabled = false) // TODO -- https://jira.broadinstitute.org/browse/GSA-722
public void testHaplotypeCallerMultiSampleGGAMultiAllelic() {
HCTestComplexGGA(NA12878_CHR20_BAM, "-L 20:133041-133161 -L 20:300207-300337",
"efc571f7b64bc13849b0776c4951dadb");
"23a4bfa0300683d8cf2ec16ce96e89ad");
}
private void HCTestComplexVariants(String bam, String args, String md5) {
@ -113,7 +113,7 @@ public class HaplotypeCallerIntegrationTest extends WalkerTest {
@Test
public void testHaplotypeCallerMultiSampleComplex() {
HCTestComplexVariants(privateTestDir + "AFR.complex.variants.bam", "", "3312875416a1a4274a864977effd0afa");
HCTestComplexVariants(privateTestDir + "AFR.complex.variants.bam", "", "fa55ef57354d1f69dabae711bc09b62e");
}
private void HCTestSymbolicVariants(String bam, String args, String md5) {
@ -124,7 +124,7 @@ public class HaplotypeCallerIntegrationTest extends WalkerTest {
@Test
public void testHaplotypeCallerSingleSampleSymbolic() {
HCTestSymbolicVariants(NA12878_CHR20_BAM, "", "23956e572f19ff26d25bbdfaa307675b");
HCTestSymbolicVariants(NA12878_CHR20_BAM, "", "855827f901b63b41dcd37dd49dd3a1ac");
}
private void HCTestIndelQualityScores(String bam, String args, String md5) {
@ -135,7 +135,7 @@ public class HaplotypeCallerIntegrationTest extends WalkerTest {
@Test
public void testHaplotypeCallerSingleSampleIndelQualityScores() {
HCTestIndelQualityScores(NA12878_RECALIBRATED_BAM, "", "1255f466aa2d288f015cd55d8fece1ac");
HCTestIndelQualityScores(NA12878_RECALIBRATED_BAM, "", "c0ac5a1f75c66052b19684eb37c088cb");
}
// That problem bam came from a user on the forum and it spotted a problem where the ReadClipper
@ -146,14 +146,14 @@ public class HaplotypeCallerIntegrationTest extends WalkerTest {
@Test
public void HCTestProblematicReadsModifiedInActiveRegions() {
final String base = String.format("-T HaplotypeCaller -R %s -I %s", REF, privateTestDir + "haplotype-problem-4.bam") + " --no_cmdline_in_header -o %s -minPruning 3 -L 4:49139026-49139965";
final WalkerTestSpec spec = new WalkerTestSpec(base, Arrays.asList("5ac992d47aa6b7c220e5bb7c07444de1"));
final WalkerTestSpec spec = new WalkerTestSpec(base, Arrays.asList("866406b43d22a262b2d852e7252eb430"));
executeTest("HCTestProblematicReadsModifiedInActiveRegions: ", spec);
}
@Test
public void HCTestStructuralIndels() {
final String base = String.format("-T HaplotypeCaller -R %s -I %s", REF, privateTestDir + "AFR.structural.indels.bam") + " --no_cmdline_in_header -o %s -minPruning 6 -L 20:8187565-8187800 -L 20:18670537-18670730";
final WalkerTestSpec spec = new WalkerTestSpec(base, Arrays.asList("bd8c30b99d0ac7c4108e3d88c272a996"));
final WalkerTestSpec spec = new WalkerTestSpec(base, Arrays.asList("a77ac53d67937feebfba22a9336a5421"));
executeTest("HCTestStructuralIndels: ", spec);
}
@ -175,7 +175,7 @@ public class HaplotypeCallerIntegrationTest extends WalkerTest {
public void HCTestReducedBam() {
WalkerTest.WalkerTestSpec spec = new WalkerTest.WalkerTestSpec(
"-T HaplotypeCaller -R " + b37KGReference + " --no_cmdline_in_header -I " + privateTestDir + "bamExample.ReducedRead.ADAnnotation.bam -o %s -L 1:67,225,396-67,288,518", 1,
Arrays.asList("0fa19ec5cf737a3445544b59ecc995e9"));
Arrays.asList("9f0bb0b97857c66937de39670e195d00"));
executeTest("HC calling on a ReducedRead BAM", spec);
}
@ -183,7 +183,7 @@ public class HaplotypeCallerIntegrationTest extends WalkerTest {
public void testReducedBamWithReadsNotFullySpanningDeletion() {
WalkerTest.WalkerTestSpec spec = new WalkerTest.WalkerTestSpec(
"-T HaplotypeCaller -R " + b37KGReference + " --no_cmdline_in_header -I " + privateTestDir + "reduced.readNotFullySpanningDeletion.bam -o %s -L 1:167871297", 1,
Arrays.asList("5f4cbdcc9bffee6bba258dfac89492ed"));
Arrays.asList("255947f39455c87c561be4aee4cab651"));
executeTest("test calling on a ReducedRead BAM where the reads do not fully span a deletion", spec);
}
}

388
protected/java/test/org/broadinstitute/sting/utils/pairhmm/PairHMMUnitTest.java
View File

@ -52,19 +52,29 @@ package org.broadinstitute.sting.utils.pairhmm;
import org.broadinstitute.sting.BaseTest;
import org.broadinstitute.sting.gatk.GenomeAnalysisEngine;
import org.broadinstitute.sting.utils.BaseUtils;
import org.broadinstitute.sting.utils.MathUtils;
import org.broadinstitute.sting.utils.QualityUtils;
import org.broadinstitute.sting.utils.Utils;
import org.testng.Assert;
import org.testng.annotations.DataProvider;
import org.testng.annotations.Test;
import java.util.*;
import java.util.ArrayList;
import java.util.Arrays;
import java.util.List;
import java.util.Random;
public class PairHMMUnitTest extends BaseTest {
private final static boolean ALLOW_READS_LONGER_THAN_HAPLOTYPE = true;
private final static boolean DEBUG = false;
final static boolean EXTENSIVE_TESTING = true;
PairHMM exactHMM = new ExactPairHMM(); // the log truth implementation
PairHMM originalHMM = new OriginalPairHMM(); // the reference implementation
PairHMM cachingHMM = new CachingPairHMM();
PairHMM loglessHMM = new LoglessCachingPairHMM();
final PairHMM exactHMM = new Log10PairHMM(true); // the log truth implementation
final PairHMM originalHMM = new Log10PairHMM(false); // the reference implementation
final PairHMM loglessHMM = new LoglessCachingPairHMM();
private List<PairHMM> getHMMs() {
return Arrays.asList(exactHMM, originalHMM, loglessHMM);
}
// --------------------------------------------------------------------------------
//
@ -99,8 +109,18 @@ public class PairHMMUnitTest extends BaseTest {
readBasesWithContext = asBytes(read, false, false);
}
public double expectedLogL() {
return (expectedQual / -10.0) + 0.03 ;
public double expectedLogL(final PairHMM hmm) {
return (expectedQual / -10.0) + 0.03 +
hmm.getNPotentialXStartsLikelihoodPenaltyLog10(refBasesWithContext.length, readBasesWithContext.length);
}
public double getTolerance(final PairHMM hmm) {
if ( hmm instanceof LoglessCachingPairHMM )
return toleranceFromExact();
if ( hmm instanceof Log10PairHMM ) {
return ((Log10PairHMM)hmm).isDoingExactLog10Calculations() ? toleranceFromExact() : toleranceFromReference();
} else
return toleranceFromTheoretical();
}
public double toleranceFromTheoretical() {
@ -108,7 +128,7 @@ public class PairHMMUnitTest extends BaseTest {
}
public double toleranceFromReference() {
return 1E-4;
return 1E-3; // has to be very tolerant -- this approximation is quite approximate
}
public double toleranceFromExact() {
@ -220,10 +240,10 @@ public class PairHMMUnitTest extends BaseTest {
for( int iii = 0; iii < readSize; iii++) {
read += (char) BaseUtils.BASES[random.nextInt(4)];
