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align.c
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align.c
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/* The MIT License
Copyright (c) 2018- Dana-Farber Cancer Institute
2017-2018 Broad Institute, Inc.
Permission is hereby granted, free of charge, to any person obtaining
a copy of this software and associated documentation files (the
"Software"), to deal in the Software without restriction, including
without limitation the rights to use, copy, modify, merge, publish,
distribute, sublicense, and/or sell copies of the Software, and to
permit persons to whom the Software is furnished to do so, subject to
the following conditions:
The above copyright notice and this permission notice shall be
included in all copies or substantial portions of the Software.
THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF
MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND
NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS
BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN
ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN
CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE
SOFTWARE.
Modified Copyright (C) 2021 Intel Corporation
Contacts: Saurabh Kalikar <[email protected]>;
Vasimuddin Md <[email protected]>; Sanchit Misra <[email protected]>;
Chirag Jain <[email protected]>; Heng Li <[email protected]>
*/
#include <assert.h>
#include <string.h>
#include <stdlib.h>
#include <math.h>
#include "minimap.h"
#include "mmpriv.h"
#include "ksw2.h"
#include "ksw2_extd2_avx.h"
#include <x86intrin.h>
extern uint64_t avg;
extern uint64_t alignment_time;
extern void *km1;
extern uint64_t km_size;// = 500000000; // 500 MB
extern int km_top;
static void ksw_gen_simple_mat(int m, int8_t *mat, int8_t a, int8_t b, int8_t sc_ambi)
{
int i, j;
a = a < 0? -a : a;
b = b > 0? -b : b;
sc_ambi = sc_ambi > 0? -sc_ambi : sc_ambi;
for (i = 0; i < m - 1; ++i) {
for (j = 0; j < m - 1; ++j)
mat[i * m + j] = i == j? a : b;
mat[i * m + m - 1] = sc_ambi;
}
for (j = 0; j < m; ++j)
mat[(m - 1) * m + j] = sc_ambi;
}
static inline void mm_seq_rev(uint32_t len, uint8_t *seq)
{
uint32_t i;
uint8_t t;
for (i = 0; i < len>>1; ++i)
t = seq[i], seq[i] = seq[len - 1 - i], seq[len - 1 - i] = t;
}
static inline void update_max_zdrop(int32_t score, int i, int j, int32_t *max, int *max_i, int *max_j, int e, int *max_zdrop, int pos[2][2])
{
if (score < *max) {
int li = i - *max_i;
int lj = j - *max_j;
int diff = li > lj? li - lj : lj - li;
int z = *max - score - diff * e;
if (z > *max_zdrop) {
*max_zdrop = z;
pos[0][0] = *max_i, pos[0][1] = i;
pos[1][0] = *max_j, pos[1][1] = j;
}
} else *max = score, *max_i = i, *max_j = j;
}
static int mm_test_zdrop(void *km, const mm_mapopt_t *opt, const uint8_t *qseq, const uint8_t *tseq, uint32_t n_cigar, uint32_t *cigar, const int8_t *mat)
{
uint32_t k;
int32_t score = 0, max = INT32_MIN, max_i = -1, max_j = -1, i = 0, j = 0, max_zdrop = 0;
int pos[2][2] = {{-1, -1}, {-1, -1}}, q_len, t_len;
// find the score and the region where score drops most along diagonal
for (k = 0, score = 0; k < n_cigar; ++k) {
uint32_t l, op = cigar[k]&0xf, len = cigar[k]>>4;
if (op == MM_CIGAR_MATCH) {
for (l = 0; l < len; ++l) {
score += mat[tseq[i + l] * 5 + qseq[j + l]];
update_max_zdrop(score, i+l, j+l, &max, &max_i, &max_j, opt->e, &max_zdrop, pos);
}
i += len, j += len;
} else if (op == MM_CIGAR_INS || op == MM_CIGAR_DEL || op == MM_CIGAR_N_SKIP) {
score -= opt->q + opt->e * len;
if (op == MM_CIGAR_INS) j += len;
else i += len;
update_max_zdrop(score, i, j, &max, &max_i, &max_j, opt->e, &max_zdrop, pos);
}
}
// test if there is an inversion in the most dropped region
q_len = pos[1][1] - pos[1][0], t_len = pos[0][1] - pos[0][0];
if (!(opt->flag&(MM_F_SPLICE|MM_F_SR|MM_F_FOR_ONLY|MM_F_REV_ONLY)) && max_zdrop > opt->zdrop_inv && q_len < opt->max_gap && t_len < opt->max_gap) {
uint8_t *qseq2;
void *qp;
int q_off, t_off;
qseq2 = (uint8_t*)kmalloc(km, q_len);
for (i = 0; i < q_len; ++i) {
int c = qseq[pos[1][1] - i - 1];
qseq2[i] = c >= 4? 4 : 3 - c;
}
qp = ksw_ll_qinit(km, 2, q_len, qseq2, 5, mat);
score = ksw_ll_i16(qp, t_len, tseq + pos[0][0], opt->q, opt->e, &q_off, &t_off);
kfree(km, qseq2);
kfree(km, qp);
if (score >= opt->min_chain_score * opt->a && score >= opt->min_dp_max)
return 2; // there is a potential inversion
}
return max_zdrop > opt->zdrop? 1 : 0;
}
