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hmm_lib.c
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hmm_lib.c
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#include <stdio.h>
#include <math.h>
#include <string.h>
#include <limits.h>
#include <float.h>
#include <stdlib.h>
#include <ctype.h>
#include "hmm.h"
#include "util_lib.h"
void viterbi(HMM *hmm_ptr, char *O, FILE *fp_out, FILE *fp_aa, FILE *fp_dna,
char *head, int whole_genome, int format) {
double max_dbl = 10000000000.0;
int debug = 0;
int *vpath; /* optimal path after backtracking */
double **alpha; /* viterbi prob array */
int **path; /* viterbi path array */
int i, j, l, m, n, x, y, z, t, jj, kk;
int temp_t;
int ag_num;
int orf_start = 0;
int orf_strand = 0;
int print_save;
int frame_save;
int orf_save;
double prob_save, start_freq;
int best;
int from, from0, to; /*from0: i-2 position, from: i-1 position */
int from2; /* from2: i-2, i-1 for condition in emission
probability */
double temp_alpha, temp, prob, prob2;
int len_seq;
int gene_len;
int count_ag;
int temp_strand;
int num_d; /* the number of delete */
int freq_id;
double h_kd, r_kd, p_kd;
int codon_start;
char dna[300000];
char dna1[300000];
char dna_f[300000];
char dna_f1[300000];
char protein[100000];
int dna_id = 0;
int dna_f_id = 0;
int out_nt;
int start_t;
int end_t;
int prev_match;
int start_orf;
int frame;
double final_score;
int insert[100];
int delete[100];
int insert_id, delete_id;
char *head_short = NULL;
char delimi[] = " ";
int temp_i[6] = { 0, 0, 0, 0, 0, 0 };
int temp_i_1[6] = { 0, 0, 0, 0, 0, 0 };
int num_N = 0;
/***************************************************************/
/* initialize */
/***************************************************************/
if (whole_genome == 1) {
gene_len = 120;
} else {
gene_len = 60;
}
len_seq = strlen(O);
alpha = (double **) dmatrix(hmm_ptr->N, len_seq);
path = (int **) imatrix(hmm_ptr->N, len_seq);
vpath = (int *) ivector(len_seq);
for (i = 0; i < hmm_ptr->N; i++) {
alpha[i][0] = -1 * log(hmm_ptr->pi[i]);
}
/* stop state */
if ((O[0] == 'T' || O[0] == 't')
&& (((O[1] == 'A' || O[1] == 'a') && (O[2] == 'A' || O[2] == 'a'))
|| ((O[1] == 'A' || O[1] == 'a')
&& (O[2] == 'G' || O[2] == 'g'))
|| ((O[1] == 'G' || O[1] == 'g')
&& (O[2] == 'A' || O[2] == 'a')))) {
alpha[E_STATE][0] = max_dbl;
alpha[E_STATE][1] = max_dbl;
path[E_STATE][1] = E_STATE;
path[E_STATE][2] = E_STATE;
alpha[M6_STATE][2] = max_dbl;
alpha[M5_STATE][1] = max_dbl;
alpha[M4_STATE][0] = max_dbl;
alpha[M3_STATE][2] = max_dbl;
alpha[M2_STATE][1] = max_dbl;
alpha[M1_STATE][0] = max_dbl;
if ((O[1] == 'A' || O[1] == 'a') && (O[2] == 'A' || O[2] == 'a')) {
alpha[E_STATE][2] = alpha[E_STATE][2] - log(0.53);
} else if ((O[1] == 'A' || O[1] == 'a')
&& (O[2] == 'G' || O[2] == 'g')) {
alpha[E_STATE][2] = alpha[E_STATE][2] - log(0.16);
} else if ((O[1] == 'G' || O[1] == 'g')
&& (O[2] == 'A' || O[2] == 'a')) {
