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package org.broadinstitute.gatk.utils.genotyper;
import htsjdk.samtools.SAMFileHeader;
import htsjdk.variant.variantcontext.Allele;
import org.broadinstitute.gatk.engine.GenomeAnalysisEngine;
import org.broadinstitute.gatk.tools.walkers.genotyper.*;
import org.broadinstitute.gatk.utils.GenomeLoc;
import org.broadinstitute.gatk.utils.GenomeLocParser;
import org.broadinstitute.gatk.utils.MathUtils;
import org.broadinstitute.gatk.utils.sam.ArtificialSAMUtils;
import org.broadinstitute.gatk.utils.sam.GATKSAMRecord;
import org.broadinstitute.gatk.utils.variant.GATKVariantContextUtils;
import org.testng.Assert;
import org.testng.SkipException;
import org.testng.annotations.DataProvider;
import org.testng.annotations.Test;
import java.util.*;
/**
* Test code for {@link ReadLikelihoods}
*
* @author Valentin Ruano-Rubio <valentin@broadinstitute.org>
*/
public class ReadLikelihoodsUnitTest
{
private static final double EPSILON = 1e-6;
private static final int ODD_READ_START = 101;
private static final int EVEN_READ_START = 1;
@Test(dataProvider = "dataSets")
public void testInstantiationAndQuery(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads) {
final ReadLikelihoods<Allele> result = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
Assert.assertEquals(result.sampleCount(), samples.length);
Assert.assertEquals(result.alleleCount(), alleles.length);
testSampleQueries(samples, reads, result);
testAlleleQueries(alleles, result);
testLikelihoodMatrixQueries(samples, result, null);
}
@Test(dataProvider = "dataSets")
public void testLikelihoodFillingAndQuery(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads) {
final ReadLikelihoods<Allele> result = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
final double[][][] likelihoods = fillWithRandomLikelihoods(samples, alleles, result);
testLikelihoodMatrixQueries(samples, result, likelihoods);
}
private double[][][] fillWithRandomLikelihoods(final String[] samples, final Allele[] alleles, final ReadLikelihoods<Allele> result) {
final Random rnd = GenomeAnalysisEngine.getRandomGenerator();
final double[][][] likelihoods = new double[samples.length][alleles.length][];
for (int s = 0; s < likelihoods.length; s++) {
final ReadLikelihoods.Matrix<Allele> sampleLikelihoods = result.sampleMatrix(s);
for (int a = 0; a < likelihoods[s].length; a++) {
likelihoods[s][a] = new double[result.sampleReadCount(s)];
for (int r = 0; r < likelihoods[s][a].length; r++)
sampleLikelihoods.set(a,r,likelihoods[s][a][r] = -Math.abs(rnd.nextGaussian()));
}
}
return likelihoods;
}
@Test(dataProvider = "dataSets")
public void testBestAlleles(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads) {
final ReadLikelihoods<Allele> original = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
fillWithRandomLikelihoods(samples,alleles,original);
final int alleleCount = alleles.length;
for (int s = 0; s < samples.length; s++) {
final int sampleReadCount = original.sampleReadCount(s);
final ReadLikelihoods.Matrix<Allele> sampleMatrix = original.sampleMatrix(s);
final double[] bestLkArray = new double[sampleReadCount];
final int[] bestIndexArray = new int[sampleReadCount];
final double[] confidenceArray = new double[sampleReadCount];
for (int r = 0; r < sampleReadCount; r++) {
int bestAlleleIndex = -1;
double bestAlleleLk = Double.NEGATIVE_INFINITY;
double secondBestAlleleLk = Double.NEGATIVE_INFINITY;
for (int a = 0; a < alleleCount; a++) {
final double lk = sampleMatrix.get(a,r);
if (lk > bestAlleleLk) {
secondBestAlleleLk = bestAlleleLk;
bestAlleleLk = lk;
bestAlleleIndex = a;
} else if (lk > secondBestAlleleLk) {
secondBestAlleleLk = lk;
}
}
bestLkArray[r] = bestAlleleLk;
confidenceArray[r] = bestAlleleLk - secondBestAlleleLk;
bestIndexArray[r] = bestAlleleIndex;
}
final Collection<ReadLikelihoods<Allele>.BestAllele> bestAlleles = original.bestAlleles();
for (final ReadLikelihoods<Allele>.BestAllele bestAllele : bestAlleles) {
final int readIndex = original.readIndex(s,bestAllele.read);
if (readIndex == -1) continue;
Assert.assertEquals(bestLkArray[readIndex],bestAllele.likelihood);
Assert.assertEquals(bestAllele.allele,alleles[bestIndexArray[readIndex]]);
Assert.assertEquals(bestAllele.confidence,confidenceArray[readIndex],EPSILON);
}
}
}
@Test(dataProvider = "dataSets")
public void testBestAlleleMap(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads) {
