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hmm_lib.c
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#include <stdio.h>
#include <math.h>
#include <string.h>
#include <stdlib.h>
#if !defined(__APPLE__)
#include <malloc.h>
#include <values.h>
#else
#include <limits.h>
#endif
#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, t,kk;
int temp_t;
double start_freq;
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, prob;
int len_seq;
int gene_len;
int num_d; /* the number of delete */
int freq_id;
double h_kd, r_kd, p_kd;
int codon_start=0;
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=0;
int start_orf=0;
int frame;
double final_score;
int insert[100];
int delete[100];
int insert_id=0, delete_id=0;
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){
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) && temp_i[j-I1_STATE] >=1 &&
(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){
/* 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){
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) &&
(j-I1_STATE_1 >=1) &&
(temp_i_1[j-I1_STATE_1] >=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){
/* 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 ((t > 5) && 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){
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;
}
temp_alpha = alpha[E_STATE_1][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_1;
}
alpha[R_STATE][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=-60; i<=-3; i++){
if(t+i >=0 && 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])]);
}
}
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;
alpha[S_STATE_1][t+1] = max_dbl;
alpha[S_STATE_1][t+2] = alpha[R_STATE][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;
temp_alpha = alpha[E_STATE_1][t-1] - log(hmm_ptr->tr[TR_ES]);
if (temp_alpha < alpha[S_STATE_1][t+2]){
alpha[S_STATE_1][t+2] = temp_alpha;
path[S_STATE_1][t] = E_STATE_1;
}
temp_alpha = alpha[E_STATE][t-1] - log(hmm_ptr->tr[TR_ES1]);
if (temp_alpha < alpha[S_STATE_1][t+2]){
alpha[S_STATE_1][t+2] = temp_alpha;
path[S_STATE_1][t] = E_STATE;
}
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 >=0 && 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;
}
temp_alpha = alpha[E_STATE_1][t-1] - log(hmm_ptr->tr[TR_ES1]);
if (temp_alpha < alpha[S_STATE][t+2]){
alpha[S_STATE][t+2] = temp_alpha;
path[S_STATE][t] = E_STATE_1;
}
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++){
if(t+i >=0 && 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])]);
}
}
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++){
if(t+i >=0 && 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])]);
}
}
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;
}
}
}
/* 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]); */
}
codon_start=0;
start_t=-1;
for (t=0; t<len_seq; t++){
if (codon_start==0 && start_t < 0 &&
((vpath[t]>=M1_STATE && vpath[t]<=M6_STATE) ||
(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){
codon_start=1;
}else{
codon_start=-1;
}
}else if (codon_start!=0 && (vpath[t]==E_STATE || vpath[t]==E_STATE_1 || t==len_seq-1)){
if (vpath[t]==E_STATE || vpath[t]==E_STATE_1){
end_t=t+3;
}else{
end_t=t+1;
/* FGS1.12 start: remove incomplete codon */
temp_t = t;
while(vpath[temp_t] != M1_STATE && vpath[temp_t] != M4_STATE && vpath[temp_t] != M1_STATE_1 && vpath[temp_t] != M4_STATE_1){
dna_f[dna_f_id] = '\0';
dna_f_id--;
dna[dna_id] = '\0';
dna_id--;
temp_t--;
}
/* FGS1.12 end: remove incomplete codon */
}
final_score = (alpha[vpath[end_t-4]][end_t-4]- alpha[vpath[start_t+2]][start_t+2] )/(end_t-start_t-5);
frame = start_orf%3;
if (frame==0){
frame=3;
}
if (dna_id > gene_len ){
if (codon_start==1){
fprintf(fp_out, "%d\t%d\t+\t%d\t%lf\t", start_t, end_t, frame, final_score);
/* printf("mina %d\t%d\t+\t%d\t%lf\t", start_t, end_t, frame, final_score); */
fprintf(fp_out, "I:");
for (i=0; i<insert_id; i++){
fprintf(fp_out, "%d,", insert[i]);
}
fprintf(fp_out, "\tD:");
for (i=0; i<delete_id; i++){
fprintf(fp_out, "%d,", delete[i]);
}
fprintf(fp_out, "\n");
fprintf(fp_aa, "%s_%d_%d_+\n", head_short, start_t, end_t);
fprintf(fp_dna, "%s_%d_%d_+\n", head_short, start_t, end_t);
get_protein(dna,protein,1);
fprintf(fp_aa, "%s\n", protein);
if (format==0){
fprintf(fp_dna, "%s\n", dna);
}else if (format==1){
