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/* Copyright (C) 2013 Ion Torrent Systems, Inc. All Rights Reserved */
//! @file BAMWalkerEngine.h
//! @ingroup VariantCaller
//! @brief Streamed BAM reader
#include "BAMWalkerEngine.h"
#include <algorithm>
#include <errno.h>
#include <limits.h>
#include <set>
#include "ReferenceReader.h"
BAMWalkerEngine::BAMWalkerEngine()
{
targets_manager_ = NULL;
next_target_ = NULL;
next_position_ = 0;
last_processed_chr_ = 0;
last_processed_pos_ = 0;
has_more_alignments_ = true;
has_more_positions_ = true;
tmp_begin_ = NULL;
tmp_end_ = NULL;
processing_first_ = NULL;
processing_last_ = NULL;
alignments_first_ = NULL;
alignments_last_ = NULL;
read_counter_ = 0;
recycle_ = NULL;
recycle_size_ = 0;
first_excess_read_ = 0;
first_useful_read_ = 0;
bam_writing_enabled_ = false;
pthread_mutex_init(&recycle_mutex_, NULL);
temp_read_size = 100;
temp_reads.resize(temp_read_size);
next_temp_read = NULL;
}
BAMWalkerEngine::~BAMWalkerEngine()
{
pthread_mutex_destroy(&recycle_mutex_);
}
void BAMWalkerEngine::Initialize(const ReferenceReader& ref_reader, TargetsManager& targets_manager,
const vector<string>& bam_filenames, const string& postprocessed_bam, int px)
{
InitializeBAMs(ref_reader, bam_filenames);
targets_manager_ = &targets_manager;
next_target_ = &targets_manager_->merged.front();
next_position_ = next_target_->begin;
prefix_exclude = px;
// BAM writing init
if (not postprocessed_bam.empty()) {
bam_writing_enabled_ = true;
SamHeader tmp_header = bam_header_;
tmp_header.Comments.clear();
tmp_header.Programs.Clear();
bam_writer_.SetCompressionMode(BamWriter::Compressed);
//bam_writer_.SetNumThreads(4);
if (not bam_writer_.Open(postprocessed_bam, tmp_header, bam_reader_.GetReferenceData())) {
cerr << "ERROR: Could not open postprocessed BAM file for writing : " << bam_writer_.GetErrorString();
exit(1);
}
}
}
void BAMWalkerEngine::Close()
{
if (bam_writing_enabled_)
bam_writer_.Close();
bam_reader_.Close();
}
// open BAM input file
void BAMWalkerEngine::InitializeBAMs(const ReferenceReader& ref_reader, const vector<string>& bam_filenames)
{
if (not bam_reader_.SetExplicitMergeOrder(BamMultiReader::MergeByCoordinate)) {
cerr << "ERROR: Could not set merge order to BamMultiReader::MergeByCoordinate" << endl;
exit(1);
}
if (not bam_reader_.Open(bam_filenames)) {
cerr << "ERROR: Could not open input BAM file(s) : " << bam_reader_.GetErrorString() << endl;
exit(1);
}
if (not bam_reader_.LocateIndexes()) {
cerr << "ERROR: Could not open BAM index file(s) : " << bam_reader_.GetErrorString() << endl;
exit(1);
}
// BAM multi reader combines the read group information of the different BAMs but does not merge comment sections
bam_header_ = bam_reader_.GetHeader();
if (!bam_header_.HasReadGroups()) {
cerr << "ERROR: there is no read group in BAM files specified" << endl;
exit(1);
}
// Manually merge comment sections of BAM files if we have more than one BAM file
if (bam_filenames.size() > 1) {
unsigned int num_duplicates = 0;
unsigned int num_merged = 0;
for (unsigned int bam_idx = 0; bam_idx < bam_filenames.size(); bam_idx++) {
BamReader reader;
if (not reader.Open(bam_filenames.at(bam_idx))) {
cerr << "TVC ERROR: Failed to open input BAM file " << reader.GetErrorString() << endl;
exit(1);
}
SamHeader header = reader.GetHeader();
for (unsigned int i_co = 0; i_co < header.Comments.size(); i_co++) {
// Step 1: Check if this comment is already part of the merged header
unsigned int m_co = 0;
