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#include <stdio.h>
#include <stdlib.h>
#include <ctype.h>
#include <assert.h>
#include "sam.h"
typedef struct {
int k, x, y, end;
} cstate_t;
static cstate_t g_cstate_null = { -1, 0, 0, 0 };
typedef struct __linkbuf_t {
bam1_t b;
uint32_t beg, end;
cstate_t s;
struct __linkbuf_t *next;
} lbnode_t;
/* --- BEGIN: Memory pool */
typedef struct {
int cnt, n, max;
lbnode_t **buf;
} mempool_t;
static mempool_t *mp_init()
{
mempool_t *mp;
mp = (mempool_t*)calloc(1, sizeof(mempool_t));
return mp;
}
static void mp_destroy(mempool_t *mp)
{
int k;
for (k = 0; k < mp->n; ++k) {
free(mp->buf[k]->b.data);
free(mp->buf[k]);
}
free(mp->buf);
free(mp);
}
static inline lbnode_t *mp_alloc(mempool_t *mp)
{
++mp->cnt;
if (mp->n == 0) return (lbnode_t*)calloc(1, sizeof(lbnode_t));
else return mp->buf[--mp->n];
}
static inline void mp_free(mempool_t *mp, lbnode_t *p)
{
--mp->cnt; p->next = 0; // clear lbnode_t::next here
if (mp->n == mp->max) {
mp->max = mp->max? mp->max<<1 : 256;
mp->buf = (lbnode_t**)realloc(mp->buf, sizeof(lbnode_t*) * mp->max);
}
mp->buf[mp->n++] = p;
}
/* --- END: Memory pool */
/* --- BEGIN: Auxiliary functions */
/* s->k: the index of the CIGAR operator that has just been processed.
s->x: the reference coordinate of the start of s->k
s->y: the query coordiante of the start of s->k
*/
static inline int resolve_cigar2(bam_pileup1_t *p, uint32_t pos, cstate_t *s)
{
#define _cop(c) ((c)&BAM_CIGAR_MASK)
#define _cln(c) ((c)>>BAM_CIGAR_SHIFT)
bam1_t *b = p->b;
bam1_core_t *c = &b->core;
uint32_t *cigar = bam1_cigar(b);
int k, is_head = 0;
// determine the current CIGAR operation
// fprintf(stderr, "%s\tpos=%d\tend=%d\t(%d,%d,%d)\n", bam1_qname(b), pos, s->end, s->k, s->x, s->y);
if (s->k == -1) { // never processed
is_head = 1;
if (c->n_cigar == 1) { // just one operation, save a loop
if (_cop(cigar[0]) == BAM_CMATCH || _cop(cigar[0]) == BAM_CEQUAL || _cop(cigar[0]) == BAM_CDIFF) s->k = 0, s->x = c->pos, s->y = 0;
} else { // find the first match or deletion
for (k = 0, s->x = c->pos, s->y = 0; k < c->n_cigar; ++k) {
int op = _cop(cigar[k]);
int l = _cln(cigar[k]);
if (op == BAM_CMATCH || op == BAM_CDEL || op == BAM_CEQUAL || op == BAM_CDIFF) break;
else if (op == BAM_CREF_SKIP) s->x += l;
else if (op == BAM_CINS || op == BAM_CSOFT_CLIP) s->y += l;
}
assert(k < c->n_cigar);
s->k = k;
}
} else { // the read has been processed before
int op, l = _cln(cigar[s->k]);
if (pos - s->x >= l) { // jump to the next operation
assert(s->k < c->n_cigar); // otherwise a bug: this function should not be called in this case
op = _cop(cigar[s->k+1]);
if (op == BAM_CMATCH || op == BAM_CDEL || op == BAM_CREF_SKIP || op == BAM_CEQUAL || op == BAM_CDIFF) { // jump to the next without a loop
if (_cop(cigar[s->k]) == BAM_CMATCH|| _cop(cigar[s->k]) == BAM_CEQUAL || _cop(cigar[s->k]) == BAM_CDIFF) s->y += l;
s->x += l;
++s->k;
} else { // find the next M/D/N/=/X
if (_cop(cigar[s->k]) == BAM_CMATCH|| _cop(cigar[s->k]) == BAM_CEQUAL || _cop(cigar[s->k]) == BAM_CDIFF) s->y += l;
s->x += l;
for (k = s->k + 1; k < c->n_cigar; ++k) {
op = _cop(cigar[k]), l = _cln(cigar[k]);
if (op == BAM_CMATCH || op == BAM_CDEL || op == BAM_CREF_SKIP || op == BAM_CEQUAL || op == BAM_CDIFF) break;
else if (op == BAM_CINS || op == BAM_CSOFT_CLIP) s->y += l;