alpha[E_STATE][2] = alpha[E_STATE][2] - log(0.30);
}
}
if ((O[2] == 'A' || O[0] == 'a')
&& (((O[0] == 'T' || O[0] == 't') && (O[1] == 'T' || O[1] == 't'))
|| ((O[0] == 'C' || O[0] == 'c')
&& (O[1] == 'T' || O[1] == 't'))
|| ((O[0] == 'T' || O[0] == 't')
&& (O[1] == 'C' || O[1] == 'c')))) {
alpha[S_STATE_1][0] = max_dbl;
alpha[S_STATE_1][1] = max_dbl;
alpha[S_STATE_1][2] = alpha[S_STATE][0];
path[S_STATE_1][1] = S_STATE_1;
path[S_STATE_1][2] = S_STATE_1;
alpha[M3_STATE_1][2] = max_dbl;
alpha[M6_STATE_1][2] = max_dbl;
if ((O[0] == 'T' || O[0] == 't') && (O[1] == 'T' || O[1] == 't')) {
alpha[S_STATE_1][2] = alpha[S_STATE_1][2] - log(0.53);
} else if ((O[0] == 'C' || O[0] == 'c')
&& (O[1] == 'T' || O[1] == 't')) {
alpha[S_STATE_1][2] = alpha[S_STATE_1][2] - log(0.16);
} else if ((O[0] == 'T' || O[0] == 't')
&& (O[1] == 'C' || O[1] == 'c')) {
alpha[S_STATE_1][2] = alpha[S_STATE_1][2] - log(0.30);
}
}
/******************************************************************/
/* fill out the rest of the columns */
/******************************************************************/
for (t = 1; t < len_seq; t++) {
from = nt2int(O[t - 1]);
if (t > 1) {
from0 = nt2int(O[t - 2]);
} else {
from0 = 2;
}
to = nt2int(O[t]);
/* if DNA is other than ACGT, do it later */
if (from == 4) {
from = 2;
}
if (from0 == 4) {
from0 = 2;
}
if (to == 4) {
to = 2;
num_N += 1;
} else {
num_N = 0;
}
from2 = from0 * 4 + from;
/******************/
/* M state */
/******************/
for (i = M1_STATE; i <= M6_STATE; i++) {
if (alpha[i][t] < max_dbl) {
if (t == 0) {
} else {
if (i == M1_STATE) {
/* from M state */
j = M6_STATE;
alpha[i][t] = alpha[j][t - 1] - log(hmm_ptr->tr[TR_GG])
- log(hmm_ptr->tr[TR_MM])
- log(hmm_ptr->e_M[0][from2][to]);
path[i][t] = j;
/* from D state */
if (whole_genome == 0) {
for (j = M5_STATE; j >= M1_STATE; j--) {
if (j >= i) {
num_d = i - j + 6;
} else if (j + 1 < i) {
num_d = i - j;
} else {
num_d = -10;
}
if (num_d > 0) {
temp_alpha = alpha[j][t - 1]
- log(hmm_ptr->tr[TR_MD])
- log(hmm_ptr->e_M[0][from2][to])
- log(0.25) * (num_d - 1)
- log(hmm_ptr->tr[TR_DD])
* (num_d - 2)
- log(hmm_ptr->tr[TR_DM]);
if (temp_alpha < alpha[i][t]) {
alpha[i][t] = temp_alpha;
path[i][t] = j;
}
}
}
}
/* from Start state */
temp_alpha = alpha[S_STATE][t - 1]
- log(hmm_ptr->e_M[0][from2][to]);
if (temp_alpha < alpha[i][t]) {
alpha[i][t] = temp_alpha;
path[i][t] = S_STATE;
}
} else { /*i ==M2-M6*/
/* from M state */
j = i - 1;
alpha[i][t] = alpha[j][t - 1] - log(hmm_ptr->tr[TR_MM])
- log(hmm_ptr->e_M[i - M1_STATE][from2][to]);
path[i][t] = j;
/* from D state */
if (whole_genome == 0) {
for (j = M6_STATE; j >= M1_STATE; j--) {
if (j >= i) {
num_d = i - j + 6;
} else if (j + 1 < i) {
num_d = i - j;
} else {
num_d = -10;
}
if (num_d > 0) {
temp_alpha =
alpha[j][t - 1]
- log(hmm_ptr->tr[TR_MD])
- log(
hmm_ptr->e_M[i
- M1_STATE][from2][to])
- log(0.25) * (num_d - 1)
- log(hmm_ptr->tr[TR_DD])
* (num_d - 2)
- log(hmm_ptr->tr[TR_DM]);
