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1 #include <stdio.h>
2 #include <stdlib.h>
3 #include <ctype.h>
4 #include <assert.h>
5 #include "sam.h"
6
7 typedef struct {
8         int k, x, y, end;
9 } cstate_t;
10
11 static cstate_t g_cstate_null = { -1, 0, 0, 0 };
12
13 typedef struct __linkbuf_t {
14         bam1_t b;
15         uint32_t beg, end;
16         cstate_t s;
17         struct __linkbuf_t *next;
18 } lbnode_t;
19
20 /* --- BEGIN: Memory pool */
21
22 typedef struct {
23         int cnt, n, max;
24         lbnode_t **buf;
25 } mempool_t;
26
27 static mempool_t *mp_init()
28 {
29         mempool_t *mp;
30         mp = (mempool_t*)calloc(1, sizeof(mempool_t));
31         return mp;
32 }
33 static void mp_destroy(mempool_t *mp)
34 {
35         int k;
36         for (k = 0; k < mp->n; ++k) {
37                 free(mp->buf[k]->b.data);
38                 free(mp->buf[k]);
39         }
40         free(mp->buf);
41         free(mp);
42 }
43 static inline lbnode_t *mp_alloc(mempool_t *mp)
44 {
45         ++mp->cnt;
46         if (mp->n == 0) return (lbnode_t*)calloc(1, sizeof(lbnode_t));
47         else return mp->buf[--mp->n];
48 }
49 static inline void mp_free(mempool_t *mp, lbnode_t *p)
50 {
51         --mp->cnt; p->next = 0; // clear lbnode_t::next here
52         if (mp->n == mp->max) {
53                 mp->max = mp->max? mp->max<<1 : 256;
54                 mp->buf = (lbnode_t**)realloc(mp->buf, sizeof(lbnode_t*) * mp->max);
55         }
56         mp->buf[mp->n++] = p;
57 }
58
59 /* --- END: Memory pool */
60
61 /* --- BEGIN: Auxiliary functions */
62
63 /* s->k: the index of the CIGAR operator that has just been processed.
64    s->x: the reference coordinate of the start of s->k
65    s->y: the query coordiante of the start of s->k
66  */
67 static inline int resolve_cigar2(bam_pileup1_t *p, uint32_t pos, cstate_t *s)
68 {
69 #define _cop(c) ((c)&BAM_CIGAR_MASK)
70 #define _cln(c) ((c)>>BAM_CIGAR_SHIFT)
71
72         bam1_t *b = p->b;
73         bam1_core_t *c = &b->core;
74         uint32_t *cigar = bam1_cigar(b);
75         int k, is_head = 0;
76         // determine the current CIGAR operation
77 //      fprintf(stderr, "%s\tpos=%d\tend=%d\t(%d,%d,%d)\n", bam1_qname(b), pos, s->end, s->k, s->x, s->y);
78         if (s->k == -1) { // never processed
79                 is_head = 1;
80                 if (c->n_cigar == 1) { // just one operation, save a loop
81                         if (_cop(cigar[0]) == BAM_CMATCH) s->k = 0, s->x = c->pos, s->y = 0;
82                 } else { // find the first match
83                         for (k = 0, s->x = c->pos, s->y = 0; k < c->n_cigar; ++k) {
84                                 int op = _cop(cigar[k]);
85                                 int l = _cln(cigar[k]);
86                                 if (op == BAM_CMATCH) break;
87                                 else if (op == BAM_CDEL || op == BAM_CREF_SKIP) s->x += l;
88                                 else if (op == BAM_CINS || op == BAM_CSOFT_CLIP) s->y += l;
89                         }
90                         assert(k < c->n_cigar);
91                         s->k = k;
92                 }
93         } else { // the read has been processed before
94                 int op, l = _cln(cigar[s->k]);
95                 if (pos - s->x >= l) { // jump to the next operation
96                         assert(s->k < c->n_cigar); // otherwise a bug: this function should not be called in this case
97                         op = _cop(cigar[s->k+1]);
98                         if (op == BAM_CMATCH || op == BAM_CDEL || op == BAM_CREF_SKIP) { // jump to the next without a loop
99                                 if (_cop(cigar[s->k]) == BAM_CMATCH) s->y += l;
100                                 s->x += l;
101                                 ++s->k;
102                         } else { // find the next M/D/N
103                                 if (_cop(cigar[s->k]) == BAM_CMATCH) s->y += l;
104                                 s->x += l;
105                                 for (k = s->k + 1; k < c->n_cigar; ++k) {
106                                         op = _cop(cigar[k]), l = _cln(cigar[k]);
107                                         if (op == BAM_CMATCH || op == BAM_CDEL || op == BAM_CREF_SKIP) break;
108                                         else if (op == BAM_CINS || op == BAM_CSOFT_CLIP) s->y += l;
109                                 }
110                                 s->k = k;
111                         }
112                         assert(s->k < c->n_cigar); // otherwise a bug
113                 } // else, do nothing
114         }
