File: bubble.c

package info (click to toggle)
fermi-lite 0.1-5
  • links: PTS, VCS
  • area: main
  • in suites: bullseye, buster, sid
  • size: 652 kB
  • sloc: ansic: 5,157; makefile: 63; sh: 13
file content (367 lines) | stat: -rw-r--r-- 12,080 bytes parent folder | download | duplicates (4)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
#include <limits.h>
#include <stdio.h>
#include "mag.h"
#include "kvec.h"
#include "ksw.h"
#include "internal.h"
#include "khash.h"
KHASH_DECLARE(64, uint64_t, uint64_t)

typedef khash_t(64) hash64_t;

#define MAX_N_DIFF 2.01 // for evaluating alignment after SW
#define MAX_R_DIFF 0.1
#define L_DIFF_COEF 0.2 // n_diff=|l_0 - l_1|*L_DIFF_COEF

#define edge_mark_del(_x) ((_x).x = (uint64_t)-2, (_x).y = 0)
#define edge_is_del(_x)   ((_x).x == (uint64_t)-2 || (_x).y == 0)

static int fm_verbose = 1;

/******************
 * Closed bubbles *
 ******************/

typedef struct {
	uint64_t id;
	int cnt[2];
	int n[2][2], d[2][2];
	uint64_t v[2][2];
} trinfo_t;

const trinfo_t g_trinull = {-1, {0, 0}, {{INT_MIN, INT_MIN}, {INT_MIN, INT_MIN}}, {{INT_MIN, INT_MIN}, {INT_MIN, INT_MIN}}, {{-1, -1}, {-1, -1}}};

typedef struct {
	int n, m;
	trinfo_t **buf;
} tipool_t;

struct mogb_aux {
	tipool_t pool;
	ku64_v stack;
	hash64_t *h;
};

mogb_aux_t *mag_b_initaux(void)
{
	mogb_aux_t *aux = calloc(1, sizeof(mogb_aux_t));
	aux->h = kh_init(64);
	return aux;
}

void mag_b_destroyaux(mogb_aux_t *b)
{
	int i;
	for (i = 0; i < b->pool.m; ++i)
		free(b->pool.buf[i]);
	free(b->pool.buf); free(b->stack.a);
	kh_destroy(64, b->h);
	free(b);
}

#define tiptr(p) ((trinfo_t*)(p)->ptr)

static inline trinfo_t *tip_alloc(tipool_t *pool, uint32_t id)
{ // allocate an object from the memory pool
	trinfo_t *p;
	if (pool->n == pool->m) {
		int i, new_m = pool->m? pool->m<<1 : 256;
		pool->buf = realloc(pool->buf, new_m * sizeof(void*));
		for (i = pool->m; i < new_m; ++i)
			pool->buf[i] = malloc(sizeof(trinfo_t));
		pool->m = new_m;
	}
	p = pool->buf[pool->n++];
	*p = g_trinull;
	p->id = id;
	return p;
}

static void backtrace(mag_t *g, uint64_t end, uint64_t start, hash64_t *h)
{
	while (end>>32 != start) {
		int ret;
		kh_put(64, h, end>>33, &ret);
		end = tiptr(&g->v.a[end>>33])->v[(end>>32^1)&1][end&1];
	}
}

void mag_vh_simplify_bubble(mag_t *g, uint64_t idd, int max_vtx, int max_dist, mogb_aux_t *a)
{
	int i, n_pending = 0;
	magv_t *p, *q;