final ReadLikelihoods<Allele> original = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
fillWithRandomLikelihoods(samples,alleles,original);
final Map<Allele,List<GATKSAMRecord>> expected = new HashMap<>(alleles.length);
for (final Allele allele : alleles)
expected.put(allele,new ArrayList<GATKSAMRecord>());
final int alleleCount = alleles.length;
for (int s = 0; s < samples.length; s++) {
final int sampleReadCount = original.sampleReadCount(s);
final ReadLikelihoods.Matrix<Allele> sampleMatrix = original.sampleMatrix(s);
for (int r = 0; r < sampleReadCount; r++) {
int bestAlleleIndex = -1;
double bestAlleleLk = Double.NEGATIVE_INFINITY;
double secondBestAlleleLk = Double.NEGATIVE_INFINITY;
for (int a = 0; a < alleleCount; a++) {
final double lk = sampleMatrix.get(a,r);
if (lk > bestAlleleLk) {
secondBestAlleleLk = bestAlleleLk;
bestAlleleLk = lk;
bestAlleleIndex = a;
} else if (lk > secondBestAlleleLk) {
secondBestAlleleLk = lk;
}
}
if ((bestAlleleLk - secondBestAlleleLk) > ReadLikelihoods.BestAllele.INFORMATIVE_THRESHOLD)
expected.get(alleles[bestAlleleIndex]).add(sampleMatrix.readAt(r));
}
}
final Map<Allele,List<GATKSAMRecord>> actual = original.readsByBestAlleleMap();
Assert.assertEquals(actual.size(),alleles.length);
for (final Allele allele : alleles) {
final List<GATKSAMRecord> expectedList = expected.get(allele);
final List<GATKSAMRecord> actualList = actual.get(allele);
final Set<GATKSAMRecord> expectedSet = new HashSet<>(expectedList);
final Set<GATKSAMRecord> actualSet = new HashSet<>(actualList);
Assert.assertEquals(actualSet,expectedSet);
}
}
@Test(dataProvider = "dataSets")
public void testFilterPoorlyModeledReads(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads) {
final ReadLikelihoods<Allele> original = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
for (int s = 0; s < samples.length; s++) {
final int sampleReadCount = original.sampleReadCount(s);
for (int r = 0; r < sampleReadCount; r++) {
if ((r & 1) == 0) continue;
for (int a = 0; a < alleles.length; a++)
original.sampleMatrix(s).set(a,r,-10000);
}
}
final ReadLikelihoods<Allele> result = original.clone();
result.filterPoorlyModeledReads(2.0);
for (int s = 0; s < samples.length; s++) {
final int oldSampleReadCount = original.sampleReadCount(s);
final int newSampleReadCount = result.sampleReadCount(s);
Assert.assertEquals(newSampleReadCount,(oldSampleReadCount + 1) / 2);
final ReadLikelihoods.Matrix<Allele> newSampleMatrix = result.sampleMatrix(s);
final ReadLikelihoods.Matrix<Allele> oldSampleMatrix = original.sampleMatrix(s);
for (int r = 0 ; r < newSampleReadCount; r++) {
Assert.assertEquals(original.readIndex(s, result.sampleReads(s).get(r)), r * 2);
for (int a = 0; a < alleles.length; a++) {
Assert.assertEquals(newSampleMatrix.get(a,r),oldSampleMatrix.get(a,r*2));
}
}
}
}
@Test(dataProvider = "dataSets")
public void testFilterReadsToOverlap(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads) {
final ReadLikelihoods<Allele> original = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
final GenomeLoc evenReadOverlap = locParser.createGenomeLoc(SAM_HEADER.getSequenceDictionary().getSequences().get(0).getSequenceName(),EVEN_READ_START ,EVEN_READ_START );
fillWithRandomLikelihoods(samples,alleles,original);
final ReadLikelihoods<Allele> result = original.clone();
result.filterToOnlyOverlappingUnclippedReads(evenReadOverlap);
final double[][][] newLikelihoods = new double[samples.length][alleles.length][];
for (int s = 0; s < samples.length ; s++)
for (int a = 0; a < alleles.length; a++) {
newLikelihoods[s][a] = new double[(original.sampleReadCount(s) + 1) / 2];
final ReadLikelihoods.Matrix<Allele> sampleMatrix = original.sampleMatrix(s);
for (int r = 0; r < newLikelihoods[s][a].length; r++) {
Assert.assertEquals(result.readIndex(s,sampleMatrix.readAt(r << 1)),r);
newLikelihoods[s][a][r] = sampleMatrix.get(a, r << 1);
}
}
testLikelihoodMatrixQueries(samples,result,newLikelihoods);
}
@Test(dataProvider = "marginalizationDataSets")
public void testMarginalizationWithOverlap(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads, final Map<Allele,List<Allele>> newToOldAlleleMapping) {
final ReadLikelihoods<Allele> original = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
