PRIVATE void
make_pscores(vrna_fold_compound_t *vc){
/* calculate co-variance bonus for each pair depending on */
/* compensatory/consistent mutations and incompatible seqs */
/* should be 0 for conserved pairs, >0 for good pairs */
#define NONE -10000 /* score for forbidden pairs */
char *structure = NULL;
int i,j,k,l,s, max_span, turn;
float **dm;
int olddm[7][7]={{0,0,0,0,0,0,0}, /* hamming distance between pairs */
{0,0,2,2,1,2,2} /* CG */,
{0,2,0,1,2,2,2} /* GC */,
{0,2,1,0,2,1,2} /* GU */,
{0,1,2,2,0,2,1} /* UG */,
{0,2,2,1,2,0,2} /* AU */,
{0,2,2,2,1,2,0} /* UA */};
short **S = vc->S;
char **AS = vc->sequences;
int n_seq = vc->n_seq;
vrna_md_t *md = (vc->params) ? &(vc->params->model_details) : &(vc->exp_params->model_details);
int *pscore = vc->pscore; /* precomputed array of pair types */
int *indx = vc->jindx;
int *my_iindx = vc->iindx;
int n = vc->length;
turn = md->min_loop_size;
if (md->ribo) {
if (RibosumFile !=NULL) dm=readribosum(RibosumFile);
else dm=get_ribosum((const char **)AS, n_seq, n);
}
else { /*use usual matrix*/
dm = vrna_alloc(7*sizeof(float*));
for (i=0; i<7;i++) {
dm[i] = vrna_alloc(7*sizeof(float));
for (j=0; j<7; j++)
dm[i][j] = (float) olddm[i][j];
}
}
max_span = md->max_bp_span;
if((max_span < turn+2) || (max_span > n))
max_span = n;
for (i=1; i<n; i++) {
for (j=i+1; (j<i+turn+1) && (j<=n); j++)
pscore[indx[j]+i] = NONE;
for (j=i+turn+1; j<=n; j++) {
int pfreq[8]={0,0,0,0,0,0,0,0};
double score;
for (s=0; s<n_seq; s++) {
int type;
if (S[s][i]==0 && S[s][j]==0) type = 7; /* gap-gap */
else {
if ((AS[s][i] == '~')||(AS[s][j] == '~')) type = 7;
else type = md->pair[S[s][i]][S[s][j]];
}
pfreq[type]++;
}
if (pfreq[0]*2+pfreq[7]>n_seq) { pscore[indx[j]+i] = NONE; continue;}
for (k=1,score=0; k<=6; k++) /* ignore pairtype 7 (gap-gap) */
for (l=k; l<=6; l++)
score += pfreq[k]*pfreq[l]*dm[k][l];
/* counter examples score -1, gap-gap scores -0.25 */
pscore[indx[j]+i] = md->cv_fact *
((UNIT*score)/n_seq - md->nc_fact*UNIT*(pfreq[0] + pfreq[7]*0.25));
if((j - i + 1) > max_span){
pscore[indx[j]+i] = NONE;
}
}
}
if (md->noLP) /* remove unwanted pairs */
for (k=1; k<n-turn-1; k++)
for (l=1; l<=2; l++) {
int type,ntype=0,otype=0;
i=k; j = i+turn+l;
type = pscore[indx[j]+i];
while ((i>=1)&&(j<=n)) {
if ((i>1)&&(j<n)) ntype = pscore[indx[j+1]+i-1];
if ((otype<md->cv_fact*MINPSCORE)&&(ntype<md->cv_fact*MINPSCORE)) /* too many counterexamples */
pscore[indx[j]+i] = NONE; /* i.j can only form isolated pairs */
otype = type;
type = ntype;
i--; j++;
}
}
if (fold_constrained&&(structure!=NULL)) {
int psij, hx, hx2, *stack, *stack2;
stack = vrna_alloc(sizeof(int)*(n+1));
stack2 = vrna_alloc(sizeof(int)*(n+1));
for(hx=hx2=0, j=1; j<=n; j++) {
switch (structure[j-1]) {
case 'x': /* can't pair */
for (l=1; l<j-turn; l++) pscore[indx[j]+l] = NONE;
for (l=j+turn+1; l<=n; l++) pscore[indx[l]+j] = NONE;
break;
case '(':
stack[hx++]=j;
/* fallthrough */
case '[':
stack2[hx2++]=j;
/* fallthrough */
case '<': /* pairs upstream */
for (l=1; l<j-turn; l++) pscore[indx[j]+l] = NONE;
break;
case ']':
if (hx2<=0) {
fprintf(stderr, "%s\n", structure);
vrna_message_error("unbalanced brackets in constraints");
}
i = stack2[--hx2];
pscore[indx[j]+i]=NONE;
break;
case ')':
if (hx<=0) {
fprintf(stderr, "%s\n", structure);
vrna_message_error("unbalanced brackets in constraints");
}
i = stack[--hx];
psij = pscore[indx[j]+i]; /* store for later */
for (k=j; k<=n; k++)
for (l=i; l<=j; l++)
pscore[indx[k]+l] = NONE;
for (l=i; l<=j; l++)
for (k=1; k<=i; k++)
pscore[indx[l]+k] = NONE;
for (k=i+1; k<j; k++)
pscore[indx[k]+i] = pscore[indx[j]+k] = NONE;
pscore[indx[j]+i] = (psij>0) ? psij : 0;
/* fallthrough */
case '>': /* pairs downstream */
for (l=j+turn+1; l<=n; l++) pscore[indx[l]+j] = NONE;
break;
}
}
if (hx!=0) {
fprintf(stderr, "%s\n", structure);
vrna_message_error("unbalanced brackets in constraint string");
}
free(stack); free(stack2);