if (temp_alpha < alpha[i][t]) {
alpha[i][t] = temp_alpha;
path[i][t] = j;
}
}
}
}
}
/* from I state */
if (i == M1_STATE) {
j = I6_STATE;
} else {
j = I1_STATE + (i - M1_STATE - 1);
}
/* to aviod stop codon */
if (t < 2) {
} else if ((i == M2_STATE || i == M5_STATE)
&& (O[temp_i[j - I1_STATE]] == 'T'
|| O[temp_i[j - I1_STATE]] == 't')
&& (((O[t] == 'A' || O[t] == 'a')
&& (O[t + 1] == 'A' || O[t + 1] == 'a'))
|| ((O[t] == 'A' || O[t] == 'a')
&& (O[t + 1] == 'G'
|| O[t + 1] == 'g'))
|| ((O[t] == 'G' || O[t] == 'g')
&& (O[t + 1] == 'A'
|| O[t + 1] == 'a')))) {
} else if ((i == M3_STATE || i == M6_STATE)
&& (O[temp_i[j - I1_STATE] - 1] == 'T'
|| O[temp_i[j - I1_STATE] - 1] == 't')
&& (((O[temp_i[j - I1_STATE]] == 'A'
|| O[temp_i[j - I1_STATE]] == 'a')
&& (O[t] == 'A' || O[t] == 'a'))
|| ((O[temp_i[j - I1_STATE]] == 'A'
|| O[temp_i[j - I1_STATE]] == 'a')
&& (O[t] == 'G' || O[t] == 'g'))
|| ((O[temp_i[j - I1_STATE]] == 'G'
|| O[temp_i[j - I1_STATE]] == 'g')
&& (O[t] == 'A' || O[t] == 'a')))) {
} else {
temp_alpha = alpha[j][t - 1] - log(hmm_ptr->tr[TR_IM])
- log(0.25);
if (temp_alpha < alpha[i][t]) {
alpha[i][t] = temp_alpha;
path[i][t] = j;
}
}
}
}
}
/******************/
/* I state */
/******************/
for (i = I1_STATE; i <= I6_STATE; i++) {
if (t == 0) {
} else {
/* from I state */
j = i;
alpha[i][t] = alpha[j][t - 1] - log(hmm_ptr->tr[TR_II])
- log(hmm_ptr->tr_I_I[from][to]);
path[i][t] = j;
/* from M state */
j = i - I1_STATE + M1_STATE;
if (i == I6_STATE) {
temp_alpha = alpha[j][t - 1] - log(hmm_ptr->tr[TR_GG])
- log(hmm_ptr->tr[TR_MI])
- log(hmm_ptr->tr_M_I[from][to]);
} else {
temp_alpha = alpha[j][t - 1] - log(hmm_ptr->tr[TR_MI])
- log(hmm_ptr->tr_M_I[from][to]);
}
if (temp_alpha < alpha[i][t]) {
alpha[i][t] = temp_alpha;
path[i][t] = j;
temp_i[i - I1_STATE] = t - 1;
}
}
}
/******************/
/* M' state */
/******************/
for (i = M1_STATE_1; i <= M6_STATE_1; i++) {
if ((i == M1_STATE_1 || i == M4_STATE_1) && t >= 3
&& (((O[t - 3] == 'T' || O[t - 3] == 't')
&& (O[t - 2] == 'T' || O[t - 2] == 't')
&& (O[t - 1] == 'A' || O[t - 1] == 'a'))
|| ((O[t - 3] == 'C' || O[t - 3] == 'c')
&& (O[t - 2] == 'T' || O[t - 2] == 't')
&& (O[t - 1] == 'A' || O[t - 1] == 'a'))
|| ((O[t - 3] == 'T' || O[t - 3] == 't')
&& (O[t - 2] == 'C' || O[t - 2] == 'c')
&& (O[t - 1] == 'A' || O[t - 1] == 'a')))) {
/* from Start state since this is actually stop codon in minus strand */
alpha[i][t] = alpha[S_STATE_1][t - 1]
- log(hmm_ptr->e_M_1[i - M1_STATE_1][from2][to]);
path[i][t] = S_STATE_1;
} else {
if (t == 0) {
} else {
if (i == M1_STATE_1) {
/* from M state */
j = M6_STATE_1;
alpha[i][t] = alpha[j][t - 1] - log(hmm_ptr->tr[TR_GG])
- log(hmm_ptr->tr[TR_MM])
- log(hmm_ptr->e_M_1[0][from2][to]);
path[i][t] = j;
/* from D state */
if (whole_genome == 0) {
for (j = M5_STATE_1; j >= M1_STATE_1; j--) {
if (j >= i) {
num_d = i - j + 6;
} else if (j + 1 < i) {
num_d = i - j;
} else {
num_d = -10;
}
