/* The MIT License Copyright (c) 2008 Genome Research Ltd (GRL). Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the "Software"), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions: The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software. THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE. */ /* Contact: Heng Li */ #include #include #include #include #include #include #include "utils.h" #include "bwt.h" #include "kvec.h" #ifdef USE_MALLOC_WRAPPERS # include "malloc_wrap.h" #endif void bwt_gen_cnt_table(bwt_t *bwt) { int i, j; for (i = 0; i != 256; ++i) { uint32_t x = 0; for (j = 0; j != 4; ++j) x |= (((i&3) == j) + ((i>>2&3) == j) + ((i>>4&3) == j) + (i>>6 == j)) << (j<<3); bwt->cnt_table[i] = x; } } static inline bwtint_t bwt_invPsi(const bwt_t *bwt, bwtint_t k) // compute inverse CSA { bwtint_t x = k - (k > bwt->primary); x = bwt_B0(bwt, x); x = bwt->L2[x] + bwt_occ(bwt, k, x); return k == bwt->primary? 0 : x; } // bwt->bwt and bwt->occ must be precalculated void bwt_cal_sa(bwt_t *bwt, int intv) { bwtint_t isa, sa, i; // S(isa) = sa int intv_round = intv; kv_roundup32(intv_round); xassert(intv_round == intv, "SA sample interval is not a power of 2."); xassert(bwt->bwt, "bwt_t::bwt is not initialized."); if (bwt->sa) free(bwt->sa); bwt->sa_intv = intv; bwt->n_sa = (bwt->seq_len + intv) / intv; bwt->sa = (bwtint_t*)calloc(bwt->n_sa, sizeof(bwtint_t)); // calculate SA value isa = 0; sa = bwt->seq_len; for (i = 0; i < bwt->seq_len; ++i) { if (isa % intv == 0) bwt->sa[isa/intv] = sa; --sa; isa = bwt_invPsi(bwt, isa); } if (isa % intv == 0) bwt->sa[isa/intv] = sa; bwt->sa[0] = (bwtint_t)-1; // before this line, bwt->sa[0] = bwt->seq_len } bwtint_t bwt_sa(const bwt_t *bwt, bwtint_t k) { bwtint_t sa = 0, mask = bwt->sa_intv - 1; while (k & mask) { ++sa; k = bwt_invPsi(bwt, k); } /* without setting bwt->sa[0] = -1, the following line should be changed to (sa + bwt->sa[k/bwt->sa_intv]) % (bwt->seq_len + 1) */ return sa + bwt->sa[k/bwt->sa_intv]; } static inline int __occ_aux(uint64_t y, int c) { // reduce nucleotide counting to bits counting y = ((c&2)? y : ~y) >> 1 & ((c&1)? y : ~y) & 0x5555555555555555ull; // count the number of 1s in y y = (y & 0x3333333333333333ull) + (y >> 2 & 0x3333333333333333ull); return ((y + (y >> 4)) & 0xf0f0f0f0f0f0f0full) * 0x101010101010101ull >> 56; } bwtint_t bwt_occ(const bwt_t *bwt, bwtint_t k, ubyte_t c) { bwtint_t n; uint32_t *p, *end; if (k == bwt->seq_len) return bwt->L2[c+1] - bwt->L2[c]; if (k == (bwtint_t)(-1)) return 0; k -= (k >= bwt->primary); // because $ is not in bwt // retrieve Occ at k/OCC_INTERVAL n = ((bwtint_t*)(p = bwt_occ_intv(bwt, k)))[c]; p += sizeof(bwtint_t); // jump to the start of the first BWT cell // calculate