X-Git-Url: https://git.donarmstrong.com/?a=blobdiff_plain;f=kaln.c;h=d8edb91f13ef1dc8aabd0b066068b7a6c8b98baa;hb=4c8358db36b9d83a4aaa176a8f2c072ef5cc534d;hp=ec8c6dfd836acdf0f3724950b2535364e7f49230;hpb=8587a0ee0b25743a072ec67ede7076e5e24e4573;p=samtools.git diff --git a/kaln.c b/kaln.c index ec8c6df..d8edb91 100644 --- a/kaln.c +++ b/kaln.c @@ -371,150 +371,189 @@ uint32_t *ka_global_core(uint8_t *seq1, int len1, uint8_t *seq2, int len2, const return cigar; } -/*************************** - * Probabilistic extension * - ***************************/ +/***************************************** + * Probabilistic banded glocal alignment * + *****************************************/ + +static float g_qual2prob[256]; #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 = { 0.0001, 0.1, 10 }; +ka_probpar_t ka_probpar_def = { 0.001, 0.1, 10 }; /* - The profile HMM is: - - /\ /\ /\ /\ /\ - I[0] I[1] I[k-1] I[k] I[L] - ^ \ ^ \ \ ^ \ ^ \ \ ^ - | \ | \ \ | \ | \ \ | - M[0] -> M[1] -> ... -> M[k-1] -> M[k] -> ... -> M[L] M[L+1] - \ \/ \/ \/ \/ / - \ /\ /\ /\ /\ / - D[1] -> -> D[k-1] -> D[k] -> - \/ \/ \/ - - Every {M,I}[k], k=0..L connects M[L+1] at the same probability, while - no D[k], k=1..L-1 connects M[L+1]. This means an alignment can end up - with M or I but not D. - - Deletions are dumb states which do not emit residues. Frankly, I am - not sure if they are handled properly in the following - implementation. This is a potential concern to be resolved in future. + 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]. */ -int ka_prob_extend(uint8_t *_ref, int l_ref, uint8_t *_query, int l_query, float *_qual, +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, m[9], f_sink, sI, sM, pf, pb, pD; - float *qual; - uint8_t *ref, *query; + 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; - qual = _qual - 1; - bw = c->bw; - bw2 = c->bw * 2 + 1; + 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)); + 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)); } - // initialize m - sM = sI = 1. / (2 * l_query + 2); + 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] = 1.; - // f[1..l_query]; core loop - for (i = 1; i <= l_query; ++i) { - double *fi = f[i], *fi1 = f[i-1]; - int beg = 0, end = l_ref, x; - x = i - bw; beg = beg > x? beg : x; - x = i + bw; end = end < x? end : x; - for (k = beg; k <= end; ++k) { + 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] / 3.; + set_u(u, bw, 1, k); + fi[u+0] = e * bM; fi[u+1] = .25 * 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; + int beg = 1, end = l_ref, x, _beg, _end; + 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; + // FIXME: the following line can be optimized without branching e = (ref[k] > 3 || query[i] > 3)? 1. : ref[k] == query[i]? 1. - qual[i] : qual[i] / 3.; 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] = .25 * (m[1] * fi1[v10+0] + m[4] * fi1[v10+1]); fi[u+2] = m[2] * fi[v01+0] + m[8] * fi[v01+2]; - fprintf(stderr, "F (%d,%d;%d): %lg,%lg,%lg\n", i, k, u, fi[u], fi[u+1], fi[u+2]); // DEBUG + 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; k <= _end; ++k) fi[k] /= sum; } - // sink - for (k = 0, f_sink = 0.; k <= l_ref; ++k) { - int u; - set_u(u, bw, l_query, k); - if (u < 3 || u >= bw2*3+3) continue; - f_sink += f[l_query][u+0] * sM + f[l_query][u+1] * sI; + { // 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 } - pf = f_sink; /*** backward ***/ - // sink - for (k = 0; k <= l_ref; ++k) { + // 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; bi[u+1] = sI; + 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]; core loop - for (i = l_query - 1; i > 0; --i) { - int beg = 0, end = l_ref, x; - double *bi = b[i], *bi1 = b[i+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); 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; + // FIXME: the following can be optimized without branching e = k >= l_ref? 0 : (ref[k+1] > 3 || query[i+1] > 3)? 1. : ref[k+1] == query[i+1]? 1. - qual[i+1] : qual[i+1] / 3.; 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); bi[u+0] = e * m[0] * bi1[v11+0] + .25 * m[1] * bi1[v10+1] + m[2] * bi[v01+2]; bi[u+1] = e * m[3] * bi1[v11+0] + .25 * m[4] * bi1[v10+1]; - bi[u+2] = e * m[6] * bi1[v11+0] + m[8] * bi[v01+2]; - fprintf(stderr, "B (%d,%d;%d): %lg,%lg,%lg\n", i, k, u, bi[u], bi[u+1], bi[u+2]); // DEBUG + // FIXME: I do not know why I need this (i>1) factor, but only with it the result makes sense. + bi[u+2] = (e * m[6] * bi1[v11+0] + 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; + y = s[i]; + for (k = _beg; k <= _end; ++k) bi[k] /= y; } - { // the "zero" coordinate (i==k==0) - double *bi = b[0], *bi1 = b[1]; - int u, v11, v01, v10; - double e = (ref[1] > 3 || query[1] > 3)? 1. : ref[1] == query[1]? 1. - qual[1] : qual[1] / 3.; - set_u(u, bw, 0, 0); set_u(v11, bw, 1, 1); set_u(v10, bw, 1, 0); set_u(v01, bw, 0, 1); - bi[u+0] = e * m[0] * bi1[v11+0] + .25 * m[1] * bi1[v10+1] + m[2] * bi[v01+2]; + { // 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] / 3.; + set_u(u, bw, 1, k); + if (u < 3 || u >= bw2*3+3) continue; + sum += e * b[1][u+0] * bM + .25 * 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 } - set_u(k, bw, 0, 0); - pb = b[0][k]; - pD = (pf + pb) / 2.; - is_diff = fabs(pb/pf - 1.) > 1e-7? 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 = 0, end = l_ref, x, max_k = -1; + 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<<2 | 0; sum += z; - z = fi[u+1] * bi[u+1]; if (z > max) max = z, max_k = k<<2 | 1; sum += z; + 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 /= pD; // if everything works as is expected, sum == 1.0 + max /= sum; sum *= s[i]; // if everything works as is expected, sum == 1.0 if (state) state[i-1] = max_k; - if (q) q[i-1] = -4.343 * log(1. - max); + if (q) k = -4.343 * log(1. - max), q[i-1] = k > 100? 99 : k; #ifdef _MAIN - fprintf(stderr, "[%d],%d,%lg,%d:%d,%lg\n", is_diff, i, sum, max_k>>2, max_k&3, max); // DEBUG + 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(f); free(b); free(s); free(_qual); return 0; } @@ -523,10 +562,10 @@ 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"; // FIXME: the output is not so right given this input!!! - static float qual[4] = {.01, .01, .01, .01}; - ka_prob_extend(ref, l_ref, query, l_query, qual, &ka_probpar_def, 0, 0); + 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