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hmm_lib.c
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hmm_lib.c
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#include "util_lib.h"
void viterbi(HMM *hmm_ptr, char *O, char* output_buffer, char* aa_buffer,
char *dna_buffer, char *sequence_head, int whole_genome, int format,
int len_seq, char* dna, char* dna1, char* dna_f, char* dna_f1,
char* protein, int* insert, int* c_delete, char* temp_str_ptr) {
int *vpath; // optimal path after backtracking
int **path; // viterbi path array
double **alpha; // viterbi prob array
int i, j, t, kk;
int from, from0, to; /*from0: i-2 position, from: i-1 position */
int from2; /* from2: i-2, i-1 for condition in probability */
int gene_len;
int num_d; /* the number of delete */
int freq_id;
double h_kd, r_kd, p_kd;
double temp_alpha, prob;
double start_freq;
double final_score;
int codon_start = 0;
int dna_id = 0;
int dna_f_id = 0;
int out_nt;
int start_t = -1;
int end_t;
int prev_match;
int start_orf;
int frame;
int insert_id, delete_id;
int temp_i[6] = {0,0,0,0,0,0};
int temp_i_1[6] = {1,1,1,1,1,1};
int num_N = 0;
/***************************************************************/
/* initialize */
/***************************************************************/
for(i =0; i < strlen(O); i++) {
if( O[i]=='a' ) O[i]='A';
if( O[i]=='t' ) O[i]='T';
if( O[i]=='c' ) O[i]='C';
if( O[i]=='g' ) O[i]='G';
}
if (whole_genome==1) {
gene_len = 120;
} else {
gene_len = 60;
}
alpha = (double **)dmatrix(len_seq);
path = (int **)imatrix(len_seq);
vpath = (int *)ivector(len_seq);
for (i = 0; i < NUM_STATE; i++) {
alpha[i][0] = -1 * (hmm_ptr->pi[i]);
}
/* stop state */
if ((O[0] == 'T') && (((O[1] == 'A') && (O[2] == 'A')) ||
((O[1] == 'A') && (O[2] == 'G')) || ((O[1] == 'G') && (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[2] == 'A')) {
alpha[E_STATE][2] = alpha[E_STATE][2] - LOG_53;
} else if ((O[1] == 'A') && (O[2] == 'G')) {
alpha[E_STATE][2] = alpha[E_STATE][2] - LOG_16;
} else if ((O[1] == 'G') && (O[2] == 'A')) {
alpha[E_STATE][2] = alpha[E_STATE][2] - LOG_30;
}
}
if ((O[2] == 'A') &&
(((O[0] == 'T') && (O[1] == 'T')) ||
((O[0] == 'C') && (O[1] == 'T')) ||
((O[0] == 'T') && (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[1] == 'T')) {
alpha[S_STATE_1][2] = alpha[S_STATE_1][2] - LOG_53;
} else if ((O[0] == 'C') && (O[1] == 'T')) {
alpha[S_STATE_1][2] = alpha[S_STATE_1][2] - LOG_16;
} else if ((O[0] == 'T') && (O[1] == 'C')) {
alpha[S_STATE_1][2] = alpha[S_STATE_1][2] - LOG_30;
}
}
int multiple=0;
/******************************************************************/
/* 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] - (hmm_ptr->tr[TR_GG]) - (hmm_ptr->tr[TR_MM]) - (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] - (hmm_ptr->tr[TR_MD]) -
(hmm_ptr->e_M[0][from2][to])
- LOG_25*(num_d-1) - (hmm_ptr->tr[TR_DD])*(num_d-2) -