if (num_d > 0) {
temp_alpha = alpha[j][t - 1]
- log(hmm_ptr->tr[TR_MD])
- log(hmm_ptr->e_M_1[0][from2][to])
- log(0.25) * (num_d - 1)
- log(hmm_ptr->tr[TR_DD])
* (num_d - 2)
- log(hmm_ptr->tr[TR_DM]);
if (temp_alpha < alpha[i][t]) {
alpha[i][t] = temp_alpha;
path[i][t] = j;
}
}
}
}
} else {
/* from M state */
j = i - 1;
alpha[i][t] =
alpha[j][t - 1] - log(hmm_ptr->tr[TR_MM])
- log(
hmm_ptr->e_M_1[i - M1_STATE_1][from2][to]);
path[i][t] = j;
/* from D state */
if (whole_genome == 0) {
for (j = M6_STATE_1; j >= M1_STATE_1; j--) {
if (j >= i) {
num_d = i - j + 6;
} else if (j + 1 < i) {
num_d = i - j;
} else {
num_d = -10;
}
if (num_d > 0) {
temp_alpha =
alpha[j][t - 1]
- log(hmm_ptr->tr[TR_MD])
- log(
hmm_ptr->e_M_1[i
- M1_STATE_1][from2][to])
- log(0.25) * (num_d - 1)
- log(hmm_ptr->tr[TR_DD])
* (num_d - 2)
- log(hmm_ptr->tr[TR_DM]);
if (temp_alpha < alpha[i][t]) {
alpha[i][t] = temp_alpha;
path[i][t] = j;
}
}
}
}
}
/* from I state */
if (i == M1_STATE_1) {
j = I6_STATE_1;
} else {
j = I1_STATE_1 + (i - M1_STATE_1 - 1);
}
/* to aviod stop codon */
/* to aviod stop codon */
if (t < 2) {
} else if ((i == M2_STATE_1 || i == M5_STATE_1)
&& (O[t + 1] == 'A' || O[t + 1] == 'a')
&& (((O[temp_i_1[j - I1_STATE_1]] == 'T'
|| O[temp_i_1[j - I1_STATE_1]] == 't')
&& (O[t] == 'T' || O[t] == 't'))
|| ((O[temp_i_1[j - I1_STATE_1]] == 'C'
|| O[temp_i_1[j - I1_STATE_1]]
== 'c')
&& (O[t] == 'T' || O[t] == 't'))
|| ((O[temp_i_1[j - I1_STATE_1]] == 'T'
|| O[temp_i_1[j - I1_STATE_1]]
== 't')
&& (O[t] == 'C' || O[t] == 'c')))) {
} else if ((i == M3_STATE_1 || i == M6_STATE_1)
&& (O[t] == 'A' || O[t] == 'a')
&& (((O[temp_i_1[j - I1_STATE_1] - 1] == 'T'
|| O[temp_i_1[j - I1_STATE_1] - 1] == 't')
&& (O[temp_i_1[j - I1_STATE_1]] == 'T'
|| O[temp_i_1[j - I1_STATE_1]]
== 't'))
||
((O[temp_i_1[j - I1_STATE_1] - 1] == 'C'
|| O[temp_i_1[j - I1_STATE_1] - 1]
== 'c')
&& (O[temp_i_1[j - I1_STATE_1]]
== 'T'
|| O[temp_i_1[j - I1_STATE_1]]
== 't'))
||
((O[temp_i_1[j - I1_STATE_1] - 1] == 'T'
|| O[temp_i_1[j - I1_STATE_1] - 1]
== 't')
&& (O[temp_i_1[j - I1_STATE_1]]
== 'C'
|| O[temp_i_1[j - I1_STATE_1]]
== 'c')))) {
} else {
temp_alpha = alpha[j][t - 1] - log(hmm_ptr->tr[TR_IM])
- log(0.25);
if (temp_alpha < alpha[i][t]) {
alpha[i][t] = temp_alpha;
path[i][t] = j;
}
}
}
}
}
/******************/
/* I' state */
/******************/
for (i = I1_STATE_1; i <= I6_STATE_1; i++) {
if (t == 0) {
} else {
/* from I state */
j = i;
alpha[i][t] = alpha[j][t - 1] - log(hmm_ptr->tr[TR_II])
- log(hmm_ptr->tr_I_I[from][to]);
path[i][t] = j;
/* from M state */
if (path[S_STATE_1][t - 3] != R_STATE
&& path[S_STATE_1][t - 4] != R_STATE
&& path[S_STATE_1][t - 5] != R_STATE) {
j = i - I1_STATE_1 + M1_STATE_1;
if (i == I6_STATE_1) {
temp_alpha = alpha[j][t - 1] - log(hmm_ptr->tr[TR_GG])
- log(hmm_ptr->tr[TR_MI])
- log(hmm_ptr->tr_M_I[from][to]);
} else {
temp_alpha = alpha[j][t - 1] - log(hmm_ptr->tr[TR_MI])
- log(hmm_ptr->tr_M_I[from][to]);
}