final GenomeLoc evenReadOverlap = locParser.createGenomeLoc(SAM_HEADER.getSequenceDictionary().getSequences().get(0).getSequenceName(),EVEN_READ_START ,EVEN_READ_START );
fillWithRandomLikelihoods(samples, alleles, original);
final ReadLikelihoods<Allele> marginalized = original.marginalize(newToOldAlleleMapping,evenReadOverlap);
Assert.assertNotNull(marginalized);
Assert.assertEquals(newToOldAlleleMapping.size(),marginalized.alleleCount());
for (int a = 0; a < marginalized.alleleCount(); a++) {
final List<Allele> oldAlleles = newToOldAlleleMapping.get(marginalized.alleleAt(a));
Assert.assertNotNull(oldAlleles);
for (int s = 0; s < samples.length; s++) {
final ReadLikelihoods.Matrix<Allele> oldSmapleLikelihoods = original.sampleMatrix(s);
final ReadLikelihoods.Matrix<Allele> sampleLikelihoods = marginalized.sampleMatrix(s);
final int sampleReadCount = sampleLikelihoods.readCount();
final int oldSampleReadCount = oldSmapleLikelihoods.readCount();
Assert.assertEquals(sampleReadCount,(oldSampleReadCount + 1) / 2);
for (int r = 0; r < sampleReadCount; r++) {
double oldBestLk = Double.NEGATIVE_INFINITY;
for (final Allele oldAllele : oldAlleles) {
oldBestLk = Math.max(oldSmapleLikelihoods.get(original.alleleIndex(oldAllele),r << 1), oldBestLk);
}
Assert.assertEquals(sampleLikelihoods.get(a,r),oldBestLk);
}
}
}
}
@Test(dataProvider = "marginalizationDataSets")
public void testMarginalization(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads, final Map<Allele,List<Allele>> newToOldAlleleMapping) {
final ReadLikelihoods<Allele> original = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
fillWithRandomLikelihoods(samples, alleles, original);
final ReadLikelihoods<Allele> marginalized = original.marginalize(newToOldAlleleMapping);
Assert.assertNotNull(marginalized);
Assert.assertEquals(newToOldAlleleMapping.size(),marginalized.alleleCount());
for (int a = 0; a < marginalized.alleleCount(); a++) {
final List<Allele> oldAlleles = newToOldAlleleMapping.get(marginalized.alleleAt(a));
Assert.assertNotNull(oldAlleles);
for (int s = 0; s < samples.length; s++) {
final ReadLikelihoods.Matrix<Allele> oldSmapleLikelihoods = original.sampleMatrix(s);
final ReadLikelihoods.Matrix<Allele> sampleLikelihoods = marginalized.sampleMatrix(s);
final int sampleReadCount = sampleLikelihoods.readCount();
final int oldSampleReadCount = oldSmapleLikelihoods.readCount();
Assert.assertEquals(oldSampleReadCount,sampleReadCount);
for (int r = 0; r < sampleReadCount; r++) {
double oldBestLk = Double.NEGATIVE_INFINITY;
for (final Allele oldAllele : oldAlleles) {
oldBestLk = Math.max(oldSmapleLikelihoods.get(original.alleleIndex(oldAllele),r), oldBestLk);
}
Assert.assertEquals(sampleLikelihoods.get(a,r),oldBestLk);
}
}
}
}
@Test(dataProvider = "dataSets")
public void testNormalizeBestToZero(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads) {
final ReadLikelihoods<Allele> original = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
final double[][][] originalLikelihoods = fillWithRandomLikelihoods(samples,alleles,original);
final ReadLikelihoods<Allele> result= original.clone();
result.normalizeLikelihoods(true, Double.NEGATIVE_INFINITY);
testAlleleQueries(alleles,result);
final int alleleCount = alleles.length;
final double[][][] newLikelihoods = new double[originalLikelihoods.length][alleles.length][];
for (int s = 0; s < samples.length; s++) {
final int sampleReadCount = original.sampleReadCount(s);
for (int a = 0; a < alleleCount; a++)
newLikelihoods[s][a] = new double[sampleReadCount];
for (int r = 0; r < sampleReadCount; r++) {
double bestLk = originalLikelihoods[s][0][r];
for (int a = 1; a < alleleCount; a++) {
bestLk = Math.max(bestLk,originalLikelihoods[s][a][r]);
}
for (int a = 0; a < alleleCount; a++) {
newLikelihoods[s][a][r] = originalLikelihoods[s][a][r] - bestLk;
}
}
}
testLikelihoodMatrixQueries(samples,result,newLikelihoods);
}
@Test(dataProvider = "dataSets")
public void testNormalizeCapWorstLK(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads) {
final ReadLikelihoods<Allele> original = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
final double[][][] originalLikelihoods = fillWithRandomLikelihoods(samples,alleles,original);
final ReadLikelihoods<Allele> result= original.clone();
result.normalizeLikelihoods(false, - 0.001);
testAlleleQueries(alleles,result);
final int alleleCount = alleles.length;
final double[][][] newLikelihoods = new double[originalLikelihoods.length][alleles.length][];