Occ up to the last k/32 end = p + (((k>>5) - ((k&~OCC_INTV_MASK)>>5))<<1); for (; p < end; p += 2) n += __occ_aux((uint64_t)p[0]<<32 | p[1], c); // calculate Occ n += __occ_aux(((uint64_t)p[0]<<32 | p[1]) & ~((1ull<<((~k&31)<<1)) - 1), c); if (c == 0) n -= ~k&31; // corrected for the masked bits return n; } // an analogy to bwt_occ() but more efficient, requiring k <= l void bwt_2occ(const bwt_t *bwt, bwtint_t k, bwtint_t l, ubyte_t c, bwtint_t *ok, bwtint_t *ol) { bwtint_t _k, _l; _k = (k >= bwt->primary)? k-1 : k; _l = (l >= bwt->primary)? l-1 : l; if (_l/OCC_INTERVAL != _k/OCC_INTERVAL || k == (bwtint_t)(-1) || l == (bwtint_t)(-1)) { *ok = bwt_occ(bwt, k, c); *ol = bwt_occ(bwt, l, c); } else { bwtint_t m, n, i, j; uint32_t *p; if (k >= bwt->primary) --k; if (l >= bwt->primary) --l; n = ((bwtint_t*)(p = bwt_occ_intv(bwt, k)))[c]; p += sizeof(bwtint_t); // calculate *ok j = k >> 5 << 5; for (i = k/OCC_INTERVAL*OCC_INTERVAL; i < j; i += 32, p += 2) n += __occ_aux((uint64_t)p[0]<<32 | p[1], c); m = n; n += __occ_aux(((uint64_t)p[0]<<32 | p[1]) & ~((1ull<<((~k&31)<<1)) - 1), c); if (c == 0) n -= ~k&31; // corrected for the masked bits *ok = n; // calculate *ol j = l >> 5 << 5; for (; i < j; i += 32, p += 2) m += __occ_aux((uint64_t)p[0]<<32 | p[1], c); m += __occ_aux(((uint64_t)p[0]<<32 | p[1]) & ~((1ull<<((~l&31)<<1)) - 1), c); if (c == 0) m -= ~l&31; // corrected for the masked bits *ol = m; } } #define __occ_aux4(bwt, b) \ ((bwt)->cnt_table[(b)&0xff] + (bwt)->cnt_table[(b)>>8&0xff] \ + (bwt)->cnt_table[(b)>>16&0xff] + (bwt)->cnt_table[(b)>>24]) void bwt_occ4(const bwt_t *bwt, bwtint_t k, bwtint_t cnt[4]) { bwtint_t x; uint32_t *p, tmp, *end; if (k == (bwtint_t)(-1)) { memset(cnt, 0, 4 * sizeof(bwtint_t)); return; } k -= (k >= bwt->primary); // because $ is not in bwt p = bwt_occ_intv(bwt, k); memcpy(cnt, p, 4 * sizeof(bwtint_t)); p += sizeof(bwtint_t); // sizeof(bwtint_t) = 4*(sizeof(bwtint_t)/sizeof(uint32_t)) end = p + ((k>>4) - ((k&~OCC_INTV_MASK)>>4)); // this is the end point of the following loop for (x = 0; p < end; ++p) x += __occ_aux4(bwt, *p); tmp = *p & ~((1U<<((~k&15)<<1)) - 1); x += __occ_aux4(bwt, tmp) - (~k&15); cnt[0] += x&0xff; cnt[1] += x>>8&0xff; cnt[2] += x>>16&0xff; cnt[3] += x>>24; } // an analogy to bwt_occ4() but more efficient, requiring k <= l void bwt_2occ4(const bwt_t *bwt, bwtint_t k, bwtint_t l, bwtint_t cntk[4], bwtint_t cntl[4]) { bwtint_t _k, _l; _k = k - (k >= bwt->primary); _l = l - (l >= bwt->primary); if (_l>>OCC_INTV_SHIFT != _k>>OCC_INTV_SHIFT || k == (bwtint_t)(-1) || l == (bwtint_t)(-1)) { bwt_occ4(bwt, k, cntk); bwt_occ4(bwt, l, cntl); } else { bwtint_t x, y; uint32_t *p, tmp, *endk, *endl; k -= (k >= bwt->primary); // because $ is not