void Device::write_log(const TraceIPC::packet_rw &pak_rw)
{
log_entry entry;
entry.offset = pak_rw.offset;
entry.value = pak_rw.value;
entry.new_value = pak_rw.is_write ? pak_rw.new_value : pak_rw.value;
entry.time = pak_rw.time;
entry.cpu_pc = pak_rw.cpu_pc;
entry.cpu_id = pak_rw.cpu_id;
entry.is_write = pak_rw.is_write;
entry.is_error = !is_offset_valid(pak_rw.offset);
entry.is_irq = false;
entry.clk_disabled = pak_rw.clk_disabled;
entry.in_reset = pak_rw.in_reset;
entry.custom = 0;
entry.rw_size = pak_rw.size * 8;
write_log(entry);
}
gchar* offset_to_ptr(GMappedFile* file, guint32 rva, guint32 size)
{
g_return_val_if_fail(is_offset_valid(file, rva, size), NULL);
return g_mapped_file_get_contents(file) + rva;
}
std::vector<AlignedPair> adaptive_banded_simple_event_align(SquiggleRead& read, const PoreModel& pore_model, const std::string& sequence)
{
size_t strand_idx = 0;
size_t k = pore_model.k;
const Alphabet* alphabet = pore_model.pmalphabet;
size_t n_events = read.events[strand_idx].size();
size_t n_kmers = sequence.size() - k + 1;
// backtrack markers
const uint8_t FROM_D = 0;
const uint8_t FROM_U = 1;
const uint8_t FROM_L = 2;
// qc
double min_average_log_emission = -5.0;
int max_gap_threshold = 50;
// banding
int bandwidth = ALN_BANDWIDTH;
int half_bandwidth = bandwidth / 2;
// transition penalties
double events_per_kmer = (double)n_events / n_kmers;
double p_stay = 1 - (1 / (events_per_kmer + 1));
// setting a tiny skip penalty helps keep the true alignment within the adaptive band
// this was empirically determined
double epsilon = 1e-10;
double lp_skip = log(epsilon);
double lp_stay = log(p_stay);
double lp_step = log(1.0 - exp(lp_skip) - exp(lp_stay));
double lp_trim = log(0.01);
// dp matrix
size_t n_rows = n_events + 1;
size_t n_cols = n_kmers + 1;
size_t n_bands = n_rows + n_cols;
// Initialize
// Precompute k-mer ranks to avoid doing this in the inner loop
std::vector<size_t> kmer_ranks(n_kmers);
for(size_t i = 0; i < n_kmers; ++i) {
kmer_ranks[i] = alphabet->kmer_rank(sequence.substr(i, k).c_str(), k);
}
float* bands = (float*)malloc(sizeof(float) * n_bands * bandwidth);
if(bands==NULL){
fprintf(stderr,"Memory allocation failed at %s\n",__func__);
exit(1);
}
uint8_t* trace = (uint8_t*)malloc(sizeof(uint8_t) * n_bands * bandwidth);
if(trace==NULL){
fprintf(stderr,"Memory allocation failed at %s\n",__func__);
exit(1);
}
for (size_t i = 0; i < n_bands; i++) {
for (int j = 0; j < bandwidth; j++) {
BAND_ARRAY(i,j) = -INFINITY;
TRACE_ARRAY(i,j) = 0;
}
}
// Keep track of the event/kmer index for the lower left corner of the band
// these indices are updated at every iteration to perform the adaptive banding
// Only the first two bands have their coordinates initialized, the rest are computed adaptively
struct EventKmerPair
{
int event_idx;
int kmer_idx;
};
std::vector<EventKmerPair> band_lower_left(n_bands);
// initialize range of first two bands
band_lower_left[0].event_idx = half_bandwidth - 1;
band_lower_left[0].kmer_idx = -1 - half_bandwidth;
band_lower_left[1] = move_down(band_lower_left[0]);
// band 0: score zero in the central cell
int start_cell_offset = band_kmer_to_offset(0, -1);
assert(is_offset_valid(start_cell_offset));
assert(band_event_to_offset(0, -1) == start_cell_offset);
BAND_ARRAY(0,start_cell_offset) = 0.0f;
// band 1: first event is trimmed
int first_trim_offset = band_event_to_offset(1, 0);
assert(kmer_at_offset(1, first_trim_offset) == -1);
assert(is_offset_valid(first_trim_offset));
BAND_ARRAY(1,first_trim_offset) = lp_trim;
TRACE_ARRAY(1,first_trim_offset) = FROM_U;
int fills = 0;
#ifdef DEBUG_ADAPTIVE