for (int s = 0; s < samples.length; s++) {
final int sampleReadCount = original.sampleReadCount(s);
for (int a = 0; a < alleleCount; a++)
newLikelihoods[s][a] = new double[sampleReadCount];
for (int r = 0; r < sampleReadCount; r++) {
double bestAltLk = Double.NEGATIVE_INFINITY;
for (int a = 0; a < alleleCount; a++) {
if (alleles[a].isReference())
continue;
bestAltLk = Math.max(bestAltLk,originalLikelihoods[s][a][r]);
}
if (bestAltLk == Double.NEGATIVE_INFINITY)
for (int a = 0; a < alleleCount; a++) {
newLikelihoods[s][a][r] = originalLikelihoods[s][a][r];
}
else
for (int a = 0; a < alleleCount; a++) {
newLikelihoods[s][a][r] = Math.max(originalLikelihoods[s][a][r],bestAltLk - 0.001);
}
}
}
testLikelihoodMatrixQueries(samples,result,newLikelihoods);
}
@Test(dataProvider = "dataSets")
public void testNormalizeCapWorstLKAndBestToZero(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads) {
final ReadLikelihoods<Allele> original = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
final double[][][] originalLikelihoods = fillWithRandomLikelihoods(samples,alleles,original);
final ReadLikelihoods<Allele> result= original.clone();
result.normalizeLikelihoods(true, - 0.001);
testAlleleQueries(alleles,result);
final int alleleCount = alleles.length;
final double[][][] newLikelihoods = new double[originalLikelihoods.length][alleles.length][];
for (int s = 0; s < samples.length; s++) {
final int sampleReadCount = original.sampleReadCount(s);
for (int a = 0; a < alleleCount; a++)
newLikelihoods[s][a] = new double[sampleReadCount];
for (int r = 0; r < sampleReadCount; r++) {
double bestAltLk = Double.NEGATIVE_INFINITY;
double bestLk = Double.NEGATIVE_INFINITY;
for (int a = 0; a < alleleCount; a++) {
bestLk = Math.max(bestLk,originalLikelihoods[s][a][r]);
if (alleles[a].isReference())
continue;
bestAltLk = Math.max(bestAltLk,originalLikelihoods[s][a][r]);
}
if (bestAltLk == Double.NEGATIVE_INFINITY)
for (int a = 0; a < alleleCount; a++) {
newLikelihoods[s][a][r] = originalLikelihoods[s][a][r] - bestLk;
}
else
for (int a = 0; a < alleleCount; a++) {
newLikelihoods[s][a][r] = Math.max(originalLikelihoods[s][a][r],bestAltLk - 0.001) - bestLk;
}
}
}
testLikelihoodMatrixQueries(samples,result,newLikelihoods);
}
@Test(dataProvider = "dataSets")
public void testAddMissingAlleles(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads) {
final ReadLikelihoods<Allele> original = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
final double[][][] originalLikelihoods = fillWithRandomLikelihoods(samples,alleles,original);
final ReadLikelihoods<Allele> result = original.clone();
// If all the alleles pass are present in the read-likelihoods collection there is no change.
result.addMissingAlleles(result.alleles(),Double.NEGATIVE_INFINITY);
testLikelihoodMatrixQueries(samples,result,originalLikelihoods);
// If the allele list passed is empty there is no effect.
result.addMissingAlleles(Collections.EMPTY_LIST,Double.NEGATIVE_INFINITY);
testLikelihoodMatrixQueries(samples,result,originalLikelihoods);
final Allele newOne;
final Allele newTwo;
final Allele newThree;
// We add a single missing.
result.addMissingAlleles(Arrays.asList(newOne = Allele.create("ACCCCCAAAATTTAAAGGG".getBytes(),false)),-12345.6);
Assert.assertEquals(result.alleleCount(), original.alleleCount() + 1);
// We add too more amongst exisisting alleles:
result.addMissingAlleles(Arrays.asList(newTwo = Allele.create("ATATATTATATTAATATT".getBytes(), false),result.alleleAt(1),
result.alleleAt(0),newThree = Allele.create("TGTGTGTATTG".getBytes(),false),Allele.create("ACCCCCAAAATTTAAAGGG".getBytes(),false)),-6.54321);
Assert.assertEquals(original.alleleCount()+3,result.alleleCount());
final List<Allele> expectedAlleles = new ArrayList<>(original.alleles());
expectedAlleles.add(newOne); expectedAlleles.add(newTwo); expectedAlleles.add(newThree);
Assert.assertEquals(result.alleles(),expectedAlleles);
final double[][][] newLikelihoods = new double[originalLikelihoods.length][][];
for (int s = 0; s < samples.length; s++) {
newLikelihoods[s] = Arrays.copyOf(originalLikelihoods[s],originalLikelihoods[s].length + 3);
final int sampleReadCount = original.sampleReadCount(s);
final int originalAlleleCount = originalLikelihoods[s].length;
newLikelihoods[s][originalAlleleCount] = new double[sampleReadCount];