	p = &g->v.a[idd>>1];
	if (p->len < 0 || p->nei[idd&1].n < 2) return; // stop if p is deleted or it has 0 or 1 neighbor
	// reset aux data
	a->stack.n = a->pool.n = 0;
	if (kh_n_buckets(a->h) >= 64) {
		kh_destroy(64, a->h);
		a->h = kh_init(64);
	} else kh_clear(64, a->h);
	// add the initial vertex
	p->ptr = tip_alloc(&a->pool, idd>>1);
	tiptr(p)->d[(idd&1)^1][0] = -p->len;
	tiptr(p)->n[(idd&1)^1][0] = -p->nsr;
	kv_push(uint64_t, a->stack, idd^1);
	// essentially a topological sorting
	while (a->stack.n) {
		uint64_t x, y;
		ku128_v *r;
		if (a->stack.n == 1 && a->stack.a[0] != (idd^1) && n_pending == 0) break; // found the other end of the bubble
		x = kv_pop(a->stack);
		p = &g->v.a[x>>1];
		//printf("%lld:%lld\n", p->k[0], p->k[1]);
		r = &p->nei[(x&1)^1]; // we will look the the neighbors from the other end of the unitig
		if (a->pool.n > max_vtx || tiptr(p)->d[x&1][0] > max_dist || tiptr(p)->d[x&1][1] > max_dist || r->n == 0) break; // we failed
		// set the distance to p's neighbors
		for (i = 0; i < r->n; ++i) {
			int nsr, dist, which;
			if ((int64_t)r->a[i].x < 0) continue;
			y = mag_tid2idd(g->h, r->a[i].x);
			if (y == (idd^1)) { // there is a loop involving the initial vertex
				a->stack.n = 0;
				break; // not a bubble; stop; this will jump out of the while() loop
			}
			q = &g->v.a[y>>1];
			if (q->ptr == 0) { // has not been attempted
				q->ptr = tip_alloc(&a->pool, y>>1), ++n_pending;
				mag_v128_clean(&q->nei[y&1]); // make sure there are no deleted edges
			}
			nsr  = tiptr(p)->n[x&1][0] + p->nsr; which = 0;
			dist = tiptr(p)->d[x&1][0] + p->len - r->a[i].y;
			//printf("01 [%d]\t[%d,%d]\t[%d,%d]\n", i, tiptr(q)->n[y&1][0], tiptr(q)->n[y&1][1], tiptr(q)->d[y&1][0], tiptr(q)->d[y&1][1]);
			// test and possibly update the tentative distance
			if (nsr > tiptr(q)->n[y&1][0]) { // then move the best to the 2nd best and update the best
				tiptr(q)->n[y&1][1] = tiptr(q)->n[y&1][0]; tiptr(q)->n[y&1][0] = nsr;
				tiptr(q)->v[y&1][1] = tiptr(q)->v[y&1][0]; tiptr(q)->v[y&1][0] = (x^1)<<32|i<<1|which;
				tiptr(q)->d[y&1][1] = tiptr(q)->d[y&1][0]; tiptr(q)->d[y&1][0] = dist;
				nsr  = tiptr(p)->n[x&1][1] + p->nsr; which = 1; // now nsr is the 2nd best
				dist = tiptr(p)->d[x&1][1] + p->len - r->a[i].y;
			}
			if (nsr > tiptr(q)->n[y&1][1]) // update the 2nd best
				tiptr(q)->n[y&1][1] = nsr, tiptr(q)->v[y&1][1] = (x^1)<<32|i<<1|which, tiptr(q)->d[y&1][1] = dist;
			if (++tiptr(q)->cnt[y&1] == q->nei[y&1].n) { // all q's predecessors have been processed; then push
				kv_push(uint64_t, a->stack, y);
				--n_pending;
			}
		}
	}
	if (n_pending == 0 && a->stack.n == 1) { // found a bubble
		uint64_t x = a->stack.a[0];
		p = &g->v.a[x>>1];
		//printf("(%d,%d)\t(%d,%d)\n", tiptr(p)->n[x&1][0], tiptr(p)->n[x&1][1], tiptr(p)->d[x&1][0], tiptr(p)->d[x&1][1]);
		backtrace(g, tiptr(p)->v[x&1][0], idd, a->h);
		backtrace(g, tiptr(p)->v[x&1][1], idd, a->h);
	}
	for (i = 0; i < a->pool.n; ++i) // reset p->ptr
		g->v.a[a->pool.buf[i]->id].ptr = 0;
	if (kh_size(a->h)) { // bubble detected; then remove verticies not in the top two paths
		for (i = 1; i < a->pool.n; ++i) { // i=0 corresponds to the initial vertex which we want to exclude
			uint64_t id = a->pool.buf[i]->id;
			if (id != a->stack.a[0]>>1 && kh_get(64, a->h, id) == kh_end(a->h)) // not in the top two paths
				mag_v_del(g, &g->v.a[id]);
		}
	}
}

void mag_g_simplify_bubble(mag_t *g, int max_vtx, int max_dist)
{
	int64_t i;
	mogb_aux_t *a;
	a = mag_b_initaux();
	for (i = 0; i < g->v.n; ++i) {
		mag_vh_simplify_bubble(g, i<<1|0, max_vtx, max_dist, a);
		mag_vh_simplify_bubble(g, i<<1|1, max_vtx, max_dist, a);
	}
	mag_b_destroyaux(a);
	mag_g_merge(g, 0, 0);
}

int mag_vh_pop_simple(mag_t *g, uint64_t idd, float max_cov, float max_frac, int aggressive)
{
	magv_t *p = &g->v.a[idd>>1], *q[2];
	ku128_v *r;
	int i, j, k, dir[2], l[2], ret = -1;
	char *seq[2], *cov[2];
	float n_diff, r_diff, avg[2], max_n_diff = aggressive? MAX_N_DIFF * 2. : MAX_N_DIFF;

