int main(int argc, char *argv[]) {
char c;
int opt_idx;
Vector *newfreqs = vec_new(4);
TreeModel *mod;
struct option long_opts[] = {
{"help", 0, 0, 'h'},
{0, 0, 0, 0}
};
while ((c = getopt_long(argc, argv, "h", long_opts, &opt_idx)) != -1) {
switch (c) {
case 'h':
printf("%s", HELP);
exit(0);
case '?':
die("Bad argument. Try 'modFreqs -h'.\n");
}
}
if (optind != argc - 2 && optind != argc - 5)
die("ERROR: Wrong number of arguments. Try 'modFreqs -h'.\n");
set_seed(-1);
mod = tm_new_from_file(phast_fopen(argv[optind], "r"), 1);
if (!tm_is_reversible(mod))
die("ERROR: reversible input model required.\n");
if (mod->order != 0)
die("ERROR: single nucleotide model required.\n");
if (strcmp(mod->rate_matrix->states, DEFAULT_ALPHABET) != 0)
die("ERROR: default nucleotide alphabet required.\n");
if (optind == argc - 2) {
double gc = get_arg_dbl_bounds(argv[optind+1], 0, 1);
vec_set(newfreqs, 0, (1-gc)/2);
vec_set(newfreqs, 1, gc/2);
vec_set(newfreqs, 2, gc/2);
vec_set(newfreqs, 3, (1-gc)/2);
}
else {
vec_set(newfreqs, 0, get_arg_dbl_bounds(argv[optind+1], 0, 1));
vec_set(newfreqs, 1, get_arg_dbl_bounds(argv[optind+2], 0, 1));
vec_set(newfreqs, 2, get_arg_dbl_bounds(argv[optind+3], 0, 1));
vec_set(newfreqs, 3, get_arg_dbl_bounds(argv[optind+4], 0, 1));
pv_normalize(newfreqs);
}
tm_mod_freqs(mod, newfreqs);
tm_print(stdout, mod);
return 0;
}
int main(int argc, char *argv[]) {
char c;
int i, j, t, opt_idx, ntrees, nleaves = -1;
TreeNode *n, *node_i, *node_j, *lca, *nametree = NULL;
TreeNode **tree;
List *leaves, ***distance, *tree_fnames, *tot_dist;
int mod = FALSE;
char **leaf_name;
String *trees_arg;
FILE *F;
struct option long_opts[] = {
{"mod", 0, 0, 'm'},
{"tree", 1, 0, 't'},
{"help", 0, 0, 'h'},
{0, 0, 0, 0}
};
while ((c = getopt_long(argc, argv, "mt:h", long_opts, &opt_idx)) != -1) {
switch (c) {
case 'm':
mod = TRUE;
break;
case 't':
if (optarg[0] == '(')
nametree = tr_new_from_string(optarg);
else
nametree = tr_new_from_file(phast_fopen(optarg, "r"));
break;
case 'h':
usage(argv[0]);
case '?':
die("Bad argument. Try '%s -h'.\n", argv[0]);
}
}
if (optind > argc - 1)
die("Input filename required. Try '%s -h'.\n", argv[0]);
set_seed(-1);
/* build a comma-delimited list and pass to get_arg_list; allows
possibility of reading from file via '*' operator */
trees_arg = str_new(1000);
for (i = optind; i < argc; i++) {
str_append_charstr(trees_arg, argv[i]);
if (i < argc - 1) str_append_char(trees_arg, ',');
}
tree_fnames = get_arg_list(trees_arg->chars);
ntrees = lst_size(tree_fnames);
tree = smalloc(ntrees * sizeof(void*));
/* read trees */
for (t = 0; t < ntrees; t++) {
String *fname = lst_get_ptr(tree_fnames, t);
if (mod) {
TreeModel *m = tm_new_from_file(F = phast_fopen(fname->chars, "r"), 1);
tree[t] = tr_create_copy(m->tree);
tm_free(m);
