public double[] computeReadHaplotypeLikelihoods(
ReadBackedPileup pileup, HashMap<Allele, Haplotype> haplotypesInVC) {
double[][] haplotypeLikehoodMatrix = new double[haplotypesInVC.size()][haplotypesInVC.size()];
double readLikelihoods[][] = new double[pileup.getReads().size()][haplotypesInVC.size()];
int i = 0;
for (GATKSAMRecord read : pileup.getReads()) {
if (ReadUtils.is454Read(read)) {
continue;
}
// for each read/haplotype combination, compute likelihoods, ie -10*log10(Pr(R | Hi))
// = sum_j(-10*log10(Pr(R_j | Hi) since reads are assumed to be independent
int j = 0;
for (Map.Entry<Allele, Haplotype> a : haplotypesInVC.entrySet()) {
readLikelihoods[i][j] = computeReadLikelihoodGivenHaplotype(a.getValue(), read);
if (DEBUG) {
System.out.print(read.getReadName() + " ");
System.out.format(
"%d %d S:%d US:%d E:%d UE:%d C:%s %3.4f\n",
i,
j,
read.getAlignmentStart(),
read.getUnclippedStart(),
read.getAlignmentEnd(),
read.getUnclippedEnd(),
read.getCigarString(),
readLikelihoods[i][j]);
}
j++;
}
i++;
}
for (i = 0; i < haplotypesInVC.size(); i++) {
for (int j = i; j < haplotypesInVC.size(); j++) {
// combine likelihoods of haplotypeLikelihoods[i], haplotypeLikelihoods[j]
// L(Hi, Hj) = sum_reads ( Pr(R|Hi)/2 + Pr(R|Hj)/2)
// readLikelihoods[k][j] has log10(Pr(R_k) | H[j] )
double[] readLikelihood = new double[2]; // diploid sample
for (int readIdx = 0; readIdx < pileup.getReads().size(); readIdx++) {
readLikelihood[0] = -readLikelihoods[readIdx][i] / 10;
readLikelihood[1] = -readLikelihoods[readIdx][j] / 10;
// Compute log10(10^x1/2 + 10^x2/2) = log10(10^x1+x0^x2)-log10(2)
// First term is approximated by Jacobian log with table lookup.
// Second term is a constant added to both likelihoods so will be ignored
haplotypeLikehoodMatrix[i][j] +=
MathUtils.approximateLog10SumLog10(readLikelihood[0], readLikelihood[1]);
}
}
}
return getHaplotypeLikelihoods(haplotypeLikehoodMatrix);
}
/**
* Computes an allele biased version of the given pileup
*
* @param pileup the original pileup
* @param downsamplingFraction the fraction of total reads to remove per allele
* @return allele biased pileup
*/
public static ReadBackedPileup createAlleleBiasedBasePileup(
final ReadBackedPileup pileup, final double downsamplingFraction) {
// special case removal of all or no reads
if (downsamplingFraction <= 0.0) return pileup;
if (downsamplingFraction >= 1.0)
return new ReadBackedPileupImpl(pileup.getLocation(), new ArrayList<PileupElement>());
final PileupElementList[] alleleStratifiedElements = new PileupElementList[4];
for (int i = 0; i < 4; i++) alleleStratifiedElements[i] = new PileupElementList();
// start by stratifying the reads by the alleles they represent at this position
for (final PileupElement pe : pileup) {
final int baseIndex = BaseUtils.simpleBaseToBaseIndex(pe.getBase());
if (baseIndex != -1) alleleStratifiedElements[baseIndex].add(pe);
}
// make a listing of allele counts and calculate the total count
final int[] alleleCounts = calculateAlleleCounts(alleleStratifiedElements);
final int totalAlleleCount = (int) MathUtils.sum(alleleCounts);
// do smart down-sampling
final int numReadsToRemove = (int) (totalAlleleCount * downsamplingFraction); // floor
final int[] targetAlleleCounts = runSmartDownsampling(alleleCounts, numReadsToRemove);
final HashSet<PileupElement> readsToRemove = new HashSet<PileupElement>(numReadsToRemove);
for (int i = 0; i < 4; i++) {
final PileupElementList alleleList = alleleStratifiedElements[i];
// if we don't need to remove any reads, then don't
if (alleleCounts[i] > targetAlleleCounts[i])
readsToRemove.addAll(
downsampleElements(
alleleList, alleleCounts[i], alleleCounts[i] - targetAlleleCounts[i]));
}
// we need to keep the reads sorted because the FragmentUtils code will expect them in
// coordinate order and will fail otherwise
final List<PileupElement> readsToKeep =
new ArrayList<PileupElement>(totalAlleleCount - numReadsToRemove);
for (final PileupElement pe : pileup) {
if (!readsToRemove.contains(pe)) {
readsToKeep.add(pe);
}
}
return new ReadBackedPileupImpl(
pileup.getLocation(), new ArrayList<PileupElement>(readsToKeep));
}
public Event map(RefMetaDataTracker tracker, ReferenceContext ref, AlignmentContext context) {
boolean hasIndel = false;
boolean hasInsertion = false;
boolean hasPointEvent = false;
int furthestStopPos = -1;
// look at the rods for indels or SNPs
if (tracker != null) {
for (VariantContext vc : tracker.getValues(known)) {
switch (vc.getType()) {
case INDEL:
hasIndel = true;
if (vc.isSimpleInsertion()) hasInsertion = true;
break;
case SNP:
hasPointEvent = true;
break;
case MIXED:
hasPointEvent = true;
hasIndel = true;
if (vc.isSimpleInsertion()) hasInsertion = true;
break;
default:
break;
}
if (hasIndel) furthestStopPos = vc.getEnd();
}
}
// look at the normal context to get deletions and positions with high entropy
final ReadBackedPileup pileup = context.getBasePileup();
int mismatchQualities = 0, totalQualities = 0;
final byte refBase = ref.getBase();
for (PileupElement p : pileup) {
// check the ends of the reads to see how far they extend
furthestStopPos = Math.max(furthestStopPos, p.getRead().getAlignmentEnd());
// is it a deletion or insertion?
if (p.isDeletion() || p.isBeforeInsertion()) {
hasIndel = true;
if (p.isBeforeInsertion()) hasInsertion = true;
}
// look for mismatches
else if (lookForMismatchEntropy) {
if (p.getBase() != refBase) mismatchQualities += p.getQual();
totalQualities += p.getQual();
}
}
// make sure we're supposed to look for high entropy
if (lookForMismatchEntropy
&& pileup.getNumberOfElements() >= minReadsAtLocus
&& (double) mismatchQualities / (double) totalQualities >= mismatchThreshold)
hasPointEvent = true;
// return null if no event occurred
if (!hasIndel && !hasPointEvent) return null;
// return null if we didn't find any usable reads/rods associated with the event
if (furthestStopPos == -1) return null;
GenomeLoc eventLoc = context.getLocation();
if (hasInsertion)
eventLoc =
getToolkit()
.getGenomeLocParser()
.createGenomeLoc(eventLoc.getContig(), eventLoc.getStart(), eventLoc.getStart() + 1);
EVENT_TYPE eventType =
(hasIndel
? (hasPointEvent ? EVENT_TYPE.BOTH : EVENT_TYPE.INDEL_EVENT)
: EVENT_TYPE.POINT_EVENT);
return new Event(eventLoc, furthestStopPos, eventType);
}