Arrays.fill(newLikelihoods[s][originalAlleleCount],-12345.6);
newLikelihoods[s][originalAlleleCount+1] = new double[sampleReadCount];
Arrays.fill(newLikelihoods[s][originalAlleleCount+1],-6.54321);
newLikelihoods[s][originalAlleleCount+2] = new double[sampleReadCount];
Arrays.fill(newLikelihoods[s][originalAlleleCount+2],-6.54321);
}
testLikelihoodMatrixQueries(samples,result,newLikelihoods);
}
@Test(dataProvider = "dataSets")
public void testAddNonRefAllele(final String[] samples, final Allele[] alleles, final Map<String,List<GATKSAMRecord>> reads) {
final ReadLikelihoods<Allele> original = new ReadLikelihoods<>(new IndexedSampleList(samples), new IndexedAlleleList<>(alleles), reads);
final double[][][] originalLikelihoods = fillWithRandomLikelihoods(samples,alleles,original);
final ReadLikelihoods<Allele> result = original.clone();
result.addNonReferenceAllele(GATKVariantContextUtils.NON_REF_SYMBOLIC_ALLELE);
Assert.assertEquals(result.alleleCount(),original.alleleCount() + 1);
Assert.assertEquals(result.alleleIndex(GATKVariantContextUtils.NON_REF_SYMBOLIC_ALLELE),result.alleleCount() - 1);
final double[][][] newLikelihoods = new double[originalLikelihoods.length][][];
for (int s = 0; s < samples.length; s++) {
newLikelihoods[s] = Arrays.copyOf(originalLikelihoods[s],originalLikelihoods[s].length + 1);
final int sampleReadCount = original.sampleReadCount(s);
final int ordinaryAlleleCount = originalLikelihoods[s].length;
newLikelihoods[s][ordinaryAlleleCount] = new double[sampleReadCount];
for (int r = 0; r < sampleReadCount; r++) {
double bestLk = newLikelihoods[s][0][r];
double secondBestLk = Double.NEGATIVE_INFINITY;
for (int a = 1; a < ordinaryAlleleCount; a++) {
final double lk = originalLikelihoods[s][a][r];
if (lk > bestLk) {
secondBestLk = bestLk;
bestLk = lk;
} else if (lk > secondBestLk) {
secondBestLk = lk;
}
}
final double expectedNonRefLk = Double.isInfinite(secondBestLk) ? bestLk : secondBestLk;
newLikelihoods[s][ordinaryAlleleCount][r] = expectedNonRefLk;
}
}
testLikelihoodMatrixQueries(samples,result,newLikelihoods);
}
private void testLikelihoodMatrixQueries(String[] samples, ReadLikelihoods<Allele> result, final double[][][] likelihoods) {
for (final String sample : samples) {
final int sampleIndex = result.sampleIndex(sample);
final int sampleReadCount = result.sampleReadCount(sampleIndex);
final int alleleCount = result.alleleCount();
Assert.assertEquals(result.alleleCount(), alleleCount);
for (int a = 0; a < alleleCount; a++) {
Assert.assertEquals(result.sampleReadCount(sampleIndex),sampleReadCount);
for (int r = 0; r < sampleReadCount; r++)
Assert.assertEquals(result.sampleMatrix(sampleIndex).get(a,r),
likelihoods == null ? 0.0 : likelihoods[sampleIndex][a][r], EPSILON);
}
}
}
private void testAlleleQueries(Allele[] alleles, ReadLikelihoods<Allele> result) {
final Set<Integer> alleleIndices = new HashSet<>();
for (final Allele allele : alleles) {
final int alleleIndex = result.alleleIndex(allele);
Assert.assertTrue(alleleIndex >= 0);
Assert.assertFalse(alleleIndices.contains(alleleIndex));
alleleIndices.add(alleleIndex);
Assert.assertSame(allele,alleles[alleleIndex]);
}
}
private void testSampleQueries(String[] samples, Map<String, List<GATKSAMRecord>> reads, ReadLikelihoods<Allele> result) {
final Set<Integer> sampleIds = new HashSet<>(samples.length);
for (final String sample : samples) {
final int sampleIndex = result.sampleIndex(sample);
Assert.assertTrue(sampleIndex >= 0);
Assert.assertFalse(sampleIds.contains(sampleIndex));
sampleIds.add(sampleIndex);
final List<GATKSAMRecord> sampleReads = result.sampleReads(sampleIndex);
final Set<GATKSAMRecord> sampleReadsSet = new HashSet<>(sampleReads);
final List<GATKSAMRecord> expectedSampleReadArray = reads.get(sample);
final Set<GATKSAMRecord> expectedSampleReadsSet = new HashSet<>(expectedSampleReadArray);
Assert.assertEquals(sampleReadsSet,expectedSampleReadsSet);
final int sampleReadCount = sampleReads.size();
for (int r = 0; r < sampleReadCount; r++) {
Assert.assertSame(sampleReads.get(r), expectedSampleReadArray.get(r));
final int readIndex = result.readIndex(sampleIndex, sampleReads.get(r));
Assert.assertEquals(readIndex,r);
}
}
}
private String[][] SAMPLE_SETS = new String[][] {
{"A","B","C"},
{"A"},
{"C","A","D","E","Salsa","Gazpacho"},
};
private Allele[][] ALLELE_SETS = new Allele[][] {
{Allele.create("A",true), Allele.create("T"), Allele.create("C")},
