PRIVATE char *backtrack_XS(int k, int l, const int i, const int j, const int max_interaction_length) {
/* backtrack structure going backwards from i, and forwards from j
return structure in bracket notation with & as separator */
int p, q, type, type2, E, traced, i0, j0;
char *st1, *st2, *struc;
st1 = (char *) vrna_alloc(sizeof(char)*(i-k+2));
st1[i-k+1]='\0';
st2 = (char *) vrna_alloc(sizeof(char)*(l-j+2));
st2[l-j+1]='\0';
i0=k; j0=l;
while (k<=i && l>=j) {
E = c3[j-11][max_interaction_length-i+k-1][l-j]; traced=0;
st1[k-i0] = '(';
st2[l-j] = ')';
type=ptype[indx[l]+k];
if (!type) vrna_message_error("backtrack failed in fold duplex bli");
for (p=k+1; p<=i; p++) {
for (q=l-1; q>=j; q--) {
int LE;
if (p-k+l-q-2>MAXLOOP) break;
type2=ptype[indx[q]+p];
if (!type2) continue;
LE = E_IntLoop(p-k-1, l-q-1, type, rtype[type2], SS1[k+1], SS1[l-1], SS1[p-1], SS1[q+1], P);
if (E == c3[j-11][max_interaction_length-i+p-1][q-j]+LE) {
traced=1;
k=p; l=q;
break;
}
}
if (traced) break;
}
if (!traced) {
E-=E_ExtLoop(type2, ((k<i)?SS1[k+1]:-1), ((l>j-1)? SS1[l-1]:-1), P);
break;
if (E != P->DuplexInit) {
vrna_message_error("backtrack failed in fold duplex bal");
} else break;
}
}
struc = (char *) vrna_alloc(k-i0+1+j0-l+1+2);
for (p=0; p<=i-i0; p++){
if (!st1[p]) st1[p] = '.';
}
for (p=0; p<=j0-j; p++) {
if (!st2[p]) {
st2[p] = '.';
}
}
strcpy(struc, st1);
strcat(struc, "&");
strcat(struc, st2);
free(st1); free(st2);
return struc;
}
PUBLIC vrna_plist_t *
stackProb(double cutoff){
if(!(backward_compat_compound && backward_compat)){
vrna_message_error("stackProb: run pf_fold() first!");
} else if( !backward_compat_compound->exp_matrices->probs){
vrna_message_error("stackProb: probs==NULL!");
}
return vrna_stack_prob(backward_compat_compound, cutoff);
}
PRIVATE int decode(char *id)
{
int n, quit, i;
char label[100], *code;
n = 0;
quit = 0;
code = coding;
while (!quit) {
for (i = 0; code[i] != sep; i++) {
if (code[i] == '\0') {
quit = 1;
break;
}
label[i] = code[i];
}
label[i] = '\0';
if (strcmp(id, label) == 0) return (n);
code += (i+1);
n++;
}
vrna_message_error("Syntax error: node identifier \"%s\" not found "
"in coding string \"%s\"\n"
"Exiting",
id, coding);
exit(0);
}
PUBLIC void *
vrna_alloc(unsigned size){
void *pointer;
if ( (pointer = (void *) calloc(1, (size_t) size)) == NULL) {
#ifdef EINVAL
if (errno==EINVAL) {
fprintf(stderr,"vrna_alloc: requested size: %d\n", size);
vrna_message_error("Memory allocation failure -> EINVAL");
}
if (errno==ENOMEM)
#endif
vrna_message_error("Memory allocation failure -> no memory");
}
return pointer;
}
PUBLIC void *
vrna_realloc(void *p, unsigned size){
if (p == NULL)
return vrna_alloc(size);
p = (void *) realloc(p, size);
if (p == NULL) {
#ifdef EINVAL
if (errno==EINVAL) {
fprintf(stderr,"vrna_realloc: requested size: %d\n", size);
vrna_message_error("vrna_realloc allocation failure -> EINVAL");
}
if (errno==ENOMEM)
#endif
vrna_message_error("vrna_realloc allocation failure -> no memory");
}
return p;
}
PUBLIC char *
centroid( int length,
double *dist) {
if (pr==NULL)
vrna_message_error("pr==NULL. You need to call pf_fold() before centroid()");
return vrna_centroid_from_probs(length, dist, pr);
}
PUBLIC double
mean_bp_distance(int length){
if(backward_compat_compound)
if(backward_compat_compound->exp_matrices)
if(backward_compat_compound->exp_matrices->probs)
return vrna_mean_bp_distance(backward_compat_compound);
vrna_message_error("mean_bp_distance: you need to call vrna_pf_fold first");
return 0.; /* we will never get to this point */
}
PRIVATE char *get_array1(int *arr, int size)
{
int i, p, pos, pp, r, last;
char *line, buf[16];
i = last = 0;
while( i<size ) {
line = get_line(fp);
if (!line) vrna_message_error("unexpected end of file in get_array1");
ignore_comment(line);
pos=0;
while ((i<size)&&(sscanf(line+pos,"%15s%n", buf, &pp)==1)) {
pos += pp;
if (buf[0]=='*') {i++; continue;}
else if (buf[0]=='x') { /* should only be used for loop parameters */
if (i==0) vrna_message_error("can't extrapolate first value");