phast_fclose(F);
}
else
tree[t] = tr_new_from_file(phast_fopen(fname->chars, "r"));
}
/* initialization */
nleaves = (tree[0]->nnodes + 1)/2;
leaves = lst_new_ptr(nleaves);
distance = smalloc(nleaves * sizeof(void*));
leaf_name = smalloc(nleaves * sizeof(void*));
for (i = 0; i < nleaves; i++) {
distance[i] = smalloc(nleaves * sizeof(void*));
for (j = i+1; j < nleaves; j++)
distance[i][j] = lst_new_dbl(ntrees);
}
if (nametree == NULL) nametree = tree[0];
for (i = 0, j = 0; i < lst_size(nametree->nodes); i++) {
n = lst_get_ptr(nametree->nodes, i);
if (n->lchild == NULL && n->rchild == NULL)
leaf_name[j++] = n->name;
}
tot_dist = lst_new_dbl(ntrees);
/* now compute distances */
for (t = 0; t < ntrees; t++) {
/* obtain list of leaves */
lst_clear(leaves);
for (i = 0; i < lst_size(tree[t]->nodes); i++) {
n = lst_get_ptr(tree[t]->nodes, i);
if (n->lchild == NULL && n->rchild == NULL)
lst_push_ptr(leaves, n);
}
if (lst_size(leaves) != nleaves)
die("ERROR: trees have different numbers of leaves.\n");
/* look at all pairs */
for (i = 0; i < nleaves; i++) {
node_i = lst_get_ptr(leaves, i);
for (j = i+1; j < nleaves; j++) {
double dist = 0;
node_j = lst_get_ptr(leaves, j);
/* because ids are assigned in pre-order, the first ancestor of
node j that has an id less than i is the LCA of i and j; we
seek the sum of distances from both i and j to this node */
for (n = node_j; n->id >= node_i->id; n = n->parent)
dist += n->dparent;
lca = n;
for (n = node_i; n != lca; n = n->parent)
dist += n->dparent;
lst_push_dbl(distance[i][j], dist);
}
}
lst_push_dbl(tot_dist, tr_total_len(tree[t]));
}
/* print distances and (optionally) stats */
if (ntrees == 1) {
for (i = 0; i < nleaves; i++) {
for (j = i+1; j < nleaves; j++) {
printf ("%s\t%s\t%f\n", leaf_name[i], leaf_name[j],
lst_get_dbl(distance[i][j], 0));
}
}
printf ("%s\t%s\t%f\n", "(total)", "-", lst_get_dbl(tot_dist, 0));
}
else {
double mean, stdev;
double quantiles[] = {0, 0.025, 0.05, 0.5, 0.95, 0.975, 1};
double quantile_vals[7];
printf("%-15s %-15s %9s %9s %9s %9s %9s %9s %9s %9s %9s\n", "leaf1",
"leaf2", "mean", "stdev", "median", "min", "max", "95%_min",
"95%_max", "90%_min", "90%_max");
for (i = 0; i < nleaves; i++) {
for (j = i+1; j < nleaves; j++) {
mean = lst_dbl_mean(distance[i][j]);
stdev = lst_dbl_stdev(distance[i][j]);
lst_qsort_dbl(distance[i][j], ASCENDING);
lst_dbl_quantiles(distance[i][j], quantiles, 7, quantile_vals);
printf("%-15s %-15s %9.5f %9.5f %9.5f %9.5f %9.5f %9.5f %9.5f %9.5f %9.5f\n",
leaf_name[i], leaf_name[j], mean, stdev, quantile_vals[3], quantile_vals[0],
quantile_vals[6], quantile_vals[1], quantile_vals[5], quantile_vals[2],
quantile_vals[4]);
}
}
/* also do total branch len */
mean = lst_dbl_mean(tot_dist);
stdev = lst_dbl_stdev(tot_dist);
lst_qsort_dbl(tot_dist, ASCENDING);
