#include #include #include #include #include "mmpriv.h" #include "kalloc.h" #include "krmq.h" static int64_t mg_chain_bk_end(int32_t max_drop, const mm128_t *z, const int32_t *f, const int64_t *p, int32_t *t, int64_t k) { int64_t i = z[k].y, end_i = -1, max_i = i; int32_t max_s = 0; if (i < 0 || t[i] != 0) return i; do { int32_t s; t[i] = 2; end_i = i = p[i]; s = i < 0? z[k].x : (int32_t)z[k].x - f[i]; if (s > max_s) max_s = s, max_i = i; else if (max_s - s > max_drop) break; } while (i >= 0 && t[i] == 0); for (i = z[k].y; i >= 0 && i != end_i; i = p[i]) // reset modified t[] t[i] = 0; return max_i; } uint64_t *mg_chain_backtrack(void *km, int64_t n, const int32_t *f, const int64_t *p, int32_t *v, int32_t *t, int32_t min_cnt, int32_t min_sc, int32_t max_drop, int32_t *n_u_, int32_t *n_v_) { mm128_t *z; uint64_t *u; int64_t i, k, n_z, n_v; int32_t n_u; *n_u_ = *n_v_ = 0; for (i = 0, n_z = 0; i < n; ++i) // precompute n_z if (f[i] >= min_sc) ++n_z; if (n_z == 0) return 0; KMALLOC(km, z, n_z); for (i = 0, k = 0; i < n; ++i) // populate z[] if (f[i] >= min_sc) z[k].x = f[i], z[k++].y = i; radix_sort_128x(z, z + n_z); memset(t, 0, n * 4); for (k = n_z - 1, n_v = n_u = 0; k >= 0; --k) { // precompute n_u if (t[z[k].y] == 0) { int64_t n_v0 = n_v, end_i; int32_t sc; end_i = mg_chain_bk_end(max_drop, z, f, p, t, k); for (i = z[k].y; i != end_i; i = p[i]) ++n_v, t[i] = 1; sc = i < 0? z[k].x : (int32_t)z[k].x - f[i]; if (sc >= min_sc && n_v > n_v0 && n_v - n_v0 >= min_cnt) ++n_u; else n_v = n_v0; } } KMALLOC(km, u, n_u); memset(t, 0, n * 4); for (k = n_z - 1, n_v = n_u = 0; k >= 0; --k) { // populate u[] if (t[z[k].y] == 0) { int64_t n_v0 = n_v, end_i; int32_t sc; end_i = mg_chain_bk_end(max_drop, z, f, p, t, k); for (i = z[k].y; i != end_i; i = p[i]) v[n_v++] = i, t[i] = 1; sc = i < 0? z[k].x : (int32_t)z[k].x - f[i]; if (sc >= min_sc && n_v > n_v0 && n_v - n_v0 >= min_cnt) u[n_u++] = (uint64_t)sc << 32 | (n_v - n_v0); else n_v = n_v0; } } kfree(km, z); assert(n_v < INT32_MAX); *n_u_ = n_u, *n_v_ = n_v; return u; } static mm128_t *compact_a(void *km, int32_t n_u, uint64_t *u, int32_t n_v, int32_t *v, mm128_t *a) { mm128_t *b, *w; uint64_t *u2; int64_t i, j, k; // write the result to b[] KMALLOC(km, b, n_v); for (i = 0, k = 0; i < n_u; ++i) { int32_t k0 = k, ni = (int32_t)u[i]; for (j = 0; j < ni; ++j) b[k++] = a[v[k0 + (ni - j - 1)]]; } kfree(km, v); // sort u[] and a[] by the target position, such that adjacent chains may be joined KMALLOC(km, w, n_u); for (i = k = 0; i < n_u; ++i) { w[i].x = b[k].x, w[i].y = (uint64_t)k<<32|i; k += (int32_t)u[i]; } radix_sort_128x(w, w + n_u); KMALLOC(km, u2, n_u); for (i = k = 0; i < n_u; ++i) { int32_t j = (int32_t)w[i].y, n = (int32_t)u[j]; u2[i] = u[j]; memcpy(&a[k], &b[w[i].y>>32], n * sizeof(mm128_t)); k += n; } memcpy(u, u2, n_u * 8); memcpy(b, a, k * sizeof(mm128_t)); // write _a_ to _b_ and deallocate _a_ because _a_ is oversized, sometimes a lot