#include #include #include #include #include #include #include #include "ksort.h" #include "kvec.h" #include "khash.h" #include "kseq.h" KSTREAM_INIT(gzFile, gzread, 0x10000) static int lo_verbose = 3; /*********************** * Core data structure * ***********************/ #define LO_T_C1 8 #define LO_T_C2 12 #define LO_T_I 16 typedef struct { int min_ext, fuzzy_dist; int min_n_ovlp; float min_aln_ratio; } lo_opt_t; typedef struct { uint32_t dist:31, reduced:1; uint32_t id:31, ori:1; } lo_nei_t; typedef kvec_t(lo_nei_t) lo_nei_v; #define nei_lt(a, b) ((a).dist < (b).dist) KSORT_INIT(nei, lo_nei_t, nei_lt) #define LO_VF_CONTAINED 0x1 #define LO_VF_LACK_OVLP 0x2 typedef struct { int id; int flag:16, state:16; char *name; lo_nei_v *nei[2]; } vertex_t; typedef kvec_t(vertex_t) vertex_v; #define lo_skipped(v) ((v)->flag & (LO_VF_CONTAINED|LO_VF_LACK_OVLP)) typedef struct { int type:16, reduced:16; int l[2], s[2], e[2], d[2]; // length, start and end float usc; } edgeinfo_t; KHASH_MAP_INIT_INT64(edge, edgeinfo_t) typedef khash_t(edge) ehash_t; KHASH_MAP_INIT_STR(name, int) typedef khash_t(name) nhash_t; typedef struct { nhash_t *n; ehash_t *e; vertex_v v; } ograph_t; void lo_opt_init(lo_opt_t *opt) { opt->min_ext = 50; opt->min_aln_ratio = 0.9; opt->min_n_ovlp = 1; opt->fuzzy_dist = 100; } const char *lo_edge_label[] = { ">>", "><", "<>", "<<", "??", "??", "??", "??", "C1", "??", "??", "??", "C2", "??", "??", "??", "IN" }; /********** * Parser * **********/ ograph_t *lo_graph_init() { ograph_t *g; g = calloc(1, sizeof(ograph_t)); g->n = kh_init(name); g->e = kh_init(edge); return g; } void lo_print_edge(const ograph_t *g) { khint_t k; for (k = 0; k != kh_end(g->e); ++k) { if (kh_exist(g->e, k) && !kh_val(g->e, k).reduced) { int id[2]; edgeinfo_t *e = &kh_val(g->e, k); id[0] = kh_key(g->e, k)>>32; id[1] = (uint32_t)kh_key(g->e, k); if (e->s[1] < e->e[1]) printf("%s\t%s\t%d\t%d\t%d\t%s\t%d\t%d\t%d\t%.3f\n", lo_edge_label[e->type], g->v.a[id[0]].name, e->l[0], e->s[0], e->e[0], g->v.a[id[1]].name, e->l[1], e->s[1], e->e[1], e->usc); else printf("%s\t%s\t%d\t%d\t%d\t%s\t%d\t%d\t%d\t%.3f\n", lo_edge_label[e->type], g->v.a[id[0]].name, e->l[0], e->e[0], e->s[0], g->v.a[id[1]].name, e->l[1], e->e[1], e->s[1], e->usc); } } } int lo_infer_edge_type(const lo_opt_t *opt, int l[2], int s[2], int e[2], int d[2]) { int el, x[2], a[2], r[2]; // x: eXtended length, a: Aligned length; r: Remaining length int t[2][2], type; t[0][1] = s[1], t[1][1] = l[1] - e[1]; if (s[0] < e[0]) t[0][0] = s[0], t[1][0] = l[0] - e[0]; else t[0][0] = l[0] - s[0], t[1][0] = e[0]; x[0] = a[0] = abs(e[0] - s[0]); x[1] = a[1] = e[1] - s[1]; r[0] = t[0][0] - t[0][1]; r[1] = t[1][1] - t[1][0]; el = r[0] < 0? t[0][0] : t[0][1]; el += r[1] < 0? t[1][1] : t[1][0]; x[0] += el, x[1] += el; d[0] = d[1] = -1; if ((double)a[0] / x[0] >= opt->min_aln_ratio && (double)a[1] / x[1] >= opt->min_aln_ratio) { if ((r[0] >= opt->min_ext && r[1] >= opt->min_ext) || (r[0] <= -opt->min_ext && r[1] <= -opt->min_ext)) { // suffix-prefix match type = s[0] < e[0]? 