{Allele.create("A",true)},
{Allele.create("ATTTA"), Allele.create("A",true)},
{Allele.create("A"), Allele.create("AT",true)},
{Allele.create("A",false), Allele.create("AT",false)},
};
@DataProvider(name="marginalizationDataSets")
public Object[][] marginalizationDataSets() {
try {
final Random rnd = GenomeAnalysisEngine.getRandomGenerator();
final Object[][] result = new Object[SAMPLE_SETS.length * ALLELE_SETS.length * ALLELE_SETS.length][];
int nextIndex = 0;
for (int s = 0; s < SAMPLE_SETS.length; s++) {
for (int a = 0; a < ALLELE_SETS.length; a++) {
for (int b = 0; b < ALLELE_SETS.length; b++) {
if (ALLELE_SETS[b].length < ALLELE_SETS[a].length)
result[nextIndex++] = new Object[]{SAMPLE_SETS[s], ALLELE_SETS[a],
dataSetReads(SAMPLE_SETS[s], rnd), randomAlleleMap(ALLELE_SETS[a], ALLELE_SETS[b])
};
}
}
}
return Arrays.copyOf(result,nextIndex);
}catch (final Throwable e) {
throw new RuntimeException(e);
}
}
private Map<Allele,List<Allele>> randomAlleleMap(final Allele[] fromAlleles, final Allele[] toAlleles) {
final Map<Allele,List<Allele>> result = new HashMap<>(toAlleles.length);
for (final Allele toAllele : toAlleles )
result.put(toAllele,new ArrayList<Allele>(fromAlleles.length));
final ArrayList<Allele> remaining = new ArrayList<>(Arrays.asList(fromAlleles));
int nextToIndex = 0;
final Random rnd = GenomeAnalysisEngine.getRandomGenerator();
for (int i = 0; i < fromAlleles.length; i++) {
final int fromAlleleIndex = rnd.nextInt(remaining.size());
result.get(toAlleles[nextToIndex]).add(remaining.remove(fromAlleleIndex));
nextToIndex = (nextToIndex + 1) % toAlleles.length;
}
return result;
}
@DataProvider(name="dataSets")
public Object[][] dataSets() {
try {
final Random rnd = GenomeAnalysisEngine.getRandomGenerator();
final Object[][] result = new Object[SAMPLE_SETS.length * ALLELE_SETS.length][];
int nextIndex = 0;
for (int s = 0; s < SAMPLE_SETS.length; s++)
for (int a = 0; a < ALLELE_SETS.length; a++) {
result[nextIndex++] = new Object[]{SAMPLE_SETS[s], ALLELE_SETS[a],
dataSetReads(SAMPLE_SETS[s], rnd)
};
}
return result;
}catch (final Throwable e) {
throw new RuntimeException(e);
}
}
private Map<String,List<GATKSAMRecord>> dataSetReads(final String[] samples,
final Random rnd) {
final Map<String,List<GATKSAMRecord>> result = new HashMap<>(samples.length);
for (final String sample : samples) {
final int readCount = rnd.nextInt(100);
final List<GATKSAMRecord> reads = new ArrayList<>(readCount);
for (int r = 0; r < readCount; r++) {
final int alignmentStart = (r & 1) == 0 ? EVEN_READ_START : ODD_READ_START;
reads.add(ArtificialSAMUtils.createArtificialRead(SAM_HEADER,
"RRR" + sample + "00" + r, 0, alignmentStart ,"AAAAA".getBytes(), new byte[] {30,30,30,30,30}, "5M"));
}
result.put(sample,reads);
}
return result;
}
@Test(dataProvider="readCountsAndAlleleCountDataSkippingNoAlleleAndWithReference")
public void testInstantiationAndBasicQueries(final int[] readCounts, final int alleleCount, final boolean hasReference) {
final SampleList sampleList = sampleList(readCounts);
final AlleleList<Allele> alleleList = alleleList(alleleCount,hasReference);
final Map<String,List<GATKSAMRecord>> sampleToReads = ReadLikelihoodsUnitTester.sampleToReads(sampleList, readCounts);
final ReadLikelihoods<Allele> subject = new ReadLikelihoods<>(sampleList,alleleList,sampleToReads);
AlleleListUnitTester.assertAlleleList(subject, AlleleListUtils.asList(alleleList));
SampleListUnitTester.assertSampleList(subject,SampleListUtils.asList(sampleList));
if (hasReference) {
final int referenceIndex = AlleleListUtils.indexOfReference(alleleList);
Assert.assertTrue(referenceIndex >= 0);
Assert.assertEquals(AlleleListUtils.indexOfReference(alleleList),referenceIndex);
} else {
Assert.assertEquals(AlleleListUtils.indexOfReference(subject), -1);
}
testLikelihoodMatrixQueries(alleleList, sampleList, sampleToReads, subject);
testAlleleQueries(alleleList, subject);
testSampleQueries(sampleList, sampleToReads, subject);
}
@Test(dataProvider="readCountsAndAlleleCountDataSkippingNoLikelihoodsOrNoAlleleAndWithReference")
public void testLikelihoodWriting(final int[] readCounts, final int alleleCount, final boolean hasReference) {
final SampleList sampleList = sampleList(readCounts);
final AlleleList<Allele> alleleList = alleleList(alleleCount,hasReference);
final Map<String,List<GATKSAMRecord>> sampleToReads = ReadLikelihoodsUnitTester.sampleToReads(sampleList,readCounts);