(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] - (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] - (hmm_ptr->tr[TR_MM]) -
(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] - (hmm_ptr->tr[TR_MD]) -
(hmm_ptr->e_M[i-M1_STATE][from2][to])
- LOG_25*(num_d-1) - (hmm_ptr->tr[TR_DD])*(num_d-2) -
(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[t] == 'A') && (O[t+1] =='A')) ||
((O[t] == 'A') && (O[t+1] =='G')) ||
((O[t] == 'G') && (O[t+1] =='A')))) {
} else if (((j-I1_STATE > 0) && (temp_i[j-I1_STATE]>0)) && ((i==M3_STATE || i==M6_STATE) && (O[temp_i[j-I1_STATE]-1] == 'T') &&
(((O[temp_i[j-I1_STATE]] == 'A') && (O[t] =='A')) ||
((O[temp_i[j-I1_STATE]] == 'A') && (O[t] =='G')) ||
((O[temp_i[j-I1_STATE]] == 'G') && (O[t] =='A'))))) {
} else {
temp_alpha = alpha[j][t-1] - (hmm_ptr->tr[TR_IM]) - LOG_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] - (hmm_ptr->tr[TR_II]) -
(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] - (hmm_ptr->tr[TR_GG]) -
(hmm_ptr->tr[TR_MI]) -(hmm_ptr->tr_M_I[from][to]);
} else {
temp_alpha = alpha[j][t-1] -
(hmm_ptr->tr[TR_MI]) -(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-2] == 'T') && (O[t-1] == 'A')) ||
((O[t-3] == 'C') && (O[t-2] == 'T') && (O[t-1] == 'A')) ||
((O[t-3] == 'T') && (O[t-2] == 'C') && (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] -
(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] - (hmm_ptr->tr[TR_GG]) -
(hmm_ptr->tr[TR_MM]) - (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] - (hmm_ptr->tr[TR_MD]) -
(hmm_ptr->e_M_1[0][from2][to])
- LOG_25*(num_d-1) - (hmm_ptr->tr[TR_DD])*(num_d-2) -
(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] - (hmm_ptr->tr[TR_MM]) -
(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] - (hmm_ptr->tr[TR_MD]) -
(hmm_ptr->e_M_1[i-M1_STATE_1][from2][to])
- LOG_25*(num_d-1) - (hmm_ptr->tr[TR_DD])*(num_d-2) -
(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);
}
//!! 11 --> 16
//!! What is the actual point of -1
/* to aviod stop codon */
if (t<2) {
} else if((i==M2_STATE_1 ||
i==M5_STATE_1) &&
(O[t+1] == 'A' ) &&
(((O[temp_i_1[j-I1_STATE_1]] == 'T') && (O[t] =='T')) ||
((O[temp_i_1[j-I1_STATE_1]] == 'C') && (O[t] =='T')) ||
((O[temp_i_1[j-I1_STATE_1]] == 'T') && (O[t] =='C')))) {
} else if ((i==M3_STATE_1 ||
i==M6_STATE_1) &&
(O[t] == 'A' ) &&
(((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]-1] == 'C') && (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]] =='C')))) {
} else {
temp_alpha = alpha[j][t-1] - (hmm_ptr->tr[TR_IM]) - LOG_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] - (hmm_ptr->tr[TR_II]) -
(hmm_ptr->tr_I_I[from][to]);
path[i][t] = j;
if(t<5) continue;
/* 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] - (hmm_ptr->tr[TR_GG]) -
(hmm_ptr->tr[TR_MI]) -(hmm_ptr->tr_M_I[from][to]);
} else {
temp_alpha = alpha[j][t-1] -
(hmm_ptr->tr[TR_MI]) -(hmm_ptr->tr_M_I[from][to]);
}
if (temp_alpha < alpha[i][t]) {
alpha[i][t] = temp_alpha;
path[i][t] = j;
//!! We are addressing the character array with this.