static void mm_fix_cigar(mm_reg1_t *r, const uint8_t *qseq, const uint8_t *tseq, int *qshift, int *tshift)
{
mm_extra_t *p = r->p;
int32_t toff = 0, qoff = 0, to_shrink = 0;
uint32_t k;
*qshift = *tshift = 0;
if (p->n_cigar <= 1) return;
for (k = 0; k < p->n_cigar; ++k) { // indel left alignment
uint32_t op = p->cigar[k]&0xf, len = p->cigar[k]>>4;
if (len == 0) to_shrink = 1;
if (op == MM_CIGAR_MATCH) {
toff += len, qoff += len;
} else if (op == MM_CIGAR_INS || op == MM_CIGAR_DEL) {
if (k > 0 && k < p->n_cigar - 1 && (p->cigar[k-1]&0xf) == 0 && (p->cigar[k+1]&0xf) == 0) {
int l, prev_len = p->cigar[k-1] >> 4;
if (op == MM_CIGAR_INS) {
for (l = 0; l < prev_len; ++l)
if (qseq[qoff - 1 - l] != qseq[qoff + len - 1 - l])
break;
} else {
for (l = 0; l < prev_len; ++l)
if (tseq[toff - 1 - l] != tseq[toff + len - 1 - l])
break;
}
if (l > 0)
p->cigar[k-1] -= l<<4, p->cigar[k+1] += l<<4, qoff -= l, toff -= l;
if (l == prev_len) to_shrink = 1;
}
if (op == MM_CIGAR_INS) qoff += len;
else toff += len;
} else if (op == MM_CIGAR_N_SKIP) {
toff += len;
}
}
assert(qoff == r->qe - r->qs && toff == r->re - r->rs);
for (k = 0; k < p->n_cigar - 2; ++k) { // fix CIGAR like 5I6D7I
if ((p->cigar[k]&0xf) > 0 && (p->cigar[k]&0xf) + (p->cigar[k+1]&0xf) == 3) {
uint32_t l, s[3] = {0,0,0};
for (l = k; l < p->n_cigar; ++l) { // count number of adjacent I and D
uint32_t op = p->cigar[l]&0xf;
if (op == MM_CIGAR_INS || op == MM_CIGAR_DEL || p->cigar[l]>>4 == 0)
s[op] += p->cigar[l] >> 4;
else break;
}
if (s[1] > 0 && s[2] > 0 && l - k > 2) { // turn to a single I and a single D
p->cigar[k] = s[1]<<4|MM_CIGAR_INS;
p->cigar[k+1] = s[2]<<4|MM_CIGAR_DEL;
for (k += 2; k < l; ++k)
p->cigar[k] &= 0xf;
to_shrink = 1;
}
k = l;
}
}
if (to_shrink) { // squeeze out zero-length operations
int32_t l = 0;
for (k = 0; k < p->n_cigar; ++k) // squeeze out zero-length operations
if (p->cigar[k]>>4 != 0)
p->cigar[l++] = p->cigar[k];
p->n_cigar = l;
for (k = l = 0; k < p->n_cigar; ++k) // merge two adjacent operations if they are the same
if (k == p->n_cigar - 1 || (p->cigar[k]&0xf) != (p->cigar[k+1]&0xf))
p->cigar[l++] = p->cigar[k];
else p->cigar[k+1] += p->cigar[k]>>4<<4; // add length to the next CIGAR operator
p->n_cigar = l;
}
if ((p->cigar[0]&0xf) == MM_CIGAR_INS || (p->cigar[0]&0xf) == MM_CIGAR_DEL) { // get rid of leading I or D
int32_t l = p->cigar[0] >> 4;
if ((p->cigar[0]&0xf) == MM_CIGAR_INS) {
if (r->rev) r->qe -= l;
else r->qs += l;
*qshift = l;
} else r->rs += l, *tshift = l;
--p->n_cigar;
memmove(p->cigar, p->cigar + 1, p->n_cigar * 4);
}
}
static void mm_update_cigar_eqx(mm_reg1_t *r, const uint8_t *qseq, const uint8_t *tseq) // written by @armintoepfer
{
uint32_t n_EQX = 0;
uint32_t k, l, m, cap, toff = 0, qoff = 0, n_M = 0;
mm_extra_t *p;
if (r->p == 0) return;
for (k = 0; k < r->p->n_cigar; ++k) {
uint32_t op = r->p->cigar[k]&0xf, len = r->p->cigar[k]>>4;
if (op == MM_CIGAR_MATCH) {
while (len > 0) {
for (l = 0; l < len && qseq[qoff + l] == tseq[toff + l]; ++l) {} // run of "="; TODO: N<=>N is converted to "="
if (l > 0) { ++n_EQX; len -= l; toff += l; qoff += l; }
for (l = 0; l < len && qseq[qoff + l] != tseq[toff + l]; ++l) {} // run of "X"
if (l > 0) { ++n_EQX; len -= l; toff += l; qoff += l; }
}
++n_M;
} else if (op == MM_CIGAR_INS) {
qoff += len;
} else if (op == MM_CIGAR_DEL) {
toff += len;
} else if (op == MM_CIGAR_N_SKIP) {
toff += len;
}
}
// update in-place if we can
if (n_EQX == n_M) {
for (k = 0; k < r->p->n_cigar; ++k) {
uint32_t op = r->p->cigar[k]&0xf, len = r->p->cigar[k]>>4;
if (op == MM_CIGAR_MATCH) r->p->cigar[k] = len << 4 | MM_CIGAR_EQ_MATCH;
}
return;
}
// allocate new storage
cap = r->p->n_cigar + (n_EQX - n_M) + sizeof(mm_extra_t);
kroundup32(cap);
p = (mm_extra_t*)calloc(cap, 4);
memcpy(p, r->p, sizeof(mm_extra_t));
p->capacity = cap;
// update cigar while copying
toff = qoff = m = 0;
for (k = 0; k < r->p->n_cigar; ++k) {
uint32_t op = r->p->cigar[k]&0xf, len = r->p->cigar[k]>>4;
if (op == MM_CIGAR_MATCH) {
while (len > 0) {
// match
for (l = 0; l < len && qseq[qoff + l] == tseq[toff + l]; ++l) {}
if (l > 0) p->cigar[m++] = l << 4 | MM_CIGAR_EQ_MATCH;
len -= l;
toff += l, qoff += l;
// mismatch
for (l = 0; l < len && qseq[qoff + l] != tseq[toff + l]; ++l) {}
if (l > 0) p->cigar[m++] = l << 4 | MM_CIGAR_X_MISMATCH;
len -= l;
toff += l, qoff += l;
}
continue;
} else if (op == MM_CIGAR_INS) {
qoff += len;
} else if (op == MM_CIGAR_DEL) {
