X-Git-Url: http://woldlab.caltech.edu/gitweb/?p=samtools.git;a=blobdiff_plain;f=kaln.c;h=9c0bbaa437ff5654d7a181b496bb9d58c9c30558;hp=680779113ce7c2220434727cf578845d1e840d40;hb=aa08abe5f0b84ee0dd3491f00fe357d661c08e0c;hpb=62781a2daa24d74a3c590e2669fad1fa7cabf933 diff --git a/kaln.c b/kaln.c index 6807791..9c0bbaa 100644 --- a/kaln.c +++ b/kaln.c @@ -73,9 +73,19 @@ int aln_sm_blast[] = { -2, -2, -2, -2, -2 }; +int aln_sm_qual[] = { + 0, -23, -23, -23, 0, + -23, 0, -23, -23, 0, + -23, -23, 0, -23, 0, + -23, -23, -23, 0, 0, + 0, 0, 0, 0, 0 +}; + ka_param_t ka_param_blast = { 5, 2, 5, 2, aln_sm_blast, 5, 50 }; ka_param_t ka_param_aa2aa = { 10, 2, 10, 2, aln_sm_blosum62, 22, 50 }; +ka_param2_t ka_param2_qual = { 37, 11, 37, 11, 37, 11, 0, 0, aln_sm_qual, 5, 50 }; + static uint32_t *ka_path2cigar32(const path_t *path, int path_len, int *n_cigar) { int i, n; @@ -176,7 +186,7 @@ static uint32_t *ka_path2cigar32(const path_t *path, int path_len, int *n_cigar) } typedef struct { - uint8_t Mt:3, It:2, Dt:2; + uint8_t Mt:3, It:2, Dt:3; } dpcell_t; typedef struct { @@ -208,7 +218,7 @@ uint32_t *ka_global_core(uint8_t *seq1, int len1, uint8_t *seq2, int len2, const score_matrix = ap->matrix; N_MATRIX_ROW = ap->row; - *n_cigar = 0; + if (n_cigar) *n_cigar = 0; if (len1 == 0 || len2 == 0) return 0; /* calculate b1 and b2 */ @@ -371,211 +381,106 @@ uint32_t *ka_global_core(uint8_t *seq1, int len1, uint8_t *seq2, int len2, const return cigar; } -/***************************************** - * Probabilistic banded glocal alignment * - *****************************************/ - -static float g_qual2prob[256]; - -#define EI .25 -#define EM .3333333333333 -#define set_u(u, b, i, k) { int x=(i)-(b); x=x>0?x:0; (u)=((k)-x+1)*3; } - -ka_probpar_t ka_probpar_def = { 0.001, 0.1, 10 }; - -/* - The topology of the profile HMM: - - /\ /\ /\ /\ - I[1] I[k-1] I[k] I[L] - ^ \ \ ^ \ ^ \ \ ^ - | \ \ | \ | \ \ | - M[0] M[1] -> ... -> M[k-1] -> M[k] -> ... -> M[L] M[L+1] - \ \/ \/ \/ / - \ /\ /\ /\ / - -> D[k-1] -> D[k] -> - - M[0] points to every {M,I}[k] and every {M,I}[k] points M[L+1]. - - On input, _ref is the reference sequence and _query is the query - sequence. Both are sequences of 0/1/2/3/4 where 4 stands for an - ambiguous residue. iqual is the base quality. c sets the gap open - probability, gap extension probability and band width. - - On output, state and q are arrays of length l_query. The higher 30 - bits give the reference position the query base is matched to and the - lower two bits can be 0 (an alignment match) or 1 (an - insertion). q[i] gives the phred scaled posterior probability of - state[i] being wrong. - */ -int ka_prob_glocal(const uint8_t *_ref, int l_ref, const uint8_t *_query, int l_query, const uint8_t *iqual, - const ka_probpar_t *c, int *state, uint8_t *q) +typedef struct { + int M, I, D; +} score_aux_t; + +#define MINUS_INF -0x40000000 + +// matrix: len2 rows and len1 columns +int ka_global_score(const uint8_t *_seq1, int len1, const uint8_t *_seq2, int len2, const ka_param2_t *ap) { - double **f, **b, *s, m[9], sI, sM, bI, bM, pb; - float *qual, *_qual; - const uint8_t *ref, *query; - int bw, bw2, i, k, is_diff = 