kfree(km, a); kfree(km, w); kfree(km, u2); return b; } static inline int32_t comput_sc(const mm128_t *ai, const mm128_t *aj, int32_t max_dist_x, int32_t max_dist_y, int32_t bw, float chn_pen_gap, float chn_pen_skip, int is_cdna, int n_seg) { int32_t dq = (int32_t)ai->y - (int32_t)aj->y, dr, dd, dg, q_span, sc; int32_t sidi = (ai->y & MM_SEED_SEG_MASK) >> MM_SEED_SEG_SHIFT; int32_t sidj = (aj->y & MM_SEED_SEG_MASK) >> MM_SEED_SEG_SHIFT; if (dq <= 0 || dq > max_dist_x) return INT32_MIN; dr = (int32_t)(ai->x - aj->x); if (sidi == sidj && (dr == 0 || dq > max_dist_y)) return INT32_MIN; dd = dr > dq? dr - dq : dq - dr; if (sidi == sidj && dd > bw) return INT32_MIN; if (n_seg > 1 && !is_cdna && sidi == sidj && dr > max_dist_y) return INT32_MIN; dg = dr < dq? dr : dq; q_span = aj->y>>32&0xff; sc = q_span < dg? q_span : dg; if (dd || dg > q_span) { float lin_pen, log_pen; lin_pen = chn_pen_gap * (float)dd + chn_pen_skip * (float)dg; log_pen = dd >= 1? mg_log2(dd + 1) : 0.0f; // mg_log2() only works for dd>=2 if (is_cdna || sidi != sidj) { if (sidi != sidj && dr == 0) ++sc; // possibly due to overlapping paired ends; give a minor bonus else if (dr > dq || sidi != sidj) sc -= (int)(lin_pen < log_pen? lin_pen : log_pen); // deletion or jump between paired ends else sc -= (int)(lin_pen + .5f * log_pen); } else sc -= (int)(lin_pen + .5f * log_pen); } return sc; } /* Input: * a[].x: tid<<33 | rev<<32 | tpos * a[].y: flags<<40 | q_span<<32 | q_pos * Output: * n_u: #chains * u[]: score<<32 | #anchors (sum of lower 32 bits of u[] is the returned length of a[]) * input a[] is deallocated on return */ mm128_t *mg_lchain_dp(int max_dist_x, int max_dist_y, int bw, int max_skip, int max_iter, int min_cnt, int min_sc, float chn_pen_gap, float chn_pen_skip, int is_cdna, int n_seg, int64_t n, mm128_t *a, int *n_u_, uint64_t **_u, void *km) { // TODO: make sure this works when n has more than 32 bits int32_t *f, *t, *v, n_u, n_v, mmax_f = 0, max_drop = bw; int64_t *p, i, j, max_ii, st = 0, n_iter = 0; uint64_t *u; if (_u) *_u = 0, *n_u_ = 0; if (n == 0 || a == 0) { kfree(km, a); return 0; } if (max_dist_x < bw) max_dist_x = bw; if (max_dist_y < bw && !is_cdna) max_dist_y = bw; if (is_cdna) max_drop = INT32_MAX; KMALLOC(km, p, n); KMALLOC(km, f, n); KMALLOC(km, v, n); KCALLOC(km, t, n); // fill the score and backtrack arrays for (i = 0, max_ii = -1; i < n; ++i) { int64_t max_j = -1, end_j; int32_t max_f = a[i].y>>32&0xff, n_skip = 0; while (st < i && (a[i].x>>32 != a[st].x>>32 || a[i].x > a[st].x + max_dist_x)) ++st; if (i - st > max_iter) st = i - max_iter; for (j = i - 1; j >= st; --j) { int32_t sc; sc = comput_sc(&a[i], &a[j], max_dist_x, max_dist_y, bw, chn_pen_gap, chn_pen_skip, is_cdna, n_seg); ++n_iter; if (sc == INT32_MIN) continue; sc += f[j]; if (sc > max_f) { max_f = sc, max_j = j; if (n_skip > 0) --n_skip; } else if (t[j] == (int32_t)i) { if (++n_skip > max_skip) break; } if (p[j] >= 0) t[p[j]] = i; } end_j = j; if (max_ii < 