}
s->k = k;
}
assert(s->k < c->n_cigar); // otherwise a bug
} // else, do nothing
}
{ // collect pileup information
int op, l;
op = _cop(cigar[s->k]); l = _cln(cigar[s->k]);
p->is_del = p->indel = p->is_refskip = 0;
if (s->x + l - 1 == pos && s->k + 1 < c->n_cigar) { // peek the next operation
int op2 = _cop(cigar[s->k+1]);
int l2 = _cln(cigar[s->k+1]);
if (op2 == BAM_CDEL) p->indel = -(int)l2;
else if (op2 == BAM_CINS) p->indel = l2;
else if (op2 == BAM_CPAD && s->k + 2 < c->n_cigar) { // no working for adjacent padding
int l3 = 0;
for (k = s->k + 2; k < c->n_cigar; ++k) {
op2 = _cop(cigar[k]); l2 = _cln(cigar[k]);
if (op2 == BAM_CINS) l3 += l2;
else if (op2 == BAM_CDEL || op2 == BAM_CMATCH || op2 == BAM_CREF_SKIP || op2 == BAM_CEQUAL || op2 == BAM_CDIFF) break;
}
if (l3 > 0) p->indel = l3;
}
}
if (op == BAM_CMATCH || op == BAM_CEQUAL || op == BAM_CDIFF) {
p->qpos = s->y + (pos - s->x);
} else if (op == BAM_CDEL || op == BAM_CREF_SKIP) {
p->is_del = 1; p->qpos = s->y; // FIXME: distinguish D and N!!!!!
p->is_refskip = (op == BAM_CREF_SKIP);
} // cannot be other operations; otherwise a bug
p->is_head = (pos == c->pos); p->is_tail = (pos == s->end);
}
return 1;
}
/* --- END: Auxiliary functions */
/*******************
* pileup iterator *
*******************/
struct __bam_plp_t {
mempool_t *mp;
lbnode_t *head, *tail, *dummy;
int32_t tid, pos, max_tid, max_pos;
int is_eof, flag_mask, max_plp, error, maxcnt;
bam_pileup1_t *plp;
// for the "auto" interface only
bam1_t *b;
bam_plp_auto_f func;
void *data;
};
bam_plp_t bam_plp_init(bam_plp_auto_f func, void *data)
{
bam_plp_t iter;
iter = calloc(1, sizeof(struct __bam_plp_t));
iter->mp = mp_init();
iter->head = iter->tail = mp_alloc(iter->mp);
iter->dummy = mp_alloc(iter->mp);
iter->max_tid = iter->max_pos = -1;
iter->flag_mask = BAM_DEF_MASK;
iter->maxcnt = 8000;
if (func) {
iter->func = func;
iter->data = data;
iter->b = bam_init1();
}
return iter;
}
void bam_plp_destroy(bam_plp_t iter)
{
mp_free(iter->mp, iter->dummy);
mp_free(iter->mp, iter->head);
if (iter->mp->cnt != 0)
fprintf(stderr, "[bam_plp_destroy] memory leak: %d. Continue anyway.\n", iter->mp->cnt);
mp_destroy(iter->mp);
if (iter->b) bam_destroy1(iter->b);
free(iter->plp);
free(iter);
}
const bam_pileup1_t *bam_plp_next(bam_plp_t iter, int *_tid, int *_pos, int *_n_plp)
{
if (iter->error) { *_n_plp = -1; return 0; }
*_n_plp = 0;
if (iter->is_eof && iter->head->next == 0) return 0;
while (iter->is_eof || iter->max_tid > iter->tid || (iter->max_tid == iter->tid && iter->max_pos > iter->pos)) {
int n_plp = 0;
lbnode_t *p, *q;
// write iter->plp at iter->pos
iter->dummy->next = iter->head;
for (p = iter->head, q = iter->dummy; p->next; q = p, p = p->next) {
if (p->b.core.tid < iter->tid || (p->b.core.tid == iter->tid && p->end <= iter->pos)) { // then remove
q->next = p->next; mp_free(iter->mp, p); p = q;
} else if (p->b.core.tid == iter->tid && p->beg <= iter->pos) { // here: p->end > pos; then add to pileup
if (n_plp == iter->max_plp) { // then double the capacity
iter->max_plp = iter->max_plp? iter->max_plp<<1 : 256;
iter->plp = (bam_pileup1_t*)realloc(iter->plp, sizeof(bam_pileup1_t) * iter->max_plp);
}
iter->plp[n_plp].b = &p->b;
if (resolve_cigar2(iter->plp + n_plp, iter->pos, &p->s)) ++n_plp; // actually always true...