lst_dbl_quantiles(tot_dist, quantiles, 7, quantile_vals);
printf("%-15s %-15s %9.5f %9.5f %9.5f %9.5f %9.5f %9.5f %9.5f %9.5f %9.5f\n",
"(total)", "-", mean, stdev, quantile_vals[3], quantile_vals[0],
quantile_vals[6], quantile_vals[1], quantile_vals[5], quantile_vals[2],
quantile_vals[4]);
}
return 0;
}
int main(int argc, char *argv[]) {
FILE *infile;
char c;
int opt_idx;
msa_format_type msa_format;
struct bgchmm_struct *b = bgchmm_struct_new(0);
struct option long_opts[] = {
{"bgc", 1, 0, 'B'},
{"estimate-bgc", 1, 0, 'b'},
{"bgc-exp-length", 1, 0, 'L'},
{"estimate-bgc-exp-length", 1, 0, 'l'},
{"bgc-target-coverage", 1, 0, 'C'},
{"estimate-bgc-target-coverage", 1, 0, 'c'},
{"rho", 1, 0, 'R'},
{"cons-exp-length", 1, 0, 'E'},
{"cons-target-coverage", 1, 0, 'T'},
{"scale", 1, 0, 'S'},
{"estimate-scale", 1, 0, 's'},
{"eqfreqs-from-msa", 1, 0, 'f'},
{"output-tracts", 1, 0, 'g'},
{"posteriors", 1, 0, 'p'},
{"output-mods", 1, 0, 'm'},
{"help", 0, 0, 'h'},
{0,0,0,0}};
while ((c = getopt_long(argc, argv, "B:b:L:l:C:c:R:E:T:S:s:f:g:p:m:Wh", long_opts, &opt_idx))
!= -1) {
switch (c) {
case 'B':
b->bgc = get_arg_dbl_bounds(optarg, 0, INFTY);
break;
case 'b':
b->estimate_bgc = get_arg_int_bounds(optarg, 0, 1);
break;
case 'L':
b->bgc_expected_length = get_arg_dbl_bounds(optarg, 0, INFTY);
break;
case 'l':
b->estimate_bgc_expected_length = get_arg_int_bounds(optarg, 0, 1);
break;
case 'C':
b->bgc_target_coverage = get_arg_dbl_bounds(optarg, 0, 1);
break;
case 'c':
b->estimate_bgc_target_coverage = get_arg_int_bounds(optarg, 0, 1);
break;
case 'R':
b->rho = get_arg_dbl_bounds(optarg, 0, INFTY);
if (b->rho > 1.0) phast_warning("Warning: rho is a scale for conserved states and is usually less than 1, got %f", b->rho);
break;
case 'E':
b->cons_expected_length = get_arg_dbl_bounds(optarg, 0, INFTY);
break;
case 'T':
b->cons_target_coverage = get_arg_dbl_bounds(optarg, 0, 1);
break;
case 'S':
b->scale = get_arg_dbl_bounds(optarg, 0, INFTY);
break;
case 's':
b->estimate_scale = get_arg_int_bounds(optarg, 0, 1);
break;
case 'f':
b->eqfreqs_from_msa = get_arg_int_bounds(optarg, 0, 1);
break;
case 'g':
b->tract_fn = optarg;
break;
case 'p':
if (strcasecmp(optarg, "none")==0)
b->post_probs = NONE;
else if (strcasecmp(optarg, "wig")==0)
b->post_probs = WIG;
else if (strcasecmp(optarg, "full")==0)
b->post_probs = FULL;
else die("--posteriors option expects either none, wig, or full, got %s", optarg);
break;
case 'm':
b->mods_fn = optarg;
break;
case 'W':
b->post_probs = NONE;
break;
case 'h':
printf("%s", HELP);
exit(0);
case '?':
default:
die("Bad argument. Try '%s -h'.\n", argv[0]);
}
}
if (optind != argc - 3)
die("ERROR: extra or missing arguments. Try '%s -h'.\n", argv[0]);
/* read the MSA and make sure there are no sufficient stats (we want to get these