in bwt l -= (l >= bwt->primary); p = bwt_occ_intv(bwt, k); memcpy(cntk, p, 4 * sizeof(bwtint_t)); p += sizeof(bwtint_t); // sizeof(bwtint_t) = 4*(sizeof(bwtint_t)/sizeof(uint32_t)) // prepare cntk[] endk = p + ((k>>4) - ((k&~OCC_INTV_MASK)>>4)); endl = p + ((l>>4) - ((l&~OCC_INTV_MASK)>>4)); for (x = 0; p < endk; ++p) x += __occ_aux4(bwt, *p); y = x; tmp = *p & ~((1U<<((~k&15)<<1)) - 1); x += __occ_aux4(bwt, tmp) - (~k&15); // calculate cntl[] and finalize cntk[] for (; p < endl; ++p) y += __occ_aux4(bwt, *p); tmp = *p & ~((1U<<((~l&15)<<1)) - 1); y += __occ_aux4(bwt, tmp) - (~l&15); memcpy(cntl, cntk, 4 * sizeof(bwtint_t)); cntk[0] += x&0xff; cntk[1] += x>>8&0xff; cntk[2] += x>>16&0xff; cntk[3] += x>>24; cntl[0] += y&0xff; cntl[1] += y>>8&0xff; cntl[2] += y>>16&0xff; cntl[3] += y>>24; } } int bwt_match_exact(const bwt_t *bwt, int len, const ubyte_t *str, bwtint_t *sa_begin, bwtint_t *sa_end) { bwtint_t k, l, ok, ol; int i; k = 0; l = bwt->seq_len; for (i = len - 1; i >= 0; --i) { ubyte_t c = str[i]; if (c > 3) return 0; // no match bwt_2occ(bwt, k - 1, l, c, &ok, &ol); k = bwt->L2[c] + ok + 1; l = bwt->L2[c] + ol; if (k > l) break; // no match } if (k > l) return 0; // no match if (sa_begin) *sa_begin = k; if (sa_end) *sa_end = l; return l - k + 1; } int bwt_match_exact_alt(const bwt_t *bwt, int len, const ubyte_t *str, bwtint_t *k0, bwtint_t *l0) { int i; bwtint_t k, l, ok, ol; k = *k0; l = *l0; for (i = len - 1; i >= 0; --i) { ubyte_t c = str[i]; if (c > 3) return 0; // there is an N here. no match bwt_2occ(bwt, k - 1, l, c, &ok, &ol); k = bwt->L2[c] + ok + 1; l = bwt->L2[c] + ol; if (k > l) return 0; // no match } *k0 = k; *l0 = l; return l - k + 1; } /********************* * Bidirectional BWT * *********************/ void bwt_extend(const bwt_t *bwt, const bwtintv_t *ik, bwtintv_t ok[4], int is_back) { bwtint_t tk[4], tl[4]; int i; bwt_2occ4(bwt, ik->x[!is_back] - 1, ik->x[!is_back] - 1 + ik->x[2], tk, tl); for (i = 0; i != 4; ++i) { ok[i].x[!is_back] = bwt->L2[i] + 1 + tk[i]; ok[i].x[2] = tl[i] - tk[i]; } ok[3].x[is_back] = ik->x[is_back] + (ik->x[!is_back] <= bwt->primary && ik->x[!is_back] + ik->x[2] - 1 >= bwt->primary); ok[2].x[is_back] = ok[3].x[is_back] + ok[3].x[2]; ok[1].x[is_back] = ok[2].x[is_back] + ok[2].x[2]; ok[0].x[is_back] = ok[1].x[is_back] + ok[1].x[2]; } static void bwt_reverse_intvs(bwtintv_v *p) { if (p->n > 1) { int j; for (j = 0; j < p->n>>1; ++j) { bwtintv_t tmp = p->a[p->n - 1 - j]; p->a[p->n - 1 - j] = p->a[j]; p->a[j] = tmp; } } } // NOTE: $max_intv is not currently used in BWA-MEM int bwt_smem1a(const bwt_t *bwt, int len, const uint8_t *q, int x, int min_intv, uint64_t max_intv, bwtintv_v *mem, bwtintv_v *tmpvec[2]) { int i, j, c, ret; bwtintv_t