0 || a[i].x - a[max_ii].x > (int64_t)max_dist_x) { int32_t max = INT32_MIN; max_ii = -1; for (j = i - 1; j >= st; --j) if (max < f[j]) max = f[j], max_ii = j; } if (max_ii >= 0 && max_ii < end_j) { int32_t tmp; tmp = comput_sc(&a[i], &a[max_ii], max_dist_x, max_dist_y, bw, chn_pen_gap, chn_pen_skip, is_cdna, n_seg); if (tmp != INT32_MIN && max_f < tmp + f[max_ii]) max_f = tmp + f[max_ii], max_j = max_ii; } f[i] = max_f, p[i] = max_j; v[i] = max_j >= 0 && v[max_j] > max_f? v[max_j] : max_f; // v[] keeps the peak score up to i; f[] is the score ending at i, not always the peak if (max_ii < 0 || (a[i].x - a[max_ii].x <= (int64_t)max_dist_x && f[max_ii] < f[i])) max_ii = i; if (mmax_f < max_f) mmax_f = max_f; } u = mg_chain_backtrack(km, n, f, p, v, t, min_cnt, min_sc, max_drop, &n_u, &n_v); *n_u_ = n_u, *_u = u; // NB: note that u[] may not be sorted by score here kfree(km, p); kfree(km, f); kfree(km, t); if (n_u == 0) { kfree(km, a); kfree(km, v); return 0; } return compact_a(km, n_u, u, n_v, v, a); } typedef struct lc_elem_s { int32_t y; int64_t i; double pri; KRMQ_HEAD(struct lc_elem_s) head; } lc_elem_t; #define lc_elem_cmp(a, b) ((a)->y < (b)->y? -1 : (a)->y > (b)->y? 1 : ((a)->i > (b)->i) - ((a)->i < (b)->i)) #define lc_elem_lt2(a, b) ((a)->pri < (b)->pri) KRMQ_INIT(lc_elem, lc_elem_t, head, lc_elem_cmp, lc_elem_lt2) KALLOC_POOL_INIT(rmq, lc_elem_t) static inline int32_t comput_sc_simple(const mm128_t *ai, const mm128_t *aj, float chn_pen_gap, float chn_pen_skip, int32_t *exact, int32_t *width) { int32_t dq = (int32_t)ai->y - (int32_t)aj->y, dr, dd, dg, q_span, sc; dr = (int32_t)(ai->x - aj->x); *width = dd = dr > dq? dr - dq : dq - dr; dg = dr < dq? dr : dq; q_span = aj->y>>32&0xff; sc = q_span < dg? q_span : dg; if (exact) *exact = (dd == 0 && dg <= q_span); if (dd || dq > q_span) { float lin_pen, log_pen; lin_pen = chn_pen_gap * (float)dd + chn_pen_skip * (float)dg; log_pen = dd >= 1? mg_log2(dd + 1) : 0.0f; // mg_log2() only works for dd>=2 sc -= (int)(lin_pen + .5f * log_pen); } return sc; } mm128_t *mg_lchain_rmq(int max_dist, int max_dist_inner, int bw, int max_chn_skip, int cap_rmq_size, int min_cnt, int min_sc, float chn_pen_gap, float chn_pen_skip, int64_t n, mm128_t *a, int *n_u_, uint64_t **_u, void *km) { int32_t *f,*t, *v, n_u, n_v, mmax_f = 0, max_rmq_size = 0, max_drop = bw; int64_t *p, i, i0, st = 0, st_inner = 0, n_iter = 0; uint64_t *u; lc_elem_t *root = 0, *root_inner = 0; void *mem_mp = 0; kmp_rmq_t *mp; if (_u) *_u = 0, *n_u_ = 0; if (n == 0 || a == 0) { kfree(km, a); return 0; } if (max_dist < bw) max_dist = bw; if (max_dist_inner <= 0 || max_dist_inner >= max_dist) max_dist_inner = 0; KMALLOC(km, p, n); KMALLOC(km, f, n); KCALLOC(km, t, n); KMALLOC(km, v, n); mem_mp = km_init2(km, 0x10000); mp = kmp_init_rmq(mem_mp); // fill the score and backtrack arrays for (i = i0 = 0; i < n; ++i) { int64_t max_j = -1; int32_t q_span = a[i].y>>32&0xff, max_f = q_span; lc_elem_t