115         { // collect pileup information
116                 int op, l;
117                 op = _cop(cigar[s->k]);
118                 l = _cln(cigar[s->k]);
119                 p->is_del = p->indel = p->is_refskip = 0;
120                 if (op == BAM_CMATCH) {
121                         p->qpos = s->y + (pos - s->x);
122                         if (s->x + l - 1 == pos && s->k + 1 < c->n_cigar) { // peek the next operation
123                                 int op2 = _cop(cigar[s->k+1]);
124                                 int l2 = _cln(cigar[s->k+1]);
125                                 if (op2 == BAM_CDEL) p->indel = -(int)l2;
126                                 else if (op2 == BAM_CINS) p->indel = l2;
127                                 else if (op2 == BAM_CPAD && s->k + 2 < c->n_cigar) { // no working for adjacent padding
128                                         op2 = _cop(cigar[s->k+2]); l2 = _cln(cigar[s->k+2]);
129                                         if (op2 == BAM_CDEL) p->indel = -(int)l2;
130                                         else if (op2 == BAM_CINS) p->indel = l2;
131                                 }
132                         }
133                 } else if (op == BAM_CDEL || op == BAM_CREF_SKIP) {
134                         p->is_del = 1; p->qpos = s->y; // FIXME: distinguish D and N!!!!!
135                         p->is_refskip = (op == BAM_CREF_SKIP);
136                 } // cannot be other operations; otherwise a bug
137                 p->is_head = (pos == c->pos); p->is_tail = (pos == s->end);
138         }
139         return 1;
140 }
141
142 /* --- END: Auxiliary functions */
143
144 /*******************
145  * pileup iterator *
146  *******************/
147
148 struct __bam_plp_t {
149         mempool_t *mp;
150         lbnode_t *head, *tail, *dummy;
151         int32_t tid, pos, max_tid, max_pos;
152         int is_eof, flag_mask, max_plp, error;
153         bam_pileup1_t *plp;
154         // for the "auto" interface only
155         bam1_t *b;
156         bam_plp_auto_f func;
157         void *data;
158 };
159
160 bam_plp_t bam_plp_init(bam_plp_auto_f func, void *data)
161 {
162         bam_plp_t iter;
163         iter = calloc(1, sizeof(struct __bam_plp_t));
164         iter->mp = mp_init();
165         iter->head = iter->tail = mp_alloc(iter->mp);
166         iter->dummy = mp_alloc(iter->mp);
167         iter->max_tid = iter->max_pos = -1;
168         iter->flag_mask = BAM_DEF_MASK;
169         if (func) {
170                 iter->func = func;
171                 iter->data = data;
172                 iter->b = bam_init1();
173         }
174         return iter;
175 }
176
177 void bam_plp_destroy(bam_plp_t iter)
178 {
179         mp_free(iter->mp, iter->dummy);
180         mp_free(iter->mp, iter->head);
181         if (iter->mp->cnt != 0)
182                 fprintf(stderr, "[bam_plp_destroy] memory leak: %d. Continue anyway.\n", iter->mp->cnt);
183         mp_destroy(iter->mp);
184         if (iter->b) bam_destroy1(iter->b);
185         free(iter->plp);
186         free(iter);
187 }
188
189 const bam_pileup1_t *bam_plp_next(bam_plp_t iter, int *_tid, int *_pos, int *_n_plp)
190 {
191         if (iter->error) { *_n_plp = -1; return 0; }
192         *_n_plp = 0;
193         if (iter->is_eof && iter->head->next == 0) return 0;
194         while (iter->is_eof || iter->max_tid > iter->tid || (iter->max_tid == iter->tid && iter->max_pos > iter->pos)) {
195                 int n_plp = 0;
196                 lbnode_t *p, *q;
197                 // write iter->plp at iter->pos
198                 iter->dummy->next = iter->head;
199                 for (p = iter->head, q = iter->dummy; p->next; q = p, p = p->next) {
200                         if (p->b.core.tid < iter->tid || (p->b.core.tid == iter->tid && p->end <= iter->pos)) { // then remove
201                                 q->next = p->next; mp_free(iter->mp, p); p = q;
202                         } else if (p->b.core.tid == iter->tid && p->beg <= iter->pos) { // here: p->end > pos; then add to pileup
203                                 if (n_plp == iter->max_plp) { // then double the capacity
204                                         iter->max_plp = iter->max_plp? iter->max_plp<<1 : 256;
205                                         iter->plp = (bam_pileup1_t*)realloc(iter->plp, sizeof(bam_pileup1_t) * iter->max_plp);
206                                 }
207                                 iter->plp[n_plp].b = &p->b;
208                                 if (resolve_cigar2(iter->plp + n_plp, iter->pos, &p->s)) ++n_plp; // actually always true...
