X-Git-Url: http://woldlab.caltech.edu/gitweb/?p=samtools.git;a=blobdiff_plain;f=kaln.c;h=680779113ce7c2220434727cf578845d1e840d40;hp=9fa40d0be3999e66b885486d7a03e50994bfbfdd;hb=85bb95099e58e20cc03456b7528248f7baed4db4;hpb=317f5e8dd22cc9e1e5e05fbcaeb3b9aca7447351 diff --git a/kaln.c b/kaln.c index 9fa40d0..6807791 100644 --- a/kaln.c +++ b/kaln.c @@ -27,6 +27,7 @@ #include #include #include +#include #include "kaln.h" #define FROM_M 0 @@ -72,8 +73,8 @@ int aln_sm_blast[] = { -2, -2, -2, -2, -2 }; -ka_param_t ka_param_blast = { 5, 2, 2, aln_sm_blast, 5, 50 }; -ka_param_t ka_param_aa2aa = { 10, 2, 2, aln_sm_blosum62, 22, 50 }; +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 }; static uint32_t *ka_path2cigar32(const path_t *path, int path_len, int *n_cigar) { @@ -141,13 +142,13 @@ static uint32_t *ka_path2cigar32(const path_t *path, int path_len, int *n_cigar) } #define set_end_I(II, cur, p) \ { \ - if (gap_end >= 0) { \ - if ((p)->M - gap_open > (p)->I) { \ + if (gap_end_ext >= 0) { \ + if ((p)->M - gap_end_open > (p)->I) { \ (cur)->It = FROM_M; \ - (II) = (p)->M - gap_open - gap_end; \ + (II) = (p)->M - gap_end_open - gap_end_ext; \ } else { \ (cur)->It = FROM_I; \ - (II) = (p)->I - gap_end; \ + (II) = (p)->I - gap_end_ext; \ } \ } else set_I(II, cur, p); \ } @@ -163,13 +164,13 @@ static uint32_t *ka_path2cigar32(const path_t *path, int path_len, int *n_cigar) } #define set_end_D(DD, cur, p) \ { \ - if (gap_end >= 0) { \ - if ((p)->M - gap_open > (p)->D) { \ + if (gap_end_ext >= 0) { \ + if ((p)->M - gap_end_open > (p)->D) { \ (cur)->Dt = FROM_M; \ - (DD) = (p)->M - gap_open - gap_end; \ + (DD) = (p)->M - gap_end_open - gap_end_ext; \ } else { \ (cur)->Dt = FROM_D; \ - (DD) = (p)->D - gap_end; \ + (DD) = (p)->D - gap_end_ext; \ } \ } else set_D(DD, cur, p); \ } @@ -195,13 +196,14 @@ uint32_t *ka_global_core(uint8_t *seq1, int len1, uint8_t *seq2, int len2, const uint8_t type, ctype; uint32_t *cigar = 0; - int gap_open, gap_ext, gap_end, b; + int gap_open, gap_ext, gap_end_open, gap_end_ext, b; int *score_matrix, N_MATRIX_ROW; /* initialize some align-related parameters. just for compatibility */ gap_open = ap->gap_open; gap_ext = ap->gap_ext; - gap_end = ap->gap_end; + gap_end_open = ap->gap_end_open; + gap_end_ext = ap->gap_end_ext; b = ap->band_width; score_matrix = ap->matrix; N_MATRIX_ROW = ap->row; @@ -368,3 +370,212 @@ 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) +{ + 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 + } + /*** 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]; + } + // 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 + } + // 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; + } + set_u(k, bw, 0, 0); + pb = b[0][k] = sum / s[0]; // if everything works as is expected, pb == 1.0 + } + 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; + } + 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]); + } + free(f); free(b); free(s); free(_qual); + return 0; +} + +#ifdef _MAIN +int main() +{ + 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); + return 0; +} +#endif