final ReadLikelihoods<Allele> subject = new ReadLikelihoods<>(sampleList,alleleList,sampleToReads);
final int sampleCount = readCounts.length;
int totalLikelihoodsSet = 0;
int expectedLikelihoodsSet = 0;
for (int s = 0; s < sampleCount; s++) {
expectedLikelihoodsSet += readCounts[s] * alleleCount;
final ReadLikelihoods.Matrix<Allele> matrix = subject.sampleMatrix(s);
final int readCount = matrix.readCount();
for (int a = 0; a < alleleCount; a++)
for (int r = 0; r < readCount; r++) {
final double likelihood = testLikelihood(s, a, r);
Assert.assertNotEquals(likelihood,0); //Paranoia
totalLikelihoodsSet++;
matrix.set(a,r,likelihood);
Assert.assertEquals(matrix.get(a, r),likelihood);
}
}
Assert.assertEquals(totalLikelihoodsSet,expectedLikelihoodsSet);
}
@Test(dependsOnMethods={"testLikelihoodWriting","testInstantiationAndBasicQueries"},
dataProvider="readCountsAndAlleleCountDataSkippingNoAlleleAndWithReference")
public void testMapConversion(final int[] readCounts, final int alleleCount, final boolean hasReference) {
final SampleList sampleList = sampleList(readCounts);
final AlleleList<Allele> alleleList = alleleList(alleleCount,hasReference);
final Map<String,List<GATKSAMRecord>> sampleToReads = ReadLikelihoodsUnitTester.sampleToReads(sampleList,readCounts);
final Set<Allele> alleleWithLikelihoodsSet = new HashSet<>();
final Set<GATKSAMRecord> readsWithLikelihoodsSet = new HashSet<>();
final Map<String,PerReadAlleleLikelihoodMap> map = new HashMap<>(sampleList.sampleCount());
final int sampleCount = sampleList.sampleCount();
for (int s = 0; s < sampleCount; s++) {
final String sample = sampleList.sampleAt(s);
final PerReadAlleleLikelihoodMap perSampleMap = new PerReadAlleleLikelihoodMap();
final List<GATKSAMRecord> reads = sampleToReads.get(sample);
for (int a = 0; a < alleleCount; a++)
for (int r = 0; r < reads.size(); r++) {
perSampleMap.add(reads.get(r), alleleList.alleleAt(a), testLikelihood(s, a, r));
alleleWithLikelihoodsSet.add(alleleList.alleleAt(a));
readsWithLikelihoodsSet.add(reads.get(r));
}
map.put(sample,perSampleMap);
}
ReadLikelihoods<Allele> subject = ReadLikelihoods.fromPerAlleleReadLikelihoodsMap(map);
for (int s = 0; s < sampleCount; s++) {
final String sample = sampleList.sampleAt(s);
final int sIndex = subject.sampleIndex(sample);
Assert.assertTrue(sIndex >= 0);
Assert.assertTrue(sIndex < sampleCount);
final int sampleReadCount = sampleToReads.get(sample).size();
final ReadLikelihoods.Matrix<Allele> sampleLikelihoods = subject.sampleMatrix(sIndex);
for (int a = 0; a < alleleCount; a++) {
final Allele allele = alleleList.alleleAt(a);
final int aIndex = subject.alleleIndex(allele);
Assert.assertEquals(aIndex >= 0,alleleWithLikelihoodsSet.contains(allele));
Assert.assertTrue(aIndex < alleleCount);
if (aIndex == -1) continue;
for (int r = 0; r < sampleReadCount; r++) {
final GATKSAMRecord read = sampleToReads.get(sample).get(r);
final int rIndex = subject.readIndex(sIndex,read);
final int rIndex2 = sampleLikelihoods.readIndex(read);
Assert.assertEquals(rIndex,rIndex2);
Assert.assertEquals(rIndex >= 0,readsWithLikelihoodsSet.contains(read));
Assert.assertTrue(rIndex < sampleReadCount);
if (rIndex == -1)
continue;
final double likelihood = sampleLikelihoods.get(aIndex,rIndex);
Assert.assertEquals(likelihood,testLikelihood(s,a,r));
}
}
}
}
private double testLikelihood(final int sampleIndex, final int alleleIndex, final int readIndex) {
return - Math.abs(31 * (sampleIndex + 1) + 101 * alleleIndex + 1009 * readIndex);
}
private final Random rnd = GenomeAnalysisEngine.getRandomGenerator();
private void testLikelihoodMatrixQueries(final AlleleList<Allele> alleles, final SampleList samples,
final Map<String,List<GATKSAMRecord>> sampleToReads, ReadLikelihoods<Allele> result) {
for (final String sample : SampleListUtils.asList(samples)) {
final int sampleIndex = result.sampleIndex(sample);
final ReadLikelihoods.Matrix<Allele> likelihoodMatrix = result.sampleMatrix(sampleIndex);
final int sampleReadCount = sampleToReads.get(sample).size();
final List<GATKSAMRecord> reads = sampleToReads.get(sample);
Assert.assertEquals(likelihoodMatrix.alleleCount(), alleles.alleleCount());
Assert.assertEquals(likelihoodMatrix.readCount(), sampleReadCount);
for (int a = 0; a < likelihoodMatrix.alleleCount(); a++) {