while (m_co < bam_header_.Comments.size() and bam_header_.Comments.at(m_co) != header.Comments.at(i_co))
m_co++;
if (m_co < bam_header_.Comments.size()){
num_duplicates++;
continue;
}
// Add comment line to merged header if it is a new one
num_merged++;
bam_header_.Comments.push_back(header.Comments.at(i_co));
}
}
// Verbose what we did
cout << "Merged " << num_merged << " unique comment lines into combined BAM header. Encountered " << num_duplicates << " duplicate comments." << endl;
}
//
// Reference sequences in the bam file must match that in the fasta file
//
vector<RefData> referenceSequences = bam_reader_.GetReferenceData();
if ((int)referenceSequences.size() != ref_reader.chr_count()) {
cerr << "ERROR: Reference in BAM file does not match fasta file" << endl
<< " BAM has " << referenceSequences.size()
<< " chromosomes while fasta has " << ref_reader.chr_count() << endl;
exit(1);
}
for (int chr_idx = 0; chr_idx < ref_reader.chr_count(); ++chr_idx) {
if (referenceSequences[chr_idx].RefName != ref_reader.chr_str(chr_idx)) {
cerr << "ERROR: Reference in BAM file does not match fasta file" << endl
<< " Chromosome #" << (chr_idx+1) << "in BAM is " << referenceSequences[chr_idx].RefName
<< " while fasta has " << ref_reader.chr_str(chr_idx) << endl;
exit(1);
}
if (referenceSequences[chr_idx].RefLength != ref_reader.chr_size(chr_idx)) {
cerr << "ERROR: Reference in BAM file does not match fasta file" << endl
<< " Chromosome " << referenceSequences[chr_idx].RefName
<< "in BAM has length " << referenceSequences[chr_idx].RefLength
<< " while fasta has " << ref_reader.chr_size(chr_idx) << endl;
exit(1);
}
}
//
// Retrieve BaseCaller and TMAP version strings from BAM header
//
set<string> basecaller_versions;
set<string> tmap_versions;
for (SamProgramIterator I = bam_header_.Programs.Begin(); I != bam_header_.Programs.End(); ++I) {
if (I->ID.substr(0,2) == "bc")
basecaller_versions.insert(I->Version);
if (I->ID.substr(0,4) == "tmap")
tmap_versions.insert(I->Version);
}
basecaller_version_ = "";
for (set<string>::const_iterator I = basecaller_versions.begin(); I != basecaller_versions.end(); ++I) {
if (not basecaller_version_.empty())
basecaller_version_ += ", ";
basecaller_version_ += *I;
}
tmap_version_ = "";
for (set<string>::const_iterator I = tmap_versions.begin(); I != tmap_versions.end(); ++I) {
if (not tmap_version_.empty())
tmap_version_ += ", ";
tmap_version_ += *I;
}
}
bool BAMWalkerEngine::EligibleForReadRemoval()
{
return alignments_first_ and alignments_first_->read_number+100 < first_useful_read_;
}
void BAMWalkerEngine::RequestReadRemovalTask(Alignment*& removal_list)
{
removal_list = alignments_first_;
Alignment *list_end = removal_list;
while (alignments_first_ and alignments_first_->read_number < first_useful_read_) {
list_end = alignments_first_;
alignments_first_ = alignments_first_->next;
}
if (list_end == removal_list)
removal_list = NULL;
else
list_end->next = NULL;
}
void BAMWalkerEngine::SaveAlignments(Alignment* removal_list)
{
if (not bam_writing_enabled_)
return;
// if (!removal_list) removal_list = alignments_first_;
for (Alignment *current_read = removal_list; current_read; current_read = current_read->next) {
if (not current_read->worth_saving)
continue;
current_read->alignment.RemoveTag("ZM");
current_read->alignment.RemoveTag("ZP");
current_read->alignment.RemoveTag("PG");
bam_writer_.SaveAlignment(current_read->alignment);
}
}
void BAMWalkerEngine::FinishReadRemovalTask(Alignment* removal_list)