0 : 2; if (r[0] < 0) type ^= 3, d[0] = -r[1], d[1] = -r[0]; // reverse the direction else d[0] = r[0], d[1] = r[1]; } else type = (double)x[0] / l[0] > (double)x[1] / l[1]? LO_T_C1 : LO_T_C2; } else type = LO_T_I; // internal local match; not a suffix-prefix match return type; } ograph_t *lo_graph_parse(const lo_opt_t *opt, kstream_t *ks) { ograph_t *g; kstring_t str = {0,0,0}; char *p, *q; khint_t k; int dret, absent; g = lo_graph_init(); while (ks_getuntil(ks, KS_SEP_LINE, &str, &dret) >= 0) { int i, id[2]; edgeinfo_t e; for (p = q = str.s, i = 0;; ++q) { if (*q != '\t' && *q != 0) continue; if (i == 0 || i == 4) { int c = *q; *q = 0; k = kh_get(name, g->n, p); if (k == kh_end(g->n)) { // a new entry vertex_t *z; z = kv_pushp(vertex_t, g->v); z->id = kh_size(g->n); z->name = strdup(p); z->flag = z->state = 0; z->nei[0] = z->nei[1] = 0; // don't initialize the neighbor list right now k = kh_put(name, g->n, z->name, &absent); assert(absent); kh_val(g->n, k) = z->id; } id[(i==4)] = kh_val(g->n, k); *q = c; } else if (i == 1) e.l[0] = strtol(p, &p, 10); else if (i == 2) e.s[0] = strtol(p, &p, 10); else if (i == 3) e.e[0] = strtol(p, &p, 10); else if (i == 5) e.l[1] = strtol(p, &p, 10); else if (i == 6) e.s[1] = strtol(p, &p, 10); else if (i == 7) e.e[1] = strtol(p, &p, 10); else if (i == 8) e.usc = strtod(p, &p); ++i; p = q + 1; if (*q == 0) break; } if (i < 9) continue; // not enough fields e.type = lo_infer_edge_type(opt, e.l, e.s, e.e, e.d); if (e.type == LO_T_C1) { g->v.a[id[0]].flag |= LO_VF_CONTAINED; } else if (e.type == LO_T_C2) { g->v.a[id[1]].flag |= LO_VF_CONTAINED; } else if (e.type < 4) { // a suffix-prefix overlap uint64_t x = (uint64_t)id[0]<<32 | id[1]; int sc_new, sc_old; edgeinfo_t *f; k = kh_put(edge, g->e, x, &absent); f = &kh_val(g->e, k); sc_old = f->usc * (abs(f->s[0] - f->e[0]) > abs(f->s[1] - f->e[1])? abs(f->s[0] - f->e[0]) : abs(f->s[1] - f->e[1])); sc_new = e.usc * (abs(e.s[0] - e.e[0]) > abs(e.s[1] - e.e[1])? abs(e.s[0] - e.e[0]) : abs(e.s[1] - e.e[1])); if (absent || sc_old < sc_new) // TODO: compare the total score, not unit score! kh_val(g->e, k) = e; } } free(str.s); if (lo_verbose >= 3) fprintf(stderr, "[M::%s] read %d edges\n", __func__, kh_size(g->e)); return g; } void lo_graph_destroy(ograph_t *g) { int i; for (i = 0; i < g->v.n; ++i) { if (g->v.a[i].nei[0]) free(g->v.a[i].nei[0]->a); if (g->v.a[i].nei[1]) free(g->v.a[i].nei[1]->a); free(g->v.a[i].name); } free(g->v.a); kh_destroy(edge, g->e); kh_destroy(name, g->n); free(g); } /****************** * Graph routines * ******************/ #define lo_swap(tmp, a, b) ((tmp) = (a), (a) = (b), (b) = (tmp)) static inline void lo_flip_edge(edgeinfo_t *e) { int tmp; lo_swap(tmp, e->l[0], e->l[1]); lo_swap(tmp, e->s[0], e->s[1]); lo_swap(tmp, e->e[0], e->e[1]); lo_swap(tmp, e->d[0], e->d[1]); e->type = ((e->type&1)<<1 | (e->type&2)>>1) ^ 3; } void lo_add_missing(ograph_t *g) { khint_t k, l; int absent; ehash_t *added; added = kh_init(edge); for (k = 0; k != kh_end(g->e); ++k) { int id[2]; if (!kh_exist(g->e, k)) continue; id[0] = kh_key(g->e, k)>>32; id[1] = (uint32_t)kh_key(g->e, k); if (!lo_skipped(&g->v.a[id[0]]) && !lo_skipped(&g->v.a[id[1]])) { uint64_t key2 = (uint64_t)id[1]<<32|id[0]; l = kh_get(edge, g->e, key2); if (l == kh_end(g->e)) { l = kh_put(edge, added, key2, &absent); kh_val(added, l) = kh_val(g->e, k); lo_flip_edge(&kh_val(added, l)); } } } for (k = 0; k != kh_end(added); ++k) { if (!kh_exist(added, k)) continue; l = kh_put(edge, g->e, kh_key(added, k), &absent); assert(absent); kh_val(g->e, l) = kh_val(added, k); } if (lo_verbose >= 3) fprintf(stderr, "[M::%s] added %d missing edges. %d edges remain in total.\n", __func__, kh_size(added), kh_size(g->e)); kh_destroy(edge, added); } void lo_rm_skipped(ograph_t *g) { khint_t k; int n_del = 0; for (k = 0; k != kh_end(g->e); ++k) { int id[2]; if (!kh_exist(g->e, k)) continue; id[0] = kh_key(g->e, k)>>32; id[1] = (uint32_t)kh_key(g->e, k); if (lo_skipped(&g->v.a[id[0]]) || lo_skipped(&g->v.a[id[1]])) { ++n_del; kh_del(edge, g->e, k); // kh_del() will not trigger rehash } } if (lo_verbose >= 3) fprintf(stderr, "[M::%s] removed %d edges; %d remain\n", __func__, n_del, kh_size(g->e)); } void lo_rm_conflict(ograph_t *g) { } void lo_mark_lack_ovlp(ograph_t *g, int min_n_ovlp) // can only be called before lo_populate_nei() { int *count, i, n_marked = 0; khint_t k; count = calloc(g->v.n<<1, sizeof(int)); for (k = 0; k != kh_end(g->e); ++k) { int id[2]; edgeinfo_t *e; if (!kh_exist(g->e, k) || kh_val(g->e, k).type >= 4) continue; e = &kh_val(g->e, k); id[0] = kh_key(g->e, k)>>32; id[1] = (uint32_t)kh_key(g->e, k); ++count[id[0]<<1|(e->type>>1^1)]; ++count[id[1]|(e->type&1)]; } for (i = 0; i < g->v.n; ++i) if (!lo_skipped(&g->v.a[i]) && (count[i<<1|0] < min_n_ovlp || count[i<<1|1] < min_n_ovlp)) g->v.a[i].flag |= LO_VF_LACK_OVLP, ++n_marked; free(count); if (lo_verbose >= 3) fprintf(stderr, "[M::%s] %d vertices to be dropped due to lack of overlaps\n", __func__, n_marked); } void lo_print_nei(ograph_t *g) { int i; for (i = 0; i < g->v.n; ++i) { vertex_t *p = &g->v.a[i]; if (!lo_skipped(p) && p->nei[0]) { int j, k; printf("%s\t%ld,%ld", p->name, p->nei[0]->n, p->nei[1]->n); for (j = 0; j < 2; ++j) { if (p->nei[j]->n) { putchar('\t'); for (k = 0; k < p->nei[j]->n; ++k) { lo_nei_t *q = &p->nei[j]->a[k]; if (k) putchar(','); printf("%s%c%d:%c", g->v.a[q->id].name, "<>"[q->ori], q->dist, "+-"[q->reduced]); } } else printf("\t*"); } putchar('\n'); } } } void lo_populate_nei(ograph_t *g) { int i; khint_t k; for (i = 0; i < g->v.n; ++i) { if (lo_skipped(&g->v.a[i])) continue; g->v.a[i].nei[0] = calloc(1, sizeof(lo_nei_v)); g->v.a[i].nei[1] = calloc(1, sizeof(lo_nei_v)); } for (k = 0; k != kh_end(g->e); ++k) { int id[2]; edgeinfo_t *e; lo_nei_t *p; if (!kh_exist(g->e, k)) continue; id[0] = kh_key(g->e, k)>>32; id[1] = (uint32_t)kh_key(g->e, k); if (id[0] > id[1]) continue; e = &kh_val(g->e, k); p = kv_pushp(lo_nei_t, *g->v.a[id[0]].nei[e->type>>1^1]); p->dist = e->d[0], p->id = id[1], p->ori = e->type&1, p->reduced = 0; p = kv_pushp(lo_nei_t, *g->v.a[id[1]].nei[e->type&1]); p->dist = e->d[1], p->id = id[0], p->ori = e->type>>1^1, p->reduced = 0; } for (i = 0; i < g->v.n; ++i) { vertex_t *p = &g->v.a[i]; if (p->nei[0]) ks_introsort(nei, p->nei[0]->n, p->nei[0]->a); if (p->nei[1]) ks_introsort(nei, p->nei[1]->n, p->nei[1]->a); } } static inline edgeinfo_t *lo_get_edge(ehash_t *e, int id0, int id1) { khint_t k; k = kh_get(edge, e, (uint64_t)id0<<32 | id1); return k == kh_end(e)? 0 : &kh_val(e, k); } void lo_trans_reduce(ograph_t *g, int fd) // fd: fuzzy distance { int i, j, k, l; for (i = 0; i < g->v.n; ++i) g->v.a[i].state = 0; for (i = 0; i < g->v.n; ++i) { vertex_t *pi = &g->v.a[i]; if (pi->nei[0] == 0) continue; for (j = 0; j < 2; ++j) { int max; lo_nei_v *q = pi->nei[j]; if (q->n == 0) continue; for (k = 0; k < q->n; ++k) g->v.a[q->a[k].id].state = 1; max = q->a[q->n - 1].dist + fd; // loop between line 9--14 for (k = 0; k < q->n; ++k) { vertex_t *pk = &g->v.a[q->a[k].id]; if (pk->state == 1) { lo_nei_v *r = pk->nei[q->a[k].ori^1]; for (l = 0; l < r->n; ++l) if (r->a[l].dist + q->a[k].dist < max && g->v.a[r->a[l].id].state == 1) g->v.a[r->a[l].id].state = 2; } } // loop between line 20--23 for (k = 0; k < q->n; ++k) { if (g->v.a[q->a[k].id].state == 2) { edgeinfo_t *e; e = lo_get_edge(g->e, i, q->a[k].id); e->reduced = 1; e = lo_get_edge(g->e, q->a[k].id, i); e->reduced = 1; } g->v.a[q->a[k].id].state = 0; } } } for (i = 0; i < g->v.n; ++i) { vertex_t *pi = &g->v.a[i]; if (pi->nei[0] == 0) continue; for (j = 0; j < 2; ++j) { lo_nei_v *q = pi->nei[j]; for (k = 0; k < q->n; ++k) q->a[k].reduced = lo_get_edge(g->e, i, q->a[k].id)->reduced; } } if (lo_verbose == 4) lo_print_edge(g); if (lo_verbose == 5) lo_print_nei(g); } /***************** * Main function * *****************/ int main_layout(int argc, char *argv[]) { gzFile fp; kstream_t *ks; lo_opt_t opt; ograph_t *g; int c; lo_opt_init(&opt); while ((c = getopt(argc, argv, "v:d:o:")) >= 0) { if (c == 'v') lo_verbose = atoi(optarg); else if (c == 'd') opt.fuzzy_dist = atoi(optarg); else if (c == 'o') opt.min_n_ovlp = atoi(optarg); } if (argc == optind && isatty(fileno(stdin))) { fprintf(stderr, "Usage: bwa layout \n"); return 1; } fp = (optind == argc && !isatty(fileno(stdin))) || strcmp(argv[optind], "-") == 0? gzdopen(fileno(stdin), "r") : gzopen(argv[optind], "r"); ks = ks_init(fp); g = lo_graph_parse(&opt, ks); lo_rm_skipped(g); lo_add_missing(g); lo_rm_conflict(g); lo_mark_lack_ovlp(g, opt.min_n_ovlp); lo_rm_skipped(g); lo_populate_nei(g); if (lo_verbose == 6) lo_print_edge(g); lo_trans_reduce(g, opt.fuzzy_dist); lo_graph_destroy(g); ks_destroy(ks); gzclose(fp); return 0; }