later depending on whether coding/noncoding, tuple size will be 3 or 1)
*/
infile = phast_fopen(argv[optind], "r");
msa_format = msa_format_for_content(infile, 1);
if (msa_format == MAF)
b->msa = maf_read(infile, NULL, 1, NULL, NULL, NULL, 0, 1, NULL, NO_STRIP, 0);
else b->msa = msa_new_from_file_define_format(infile, msa_format, NULL);
fclose(infile);
infile = phast_fopen(argv[optind+1], "r");
b->mod = tm_new_from_file(infile, 1);
fclose(infile);
b->foregd_branch = argv[optind+2];
bgcHmm(b);
return 0;
}
int main(int argc, char *argv[]) {
char c;
int opt_idx, node;
FILE *out_f = NULL, *msa_f, *mod_f;
char *out_root;
TreeModel *mod;
MSA *msa;
char out_fname[STR_MED_LEN];
struct option long_opts[] = {
{"refseq", 1, 0, 'r'},
{"msa-format", 1, 0, 'i'},
{"seqs", 1, 0, 's'},
{"exclude", 0, 0, 'x'},
{"no-probs", 0, 0, 'n'},
{"suff-stats", 0, 0, 'S'},
{"encode", 1, 0, 'e'},
{"keep-gaps", 0, 0, 'k'},
{"gibbs", 1, 0, 'G'},
{"help", 0, 0, 'h'},
{0, 0, 0, 0}
};
/* arguments and defaults for options */
FILE *refseq_f = NULL;
msa_format_type msa_format = UNKNOWN_FORMAT;
int suff_stats = FALSE, exclude = FALSE, keep_gaps = FALSE, do_probs = TRUE;
List *seqlist = NULL;
PbsCode *code = NULL;
int gibbs_nsamples = -1;
while ((c = (char)getopt_long(argc, argv, "r:i:s:e:knxSh", long_opts, &opt_idx)) != -1) {
switch (c) {
case 'r':
refseq_f = phast_fopen(optarg, "r");
break;
case 'i':
msa_format = msa_str_to_format(optarg);
if (msa_format == UNKNOWN_FORMAT)
die("ERROR: unrecognized alignment format.\n");
break;
case 'S':
suff_stats = TRUE;
break;
case 'e':
code = pbs_new_from_file(phast_fopen(optarg, "r"));
break;
case 's':
seqlist = get_arg_list(optarg);
break;
case 'x':
exclude = TRUE;
break;
case 'n':
do_probs = FALSE;
break;
case 'k':
keep_gaps = TRUE;
break;
case 'G':
gibbs_nsamples = get_arg_int_bounds(optarg, 1, INFTY);
break;
case 'h':
printf("%s", HELP);
exit(0);
case '?':
die("Bad argument. Try 'prequel -h'.\n");
}
}
if (optind != argc - 3)
die("Three arguments required. Try 'prequel -h'.\n");
set_seed(-1);
if (!do_probs && (suff_stats || code != NULL))
die("ERROR: --no-probs can't be used with --suff-stats or --encode.\n");
msa_f = phast_fopen(argv[optind], "r");
if (msa_format == UNKNOWN_FORMAT)
msa_format = msa_format_for_content(msa_f, 1);
fprintf(stderr, "Reading alignment from %s...\n", argv[optind]);
if (msa_format == MAF) {
msa = maf_read(msa_f, refseq_f, 1, NULL, NULL, NULL, -1, !suff_stats, NULL,
NO_STRIP, FALSE);
/* (no need to store order if suff_stats mode) */
}
else
msa = msa_new_from_file_define_format(msa_f, msa_format, NULL);
if (msa->ss == NULL) {
fprintf(stderr, "Extracting sufficient statistics...\n");
ss_from_msas(msa, 1, TRUE, NULL, NULL, NULL, -1, 0);
}
else if (msa->ss->tuple_idx == NULL && !suff_stats)