	if (p->len < 0 || p->nei[idd&1].n != 2) return ret; // deleted or no bubble
	r = &p->nei[idd&1];
	for (j = 0; j < 2; ++j) {
		uint64_t x;
		if ((int64_t)r->a[j].x < 0) return ret;
		x = mag_tid2idd(g->h, r->a[j].x);
		dir[j] = x&1;
		q[j] = &g->v.a[x>>1];
		if (q[j]->nei[0].n != 1 || q[j]->nei[1].n != 1) return ret; // no bubble
		l[j] = q[j]->len - (int)(q[j]->nei[0].a->y + q[j]->nei[1].a->y);
	}
	if (q[0]->nei[dir[0]^1].a->x != q[1]->nei[dir[1]^1].a->x) return ret; // no bubble
	for (j = 0; j < 2; ++j) { // set seq[] and cov[], and compute avg[]
		if (l[j] > 0) {
			seq[j] = malloc(l[j]<<1);
			cov[j] = seq[j] + l[j];
			for (i = 0; i < l[j]; ++i) {
				seq[j][i] = q[j]->seq[i + q[j]->nei[0].a->y];
				cov[j][i] = q[j]->cov[i + q[j]->nei[0].a->y];
			}
			if (dir[j]) {
				seq_revcomp6(l[j], (uint8_t*)seq[j]);
				seq_reverse(l[j], (uint8_t*)cov[j]);
			}
			for (i = 0, avg[j] = 0.; i < l[j]; ++i) {
				--seq[j][i]; // change DNA6 encoding to DNA4 for SW below
				avg[j] += cov[j][i] - 33;
			}
			avg[j] /= l[j];
		} else { // l[j] <= 0; this may happen around a tandem repeat
			int beg, end;
			seq[j] = cov[j] = 0;
			beg = q[j]->nei[0].a->y; end = q[j]->len - q[j]->nei[1].a->y;
			if (beg > end) beg ^= end, end ^= beg, beg ^= end; // swap
			if (beg < end) {
				for (i = beg, avg[j] = 0.; i < end; ++i)
					avg[j] += q[j]->cov[i] - 33;
				avg[j] /= end - beg;
			} else avg[j] = q[j]->cov[beg] - 33; // FIXME: when q[j] is contained, weird thing may happen
		}
	}
	ret = 1;
	if (l[0] > 0 && l[1] > 0) { // then do SW to compute n_diff and r_diff
		int8_t mat[16];
		kswr_t aln;
		for (i = k = 0; i < 4; ++i)
			for (j = 0; j < 4; ++j)
				mat[k++] = i == j? 5 : -4;
		aln = ksw_align(l[0], (uint8_t*)seq[0], l[1], (uint8_t*)seq[1], 4, mat, 5, 2, 0, 0);
		n_diff = ((l[0] < l[1]? l[0] : l[1]) * 5. - aln.score) / (5. + 4.); // 5: matching score; -4: mismatchig score
		r_diff = n_diff / ((l[0] + l[1]) / 2.);
		//fprintf(stderr, "===> %f %f <===\n", n_diff, r_diff); for (j = 0; j < 2; ++j) { for (i = 0; i < l[j]; ++i) fputc("ACGTN"[(int)seq[j][i]], stderr); fputc('\n', stderr); }
	} else {
		n_diff = abs(l[0] - l[1]) * L_DIFF_COEF;
		r_diff = 1.;
		//fprintf(stderr, "---> (%d,%d) <---\n", l[0], l[1]);
	}
	if (n_diff < max_n_diff || r_diff < MAX_R_DIFF) {
		j = avg[0] < avg[1]? 0 : 1;
		if (aggressive || (avg[j] < max_cov && avg[j] / (avg[j^1] + avg[j]) < max_frac)) {
			mag_v_del(g, q[j]);
			ret = 2;
		}
	}
	free(seq[0]); free(seq[1]);
	return ret;
}

void mag_g_pop_simple(mag_t *g, float max_cov, float max_frac, int min_merge_len, int aggressive)
{
	int64_t i, n_examined = 0, n_popped = 0;
	int ret;

	for (i = 0; i < g->v.n; ++i) {
		ret = mag_vh_pop_simple(g, i<<1|0, max_cov, max_frac, aggressive);
		if (ret >= 1) ++n_examined;
		if (ret >= 2) ++n_popped;
		ret = mag_vh_pop_simple(g, i<<1|1, max_cov, max_frac, aggressive);
		if (ret >= 1) ++n_examined;
		if (ret >= 2) ++n_popped;
	}
	if (fm_verbose >= 3)
		fprintf(stderr, "[M::%s] examined %ld bubbles and popped %ld\n", __func__, (long)n_examined, (long)n_popped);
	mag_g_merge(g, 0, min_merge_len);
}