s, *q, *r, lo, hi; // add in-range anchors if (i0 < i && a[i0].x != a[i].x) { int64_t j; for (j = i0; j < i; ++j) { q = kmp_alloc_rmq(mp); q->y = (int32_t)a[j].y, q->i = j, q->pri = -(f[j] + 0.5 * chn_pen_gap * ((int32_t)a[j].x + (int32_t)a[j].y)); krmq_insert(lc_elem, &root, q, 0); if (max_dist_inner > 0) { r = kmp_alloc_rmq(mp); *r = *q; krmq_insert(lc_elem, &root_inner, r, 0); } } i0 = i; } // get rid of active chains out of range while (st < i && (a[i].x>>32 != a[st].x>>32 || a[i].x > a[st].x + max_dist || krmq_size(head, root) > cap_rmq_size)) { s.y = (int32_t)a[st].y, s.i = st; if ((q = krmq_find(lc_elem, root, &s, 0)) != 0) { q = krmq_erase(lc_elem, &root, q, 0); kmp_free_rmq(mp, q); } ++st; } if (max_dist_inner > 0) { // similar to the block above, but applied to the inner tree while (st_inner < i && (a[i].x>>32 != a[st_inner].x>>32 || a[i].x > a[st_inner].x + max_dist_inner || krmq_size(head, root_inner) > cap_rmq_size)) { s.y = (int32_t)a[st_inner].y, s.i = st_inner; if ((q = krmq_find(lc_elem, root_inner, &s, 0)) != 0) { q = krmq_erase(lc_elem, &root_inner, q, 0); kmp_free_rmq(mp, q); } ++st_inner; } } // RMQ lo.i = INT32_MAX, lo.y = (int32_t)a[i].y - max_dist; hi.i = 0, hi.y = (int32_t)a[i].y; if ((q = krmq_rmq(lc_elem, root, &lo, &hi)) != 0) { int32_t sc, exact, width, n_skip = 0; int64_t j = q->i; assert(q->y >= lo.y && q->y <= hi.y); sc = f[j] + comput_sc_simple(&a[i], &a[j], chn_pen_gap, chn_pen_skip, &exact, &width); if (width <= bw && sc > max_f) max_f = sc, max_j = j; if (!exact && root_inner && (int32_t)a[i].y > 0) { lc_elem_t *lo, *hi; s.y = (int32_t)a[i].y - 1, s.i = n; krmq_interval(lc_elem, root_inner, &s, &lo, &hi); if (lo) { const lc_elem_t *q; int32_t width, n_rmq_iter = 0; krmq_itr_t(lc_elem) itr; krmq_itr_find(lc_elem, root_inner, lo, &itr); while ((q = krmq_at(&itr)) != 0) { if (q->y < (int32_t)a[i].y - max_dist_inner) break; ++n_rmq_iter; j = q->i; sc = f[j] + comput_sc_simple(&a[i], &a[j], chn_pen_gap, chn_pen_skip, 0, &width); if (width <= bw) { if (sc > max_f) { max_f = sc, max_j = j; if (n_skip > 0) --n_skip; } else if (t[j] == (int32_t)i) { if (++n_skip > max_chn_skip) break; } if (p[j] >= 0) t[p[j]] = i; } if (!krmq_itr_prev(lc_elem, &itr)) break; } n_iter += n_rmq_iter; } } } // set max assert(max_j < 0 || (a[max_j].x < a[i].x && (int32_t)a[max_j].y < (int32_t)a[i].y)); f[i] = max_f, p[i] = max_j; v[i] = max_j >= 0 && v[max_j] > max_f? v[max_j] : max_f; // v[] keeps the peak score up to i; f[] is the score ending at i, not always the peak if (mmax_f < max_f) mmax_f = max_f; if (max_rmq_size < krmq_size(head, root)) max_rmq_size = krmq_size(head, root); } km_destroy(mem_mp); u = mg_chain_backtrack(km, n, f, p, v, t, min_cnt, min_sc, max_drop, &n_u, &n_v); *n_u_ = n_u, *_u = u; // NB: note that u[] may not be sorted by score here kfree(km, p); kfree(km, f); kfree(km, t); if (n_u == 0) { kfree(km, a); kfree(km, v); return 0; } return compact_a(km, n_u, u, n_v, v, a); }