From 35370d90d93e348c368ead87db4c91f09cbab79a Mon Sep 17 00:00:00 2001 From: Heng Li Date: Tue, 28 Sep 2010 16:32:08 +0000 Subject: [PATCH] Implement the glocal HMM; discard the extention HMM --- kaln.c | 119 ++++++++++++++++++++++++++++++--------------------------- kaln.h | 6 ++- 2 files changed, 68 insertions(+), 57 deletions(-) diff --git a/kaln.c b/kaln.c index b20ae6f..4be7901 100644 --- a/kaln.c +++ b/kaln.c @@ -377,44 +377,38 @@ uint32_t *ka_global_core(uint8_t *seq1, int len1, uint8_t *seq2, int len2, const #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 float *_qual, const ka_probpar_t *c, int *state, uint8_t *q) { - double **f, **b, *s, m[9], sI, sM, pb; - float *qual; - uint8_t *ref, *query; + double **f, **b, *s, m[9], sI, sM, bI, bM, pb; + const float *qual; + const uint8_t *ref, *query; int bw, bw2, i, k, is_diff = 0; /*** initialization ***/ - ref = _ref - 1; // change to 1-based coordinate - query = _query - 1; - qual = _qual - 1; - bw = c->bw; - bw2 = c->bw * 2 + 1; - // allocate forward and backward matrices f[][] and b[][] + ref = _ref - 1; query = _query - 1; qual = _qual - 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) { @@ -427,29 +421,30 @@ int ka_prob_extend(uint8_t *_ref, int l_ref, uint8_t *_query, int l_query, float 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.; - { // write D cells - int beg = 1, end = l_ref, x, _beg, _end; - double sum; - x = 0 - bw; beg = beg > x? beg : x; - x = 0 + bw; end = end < x? end : x; + 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, v01; - set_u(u, bw, 0, k); set_u(v01, bw, 0, k-1); - sum += (f[0][u+2] = m[2] * f[0][v01+0] + m[8] * f[0][v01+2]); + 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 to avoid floating point underflow - s[0] = sum; - set_u(_beg, bw, 0, 0); set_u(_end, bw, 0, end); _end += 2; - for (k = _beg; k <= _end; ++k) f[0][k] /= sum; + // 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[1..l_query]; core loop - for (i = 1; i <= l_query; ++i) { + // f[2..l_query] + for (i = 2; i <= l_query; ++i) { double *fi = f[i], *fi1 = f[i-1], sum; - int beg = 0, end = l_ref, x, _beg, _end; + 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) { @@ -469,9 +464,9 @@ int ka_prob_extend(uint8_t *_ref, int l_ref, uint8_t *_query, int l_query, float set_u(_beg, bw, i, beg); set_u(_end, bw, i, end); _end += 2; for (k = _beg; k <= _end; ++k) fi[k] /= sum; } - { // sink (actually f[l_query+1]) + { // f[l_query+1] double sum; - for (k = 0, sum = 0.; k <= l_ref; ++k) { + 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; @@ -481,16 +476,16 @@ int ka_prob_extend(uint8_t *_ref, int l_ref, uint8_t *_query, int l_query, float } /*** 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 = 0; k <= l_ref; ++k) { + 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]; core loop - for (i = l_query - 1; i >= 0; --i) { - int beg = 0, end = l_ref, x, _beg, _end; + // 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]; x = i - bw; beg = beg > x? beg : x; x = i + bw; end = end < x? end : x; @@ -502,15 +497,27 @@ int ka_prob_extend(uint8_t *_ref, int l_ref, uint8_t *_query, int l_query, float 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]; + // FIXME: I do not know why I need this (i>1) factor, but only with it the result is correct + bi[u+2] = (e * m[6] * bi1[v11+0] + m[8] * bi[v01+2]) * (i > 1); // 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; k <= _end; ++k) bi[k] /= s[i]; } - set_u(k, bw, 0, 0); - pb = b[0][k]; // if everything works as is expected, pb==1 + { // 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]; + } is_diff = fabs(pb - 1.) > 1e-7? 1 : 0; /*** MAP ***/ for (i = 1; i <= l_query; ++i) { @@ -548,7 +555,7 @@ int main() 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); + ka_prob_glocal(ref, l_ref, query, l_query, qual, &ka_probpar_def, 0, 0); return 0; } #endif diff --git a/kaln.h b/kaln.h index 74da142..3bcaac1 100644 --- a/kaln.h +++ b/kaln.h @@ -50,12 +50,16 @@ typedef struct { extern "C" { #endif - uint32_t *ka_global_core(uint8_t *seq1, int len1, uint8_t *seq2, int len2, const ka_param_t *ap, int *_score, int *n_cigar); + uint32_t *ka_global_core(uint8_t *seq1, int len1, uint8_t *seq2, int len2, const ka_param_t *ap, + int *_score, int *n_cigar); + int ka_prob_glocal(const uint8_t *_ref, int l_ref, const uint8_t *_query, int l_query, const float *_qual, + const ka_probpar_t *c, int *state, uint8_t *q); #ifdef __cplusplus } #endif extern ka_param_t ka_param_blast; /* = { 5, 2, 5, 2, aln_sm_blast, 5, 50 }; */ +extern ka_probpar_t ka_probpar_def; /* { 0.0001, 0.1, 10 } */ #endif -- 2.39.2