}
}
iter->head = iter->dummy->next; // dummy->next may be changed
*_n_plp = n_plp; *_tid = iter->tid; *_pos = iter->pos;
// update iter->tid and iter->pos
if (iter->head->next) {
if (iter->tid > iter->head->b.core.tid) {
fprintf(stderr, "[%s] unsorted input. Pileup aborts.\n", __func__);
iter->error = 1;
*_n_plp = -1;
return 0;
}
}
if (iter->tid < iter->head->b.core.tid) { // come to a new reference sequence
iter->tid = iter->head->b.core.tid; iter->pos = iter->head->beg; // jump to the next reference
} else if (iter->pos < iter->head->beg) { // here: tid == head->b.core.tid
iter->pos = iter->head->beg; // jump to the next position
} else ++iter->pos; // scan contiguously
// return
if (n_plp) return iter->plp;
if (iter->is_eof && iter->head->next == 0) break;
}
return 0;
}
int bam_plp_push(bam_plp_t iter, const bam1_t *b)
{
if (iter->error) return -1;
if (b) {
if (b->core.tid < 0) return 0;
if (b->core.flag & iter->flag_mask) return 0;
if (iter->tid == b->core.tid && iter->pos == b->core.pos && iter->mp->cnt > iter->maxcnt) return 0;
bam_copy1(&iter->tail->b, b);
iter->tail->beg = b->core.pos; iter->tail->end = bam_calend(&b->core, bam1_cigar(b));
iter->tail->s = g_cstate_null; iter->tail->s.end = iter->tail->end - 1; // initialize cstate_t
if (b->core.tid < iter->max_tid) {
fprintf(stderr, "[bam_pileup_core] the input is not sorted (chromosomes out of order)\n");
iter->error = 1;
return -1;
}
if ((b->core.tid == iter->max_tid) && (iter->tail->beg < iter->max_pos)) {
fprintf(stderr, "[bam_pileup_core] the input is not sorted (reads out of order)\n");
iter->error = 1;
return -1;
}
iter->max_tid = b->core.tid; iter->max_pos = iter->tail->beg;
if (iter->tail->end > iter->pos || iter->tail->b.core.tid > iter->tid) {
iter->tail->next = mp_alloc(iter->mp);
iter->tail = iter->tail->next;
}
} else iter->is_eof = 1;
return 0;
}
const bam_pileup1_t *bam_plp_auto(bam_plp_t iter, int *_tid, int *_pos, int *_n_plp)
{
const bam_pileup1_t *plp;
if (iter->func == 0 || iter->error) { *_n_plp = -1; return 0; }
if ((plp = bam_plp_next(iter, _tid, _pos, _n_plp)) != 0) return plp;
else { // no pileup line can be obtained; read alignments
*_n_plp = 0;
if (iter->is_eof) return 0;
while (iter->func(iter->data, iter->b) >= 0) {
if (bam_plp_push(iter, iter->b) < 0) {
*_n_plp = -1;
return 0;
}
if ((plp = bam_plp_next(iter, _tid, _pos, _n_plp)) != 0) return plp;
// otherwise no pileup line can be returned; read the next alignment.
