/**
* Loop over all of the reads in this likelihood map and realign them to its most likely haplotype
*
* @param haplotypes the collection of haplotypes
* @param paddedReferenceLoc the active region
*/
public void realignReadsToMostLikelyHaplotype(
final Collection<Haplotype> haplotypes, final GenomeLoc paddedReferenceLoc) {
// we need to remap the Alleles back to the Haplotypes; inefficient but unfortunately this is a
// requirement currently
final Map<Allele, Haplotype> alleleToHaplotypeMap = new HashMap<>(haplotypes.size());
Haplotype refHaplotype = null;
for (final Haplotype haplotype : haplotypes) {
alleleToHaplotypeMap.put(Allele.create(haplotype.getBases()), haplotype);
if (refHaplotype == null && haplotype.isReference()) refHaplotype = haplotype;
}
final Map<GATKSAMRecord, Map<Allele, Double>> newLikelihoodReadMap =
new LinkedHashMap<>(likelihoodReadMap.size());
for (final Map.Entry<GATKSAMRecord, Map<Allele, Double>> entry : likelihoodReadMap.entrySet()) {
final MostLikelyAllele bestAllele =
PerReadAlleleLikelihoodMap.getMostLikelyAllele(entry.getValue());
final GATKSAMRecord alignedToRef =
AlignmentUtils.createReadAlignedToRef(
entry.getKey(),
alleleToHaplotypeMap.get(bestAllele.getMostLikelyAllele()),
refHaplotype,
paddedReferenceLoc.getStart(),
bestAllele.isInformative());
newLikelihoodReadMap.put(alignedToRef, entry.getValue());
}
likelihoodReadMap.clear();
likelihoodReadMap.putAll(newLikelihoodReadMap);
}
public double computeReadLikelihoodGivenHaplotype(Haplotype haplotype, SAMRecord read) {
long numStartClippedBases = 0;
long numEndClippedBases = 0;
byte[] unclippedReadQuals = read.getBaseQualities();
byte[] unclippedReadBases = read.getReadBases();
// Do a stricter base clipping than provided by CIGAR string, since this one may be too
// conservative,
// and may leave a string of Q2 bases still hanging off the reads.
for (int i = 0; i < read.getReadLength(); i++) {
if (unclippedReadQuals[i] < BASE_QUAL_THRESHOLD) numStartClippedBases++;
else break;
}
for (int i = read.getReadLength() - 1; i >= 0; i--) {
if (unclippedReadQuals[i] < BASE_QUAL_THRESHOLD) numEndClippedBases++;
else break;
}
// System.out.format("numstart: %d numend: %d\n", numStartClippedBases, numEndClippedBases);
if (numStartClippedBases + numEndClippedBases >= read.getReadLength()) {
return 0; /// Double.POSITIVE_INFINITY;
}
byte[] readBases =
Arrays.copyOfRange(
unclippedReadBases,
(int) numStartClippedBases,
(int) (read.getReadBases().length - numEndClippedBases));
byte[] readQuals =
Arrays.copyOfRange(
unclippedReadQuals,
(int) numStartClippedBases,
(int) (read.getReadBases().length - numEndClippedBases));
int readLength = readBases.length;
// initialize path metric and traceback memories for Viterbi computation
pathMetricArray = new double[readLength + 1][PATH_METRIC_TABLE_LENGTH];
bestStateIndexArray = new int[readLength + 1][PATH_METRIC_TABLE_LENGTH];
for (int k = 1; k < PATH_METRIC_TABLE_LENGTH; k++) pathMetricArray[0][k] = 0;
/*
if (doSimpleCalculationModel) {
// No Viterbi algorithm - assume no sequencing indel artifacts,
// so we can collapse computations and pr(read | haplotype) is just probability of observing overlap
// of read with haplotype.