p = arr[last] + (int) (0.5+ lxc37*log(((double) i)/(double)(last)));
}
else if (strcmp(buf,"DEF") == 0) p = DEF;
else if (strcmp(buf,"INF") == 0) p = INF;
else if (strcmp(buf,"NST") == 0) p = NST;
else {
r=sscanf(buf,"%d", &p);
if (r!=1) {
return line+pos;
fprintf(stderr, "can't interpret `%s' in get_array1\n", buf);
exit(1);
}
last = i;
}
arr[i++]=p;
}
free(line);
}
return NULL;
}
PUBLIC void
alloc_sequence_arrays(const char **sequences,
short ***S,
short ***S5,
short ***S3,
unsigned short ***a2s,
char ***Ss,
int circ){
unsigned int s, n_seq, length;
if(sequences[0] != NULL){
length = strlen(sequences[0]);
for (s=0; sequences[s] != NULL; s++);
n_seq = s;
*S = (short **) vrna_alloc((n_seq+1) * sizeof(short *));
*S5 = (short **) vrna_alloc((n_seq+1) * sizeof(short *));
*S3 = (short **) vrna_alloc((n_seq+1) * sizeof(short *));
*a2s = (unsigned short **) vrna_alloc((n_seq+1) * sizeof(unsigned short *));
*Ss = (char **) vrna_alloc((n_seq+1) * sizeof(char *));
for (s=0; s<n_seq; s++) {
if(strlen(sequences[s]) != length) vrna_message_error("uneqal seqence lengths");
(*S5)[s] = (short *) vrna_alloc((length + 2) * sizeof(short));
(*S3)[s] = (short *) vrna_alloc((length + 2) * sizeof(short));
(*a2s)[s] = (unsigned short *)vrna_alloc((length + 2) * sizeof(unsigned short));
(*Ss)[s] = (char *) vrna_alloc((length + 2) * sizeof(char));
(*S)[s] = (short *) vrna_alloc((length + 2) * sizeof(short));
encode_ali_sequence(sequences[s], (*S)[s], (*S5)[s], (*S3)[s], (*Ss)[s], (*a2s)[s], circ);
}
(*S5)[n_seq] = NULL;
(*S3)[n_seq] = NULL;
(*a2s)[n_seq] = NULL;
(*Ss)[n_seq] = NULL;
(*S)[n_seq] = NULL;
}
else vrna_message_error("alloc_sequence_arrays: no sequences in the alignment!");
}
PUBLIC double
mean_bp_distance_pr(int length,
FLT_OR_DBL *p){
double d=0;
int *index = vrna_idx_row_wise((unsigned int) length);
if (p==NULL)
vrna_message_error("p==NULL. You need to supply a valid probability matrix for mean_bp_distance_pr()");
d = wrap_mean_bp_distance(p, length, index, TURN);
free(index);
return d;
}
/* get the free energy of a subsequence from the q[] array */
PUBLIC double
get_subseq_F( int i,
int j){
if(backward_compat_compound)
if(backward_compat_compound->exp_matrices)
if(backward_compat_compound->exp_matrices->q){
int *my_iindx = backward_compat_compound->iindx;
vrna_exp_param_t *pf_params = backward_compat_compound->exp_params;
FLT_OR_DBL *q = backward_compat_compound->exp_matrices->q;
return ((-log(q[my_iindx[i]-j])-(j-i+1)*log(pf_params->pf_scale))*pf_params->kT/1000.0);
}
vrna_message_error("call pf_fold() to fill q[] array before calling get_subseq_F()");
return 0.; /* we will never get to this point */
}
PRIVATE void ignore_comment(char * line)
{
/* excise C style comments */
/* only one comment per line, no multiline comments */
char *cp1, *cp2;
if ((cp1=strstr(line, "/*"))) {
cp2 = strstr(cp1, "*/");
if (cp2==NULL)
vrna_message_error("unclosed comment in parameter file");
/* can't use strcpy for overlapping strings */
for (cp2+=2; *cp2!='\0'; cp2++, cp1++)
*cp1 = *cp2;
*cp1 = '\0';
}
return;
}
PUBLIC char *settype(enum parset s){
switch(s){
case S: return "stack";
case S_H: return "stack_enthalpies";
case HP: return "hairpin";
case HP_H: return "hairpin_enthalpies";
case B: return "bulge";
case B_H: return "bulge_enthalpies";
case IL: return "interior";
case IL_H: return "interior_enthalpies";
case MME: return "mismatch_exterior";
case MME_H: return "mismatch_exterior_enthalpies";
case MMH: return "mismatch_hairpin";
case MMH_H: return "mismatch_hairpin_enthalpies";
case MMI: return "mismatch_interior";
case MMI_H: return "mismatch_interior_enthalpies";
case MMI1N: return "mismatch_interior_1n";
case MMI1N_H: return "mismatch_interior_1n_enthalpies";
case MMI23: return "mismatch_interior_23";
case MMI23_H: return "mismatch_interior_23_enthalpies";
case MMM: return "mismatch_multi";
case MMM_H: return "mismatch_multi_enthalpies";
case D5: return "dangle5";
case D5_H: return "dangle5_enthalpies";
case D3: return "dangle3";