}
new BasicLikelihoodTestProvider(ref, read, baseQual, indelQual, indelQual, -0, gcp);
new BasicLikelihoodTestProvider(ref, read, baseQual, indelQual, indelQual, -0, gcp, true, false);
new BasicLikelihoodTestProvider(ref, read, baseQual, indelQual, indelQual, -0, gcp, false, true);
new BasicLikelihoodTestProvider(ref, read, baseQual, indelQual, indelQual, -0, gcp, true, true);
for ( final boolean leftFlank : Arrays.asList(true, false) )
for ( final boolean rightFlank : Arrays.asList(true, false) )
new BasicLikelihoodTestProvider(ref, read, baseQual, indelQual, indelQual, -0, gcp, leftFlank, rightFlank);
}
}
}
@ -233,32 +253,38 @@ public class PairHMMUnitTest extends BaseTest {
return BasicLikelihoodTestProvider.getTests(BasicLikelihoodTestProvider.class);
}
@Test(dataProvider = "BasicLikelihoodTestProvider", enabled = true)
@Test(enabled = !DEBUG, dataProvider = "BasicLikelihoodTestProvider")
public void testBasicLikelihoods(BasicLikelihoodTestProvider cfg) {
double exactLogL = cfg.calcLogL( exactHMM, true );
double calculatedLogL = cfg.calcLogL( originalHMM, true );
double optimizedLogL = cfg.calcLogL( cachingHMM, true );
double loglessLogL = cfg.calcLogL( loglessHMM, true );
double expectedLogL = cfg.expectedLogL();
//logger.warn(String.format("Test: logL calc=%.2f optimized=%.2f logless=%.2f expected=%.2f for %s", calculatedLogL, optimizedLogL, loglessLogL, expectedLogL, cfg.toString()));
Assert.assertEquals(exactLogL, expectedLogL, cfg.toleranceFromTheoretical());
Assert.assertEquals(calculatedLogL, expectedLogL, cfg.toleranceFromTheoretical());
Assert.assertEquals(optimizedLogL, calculatedLogL, cfg.toleranceFromReference());
Assert.assertEquals(loglessLogL, exactLogL, cfg.toleranceFromExact());
if ( ALLOW_READS_LONGER_THAN_HAPLOTYPE || cfg.read.length() <= cfg.ref.length() ) {
final double exactLogL = cfg.calcLogL( exactHMM, true );
for ( final PairHMM hmm : getHMMs() ) {
double actualLogL = cfg.calcLogL( hmm, true );
double expectedLogL = cfg.expectedLogL(hmm);
// compare to our theoretical expectation with appropriate tolerance
Assert.assertEquals(actualLogL, expectedLogL, cfg.toleranceFromTheoretical(), "Failed with hmm " + hmm);
// compare to the exact reference implementation with appropriate tolerance
Assert.assertEquals(actualLogL, exactLogL, cfg.getTolerance(hmm), "Failed with hmm " + hmm);
Assert.assertTrue(MathUtils.goodLog10Probability(actualLogL), "Bad log10 likelihood " + actualLogL);
}
}
}
@Test(dataProvider = "OptimizedLikelihoodTestProvider", enabled = true)
@Test(enabled = !DEBUG, dataProvider = "OptimizedLikelihoodTestProvider")
public void testOptimizedLikelihoods(BasicLikelihoodTestProvider cfg) {
double exactLogL = cfg.calcLogL( exactHMM, false );
double calculatedLogL = cfg.calcLogL( originalHMM, false );
double optimizedLogL = cfg.calcLogL( cachingHMM, false );
double loglessLogL = cfg.calcLogL( loglessHMM, false );
//logger.warn(String.format("Test: logL calc=%.2f optimized=%.2f logless=%.2f expected=%.2f for %s", calculatedLogL, optimizedLogL, loglessLogL, expectedLogL, cfg.toString()));
Assert.assertEquals(optimizedLogL, calculatedLogL, cfg.toleranceFromReference(), String.format("Test: logL calc=%.2f optimized=%.2f logless=%.2f expected=%.2f for %s", calculatedLogL, optimizedLogL, loglessLogL, exactLogL, cfg.toString()));
Assert.assertEquals(loglessLogL, exactLogL, cfg.toleranceFromExact(), String.format("Test: logL calc=%.2f optimized=%.2f logless=%.2f expected=%.2f for %s", calculatedLogL, optimizedLogL, loglessLogL, exactLogL, cfg.toString()));
if ( ALLOW_READS_LONGER_THAN_HAPLOTYPE || cfg.read.length() <= cfg.ref.length() ) {
double exactLogL = cfg.calcLogL( exactHMM, false );
for ( final PairHMM hmm : getHMMs() ) {
double calculatedLogL = cfg.calcLogL( hmm, false );
// compare to the exact reference implementation with appropriate tolerance
Assert.assertEquals(calculatedLogL, exactLogL, cfg.getTolerance(hmm), String.format("Test: logL calc=%.2f expected=%.2f for %s with hmm %s", calculatedLogL, exactLogL, cfg.toString(), hmm));
Assert.assertTrue(MathUtils.goodLog10Probability(calculatedLogL), "Bad log10 likelihood " + calculatedLogL);
}
}
}
@Test
@Test(enabled = !DEBUG)
public void testMismatchInEveryPositionInTheReadWithCenteredHaplotype() {
byte[] haplotype1 = "TTCTCTTCTGTTGTGGCTGGTT".getBytes();
@ -285,11 +311,12 @@ public class PairHMMUnitTest extends BaseTest {
System.out.format("H:%s\nR: %s\n Pos:%d Result:%4.2f\n",new String(haplotype1), new String(mread), k,res1);
Assert.assertEquals(res1, -2.0, 1e-2);
// - log10 is because of number of start positions
Assert.assertEquals(res1, -2.0 - Math.log10(originalHMM.getNPotentialXStarts(haplotype1.length, mread.length)), 1e-2);
}
}
@Test
@Test(enabled = ! DEBUG)
public void testMismatchInEveryPositionInTheRead() {
byte[] haplotype1 = "TTCTCTTCTGTTGTGGCTGGTT".getBytes();
@ -316,7 +343,298 @@ public class PairHMMUnitTest extends BaseTest {
System.out.format("H:%s\nR: %s\n Pos:%d Result:%4.2f\n",new String(haplotype1), new String(mread), k,res1);
Assert.assertEquals(res1, -2.0, 1e-2);
// - log10 is because of number of start positions
Assert.assertEquals(res1, -2.0 - Math.log10(originalHMM.getNPotentialXStarts(haplotype1.length, mread.length)), 1e-2);
}
}
@DataProvider(name = "HMMProvider")
public Object[][] makeHMMProvider() {
List<Object[]> tests = new ArrayList<Object[]>();
for ( final int readSize : Arrays.asList(1, 2, 5, 10) ) {
for ( final int refSize : Arrays.asList(1, 2, 5, 10) ) {
if ( refSize > readSize ) {
for ( final PairHMM hmm : getHMMs() )
tests.add(new Object[]{hmm, readSize, refSize});
}
}
}
return tests.toArray(new Object[][]{});
}
@Test(enabled = !DEBUG, dataProvider = "HMMProvider")
void testMultipleReadMatchesInHaplotype(final PairHMM hmm, final int readSize, final int refSize) {
byte[] readBases = Utils.dupBytes((byte)'A', readSize);
byte[] refBases = ("CC" + new String(Utils.dupBytes((byte)'A', refSize)) + "GGA").getBytes();
byte baseQual = 20;
byte insQual = 37;
byte delQual = 37;
byte gcp = 10;
hmm.initialize(readBases.length, refBases.length);
double d = hmm.computeReadLikelihoodGivenHaplotypeLog10( refBases, readBases,
Utils.dupBytes(baseQual, readBases.length),
Utils.dupBytes(insQual, readBases.length),
Utils.dupBytes(delQual, readBases.length),
Utils.dupBytes(gcp, readBases.length), 0, true);
Assert.assertTrue(d <= 0.0, "Likelihoods should be <= 0 but got "+ d);
}
@Test(enabled = !DEBUG, dataProvider = "HMMProvider")
void testAllMatchingRead(final PairHMM hmm, final int readSize, final int refSize) {