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] - (hmm_ptr->tr_R_R[from][to]) - (hmm_ptr->tr[TR_RR]);
path[R_STATE][t] = R_STATE;
temp_alpha = alpha[E_STATE][t-1] - (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] - (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_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+1] == 'A') && (O[t+2] == 'A')) ||
((O[t+1] == 'A') && (O[t+2] == 'G')) ||
((O[t+1] == 'G') && (O[t+2] == 'A')))) {
alpha[E_STATE][t+2] = max_dbl;
/* transition from frame4,frame5,and frame6 */
temp_alpha = alpha[M6_STATE][t-1] - (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] - (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+2] == 'A')) {
alpha[E_STATE][t+2] = alpha[E_STATE][t+2] - (0.54);
} else if ((O[t+1] == 'A') && (O[t+2] == 'G')) {
alpha[E_STATE][t+2] = alpha[E_STATE][t+2] - LOG_16;
} else if((O[t+1] == 'G') && (O[t+2] == 'A')) {
alpha[E_STATE][t+2] = alpha[E_STATE][t+2] - LOG_30;
}
/* adjustment based on probability distribution */
start_freq=0;
freq_id = 0;
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 -= (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 += (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] == 'T') && (O[t+1] == 'T')) ||
((O[t] == 'C') && (O[t+1] == 'T')) ||
((O[t] == 'T') && (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] - (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] - (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] - (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+1] == 'T')) {
alpha[S_STATE_1][t+2] = alpha[S_STATE_1][t+2] - (0.54);
} else if ((O[t] == 'C') && (O[t+1] == 'T')) {
alpha[S_STATE_1][t+2] = alpha[S_STATE_1][t+2] - LOG_16;
} else if((O[t] == 'T') && (O[t+1] == 'C')) {
alpha[S_STATE_1][t+2] = alpha[S_STATE_1][t+2] - LOG_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 -= (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+2] == 'G')&&
((O[t] == 'A') || (O[t] == 'G') || (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] - (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] - (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] - (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') {
alpha[S_STATE][t+2] = alpha[S_STATE][t+2] - LOG_83;
} else if (O[t] == 'G') {
alpha[S_STATE][t+2] = alpha[S_STATE][t+2] - LOG_10;
} else if(O[t] == 'T') {
alpha[S_STATE][t+2] = alpha[S_STATE][t+2] - LOG_07;
}
/* adjustment based on probability distribution */
start_freq=0;
freq_id = 0;
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 -= (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 += (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+1] == 'A') &&
((O[t+2] == 'T') || (O[t+2] == 'C') || (O[t+2] == 'A'))) {
/* transition from frame6 */
alpha[E_STATE_1][t+2] = alpha[M6_STATE_1][t-1] - (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') {
alpha[E_STATE_1][t+2] = alpha[E_STATE_1][t+2] - LOG_83;
} else if (O[t+2] == 'C' ) {
alpha[E_STATE_1][t+2] = alpha[E_STATE_1][t+2] - LOG_10;
} else if(O[t+2] == 'A' ) {
alpha[E_STATE_1][t+2] = alpha[E_STATE_1][t+2] - LOG_07;
}
/* adjustment based on probability distribution */
start_freq=0;
freq_id = 0;
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 -= (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 += (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;
}
}
}
}
/***********************************************************/
/* backtrack array to find the optimal path */
/***********************************************************/
sprintf(output_buffer, "%s\n", sequence_head);
/* find the state for O[N] with the highest probability */
prob = max_dbl;
for (i = 0; i < NUM_STATE; i++) {
if (alpha[i][len_seq-1] < prob) {
prob = alpha[i][len_seq-1];
vpath[len_seq-1] = i;
}
}
/* backtrack the opitmal path */
for(t=len_seq-2; t>=0; t--) {
if(t+1 < 0 || vpath[t+1] < 0) continue;
vpath[t] = path[vpath[t+1]][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)) {
stopMemset(dna, STRINGLEN);
stopMemset(dna1, STRINGLEN);//
stopMemset(dna_f, STRINGLEN);//
stopMemset(dna_f1, STRINGLEN);//
stopMemset(protein, STRINGLEN);
stopMemset(insert, STRINGLEN);//
stopMemset(c_delete, STRINGLEN);//
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 */
int 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;
}
//!! Transfer all of the output buffer writing code to another function. Modularize this.
if (dna_id > gene_len) {
print_outputs(codon_start, start_t, end_t, frame, output_buffer, aa_buffer, dna_buffer, sequence_head,
dna, dna1, dna_f, dna_f1, protein, insert, c_delete, insert_id, delete_id, format, temp_str_ptr,multiple);
multiple++;
}
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) {
c_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);
free_imatrix(path);
free(vpath);
vpath = 0;
dna = 0;
dna1 = 0;
dna_f = 0;
dna_f = 0;
protein = 0;
}
void get_prob_from_cg(HMM *hmm_ptr, TRAIN *train_ptr, char *O, int len_seq) {
int cg_id = -1;
int cg_count=0;
int i,j,k;
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));
}
//!! This function is for some strange reason definetly leaking memory. Need to find out why.
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++) {
//!! This causes a memory leak for unknown reasons.
fscanf(fp, "%s %lf", name, &prob);
hmm_ptr->tr[tr2int(name)] = log(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])] = log(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])] = log(prob);
}
/* PI */
fscanf(fp, "%s", head);
for (i=0; i<NUM_STATE; i++) {
fscanf(fp, "%s %lf", name, &prob);
hmm_ptr->pi[i] = log(prob);
}
fclose(fp);
/****************************************************/
/* M state transition */
/****************************************************/
fpm = fopen (mfilename , "r");