toff += len;
} else if (op == MM_CIGAR_N_SKIP) {
toff += len;
}
p->cigar[m++] = r->p->cigar[k];
}
p->n_cigar = m;
free(r->p);
r->p = p;
}
static void mm_update_extra(mm_reg1_t *r, const uint8_t *qseq, const uint8_t *tseq, const int8_t *mat, int8_t q, int8_t e, int is_eqx, int log_gap)
{
uint32_t k, l;
int32_t qshift, tshift, toff = 0, qoff = 0;
double s = 0.0, max = 0.0;
mm_extra_t *p = r->p;
if (p == 0) return;
mm_fix_cigar(r, qseq, tseq, &qshift, &tshift);
qseq += qshift, tseq += tshift; // qseq and tseq may be shifted due to the removal of leading I/D
r->blen = r->mlen = 0;
for (k = 0; k < p->n_cigar; ++k) {
uint32_t op = p->cigar[k]&0xf, len = p->cigar[k]>>4;
if (op == MM_CIGAR_MATCH) {
int n_ambi = 0, n_diff = 0;
for (l = 0; l < len; ++l) {
int cq = qseq[qoff + l], ct = tseq[toff + l];
if (ct > 3 || cq > 3) ++n_ambi;
else if (ct != cq) ++n_diff;
s += mat[ct * 5 + cq];
if (s < 0) s = 0;
else max = max > s? max : s;
}
r->blen += len - n_ambi, r->mlen += len - (n_ambi + n_diff), p->n_ambi += n_ambi;
toff += len, qoff += len;
} else if (op == MM_CIGAR_INS) {
int n_ambi = 0;
for (l = 0; l < len; ++l)
if (qseq[qoff + l] > 3) ++n_ambi;
r->blen += len - n_ambi, p->n_ambi += n_ambi;
if (log_gap) s -= q + (double)e * mg_log2(1.0 + len);
else s -= q + e;
if (s < 0) s = 0;
qoff += len;
} else if (op == MM_CIGAR_DEL) {
int n_ambi = 0;
for (l = 0; l < len; ++l)
if (tseq[toff + l] > 3) ++n_ambi;
r->blen += len - n_ambi, p->n_ambi += n_ambi;
if (log_gap) s -= q + (double)e * mg_log2(1.0 + len);
else s -= q + e;
if (s < 0) s = 0;
toff += len;
} else if (op == MM_CIGAR_N_SKIP) {
toff += len;
}
}
p->dp_max = (int32_t)(max + .499);
assert(qoff == r->qe - r->qs && toff == r->re - r->rs);
if (is_eqx) mm_update_cigar_eqx(r, qseq, tseq); // NB: it has to be called here as changes to qseq and tseq are not returned
}
static void mm_append_cigar(mm_reg1_t *r, uint32_t n_cigar, uint32_t *cigar) // TODO: this calls the libc realloc()
{
mm_extra_t *p;
if (n_cigar == 0) return;
if (r->p == 0) {
uint32_t capacity = n_cigar + sizeof(mm_extra_t)/4;
kroundup32(capacity);
r->p = (mm_extra_t*)calloc(capacity, 4);
r->p->capacity = capacity;
} else if (r->p->n_cigar + n_cigar + sizeof(mm_extra_t)/4 > r->p->capacity) {
r->p->capacity = r->p->n_cigar + n_cigar + sizeof(mm_extra_t)/4;
kroundup32(r->p->capacity);
r->p = (mm_extra_t*)realloc(r->p, r->p->capacity * 4);
//klocwork fix
assert(r->p);
}
p = r->p;
if (p->n_cigar > 0 && (p->cigar[p->n_cigar-1]&0xf) == (cigar[0]&0xf)) { // same CIGAR op at the boundary
p->cigar[p->n_cigar-1] += cigar[0]>>4<<4;
if (n_cigar > 1) memcpy(p->cigar + p->n_cigar, cigar + 1, (n_cigar - 1) * 4);
p->n_cigar += n_cigar - 1;
} else {
memcpy(p->cigar + p->n_cigar, cigar, n_cigar * 4);
p->n_cigar += n_cigar;
}
}
#if 0
static void mm_align_pair(void *km, const mm_mapopt_t *opt, int qlen, const uint8_t *qseq, int tlen, const uint8_t *tseq, const uint8_t *junc, const int8_t *mat, int w, int end_bonus, int zdrop, int flag, ksw_extz_t *ez)
{
if (mm_dbg_flag & MM_DBG_PRINT_ALN_SEQ) {
int i;
fprintf(stderr, "===> q=(%d,%d), e=(%d,%d), bw=%d, flag=%d, zdrop=%d <===\n", opt->q, opt->q2, opt->e, opt->e2, w, flag, opt->zdrop);
for (i = 0; i < tlen; ++i) fputc("ACGTN"[tseq[i]], stderr);
fputc('\n', stderr);
for (i = 0; i < qlen; ++i) fputc("ACGTN"[qseq[i]], stderr);
fputc('\n', stderr);
}
if (opt->max_sw_mat > 0 && (int64_t)tlen * qlen > opt->max_sw_mat) {
ksw_reset_extz(ez);
ez->zdropped = 1;
} else if (opt->flag & MM_F_SPLICE)
ksw_exts2_sse(km, qlen, qseq, tlen, tseq, 5, mat, opt->q, opt->e, opt->q2, opt->noncan, zdrop, opt->junc_bonus, flag, junc, ez);
else if (opt->q == opt->q2 && opt->e == opt->e2)
ksw_extz2_sse(km, qlen, qseq, tlen, tseq, 5, mat, opt->q, opt->e, w, zdrop, end_bonus, flag, ez);
else
ksw_extd2_sse(km, qlen, qseq, tlen, tseq, 5, mat, opt->q, opt->e, opt->q2, opt->e2, w, zdrop, end_bonus, flag, ez);
if (mm_dbg_flag & MM_DBG_PRINT_ALN_SEQ) {
int i;
fprintf(stderr, "score=%d, cigar=", ez->score);
for (i = 0; i < ez->n_cigar; ++i)
fprintf(stderr, "%d%c", ez->cigar[i]>>4, MM_CIGAR_STR[ez->cigar[i]&0xf]);
fprintf(stderr, "\n");
}
}
#endif
#if 1
static void mm_align_pair(void *km, const mm_mapopt_t *opt, int qlen, const uint8_t *qseq, int tlen, const uint8_t *tseq, const uint8_t *junc, const int8_t *mat, int w, int end_bonus, int zdrop, int flag, ksw_extz_t *ez)
{
#ifdef MANUAL_PROFILING
uint64_t align_start = __rdtsc();
