// Check that all the strings in the vector align to the same coordinates
// of the passed in sequence
bool HapgenUtil::checkAlignmentsAreConsistent(const std::string& refString, const StringVector& queries)
{
if(queries.empty())
return true;
// Perform local alignments of each query to the refString
LocalAlignmentResultVector alignments;
for(size_t i = 0; i < queries.size(); ++i)
alignments.push_back(StdAlnTools::localAlignment(refString, queries[i]));
size_t i = 0;
for(size_t j = 1; j < alignments.size(); ++j)
{
if(alignments[i].targetStartIndex != alignments[j].targetStartIndex ||
alignments[j].targetEndIndex != alignments[j].targetEndIndex)
{
std::cerr << "Warning: inconsistent alignments found for haplotype realignment\n";
std::cerr << "A[" << i << "]: " << alignments[i] << "\n";
std::cerr << "A[" << j << "]: " << alignments[j] << "\n";
return false;
}
}
return true;
}
// Align a bunch of reads locally to a sequence
LocalAlignmentResultVector HapgenUtil::alignReadsLocally(const std::string& target, const SeqItemVector& reads)
{
LocalAlignmentResultVector results;
for(size_t i = 0; i < reads.size(); ++i)
{
LocalAlignmentResult fwdAR = StdAlnTools::localAlignment(target, reads[i].seq.toString());
LocalAlignmentResult rcAR = StdAlnTools::localAlignment(target, reverseComplement(reads[i].seq.toString()));
results.push_back(fwdAR.score > rcAR.score ? fwdAR : rcAR);
}
return results;
}
// Compute the best alignment of the haplotype collection to the reference
DindelReturnCode DindelUtil::computeBestAlignment(const StringVector& inHaplotypes,
const SeqItemVector& variantMates,
const SeqItemVector& variantRCMates,
const GraphCompareParameters& parameters,
HapgenAlignment& bestAlignment)
{
size_t MAX_DEPTH = 2000;
if(variantMates.size() + variantRCMates.size() > MAX_DEPTH)
return DRC_OVER_DEPTH;
//
// Align the haplotypes to the reference genome to generate candidate alignments
//
HapgenAlignmentVector candidateAlignments;
for(size_t i = 0; i < inHaplotypes.size(); ++i)
HapgenUtil::alignHaplotypeToReferenceBWASW(inHaplotypes[i], parameters.referenceIndex, candidateAlignments);
// Remove duplicate or bad alignment pairs
HapgenUtil::coalesceAlignments(candidateAlignments);
if(candidateAlignments.empty())
return DRC_NO_ALIGNMENT;
//
// Score each candidate alignment against the mates of all the variant reads
//
int bestCandidate = -1;
double bestAverageScoreFrac = 0.0f;
double secondBest = 0.0f;
for(size_t i = 0; i < candidateAlignments.size(); ++i)
{
// Compute the average score of the reads' mates to the flanking sequence
StringVector referenceFlanking;
StringVector referenceHaplotypes;
HapgenUtil::makeFlankingHaplotypes(candidateAlignments[i], parameters.pRefTable,
1000, inHaplotypes, referenceFlanking, referenceHaplotypes);
// If valid flanking haplotypes could not be made, skip this alignment
if(referenceFlanking.empty())
continue;
// Realign the mates
LocalAlignmentResultVector localAlignments = HapgenUtil::alignReadsLocally(referenceFlanking[0], variantMates);
LocalAlignmentResultVector localAlignmentsRC = HapgenUtil::alignReadsLocally(referenceFlanking[0], variantRCMates);
// Merge alignments
localAlignments.insert(localAlignments.end(), localAlignmentsRC.begin(), localAlignmentsRC.end());
double sum = 0.0f;
double count = 0.0f;
for(size_t j = 0; j < localAlignments.size(); ++j)
{
double max_score = localAlignments[j].queryEndIndex - localAlignments[j].queryStartIndex + 1;
double frac = (double)localAlignments[j].score / max_score;
//printf("Score: %d frac: %lf\n", localAlignments[j].score, frac);
sum += frac;
count += 1;
}
double score = sum / count;
if(score > bestAverageScoreFrac)
{
secondBest = bestAverageScoreFrac;
bestAverageScoreFrac = score;
bestCandidate = i;
}
else if(score > secondBest)
{
secondBest = score;
}
//printf("Alignment %zu mate-score: %lf\n", i, score);
}
if(bestCandidate == -1)
return DRC_NO_ALIGNMENT;
/*
if(bestAverageScoreFrac < 0.9f)
return DRC_POOR_ALIGNMENT;
if(bestAverageScoreFrac - secondBest < 0.05f)
return DRC_AMBIGUOUS_ALIGNMENT;
*/
bestAlignment = candidateAlignments[bestCandidate];
return DRC_OK;
}