}
bam_plp_push(iter, 0);
if ((plp = bam_plp_next(iter, _tid, _pos, _n_plp)) != 0) return plp;
return 0;
}
}
void bam_plp_reset(bam_plp_t iter)
{
lbnode_t *p, *q;
iter->max_tid = iter->max_pos = -1;
iter->tid = iter->pos = 0;
iter->is_eof = 0;
for (p = iter->head; p->next;) {
q = p->next;
mp_free(iter->mp, p);
p = q;
}
iter->head = iter->tail;
}
void bam_plp_set_mask(bam_plp_t iter, int mask)
{
iter->flag_mask = mask < 0? BAM_DEF_MASK : (BAM_FUNMAP | mask);
}
void bam_plp_set_maxcnt(bam_plp_t iter, int maxcnt)
{
iter->maxcnt = maxcnt;
}
/*****************
* callback APIs *
*****************/
int bam_pileup_file(bamFile fp, int mask, bam_pileup_f func, void *func_data)
{
bam_plbuf_t *buf;
int ret;
bam1_t *b;
b = bam_init1();
buf = bam_plbuf_init(func, func_data);
bam_plbuf_set_mask(buf, mask);
while ((ret = bam_read1(fp, b)) >= 0)
bam_plbuf_push(b, buf);
bam_plbuf_push(0, buf);
bam_plbuf_destroy(buf);
bam_destroy1(b);
return 0;
}
void bam_plbuf_set_mask(bam_plbuf_t *buf, int mask)
{
bam_plp_set_mask(buf->iter, mask);
}
void bam_plbuf_reset(bam_plbuf_t *buf)
{
bam_plp_reset(buf->iter);
}
bam_plbuf_t *bam_plbuf_init(bam_pileup_f func, void *data)
{
bam_plbuf_t *buf;
buf = calloc(1, sizeof(bam_plbuf_t));
buf->iter = bam_plp_init(0, 0);
buf->func = func;
buf->data = data;
return buf;
}
void bam_plbuf_destroy(bam_plbuf_t *buf)
{
bam_plp_destroy(buf->iter);
free(buf);
}
int bam_plbuf_push(const bam1_t *b, bam_plbuf_t *buf)
{
int ret, n_plp, tid, pos;
const bam_pileup1_t *plp;
ret = bam_plp_push(buf->iter, b);
if (ret < 0) return ret;
while ((plp = bam_plp_next(buf->iter, &tid, &pos, &n_plp)) != 0)
buf->func(tid, pos, n_plp, plp, buf->data);
return 0;
}
/***********
* mpileup *
***********/
struct __bam_mplp_t {
int n;
uint64_t min, *pos;
bam_plp_t *iter;
int *n_plp;
const bam_pileup1_t **plp;
};
bam_mplp_t bam_mplp_init(int n, bam_plp_auto_f func, void **data)
{
int i;
bam_mplp_t iter;
iter = calloc(1, sizeof(struct __bam_mplp_t));
iter->pos = calloc(n, 8);
iter->n_plp = calloc(n, sizeof(int));
iter->plp = calloc(n, sizeof(void*));
iter->iter = calloc(n, sizeof(void*));
iter->n = n;
iter->min = (uint64_t)-1;
for (i = 0; i < n; ++i) {
iter->iter[i] = bam_plp_init(func, data[i]);
iter->pos[i] = iter->min;
}
return iter;
}
void bam_mplp_set_maxcnt(bam_mplp_t iter, int maxcnt)
{
int i;
for (i = 0; i < iter->n; ++i)
iter->iter[i]->maxcnt = maxcnt;
}
void bam_mplp_destroy(bam_mplp_t iter)
{
int i;
for (i = 0; i < iter->n; ++i) bam_plp_destroy(iter->iter[i]);
free(iter->iter); free(iter->pos); free(iter->n_plp); free(iter->plp);
free(iter);
}
int bam_mplp_auto(bam_mplp_t iter, int *_tid, int *_pos, int *n_plp, const bam_pileup1_t **plp)
{
int i, ret = 0;
uint64_t new_min = (uint64_t)-1;
for (i = 0; i < iter->n; ++i) {
if (iter->pos[i] == iter->min) {
int tid, pos;
iter->plp[i] = bam_plp_auto(iter->iter[i], &tid, &pos, &iter->n_plp[i]);
iter->pos[i] = (uint64_t)tid<<32 | pos;
}
if (iter->plp[i] && iter->pos[i] < new_min) new_min = iter->pos[i];
}
iter->min = new_min;
if (new_min == (uint64_t)-1) return 0;
*_tid = new_min>>32; *_pos = (uint32_t)new_min;
for (i = 0; i < iter->n; ++i) {
if (iter->pos[i] == iter->min) { // FIXME: valgrind reports "uninitialised value(s) at this line"
n_plp[i] = iter->n_plp[i], plp[i] = iter->plp[i];
++ret;
} else n_plp[i] = 0, plp[i] = 0;
}
return ret;
}
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