byte[] readBases = Utils.dupBytes((byte)'A', readSize);
byte[] refBases = Utils.dupBytes((byte)'A', refSize);
byte baseQual = 20;
byte insQual = 100;
byte delQual = 100;
byte gcp = 100;
hmm.initialize(readBases.length, refBases.length);
double d = hmm.computeReadLikelihoodGivenHaplotypeLog10( refBases, readBases,
Utils.dupBytes(baseQual, readBases.length),
Utils.dupBytes(insQual, readBases.length),
Utils.dupBytes(delQual, readBases.length),
Utils.dupBytes(gcp, readBases.length), 0, true);
final double expected = Math.log10(Math.pow(1.0 - QualityUtils.qualToErrorProb(baseQual), readBases.length));
Assert.assertEquals(d, expected, 1e-3, "Likelihoods should sum to just the error prob of the read");
}
@DataProvider(name = "HMMProviderWithBigReads")
public Object[][] makeBigReadHMMProvider() {
List<Object[]> tests = new ArrayList<Object[]>();
final String read1 = "ACCAAGTAGTCACCGT";
final String ref1 = "ACCAAGTAGTCACCGTAACG";
for ( final int nReadCopies : Arrays.asList(1, 2, 10, 20, 50) ) {
for ( final int nRefCopies : Arrays.asList(1, 2, 10, 20, 100) ) {
if ( nRefCopies > nReadCopies ) {
for ( final PairHMM hmm : getHMMs() ) {
final String read = Utils.dupString(read1, nReadCopies);
final String ref = Utils.dupString(ref1, nRefCopies);
tests.add(new Object[]{hmm, read, ref});
}
}
}
}
return tests.toArray(new Object[][]{});
}
@Test(enabled = !DEBUG, dataProvider = "HMMProviderWithBigReads")
void testReallyBigReads(final PairHMM hmm, final String read, final String ref) {
byte[] readBases = read.getBytes();
byte[] refBases = ref.getBytes();
byte baseQual = 30;
byte insQual = 40;
byte delQual = 40;
byte gcp = 10;
hmm.initialize(readBases.length, refBases.length);
double d = hmm.computeReadLikelihoodGivenHaplotypeLog10( refBases, readBases,
Utils.dupBytes(baseQual, readBases.length),
Utils.dupBytes(insQual, readBases.length),
Utils.dupBytes(delQual, readBases.length),
Utils.dupBytes(gcp, readBases.length), 0, true);
Assert.assertTrue(MathUtils.goodLog10Probability(d), "Likelihoods = " + d +" was bad for a read with " + read.length() + " bases and ref with " + ref.length() + " bases");
}
@Test(enabled = !DEBUG)
void testPreviousBadValue() {
byte[] readBases = "A".getBytes();
byte[] refBases = "AT".getBytes();
byte baseQual = 30;
byte insQual = 40;
byte delQual = 40;
byte gcp = 10;
exactHMM.initialize(readBases.length, refBases.length);
double d = exactHMM.computeReadLikelihoodGivenHaplotypeLog10( refBases, readBases,
Utils.dupBytes(baseQual, readBases.length),
Utils.dupBytes(insQual, readBases.length),
Utils.dupBytes(delQual, readBases.length),
Utils.dupBytes(gcp, readBases.length), 0, true);
//exactHMM.dumpMatrices();
loglessHMM.initialize(readBases.length, refBases.length);
double logless = loglessHMM.computeReadLikelihoodGivenHaplotypeLog10( refBases, readBases,
Utils.dupBytes(baseQual, readBases.length),
Utils.dupBytes(insQual, readBases.length),
Utils.dupBytes(delQual, readBases.length),
Utils.dupBytes(gcp, readBases.length), 0, true);
loglessHMM.dumpMatrices();
}
@DataProvider(name = "JustHMMProvider")
public Object[][] makeJustHMMProvider() {
List<Object[]> tests = new ArrayList<Object[]>();
for ( final PairHMM hmm : getHMMs() ) {
tests.add(new Object[]{hmm});
}
return tests.toArray(new Object[][]{});
}
@Test(enabled = !DEBUG, dataProvider = "JustHMMProvider")
void testMaxLengthsBiggerThanProvidedRead(final PairHMM hmm) {
for ( int nExtraMaxSize = 0; nExtraMaxSize < 100; nExtraMaxSize++ ) {
byte[] readBases = "CTATCTTAGTAAGCCCCCATACCTGCAAATTTCAGGATGTCTCCTCCAAAAATCAACA".getBytes();
byte[] refBases = "CTATCTTAGTAAGCCCCCATACCTGCAAATTTCAGGATGTCTCCTCCAAAAATCAAAACTTCTGAGAAAAAAAAAAAAAATTAAATCAAACCCTGATTCCTTAAAGGTAGTAAAAAAACATCATTCTTTCTTAGTGGAATAGAAACTAGGTCAAAAGAACAGTGATTC".getBytes();
byte gcp = 10;
byte[] quals = new byte[]{35,34,31,32,35,34,32,31,36,30,31,32,36,34,33,32,32,32,33,32,30,35,33,35,36,36,33,33,33,32,32,32,37,33,36,35,33,32,34,31,36,35,35,35,35,33,34,31,31,30,28,27,26,29,26,25,29,29};
byte[] insQual = new byte[]{46,46,46,46,46,47,45,46,45,48,47,44,45,48,46,43,43,42,48,48,45,47,47,48,48,47,48,45,38,47,45,39,47,48,47,47,48,46,49,48,49,48,46,47,48,44,44,43,39,32,34,36,46,48,46,44,45,45};
byte[] delQual = new byte[]{44,44,44,43,45,44,43,42,45,46,45,43,44,47,45,40,40,40,45,46,43,45,45,44,46,46,46,43,35,44,43,36,44,45,46,46,44,44,47,43,47,45,45,45,46,45,45,46,44,35,35,35,45,47,45,44,44,43};
final int maxHaplotypeLength = refBases.length + nExtraMaxSize;
final int maxReadLength = readBases.length + nExtraMaxSize;
hmm.initialize(maxReadLength, maxHaplotypeLength);
double d = hmm.computeReadLikelihoodGivenHaplotypeLog10( refBases, readBases,
quals,
insQual,
delQual,
Utils.dupBytes(gcp, readBases.length), 0, true);
Assert.assertTrue(MathUtils.goodLog10Probability(d), "Likelihoods = " + d +" was bad for a read with " + readBases.length + " bases and ref with " + refBases.length + " bases");
}
}
@DataProvider(name = "HaplotypeIndexingProvider")
public Object[][] makeHaplotypeIndexingProvider() {
List<Object[]> tests = new ArrayList<Object[]>();
final String root1 = "ACGTGTCAAACCGGGTT";
final String root2 = "ACGTGTCACACTGGGTT"; // differs in two locations
final String read1 = "ACGTGTCACACTGGATT"; // 1 diff from 2, 2 diff from root1
final String read2 = root1; // same as root1
final String read3 = root2; // same as root2
final String read4 = "ACGTGTCACACTGGATTCGAT";
final String read5 = "CCAGTAACGTGTCACACTGGATTCGAT";
// for ( final String read : Arrays.asList(read2) ) {
for ( final String read : Arrays.asList(read1, read2, read3, read4, read5) ) {
for ( final PairHMM hmm : getHMMs() ) {
// int readLength = read.length(); {
for ( int readLength = 10; readLength < read.length(); readLength++ ) {
final String myRead = read.substring(0, readLength);
tests.add(new Object[]{hmm, root1, root2, myRead});
}
}
}
return tests.toArray(new Object[][]{});
}
@Test(enabled = !DEBUG, dataProvider = "HaplotypeIndexingProvider")
void testHaplotypeIndexing(final PairHMM hmm, final String root1, final String root2, final String read) {
final double TOLERANCE = 1e-9;
final String prefix = "AACCGGTTTTTGGGCCCAAACGTACGTACAGTTGGTCAACATCGATCAGGTTCCGGAGTAC";
final int maxReadLength = read.length();
final int maxHaplotypeLength = prefix.length() + root1.length();
// the initialization occurs once, at the start of the evalution of reads
hmm.initialize(maxReadLength, maxHaplotypeLength);
for ( int prefixStart = prefix.length(); prefixStart >= 0; prefixStart-- ) {
final String myPrefix = prefix.substring(prefixStart, prefix.length());