if (temp_alpha < alpha[i][t]) {
alpha[i][t] = temp_alpha;
path[i][t] = j;
temp_i_1[i - I1_STATE_1] = t - 1;
}
}
}
}
/***********************/
/* Non_coding state */
/***********************/
if (t == 0) {
} else {
alpha[R_STATE][t] = alpha[R_STATE][t - 1]
- log(hmm_ptr->tr_R_R[from][to]) - log(hmm_ptr->tr[TR_RR]);
path[R_STATE][t] = R_STATE;
temp_alpha = alpha[E_STATE][t - 1] - log(hmm_ptr->tr[TR_ER]);
if (temp_alpha < alpha[R_STATE][t]) {
alpha[R_STATE][t] = temp_alpha;
path[R_STATE][t] = E_STATE;
}
alpha[R_STATE][t] -= log(0.95);
}
/***********************/
/* R1 */
/***********************/
if (t == 0) {
} else {
alpha[R_STATE_1][t] = alpha[R_STATE_1][t - 1]
- log(hmm_ptr->tr_R_R[from][to]) - log(hmm_ptr->tr[TR_RR]);
path[R_STATE_1][t] = R_STATE_1;
alpha[R_STATE_1][t] -= log(0.95);
}
/***********************/
/* R2 */
/***********************/
if (t == 0) {
} else {
alpha[R_STATE_2][t] = alpha[R_STATE_2][t - 1]
- log(hmm_ptr->tr_R_R[from][to]);
path[R_STATE_2][t] = R_STATE_2;
temp_alpha = alpha[E_STATE_1][t - 1];
if (temp_alpha < alpha[R_STATE_2][t]) {
alpha[R_STATE_2][t] = temp_alpha;
path[R_STATE_2][t] = E_STATE_1;
}
alpha[R_STATE_2][t] -= log(0.95);
}
/******************/
/* END state */
/******************/
if (alpha[E_STATE][t] == 0) {
alpha[E_STATE][t] = max_dbl;
path[E_STATE][t] = NOSTATE;
if (t < len_seq - 2 && (O[t] == 'T' || O[t] == 't')
&& (((O[t + 1] == 'A' || O[t + 1] == 'a')
&& (O[t + 2] == 'A' || O[t + 2] == 'a'))
|| ((O[t + 1] == 'A' || O[t + 1] == 'a')
&& (O[t + 2] == 'G' || O[t + 2] == 'g'))
|| ((O[t + 1] == 'G' || O[t + 1] == 'g')
&& (O[t + 2] == 'A' || O[t + 2] == 'a')))) {
alpha[E_STATE][t + 2] = max_dbl;
/* transition from frame4,frame5,and frame6 */
temp_alpha = alpha[M6_STATE][t - 1] - log(hmm_ptr->tr[TR_GE]);
if (temp_alpha < alpha[E_STATE][t + 2]) {
alpha[E_STATE][t + 2] = temp_alpha;
path[E_STATE][t] = M6_STATE;
}
/* transition from frame1,frame2,and frame3 */
temp_alpha = alpha[M3_STATE][t - 1] - log(hmm_ptr->tr[TR_GE]);
if (temp_alpha < alpha[E_STATE][t + 2]) {
alpha[E_STATE][t + 2] = temp_alpha;
path[E_STATE][t] = M3_STATE;
}
alpha[E_STATE][t] = max_dbl;
alpha[E_STATE][t + 1] = max_dbl;
path[E_STATE][t + 1] = E_STATE;
path[E_STATE][t + 2] = E_STATE;
alpha[M6_STATE][t + 2] = max_dbl;
alpha[M5_STATE][t + 1] = max_dbl;
alpha[M4_STATE][t] = max_dbl;
alpha[M3_STATE][t + 2] = max_dbl;
alpha[M2_STATE][t + 1] = max_dbl;
alpha[M1_STATE][t] = max_dbl;
if ((O[t + 1] == 'A' || O[t + 1] == 'a')
&& (O[t + 2] == 'A' || O[t + 2] == 'a')) {
alpha[E_STATE][t + 2] = alpha[E_STATE][t + 2] - log(0.54);
} else if ((O[t + 1] == 'A' || O[t + 1] == 'a')
&& (O[t + 2] == 'G' || O[t + 2] == 'g')) {
alpha[E_STATE][t + 2] = alpha[E_STATE][t + 2] - log(0.16);
} else if ((O[t + 1] == 'G' || O[t + 1] == 'g')
&& (O[t + 2] == 'A' || O[t + 2] == 'a')) {
alpha[E_STATE][t + 2] = alpha[E_STATE][t + 2] - log(0.30);
}
/* adjustment based on probability distribution */
start_freq=0;