case D3_H: return "dangle3_enthalpies";
case INT11: return "int11";
case INT11_H: return "int11_enthalpies";
case INT21: return "int21";
case INT21_H: return "int21_enthalpies";
case INT22: return "int22";
case INT22_H: return "int22_enthalpies";
case ML: return "ML_params";
case NIN: return "NINIO";
case TRI: return "Triloops";
case TL: return "Tetraloops";
case HEX: return "Hexaloops";
case QUIT: return "END";
case MISC: return "Misc";
default: vrna_message_error("\nThe answer is: 42\n");
}
return "";
}
PRIVATE double PrfEditCost(int i, int j, const float *T1, const float *T2)
{
double dist;
int k, kmax;
kmax = (int) T1[1];
if ((int) T2[1] != kmax) vrna_message_error("inconsistent Profiles in PrfEditCost");
if(i==0) {
for(dist = 0. ,k=0 ; k<kmax ; k++)
dist += T2[j*kmax+k];
}
if(j==0) {
for(dist = 0. ,k=0 ; k<kmax ; k++)
dist += T1[i*kmax+k];
}
if((i>0)&&(j>0)) {
for(dist = 2.,k=0; k<kmax; k++)
dist -= 2.*average(T1[i*kmax+k],T2[j*kmax+k]);
}
return dist;
}
PUBLIC double
mean_bp_dist(int length) {
/* compute the mean base pair distance in the thermodynamic ensemble */
/* <d> = \sum_{a,b} p_a p_b d(S_a,S_b)
this can be computed from the pair probs p_ij as
<d> = \sum_{ij} p_{ij}(1-p_{ij}) */
int i, j, *my_iindx;
double d = 0;
if (pr==NULL)
vrna_message_error("pr==NULL. You need to call pf_fold() before mean_bp_dist()");
my_iindx = vrna_idx_row_wise(length);
for (i=1; i<=length; i++)
for (j=i+TURN+1; j<=length; j++)
d += pr[my_iindx[i]-j] * (1-pr[my_iindx[i]-j]);
free(my_iindx);
return 2*d;
}
PRIVATE void usage(void)
{
vrna_message_error("usage: AnalyseSeqs [-X[bswnm]] [-Q] [-M{mask}] \n"
" [-D{H|A[,cost]|G[,cost1,cost2]}] [-d{D|B|H|S}]");
exit(0);
}
PRIVATE void
pf_linear(vrna_fold_compound_t *vc){
char *hard_constraints;
int n, i,j, k, ij, d, *my_iindx, *jindx, with_gquad, turn,
with_ud, hc_decompose;
FLT_OR_DBL temp, Qmax, qbt1, *q, *qb, *qm, *qm1, *q1k, *qln;
double max_real;
vrna_ud_t *domains_up;
vrna_md_t *md;
vrna_hc_t *hc;
vrna_mx_pf_t *matrices;
vrna_mx_pf_aux_el_t *aux_mx_el;
vrna_mx_pf_aux_ml_t *aux_mx_ml;
vrna_exp_param_t *pf_params;
n = vc->length;
my_iindx = vc->iindx;
jindx = vc->jindx;
matrices = vc->exp_matrices;
pf_params = vc->exp_params;
hc = vc->hc;
domains_up = vc->domains_up;
q = matrices->q;
qb = matrices->qb;
qm = matrices->qm;
qm1 = matrices->qm1;
q1k = matrices->q1k;
qln = matrices->qln;
md = &(pf_params->model_details);
with_gquad = md->gquad;
turn = md->min_loop_size;
hard_constraints = hc->matrix;
with_ud = (domains_up && domains_up->exp_energy_cb);
Qmax = 0;
max_real = (sizeof(FLT_OR_DBL) == sizeof(float)) ? FLT_MAX : DBL_MAX;
if (with_ud && domains_up->exp_prod_cb)
domains_up->exp_prod_cb(vc, domains_up->data);
if(with_gquad){
free(vc->exp_matrices->G);
vc->exp_matrices->G = get_gquad_pf_matrix(vc->sequence_encoding2, vc->exp_matrices->scale, vc->exp_params);
}
/* init auxiliary arrays for fast exterior/multibranch loops */
aux_mx_el = vrna_exp_E_ext_fast_init(vc);
aux_mx_ml = vrna_exp_E_ml_fast_init(vc);
/*array initialization ; qb,qm,q
qb,qm,q (i,j) are stored as ((n+1-i)*(n-i) div 2 + n+1-j */
for (d=0; d<=turn; d++)
for (i=1; i<=n-d; i++) {
j=i+d;
ij = my_iindx[i]-j;
qb[ij] = 0.0;
}
for (j = turn + 2; j <= n; j++) {
for (i = j - turn - 1; i >= 1; i--) {
/* construction of partition function of segment i,j */
/* firstly that given i binds j : qb(i,j) */
ij = my_iindx[i] - j;
hc_decompose = hard_constraints[jindx[j] + i];
qbt1 = 0;
if(hc_decompose){
/* process hairpin loop(s) */
qbt1 += vrna_exp_E_hp_loop(vc, i, j);
/* process interior loop(s) */
qbt1 += vrna_exp_E_int_loop(vc, i, j);
/* process multibranch loop(s) */
qbt1 += vrna_exp_E_mb_loop_fast(vc, i, j, aux_mx_ml->qqm1);
}
qb[ij] = qbt1;
/* Multibranch loop */
qm[ij] = vrna_exp_E_ml_fast(vc, i, j, aux_mx_ml);
if (qm1)
qm1[jindx[j] + i] = aux_mx_ml->qqm[i]; /* for stochastic backtracking and circfold */
/* Exterior loop */
q[ij] = temp = vrna_exp_E_ext_fast(vc, i, j, aux_mx_el);
if (temp>Qmax) {
Qmax = temp;
if (Qmax>max_real/10.)