0; - - /*** initialization ***/ - ref = _ref - 1; query = _query - 1; // change to 1-based coordinate - bw = l_ref > l_query? l_ref : l_query; - if (bw > c->bw) bw = c->bw; - if (bw < abs(l_ref - l_query)) bw = abs(l_ref - l_query); - bw2 = bw * 2 + 1; - // allocate the forward and backward matrices f[][] and b[][] and the scaling array s[] - f = calloc(l_query+1, sizeof(void*)); - b = calloc(l_query+1, sizeof(void*)); - for (i = 0; i <= l_query; ++i) { - f[i] = calloc(bw2 * 3 + 6, sizeof(double)); // FIXME: this is over-allocated for very short seqs - b[i] = calloc(bw2 * 3 + 6, sizeof(double)); - } - s = calloc(l_query+2, sizeof(double)); // s[] is the scaling factor to avoid underflow - // initialize qual - _qual = calloc(l_query, sizeof(float)); - if (g_qual2prob[0] == 0) - for (i = 0; i < 256; ++i) - g_qual2prob[i] = pow(10, -i/10.); - for (i = 0; i < l_query; ++i) _qual[i] = g_qual2prob[iqual? iqual[i] : 30]; - qual = _qual - 1; - // initialize transition probability - sM = sI = 1. / (2 * l_query + 2); // the value here seems not to affect results; FIXME: need proof - m[0*3+0] = (1 - c->d - c->d) * (1 - sM); m[0*3+1] = m[0*3+2] = c->d * (1 - sM); - m[1*3+0] = (1 - c->e) * (1 - sI); m[1*3+1] = c->e * (1 - sI); m[1*3+2] = 0.; - m[2*3+0] = 1 - c->e; m[2*3+1] = 0.; m[2*3+2] = c->e; - bM = (1 - c->d) / l_query; bI = c->d / l_query; // (bM+bI)*l_query==1 - /*** forward ***/ - // f[0] - set_u(k, bw, 0, 0); - f[0][k] = s[0] = 1.; - { // f[1] - double *fi = f[1], sum; - int beg = 1, end = l_ref < bw + 1? l_ref : bw + 1, _beg, _end; - for (k = beg, sum = 0.; k <= end; ++k) { - int u; - double e = (ref[k] > 3 || query[1] > 3)? 1. : ref[k] == query[1]? 1. - qual[1] : qual[1] * EM; - set_u(u, bw, 1, k); - fi[u+0] = e * bM; fi[u+1] = EI * bI; - sum += fi[u] + fi[u+1]; - } - // rescale - s[1] = sum; - set_u(_beg, bw, 1, beg); set_u(_end, bw, 1, end); _end += 2; - for (k = _beg; k <= _end; ++k) fi[k] /= sum; - } - // f[2..l_query] - for (i = 2; i <= l_query; ++i) { - double *fi = f[i], *fi1 = f[i-1], sum, qli = qual[i]; - int beg = 1, end = l_ref, x, _beg, _end; - uint8_t qyi = query[i]; - x = i - bw; beg = beg > x? beg : x; // band start - x = i + bw; end = end < x? end : x; // band end - for (k = beg, sum = 0.; k <= end; ++k) { - int u, v11, v01, v10; - double e; - e = (ref[k] > 3 || qyi > 3)? 1. : ref[k] == qyi? 1. - qli : qli * EM; - set_u(u, bw, i, k); set_u(v11, bw, i-1, k-1); set_u(v10, bw, i-1, k); set_u(v01, bw, i, k-1); - fi[u+0] = e * (m[0] * fi1[v11+0] + m[3] * fi1[v11+1] + m[6] * fi1[v11+2]); - fi[u+1] = EI * (m[1] * fi1[v10+0] + m[4] * fi1[v10+1]); - fi[u+2] = m[2] * fi[v01+0] + m[8] * fi[v01+2]; - sum += fi[u] + fi[u+1] + fi[u+2]; -// fprintf(stderr, "F (%d,%d;%d): %lg,%lg,%lg\n", i, k, u, fi[u], fi[u+1], fi[u+2]); // DEBUG - } - // rescale - s[i] = sum; - set_u(_beg, bw, i, beg); set_u(_end, bw, i, end); _end += 2; - for (k = _beg, sum = 1./sum; k <= _end; ++k) fi[k] *= sum; - } - { // f[l_query+1] - double sum; - for (k = 1, sum = 0.; k <= l_ref; ++k) { - int u; - set_u(u, bw, l_query, k); - if (u < 3 || u >= bw2*3+3) continue; - sum += f[l_query][u+0] * sM + f[l_query][u+1] * sI; - } - s[l_query+1] = sum; // the last