{
pthread_mutex_lock(&recycle_mutex_);
while (removal_list) {
Alignment *excess = removal_list;
removal_list = removal_list->next;
if (recycle_size_ > 55000) {
delete excess;
} else {
excess->next = recycle_;
recycle_ = excess;
recycle_size_++;
}
}
pthread_mutex_unlock(&recycle_mutex_);
}
bool BAMWalkerEngine::EligibleForGreedyRead()
{
if (not has_more_alignments_)
return false;
return read_counter_ < (first_excess_read_ + 10000);
}
bool BAMWalkerEngine::ReadyForNextPosition()
{
// Try Getting More Reads - if just starting
if (not alignments_last_)
return false;
// Try Getting More Reads - if target regions positions have been processed, but there are more reads
if (not has_more_positions_) // and has_more_alignments_)
return false;
// Try Generating a Variant - if processed reads are ahead of current position
if (last_processed_chr_ > next_target_->chr or
(last_processed_chr_ == next_target_->chr and last_processed_pos_ > next_position_))
return true;
// Try Generating a Variant (or quitting) - if all reads have been loaded and processed
if (not has_more_alignments_ and not processing_first_)
return true;
return false;
}
void BAMWalkerEngine::RequestReadProcessingTask(Alignment* & new_read)
{
pthread_mutex_lock(&recycle_mutex_);
if (recycle_) {
new_read = recycle_;
recycle_ = recycle_->next;
recycle_size_--;
pthread_mutex_unlock(&recycle_mutex_);
new_read->Reset();
} else {
pthread_mutex_unlock(&recycle_mutex_);
try {
new_read = new Alignment;
}
catch(std::bad_alloc& exc)
{
cerr << "ERROR: failed to allocate memory in reading BAM in BAMWalkerEngine::RequestReadProcessingTask" << endl;
exit(1);
}
}
new_read->read_number = read_counter_++;
if (alignments_last_)
alignments_last_->next = new_read;
else
alignments_first_ = new_read;
alignments_last_ = new_read;
// Add new read to the end of the "processing" list
if (processing_last_) {
processing_last_->processing_next = new_read;
new_read->processing_prev = processing_last_;
processing_last_ = new_read;
} else {
processing_first_ = new_read;
processing_last_ = new_read;
}
}
static int prefix_exclude_ = 6;
static bool myorder(BamAlignment *A, BamAlignment *B)
{
return (A->Name.substr(prefix_exclude_).compare(B->Name.substr(prefix_exclude_)) > 0);
}
bool BAMWalkerEngine::GetNextAlignmentCore(Alignment* new_read)
{
//return has_more_alignments_ = (bam_reader_.GetNextAlignmentCore(new_read->alignment) && new_read!=NULL && new_read->alignment.RefID>=0);
// maintain a list of all reads that are in order of read name if the position is the same, ZZ
if (temp_heap.size() == 0) {
int i = 0;
if (next_temp_read) {
temp_reads[0] = *next_temp_read;
i = 1;
next_temp_read = NULL;
}
temp_heap.clear();
do {
if (!bam_reader_.GetNextAlignmentCore(temp_reads[i])) break;
temp_reads[i].BuildCharData();
if (temp_reads[i].RefID < 0) break;
if (temp_reads[i].Position != temp_reads[0].Position or temp_reads[i].RefID != temp_reads[0].RefID) {
next_temp_read = &temp_reads[i];
break;
}
i++;
if (i >= temp_read_size) {
temp_read_size *= 2;
temp_reads.resize(temp_read_size);
}
} while (1);
if (i == 0) return has_more_alignments_ = false;
for (int j = 0; j < i; j++) {
temp_heap.push_back(&temp_reads[j]);
}
if (temp_heap.size() > 1) {
prefix_exclude_ = prefix_exclude;
std::sort(temp_heap.begin(), temp_heap.end(), myorder); // sort into descending order by read Name
}
}
new_read->alignment = *(temp_heap.back()); // output read by ascending order of read Name using popback.