vrna_message_warning("Q close to overflow: %d %d %g", i,j,temp);
}
if (temp>=max_real) {
vrna_message_error("overflow in pf_fold while calculating q[%d,%d]\n"
"use larger pf_scale", i,j);
}
}
/* rotate auxiliary arrays */
vrna_exp_E_ext_fast_rotate(vc, aux_mx_el);
vrna_exp_E_ml_fast_rotate(vc, aux_mx_ml);
}
/* prefill linear qln, q1k arrays */
if(q1k && qln){
for (k=1; k<=n; k++) {
q1k[k] = q[my_iindx[1] - k];
qln[k] = q[my_iindx[k] - n];
}
q1k[0] = 1.0;
qln[n+1] = 1.0;
}
/* free memory occupied by auxiliary arrays for fast exterior/multibranch loops */
vrna_exp_E_ml_fast_free(vc, aux_mx_ml);
vrna_exp_E_ext_fast_free(vc, aux_mx_el);
}
PRIVATE void
alipf_linear( vrna_fold_compound_t *vc){
char *hard_constraints;
int i,j, ij, jij, d, turn, n, *my_iindx, *jindx, *pscore;
FLT_OR_DBL temp, Qmax, qbt1, *q, *qb, *qm, *qm1;
double kTn, max_real;
vrna_exp_param_t *pf_params;
vrna_mx_pf_t *matrices;
vrna_mx_pf_aux_el_t *aux_mx_el;
vrna_mx_pf_aux_ml_t *aux_mx_ml;
vrna_md_t *md;
vrna_hc_t *hc;
n = vc->length;
pf_params = vc->exp_params;
matrices = vc->exp_matrices;
hc = vc->hc;
my_iindx = vc->iindx;
jindx = vc->jindx;
pscore = vc->pscore; /* precomputed array of pair types */
md = &(pf_params->model_details);
q = matrices->q;
qb = matrices->qb;
qm = matrices->qm;
qm1 = matrices->qm1;
hard_constraints = hc->matrix;
turn = md->min_loop_size;
kTn = pf_params->kT/10.; /* kT in cal/mol */
Qmax = 0.;
max_real = (sizeof(FLT_OR_DBL) == sizeof(float)) ? FLT_MAX : DBL_MAX;
/* init auxiliary arrays for fast exterior/multibranch loops */
aux_mx_el = vrna_exp_E_ext_fast_init(vc);
aux_mx_ml = vrna_exp_E_ml_fast_init(vc);
/* array initialization ; qb,qm,q
qb,qm,q (i,j) are stored as ((n+1-i)*(n-i) div 2 + n+1-j */
for (d = 0; d <= turn; d++)
for (i = 1; i <= n - d; i++) {
j = i + d;
ij = my_iindx[i]-j;
qb[ij] = 0.0;
}
for (j = turn + 2; j <= n; j++) {
for (i = j - turn - 1; i >= 1; i--) {
int psc;
/* construction of partition function for segment i,j */
/* calculate pf given that i and j pair: qb(i,j) */
ij = my_iindx[i] - j;
jij = jindx[j] + i;
psc = pscore[jij];
qbt1 = 0.;
if (hard_constraints[jij]) {
/* process hairpin loop(s) */
qbt1 += vrna_exp_E_hp_loop(vc, i, j);
/* process interior loop(s) */
qbt1 += vrna_exp_E_int_loop(vc, i, j);
/* process multibranch loop(s) */
qbt1 += vrna_exp_E_mb_loop_fast(vc, i, j, aux_mx_ml->qqm1);
qbt1 *= exp(psc/kTn);
}
qb[ij] = qbt1;
/* Multibranch loop */
qm[ij] = vrna_exp_E_ml_fast(vc, i, j, aux_mx_ml);
if (qm1)
qm1[jindx[j] + i] = aux_mx_ml->qqm[i]; /* for stochastic backtracking and circfold */
/* Exterior loop */
q[ij] = temp = vrna_exp_E_ext_fast(vc, i, j, aux_mx_el);
if (temp > Qmax) {
Qmax = temp;
if (Qmax > max_real/10.)