scaling factor + +#define __score_aux(_p, _q0, _sc, _io, _ie, _do, _de) { \ + int t1, t2; \ + score_aux_t *_q; \ + _q = _q0; \ + _p->M = _q->M >= _q->I? _q->M : _q->I; \ + _p->M = _p->M >= _q->D? _p->M : _q->D; \ + _p->M += (_sc); \ + ++_q; t1 = _q->M - _io - _ie; t2 = _q->I - _ie; _p->I = t1 >= t2? t1 : t2; \ + _q = _p-1; t1 = _q->M - _do - _de; t2 = _q->D - _de; _p->D = t1 >= t2? t1 : t2; \ } - /*** backward ***/ - // b[l_query] (b[l_query+1][0]=1 and thus \tilde{b}[][]=1/s[l_query+1]; this is where s[l_query+1] comes from) - for (k = 1; k <= l_ref; ++k) { - int u; - double *bi = b[l_query]; - set_u(u, bw, l_query, k); - if (u < 3 || u >= bw2*3+3) continue; - bi[u+0] = sM / s[l_query] / s[l_query+1]; bi[u+1] = sI / s[l_query] / s[l_query+1]; + + int i, j, bw, scmat_size = ap->row, *scmat = ap->matrix, ret; + const uint8_t *seq1, *seq2; + score_aux_t *curr, *last, *swap; + bw = abs(len1 - len2) + ap->band_width; + i = len1 > len2? len1 : len2; + if (bw > i + 1) bw = i + 1; + seq1 = _seq1 - 1; seq2 = _seq2 - 1; + curr = calloc(len1 + 2, sizeof(score_aux_t)); + last = calloc(len1 + 2, sizeof(score_aux_t)); + { // the zero-th row + int x, end = len1; + score_aux_t *p; + j = 0; + x = j + bw; end = len1 < x? len1 : x; // band end + p = curr; + p->M = 0; p->I = p->D = MINUS_INF; + for (i = 1, p = &curr[1]; i <= end; ++i, ++p) + p->M = p->I = MINUS_INF, p->D = -(ap->edo + ap->ede * i); + p->M = p->I = p->D = MINUS_INF; + swap = curr; curr = last; last = swap; } - // b[l_query-1..1] - for (i = l_query - 1; i >= 1; --i) { - int beg = 1, end = l_ref, x, _beg, _end; - double *bi = b[i], *bi1 = b[i+1], y = (i > 1), qli1 = qual[i+1]; - uint8_t qyi1 = query[i+1]; - x = i - bw; beg = beg > x? beg : x; - x = i + bw; end = end < x? end : x; - for (k = end; k >= beg; --k) { - int u, v11, v01, v10; - double e; - set_u(u, bw, i, k); set_u(v11, bw, i+1, k+1); set_u(v10, bw, i+1, k); set_u(v01, bw, i, k+1); - e = (k >= l_ref? 0 : (ref[k+1] > 3 || qyi1 > 3)? 1. : ref[k+1] == qyi1? 1. - qli1 : qli1 * EM) * bi1[v11]; - bi[u+0] = e * m[0] + EI * m[1] * bi1[v10+1] + m[2] * bi[v01+2]; // bi1[v11] has been foled into e. - bi[u+1] = e * m[3] + EI * m[4] * bi1[v10+1]; - bi[u+2] = (e * m[6] + m[8] * bi[v01+2]) * y; -// fprintf(stderr, "B (%d,%d;%d): %lg,%lg,%lg\n", i, k, u, bi[u], bi[u+1], bi[u+2]); // DEBUG + for (j = 1; j < len2; ++j) { + int x, beg = 0, end = len1, *scrow, col_end; + score_aux_t *p; + x = j - bw; beg = 0 > x? 0 : x; // band start + x = j + bw; end = len1 < x? len1 : x; // band end + if (beg == 0) { // from zero-th column + p = curr; + p->M = p->D = MINUS_INF; p->I = -(ap->eio + ap->eie * j); + ++beg; // then beg = 1 } - // rescale - set_u(_beg, bw, i, beg); set_u(_end, bw, i, end); _end += 2; - for (k = _beg, y = 1./s[i]; k <= _end; ++k) bi[k] *= y; - } - { // b[0] - int beg = 1, end = l_ref < bw + 1? l_ref : bw + 1; - double sum = 0.; - for (k = end; k >= beg; --k) { - int u; - double e = (ref[k] > 3 || query[1] > 3)? 1. : ref[k] == query[1]? 