freq_id = 0;
/*
* for(i=start_i; i<=-3; i++){
* start_freq -= log(hmm_ptr->tr_E[i+60][trinucleotide(O[t+i], O[t+i+1],
* O[t+i+2])]);
* }
* */
double sub_sum = 0;
int sub_count = 0;
if (t>=60){ /* bug reported by Yu-Wei */
for(i=-60; i<=-3; i++){
if (t+i+2 < len_seq)
{
start_freq -= log(hmm_ptr->tr_E[i+60][trinucleotide(O[t+i], O[t+i+1], O[t+i+2])]);
}
}
}else{
for(i=(-1*t); i<=-3; i++){
if (t+i+2 < len_seq)
{
sub_sum += log(hmm_ptr->tr_E[i+60][trinucleotide(O[t+i], O[t+i+1], O[t+i+2])]);
}
}
sub_sum = sub_sum * 58 / (-3 + t + 1);
start_freq -= sub_sum;
}
h_kd = hmm_ptr->E_dist[2] * exp(-1*pow(start_freq-hmm_ptr->E_dist[1],2)/(2*pow(hmm_ptr->E_dist[0],2)));
r_kd = hmm_ptr->E_dist[5] * exp(-1*pow(start_freq-hmm_ptr->E_dist[4],2)/(2*pow(hmm_ptr->E_dist[3],2)));
p_kd = h_kd / (h_kd + r_kd);
if (p_kd<0.01){
p_kd=0.01;
}else if (p_kd>0.99){
p_kd=0.99;
}
alpha[E_STATE][t+2] = alpha[E_STATE][t+2] - log(p_kd);
}
}
/*************************************************/
/* START' state */
/* origianlly stop codon of genes in - strand */
/*************************************************/
if (alpha[S_STATE_1][t] == 0) {
alpha[S_STATE_1][t] = max_dbl;
path[S_STATE_1][t] = NOSTATE;
if (t < len_seq - 2 && (O[t + 2] == 'A' || O[t + 2] == 'a')
&& (((O[t] == 'T' || O[t] == 't')
&& (O[t + 1] == 'T' || O[t + 1] == 't'))
|| ((O[t] == 'C' || O[t] == 'c')
&& (O[t + 1] == 'T' || O[t + 1] == 't'))
|| ((O[t] == 'T' || O[t] == 't')
&& (O[t + 1] == 'C' || O[t + 1] == 'c')))) {
alpha[S_STATE_1][t] = max_dbl;
path[S_STATE_1][t] = R_STATE_1;
alpha[S_STATE_1][t + 1] = max_dbl;
alpha[S_STATE_1][t + 2] = alpha[R_STATE_1][t - 1]
- log(hmm_ptr->tr[TR_RS]);
path[S_STATE_1][t + 1] = S_STATE_1;
path[S_STATE_1][t + 2] = S_STATE_1;
alpha[M3_STATE_1][t + 2] = max_dbl;
alpha[M6_STATE_1][t + 2] = max_dbl;
if ((O[t] == 'T' || O[t] == 't')
&& (O[t + 1] == 'T' || O[t + 1] == 't')) {
alpha[S_STATE_1][t + 2] = alpha[S_STATE_1][t + 2]
- log(0.54);
} else if ((O[t] == 'C' || O[t] == 'c')
&& (O[t + 1] == 'T' || O[t + 1] == 't')) {
alpha[S_STATE_1][t + 2] = alpha[S_STATE_1][t + 2]
- log(0.16);
} else if ((O[t] == 'T' || O[t] == 't')
&& (O[t + 1] == 'C' || O[t + 1] == 'c')) {
alpha[S_STATE_1][t + 2] = alpha[S_STATE_1][t + 2]
- log(0.30);
}
/* adjustment based on probability distribution */
start_freq=0;
freq_id = 0;
for(i=3; i<=60; i++){
if (t+i+2 < len_seq)
{
start_freq -= log(hmm_ptr->tr_S_1[i-3][trinucleotide(O[t+i], O[t+i+1], O[t+i+2])]);
}
}
h_kd = hmm_ptr->S1_dist[2] * exp(-1*pow(start_freq-hmm_ptr->S1_dist[1],2)/(2*pow(hmm_ptr->S1_dist[0],2)));
r_kd = hmm_ptr->S1_dist[5] * exp(-1*pow(start_freq-hmm_ptr->S1_dist[4],2)/(2*pow(hmm_ptr->S1_dist[3],2)));
p_kd = h_kd / (h_kd + r_kd);
if (p_kd<0.01){
p_kd=0.01;
}else if (p_kd>0.99){
p_kd=0.99;
}
alpha[S_STATE_1][t+2] = alpha[S_STATE_1][t+2] - log(p_kd);
}
}
/************************/
/* START state */
/************************/
if (alpha[S_STATE][t] == 0) {
alpha[S_STATE][t] = max_dbl;