vrna_message_warning("Q close to overflow: %d %d %g", i,j,temp);
}
if (temp >= max_real) {
vrna_message_error("overflow in pf_fold while calculating q[%d,%d]\n"
"use larger pf_scale", i,j);
}
}
/* rotate auxiliary arrays */
vrna_exp_E_ext_fast_rotate(vc, aux_mx_el);
vrna_exp_E_ml_fast_rotate(vc, aux_mx_ml);
}
/* free memory occupied by auxiliary arrays for fast exterior/multibranch loops */
vrna_exp_E_ml_fast_free(vc, aux_mx_ml);
vrna_exp_E_ext_fast_free(vc, aux_mx_el);
}
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];
}
}
}
PUBLIC vrna_fold_compound_t *
vrna_fold_compound_TwoD(const char *sequence,
const char *s1,
const char *s2,
vrna_md_t *md_p,
unsigned int options){
int length, l, turn;
vrna_fold_compound_t *vc;
vrna_md_t md;
if(sequence == NULL) return NULL;
/* sanity check */
length = strlen(sequence);
if(length == 0)
vrna_message_error("vrna_fold_compound_TwoD: sequence length must be greater 0");
l = strlen(s1);
if(l != length)
vrna_message_error("vrna_fold_compound_TwoD: sequence and s1 differ in length");
l = strlen(s2);
if(l != length)
vrna_message_error("vrna_fold_compound_TwoD: sequence and s2 differ in length");
vc = vrna_alloc(sizeof(vrna_fold_compound_t));
vc->type = VRNA_VC_TYPE_SINGLE;
vc->length = length;
vc->sequence = strdup(sequence);
/* get a copy of the model details */
if(md_p)
md = *md_p;
else /* this fallback relies on global parameters and thus is not threadsafe */
vrna_md_set_default(&md);
/* always make uniq ML decomposition ! */
md.uniq_ML = 1;
md.compute_bpp = 0;
set_fold_compound(vc, &md, options, WITH_PTYPE | WITH_PTYPE_COMPAT);
if(!(options & VRNA_OPTION_EVAL_ONLY)){
vrna_hc_init(vc); /* add default hard constraints */
/* add DP matrices */
vrna_mx_add(vc, VRNA_MX_2DFOLD, options);
}
/* set all fields that are unique to Distance class partitioning... */
turn = vc->params->model_details.min_loop_size;
vc->reference_pt1 = vrna_ptable(s1);
vc->reference_pt2 = vrna_ptable(s2);
vc->referenceBPs1 = vrna_refBPcnt_matrix(vc->reference_pt1, turn);
vc->referenceBPs2 = vrna_refBPcnt_matrix(vc->reference_pt2, turn);
vc->bpdist = vrna_refBPdist_matrix(vc->reference_pt1, vc->reference_pt2, turn);
/* compute maximum matching with reference structure 1 disallowed */
vc->mm1 = maximumMatchingConstraint(vc->sequence, vc->reference_pt1);
/* compute maximum matching with reference structure 2 disallowed */
vc->mm2 = maximumMatchingConstraint(vc->sequence, vc->reference_pt2);
vc->maxD1 = vc->mm1[vc->iindx[1]-length] + vc->referenceBPs1[vc->iindx[1]-length];
vc->maxD2 = vc->mm2[vc->iindx[1]-length] + vc->referenceBPs2[vc->iindx[1]-length];
return vc;
}
PUBLIC vrna_fold_compound_t *
vrna_fold_compound_comparative( const char **sequences,
vrna_md_t *md_p,
unsigned int options){
int s, n_seq, length;
vrna_fold_compound_t *vc;
vrna_md_t md;
unsigned int aux_options;
aux_options = 0L;
if(sequences == NULL) return NULL;
for(s=0;sequences[s];s++); /* count the sequences */
n_seq = s;
length = strlen(sequences[0]);
/* sanity check */
if(length == 0)
vrna_message_error("vrna_fold_compound_comparative: sequence length must be greater 0");
for(s = 0; s < n_seq; s++)
if(strlen(sequences[s]) != length)
vrna_message_error("vrna_fold_compound_comparative: uneqal sequence lengths in alignment");
vc = vrna_alloc(sizeof(vrna_fold_compound_t));
vc->type = VRNA_VC_TYPE_ALIGNMENT;
vc->n_seq = n_seq;
vc->length = length;
vc->sequences = vrna_alloc(sizeof(char *) * (vc->n_seq + 1));
for(s = 0; sequences[s]; s++)
vc->sequences[s] = strdup(sequences[s]);
/* get a copy of the model details */
if(md_p)
md = *md_p;
else /* this fallback relies on global parameters and thus is not threadsafe */
vrna_md_set_default(&md);
aux_options |= WITH_PTYPE;
if(options & VRNA_OPTION_PF)