ik, ok[4]; bwtintv_v a[2], *prev, *curr, *swap; mem->n = 0; if (q[x] > 3) return x + 1; if (min_intv < 1) min_intv = 1; // the interval size should be at least 1 kv_init(a[0]); kv_init(a[1]); prev = tmpvec && tmpvec[0]? tmpvec[0] : &a[0]; // use the temporary vector if provided curr = tmpvec && tmpvec[1]? tmpvec[1] : &a[1]; bwt_set_intv(bwt, q[x], ik); // the initial interval of a single base ik.info = x + 1; for (i = x + 1, curr->n = 0; i < len; ++i) { // forward search if (ik.x[2] < max_intv) { // an interval small enough kv_push(bwtintv_t, *curr, ik); break; } else if (q[i] < 4) { // an A/C/G/T base c = 3 - q[i]; // complement of q[i] bwt_extend(bwt, &ik, ok, 0); if (ok[c].x[2] != ik.x[2]) { // change of the interval size kv_push(bwtintv_t, *curr, ik); if (ok[c].x[2] < min_intv) break; // the interval size is too small to be extended further } ik = ok[c]; ik.info = i + 1; } else { // an ambiguous base kv_push(bwtintv_t, *curr, ik); break; // always terminate extension at an ambiguous base; in this case, ia[0].info; // this will be the returned value swap = curr; curr = prev; prev = swap; for (i = x - 1; i >= -1; --i) { // backward search for MEMs c = i < 0? -1 : q[i] < 4? q[i] : -1; // c==-1 if i<0 or q[i] is an ambiguous base for (j = 0, curr->n = 0; j < prev->n; ++j) { bwtintv_t *p = &prev->a[j]; if (c >= 0 && ik.x[2] >= max_intv) bwt_extend(bwt, p, ok, 1); if (c < 0 || ik.x[2] < max_intv || ok[c].x[2] < min_intv) { // keep the hit if reaching the beginning or an ambiguous base or the intv is small enough if (curr->n == 0) { // test curr->n>0 to make sure there are no longer matches if (mem->n == 0 || i + 1 < mem->a[mem->n-1].info>>32) { // skip contained matches ik = *p; ik.info |= (uint64_t)(i + 1)<<32; kv_push(bwtintv_t, *mem, ik); } } // otherwise the match is contained in another longer match } else if (curr->n == 0 || ok[c].x[2] != curr->a[curr->n-1].x[2]) { ok[c].info = p->info; kv_push(bwtintv_t, *curr, ok[c]); } } if (curr->n == 0) break; swap = curr; curr = prev; prev = swap; } bwt_reverse_intvs(mem); // s.t. sorted by the start coordinate if (tmpvec == 0 || tmpvec[0] == 0) free(a[0].a); if (tmpvec == 0 || tmpvec[1] == 0) free(a[1].a); return ret; } int bwt_smem1(const bwt_t *bwt, int len, const uint8_t *q, int x, int min_intv, bwtintv_v *mem, bwtintv_v *tmpvec[2]) { return bwt_smem1a(bwt, len, q, x, min_intv, 0, mem, tmpvec); } int bwt_seed_strategy1(const bwt_t *bwt, int len, const uint8_t *q, int x, int min_len, int max_intv, bwtintv_t *mem) { int i, c; bwtintv_t ik, ok[4]; memset(mem, 0, sizeof(bwtintv_t)); if (q[x] > 3) return x + 1; bwt_set_intv(bwt, q[x], ik); // the initial interval of a single base for (i = x + 1; i < len; ++i) { // forward search if (q[i] < 