fprintf(fp_dna, "%s\n", dna_f);
}
}else if (codon_start==-1){
fprintf(fp_out, "%d\t%d\t-\t%d\t%lf\t", start_t, end_t, frame, final_score);
/* printf("mina %d\t%d\t-\t%d\t%lf\t", start_t, end_t, frame, final_score); */
fprintf(fp_out, "I:");
for (i=0; i<insert_id; i++){
fprintf(fp_out, "%d,", insert[i]);
}
fprintf(fp_out, "\tD:");
for (i=0; i<delete_id; i++){
fprintf(fp_out, "%d,", delete[i]);
}
fprintf(fp_out, "\n");
fprintf(fp_aa, "%s_%d_%d_-\n", head_short, start_t, end_t);
fprintf(fp_dna, "%s_%d_%d_-\n", head_short, start_t, end_t);
get_protein(dna,protein,-1);
get_rc_dna(dna, dna1);
get_rc_dna_indel(dna_f, dna_f1);
fprintf(fp_aa, "%s\n", protein);
if (format==0){
fprintf(fp_dna, "%s\n", dna1);
}else if (format==1){
fprintf(fp_dna, "%s\n", dna_f1);
}
}
}
codon_start=0;
start_t = -1;
end_t = -1;
dna_id = 0;
dna_f_id = 0;
}else if (codon_start!=0 &&
((vpath[t]>=M1_STATE && vpath[t]<=M6_STATE) ||
(vpath[t]>=M1_STATE_1 && vpath[t]<=M6_STATE_1)) &&
vpath[t]-prev_match<6){
if (vpath[t] < prev_match){
out_nt = vpath[t]+6-prev_match;
}else{
out_nt = vpath[t]-prev_match;
}
for (kk=0; kk<out_nt; kk++){ /* for deleted nt in reads */
dna_id ++;
dna[dna_id] = 'N';
dna_f_id ++;
dna_f[dna_f_id] = 'x';
if (kk>0){
delete[delete_id]=t+1;
delete_id++;
}
}
dna[dna_id]=O[t];
dna_f[dna_f_id]=O[t];
prev_match = vpath[t];
}else if (codon_start!=0 &&
((vpath[t]>=I1_STATE && vpath[t]<=I6_STATE) ||
(vpath[t]>=I1_STATE_1 && vpath[t]<=I6_STATE_1))){
dna_f_id ++;
dna_f[dna_f_id] = tolower(O[t]);
insert[insert_id]=t+1;
insert_id++;
}
else if (codon_start!=0 && vpath[t]==R_STATE){
/* for long NNNNNNNNN, pretend R state */
codon_start=0;
start_t=-1;
end_t = -1;
dna_id=0;
dna_f_id=0;
}
}
free_dmatrix(alpha, hmm_ptr->N);
free_imatrix(path, hmm_ptr->N);
free_ivector(vpath);
}
void get_prob_from_cg(HMM *hmm_ptr, TRAIN *train_ptr, char *O){
int cg_count=0;
int len_seq;
int i;
len_seq = strlen(O);
for (i=0; i<len_seq; i++){
if ((O[i] == 'C'||O[i] =='c') || (O[i] == 'G'||O[i] == 'g') ){
cg_count++;
}
}
cg_count = floor((cg_count*1.0/len_seq)*100)-26;
if (cg_count < 0){
cg_count = 0;
}else if (cg_count > 43){
cg_count = 43;
}
memcpy(hmm_ptr->e_M, train_ptr->trans[cg_count], sizeof(hmm_ptr->e_M));
memcpy(hmm_ptr->e_M_1, train_ptr->rtrans[cg_count], sizeof(hmm_ptr->e_M_1));
memcpy(hmm_ptr->tr_R_R, train_ptr->noncoding[cg_count], sizeof(hmm_ptr->tr_R_R));
memcpy(hmm_ptr->tr_S, train_ptr->start[cg_count], sizeof(hmm_ptr->tr_S));
memcpy(hmm_ptr->tr_E, train_ptr->stop[cg_count], sizeof(hmm_ptr->tr_E));
memcpy(hmm_ptr->tr_S_1, train_ptr->start1[cg_count], sizeof(hmm_ptr->tr_S_1));
memcpy(hmm_ptr->tr_E_1, train_ptr->stop1[cg_count], sizeof(hmm_ptr->tr_E_1));
memcpy(hmm_ptr->S_dist, train_ptr->S_dist[cg_count], sizeof(hmm_ptr->S_dist));
memcpy(hmm_ptr->E_dist, train_ptr->E_dist[cg_count], sizeof(hmm_ptr->E_dist));
memcpy(hmm_ptr->S1_dist, train_ptr->S1_dist[cg_count], sizeof(hmm_ptr->S1_dist));
memcpy(hmm_ptr->E1_dist, train_ptr->E1_dist[cg_count], sizeof(hmm_ptr->E1_dist));
}
void get_train_from_file(char *filename, HMM *hmm_ptr, char *mfilename, char *mfilename1, char *nfilename,
char *sfilename,char *pfilename,char *s1filename,char *p1filename,char *dfilename, TRAIN *train_ptr){
int i, j, k, p;
double prob;
FILE *fp, *fpm, *fpm1, *fpn, *fps, *fpp, *fps1, *fpp1, *fpd;
char name[10];
char head[20];
char start[10];
char end[10];
/****************************************************/
/* transition */
/****************************************************/
fp = fopen (filename , "r");
/* Transition */
fscanf(fp, "%s", head);
for (i=0; i<14; i++){
fscanf(fp, "%s %lf", name, &prob);
hmm_ptr->tr[tr2int(name)] = prob;
}
/* TransitionMI */
fscanf(fp, "%s", head);
for (i=0; i<16; i++){
fscanf(fp, "%s %s %lf\n", start, end, &prob);
hmm_ptr->tr_M_I[nt2int(start[0])][nt2int(end[0])] = prob;
}
/* TransitionII */
fscanf(fp, "%s", head);
for (i=0; i<16; i++){
fscanf(fp, "%s %s %lf", start, end, &prob);
hmm_ptr->tr_I_I[nt2int(start[0])][nt2int(end[0])] = prob;
}
/* PI */
fscanf(fp, "%s", head);
for (i=0; i<NUM_STATE; i++){
fscanf(fp, "%s %lf", name, &prob);
hmm_ptr->pi[i] = prob;
}
fclose(fp);
/****************************************************/
/* M state transition */
/****************************************************/
fpm = fopen (mfilename , "r");
for (p=0; p<44; p++){ /* cg */