aux_options |= WITH_PTYPE_COMPAT;
set_fold_compound(vc, &md, options, aux_options);
make_pscores(vc);
if(!(options & VRNA_OPTION_EVAL_ONLY)){
/* add default hard constraints */
vrna_hc_init(vc);
/* add DP matrices (if required) */
vrna_mx_add(vc, VRNA_MX_DEFAULT, options);
}
return vc;
}
PUBLIC vrna_fold_compound_t *
vrna_fold_compound( const char *sequence,
vrna_md_t *md_p,
unsigned int options){
unsigned int i, length, aux_options;
vrna_fold_compound_t *vc;
vrna_md_t md;
if(sequence == NULL) return NULL;
/* sanity check */
length = strlen(sequence);
if(length == 0)
vrna_message_error("vrna_fold_compound: sequence length must be greater 0");
vc = vrna_alloc(sizeof(vrna_fold_compound_t));
vc->type = VRNA_VC_TYPE_SINGLE;
vc->length = length;
vc->sequence = strdup(sequence);
aux_options = 0L;
/* get a copy of the model details */
if(md_p)
md = *md_p;
else
vrna_md_set_default(&md);
if(options & VRNA_OPTION_WINDOW){ /* sliding window structure prediction */
if(md.window_size <= 0)
md.window_size = (int)vc->length;
else if(md.window_size > (int)vc->length)
md.window_size = (int)vc->length;
vc->window_size = md.window_size;
if((md.max_bp_span <= 0) || (md.max_bp_span > md.window_size))
md.max_bp_span = md.window_size;
set_fold_compound(vc, &md, options, aux_options);
vc->ptype_local = vrna_alloc(sizeof(char *)*(vc->length+1));
for (i = vc->length; ( i > vc->length - vc->window_size - 5) && (i >= 0); i--){
vc->ptype_local[i] = vrna_alloc(sizeof(char)*(vc->window_size+5));
}
if(!(options & VRNA_OPTION_EVAL_ONLY)){
/* add default hard constraints */
/* vrna_hc_init(vc); */ /* no hard constraints in Lfold, yet! */
/* add DP matrices */
vrna_mx_add(vc, VRNA_MX_WINDOW, options);
}
} else { /* regular global structure prediction */
/* set window size to entire sequence */
md.window_size = (int)vc->length;
aux_options |= WITH_PTYPE;
if(options & VRNA_OPTION_PF)
aux_options |= WITH_PTYPE_COMPAT;
set_fold_compound(vc, &md, options, aux_options);
if(!(options & VRNA_OPTION_EVAL_ONLY)){
/* add default hard constraints */
vrna_hc_init(vc);
/* add DP matrices (if required) */
vrna_mx_add(vc, VRNA_MX_DEFAULT, options);
}
}
return vc;
}
int main(int argc, char *argv[])
{
int n,i,j,l;
int intty;
int outtty;
char *mask, junk[20];
char **s;
char **ss[4];
float *B;
float **dm;
Split *S;
Union *U;
char DistAlgorithm='H';
int nn[4];
short Do_Split=0, Do_Wards=0, Do_Stg=1, Do_4_Stg=0, Do_Nj=0, Do_Mat=0;
float per_digit, per_gap;
mask = vrna_alloc(sizeof(char)*54);
strcpy (mask,"%ABCDEFGHIJKLMNOPQRSTUVWXYZabcdefghijklmnopqrstuvwxyz");
for (i=1; i<argc; i++) {
if (argv[i][0]=='-') {
switch ( argv[i][1] ) {
case 'X':
if (argv[i][2]=='\0') { Do_Stg = 1 ; break; }
Do_Split = 0;
Do_Wards = 0;
Do_Stg = 0;
Do_Nj = 0;
for(j=2;j<strlen(argv[i]);j++) {
switch(argv[i][j]) {
case 's' : Do_Split = 1;
break;
case 'w' : Do_Wards = 1;
break;
case 'b' : Do_Stg = 1;
break;
case 'n' : Do_Nj = 1;
break;
case 'm' : Do_Mat = 1;
break;
default :
usage();
}
}
break;
case 'Q':
Do_4_Stg = 1;
break;
case 'M':
if(mask) { free(mask); mask = NULL; }
switch (argv[i][2] ) {
case '\0' :
usage();
break;
case 'a' :
mask = vrna_alloc(sizeof(char)*54);
strcpy(mask,
"%ABCDEFGHIJKLMNOPQRSTUVWabcdefghijklmnopqrstuvwxyz");
if(argv[i][3]=='+') mask[0] = '~'; /* make case sensitive */
break;
case 'u' :
mask = vrna_alloc(sizeof(char)*28);
strcpy(mask,"~ABCDEFGHIJKLMNOPQRSTUVW");
break;
case 'l' :
mask = vrna_alloc(sizeof(char)*28);
strcpy(mask,"~abcdefghijklmnopqrstuvwxyz");
break;
case 'c' :
mask = vrna_alloc(sizeof(char)*12);
strcpy(mask,"~1234567890");
break;
case 'n' :
mask = vrna_alloc(sizeof(char)*64);
strcpy (mask,
"%ABCDEFGHIJKLMNOPQRSTUVWabcdefghijklmnopqrstuvwxyz1234567890");