}
/*free dm */
for (i=0; i<7;i++) {
free(dm[i]);
}
free(dm);
/* copy over pscores for backward compatibility */
if(vc->pscore_pf_compat){
for(i = 1; i < n; i++)
for(j = i; j <= n; j++){
vc->pscore_pf_compat[my_iindx[i] - j] = (short)pscore[indx[j] + i];
}
}
}
PRIVATE void make_pscores(const short *const* S, const char **AS,
int n_seq, const char *structure) {
/* calculate co-variance bonus for each pair depending on */
/* compensatory/consistent mutations and incompatible seqs */
/* should be 0 for conserved pairs, >0 for good pairs */
#define NONE -10000 /* score for forbidden pairs */
int n,i,j,k,l,s;
double score;
int olddm[7][7]={{0,0,0,0,0,0,0}, /* hamming distance between pairs */
{0,0,2,2,1,2,2} /* CG */,
{0,2,0,1,2,2,2} /* GC */,
{0,2,1,0,2,1,2} /* GU */,
{0,1,2,2,0,2,1} /* UG */,
{0,2,2,1,2,0,2} /* AU */,
{0,2,2,2,1,2,0} /* UA */};
float **dm;
n=S[0][0]; /* length of seqs */
if (ribo) {
if (RibosumFile !=NULL) dm=readribosum(RibosumFile);
else dm=get_ribosum(AS,n_seq,n);
}
else { /*use usual matrix*/
dm=(float **)space(7*sizeof(float*));
for (i=0; i<7;i++) {
dm[i]=(float *)space(7*sizeof(float));
for (j=0; j<7; j++)
dm[i][j] = (float) olddm[i][j];
}
}
n=S[0][0]; /* length of seqs */
for (i=1; i<n; i++) {
for (j=i+1; (j<i+TURN+1) && (j<=n); j++)
pscore[indx[j]+i] = NONE;
for (j=i+TURN+1; j<=n; j++) {
int pfreq[8]={0,0,0,0,0,0,0,0};
for (s=0; s<n_seq; s++) {
int type;
if (S[s][i]==0 && S[s][j]==0) type = 7; /* gap-gap */
else {
if ((AS[s][i] == '~')||(AS[s][j] == '~')) type = 7;
else type = pair[S[s][i]][S[s][j]];
}
pfreq[type]++;
}
if (pfreq[0]*2+pfreq[7]>n_seq) { pscore[indx[j]+i] = NONE; continue;}
for (k=1,score=0; k<=6; k++) /* ignore pairtype 7 (gap-gap) */
for (l=k; l<=6; l++)
/* scores for replacements between pairtypes */
/* consistent or compensatory mutations score 1 or 2 */
score += pfreq[k]*pfreq[l]*dm[k][l];
/* counter examples score -1, gap-gap scores -0.25 */
pscore[indx[j]+i] = cv_fact *
((UNIT*score)/n_seq - nc_fact*UNIT*(pfreq[0] + pfreq[7]*0.25));
}
}
if (noLonelyPairs) /* remove unwanted pairs */
for (k=1; k<n-TURN-1; k++)
for (l=1; l<=2; l++) {
int type,ntype=0,otype=0;
i=k; j = i+TURN+l;
type = pscore[indx[j]+i];
while ((i>=1)&&(j<=n)) {
if ((i>1)&&(j<n)) ntype = pscore[indx[j+1]+i-1];
if ((otype<cv_fact*MINPSCORE)&&(ntype<cv_fact*MINPSCORE)) /* too many counterexamples */
pscore[indx[j]+i] = NONE; /* i.j can only form isolated pairs */
otype = type;
type = ntype;
i--; j++;
}
}
if (fold_constrained&&(structure!=NULL)) {
int psij, hx, hx2, *stack, *stack2;
stack = (int *) space(sizeof(int)*(n+1));
stack2 = (int *) space(sizeof(int)*(n+1));
for(hx=hx2=0, j=1; j<=n; j++) {
switch (structure[j-1]) {
case 'x': /* can't pair */
for (l=1; l<j-TURN; l++) pscore[indx[j]+l] = NONE;
for (l=j+TURN+1; l<=n; l++) pscore[indx[l]+j] = NONE;
break;
case '(':
stack[hx++]=j;
/* fallthrough */
case '[':
stack2[hx2++]=j;
/* fallthrough */
case '<': /* pairs upstream */
for (l=1; l<j-TURN; l++) pscore[indx[j]+l] = NONE;
break;
case ']':
if (hx2<=0) {
fprintf(stderr, "%s\n", structure);
nrerror("unbalanced brackets in constraints");
}
i = stack2[--hx2];
pscore[indx[j]+i]=NONE;
break;
case ')':
if (hx<=0) {
fprintf(stderr, "%s\n", structure);
nrerror("unbalanced brackets in constraints");
}
i = stack[--hx];
psij = pscore[indx[j]+i]; /* store for later */
for (k=j; k<=n; k++)
for (l=i; l<=j; l++)
pscore[indx[k]+l] = NONE;
for (l=i; l<=j; l++)
for (k=1; k<=i; k++)
pscore[indx[l]+k] = NONE;
for (k=i+1; k<j; k++)
pscore[indx[k]+i] = pscore[indx[j]+k] = NONE;
pscore[indx[j]+i] = (psij>0) ? psij : 0;
/* fallthrough */
case '>': /* pairs downstream */
for (l=j+TURN+1; l<=n; l++) pscore[indx[l]+j] = NONE;
break;
}
}
if (hx!=0) {
fprintf(stderr, "%s\n", structure);
nrerror("unbalanced brackets in constraint string");
}
free(stack); free(stack2);
}
/*free dm */
for (i=0; i<7;i++) {
free(dm[i]);
}
free(dm);
}
