/* The MIT License Copyright (c) 2011 by Attractive Chaos 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. */ #include #include #include #include "ksw.h" #ifdef __GNUC__ #define LIKELY(x) __builtin_expect((x),1) #define UNLIKELY(x) __builtin_expect((x),0) #else #define LIKELY(x) (x) #define UNLIKELY(x) (x) #endif const kswr_t g_defr = { 0, -1, -1, -1, -1, -1, -1 }; struct _kswq_t { int qlen, slen; uint8_t shift, mdiff, max, size; __m128i *qp, *H0, *H1, *E, *Hmax; }; /** * Initialize the query data structure * * @param size Number of bytes used to store a score; valid valures are 1 or 2 * @param qlen Length of the query sequence * @param query Query sequence * @param m Size of the alphabet * @param mat Scoring matrix in a one-dimension array * * @return Query data structure */ kswq_t *ksw_qinit(int size, int qlen, const uint8_t *query, int m, const int8_t *mat) { kswq_t *q; int slen, a, tmp, p; size = size > 1? 2 : 1; p = 8 * (3 - size); // # values per __m128i slen = (qlen + p - 1) / p; // segmented length q = (kswq_t*)malloc(sizeof(kswq_t) + 256 + 16 * slen * (m + 4)); // a single block of memory q->qp = (__m128i*)(((size_t)q + sizeof(kswq_t) + 15) >> 4 << 4); // align memory q->H0 = q->qp + slen * m; q->H1 = q->H0 + slen; q->E = q->H1 + slen; q->Hmax = q->E + slen; q->slen = slen; q->qlen = qlen; q->size = size; // compute shift tmp = m * m; for (a = 0, q->shift = 127, q->mdiff = 0; a < tmp; ++a) { // find the minimum and maximum score if (mat[a] < (int8_t)q->shift) q->shift = mat[a]; if (mat[a] > (int8_t)q->mdiff) q->mdiff = mat[a]; } q->max = q->mdiff; q->shift = 256 - q->shift; // NB: q->shift is uint8_t q->mdiff += q->shift; // this is the difference between the min and max scores // An example: p=8, qlen=19, slen=3 and segmentation: // {{0,3,6,9,12,15,18,-1},{1,4,7,10,13,16,-1,-1},{2,5,8,11,14,17,-1,-1}} if (size == 1) { int8_t *t = (int8_t*)q->qp; for (a = 0; a < m; ++a) { int i, k, nlen = slen * p; const int8_t *ma = mat + a * m; for (i = 0; i < slen; ++i) for (k = i; k < nlen; k += slen) // p iterations *t++ = (k >= qlen? 0 : ma[query[k]]) + q->shift; } } else { int16_t *t = (int16_t*)q->qp; for (a = 0; a < m; ++a) { int i, k, nlen = slen * p; const int8_t *ma = mat + a * m; for (i = 0; i < slen; ++i) for (k = i; k < nlen; k += slen) // p iterations *t++ = (k >= qlen? 0 : ma[query[k]]); } } return q; } kswr_t ksw_u8(kswq_t *q, int tlen, const uint8_t *target, int _gapo, int _gape, int xtra) // the first gap costs -(_o+_e) { int slen, i, m_b, n_b, te = -1, gmax = 0, minsc, endsc; uint64_t *b; __m128i zero, gapoe, gape, shift, *H0, *H1, *E, *Hmax; kswr_t r; #define __max_16(ret, xx) do { \ (xx) = _mm_max_epu8((xx), _mm_srli_si128((xx), 8)); \ (xx) = _mm_max_epu8((xx), _mm_srli_si128((xx), 4)); \ (xx) = _mm_max_epu8((xx), _mm_srli_si128((xx), 2)); \ (xx) = _mm_max_epu8((xx), _mm_srli_si128((xx), 1)); \ (ret) = _mm_extract_epi16((xx), 0) & 0x00ff; \ } while (0) // initialization r = g_defr; minsc = (xtra&KSW_XSUBO)? xtra&0xffff : 0x10000; endsc = (xtra&KSW_XSTOP)? xtra&0xffff : 0x10000; m_b = n_b = 0; b = 0; zero = _mm_set1_epi32(0); gapoe = _mm_set1_epi8(_gapo + _gape); gape = _mm_set1_epi8(_gape); shift = _mm_set1_epi8(q->shift); H0 = q->H0; H1 = q->H1; E = q->E; Hmax = q->Hmax; slen = q->slen; for (i = 0; i < slen; ++i) { _mm_store_si128(E + i, zero); _mm_store_si128(H0 + i, zero); _mm_store_si128(Hmax + i, zero); } // the core loop for (i = 0; i < tlen; ++i) { int j, k, cmp, imax; __m128i e, h, f = zero, max = zero, *S = q->qp + target[i] * slen; // s is the 1st score vector h = _mm_load_si128(H0 + slen - 1); // h={2,5,8,11,14,17,-1,-1} in the above example h = _mm_slli_si128(h, 1); // h=H(i-1,-1); << instead of >> because x64 is little-endian for (j = 0; LIKELY(j < slen); ++j) { /* SW cells are computed in the following order: * H(i,j) = max{H(i-1,j-1)+S(i,j), E(i,j), F(i,j)} * E(i+1,j) = max{H(i,j)-q, E(i,j)-r} * F(i,j+1) = max{H(i,j)-q, F(i,j)-r} */ // compute H'(i,j); note that at the beginning, h=H'(i-1,j-1) h = _mm_adds_epu8(h, _mm_load_si128(S + j)); h = _mm_subs_epu8(h, shift); // h=H'(i-1,j-1)+S(i,j) e = _mm_load_si128(E + j); // e=E'(i,j) h = _mm_max_epu8(h, e); h = _mm_max_epu8(h, f); // h=H'(i,j) max = _mm_max_epu8(max, h); // set max _mm_store_si128(H1 + j, h); // save to H'(i,j) // now compute E'(i+1,j) h = _mm_subs_epu8(h, gapoe); // h=H'(i,j)-gapo e = _mm_subs_epu8(e, gape); // e=E'(i,j)-gape e = _mm_max_epu8(e, h); // e=E'(i+1,j) _mm_store_si128(E + j, e); // save to E'(i+1,j) // now compute F'(i,j+1) f = _mm_subs_epu8(f, gape); f = _mm_max_epu8(f, h); // get H'(i-1,j) and prepare for the next j h = _mm_load_si128(H0 + j); // h=H'(i-1,j) } // NB: we do not need to set E(i,j) as we disallow adjecent insertion and then deletion for (k = 0; LIKELY(k < 16); ++k) { // this block mimics SWPS3; NB: H(i,j) updated in the lazy-F loop cannot exceed max f = _mm_slli_si128(f, 1); for (j = 0; LIKELY(j < slen); ++j) { h = _mm_load_si128(H1 + j); h = _mm_max_epu8(h, f); // h=H'(i,j) _mm_store_si128(H1 + j, h); h = _mm_subs_epu8(h, gapoe); f = _mm_subs_epu8(f, gape); cmp = _mm_movemask_epi8(_mm_cmpeq_epi8(_mm_subs_epu8(f, h), zero)); if (UNLIKELY(cmp == 0xffff)) goto end_loop16; } } end_loop16: //int k;for (k=0;k<16;++k)printf("%d ", ((uint8_t*)&max)[k]);printf("\n"); __max_16(imax, max); // imax is the maximum number in max if (imax >= minsc) { // write the b array; this condition adds branching unfornately if (n_b == 0 || (int32_t)b[n_b-1] + 1 != i) { // then append if (n_b == m_b) { m_b = m_b? m_b<<1 : 8; b = (uint64_t*)realloc(b, 8 * m_b); } b[n_b++] = (uint64_t)imax<<32 | i; } else if ((int)(b[n_b-1]>>32) < imax) b[n_b-1] = (uint64_t)imax<<32 | i; // modify the last } if (imax > gmax) { gmax = imax; te = i; // te is the end position on the target for (j = 0; LIKELY(j < slen); ++j) // keep the H1 vector _mm_store_si128(Hmax + j, _mm_load_si128(H1 + j)); if (gmax + q->shift >= 255 || gmax >= endsc) break; } S = H1; H1 = H0; H0 = S; // swap H0 and H1 } r.score = gmax + q->shift < 255? gmax : 255; r.te = te; if (r.score != 255) { // get a->qe, the end of query match; find the 2nd best score int max = -1, low, high, qlen = slen * 16; uint8_t *t = (uint8_t*)Hmax; for (i = 0; i < qlen; ++i, ++t) if ((int)*t > max) max = *t, r.qe = i / 16 + i % 16 * slen; //printf("%d,%d\n", max, gmax); if (b) { i = (r.score + q->max - 1) / q->max; low = te - i; high = te + i; for (i = 0; i < n_b; ++i) { int e = (int32_t)b[i]; if ((e < low || e > high) && (int)(b[i]>>32) > r.score2) r.score2 = b[i]>>32, r.te2 = e; } } } free(b); return r; } kswr_t ksw_i16(kswq_t *q, int tlen, const uint8_t *target, int _gapo, int _gape, int xtra) // the first gap costs -(_o+_e) { int slen, i, m_b, n_b, te = -1, gmax = 0, minsc, endsc; uint64_t *b; __m128i zero, gapoe, gape, *H0, *H1, *E, *Hmax; kswr_t r; #define __max_8(ret, xx) do { \ (xx) = _mm_max_epi16((xx), _mm_srli_si128((xx), 8)); \ (xx) = _mm_max_epi16((xx), _mm_srli_si128((xx), 4)); \ (xx) = _mm_max_epi16((xx), _mm_srli_si128((xx), 2)); \ (ret) = _mm_extract_epi16((xx), 0); \ } while (0) // initialization r = g_defr; minsc = (xtra&KSW_XSUBO)? xtra&0xffff : 0x10000; endsc = (xtra&KSW_XSTOP)? xtra&0xffff : 0x10000; m_b = n_b = 0; b = 0; zero = _mm_set1_epi32(0); gapoe = _mm_set1_epi16(_gapo + _gape); gape = _mm_set1_epi16(_gape); H0 = q->H0; H1 = q->H1; E = q->E; Hmax = q->Hmax; slen = q->slen; for (i = 0; i < slen; ++i) { _mm_store_si128(E + i, zero); _mm_store_si128(H0 + i, zero); _mm_store_si128(Hmax + i, zero); } // the core loop for (i = 0; i < tlen; ++i) { int j, k, imax; __m128i e, h, f = zero, max = zero, *S = q->qp + target[i] * slen; // s is the 1st score vector h = _mm_load_si128(H0 + slen - 1); // h={2,5,8,11,14,17,-1,-1} in the above example h = _mm_slli_si128(h, 2); for (j = 0; LIKELY(j < slen); ++j) { h = _mm_adds_epi16(h, *S++); e = _mm_load_si128(E + j); h = _mm_max_epi16(h, e); h = _mm_max_epi16(h, f); max = _mm_max_epi16(max, h); _mm_store_si128(H1 + j, h); h = _mm_subs_epu16(h, gapoe); e = _mm_subs_epu16(e, gape); e = _mm_max_epi16(e, h); _mm_store_si128(E + j, e); f = _mm_subs_epu16(f, gape); f = _mm_max_epi16(f, h); h = _mm_load_si128(H0 + j); } for (k = 0; LIKELY(k < 16); ++k) { f = _mm_slli_si128(f, 2); for (j = 0; LIKELY(j < slen); ++j) { h = _mm_load_si128(H1 + j); h = _mm_max_epi16(h, f); _mm_store_si128(H1 + j, h); h = _mm_subs_epu16(h, gapoe); f = _mm_subs_epu16(f, gape); if(UNLIKELY(!_mm_movemask_epi8(_mm_cmpgt_epi16(f, h)))) goto end_loop8; } } end_loop8: __max_8(imax, max); if (imax >= minsc) { if (n_b == 0 || (int32_t)b[n_b-1] + 1 != i) { if (n_b == m_b) { m_b = m_b? m_b<<1 : 8; b = (uint64_t*)realloc(b, 8 * m_b); } b[n_b++] = (uint64_t)imax<<32 | i; } else if ((int)(b[n_b-1]>>32) < imax) b[n_b-1] = (uint64_t)imax<<32 | i; // modify the last } if (imax > gmax) { gmax = imax; te = i; for (j = 0; LIKELY(j < slen); ++j) _mm_store_si128(Hmax + j, _mm_load_si128(H1 + j)); if (gmax >= endsc) break; } S = H1; H1 = H0; H0 = S; } r.score = gmax; r.te = te; { int max = -1, low, high, qlen = slen * 8; uint16_t *t = (uint16_t*)Hmax; for (i = 0, r.qe = -1; i < qlen; ++i, ++t) if ((int)*t > max) max = *t, r.qe = i / 8 + i % 8 * slen; if (b) { i = (r.score + q->max - 1) / q->max; low = te - i; high = te + i; for (i = 0; i < n_b; ++i) { int e = (int32_t)b[i]; if ((e < low || e > high) && (int)(b[i]>>32) > r.score2) r.score2 = b[i]>>32, r.te2 = e; } } } free(b); return r; } static void revseq(int l, uint8_t *s) { int i, t; for (i = 0; i < l>>1; ++i) t = s[i], s[i] = s[l - 1 - i], s[l - 1 - i] = t; } kswr_t ksw_align(int qlen, uint8_t *query, int tlen, uint8_t *target, int m, const int8_t *mat, int gapo, int gape, int xtra, kswq_t **qry) { int size; kswq_t *q; kswr_t r, rr; kswr_t (*func)(kswq_t*, int, const uint8_t*, int, int, int); q = (qry && *qry)? *qry : ksw_qinit((xtra&KSW_XBYTE)? 