if(argv[i][3]=='+') mask[0] = '~'; /* make case sensitive */
break;
case 'R' : /* RNA */
mask = vrna_alloc(sizeof(char)*10);
strcpy(mask,"%GCAUgcau");
if(argv[i][3]=='+') mask[0] = '~'; /* make case sensitive */
break;
case 'D' : /* DNA */
mask = vrna_alloc(sizeof(char)*10);
strcpy (mask,"%GCATgcat");
if(argv[i][3]=='+') mask[0] = '~'; /* make case sensitive */
break;
case 'A' : /* AMINOACIDS */
mask = vrna_alloc(sizeof(char)*42);
strcpy(mask,"%ACDEFGHIKLMNPQRSTVWYacdefghiklmnpqrstvwy");
if(argv[i][3]=='+') mask[0] = '~'; /* make case sensitive */
break;
case 'S' : /* SECONDARY STRUCTURES */
mask = vrna_alloc(sizeof(char)*6);
strcpy(mask,"~().^");
break;
case '%' : /* ARBITRARY ALPHABETS */
l = strlen(argv[i]);
if(argv[i][l] == '+'){
mask = vrna_alloc(sizeof(char)*(l-2));
mask[0] = '~';
for(j=1;j<=l-4;j++) mask[j] = argv[i][j+2];
mask[l-3]='\0';
}
if(argv[i][l] == '!'){
mask = vrna_alloc(sizeof(char)*(l-2));
mask[0] = '!';
for(j=1;j<=l-4;j++) mask[j] = argv[i][j+2];
mask[l-3]='\0';
}
else {
mask = vrna_alloc(sizeof(char)*(l-1));
mask[0] = '%';
for(j=1;j<=l-3;j++) mask[j] = argv[i][j+2];
mask[l-2]='\0';
}
break;
default :
usage();
}
break;
case 'D' : /* choose algorithm */
switch(argv[i][2]) {
case '\0' :
usage();
break;
case 'H' :
DistAlgorithm = 'H';
break;
case 'A' :
DistAlgorithm = 'A';
if(argv[i][3]==',') {
per_digit=-1.;
sscanf(argv[i],"%[^,],%g",junk,&per_digit);
if(per_digit<0.) usage();
per_gap = per_digit;
Set_StrEdit_GapCosts(per_digit,per_gap);
}
break;
case 'G' :
DistAlgorithm = 'G';
if(argv[i][3]==',') {
per_digit=-1.;
per_gap =-1.;
sscanf(argv[i]+4,"%f,%f",&per_digit,&per_gap);
if((per_digit<0.)||(per_gap<0)) usage();
Set_StrEdit_GapCosts(per_digit,per_gap);
}
break;
default:
usage();
}
break;
case 'd' : /* choose distance matrix */
switch(argv[i][2]) {
case 'D' : /* Dayhoff Distances */
case 'A' : /* Aminoacid Distance (Hofacker & Borstnik) */
case 'B' : /* RY distances for nucleotides */
case 'H' : /* Hogeweg's Distance for Secondary Structures */
case 'S' : /* Simple Distance (superfluous option) */
Set_StrEdit_CostMatrix(argv[i][2]);
break;
default :
usage();
}
break;
default :
usage();
}
}
}
/* END PARSING OF COMMAND LINE */
intty = isatty(fileno(stdin));
outtty= isatty(fileno(stdout));
if(intty){
if(outtty) {
printf("Input sequences; @ to mark end of input\n");
printf("%s%s\n", scale1, scale2);
}
else {
fprintf(stderr,"Input sequences; @ to mark end of input\n");
fprintf(stderr,"%s%s\n", scale1, scale2);
}
}
while ((s=read_sequence_list(&n,mask))!=NULL) {
dm = NULL;
if(Do_4_Stg) {
ss[0] = s;
nn[0] = n;
for(i=1;i<4;i++) {
ss[i] = read_sequence_list(&n,mask);
if(ss[i]==NULL) vrna_message_error("read_sequences: wrong or insufficient data.");
nn[i] = n;
}
printf_taxa_list();
B = statgeom4(ss,nn);
printf_stg(B);
SimplifiedBox(B,"box.ps"); /* This is preliminary !!! */
free(B);
for(i=0;i<4;i++){
for(j=0;j<nn[i];j++) free(ss[i][j]);
free(ss[i]);
}
/* free(ss); */ /* attempt to free a non-heap object */
}
else {
printf_taxa_list();
if(Do_Stg) {
B = statgeom(s,n);
if (B) {
printf_stg(B);
SimplifiedBox(B,"box.ps");
free(B);
}
}
if((Do_Split)||(Do_Wards)||(Do_Nj)||(Do_Mat)) {
switch(DistAlgorithm) {
case 'H' :
dm = Hamming_Distance_Matrix(s,n);
printf("> %s\n","H (Hamming Distance)");
break;
case 'A' :
dm = StrEdit_SimpleDistMatrix(s,n);
printf("> %s\n","A (Needleman-Wunsch Distance)");
break;
case 'G' :
dm = StrEdit_GotohDistMatrix(s,n);
printf("> %s\n","G (Gotoh Distance)");
break;
default:
vrna_message_error("This can't happen.");
}
}
if(Do_Split) {
S = split_decomposition(dm);
sort_Split(S);
print_Split(S);
free_Split(S);
}
if(Do_Wards) {
U = wards_cluster(dm);
printf_phylogeny(U,"W");
PSplot_phylogeny(U,"wards.ps","Ward's Method");
free(U);
}
if(Do_Nj) {
U = neighbour_joining(dm);