final String hap1 = myPrefix + root1;
final String hap2 = myPrefix + root2;
final int hapStart = PairHMM.findFirstPositionWhereHaplotypesDiffer(hap1.getBytes(), hap2.getBytes());
final double actual1 = testHaplotypeIndexingCalc(hmm, hap1, read, 0, true);
final double actual2 = testHaplotypeIndexingCalc(hmm, hap2, read, hapStart, false);
final double expected2 = testHaplotypeIndexingCalc(hmm, hap2, read, 0, true);
Assert.assertEquals(actual2, expected2, TOLERANCE, "Caching calculation failed for read " + read + " against haplotype with prefix '" + myPrefix
+ "' expected " + expected2 + " but got " + actual2 + " with hapStart of " + hapStart);
}
}
private double testHaplotypeIndexingCalc(final PairHMM hmm, final String hap, final String read, final int hapStart, final boolean recache) {
final byte[] readBases = read.getBytes();
final byte[] baseQuals = Utils.dupBytes((byte)30, readBases.length);
final byte[] insQuals = Utils.dupBytes((byte)45, readBases.length);
final byte[] delQuals = Utils.dupBytes((byte)40, readBases.length);
final byte[] gcp = Utils.dupBytes((byte)10, readBases.length);
double d = hmm.computeReadLikelihoodGivenHaplotypeLog10(
hap.getBytes(), readBases, baseQuals, insQuals, delQuals, gcp,
hapStart, recache);
Assert.assertTrue(MathUtils.goodLog10Probability(d), "Likelihoods = " + d + " was bad for read " + read + " and ref " + hap + " with hapStart " + hapStart);
return d;
}
@Test(enabled = !DEBUG)
public void testFindFirstPositionWhereHaplotypesDiffer() {
for ( int haplotypeSize1 = 10; haplotypeSize1 < 30; haplotypeSize1++ ) {
for ( int haplotypeSize2 = 10; haplotypeSize2 < 50; haplotypeSize2++ ) {
final int maxLength = Math.max(haplotypeSize1, haplotypeSize2);
final int minLength = Math.min(haplotypeSize1, haplotypeSize2);
for ( int differingSite = 0; differingSite < maxLength + 1; differingSite++) {
for ( final boolean oneIsDiff : Arrays.asList(true, false) ) {
final byte[] hap1 = Utils.dupBytes((byte)'A', haplotypeSize1);
final byte[] hap2 = Utils.dupBytes((byte)'A', haplotypeSize2);
final int expected = oneIsDiff
? makeDiff(hap1, differingSite, minLength)
: makeDiff(hap2, differingSite, minLength);
final int actual = PairHMM.findFirstPositionWhereHaplotypesDiffer(hap1, hap2);
Assert.assertEquals(actual, expected, "Bad differing site for " + new String(hap1) + " vs. " + new String(hap2));
}
}
}
}
}
private int makeDiff(final byte[] bytes, final int site, final int minSize) {
if ( site < bytes.length ) {
bytes[site] = 'C';
return Math.min(site, minSize);
} else
return minSize;
}
@DataProvider(name = "UninitializedHMMs")
public Object[][] makeUninitializedHMMs() {
List<Object[]> tests = new ArrayList<Object[]>();
tests.add(new Object[]{new LoglessCachingPairHMM()});
tests.add(new Object[]{new Log10PairHMM(true)});
return tests.toArray(new Object[][]{});
}
@Test(enabled = true, expectedExceptions = IllegalStateException.class, dataProvider = "UninitializedHMMs")
public void testNoInitializeCall(final PairHMM hmm) {
byte[] readBases = "A".getBytes();
byte[] refBases = "AT".getBytes();
byte[] baseQuals = Utils.dupBytes((byte)30, readBases.length);
// didn't call initialize => should exception out
double d = hmm.computeReadLikelihoodGivenHaplotypeLog10( refBases, readBases,
baseQuals, baseQuals, baseQuals, baseQuals, 0, true);
}
@Test(enabled = true, expectedExceptions = IllegalArgumentException.class, dataProvider = "JustHMMProvider")
public void testHapTooLong(final PairHMM hmm) {
byte[] readBases = "AAA".getBytes();
byte[] refBases = "AAAT".getBytes();
byte[] baseQuals = Utils.dupBytes((byte)30, readBases.length);
hmm.initialize(3, 3);
double d = hmm.computeReadLikelihoodGivenHaplotypeLog10( refBases, readBases,
baseQuals, baseQuals, baseQuals, baseQuals, 0, true);
}
@Test(enabled = true, expectedExceptions = IllegalArgumentException.class, dataProvider = "JustHMMProvider")
public void testReadTooLong(final PairHMM hmm) {
byte[] readBases = "AAA".getBytes();
byte[] refBases = "AAAT".getBytes();
byte[] baseQuals = Utils.dupBytes((byte)30, readBases.length);
hmm.initialize(2, 3);
double d = hmm.computeReadLikelihoodGivenHaplotypeLog10( refBases, readBases,
baseQuals, baseQuals, baseQuals, baseQuals, 0, true);
}
}

16
public/java/src/org/broadinstitute/sting/utils/Utils.java
View File

@ -308,6 +308,22 @@ public class Utils {
return join(separator, Arrays.asList(objects));
}
/**
* Create a new string thats a n duplicate copies of s
* @param s the string to duplicate
* @param nCopies how many copies?
* @return a string
*/
public static String dupString(final String s, int nCopies) {
if ( s == null || s.equals("") ) throw new IllegalArgumentException("Bad s " + s);
if ( nCopies < 1 ) throw new IllegalArgumentException("nCopies must be >= 1 but got " + nCopies);
final StringBuilder b = new StringBuilder();
for ( int i = 0; i < nCopies; i++ )
b.append(s);
return b.toString();
}
public static String dupString(char c, int nCopies) {
char[] chars = new char[nCopies];
Arrays.fill(chars, c);

132
public/java/src/org/broadinstitute/sting/utils/pairhmm/ExactPairHMM.java
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@ -1,132 +0,0 @@
/*
* Copyright (c) 2012 The Broad Institute
*
* Permission is hereby granted, free of charge, to any person
* obtaining a copy of this software and associated documentation
* files (the "Software"), to deal in the Software without
* restriction, including without limitation the rights to use,
* copy, modify, merge, publish, distribute, sublicense, and/or sell
* copies of the Software, and to permit persons to whom the
* Software is furnished to do so, subject to the following
* conditions:
*
* The above copyright notice and this permission notice shall be
* included in all copies or substantial portions of the Software.
*
* THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
* EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES
* OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND
* NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT
* HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY,
* WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING
* FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR
* THE USE OR OTHER DEALINGS IN THE SOFTWARE.
*/
package org.broadinstitute.sting.utils.pairhmm;
import com.google.java.contract.Ensures;
import com.google.java.contract.Requires;
import org.broadinstitute.sting.utils.MathUtils;
import org.broadinstitute.sting.utils.QualityUtils;
import java.util.ArrayList;
import java.util.Arrays;
/**
* Created with IntelliJ IDEA.