1 : 2, qlen, query, m, mat); if (qry && *qry == 0) *qry = q; func = q->size == 2? ksw_i16 : ksw_u8; size = q->size; r = func(q, tlen, target, gapo, gape, xtra); if (qry == 0) free(q); if ((xtra&KSW_XSTART) == 0 || ((xtra&KSW_XSUBO) && r.score < (xtra&0xffff))) return r; revseq(r.qe + 1, query); revseq(r.te + 1, target); // +1 because qe/te points to the exact end, not the position after the end q = ksw_qinit(size, r.qe + 1, query, m, mat); rr = func(q, tlen, target, gapo, gape, KSW_XSTOP | r.score); revseq(r.qe + 1, query); revseq(r.te + 1, target); free(q); if (r.score == rr.score) r.tb = r.te - rr.te, r.qb = r.qe - rr.qe; return r; } /******************************************* * Main function (not compiled by default) * *******************************************/ #ifdef _KSW_MAIN #include #include #include #include "kseq.h" KSEQ_INIT(gzFile, gzread) unsigned char seq_nt4_table[256] = { 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 4, 1, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 4, 1, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 }; int main(int argc, char *argv[]) { int c, sa = 1, sb = 3, i, j, k, forward_only = 0, max_rseq = 0; int8_t mat[25]; int gapo = 5, gape = 2, minsc = 0, xtra = KSW_XSTART; uint8_t *rseq = 0; gzFile fpt, fpq; kseq_t *kst, *ksq; // parse command line while ((c = getopt(argc, argv, "a:b:q:r:ft:1")) >= 0) { switch (c) { case 'a': sa = atoi(optarg); break; case 'b': sb = atoi(optarg); break; case 'q': gapo = atoi(optarg); break; case 'r': gape = atoi(optarg); break; case 't': minsc = atoi(optarg); break; case 'f': forward_only = 1; break; case '1': xtra |= KSW_XBYTE; break; } } if (optind + 2 > argc) { fprintf(stderr, "Usage: ksw [-1] [-f] [-a%d] [-b%d] [-q%d] [-r%d] [-t%d] \n", sa, sb, gapo, gape, minsc); return 1; } if (minsc > 0xffff) minsc = 0xffff; xtra |= KSW_XSUBO | minsc; // initialize scoring matrix for (i = k = 0; i < 4; ++i) { for (j = 0; j < 4; ++j) mat[k++] = i == j? sa : -sb; mat[k++] = 0; // ambiguous base } for (j = 0; j < 5; ++j) mat[k++] = 0; // open file fpt = gzopen(argv[optind], "r"); kst = kseq_init(fpt); fpq = gzopen(argv[optind+1], "r"); ksq = kseq_init(fpq); // all-pair alignment while (kseq_read(ksq) > 0) { kswq_t *q[2] = {0, 0}; kswr_t r; for (i = 0; i < (int)ksq->seq.l; ++i) ksq->seq.s[i] = seq_nt4_table[(int)ksq->seq.s[i]]; if (!forward_only) { // reverse if ((int)ksq->seq.m > max_rseq) { max_rseq = ksq->seq.m; rseq = (uint8_t*)realloc(rseq, max_rseq); } for (i = 0, j = ksq->seq.l - 1; i < (int)ksq->seq.l; ++i, --j) rseq[j] = ksq->seq.s[i] == 4? 4 : 3 - ksq->seq.s[i]; } gzrewind(fpt); kseq_rewind(kst); while (kseq_read(kst) > 0) { for (i = 0; i < (int)kst->seq.l; ++i) kst->seq.s[i] = seq_nt4_table[(int)kst->seq.s[i]]; r = ksw_align(ksq->seq.l, (uint8_t*)ksq->seq.s, kst->seq.l, (uint8_t*)kst->seq.s, 5, mat, gapo, gape, xtra, &q[0]); if (r.score >= minsc) printf("%s\t%d\t%d\t%s\t%d\t%d\t%d\t%d\t%d\n", kst->name.s, r.tb, r.te+1, ksq->name.s, r.qb, r.qe+1, r.score, r.score2, r.te2); if (rseq) { r = ksw_align(ksq->seq.l, rseq, kst->seq.l, (uint8_t*)kst->seq.s, 5, mat, gapo, gape, xtra, &q[1]); if (r.score >= minsc) printf("%s\t%d\t%d\t%s\t%d\t%d\t%d\t%d\t%d\n", kst->name.s, r.tb, r.te+1, ksq->name.s, (int)ksq->seq.l - r.qb, (int)ksq->seq.l - 1 - r.qe, r.score, r.score2, r.te2); } } free(q[0]); free(q[1]); } free(rseq); kseq_destroy(kst); gzclose(fpt); kseq_destroy(ksq); gzclose(fpq); return 0; } #endif