die("ERROR: ordered representation of alignment required unless --suff-stats.\n");
mod_f = phast_fopen(argv[optind+1], "r");
out_root = argv[optind+2];
mod = tm_new_from_file(mod_f, 1);
/* MH prune just like in phastcons */
int old_nnodes = mod->tree->nnodes;
List *pruned_names = lst_new_ptr(msa->nseqs);
tm_prune(mod, msa, pruned_names);
if (lst_size(pruned_names) == (old_nnodes + 1) / 2)
die("ERROR: no match for leaves of tree in alignment (leaf names must match alignment names).\n");
if (lst_size(pruned_names) > 0) {
fprintf(stderr, "WARNING: pruned away leaves of tree with no match in alignment (");
int j;
for (j = 0; j < lst_size(pruned_names); j++)
fprintf(stderr, "%s%s", ((String*)lst_get_ptr(pruned_names, j))->chars, j < lst_size(pruned_names) - 1 ? ", " : ").\n");
}
lst_free_strings(pruned_names);
tr_name_ancestors(mod->tree);
if (mod->order != 0)
die("ERROR: Only single nucleotide models are supported.\n");
if (mod->nratecats > 1)
die("ERROR: Rate variation not supported.\n");
mod->tree_posteriors = tl_new_tree_posteriors(mod, msa, TRUE, FALSE,
FALSE, FALSE, FALSE, FALSE,
FALSE);
fprintf(stderr, "Computing posterior probabilities...\n");
if (gibbs_nsamples > 0)
die("ERROR: --gibbs not implemented yet.");
/* gb_sample_ancestral_seqs(mod, msa, mod->tree_posteriors, gibbs_nsamples); */
else
tl_compute_log_likelihood(mod, msa, NULL, NULL, -1, mod->tree_posteriors);
fprintf(stderr, "Reconstructing indels by parsimony...\n");
do_indels(msa, mod);
for (node = 0; node < mod->tree->nnodes; node++) {
int i, j;
TreeNode *n = lst_get_ptr(mod->tree->nodes, node);
if (n->lchild == NULL || n->rchild == NULL) continue;
if (seqlist != NULL) {
int in_list = str_in_list_charstr(n->name, seqlist);
if ((in_list && exclude) || (!in_list && !exclude))
continue;
}
fprintf(stderr, "Writing output for ancestral node '%s'...\n",
n->name);
if (suff_stats) {
if (out_f == NULL) {
sprintf(out_fname, "%s.stats", out_root);
out_f = phast_fopen(out_fname, "w+");
fprintf(out_f, "#count\t");
for (j = 0; j < mod->rate_matrix->size; j++)
fprintf(out_f, "p(%c)%c", mod->rate_matrix->states[j],
j == mod->rate_matrix->size - 1 ? '\n' : '\t');
}
for (i = 0; i < msa->ss->ntuples; i++) {
if (mod->tree_posteriors->base_probs[0][0][node][i] == -1)
continue; /* no base this node */
fprintf(out_f, "%.0f\t", msa->ss->counts[i]);
for (j = 0; j < mod->rate_matrix->size; j++) {
fprintf(out_f, "%f%c",
mod->tree_posteriors->base_probs[0][j][node][i],
j == mod->rate_matrix->size - 1 ? '\n' : '\t');
}
}
}
else if (code == NULL && do_probs) { /* ordinary sequence-by-sequence
output */
sprintf(out_fname, "%s.%s.probs", out_root, n->name);
out_f = phast_fopen(out_fname, "w+");
fprintf(out_f, "#");
for (j = 0; j < mod->rate_matrix->size; j++)
fprintf(out_f, "p(%c)%c", mod->rate_matrix->states[j],