* User: rpoplin
* Date: 10/16/12
*/
public class ExactPairHMM extends PairHMM {
@Override
public void initialize( final int READ_MAX_LENGTH, final int HAPLOTYPE_MAX_LENGTH ) {
// M, X, and Y arrays are of size read and haplotype + 1 because of an extra column for initial conditions and + 1 to consider the final base in a non-global alignment
final int X_METRIC_LENGTH = READ_MAX_LENGTH + 2;
final int Y_METRIC_LENGTH = HAPLOTYPE_MAX_LENGTH + 2;
matchMetricArray = new double[X_METRIC_LENGTH][Y_METRIC_LENGTH];
XMetricArray = new double[X_METRIC_LENGTH][Y_METRIC_LENGTH];
YMetricArray = new double[X_METRIC_LENGTH][Y_METRIC_LENGTH];
for( int iii=0; iii < X_METRIC_LENGTH; iii++ ) {
Arrays.fill(matchMetricArray[iii], Double.NEGATIVE_INFINITY);
Arrays.fill(XMetricArray[iii], Double.NEGATIVE_INFINITY);
Arrays.fill(YMetricArray[iii], Double.NEGATIVE_INFINITY);
}
// the initial condition
matchMetricArray[1][1] = 0.0; // Math.log10(1.0);
}
@Override
public double computeReadLikelihoodGivenHaplotypeLog10( final byte[] haplotypeBases,
final byte[] readBases,
final byte[] readQuals,
final byte[] insertionGOP,
final byte[] deletionGOP,
final byte[] overallGCP,
final int hapStartIndex,
final boolean recacheReadValues ) {
// M, X, and Y arrays are of size read and haplotype + 1 because of an extra column for initial conditions and + 1 to consider the final base in a non-global alignment
final int X_METRIC_LENGTH = readBases.length + 2;
final int Y_METRIC_LENGTH = haplotypeBases.length + 2;
// ensure that all the qual scores have valid values
for( int iii = 0; iii < readQuals.length; iii++ ) {
readQuals[iii] = ( readQuals[iii] < QualityUtils.MIN_USABLE_Q_SCORE ? QualityUtils.MIN_USABLE_Q_SCORE : (readQuals[iii] > MAX_CACHED_QUAL ? MAX_CACHED_QUAL : readQuals[iii]) );
}
// simple rectangular version of update loop, slow
for( int iii = 1; iii < X_METRIC_LENGTH; iii++ ) {
for( int jjj = hapStartIndex + 1; jjj < Y_METRIC_LENGTH; jjj++ ) {
if( (iii == 1 && jjj == 1) ) { continue; }
updateCell(iii, jjj, haplotypeBases, readBases, readQuals, insertionGOP, deletionGOP, overallGCP,
matchMetricArray, XMetricArray, YMetricArray);
}
}
// final probability is the log10 sum of the last element in all three state arrays
final int endI = X_METRIC_LENGTH - 1;
final int endJ = Y_METRIC_LENGTH - 1;
return MathUtils.log10sumLog10(new double[]{matchMetricArray[endI][endJ], XMetricArray[endI][endJ], YMetricArray[endI][endJ]});
}
private void updateCell( final int indI, final int indJ, final byte[] haplotypeBases, final byte[] readBases,
final byte[] readQuals, final byte[] insertionGOP, final byte[] deletionGOP, final byte[] overallGCP,
final double[][] matchMetricArray, final double[][] XMetricArray, final double[][] YMetricArray ) {
// the read and haplotype indices are offset by one because the state arrays have an extra column to hold the initial conditions
final int im1 = indI - 1;
final int jm1 = indJ - 1;
// update the match array
double pBaseReadLog10 = 0.0; // Math.log10(1.0);
if( im1 > 0 && jm1 > 0 ) { // the emission probability is applied when leaving the state
final byte x = readBases[im1-1];
final byte y = haplotypeBases[jm1-1];
final byte qual = readQuals[im1-1];
pBaseReadLog10 = ( x == y || x == (byte) 'N' || y == (byte) 'N' ? QualityUtils.qualToProbLog10(qual) : QualityUtils.qualToErrorProbLog10(qual) );
}
final int qualIndexGOP = ( im1 == 0 ? DEFAULT_GOP + DEFAULT_GOP : ( insertionGOP[im1-1] + deletionGOP[im1-1] > MAX_CACHED_QUAL ? MAX_CACHED_QUAL : insertionGOP[im1-1] + deletionGOP[im1-1]) );
final double d0 = QualityUtils.qualToProbLog10((byte)qualIndexGOP);
final double e0 = ( im1 == 0 ? QualityUtils.qualToProbLog10(DEFAULT_GCP) : QualityUtils.qualToProbLog10(overallGCP[im1-1]) );
matchMetricArray[indI][indJ] = pBaseReadLog10 + MathUtils.log10sumLog10(new double[]{matchMetricArray[indI-1][indJ-1] + d0, XMetricArray[indI-1][indJ-1] + e0, YMetricArray[indI-1][indJ-1] + e0});
// update the X (insertion) array
final double d1 = ( im1 == 0 ? QualityUtils.qualToErrorProbLog10(DEFAULT_GOP) : QualityUtils.qualToErrorProbLog10(insertionGOP[im1-1]) );
final double e1 = ( im1 == 0 ? QualityUtils.qualToErrorProbLog10(DEFAULT_GCP) : QualityUtils.qualToErrorProbLog10(overallGCP[im1-1]) );
final double qBaseReadLog10 = 0.0; // Math.log10(1.0) -- we don't have an estimate for this emission probability so assume q=1.0
XMetricArray[indI][indJ] = qBaseReadLog10 + MathUtils.log10sumLog10(new double[]{matchMetricArray[indI-1][indJ] + d1, XMetricArray[indI-1][indJ] + e1});
// update the Y (deletion) array, with penalty of zero on the left and right flanks to allow for a local alignment within the haplotype
final double d2 = ( im1 == 0 || im1 == readBases.length ? 0.0 : QualityUtils.qualToErrorProbLog10(deletionGOP[im1-1]) );
final double e2 = ( im1 == 0 || im1 == readBases.length ? 0.0 : QualityUtils.qualToErrorProbLog10(overallGCP[im1-1]) );
final double qBaseRefLog10 = 0.0; // Math.log10(1.0) -- we don't have an estimate for this emission probability so assume q=1.0
YMetricArray[indI][indJ] = qBaseRefLog10 + MathUtils.log10sumLog10(new double[]{matchMetricArray[indI][indJ-1] + d2, YMetricArray[indI][indJ-1] + e2});
}
}

168
public/java/src/org/broadinstitute/sting/utils/pairhmm/Log10PairHMM.java 100644
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@ -0,0 +1,168 @@
/*
* Copyright (c) 2012 The Broad Institute
*
* Permission is hereby granted, free of charge, to any person
* obtaining a copy of this software and associated documentation
* files (the "Software"), to deal in the Software without
* restriction, including without limitation the rights to use,
* copy, modify, merge, publish, distribute, sublicense, and/or sell
* copies of the Software, and to permit persons to whom the
* Software is furnished to do so, subject to the following
* conditions:
*
* The above copyright notice and this permission notice shall be
* included in all copies or substantial portions of the Software.
*
* THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
* EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES
* OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND
* NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT
* HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY,
* WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING
* FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR
* THE USE OR OTHER DEALINGS IN THE SOFTWARE.
*/
package org.broadinstitute.sting.utils.pairhmm;
import com.google.java.contract.Requires;
import org.broadinstitute.sting.utils.MathUtils;
import org.broadinstitute.sting.utils.QualityUtils;
import java.util.Arrays;
/**
* Util class for performing the pair HMM for local alignment. Figure 4.3 in Durbin 1998 book.
*
* User: rpoplin
* Date: 3/1/12
*/
public class Log10PairHMM extends PairHMM {
/**
* Should we use exact log10 calculation (true), or an approximation (false)?
*/
private final boolean doExactLog10;
/**
* Create an uninitialized PairHMM
*
* @param doExactLog10 should the log10 calculations be exact (slow) or approximate (faster)
*/
public Log10PairHMM(final boolean doExactLog10) {
this.doExactLog10 = doExactLog10;
}
/**
* Is this HMM using exact log10 calculations?