#endif
if (mm_dbg_flag & MM_DBG_PRINT_ALN_SEQ) {
int i;
fprintf(stderr, "===> q=(%d,%d), e=(%d,%d), bw=%d, flag=%d, zdrop=%d <===\n", opt->q, opt->q2, opt->e, opt->e2, w, flag, opt->zdrop);
for (i = 0; i < tlen; ++i) fputc("ACGTN"[tseq[i]], stderr);
fputc('\n', stderr);
for (i = 0; i < qlen; ++i) fputc("ACGTN"[qseq[i]], stderr);
fputc('\n', stderr);
}
if (opt->max_sw_mat > 0 && (int64_t)tlen * qlen > opt->max_sw_mat) {
ksw_reset_extz(ez);
ez->zdropped = 1;
} else if (opt->flag & MM_F_SPLICE)
ksw_exts2_sse(km, qlen, qseq, tlen, tseq, 5, mat, opt->q, opt->e, opt->q2, opt->noncan, zdrop, opt->junc_bonus, flag, junc, ez);
else if (opt->q == opt->q2 && opt->e == opt->e2)
ksw_extz2_sse(km, qlen, qseq, tlen, tseq, 5, mat, opt->q, opt->e, w, zdrop, end_bonus, flag, ez);
else{
#if defined (ALIGN_AVX) && (defined(__AVX512BW__) || (defined(__AVX2__) && defined(APPLY_AVX2)))
#ifdef __AVX512BW__
ksw_extd2_avx512(km, qlen, qseq, tlen, tseq, 5, mat, opt->q, opt->e, opt->q2, opt->e2, w, zdrop, end_bonus, flag, ez);
#elif __AVX2__
avg = 0;
// uint64_t *ptr_km = (uint64_t *) km1;
// for(uint64_t itr = 0; itr < km_size/512; itr++){
// avg+=ptr_km[itr];
// }
//#ifdef MANUAL_PROFILING
// uint64_t align_start = __rdtsc();
//#endif
ksw_extd2_avx2(km, qlen, qseq, tlen, tseq, 5, mat, opt->q, opt->e, opt->q2, opt->e2, w, zdrop, end_bonus, flag, ez);
//#ifdef MANUAL_PROFILING
// alignment_time += (__rdtsc() - align_start);
//#endif
#endif
#else
ksw_extd2_sse(km, qlen, qseq, tlen, tseq, 5, mat, opt->q, opt->e, opt->q2, opt->e2, w, zdrop, end_bonus, flag, ez);
#endif
}
if (mm_dbg_flag & MM_DBG_PRINT_ALN_SEQ) {
int i;
fprintf(stderr, "score=%d, cigar=", ez->score);
for (i = 0; i < ez->n_cigar; ++i)
fprintf(stderr, "%d%c", ez->cigar[i]>>4, "MIDN"[ez->cigar[i]&0xf]);
fprintf(stderr, "\n");
}
#ifdef MANUAL_PROFILING
alignment_time += (__rdtsc() - align_start);
#endif
}
#endif
static inline int mm_get_hplen_back(const mm_idx_t *mi, uint32_t rid, uint32_t x)
{
int64_t i, off0 = mi->seq[rid].offset, off = off0 + x;
int c = mm_seq4_get(mi->S, off);
for (i = off - 1; i >= off0; --i)
if (mm_seq4_get(mi->S, i) != c) break;
return (int)(off - i);
}
static inline void mm_adjust_minier(const mm_idx_t *mi, uint8_t *const qseq0[2], mm128_t *a, int32_t *r, int32_t *q)
{
if (mi->flag & MM_I_HPC) {
const uint8_t *qseq = qseq0[a->x>>63];
int i, c;
*q = (int32_t)a->y;
for (i = *q - 1, c = qseq[*q]; i > 0; --i)
if (qseq[i] != c) break;
*q = i + 1;
c = mm_get_hplen_back(mi, a->x<<1>>33, (int32_t)a->x);
*r = (int32_t)a->x + 1 - c;
} else {
*r = (int32_t)a->x - (mi->k>>1);
*q = (int32_t)a->y - (mi->k>>1);
}
}
static int *collect_long_gaps(void *km, int as1, int cnt1, mm128_t *a, int min_gap, int *n_)
{
int i, n, *K;
*n_ = 0;
for (i = 1, n = 0; i < cnt1; ++i) { // count the number of gaps longer than min_gap
int gap = ((int32_t)a[as1 + i].y - a[as1 + i - 1].y) - ((int32_t)a[as1 + i].x - a[as1 + i - 1].x);
if (gap < -min_gap || gap > min_gap) ++n;
}
if (n <= 1) return 0;
K = (int*)kmalloc(km, n * sizeof(int));
for (i = 1, n = 0; i < cnt1; ++i) { // store the positions of long gaps
int gap = ((int32_t)a[as1 + i].y - a[as1 + i - 1].y) - ((int32_t)a[as1 + i].x - a[as1 + i - 1].x);
if (gap < -min_gap || gap > min_gap)
K[n++] = i;
}
*n_ = n;
return K;
}
static void mm_filter_bad_seeds(void *km, int as1, int cnt1, mm128_t *a, int min_gap, int diff_thres, int max_ext_len, int max_ext_cnt)
{
int max_st, max_en, n, i, k, max, *K;
K = collect_long_gaps(km, as1, cnt1, a, min_gap, &n);
if (K == 0) return;
max = 0, max_st = max_en = -1;
for (k = 0;; ++k) { // traverse long gaps
int gap, l, n_ins = 0, n_del = 0, qs, rs, max_diff = 0, max_diff_l = -1;
if (k == n || k >= max_en) {
if (max_en > 0)
for (i = K[max_st]; i < K[max_en]; ++i)
a[as1 + i].y |= MM_SEED_IGNORE;
max = 0, max_st = max_en = -1;
if (k == n) break;
}
i = K[k];
gap = ((int32_t)a[as1 + i].y - (int32_t)a[as1 + i - 1].y) - (int32_t)(a[as1 + i].x - a[as1 + i - 1].x);
if (gap > 0) n_ins += gap;
else n_del += -gap;
qs = (int32_t)a[as1 + i - 1].y;
rs = (int32_t)a[as1 + i - 1].x;
for (l = k + 1; l < n && l <= k + max_ext_cnt; ++l) {
int j = K[l], diff;
if ((int32_t)a[as1 + j].y - qs > max_ext_len || (int32_t)a[as1 + j].x - rs > max_ext_len) break;
gap = ((int32_t)a[as1 + j].y - (int32_t)a[as1 + j - 1].y) - (int32_t)(a[as1 + j].x - a[as1 + j - 1].x);
if (gap > 0) n_ins += gap;
else n_del += -gap;