j == mod->rate_matrix->size - 1 ? '\n' : '\t');
for (i = 0; i < msa->length; i++) {
if (mod->tree_posteriors->base_probs[0][0][node][msa->ss->tuple_idx[i]] == -1) {
/* no base */
if (keep_gaps) fprintf(out_f, "-\n");
/* otherwise do nothing */
}
else
for (j = 0; j < mod->rate_matrix->size; j++)
fprintf(out_f, "%f%c",
mod->tree_posteriors->base_probs[0][j][node][msa->ss->tuple_idx[i]],
j == mod->rate_matrix->size - 1 ? '\n' : '\t');
}
phast_fclose(out_f);
}
else if (code == NULL && !do_probs) { /* write point estimates
to FASTA file */
char *outseq = smalloc((msa->length + 1) * sizeof(char));
int len = 0;
for (i = 0; i < msa->length; i++) {
if (mod->tree_posteriors->base_probs[0][0][node][msa->ss->tuple_idx[i]] == -1) {
/* no base */
if (keep_gaps) outseq[len++] = GAP_CHAR;
/* otherwise do nothing */
}
else {
double maxprob = 0;
int maxidx = -1;
for (j = 0; j < mod->rate_matrix->size; j++) {
if (mod->tree_posteriors->base_probs[0][j][node][msa->ss->tuple_idx[i]] > maxprob) {
maxprob = mod->tree_posteriors->base_probs[0][j][node][msa->ss->tuple_idx[i]];
maxidx = j;
}
}
outseq[len++] = mod->rate_matrix->states[maxidx];
}
}
outseq[len] = '\0';
/* print in FASTA format */
sprintf(out_fname, "%s.%s.fa", out_root, n->name);
out_f = phast_fopen(out_fname, "w+");
print_seq_fasta(out_f, outseq, n->name, len);
phast_fclose(out_f);
sfree(outseq);
}
else { /* encoded sequence-by-sequence
output */
double error, tot_error = 0;
int ngaps = 0;
Vector *v;
unsigned *encoded;
/* first encode tuple by tuple */
v = vec_new(mod->rate_matrix->size);
encoded = smalloc(msa->ss->ntuples * sizeof(unsigned));
for (i = 0; i < msa->ss->ntuples; i++) {
if (mod->tree_posteriors->base_probs[0][0][node][i] == -1) {
encoded[i] = code->gap_code;
ngaps += msa->ss->counts[i];
}
else {
for (j = 0; j < mod->rate_matrix->size; j++)
vec_set(v, j, mod->tree_posteriors->base_probs[0][j][node][i]);
encoded[i] = pbs_get_index(code, v, &error);
tot_error += error * msa->ss->counts[i];
}
}
vec_free(v);
/* now write site by site */
sprintf(out_fname, "%s.%s.bin", out_root, n->name);
out_f = phast_fopen(out_fname, "w+");
for (i = 0; i < msa->length; i++) {
if (keep_gaps || encoded[msa->ss->tuple_idx[i]] != code->gap_code)
pbs_write_binary(code, encoded[msa->ss->tuple_idx[i]], out_f);
}
fprintf(stderr, "Average approximation error ('%s'): %f bits\n",
n->name, tot_error/(msa->length - ngaps));
sfree(encoded);
}
}
fprintf(stderr, "Done.\n");
return 0;
}
int main(int argc, char *argv[]) {
char *msa_fname = NULL, *alph = "ACGT";
msa_format_type input_format = UNKNOWN_FORMAT;
char c;
int opt_idx, seed=-1;
String *optstr;
List *tmplist = NULL;
struct phyloFit_struct *pf;
FILE *infile;
struct option long_opts[] = {
{"msa", 1, 0, 'm'},
{"tree", 1, 0, 't'},
{"subst-mod", 1, 0, 's'},
{"msa-format", 1, 0, 'i'},