path[S_STATE][t] = NOSTATE;
if (t < len_seq - 2 && (O[t + 1] == 'T' || O[t + 1] == 't')
&& (O[t + 2] == 'G' || O[t + 2] == 'g')
&& ((O[t] == 'A' || O[t] == 'a')
|| (O[t] == 'G' || O[t] == 'g')
|| (O[t] == 'T' || O[t] == 't'))) {
alpha[S_STATE][t] = max_dbl;
alpha[S_STATE][t + 1] = max_dbl;
alpha[S_STATE][t + 2] = alpha[R_STATE][t - 1]
- log(hmm_ptr->tr[TR_RS]);
path[S_STATE][t] = R_STATE;
path[S_STATE][t + 1] = S_STATE;
path[S_STATE][t + 2] = S_STATE;
temp_alpha = alpha[E_STATE][t - 1] - log(hmm_ptr->tr[TR_ES]);
if (temp_alpha < alpha[S_STATE][t + 2]) {
alpha[S_STATE][t + 2] = temp_alpha;
path[S_STATE][t] = E_STATE;
}
if ((O[t] == 'A' || O[t] == 'a')) {
alpha[S_STATE][t + 2] = alpha[S_STATE][t + 2] - log(0.83);
} else if ((O[t] == 'G' || O[t] == 'g')) {
alpha[S_STATE][t + 2] = alpha[S_STATE][t + 2] - log(0.10);
} else if ((O[t] == 'T' || O[t] == 't')) {
alpha[S_STATE][t + 2] = alpha[S_STATE][t + 2] - log(0.07);
}
/* adjustment based on probability distribution */
start_freq=0;
freq_id = 0;
/*
* for(i=-30; i<=30; i++){
* start_freq -= log(hmm_ptr->tr_S[i+30][trinucleotide(O[t+i], O[t+i+1],
* O[t+i+2])]);
* }
* */
double sub_sum = 0;
int sub_count = 0;
if (t>=30){
for(i=-30; i<=30; i++){
if (t+i+2 < len_seq)
{
start_freq -= log(hmm_ptr->tr_S[i+30][trinucleotide(O[t+i], O[t+i+1], O[t+i+2])]);
}
}
}else{
for(i=(-1*t); i<=30; i++){
if (t+i+2 < len_seq)
{
sub_sum += log(hmm_ptr->tr_S[i+30][trinucleotide(O[t+i], O[t+i+1], O[t+i+2])]);
}
}
sub_sum = sub_sum * 61 / (30 + t + 1);
start_freq -= sub_sum;
}
h_kd = hmm_ptr->S_dist[2] * exp(-1*pow(start_freq-hmm_ptr->S_dist[1],2)/(2*pow(hmm_ptr->S_dist[0],2)));
r_kd = hmm_ptr->S_dist[5] * exp(-1*pow(start_freq-hmm_ptr->S_dist[4],2)/(2*pow(hmm_ptr->S_dist[3],2)));
p_kd = h_kd / (h_kd + r_kd);
if (p_kd<0.01){
p_kd=0.01;
}else if (p_kd>0.99){
p_kd=0.99;
}
alpha[S_STATE][t+2] = alpha[S_STATE][t+2] - log(p_kd);
}
}
/**********************************************/
/* END' state */
/* origianlly start codon of genes in - strand */
/**********************************************/
if (alpha[E_STATE_1][t] == 0) {
alpha[E_STATE_1][t] = max_dbl;
path[E_STATE_1][t] = NOSTATE;
if (t < len_seq - 2 && (O[t] == 'C' || O[t] == 'c')
&& (O[t + 1] == 'A' || O[t + 1] == 'a')
&& ((O[t + 2] == 'T' || O[t + 2] == 't')
|| (O[t + 2] == 'C' || O[t + 2] == 'c')
|| (O[t + 2] == 'A' || O[t + 2] == 'a'))) {
/* transition from frame6 */
alpha[E_STATE_1][t + 2] = alpha[M6_STATE_1][t - 1]
- log(hmm_ptr->tr[TR_GE]);
path[E_STATE_1][t] = M6_STATE_1;
alpha[E_STATE_1][t] = max_dbl;
alpha[E_STATE_1][t + 1] = max_dbl;
path[E_STATE_1][t + 1] = E_STATE_1;
path[E_STATE_1][t + 2] = E_STATE_1;
if ((O[t + 2] == 'T' || O[t + 2] == 't')) {
alpha[E_STATE_1][t + 2] = alpha[E_STATE_1][t + 2]
- log(0.83);
} else if ((O[t + 2] == 'C' || O[t + 2] == 'c')) {
alpha[E_STATE_1][t + 2] = alpha[E_STATE_1][t + 2]
- log(0.10);
} else if ((O[t + 2] == 'A' || O[t + 2] == 'a')) {
alpha[E_STATE_1][t + 2] = alpha[E_STATE_1][t + 2]