diff = n_ins + n_del - abs(n_ins - n_del);
if (max_diff < diff)
max_diff = diff, max_diff_l = l;
}
if (max_diff > diff_thres && max_diff > max)
max = max_diff, max_st = k, max_en = max_diff_l;
}
kfree(km, K);
}
static void mm_filter_bad_seeds_alt(void *km, int as1, int cnt1, mm128_t *a, int min_gap, int max_ext)
{
int n, k, *K;
K = collect_long_gaps(km, as1, cnt1, a, min_gap, &n);
if (K == 0) return;
for (k = 0; k < n;) {
int i = K[k], l;
int gap1 = ((int32_t)a[as1 + i].y - (int32_t)a[as1 + i - 1].y) - ((int32_t)a[as1 + i].x - (int32_t)a[as1 + i - 1].x);
int re1 = (int32_t)a[as1 + i].x;
int qe1 = (int32_t)a[as1 + i].y;
gap1 = gap1 > 0? gap1 : -gap1;
for (l = k + 1; l < n; ++l) {
int j = K[l], gap2, q_span_pre, rs2, qs2, m;
if ((int32_t)a[as1 + j].y - qe1 > max_ext || (int32_t)a[as1 + j].x - re1 > max_ext) break;
gap2 = ((int32_t)a[as1 + j].y - (int32_t)a[as1 + j - 1].y) - (int32_t)(a[as1 + j].x - a[as1 + j - 1].x);
q_span_pre = a[as1 + j - 1].y >> 32 & 0xff;
rs2 = (int32_t)a[as1 + j - 1].x + q_span_pre;
qs2 = (int32_t)a[as1 + j - 1].y + q_span_pre;
m = rs2 - re1 < qs2 - qe1? rs2 - re1 : qs2 - qe1;
gap2 = gap2 > 0? gap2 : -gap2;
if (m > gap1 + gap2) break;
re1 = (int32_t)a[as1 + j].x;
qe1 = (int32_t)a[as1 + j].y;
gap1 = gap2;
}
if (l > k + 1) {
int j, end = K[l - 1];
for (j = K[k]; j < end; ++j)
a[as1 + j].y |= MM_SEED_IGNORE;
a[as1 + end].y |= MM_SEED_LONG_JOIN;
}
k = l;
}
kfree(km, K);
}
static void mm_fix_bad_ends(const mm_reg1_t *r, const mm128_t *a, int bw, int min_match, int32_t *as, int32_t *cnt)
{
int32_t i, l, m;
*as = r->as, *cnt = r->cnt;
if (r->cnt < 3) return;
m = l = a[r->as].y >> 32 & 0xff;
for (i = r->as + 1; i < r->as + r->cnt - 1; ++i) {
int32_t lq, lr, min, max;
int32_t q_span = a[i].y >> 32 & 0xff;
if (a[i].y & MM_SEED_LONG_JOIN) break;
lr = (int32_t)a[i].x - (int32_t)a[i-1].x;
lq = (int32_t)a[i].y - (int32_t)a[i-1].y;
min = lr < lq? lr : lq;
max = lr > lq? lr : lq;
if (max - min > l >> 1) *as = i;
l += min;
m += min < q_span? min : q_span;
if (l >= bw << 1 || (m >= min_match && m >= bw) || m >= r->mlen >> 1) break;
}
*cnt = r->as + r->cnt - *as;
m = l = a[r->as + r->cnt - 1].y >> 32 & 0xff;
for (i = r->as + r->cnt - 2; i > *as; --i) {
int32_t lq, lr, min, max;
int32_t q_span = a[i+1].y >> 32 & 0xff;
if (a[i+1].y & MM_SEED_LONG_JOIN) break;
lr = (int32_t)a[i+1].x - (int32_t)a[i].x;
lq = (int32_t)a[i+1].y - (int32_t)a[i].y;
min = lr < lq? lr : lq;
max = lr > lq? lr : lq;
if (max - min > l >> 1) *cnt = i + 1 - *as;
l += min;
m += min < q_span? min : q_span;
if (l >= bw << 1 || (m >= min_match && m >= bw) || m >= r->mlen >> 1) break;
}
}
static void mm_max_stretch(const mm_reg1_t *r, const mm128_t *a, int32_t *as, int32_t *cnt)
{
int32_t i, score, max_score, len, max_i, max_len;
*as = r->as, *cnt = r->cnt;
if (r->cnt < 2) return;
max_score = -1, max_i = -1, max_len = 0;
score = a[r->as].y >> 32 & 0xff, len = 1;
for (i = r->as + 1; i < r->as + r->cnt; ++i) {
int32_t lq, lr, q_span;
q_span = a[i].y >> 32 & 0xff;
lr = (int32_t)a[i].x - (int32_t)a[i-1].x;
lq = (int32_t)a[i].y - (int32_t)a[i-1].y;
if (lq == lr) {
score += lq < q_span? lq : q_span;
++len;
} else {
if (score > max_score)
max_score = score, max_len = len, max_i = i - len;
score = q_span, len = 1;
}
}
if (score > max_score)
max_score = score, max_len = len, max_i = i - len;
*as = max_i, *cnt = max_len;
}
static int mm_seed_ext_score(void *km, const mm_mapopt_t *opt, const mm_idx_t *mi, const int8_t mat[25], int qlen, uint8_t *qseq0[2], const mm128_t *a)
{
uint8_t *qseq, *tseq;
int q_span = a->y>>32&0xff, qs, qe, rs, re, rid, score, q_off, t_off, ext_len = opt->anchor_ext_len;
void *qp;
rid = a->x<<1>>33;
re = (uint32_t)a->x + 1, rs = re - q_span;
qe = (uint32_t)a->y + 1, qs = qe - q_span;
rs = rs - ext_len > 0? rs - ext_len : 0;
qs = qs - ext_len > 0? qs - ext_len : 0;
re = re + ext_len < (int32_t)mi->seq[rid].len? re + ext_len : mi->seq[rid].len;
qe = qe + ext_len < qlen? qe + ext_len : qlen;
tseq = (uint8_t*)kmalloc(km, re - rs);
if (opt->flag & MM_F_QSTRAND) {
qseq = qseq0[0] + qs;
mm_idx_getseq2(mi, a->x>>63, rid, rs, re, tseq);
} else {
qseq = qseq0[a->x>>63] + qs;
mm_idx_getseq(mi, rid, rs, re, tseq);
}
qp = ksw_ll_qinit(km, 2, qe - qs, qseq, 5, mat);
score = ksw_ll_i16(qp, re - rs, tseq, opt->q, opt->e, &q_off, &t_off);
kfree(km, tseq);
kfree(km, qp);
return score;
}