4) { // an A/C/G/T base c = 3 - q[i]; // complement of q[i] bwt_extend(bwt, &ik, ok, 0); if (ok[c].x[2] < max_intv && i - x >= min_len) { *mem = ok[c]; mem->info = (uint64_t)x<<32 | (i + 1); return i + 1; } ik = ok[c]; } else return i + 1; } return len; } /************************* * Read/write BWT and SA * *************************/ void bwt_dump_bwt(const char *fn, const bwt_t *bwt) { FILE *fp; fp = xopen(fn, "wb"); err_fwrite(&bwt->primary, sizeof(bwtint_t), 1, fp); err_fwrite(bwt->L2+1, sizeof(bwtint_t), 4, fp); err_fwrite(bwt->bwt, 4, bwt->bwt_size, fp); err_fflush(fp); err_fclose(fp); } void bwt_dump_sa(const char *fn, const bwt_t *bwt) { FILE *fp; fp = xopen(fn, "wb"); err_fwrite(&bwt->primary, sizeof(bwtint_t), 1, fp); err_fwrite(bwt->L2+1, sizeof(bwtint_t), 4, fp); err_fwrite(&bwt->sa_intv, sizeof(bwtint_t), 1, fp); err_fwrite(&bwt->seq_len, sizeof(bwtint_t), 1, fp); err_fwrite(bwt->sa + 1, sizeof(bwtint_t), bwt->n_sa - 1, fp); err_fflush(fp); err_fclose(fp); } static bwtint_t fread_fix(FILE *fp, bwtint_t size, void *a) { // Mac/Darwin has a bug when reading data longer than 2GB. This function fixes this issue by reading data in small chunks const int bufsize = 0x1000000; // 16M block bwtint_t offset = 0; while (size) { int x = bufsize < size? bufsize : size; if ((x = err_fread_noeof(a + offset, 1, x, fp)) == 0) break; size -= x; offset += x; } return offset; } void bwt_restore_sa(const char *fn, bwt_t *bwt) { char skipped[256]; FILE *fp; bwtint_t primary; fp = xopen(fn, "rb"); err_fread_noeof(&primary, sizeof(bwtint_t), 1, fp); xassert(primary == bwt->primary, "SA-BWT inconsistency: primary is not the same."); err_fread_noeof(skipped, sizeof(bwtint_t), 4, fp); // skip err_fread_noeof(&bwt->sa_intv, sizeof(bwtint_t), 1, fp); err_fread_noeof(&primary, sizeof(bwtint_t), 1, fp); xassert(primary == bwt->seq_len, "SA-BWT inconsistency: seq_len is not the same."); bwt->n_sa = (bwt->seq_len + bwt->sa_intv) / bwt->sa_intv; bwt->sa = (bwtint_t*)calloc(bwt->n_sa, sizeof(bwtint_t)); bwt->sa[0] = -1; fread_fix(fp, sizeof(bwtint_t) * (bwt->n_sa - 1), bwt->sa + 1); err_fclose(fp); } bwt_t *bwt_restore_bwt(const char *fn) { bwt_t *bwt; FILE *fp; bwt = (bwt_t*)calloc(1, sizeof(bwt_t)); fp = xopen(fn, "rb"); err_fseek(fp, 0, SEEK_END); bwt->bwt_size = (err_ftell(fp) - sizeof(bwtint_t) * 5) >> 2; bwt->bwt = (uint32_t*)calloc(bwt->bwt_size, 4); err_fseek(fp, 0, SEEK_SET); err_fread_noeof(&bwt->primary, sizeof(bwtint_t), 1, fp); err_fread_noeof(bwt->L2+1, sizeof(bwtint_t), 4, fp); fread_fix(fp, bwt->bwt_size<<2, bwt->bwt); bwt->seq_len = bwt->L2[4]; err_fclose(fp); bwt_gen_cnt_table(bwt); return bwt; } void bwt_destroy(bwt_t *bwt) { if (bwt == 0) return; free(bwt->sa); free(bwt->bwt); free(bwt); }