/****************
 * Open bubbles *
 ****************/

void mag_v_pop_open(mag_t *g, magv_t *p, int min_elen)
{
	int i, j, k, l, dir, max_l, l_qry;
	magv_t *q, *t;
	ku128_v *r, *s;
	uint8_t *seq;
	int8_t mat[16];

	if (p->len < 0 || p->len >= min_elen) return;
	//if (p->nei[0].n && p->nei[1].n) return; // FIXME: between this and the next line, which is better?
	if (p->nei[0].n + p->nei[1].n != 1) return;
	dir = p->nei[0].n? 0 : 1;
	// initialize the scoring system
	for (i = k = 0; i < 4; ++i)
		for (j = 0; j < 4; ++j)
			mat[k++] = i == j? 5 : -4;
	
	s = &p->nei[dir];
	for (l = 0; l < s->n; ++l) { // if we use "if (p->nei[0].n + p->nei[1].n != 1)", s->n == 1
		uint64_t v;
		kswq_t *qry;
		if ((int64_t)s->a[l].x < 0) continue;
		v = mag_tid2idd(g->h, s->a[l].x);
		q = &g->v.a[v>>1];
		if (q == p || q->nei[v&1].n == 1) continue;
		// get the query ready
		max_l = (p->len - s->a[l].y) * 2;
		seq = malloc(max_l + 1);
		if (dir == 0) { // forward strand
			for (j = s->a[l].y, k = 0; j < p->len; ++j)
				seq[k++] = p->seq[j] - 1;
		} else { // reverse
			for (j = p->len - s->a[l].y - 1, k = 0; j >= 0; --j)
				seq[k++] = 4 - p->seq[j];
		}
		l_qry = k;
		qry = ksw_qinit(2, l_qry, seq, 4, mat);
		//fprintf(stderr, "===> %lld:%lld:%d[%d], %d, %ld <===\n", p->k[0], p->k[1], s->n, l, p->nsr, q->nei[v&1].n);
		//for (j = 0; j < k; ++j) fputc("ACGTN"[(int)seq[j]], stderr); fputc('\n', stderr);

		r = &q->nei[v&1];
		for (i = 0; i < r->n; ++i) {
			uint64_t w;
			kswr_t aln;
			if (r->a[i].x == p->k[dir] || (int64_t)r->a[i].x < 0) continue;
			w = mag_tid2idd(g->h, r->a[i].x);
			// get the target sequence
			t = &g->v.a[w>>1];
			if (w&1) { // reverse strand
				for (j = t->len - r->a[i].y - 1, k = 0; j >= 0 && k < max_l; --j)
					seq[k++] = 4 - t->seq[j];
			} else {
				for (j = r->a[i].y, k = 0; j < t->len && k < max_l; ++j)
					seq[k++] = t->seq[j] - 1;
			}
			aln = ksw_align(0, 0, k, seq, 4, mat, 5, 2, 0, &qry);
			//for (j = 0; j < k; ++j) fputc("ACGTN"[(int)seq[j]], stderr); fprintf(stderr, "\t%d\t%f\n", aln.score, (l_qry * 5. - aln.score) / (5. + 4.));
			if (aln.score >= l_qry * 5 / 2) {
				double r_diff, n_diff;
				n_diff = (l_qry * 5. - aln.score) / (5. + 4.); // 5: matching score; -4: mismatchig score
				r_diff = n_diff / l_qry;
				if (n_diff < MAX_N_DIFF || r_diff < MAX_R_DIFF) break;
			}
		}

		if (i != r->n) {
			// mark delete in p and delete in q
			edge_mark_del(s->a[l]);
			for (i = 0; i < r->n; ++i)
				if (r->a[i].x == p->k[dir])
					edge_mark_del(r->a[i]);
		}
		free(seq); free(qry);
	}

	for (i = 0; i < s->n; ++i)
		if (!edge_is_del(s->a[i])) break;
	if (i == s->n) mag_v_del(g, p); // p is not connected to any other vertices
}

void mag_g_pop_open(mag_t *g, int min_elen)
{
	int64_t i;
	for (i = 0; i < g->v.n; ++i)
		mag_v_pop_open(g, &g->v.a[i], min_elen);
	if (fm_verbose >= 3)
		fprintf(stderr, "[M:%s] popped open bubbles\n", __func__);
	mag_g_merge(g, 0, 0);
}