static void mm_fix_bad_ends_splice(void *km, const mm_mapopt_t *opt, const mm_idx_t *mi, const mm_reg1_t *r, const int8_t mat[25], int qlen, uint8_t *qseq0[2], const mm128_t *a, int *as1, int *cnt1)
{ // this assumes a very crude k-mer based mode; it is not necessary to use a good model just for filtering bounary exons
int score;
double log_gap;
*as1 = r->as, *cnt1 = r->cnt;
if (r->cnt < 3) return;
log_gap = log((int32_t)a[r->as + 1].x - (int32_t)a[r->as].x);
if ((a[r->as].y>>32&0xff) < log_gap + opt->anchor_ext_shift) {
score = mm_seed_ext_score(km, opt, mi, mat, qlen, qseq0, &a[r->as]);
if ((double)score / mat[0] < log_gap + opt->anchor_ext_shift) // a more exact format is "score < log_4(gap) + shift"
++(*as1), --(*cnt1);
}
log_gap = log((int32_t)a[r->as + r->cnt - 1].x - (int32_t)a[r->as + r->cnt - 2].x);
if ((a[r->as + r->cnt - 1].y>>32&0xff) < log_gap + opt->anchor_ext_shift) {
score = mm_seed_ext_score(km, opt, mi, mat, qlen, qseq0, &a[r->as + r->cnt - 1]);
if ((double)score / mat[0] < log_gap + opt->anchor_ext_shift)
--(*cnt1);
}
}
static void mm_align1(void *km, const mm_mapopt_t *opt, const mm_idx_t *mi, int qlen, uint8_t *qseq0[2], mm_reg1_t *r, mm_reg1_t *r2, int n_a, mm128_t *a, ksw_extz_t *ez, int splice_flag)
{
int is_sr = !!(opt->flag & MM_F_SR), is_splice = !!(opt->flag & MM_F_SPLICE);
int32_t rid = a[r->as].x<<1>>33, rev = a[r->as].x>>63, as1, cnt1;
uint8_t *tseq, *qseq, *junc;
int32_t i, l, bw, bw_long, dropped = 0, extra_flag = 0, rs0, re0, qs0, qe0;
int32_t rs, re, qs, qe;
int32_t rs1, qs1, re1, qe1;
int8_t mat[25];
if (is_sr) assert(!(mi->flag & MM_I_HPC)); // HPC won't work with SR because with HPC we can't easily tell if there is a gap
r2->cnt = 0;
if (r->cnt == 0) return;
ksw_gen_simple_mat(5, mat, opt->a, opt->b, opt->sc_ambi);
bw = (int)(opt->bw * 1.5 + 1.);
bw_long = (int)(opt->bw_long * 1.5 + 1.);
if (bw_long < bw) bw_long = bw;
if (is_sr && !(mi->flag & MM_I_HPC)) {
mm_max_stretch(r, a, &as1, &cnt1);
rs = (int32_t)a[as1].x + 1 - (int32_t)(a[as1].y>>32&0xff);
qs = (int32_t)a[as1].y + 1 - (int32_t)(a[as1].y>>32&0xff);
re = (int32_t)a[as1+cnt1-1].x + 1;
qe = (int32_t)a[as1+cnt1-1].y + 1;
} else {
if (!(opt->flag & MM_F_NO_END_FLT)) {
if (is_splice)
mm_fix_bad_ends_splice(km, opt, mi, r, mat, qlen, qseq0, a, &as1, &cnt1);
else
mm_fix_bad_ends(r, a, opt->bw, opt->min_chain_score * 2, &as1, &cnt1);
} else as1 = r->as, cnt1 = r->cnt;
mm_filter_bad_seeds(km, as1, cnt1, a, 10, 40, opt->max_gap>>1, 10);
mm_filter_bad_seeds_alt(km, as1, cnt1, a, 30, opt->max_gap>>1);
mm_adjust_minier(mi, qseq0, &a[as1], &rs, &qs);
mm_adjust_minier(mi, qseq0, &a[as1 + cnt1 - 1], &re, &qe);
}
assert(cnt1 > 0);
if (is_splice) {
if (splice_flag & MM_F_SPLICE_FOR) extra_flag |= rev? KSW_EZ_SPLICE_REV : KSW_EZ_SPLICE_FOR;
if (splice_flag & MM_F_SPLICE_REV) extra_flag |= rev? KSW_EZ_SPLICE_FOR : KSW_EZ_SPLICE_REV;
if (opt->flag & MM_F_SPLICE_FLANK) extra_flag |= KSW_EZ_SPLICE_FLANK;
}
/* Look for the start and end of regions to perform DP. This sounds easy
* but is in fact tricky. Excessively small regions lead to unnecessary
* clippings and lose alignable sequences. Excessively large regions
* occasionally lead to large overlaps between two chains and may cause
* loss of alignments in corner cases. */
if (is_sr) {
qs0 = 0, qe0 = qlen;
l = qs;
l += l * opt->a + opt->end_bonus > opt->q? (l * opt->a + opt->end_bonus - opt->q) / opt->e : 0;
rs0 = rs - l > 0? rs - l : 0;
l = qlen - qe;
l += l * opt->a + opt->end_bonus > opt->q? (l * opt->a + opt->end_bonus - opt->q) / opt->e : 0;
re0 = re + l < (int32_t)mi->seq[rid].len? re + l : mi->seq[rid].len;
} else {
// compute rs0 and qs0
rs0 = (int32_t)a[r->as].x + 1 - (int32_t)(a[r->as].y>>32&0xff);
qs0 = (int32_t)a[r->as].y + 1 - (int32_t)(a[r->as].y>>32&0xff);
if (rs0 < 0) rs0 = 0; // this may happen when HPC is in use
assert(qs0 >= 0); // this should never happen, or it is logic error
rs1 = qs1 = 0;
for (i = r->as - 1, l = 0; i >= 0 && a[i].x>>32 == a[r->as].x>>32; --i) { // inspect nearby seeds
int32_t x = (int32_t)a[i].x + 1 - (int32_t)(a[i].y>>32&0xff);
int32_t y = (int32_t)a[i].y + 1 - (int32_t)(a[i].y>>32&0xff);
if (x < rs0 && y < qs0) {
if (++l > opt->min_cnt) {
l = rs0 - x > qs0 - y? rs0 - x : qs0 - y;
rs1 = rs0 - l, qs1 = qs0 - l;
if (rs1 < 0) rs1 = 0; // not strictly necessary; better have this guard for explicit
break;
}
}
}
if (qs > 0 && rs > 0) {
l = qs < opt->max_gap? qs : opt->max_gap;
qs1 = qs1 > qs - l? qs1 : qs - l;
qs0 = qs0 < qs1? qs0 : qs1; // at least include qs0