- log(0.07);
}
/* adjustment based on probability distribution */
start_freq=0;
freq_id = 0;
/*
for(i=-30; i<=30; i++){
start_freq -= log(hmm_ptr->tr_E_1[i+30][trinucleotide(O[t+i], O[t+i+1], O[t+i+2])]);
}
*/
double sub_sum = 0;
int sub_count = 0;
if (t>=30){
for(i=-30; i<=30; i++){
if (t+i+2 < len_seq)
{
start_freq -= log(hmm_ptr->tr_E_1[i+30][trinucleotide(O[t+i], O[t+i+1], O[t+i+2])]);
}
}
}else{
for(i=(-1*t); i<=30; i++){
if (t+i+2 < len_seq)
{
sub_sum += log(hmm_ptr->tr_E_1[i+30][trinucleotide(O[t+i], O[t+i+1], O[t+i+2])]);
}
}
sub_sum = sub_sum * 61 / (30 + t + 1);
start_freq -= sub_sum;
}
h_kd = hmm_ptr->E1_dist[2] *
exp(-1*pow(start_freq-hmm_ptr->E1_dist[1],2)/(2*pow(hmm_ptr->E1_dist[0],2)))
;
r_kd = hmm_ptr->E1_dist[5] *
exp(-1*pow(start_freq-hmm_ptr->E1_dist[4],2)/(2*pow(hmm_ptr->E1_dist[3],2)))
;
p_kd = h_kd / (h_kd + r_kd);
if (p_kd<0.01){
p_kd=0.01;
}else if (p_kd>0.99){
p_kd=0.99;
}
alpha[E_STATE_1][t+2] = alpha[E_STATE_1][t+2] - log(p_kd);
}
}
if (num_N>9){
for (i=0; i<NUM_STATE; i++){
if (i!=R_STATE){
alpha[i][t] = max_dbl;
path[i][t] = R_STATE;
}
}
}
// TO HERE
/* printf("%d(%c)\t", t,O[t] ); */
/* for (i = 0; i < hmm_ptr->N; i++){ */
/* printf("%lf(%d %d)\t", alpha[i][t],path[i][t], i); */
/* } */
/* printf("\n\n"); */
}
/***********************************************************/
/* backtrack array to find the optimal path */
/***********************************************************/
fprintf(fp_out, "%s\n", head);
head_short = strtok(head, delimi);
/* find the state for O[N] with the highest probability */
prob = max_dbl;
for (i = 0; i < hmm_ptr->N; i++) {
if (alpha[i][len_seq - 1] < prob) {
prob = alpha[i][len_seq - 1];
vpath[len_seq - 1] = i;
//printf("%lf, %d\n", prob, vpath[len_seq-1]);
}
}
/* backtrack the opitmal path */
for (t = len_seq - 2; t >= 0; t--) {
vpath[t] = path[vpath[t + 1]][t + 1];
/* printf("%d %d %c \n",t, vpath[t], O[t]); */
}
print_save = 0;
codon_start = 0;
start_t = -1;
for (t = 0; t < len_seq; t++) {
/*
if ((vpath[t] >= M1_STATE_1 && vpath[t] <= M6_STATE_1)
|| vpath[t] == S_STATE_1 || vpath[t] == E_STATE_1 || vpath[t] == R_STATE_1 || vpath[t] == R_STATE_2){
start_t = 1;
end_t = len_seq;
fprintf(fp_out, "%d\t%d\t-\t%d\t%lf\t", start_t, end_t, 0, 0);
fprintf(fp_out, "\n");
break;
}
*/
if (codon_start == 0 && start_t < 0
&& ((vpath[t] >= M1_STATE_1 && vpath[t] <= M6_STATE_1)
|| vpath[t] == S_STATE || vpath[t] == S_STATE_1)) {
start_t = t + 1;
}
if (codon_start == 0
&& (vpath[t] == M1_STATE || vpath[t] == M4_STATE
|| vpath[t] == M1_STATE_1 || vpath[t] == M4_STATE_1)) {
memset(dna, 0, 300000);
memset(dna1, 0, 300000);
memset(dna_f, 0, 300000);
memset(dna_f1, 0, 300000);
memset(protein, 0, 100000);
memset(insert, 0, 100);
memset(delete, 0, 100);
insert_id = 0;
delete_id = 0;
dna_id = 0;
dna_f_id = 0;
dna[dna_id] = O[t];
dna_f[dna_f_id] = O[t];
start_orf = t + 1;
prev_match = vpath[t];
if (vpath[t] < M6_STATE) {