// we need to pad ref by at least the bandwidth / 2 on either side
public BAQCalculationResult calcBAQFromHMM(SAMRecord read, byte[] ref, int refOffset) {
// todo -- need to handle the case where the cigar sum of lengths doesn't cover the whole read
Pair<Integer, Integer> queryRange = calculateQueryRange(read);
if (queryRange == null) return null; // read has Ns, or is completely clipped away
int queryStart = queryRange.getFirst();
int queryEnd = queryRange.getSecond();
BAQCalculationResult baqResult =
calcBAQFromHMM(ref, read.getReadBases(), read.getBaseQualities(), queryStart, queryEnd);
// cap quals
int readI = 0, refI = 0;
for (CigarElement elt : read.getCigar().getCigarElements()) {
int l = elt.getLength();
switch (elt.getOperator()) {
case N: // cannot handle these
return null;
case H:
case P: // ignore pads and hard clips
break;
case S:
refI += l; // move the reference too, in addition to I
case I:
// todo -- is it really the case that we want to treat I and S the same?
for (int i = readI; i < readI + l; i++) baqResult.bq[i] = baqResult.rawQuals[i];
readI += l;
break;
case D:
refI += l;
break;
case M:
for (int i = readI; i < readI + l; i++) {
int expectedPos = refI - refOffset + (i - readI);
baqResult.bq[i] =
capBaseByBAQ(
baqResult.rawQuals[i], baqResult.bq[i], baqResult.state[i], expectedPos);
}
readI += l;
refI += l;
break;
default:
throw new ReviewedGATKException(
"BUG: Unexpected CIGAR element " + elt + " in read " + read.getReadName());
}
}
if (readI != read.getReadLength()) // odd cigar string
System.arraycopy(baqResult.rawQuals, 0, baqResult.bq, 0, baqResult.bq.length);
return baqResult;
}
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;
}
public static boolean isEmpty(final SAMRecord read) {
return read.getReadBases() == null || read.getReadLength() == 0;
}