l += l * opt->a > opt->q? (l * opt->a - opt->q) / opt->e : 0;
l = l < opt->max_gap? l : opt->max_gap;
l = l < rs? l : rs;
rs1 = rs1 > rs - l? rs1 : rs - l;
rs0 = rs0 < rs1? rs0 : rs1;
rs0 = rs0 < rs? rs0 : rs;
} else rs0 = rs, qs0 = qs;
// compute re0 and qe0
re0 = (int32_t)a[r->as + r->cnt - 1].x + 1;
qe0 = (int32_t)a[r->as + r->cnt - 1].y + 1;
re1 = mi->seq[rid].len, qe1 = qlen;
for (i = r->as + r->cnt, l = 0; i < n_a && a[i].x>>32 == a[r->as].x>>32; ++i) { // inspect nearby seeds
int32_t x = (int32_t)a[i].x + 1;
int32_t y = (int32_t)a[i].y + 1;
if (x > re0 && y > qe0) {
if (++l > opt->min_cnt) {
l = x - re0 > y - qe0? x - re0 : y - qe0;
re1 = re0 + l, qe1 = qe0 + l;
break;
}
}
}
if (qe < qlen && re < (int32_t)mi->seq[rid].len) {
l = qlen - qe < opt->max_gap? qlen - qe : opt->max_gap;
qe1 = qe1 < qe + l? qe1 : qe + l;
qe0 = qe0 > qe1? qe0 : qe1; // at least include qe0
l += l * opt->a > opt->q? (l * opt->a - opt->q) / opt->e : 0;
l = l < opt->max_gap? l : opt->max_gap;
l = l < (int32_t)mi->seq[rid].len - re? l : mi->seq[rid].len - re;
re1 = re1 < re + l? re1 : re + l;
re0 = re0 > re1? re0 : re1;
} else re0 = re, qe0 = qe;
}
if (a[r->as].y & MM_SEED_SELF) {
int max_ext = r->qs > r->rs? r->qs - r->rs : r->rs - r->qs;
if (r->rs - rs0 > max_ext) rs0 = r->rs - max_ext;
if (r->qs - qs0 > max_ext) qs0 = r->qs - max_ext;
max_ext = r->qe > r->re? r->qe - r->re : r->re - r->qe;
if (re0 - r->re > max_ext) re0 = r->re + max_ext;
if (qe0 - r->qe > max_ext) qe0 = r->qe + max_ext;
}
assert(re0 > rs0);
tseq = (uint8_t*)kmalloc(km, re0 - rs0);
junc = (uint8_t*)kmalloc(km, re0 - rs0);
if (qs > 0 && rs > 0) { // left extension; probably the condition can be changed to "qs > qs0 && rs > rs0"
if (opt->flag & MM_F_QSTRAND) {
qseq = &qseq0[0][qs0];
mm_idx_getseq2(mi, rev, rid, rs0, rs, tseq);
} else {
qseq = &qseq0[rev][qs0];
mm_idx_getseq(mi, rid, rs0, rs, tseq);
}
mm_idx_bed_junc(mi, rid, rs0, rs, junc);
mm_seq_rev(qs - qs0, qseq);
mm_seq_rev(rs - rs0, tseq);
mm_seq_rev(rs - rs0, junc);
mm_align_pair(km, opt, qs - qs0, qseq, rs - rs0, tseq, junc, mat, bw, opt->end_bonus, r->split_inv? opt->zdrop_inv : opt->zdrop, extra_flag|KSW_EZ_EXTZ_ONLY|KSW_EZ_RIGHT|KSW_EZ_REV_CIGAR, ez);
if (ez->n_cigar > 0) {
mm_append_cigar(r, ez->n_cigar, ez->cigar);
r->p->dp_score += ez->max;
}
rs1 = rs - (ez->reach_end? ez->mqe_t + 1 : ez->max_t + 1);
qs1 = qs - (ez->reach_end? qs - qs0 : ez->max_q + 1);
mm_seq_rev(qs - qs0, qseq);
} else rs1 = rs, qs1 = qs;
re1 = rs, qe1 = qs;
assert(qs1 >= 0 && rs1 >= 0);
for (i = is_sr? cnt1 - 1 : 1; i < cnt1; ++i) { // gap filling
if ((a[as1+i].y & (MM_SEED_IGNORE|MM_SEED_TANDEM)) && i != cnt1 - 1) continue;
if (is_sr && !(mi->flag & MM_I_HPC)) {
re = (int32_t)a[as1 + i].x + 1;
qe = (int32_t)a[as1 + i].y + 1;
} else mm_adjust_minier(mi, qseq0, &a[as1 + i], &re, &qe);
re1 = re, qe1 = qe;
if (i == cnt1 - 1 || (a[as1+i].y&MM_SEED_LONG_JOIN) || (qe - qs >= opt->min_ksw_len && re - rs >= opt->min_ksw_len)) {
int j, bw1 = bw_long, zdrop_code;
if (a[as1+i].y & MM_SEED_LONG_JOIN)
bw1 = qe - qs > re - rs? qe - qs : re - rs;
// perform alignment
if (opt->flag & MM_F_QSTRAND) {
qseq = &qseq0[0][qs];
mm_idx_getseq2(mi, rev, rid, rs, re, tseq);
} else {
qseq = &qseq0[rev][qs];
mm_idx_getseq(mi, rid, rs, re, tseq);
}
mm_idx_bed_junc(mi, rid, rs, re, junc);
if (is_sr) { // perform ungapped alignment
assert(qe - qs == re - rs);
ksw_reset_extz(ez);
for (j = 0, ez->score = 0; j < qe - qs; ++j) {
if (qseq[j] >= 4 || tseq[j] >= 4) ez->score += opt->e2;
else ez->score += qseq[j] == tseq[j]? opt->a : -opt->b;
}
ez->cigar = ksw_push_cigar(km, &ez->n_cigar, &ez->m_cigar, ez->cigar, MM_CIGAR_MATCH, qe - qs);
} else { // perform normal gapped alignment
mm_align_pair(km, opt, qe - qs, qseq, re - rs, tseq, junc, mat, bw1, -1, opt->zdrop, extra_flag|KSW_EZ_APPROX_MAX, ez); // first pass: with approximate Z-drop
}
// test Z-drop and inversion Z-drop
if ((zdrop_code = mm_test_zdrop(km, opt, qseq, tseq, ez->n_cigar, ez->cigar, mat)) != 0)
mm_align_pair(km, opt, qe - qs, qseq, re - rs, tseq, junc, mat, bw1, -1, zdrop_code == 2? opt->zdrop_inv : opt->zdrop, extra_flag, ez); // second pass: lift approximate
// update CIGAR
if (ez->n_cigar > 0)
mm_append_cigar(r, ez->n_cigar, ez->cigar);
if (ez->zdropped) { // truncated by Z-drop; TODO: sometimes Z-drop kicks in because the next seed placement is wrong. This can be fixed in principle.