* @return true if exact, false if approximate
*/
public boolean isDoingExactLog10Calculations() {
return doExactLog10;
}
/**
* {@inheritDoc}
*/
@Override
public void initialize( final int readMaxLength, final int haplotypeMaxLength) {
super.initialize(readMaxLength, haplotypeMaxLength);
for( int iii=0; iii < X_METRIC_MAX_LENGTH; iii++ ) {
Arrays.fill(matchMetricArray[iii], Double.NEGATIVE_INFINITY);
Arrays.fill(XMetricArray[iii], Double.NEGATIVE_INFINITY);
Arrays.fill(YMetricArray[iii], Double.NEGATIVE_INFINITY);
}
}
/**
* {@inheritDoc}
*/
@Override
public double subComputeReadLikelihoodGivenHaplotypeLog10( final byte[] haplotypeBases,
final byte[] readBases,
final byte[] readQuals,
final byte[] insertionGOP,
final byte[] deletionGOP,
final byte[] overallGCP,
final int hapStartIndex,
final boolean recacheReadValues ) {
// the initial condition -- must be in subComputeReadLikelihoodGivenHaplotypeLog10 because it needs that actual
// read and haplotypes, not the maximum
matchMetricArray[1][1] = getNPotentialXStartsLikelihoodPenaltyLog10(haplotypeBases.length, readBases.length);
// M, X, and Y arrays are of size read and haplotype + 1 because of an extra column for initial conditions and + 1 to consider the final base in a non-global alignment
final int X_METRIC_LENGTH = readBases.length + 2;
final int Y_METRIC_LENGTH = haplotypeBases.length + 2;
// ensure that all the qual scores have valid values
for( int iii = 0; iii < readQuals.length; iii++ ) {
readQuals[iii] = ( readQuals[iii] < QualityUtils.MIN_USABLE_Q_SCORE ? QualityUtils.MIN_USABLE_Q_SCORE : (readQuals[iii] > MAX_CACHED_QUAL ? MAX_CACHED_QUAL : readQuals[iii]) );
}
// simple rectangular version of update loop, slow
for( int iii = 1; iii < X_METRIC_LENGTH; iii++ ) {
for( int jjj = hapStartIndex + 1; jjj < Y_METRIC_LENGTH; jjj++ ) {
if( (iii == 1 && jjj == 1) ) { continue; }
updateCell(iii, jjj, haplotypeBases, readBases, readQuals, insertionGOP, deletionGOP, overallGCP,
matchMetricArray, XMetricArray, YMetricArray);
}
}
// final probability is the log10 sum of the last element in all three state arrays
final int endI = X_METRIC_LENGTH - 1;
final int endJ = Y_METRIC_LENGTH - 1;
return myLog10SumLog10(new double[]{matchMetricArray[endI][endJ], XMetricArray[endI][endJ], YMetricArray[endI][endJ]});
}
/**
* Compute the log10SumLog10 of the values
*
* NOTE NOTE NOTE
*
* Log10PairHMM depends critically on this function tolerating values that are all -Infinity
* and the sum returning -Infinity. Note good. Needs to be fixed.
*
* NOTE NOTE NOTE
*
* @param values an array of log10 probabilities that need to be summed
* @return the log10 of the sum of the probabilities
*/
@Requires("values != null")
private double myLog10SumLog10(final double[] values) {
return doExactLog10 ? MathUtils.log10sumLog10(values) : MathUtils.approximateLog10SumLog10(values);
}
private void updateCell( final int indI, final int indJ, final byte[] haplotypeBases, final byte[] readBases,
final byte[] readQuals, final byte[] insertionGOP, final byte[] deletionGOP, final byte[] overallGCP,
final double[][] matchMetricArray, final double[][] XMetricArray, final double[][] YMetricArray ) {
// the read and haplotype indices are offset by one because the state arrays have an extra column to hold the initial conditions
final int im1 = indI - 1;
final int jm1 = indJ - 1;
// update the match array
double pBaseReadLog10 = 0.0; // Math.log10(1.0);
if( im1 > 0 && jm1 > 0 ) { // the emission probability is applied when leaving the state
final byte x = readBases[im1-1];
final byte y = haplotypeBases[jm1-1];
final byte qual = readQuals[im1-1];
pBaseReadLog10 = ( x == y || x == (byte) 'N' || y == (byte) 'N' ? QualityUtils.qualToProbLog10(qual) : QualityUtils.qualToErrorProbLog10(qual) );
}
final int qualIndexGOP = ( im1 == 0 ? DEFAULT_GOP + DEFAULT_GOP : ( insertionGOP[im1-1] + deletionGOP[im1-1] > MAX_CACHED_QUAL ? MAX_CACHED_QUAL : insertionGOP[im1-1] + deletionGOP[im1-1]) );
final double d0 = QualityUtils.qualToProbLog10((byte)qualIndexGOP);
final double e0 = ( im1 == 0 ? QualityUtils.qualToProbLog10(DEFAULT_GCP) : QualityUtils.qualToProbLog10(overallGCP[im1-1]) );
matchMetricArray[indI][indJ] = pBaseReadLog10 + myLog10SumLog10(new double[]{matchMetricArray[indI - 1][indJ - 1] + d0, XMetricArray[indI - 1][indJ - 1] + e0, YMetricArray[indI - 1][indJ - 1] + e0});
// update the X (insertion) array
final double d1 = ( im1 == 0 ? QualityUtils.qualToErrorProbLog10(DEFAULT_GOP) : QualityUtils.qualToErrorProbLog10(insertionGOP[im1-1]) );
final double e1 = ( im1 == 0 ? QualityUtils.qualToErrorProbLog10(DEFAULT_GCP) : QualityUtils.qualToErrorProbLog10(overallGCP[im1-1]) );
final double qBaseReadLog10 = 0.0; // Math.log10(1.0) -- we don't have an estimate for this emission probability so assume q=1.0
XMetricArray[indI][indJ] = qBaseReadLog10 + myLog10SumLog10(new double[]{matchMetricArray[indI - 1][indJ] + d1, XMetricArray[indI - 1][indJ] + e1});
// update the Y (deletion) array, with penalty of zero on the left and right flanks to allow for a local alignment within the haplotype
final double d2 = ( im1 == 0 || im1 == readBases.length ? 0.0 : QualityUtils.qualToErrorProbLog10(deletionGOP[im1-1]) );
final double e2 = ( im1 == 0 || im1 == readBases.length ? 0.0 : QualityUtils.qualToErrorProbLog10(overallGCP[im1-1]) );
final double qBaseRefLog10 = 0.0; // Math.log10(1.0) -- we don't have an estimate for this emission probability so assume q=1.0
YMetricArray[indI][indJ] = qBaseRefLog10 + myLog10SumLog10(new double[]{matchMetricArray[indI][indJ - 1] + d2, YMetricArray[indI][indJ - 1] + e2});
}
}

106
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@ -1,106 +0,0 @@
/*
* Copyright (c) 2012 The Broad Institute
*
* Permission is hereby granted, free of charge, to any person
* obtaining a copy of this software and associated documentation
* files (the "Software"), to deal in the Software without
* restriction, including without limitation the rights to use,
* copy, modify, merge, publish, distribute, sublicense, and/or sell
* copies of the Software, and to permit persons to whom the
* Software is furnished to do so, subject to the following
* conditions:
*
* The above copyright notice and this permission notice shall be
* included in all copies or substantial portions of the Software.
*
* THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
* EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES
* OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND
* NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT
* HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY,
* WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING
* FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR
* THE USE OR OTHER DEALINGS IN THE SOFTWARE.
*/
package org.broadinstitute.sting.utils.pairhmm;
import org.broadinstitute.sting.utils.MathUtils;
import org.broadinstitute.sting.utils.QualityUtils;
/**
* Util class for performing the pair HMM for local alignment. Figure 4.3 in Durbin 1998 book.