Assert.assertEquals(likelihoodMatrix.alleleAt(a),alleles.alleleAt(a));
for (int r = 0; r < sampleReadCount; r++) {
Assert.assertEquals(likelihoodMatrix.readAt(r),reads.get(r));
Assert.assertEquals(likelihoodMatrix.get(a, r), 0.0);
}
}
}
}
private void testAlleleQueries(final AlleleList<Allele> alleles, ReadLikelihoods<Allele> result) {
final Set<Integer> alleleIndices = new HashSet<>();
for (final Allele allele : AlleleListUtils.asList(alleles)) {
final int alleleIndex = result.alleleIndex(allele);
Assert.assertTrue(alleleIndex >= 0);
Assert.assertFalse(alleleIndices.contains(alleleIndex));
alleleIndices.add(alleleIndex);
Assert.assertSame(allele,alleles.alleleAt(alleleIndex));
}
}
private void testSampleQueries(final SampleList samples, Map<String, List<GATKSAMRecord>> reads,
final ReadLikelihoods<Allele> result) {
final Set<Integer> sampleIds = new HashSet<>(samples.sampleCount());
for (final String sample : SampleListUtils.asList(samples)) {
final int sampleIndex = result.sampleIndex(sample);
Assert.assertTrue(sampleIndex >= 0);
Assert.assertFalse(sampleIds.contains(sampleIndex));
sampleIds.add(sampleIndex);
final List<GATKSAMRecord> sampleReads = result.sampleReads(sampleIndex);
final Set<GATKSAMRecord> sampleReadsSet = new HashSet<>(sampleReads);
final List<GATKSAMRecord> expectedSampleReadArray = reads.get(sample);
final Set<GATKSAMRecord> expectedSampleReadsSet = new HashSet<>(expectedSampleReadArray);
Assert.assertEquals(sampleReadsSet,expectedSampleReadsSet);
final int sampleReadCount = sampleReads.size();
for (int r = 0; r < sampleReadCount; r++) {
Assert.assertSame(sampleReads.get(r), expectedSampleReadArray.get(r));
final int readIndex = result.readIndex(sampleIndex, sampleReads.get(r));
Assert.assertEquals(readIndex,r);
}
}
}
private AlleleList<Allele> alleleList(final int alleleCount, final boolean hasReference) {
final Allele[] alleles = AlleleListUnitTester.generateRandomAlleles(alleleCount,100);
if (hasReference) {
final int referenceIndex = rnd.nextInt(alleleCount);
alleles[referenceIndex] = Allele.create(alleles[referenceIndex].getBases(),true);
}
final AlleleList<Allele> alleleList = new IndexedAlleleList<>(alleles);
if (alleleList.alleleCount() != alleles.length)
throw new SkipException("repeated alleles, should be infrequent");
return alleleList;
}
private SAMFileHeader SAM_HEADER = ArtificialSAMUtils.createArtificialSamHeader(10, 0, 1000);
final GenomeLocParser locParser = new GenomeLocParser(SAM_HEADER.getSequenceDictionary());
private int[][] READ_COUNTS = new int[][] {
{},
{ 100 },
{ 0 },
{ 0, 0, 0 },
{ 1, 0, 1 },
{ 100, 10 , 100},
{ 1000, 10, 100, 20, 23 }
};
private int[] ALLELE_COUNTS = new int[] { 0, 1, 2, 3, 10, 20 };
@DataProvider(name="readCountsAndAlleleCountData")
public Object[][] readCountsAndAlleleCountData() {
final Object[][] result = new Object[READ_COUNTS.length * ALLELE_COUNTS.length * 2][];
int index = 0;
for (final int[] readCounts : READ_COUNTS)
for (final int alleleCount : ALLELE_COUNTS) {
result[index++] = new Object[]{ readCounts, alleleCount, false};
result[index++] = new Object[]{ readCounts, alleleCount, true};
}
return result;
}
@DataProvider(name="readCountsAndAlleleCountDataSkippingNoAlleleAndWithReference")
public Object[][] readCountsAndAlleleCountDataSkippingNoAlleleAndWithReference() {
final Object[][] raw = readCountsAndAlleleCountData();
final List<Object[]> result = new ArrayList<>(raw.length);
for (final Object[] paramSet : raw)
if (!paramSet[2].equals(true) || !paramSet[1].equals(0))
result.add(paramSet);
return result.toArray(new Object[result.size()][]);
}
@DataProvider(name="readCountsAndAlleleCountDataSkippingNoLikelihoodsOrNoAlleleAndWithReference")
public Object[][] readCountsAndAlleleCountDataSkippingNoLikelihoodsOrNoAlleleAndWithReference() {
final Object[][] raw = readCountsAndAlleleCountDataSkippingNoAlleleAndWithReference();
final List<Object[]> result = new ArrayList<>(raw.length);
for (final Object[] paramSet : raw) {
final int[] readCounts = (int[]) paramSet[0];
final long totalReadCount = MathUtils.sum(readCounts);
if (totalReadCount > 0)
result.add(paramSet);
}
return result.toArray(new Object[result.size()][]);
}
private SampleList sampleList(final int[] readCounts) {
final List<String> samples = new ArrayList<>(readCounts.length);
for (int i = 0; i < readCounts.length; i++)
samples.add("SAMPLE_" + i);
return new IndexedSampleList(samples);
}
}