if (!r->p) {
assert(ez->n_cigar == 0);
uint32_t capacity = sizeof(mm_extra_t)/4;
kroundup32(capacity);
r->p = (mm_extra_t*)calloc(capacity, 4);
r->p->capacity = capacity;
}
for (j = i - 1; j >= 0; --j)
if ((int32_t)a[as1 + j].x <= rs + ez->max_t)
break;
dropped = 1;
if (j < 0) j = 0;
r->p->dp_score += ez->max;
re1 = rs + (ez->max_t + 1);
qe1 = qs + (ez->max_q + 1);
if (cnt1 - (j + 1) >= opt->min_cnt) {
mm_split_reg(r, r2, as1 + j + 1 - r->as, qlen, a, !!(opt->flag&MM_F_QSTRAND));
if (zdrop_code == 2) r2->split_inv = 1;
}
break;
} else r->p->dp_score += ez->score;
rs = re, qs = qe;
}
}
if (!dropped && qe < qe0 && re < re0) { // right extension
if (opt->flag & MM_F_QSTRAND) {
qseq = &qseq0[0][qe];
mm_idx_getseq2(mi, rev, rid, re, re0, tseq);
} else {
qseq = &qseq0[rev][qe];
mm_idx_getseq(mi, rid, re, re0, tseq);
}
mm_idx_bed_junc(mi, rid, re, re0, junc);
mm_align_pair(km, opt, qe0 - qe, qseq, re0 - re, tseq, junc, mat, bw, opt->end_bonus, opt->zdrop, extra_flag|KSW_EZ_EXTZ_ONLY, ez);
if (ez->n_cigar > 0) {
mm_append_cigar(r, ez->n_cigar, ez->cigar);
r->p->dp_score += ez->max;
}
re1 = re + (ez->reach_end? ez->mqe_t + 1 : ez->max_t + 1);
qe1 = qe + (ez->reach_end? qe0 - qe : ez->max_q + 1);
}
assert(qe1 <= qlen);
r->rs = rs1, r->re = re1;
if (!rev || (opt->flag & MM_F_QSTRAND)) r->qs = qs1, r->qe = qe1;
else r->qs = qlen - qe1, r->qe = qlen - qs1;
assert(re1 - rs1 <= re0 - rs0);
if (r->p) {
if (opt->flag & MM_F_QSTRAND) {
mm_idx_getseq2(mi, r->rev, rid, rs1, re1, tseq);
qseq = &qseq0[0][qs1];
} else {
mm_idx_getseq(mi, rid, rs1, re1, tseq);
qseq = &qseq0[r->rev][qs1];
}
mm_update_extra(r, qseq, tseq, mat, opt->q, opt->e, opt->flag & MM_F_EQX, !(opt->flag & MM_F_SR));
if (rev && r->p->trans_strand)
r->p->trans_strand ^= 3; // flip to the read strand
}
kfree(km, tseq);
kfree(km, junc);
}
static int mm_align1_inv(void *km, const mm_mapopt_t *opt, const mm_idx_t *mi, int qlen, uint8_t *qseq0[2], const mm_reg1_t *r1, const mm_reg1_t *r2, mm_reg1_t *r_inv, ksw_extz_t *ez)
{ // NB: this doesn't work with the qstrand mode
int tl, ql, score, ret = 0, q_off, t_off;
uint8_t *tseq, *qseq;
int8_t mat[25];
void *qp;
memset(r_inv, 0, sizeof(mm_reg1_t));
if (!(r1->split&1) || !(r2->split&2)) return 0;
if (r1->id != r1->parent && r1->parent != MM_PARENT_TMP_PRI) return 0;
if (r2->id != r2->parent && r2->parent != MM_PARENT_TMP_PRI) return 0;
if (r1->rid != r2->rid || r1->rev != r2->rev) return 0;
ql = r1->rev? r1->qs - r2->qe : r2->qs - r1->qe;
tl = r2->rs - r1->re;
if (ql < opt->min_chain_score || ql > opt->max_gap) return 0;
if (tl < opt->min_chain_score || tl > opt->max_gap) return 0;
ksw_gen_simple_mat(5, mat, opt->a, opt->b, opt->sc_ambi);
tseq = (uint8_t*)kmalloc(km, tl);
mm_idx_getseq(mi, r1->rid, r1->re, r2->rs, tseq);
qseq = r1->rev? &qseq0[0][r2->qe] : &qseq0[1][qlen - r2->qs];
mm_seq_rev(ql, qseq);
mm_seq_rev(tl, tseq);
qp = ksw_ll_qinit(km, 2, ql, qseq, 5, mat);
score = ksw_ll_i16(qp, tl, tseq, opt->q, opt->e, &q_off, &t_off);
kfree(km, qp);
mm_seq_rev(ql, qseq);
mm_seq_rev(tl, tseq);
if (score < opt->min_dp_max) goto end_align1_inv;
q_off = ql - (q_off + 1), t_off = tl - (t_off + 1);
mm_align_pair(km, opt, ql - q_off, qseq + q_off, tl - t_off, tseq + t_off, 0, mat, (int)(opt->bw * 1.5), -1, opt->zdrop, KSW_EZ_EXTZ_ONLY, ez);
if (ez->n_cigar == 0) goto end_align1_inv; // should never be here
mm_append_cigar(r_inv, ez->n_cigar, ez->cigar);
r_inv->p->dp_score = ez->max;
r_inv->id = -1;
r_inv->parent = MM_PARENT_UNSET;
r_inv->inv = 1;
r_inv->rev = !r1->rev;
r_inv->rid = r1->rid;
r_inv->div = -1.0f;
if (r_inv->rev == 0) {
r_inv->qs = r2->qe + q_off;
r_inv->qe = r_inv->qs + ez->max_q + 1;
} else {
r_inv->qe = r2->qs - q_off;
r_inv->qs = r_inv->qe - (ez->max_q + 1);
}
r_inv->rs = r1->re + t_off;
r_inv->re = r_inv->rs + ez->max_t + 1;
mm_update_extra(r_inv, &qseq[q_off], &tseq[t_off], mat, opt->q, opt->e, opt->flag & MM_F_EQX, !(opt->flag & MM_F_SR));
ret = 1;
end_align1_inv:
kfree(km, tseq);
return ret;
}
static inline mm_reg1_t *mm_insert_reg(const mm_reg1_t *r, int i, int *n_regs, mm_reg1_t *regs)
{
regs = (mm_reg1_t*)realloc(regs, (*n_regs + 1) * sizeof(mm_reg1_t));
//klocwork fix
assert(regs);
if (i + 1 != *n_regs)
memmove(®s[i + 2], ®s[i + 1], sizeof(mm_reg1_t) * (*n_regs - i - 1));
regs[i + 1] = *r;
++*n_regs;
return regs;
}
static inline void mm_count_gaps(const mm_reg1_t *r, int32_t *n_gap_, int32_t *n_gapo_)
{
uint32_t i;
int32_t n_gapo = 0, n_gap = 0;
*n_gap_ = *n_gapo_ = -1;
if (r->p == 0) return;
for (i = 0; i < r->p->n_cigar; ++i) {