* User: rpoplin
* Date: 3/1/12
*/
public class OriginalPairHMM extends ExactPairHMM {
@Override
public double computeReadLikelihoodGivenHaplotypeLog10( final byte[] haplotypeBases,
final byte[] readBases,
final byte[] readQuals,
final byte[] insertionGOP,
final byte[] deletionGOP,
final byte[] overallGCP,
final int hapStartIndex,
final boolean recacheReadValues ) {
// M, X, and Y arrays are of size read and haplotype + 1 because of an extra column for initial conditions and + 1 to consider the final base in a non-global alignment
final int X_METRIC_LENGTH = readBases.length + 2;
final int Y_METRIC_LENGTH = haplotypeBases.length + 2;
// ensure that all the qual scores have valid values
for( int iii = 0; iii < readQuals.length; iii++ ) {
readQuals[iii] = ( readQuals[iii] < QualityUtils.MIN_USABLE_Q_SCORE ? QualityUtils.MIN_USABLE_Q_SCORE : (readQuals[iii] > MAX_CACHED_QUAL ? MAX_CACHED_QUAL : readQuals[iii]) );
}
// simple rectangular version of update loop, slow
for( int iii = 1; iii < X_METRIC_LENGTH; iii++ ) {
for( int jjj = hapStartIndex + 1; jjj < Y_METRIC_LENGTH; jjj++ ) {
if( (iii == 1 && jjj == 1) ) { continue; }
updateCell(iii, jjj, haplotypeBases, readBases, readQuals, insertionGOP, deletionGOP, overallGCP,
matchMetricArray, XMetricArray, YMetricArray);
}
}
// final probability is the log10 sum of the last element in all three state arrays
final int endI = X_METRIC_LENGTH - 1;
final int endJ = Y_METRIC_LENGTH - 1;
return MathUtils.approximateLog10SumLog10(matchMetricArray[endI][endJ], XMetricArray[endI][endJ], YMetricArray[endI][endJ]);
}
private void updateCell( final int indI, final int indJ, final byte[] haplotypeBases, final byte[] readBases,
final byte[] readQuals, final byte[] insertionGOP, final byte[] deletionGOP, final byte[] overallGCP,
final double[][] matchMetricArray, final double[][] XMetricArray, final double[][] YMetricArray ) {
// the read and haplotype indices are offset by one because the state arrays have an extra column to hold the initial conditions
final int im1 = indI - 1;
final int jm1 = indJ - 1;
// update the match array
double pBaseReadLog10 = 0.0; // Math.log10(1.0);
if( im1 > 0 && jm1 > 0 ) { // the emission probability is applied when leaving the state
final byte x = readBases[im1-1];
final byte y = haplotypeBases[jm1-1];
final byte qual = readQuals[im1-1];
pBaseReadLog10 = ( x == y || x == (byte) 'N' || y == (byte) 'N' ? QualityUtils.qualToProbLog10(qual) : QualityUtils.qualToErrorProbLog10(qual) );
}
final int qualIndexGOP = ( im1 == 0 ? DEFAULT_GOP + DEFAULT_GOP : ( insertionGOP[im1-1] + deletionGOP[im1-1] > MAX_CACHED_QUAL ? MAX_CACHED_QUAL : insertionGOP[im1-1] + deletionGOP[im1-1]) );
final double d0 = QualityUtils.qualToProbLog10((byte)qualIndexGOP);
final double e0 = ( im1 == 0 ? QualityUtils.qualToProbLog10(DEFAULT_GCP) : QualityUtils.qualToProbLog10(overallGCP[im1-1]) );
matchMetricArray[indI][indJ] = pBaseReadLog10 + MathUtils.approximateLog10SumLog10(matchMetricArray[indI-1][indJ-1] + d0, XMetricArray[indI-1][indJ-1] + e0, YMetricArray[indI-1][indJ-1] + e0);
// update the X (insertion) array
final double d1 = ( im1 == 0 ? QualityUtils.qualToErrorProbLog10(DEFAULT_GOP) : QualityUtils.qualToErrorProbLog10(insertionGOP[im1-1]) );
final double e1 = ( im1 == 0 ? QualityUtils.qualToErrorProbLog10(DEFAULT_GCP) : QualityUtils.qualToErrorProbLog10(overallGCP[im1-1]) );
final double qBaseReadLog10 = 0.0; // Math.log10(1.0) -- we don't have an estimate for this emission probability so assume q=1.0
XMetricArray[indI][indJ] = qBaseReadLog10 + MathUtils.approximateLog10SumLog10(matchMetricArray[indI-1][indJ] + d1, XMetricArray[indI-1][indJ] + e1);
// update the Y (deletion) array, with penalty of zero on the left and right flanks to allow for a local alignment within the haplotype
final double d2 = ( im1 == 0 || im1 == readBases.length ? 0.0 : QualityUtils.qualToErrorProbLog10(deletionGOP[im1-1]) );
final double e2 = ( im1 == 0 || im1 == readBases.length ? 0.0 : QualityUtils.qualToErrorProbLog10(overallGCP[im1-1]) );
final double qBaseRefLog10 = 0.0; // Math.log10(1.0) -- we don't have an estimate for this emission probability so assume q=1.0
YMetricArray[indI][indJ] = qBaseRefLog10 + MathUtils.approximateLog10SumLog10(matchMetricArray[indI][indJ-1] + d2, YMetricArray[indI][indJ-1] + e2);
}
}

184
public/java/src/org/broadinstitute/sting/utils/pairhmm/PairHMM.java
View File

@ -27,14 +27,18 @@ package org.broadinstitute.sting.utils.pairhmm;
import com.google.java.contract.Ensures;
import com.google.java.contract.Requires;
import org.apache.log4j.Logger;
import org.broadinstitute.sting.utils.MathUtils;
/**
* Created with IntelliJ IDEA.
* Util class for performing the pair HMM for local alignment. Figure 4.3 in Durbin 1998 book.
*
* User: rpoplin
* Date: 10/16/12
*/
public abstract class PairHMM {
protected final static Logger logger = Logger.getLogger(PairHMM.class);
protected static final Byte MAX_CACHED_QUAL = Byte.MAX_VALUE;
protected static final byte DEFAULT_GOP = (byte) 45;
protected static final byte DEFAULT_GCP = (byte) 10;
@ -44,8 +48,6 @@ public abstract class PairHMM {
EXACT,
/* PairHMM as implemented for the UnifiedGenotyper. Uses log10 sum functions accurate to only 1E-4 */
ORIGINAL,
/* Optimized version of the PairHMM which caches per-read computations */
CACHING,
/* Optimized version of the PairHMM which caches per-read computations and operations in real space to avoid costly sums of log10'ed likelihoods */
LOGLESS_CACHING
}
@ -53,18 +55,172 @@ public abstract class PairHMM {
protected double[][] matchMetricArray = null;
protected double[][] XMetricArray = null;
protected double[][] YMetricArray = null;
protected int maxHaplotypeLength, maxReadLength;
protected int X_METRIC_MAX_LENGTH, Y_METRIC_MAX_LENGTH;
private boolean initialized = false;
public abstract void initialize( final int READ_MAX_LENGTH, final int HAPLOTYPE_MAX_LENGTH );
/**
* Initialize this PairHMM, making it suitable to run against a read and haplotype with given lengths
* @param readMaxLength the max length of reads we want to use with this PairHMM
* @param haplotypeMaxLength the max length of haplotypes we want to use with this PairHMM
*/
public void initialize( final int readMaxLength, final int haplotypeMaxLength ) {
if ( readMaxLength <= 0 ) throw new IllegalArgumentException("READ_MAX_LENGTH must be > 0 but got " + readMaxLength);
if ( haplotypeMaxLength <= 0 ) throw new IllegalArgumentException("HAPLOTYPE_MAX_LENGTH must be > 0 but got " + haplotypeMaxLength);
maxHaplotypeLength = haplotypeMaxLength;
maxReadLength = readMaxLength;
// M, X, and Y arrays are of size read and haplotype + 1 because of an extra column for initial conditions and + 1 to consider the final base in a non-global alignment
X_METRIC_MAX_LENGTH = readMaxLength + 2;
Y_METRIC_MAX_LENGTH = haplotypeMaxLength + 2;
matchMetricArray = new double[X_METRIC_MAX_LENGTH][Y_METRIC_MAX_LENGTH];
XMetricArray = new double[X_METRIC_MAX_LENGTH][Y_METRIC_MAX_LENGTH];
YMetricArray = new double[X_METRIC_MAX_LENGTH][Y_METRIC_MAX_LENGTH];
initialized = true;
}
/**
* Compute the total probability of read arising from haplotypeBases given base substitution, insertion, and deletion
* probabilities.