int haplotypeIndex = initialIndexInHaplotype;
double c = 0.0;//deletionErrorProbabilities[1] +logOneMinusInsertionStartProbability;
// compute likelihood of portion of base to the left of the haplotype
for (int indR=readStartIdx-1; indR >= 0; indR--) {
byte readBase = readBases[indR];
byte readQual = readQuals[indR];
if (readQual <= 2)
continue;
double pBaseRead = getProbabilityOfReadBaseGivenXandI((byte)0, readBase, readQual, LEFT_ALIGN_INDEX, 0);
// pBaseRead has -10*log10(Prob(base[i]|haplotype[i])
pRead += pBaseRead;
}
//System.out.format("\nSt: %d Pre-Likelihood:%f\n",readStartIdx, pRead);
for (int indR=readStartIdx; indR < readBases.length; indR++) {
byte readBase = readBases[indR];
byte readQual = readQuals[indR];
byte haplotypeBase;
if (haplotypeIndex < RIGHT_ALIGN_INDEX)
haplotypeBase = haplotype.getBases()[haplotypeIndex];
else
haplotypeBase = (byte)0; // dummy
double pBaseRead = getProbabilityOfReadBaseGivenXandI(haplotypeBase, readBase, readQual, haplotypeIndex, 0);
if (haplotypeBase != 0)
pBaseRead += c;
// pBaseRead has -10*log10(Prob(base[i]|haplotype[i])
if (readQual > 3)
pRead += pBaseRead;
haplotypeIndex++;
if (haplotypeIndex >= haplotype.getBases().length)
haplotypeIndex = RIGHT_ALIGN_INDEX;
//System.out.format("H:%c R:%c RQ:%d HI:%d %4.5f %4.5f\n", haplotypeBase, readBase, (int)readQual, haplotypeIndex, pBaseRead, pRead);
}
//System.out.format("\nSt: %d Post-Likelihood:%f\n",readStartIdx, pRead);
if (DEBUG) {
System.out.println(read.getReadName());
System.out.print("Haplotype:");
for (int k=0; k <haplotype.getBases().length; k++) {
System.out.format("%c ", haplotype.getBases()[k]);
}
System.out.println();
System.out.print("Read bases: ");
for (int k=0; k <readBases.length; k++) {
System.out.format("%c ", readBases[k]);
}
System.out.format("\nLikelihood:%f\n",pRead);
}
if (read.getReadName().contains("106880")) {
System.out.println("aca");
System.out.println("Haplotype:");
for (int k=initialIndexInHaplotype; k <haplotype.getBases().length; k++) {
System.out.format("%c ", haplotype.getBases()[k]);
}
System.out.println();
System.out.println("Read bases: ");
for (int k=readStartIdx; k <readBases.length; k++) {
System.out.format("%c ", readBases[k]);
}
}
return pRead;
}
*/
// Update path metric computations based on branch metric (Add/Compare/Select operations)
// do forward direction first, ie from anchor to end of read
// outer loop
for (int indR = 0; indR < readLength; indR++) {
byte readBase = readBases[indR];
byte readQual = readQuals[indR];
for (int indX = LEFT_ALIGN_INDEX; indX <= RIGHT_ALIGN_INDEX; indX++) {
byte haplotypeBase;
if (indX > LEFT_ALIGN_INDEX && indX < RIGHT_ALIGN_INDEX)
haplotypeBase = haplotype.getBases()[indX - 1];
else haplotypeBase = readBase;
updatePathMetrics(haplotypeBase, indX, indR, readBase, readQual);
}
}
// for debugging only: compute backtracking to find optimal route through trellis. Since I'm
// only interested
// in log-likelihood of best state, this isn't really necessary.
double bestMetric = MathUtils.arrayMin(pathMetricArray[readLength]);
if (DEBUG) {
System.out.println(read.getReadName());
System.out.print("Haplotype:");
for (int k = 0; k < haplotype.getBases().length; k++) {
System.out.format("%c ", haplotype.getBases()[k]);
}
System.out.println();
System.out.print("Read bases: ");
for (int k = 0; k < readBases.length; k++) {
System.out.format("%c ", readBases[k]);
}
System.out.println();
System.out.print("Read quals: ");
for (int k = 0; k < readQuals.length; k++) {
System.out.format("%d ", (int) readQuals[k]);
}
System.out.println();
// start from last position of read, go backwards to find optimal alignment
int[] bestIndexArray = new int[readLength];
int bestIndex = MathUtils.minElementIndex(pathMetricArray[readLength]);
bestIndexArray[readLength - 1] = bestIndex;
for (int k = readLength - 2; k >= 0; k--) {
bestIndex = bestStateIndexArray[k][bestIndex];
bestIndexArray[k] = bestIndex;
}
System.out.print("Alignment: ");
for (int k = 0; k < readBases.length; k++) {
System.out.format("%d ", bestIndexArray[k]);
}
System.out.println();
}
// now just take optimum along all path metrics: that's the log likelihood of best alignment
if (DEBUG) System.out.format("Likelihood: %5.4f\n", bestMetric);
return bestMetric;
}