1. - qual[1] : qual[1] * EM; - set_u(u, bw, 1, k); - if (u < 3 || u >= bw2*3+3) continue; - sum += e * b[1][u+0] * bM + EI * b[1][u+1] * bI; + scrow = scmat + seq2[j] * scmat_size; + if (end == len1) col_end = 1, --end; + else col_end = 0; + for (i = beg, p = &curr[beg]; i <= end; ++i, ++p) + __score_aux(p, &last[i-1], scrow[(int)seq1[i]], ap->iio, ap->iie, ap->ido, ap->ide); + if (col_end) { + __score_aux(p, &last[i-1], scrow[(int)seq1[i]], ap->eio, ap->eie, ap->ido, ap->ide); + ++p; } - set_u(k, bw, 0, 0); - pb = b[0][k] = sum / s[0]; // if everything works as is expected, pb == 1.0 + p->M = p->I = p->D = MINUS_INF; +// for (i = 0; i <= len1; ++i) printf("(%d,%d,%d) ", curr[i].M, curr[i].I, curr[i].D); putchar('\n'); + swap = curr; curr = last; last = swap; } - is_diff = fabs(pb - 1.) > 1e-7? 1 : 0; - /*** MAP ***/ - for (i = 1; i <= l_query; ++i) { - double sum = 0., *fi = f[i], *bi = b[i], max = 0.; - int beg = 1, end = l_ref, x, max_k = -1; - x = i - bw; beg = beg > x? beg : x; - x = i + bw; end = end < x? end : x; - for (k = beg; k <= end; ++k) { - int u; - double z; - set_u(u, bw, i, k); - z = fi[u+0] * bi[u+0]; if (z > max) max = z, max_k = (k-1)<<2 | 0; sum += z; - z = fi[u+1] * bi[u+1]; if (z > max) max = z, max_k = (k-1)<<2 | 1; sum += z; + { // the last row + int x, beg = 0, *scrow; + score_aux_t *p; + j = len2; + x = j - bw; beg = 0 > x? 0 : x; // band start + if (beg == 0) { // from zero-th column + p = curr; + p->M = p->D = MINUS_INF; p->I = -(ap->eio + ap->eie * j); + ++beg; // then beg = 1 } - max /= sum; sum *= s[i]; // if everything works as is expected, sum == 1.0 - if (state) state[i-1] = max_k; - if (q) k = (int)(-4.343 * log(1. - max) + .499), q[i-1] = k > 100? 99 : k; -#ifdef _MAIN - fprintf(stderr, "(%.10lg,%.10lg) (%d,%d:%d)~%lg\n", pb, sum, i-1, max_k>>2, max_k&3, max); // DEBUG -#endif - } - /*** free ***/ - for (i = 0; i <= l_query; ++i) { - free(f[i]); free(b[i]); + scrow = scmat + seq2[j] * scmat_size; + for (i = beg, p = &curr[beg]; i < len1; ++i, ++p) + __score_aux(p, &last[i-1], scrow[(int)seq1[i]], ap->iio, ap->iie, ap->edo, ap->ede); + __score_aux(p, &last[i-1], scrow[(int)seq1[i]], ap->eio, ap->eie, ap->edo, ap->ede); +// for (i = 0; i <= len1; ++i) printf("(%d,%d,%d) ", curr[i].M, curr[i].I, curr[i].D); putchar('\n'); } - free(f); free(b); free(s); free(_qual); - return 0; + ret = curr[len1].M >= curr[len1].I? curr[len1].M : curr[len1].I; + ret = ret >= curr[len1].D? ret : curr[len1].D; + free(curr); free(last); + return ret; } #ifdef _MAIN -int main() +int main(int argc, char *argv[]) { - int l_ref = 5, l_query = 4; - uint8_t *ref = (uint8_t*)"\0\1\3\3\1"; - uint8_t *query = (uint8_t*)"\0\3\3\1"; -// uint8_t *query = (uint8_t*)"\1\3\3\1"; - static uint8_t qual[4] = {20, 20, 20, 20}; - ka_prob_glocal(ref, l_ref, query, l_query, qual, &ka_probpar_def, 0, 0); +// int len1 = 35, len2 = 35; +// uint8_t *seq1 = (uint8_t*)"\0\0\3\3\2\0\0\0\1\0\2\1\2\1\3\2\3\3\3\0\2\3\2\1\1\3\3\3\2\3\3\1\0\0\1"; +// uint8_t *seq2 = (uint8_t*)"\0\0\3\3\2\0\0\0\1\0\2\1\2\1\3\2\3\3\3\0\2\3\2\1\1\3\3\3\2\3\3\1\0\1\0"; + int len1 = 4, len2 = 4; + uint8_t *seq1 = (uint8_t*)"\1\0\0\1"; + uint8_t *seq2 = (uint8_t*)"\1\0\1\0"; + int sc; +// ka_global_core(seq1, 2, seq2, 1, &ka_param_qual, &sc, 0); + sc = ka_global_score(seq1, len1, seq2, len2, &ka_param2_qual); + printf("%d\n", sc); return 0; } #endif