*
* Note on using hapStartIndex. This allows you to compute the exact true likelihood of a full haplotypes
* given a read, assuming that the previous calculation read over a full haplotype, recaching the read values,
* starting only at the place where the new haplotype bases and the previous haplotype bases different. This
* index is 0-based, and can be computed with findFirstPositionWhereHaplotypesDiffer given the two haplotypes.
* Note that this assumes that the read and all associated quals values are the same.
*
* @param haplotypeBases the full sequence (in standard SAM encoding) of the haplotype, must be >= than read bases in length
* @param readBases the bases (in standard encoding) of the read, must be <= haplotype bases in length
* @param readQuals the phred-scaled per base substitition quality scores of read. Must be the same length as readBases
* @param insertionGOP the phred-scaled per base insertion quality scores of read. Must be the same length as readBases
* @param deletionGOP the phred-scaled per base deletion quality scores of read. Must be the same length as readBases
* @param overallGCP the phred-scaled gap continuation penalties scores of read. Must be the same length as readBases
* @param hapStartIndex start the hmm calculation at this offset in haplotype bases. Used in the caching calculation
* where multiple haplotypes are used, and they only diff starting at hapStartIndex
* @param recacheReadValues if false, we don't recalculate any cached results, assuming that readBases and its associated
* parameters are the same, and only the haplotype bases are changing underneath us
* @return the log10 probability of read coming from the haplotype under the provided error model
*/
public final double computeReadLikelihoodGivenHaplotypeLog10( final byte[] haplotypeBases,
final byte[] readBases,
final byte[] readQuals,
final byte[] insertionGOP,
final byte[] deletionGOP,
final byte[] overallGCP,
final int hapStartIndex,
final boolean recacheReadValues ) {
if ( ! initialized ) throw new IllegalStateException("Must call initialize before calling computeReadLikelihoodGivenHaplotypeLog10");
if ( haplotypeBases == null ) throw new IllegalArgumentException("haplotypeBases cannot be null");
if ( haplotypeBases.length > maxHaplotypeLength ) throw new IllegalArgumentException("Haplotype bases is too long, got " + haplotypeBases.length + " but max is " + maxHaplotypeLength);
if ( readBases == null ) throw new IllegalArgumentException("readBases cannot be null");
if ( readBases.length > maxReadLength ) throw new IllegalArgumentException("readBases is too long, got " + readBases.length + " but max is " + maxReadLength);
if ( readQuals.length != readBases.length ) throw new IllegalArgumentException("Read bases and read quals aren't the same size: " + readBases.length + " vs " + readQuals.length);
if ( insertionGOP.length != readBases.length ) throw new IllegalArgumentException("Read bases and read insertion quals aren't the same size: " + readBases.length + " vs " + insertionGOP.length);
if ( deletionGOP.length != readBases.length ) throw new IllegalArgumentException("Read bases and read deletion quals aren't the same size: " + readBases.length + " vs " + deletionGOP.length);
if ( overallGCP.length != readBases.length ) throw new IllegalArgumentException("Read bases and overall GCP aren't the same size: " + readBases.length + " vs " + overallGCP.length);
if ( hapStartIndex < 0 || hapStartIndex > haplotypeBases.length ) throw new IllegalArgumentException("hapStartIndex is bad, must be between 0 and haplotype length " + haplotypeBases.length + " but got " + hapStartIndex);
final double result = subComputeReadLikelihoodGivenHaplotypeLog10(haplotypeBases, readBases, readQuals, insertionGOP, deletionGOP, overallGCP, hapStartIndex, recacheReadValues);
if ( MathUtils.goodLog10Probability(result) )
return result;
else
throw new IllegalStateException("Bad likelihoods detected: " + result);
// return result;
}
/**
* To be overloaded by subclasses to actually do calculation for #computeReadLikelihoodGivenHaplotypeLog10
*/
@Requires({"readBases.length == readQuals.length", "readBases.length == insertionGOP.length", "readBases.length == deletionGOP.length",
"readBases.length == overallGCP.length", "matchMetricArray!=null", "XMetricArray!=null", "YMetricArray!=null"})
@Ensures({"!Double.isInfinite(result)", "!Double.isNaN(result)"}) // Result should be a proper log10 likelihood
public abstract double computeReadLikelihoodGivenHaplotypeLog10( final byte[] haplotypeBases,
final byte[] readBases,
final byte[] readQuals,
final byte[] insertionGOP,
final byte[] deletionGOP,
final byte[] overallGCP,
final int hapStartIndex,
final boolean recacheReadValues );
protected abstract double subComputeReadLikelihoodGivenHaplotypeLog10( final byte[] haplotypeBases,
final byte[] readBases,
final byte[] readQuals,
final byte[] insertionGOP,
final byte[] deletionGOP,
final byte[] overallGCP,
final int hapStartIndex,
final boolean recacheReadValues );
/**
* How many potential starting locations are a read with readSize bases against a haplotype with haplotypeSize bases?
*
* for example, a 3 bp read against a 5 bp haplotype could potentially start at 1, 2, 3 = 5 - 3 + 1 = 3
* the max value is necessary in the case where the read is longer than the haplotype, in which case
* there's a single unique start site by assumption
*
* @param haplotypeSize the number of bases in the haplotype we are testing
* @param readSize the number of bases in the read we are testing
* @return a positive integer >= 1
*/
@Ensures("result >= 1")
protected int getNPotentialXStarts(final int haplotypeSize, final int readSize) {
return Math.max(haplotypeSize - readSize + 1, 1);
}
/**
* The the log10 probability penalty for the number of potential start sites of the read aginst the haplotype
*
* @param haplotypeSize the number of bases in the haplotype we are testing
* @param readSize the number of bases in the read we are testing
* @return a log10 probability
*/
@Ensures("MathUtils.goodLog10Probability(result)")
protected double getNPotentialXStartsLikelihoodPenaltyLog10(final int haplotypeSize, final int readSize) {
return - Math.log10(getNPotentialXStarts(haplotypeSize, readSize));
}
/**
* Print out the core hmm matrices for debugging
*/
protected void dumpMatrices() {
dumpMatrix("matchMetricArray", matchMetricArray);
dumpMatrix("XMetricArray", XMetricArray);
dumpMatrix("YMetricArray", YMetricArray);
}
/**
* Print out in a human readable form the matrix for debugging
* @param name the name of this matrix
* @param matrix the matrix of values
*/
@Requires({"name != null", "matrix != null"})
private void dumpMatrix(final String name, final double[][] matrix) {
System.out.printf("%s%n", name);
for ( int i = 0; i < matrix.length; i++) {
System.out.printf("\t%s[%d]", name, i);
for ( int j = 0; j < matrix[i].length; j++ ) {
if ( Double.isInfinite(matrix[i][j]) )
System.out.printf(" %15s", String.format("%f", matrix[i][j]));
else
System.out.printf(" % 15.5e", matrix[i][j]);
}
System.out.println();
}
}
/**
* Compute the first position at which two haplotypes differ
*
* If the haplotypes are exact copies of each other, returns the min length of the two haplotypes.
*
* @param haplotype1 the first haplotype1
* @param haplotype2 the second haplotype1
* @return the index of the first position in haplotype1 and haplotype2 where the byte isn't the same
*/
public static int findFirstPositionWhereHaplotypesDiffer(final byte[] haplotype1, final byte[] haplotype2) {
if ( haplotype1 == null || haplotype1.length == 0 ) throw new IllegalArgumentException("Haplotype1 is bad " + haplotype1);
if ( haplotype2 == null || haplotype2.length == 0 ) throw new IllegalArgumentException("Haplotype2 is bad " + haplotype2);
for( int iii = 0; iii < haplotype1.length && iii < haplotype2.length; iii++ ) {
if( haplotype1[iii] != haplotype2[iii] ) {
return iii;
}
}
return Math.min(haplotype1.length, haplotype2.length);
}
}