temp_heap.pop_back();
return has_more_alignments_ = true;
}
void BAMWalkerEngine::FinishReadProcessingTask(Alignment* new_read, bool success)
{
new_read->processed = success;
if (success and new_read == processing_first_) {
last_processed_chr_ = new_read->alignment.RefID;
last_processed_pos_ = new_read->original_position;
// Special case. If no positions are being processed and this read ends before the next position, trigger a cleanup
if (positions_in_progress_.empty() and (new_read->alignment.RefID < next_target_->chr
or (new_read->alignment.RefID == next_target_->chr and new_read->end <= next_position_))) {
Alignment *useful_read = alignments_first_;
while (useful_read != new_read and (useful_read->alignment.RefID < next_target_->chr
or (useful_read->alignment.RefID == next_target_->chr and useful_read->end <= next_position_))) {
useful_read = useful_read->next;
}
first_useful_read_ = max(first_useful_read_,useful_read->read_number);
tmp_begin_ = NULL;
tmp_end_ = NULL;
}
if (not has_more_positions_ and positions_in_progress_.empty())
first_useful_read_ = max(first_useful_read_,new_read->read_number);
}
if (new_read->processing_prev)
new_read->processing_prev->processing_next = new_read->processing_next;
else
processing_first_ = new_read->processing_next;
if (new_read->processing_next)
new_read->processing_next->processing_prev = new_read->processing_prev;
else
processing_last_ = new_read->processing_prev;
}
void BAMWalkerEngine::BeginPositionProcessingTask(list<PositionInProgress>::iterator& position_ticket)
{
if (not tmp_begin_)
tmp_begin_ = alignments_first_;
while (tmp_begin_ and (
(tmp_begin_->alignment.RefID == next_target_->chr and tmp_begin_->end <= next_position_)
or tmp_begin_->alignment.RefID < next_target_->chr)
and tmp_begin_->processed)
tmp_begin_ = tmp_begin_->next;
if (not tmp_end_)
tmp_end_ = tmp_begin_;
while (tmp_end_ and (
(tmp_end_->alignment.RefID == next_target_->chr and tmp_end_->original_position <= next_position_)
or tmp_end_->alignment.RefID < next_target_->chr)
and tmp_end_->processed)
tmp_end_ = tmp_end_->next;
positions_in_progress_.push_back(PositionInProgress());
position_ticket = positions_in_progress_.end();
--position_ticket;
position_ticket->chr = next_target_->chr;
position_ticket->pos = next_position_;
position_ticket->target_end = next_target_->end;
position_ticket->begin = tmp_begin_;
position_ticket->end = tmp_end_;
position_ticket->start_time = time(NULL);
first_excess_read_ = tmp_end_->read_number;
}
bool BAMWalkerEngine::AdvancePosition(int position_increment, int next_hotspot_chr, long next_hotspot_position)
{
next_position_ += position_increment;
// Skip-ahead logic for sparse BAMs
if (tmp_begin_) {
int closest_chr = tmp_begin_->alignment.RefID;
int closest_pos = tmp_begin_->original_position;
if (next_hotspot_chr >= 0) {
if (next_hotspot_chr < closest_chr or (next_hotspot_chr == closest_chr and next_hotspot_position < closest_pos)) {
// actually the hotspot is closer
closest_chr = next_hotspot_chr;
closest_pos = next_hotspot_position;
}
}
if (next_target_->chr < closest_chr)
next_position_ = next_target_->end; // Just force transition to next target
else if (next_target_->chr == closest_chr and next_position_ < closest_pos)
next_position_ = closest_pos;
}
if (next_position_ >= next_target_->end) {
if (next_target_ == &targets_manager_->merged.back()) {// Can't go any further
has_more_positions_ = false;
return false;
}
next_target_++;
next_position_ = next_target_->begin;
}
return true;
}
void BAMWalkerEngine::FinishPositionProcessingTask(list<PositionInProgress>::iterator& position_ticket)
{
time_t delta = time(NULL) - position_ticket->start_time;
if (delta > 60) {
cerr<< "WARNING: Variant " << bam_reader_.GetReferenceData()[position_ticket->chr].RefName << ":" << (position_ticket->pos+1)
<<" has unexpected processing time of " << delta << " seconds." << endl;
}
if (position_ticket == positions_in_progress_.begin()) {
first_useful_read_ = max(first_useful_read_,position_ticket->begin->read_number);
positions_in_progress_.erase(position_ticket);
if (not positions_in_progress_.empty()) {
first_useful_read_ = max(first_useful_read_,positions_in_progress_.begin()->begin->read_number);
}
} else {
positions_in_progress_.erase(position_ticket);
}
}
int BAMWalkerEngine::GetRecentUnmergedTarget()
{
MergedTarget *my_next_target = next_target_;
if (my_next_target)
return my_next_target->first_unmerged;
else
return 0;
}
bool BAMWalkerEngine::MemoryContention()
{
if (positions_in_progress_.empty())
return false;
if (not alignments_first_)
return false;
if (read_counter_ - alignments_first_->read_number < 50000)
return false;
return true;
}
bool BAMWalkerEngine::IsEarlierstPositionProcessingTask(list<PositionInProgress>::iterator& position_ticket)
{
return position_ticket == positions_in_progress_.begin();
}
void BAMWalkerEngine::PrintStatus()
{
cerr<< "BAMWalkerEngine:"
<< " start=" << alignments_first_->read_number
<< " in_memory=" << read_counter_ - alignments_first_->read_number
<< " deleteable=" << first_useful_read_ - alignments_first_->read_number
<< " read_ahead=" << read_counter_ - first_excess_read_
<< " recycle=" << recycle_size_ << endl;
}
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