printf_phylogeny(U,"Nj");
PSplot_phylogeny(U,"nj.ps","Neighbor Joining");
free(U);
}
if(Do_Mat) printf_distance_matrix(dm);
}
if (dm!=NULL) free_distance_matrix(dm);
for(i=0;i<n;i++) free(s[i]);
free(s);
}
return 0;
}
PUBLIC void
nrerror(const char message[]){
vrna_message_error(message);
}
int main(int argc, char *argv[]){
struct RNAplot_args_info args_info;
char *structure, *pre, *post;
char fname[FILENAME_MAX_LENGTH], ffname[FILENAME_MAX_LENGTH];
char *rec_sequence, *rec_id, **rec_rest;
int i, length;
int istty;
char format[5]="ps";
unsigned int rec_type, read_opt;
vrna_md_t md;
structure = pre = post = NULL;
length = 0;
vrna_md_set_default(&md);
/*
#############################################
# check the command line parameters
#############################################
*/
if(RNAplot_cmdline_parser (argc, argv, &args_info) != 0) exit(1);
if(args_info.layout_type_given) rna_plot_type = args_info.layout_type_arg;
if(args_info.pre_given) pre = strdup(args_info.pre_arg);
if(args_info.post_given) post = strdup(args_info.post_arg);
if(args_info.output_format_given){
strncpy(format, args_info.output_format_arg, 4); format[4] = '\0';
}
/* free allocated memory of command line data structure */
RNAplot_cmdline_parser_free (&args_info);
/*
#############################################
# begin initializing
#############################################
*/
rec_type = read_opt = 0;
rec_id = rec_sequence = NULL;
rec_rest = NULL;
istty = isatty(fileno(stdout)) && isatty(fileno(stdin));
/* set options we wanna pass to vrna_file_fasta_read_record() */
if(istty){
read_opt |= VRNA_INPUT_NOSKIP_BLANK_LINES;
vrna_message_input_seq("Input sequence (upper or lower case) followed by structure");
}
/*
#############################################
# main loop: continue until end of file
#############################################
*/
while(
!((rec_type = vrna_file_fasta_read_record(&rec_id, &rec_sequence, &rec_rest, NULL, read_opt))
& (VRNA_INPUT_ERROR | VRNA_INPUT_QUIT))){
if(rec_id){
(void) sscanf(rec_id, ">%" XSTR(FILENAME_ID_LENGTH) "s", fname);
}
else fname[0] = '\0';
length = (int)strlen(rec_sequence);
structure = vrna_extract_record_rest_structure((const char **)rec_rest, 0, (rec_id) ? VRNA_OPTION_MULTILINE : 0);
if(!structure) vrna_message_error("structure missing");
if((int)strlen(structure) != length) vrna_message_error("structure and sequence differ in length!");
if (fname[0]!='\0'){
strcpy(ffname, fname);
strcat(ffname, "_ss");
} else
strcpy(ffname, "rna");
structure = NULL;
unsigned int struct_options = (rec_id) ? VRNA_OPTION_MULTILINE : 0;
structure = vrna_extract_record_rest_structure((const char **)rec_rest, 0, struct_options);
if(strlen(rec_sequence) != strlen(structure))
vrna_message_error("sequence and structure have unequal length");
switch (format[0]) {
case 'p':
strcat(ffname, ".ps");
(void) vrna_file_PS_rnaplot_a(rec_sequence, structure, ffname, pre, post, &md);
break;
case 'g':
strcat(ffname, ".gml");
gmlRNA(rec_sequence, structure, ffname, 'x');
break;
case 'x':
strcat(ffname, ".ss");
xrna_plot(rec_sequence, structure, ffname);
break;
case 's':
strcat(ffname, ".svg");
svg_rna_plot(rec_sequence, structure, ffname);
break;
default:
RNAplot_cmdline_parser_print_help(); exit(EXIT_FAILURE);
}
fflush(stdout);
/* clean up */
if(rec_id) free(rec_id);
free(rec_sequence);
free(structure);
/* free the rest of current dataset */
if(rec_rest){
for(i=0;rec_rest[i];i++) free(rec_rest[i]);
free(rec_rest);
}
rec_id = rec_sequence = structure = NULL;
rec_rest = NULL;
/* print user help for the next round if we get input from tty */
if(istty){
vrna_message_input_seq("Input sequence (upper or lower case) followed by structure");
}
}
return EXIT_SUCCESS;
}