209                         }
210                 }
211                 iter->head = iter->dummy->next; // dummy->next may be changed
212                 *_n_plp = n_plp; *_tid = iter->tid; *_pos = iter->pos;
213                 // update iter->tid and iter->pos
214                 if (iter->head->next) {
215                         if (iter->tid > iter->head->b.core.tid) {
216                                 fprintf(stderr, "[%s] unsorted input. Pileup aborts.\n", __func__);
217                                 iter->error = 1;
218                                 *_n_plp = -1;
219                                 return 0;
220                         }
221                 }
222                 if (iter->tid < iter->head->b.core.tid) { // come to a new reference sequence
223                         iter->tid = iter->head->b.core.tid; iter->pos = iter->head->beg; // jump to the next reference
224                 } else if (iter->pos < iter->head->beg) { // here: tid == head->b.core.tid
225                         iter->pos = iter->head->beg; // jump to the next position
226                 } else ++iter->pos; // scan contiguously
227                 // return
228                 if (n_plp) return iter->plp;
229                 if (iter->is_eof && iter->head->next == 0) break;
230         }
231         return 0;
232 }
233
234 int bam_plp_push(bam_plp_t iter, const bam1_t *b)
235 {
236         if (iter->error) return -1;
237         if (b) {
238                 if (b->core.tid < 0) return 0;
239                 if (b->core.flag & iter->flag_mask) return 0;
240                 bam_copy1(&iter->tail->b, b);
241                 iter->tail->beg = b->core.pos; iter->tail->end = bam_calend(&b->core, bam1_cigar(b));
242                 iter->tail->s = g_cstate_null; iter->tail->s.end = iter->tail->end - 1; // initialize cstate_t
243                 if (b->core.tid < iter->max_tid) {
244                         fprintf(stderr, "[bam_pileup_core] the input is not sorted (chromosomes out of order)\n");
245                         iter->error = 1;
246                         return -1;
247                 }
248                 if ((b->core.tid == iter->max_tid) && (iter->tail->beg < iter->max_pos)) {
249                         fprintf(stderr, "[bam_pileup_core] the input is not sorted (reads out of order)\n");
250                         iter->error = 1;
251                         return -1;
252                 }
253                 iter->max_tid = b->core.tid; iter->max_pos = iter->tail->beg;
254                 if (iter->tail->end > iter->pos || iter->tail->b.core.tid > iter->tid) {
255                         iter->tail->next = mp_alloc(iter->mp);
256                         iter->tail = iter->tail->next;
257                 }
258         } else iter->is_eof = 1;
259         return 0;
260 }
261
262 const bam_pileup1_t *bam_plp_auto(bam_plp_t iter, int *_tid, int *_pos, int *_n_plp)
263 {
264         const bam_pileup1_t *plp;
265         if (iter->func == 0 || iter->error) { *_n_plp = -1; return 0; }
266         if ((plp = bam_plp_next(iter, _tid, _pos, _n_plp)) != 0) return plp;
267         else {
268                 *_n_plp = 0;
269                 if (iter->is_eof) return 0;
270                 while (iter->func(iter->data, iter->b) >= 0) {
271                         if (bam_plp_push(iter, iter->b) < 0) {
272                                 *_n_plp = -1;
273                                 return 0;
274                         }
275                         if ((plp = bam_plp_next(iter, _tid, _pos, _n_plp)) != 0) return plp;
276                 }
277                 bam_plp_push(iter, 0);
278                 if ((plp = bam_plp_next(iter, _tid, _pos, _n_plp)) != 0) return plp;
279                 return 0;
280         }
281 }
282
283 void bam_plp_reset(bam_plp_t iter)
284 {
285         lbnode_t *p, *q;
286         iter->max_tid = iter->max_pos = -1;
287         iter->tid = iter->pos = 0;
288         iter->is_eof = 0;
289         for (p = iter->head; p->next;) {
290                 q = p->next;
291                 mp_free(iter->mp, p);