fprintf(stderr, "[trim] bi: %d o: %d e: %d k: %d s: %.2lf\n", 1, first_trim_offset, 0, -1, BAND_ARRAY(1,first_trim_offset));
#endif
// fill in remaining bands
for(int band_idx = 2; band_idx < n_bands; ++band_idx) {
// Determine placement of this band according to Suzuki's adaptive algorithm
// When both ll and ur are out-of-band (ob) we alternate movements
// otherwise we decide based on scores
float ll = BAND_ARRAY(band_idx - 1,0);
float ur = BAND_ARRAY(band_idx - 1,bandwidth - 1);
bool ll_ob = ll == -INFINITY;
bool ur_ob = ur == -INFINITY;
bool right = false;
if(ll_ob && ur_ob) {
right = band_idx % 2 == 1;
} else {
right = ll < ur; // Suzuki's rule
}
if(right) {
band_lower_left[band_idx] = move_right(band_lower_left[band_idx - 1]);
} else {
band_lower_left[band_idx] = move_down(band_lower_left[band_idx - 1]);
}
/*
float max_score = -INFINITY;
int tmp_max_offset = 0;
for(int tmp = 0; tmp < bandwidth; ++tmp) {
float s = bands[band_idx - 1][tmp];
if(s > max_score) {
max_score = s;
tmp_max_offset = tmp;
}
}
fprintf(stderr, "bi: %d ll: %.2f up: %.2f [%d %d] [%d %d] max: %.2f [%d %d] move: %s\n",
band_idx, bands[band_idx - 1][0], bands[band_idx - 1][bandwidth - 1],
band_lower_left[band_idx - 1].event_idx, band_lower_left[band_idx - 1].kmer_idx,
event_at_offset(band_idx - 1, bandwidth - 1), kmer_at_offset(band_idx - 1, bandwidth - 1),
max_score, event_at_offset(band_idx - 1, tmp_max_offset), kmer_at_offset(band_idx - 1, tmp_max_offset),
(right ? "RIGHT" : "DOWN"));
*/
// If the trim state is within the band, fill it in here
int trim_offset = band_kmer_to_offset(band_idx, -1);
if(is_offset_valid(trim_offset)) {
int event_idx = event_at_offset(band_idx, trim_offset);
if(event_idx >= 0 && event_idx < n_events) {
BAND_ARRAY(band_idx,trim_offset) = lp_trim * (event_idx + 1);
TRACE_ARRAY(band_idx,trim_offset) = FROM_U;
} else {
BAND_ARRAY(band_idx,trim_offset) = -INFINITY;
}
}
// Get the offsets for the first and last event and kmer
// We restrict the inner loop to only these values
int kmer_min_offset = band_kmer_to_offset(band_idx, 0);
int kmer_max_offset = band_kmer_to_offset(band_idx, n_kmers);
int event_min_offset = band_event_to_offset(band_idx, n_events - 1);
int event_max_offset = band_event_to_offset(band_idx, -1);
int min_offset = std::max(kmer_min_offset, event_min_offset);
min_offset = std::max(min_offset, 0);
int max_offset = std::min(kmer_max_offset, event_max_offset);
max_offset = std::min(max_offset, bandwidth);
for(int offset = min_offset; offset < max_offset; ++offset) {
int event_idx = event_at_offset(band_idx, offset);
int kmer_idx = kmer_at_offset(band_idx, offset);
size_t kmer_rank = kmer_ranks[kmer_idx];
int offset_up = band_event_to_offset(band_idx - 1, event_idx - 1);
int offset_left = band_kmer_to_offset(band_idx - 1, kmer_idx - 1);
int offset_diag = band_kmer_to_offset(band_idx - 2, kmer_idx - 1);
#ifdef DEBUG_ADAPTIVE
// verify loop conditions
assert(kmer_idx >= 0 && kmer_idx < n_kmers);
assert(event_idx >= 0 && event_idx < n_events);
assert(offset_diag == band_event_to_offset(band_idx - 2, event_idx - 1));
assert(offset_up - offset_left == 1);
assert(offset >= 0 && offset < bandwidth);
#endif
float up = is_offset_valid(offset_up) ? BAND_ARRAY(band_idx - 1,offset_up) : -INFINITY;
float left = is_offset_valid(offset_left) ? BAND_ARRAY(band_idx - 1,offset_left) : -INFINITY;
float diag = is_offset_valid(offset_diag) ? BAND_ARRAY(band_idx - 2,offset_diag) : -INFINITY;
float lp_emission = log_probability_match_r9(read, pore_model, kmer_rank, event_idx, strand_idx);
float score_d = diag + lp_step + lp_emission;
float score_u = up + lp_stay + lp_emission;