292                 p = q;
293         }
294         iter->head = iter->tail;
295 }
296
297 void bam_plp_set_mask(bam_plp_t iter, int mask)
298 {
299         iter->flag_mask = mask < 0? BAM_DEF_MASK : (BAM_FUNMAP | mask);
300 }
301
302 /*****************
303  * callback APIs *
304  *****************/
305
306 int bam_pileup_file(bamFile fp, int mask, bam_pileup_f func, void *func_data)
307 {
308         bam_plbuf_t *buf;
309         int ret;
310         bam1_t *b;
311         b = bam_init1();
312         buf = bam_plbuf_init(func, func_data);
313         bam_plbuf_set_mask(buf, mask);
314         while ((ret = bam_read1(fp, b)) >= 0)
315                 bam_plbuf_push(b, buf);
316         bam_plbuf_push(0, buf);
317         bam_plbuf_destroy(buf);
318         bam_destroy1(b);
319         return 0;
320 }
321
322 void bam_plbuf_set_mask(bam_plbuf_t *buf, int mask)
323 {
324         bam_plp_set_mask(buf->iter, mask);
325 }
326
327 void bam_plbuf_reset(bam_plbuf_t *buf)
328 {
329         bam_plp_reset(buf->iter);
330 }
331
332 bam_plbuf_t *bam_plbuf_init(bam_pileup_f func, void *data)
333 {
334         bam_plbuf_t *buf;
335         buf = calloc(1, sizeof(bam_plbuf_t));
336         buf->iter = bam_plp_init(0, 0);
337         buf->func = func;
338         buf->data = data;
339         return buf;
340 }
341
342 void bam_plbuf_destroy(bam_plbuf_t *buf)
343 {
344         bam_plp_destroy(buf->iter);
345         free(buf);
346 }
347
348 int bam_plbuf_push(const bam1_t *b, bam_plbuf_t *buf)
349 {
350         int ret, n_plp, tid, pos;
351         const bam_pileup1_t *plp;
352         ret = bam_plp_push(buf->iter, b);
353         if (ret < 0) return ret;
354         while ((plp = bam_plp_next(buf->iter, &tid, &pos, &n_plp)) != 0)
355                 buf->func(tid, pos, n_plp, plp, buf->data);
356         return 0;
357 }
358
359 /***********
360  * mpileup *
361  ***********/
362
363 struct __bam_mplp_t {
364         int n;
365         uint64_t min, *pos;
366         bam_plp_t *iter;
367         int *n_plp;
368         const bam_pileup1_t **plp;
369 };
370
371 bam_mplp_t bam_mplp_init(int n, bam_plp_auto_f func, void **data)
372 {
373         int i;
374         bam_mplp_t iter;
375         iter = calloc(1, sizeof(struct __bam_mplp_t));
376         iter->pos = calloc(n, 8);
377         iter->n_plp = calloc(n, sizeof(int));
378         iter->plp = calloc(n, sizeof(void*));
379         iter->iter = calloc(n, sizeof(void*));
380         iter->n = n;
381         iter->min = (uint64_t)-1;
382         for (i = 0; i < n; ++i) {
383                 iter->iter[i] = bam_plp_init(func, data[i]);
384                 iter->pos[i] = iter->min;
385         }
386         return iter;
387 }
388
389 void bam_mplp_destroy(bam_mplp_t iter)
390 {
391         int i;
392         for (i = 0; i < iter->n; ++i) bam_plp_destroy(iter->iter[i]);
393         free(iter->iter); free(iter->pos); free(iter->n_plp); free(iter->plp);
394         free(iter);
395 }
396
397 int bam_mplp_auto(bam_mplp_t iter, int *_tid, int *_pos, int *n_plp, const bam_pileup1_t **plp)
398 {
399         int i, ret = 0;
400         uint64_t new_min = (uint64_t)-1;
401         for (i = 0; i < iter->n; ++i) {
402                 if (iter->pos[i] == iter->min) {
403                         int tid, pos;
404                         iter->plp[i] = bam_plp_auto(iter->iter[i], &tid, &pos, &iter->n_plp[i]);
405                         iter->pos[i] = (uint64_t)tid<<32 | pos;
406                 }
407                 if (iter->plp[i] && iter->pos[i] < new_min) new_min = iter->pos[i];
408         }
409         iter->min = new_min;
410         if (new_min == (uint64_t)-1) return 0;
411         *_tid = new_min>>32; *_pos = (uint32_t)new_min;
412         for (i = 0; i < iter->n; ++i) {
413                 if (iter->pos[i] == iter->min) { // FIXME: valgrind reports "uninitialised value(s) at this line"
414                         n_plp[i] = iter->n_plp[i], plp[i] = iter->plp[i];
415                         ++ret;
416                 } else n_plp[i] = 0, plp[i] = 0;
417         }
418         return ret;
419 }