float score_l = left + lp_skip;
float max_score = score_d;
uint8_t from = FROM_D;
max_score = score_u > max_score ? score_u : max_score;
from = max_score == score_u ? FROM_U : from;
max_score = score_l > max_score ? score_l : max_score;
from = max_score == score_l ? FROM_L : from;
#ifdef DEBUG_ADAPTIVE
fprintf(stderr, "[adafill] offset-up: %d offset-diag: %d offset-left: %d\n", offset_up, offset_diag, offset_left);
fprintf(stderr, "[adafill] up: %.2lf diag: %.2lf left: %.2lf\n", up, diag, left);
fprintf(stderr, "[adafill] bi: %d o: %d e: %d k: %d s: %.2lf f: %d emit: %.2lf\n", band_idx, offset, event_idx, kmer_idx, max_score, from, lp_emission);
#endif
BAND_ARRAY(band_idx,offset) = max_score;
TRACE_ARRAY(band_idx,offset) = from;
fills += 1;
}
}
/*
// Debug, print some of the score matrix
for(int col = 0; col <= 10; ++col) {
for(int row = 0; row < 100; ++row) {
int kmer_idx = col - 1;
int event_idx = row - 1;
int band_idx = event_kmer_to_band(event_idx, kmer_idx);
int offset = band_kmer_to_offset(band_idx, kmer_idx);
assert(offset == band_event_to_offset(band_idx, event_idx));
assert(event_idx == event_at_offset(band_idx, offset));
fprintf(stdout, "ei: %d ki: %d bi: %d o: %d s: %.2f\n", event_idx, kmer_idx, band_idx, offset, bands[band_idx][offset]);
}
}
*/
//
// Backtrack to compute alignment
//
double sum_emission = 0;
double n_aligned_events = 0;
std::vector<AlignedPair> out;
float max_score = -INFINITY;
int curr_event_idx = 0;
int curr_kmer_idx = n_kmers -1;
// Find best score between an event and the last k-mer. after trimming the remaining evnets
for(int event_idx = 0; event_idx < n_events; ++event_idx) {
size_t band_idx = event_kmer_to_band(event_idx, curr_kmer_idx);
size_t offset = band_event_to_offset(band_idx, event_idx);
if(is_offset_valid(offset)) {
float s = BAND_ARRAY(band_idx,offset) + (n_events - event_idx) * lp_trim;
if(s > max_score) {
max_score = s;
curr_event_idx = event_idx;
}
}
}
#ifdef DEBUG_ADAPTIVE
fprintf(stderr, "[adaback] ei: %d ki: %d s: %.2f\n", curr_event_idx, curr_kmer_idx, max_score);
#endif
int curr_gap = 0;
int max_gap = 0;
while(curr_kmer_idx >= 0 && curr_event_idx >= 0) {
// emit alignment
out.push_back({curr_kmer_idx, curr_event_idx});
#ifdef DEBUG_ADAPTIVE
fprintf(stderr, "[adaback] ei: %d ki: %d\n", curr_event_idx, curr_kmer_idx);
#endif
// qc stats
size_t kmer_rank = alphabet->kmer_rank(sequence.substr(curr_kmer_idx, k).c_str(), k);
sum_emission += log_probability_match_r9(read, pore_model, kmer_rank, curr_event_idx, strand_idx);
n_aligned_events += 1;
size_t band_idx = event_kmer_to_band(curr_event_idx, curr_kmer_idx);
size_t offset = band_event_to_offset(band_idx, curr_event_idx);
assert(band_kmer_to_offset(band_idx, curr_kmer_idx) == offset);
uint8_t from = TRACE_ARRAY(band_idx,offset);
if(from == FROM_D) {
curr_kmer_idx -= 1;
curr_event_idx -= 1;
curr_gap = 0;
} else if(from == FROM_U) {
curr_event_idx -= 1;
curr_gap = 0;
} else {
curr_kmer_idx -= 1;
curr_gap += 1;
max_gap = std::max(curr_gap, max_gap);
}
}
std::reverse(out.begin(), out.end());
// QC results
double avg_log_emission = sum_emission / n_aligned_events;
bool spanned = out.front().ref_pos == 0 && out.back().ref_pos == n_kmers - 1;
bool failed = false;
if(avg_log_emission < min_average_log_emission || !spanned || max_gap > max_gap_threshold) {
failed = true;
out.clear();
}
free(bands);
free(trace);
//fprintf(stderr, "ada\t%s\t%s\t%.2lf\t%zu\t%.2lf\t%d\t%d\t%d\n", read.read_name.substr(0, 6).c_str(), failed ? "FAILED" : "OK", events_per_kmer, sequence.size(), avg_log_emission, curr_event_idx, max_gap, fills);
return out;
}