{"nrates", 1, 0, 'k'},
{"alpha", 1, 0, 'a'},
{"features", 1, 0, 'g'},
{"catmap", 1, 0, 'c'},
{"log", 1, 0, 'l'},
{"out-root", 1, 0, 'o'},
{"EM", 0, 0, 'E'},
{"error", 1, 0, 'e'},
{"precision", 1, 0, 'p'},
{"do-cats", 1, 0, 'C'},
{"non-overlapping", 0, 0, 'V'},
{"markov", 0, 0, 'N'},
{"reverse-groups", 1, 0, 'R'},
{"init-model", 1, 0, 'M'},
{"init-random", 0, 0, 'r'},
{"init-parsimony", 0, 0, 'y'},
{"print-parsimony", 1, 0, 'Y'},
{"lnl", 0, 0, 'L'},
{"scale-only", 0, 0, 'B'},
{"scale-subtree", 1, 0, 'S'},
{"estimate-freqs", 0, 0, 'F'},
{"sym-freqs", 0, 0, 'W'},
{"no-freqs", 0, 0, 'f'},
{"no-rates", 0, 0, 'n'},
{"no-opt", 1, 0, 'O'},
{"min-informative", 1, 0, 'I'},
{"gaps-as-bases", 0, 0, 'G'},
{"quiet", 0, 0, 'q'},
{"help", 0, 0, 'h'},
{"windows", 1, 0, 'w'},
{"windows-explicit", 1, 0, 'v'},
{"ancestor", 1, 0, 'A'},
{"post-probs", 0, 0, 'P'},
{"expected-subs", 0, 0, 'X'},
{"expected-total-subs", 0, 0, 'Z'},
{"expected-subs-col", 0, 0, 'J'},
{"column-probs", 0, 0, 'U'},
{"rate-constants", 1, 0, 'K'},
{"ignore-branches", 1, 0, 'b'},
{"clock", 0, 0, 'z'},
{"alt-model", 1, 0, 'd'},
{"label-branches", 1, 0, 0},
{"label-subtree", 1, 0, 0},
{"selection", 1, 0, 0},
{"bound", 1, 0, 'u'},
{"seed", 1, 0, 'D'},
{0, 0, 0, 0}
};
// NOTE: remaining shortcuts left: HjQx
pf = phyloFit_struct_new(0);
while ((c = (char)getopt_long(argc, argv, "m:t:s:g:c:C:i:o:k:a:l:w:v:M:p:A:I:K:S:b:d:O:u:Y:e:D:GVENRqLPXZUBFfnrzhWyJ", long_opts, &opt_idx)) != -1) {
switch(c) {
case 'm':
msa_fname = optarg;
break;
case 't':
if (optarg[0] == '(') /* in this case, assume topology given
at command line */
pf->tree = tr_new_from_string(optarg);
else
pf->tree = tr_new_from_file(phast_fopen(optarg, "r"));
break;
case 's':
pf->subst_mod = tm_get_subst_mod_type(optarg);
if (pf->subst_mod == UNDEF_MOD)
die("ERROR: illegal substitution model. Type \"phyloFit -h\" for usage.\n");
break;
case 'g':
pf->gff = gff_read_set(phast_fopen(optarg, "r"));
break;
case 'c':
pf->cm = cm_new_string_or_file(optarg);
break;
case 'C':
pf->cats_to_do_str = get_arg_list(optarg);
break;
case 'V':
pf->nonoverlapping = TRUE;
break;
case 'o':
pf->output_fname_root = optarg;
break;
case 'k':
pf->nratecats = get_arg_int_bounds(optarg, 0, INFTY);
break;
case 'a':
pf->alpha = get_arg_dbl(optarg);
break;
case 'R':
pf->reverse_group_tag = optarg;
break;
case 'i':
input_format = msa_str_to_format(optarg);
if (input_format == UNKNOWN_FORMAT)
die("ERROR: unrecognized alignment format. Type 'phyloFit -h' for usage.\n");
break;
case 'l':
if (!strcmp(optarg, "-"))
pf->logf = stderr;
else pf->logf = phast_fopen(optarg, "w+");
break;
case 'N':
pf->use_conditionals = 1;
break;
case 'w':
tmplist = get_arg_list(optarg);
if (lst_size(tmplist) != 2 ||
str_as_int(lst_get_ptr(tmplist, 0), &(pf->window_size)) != 0 ||
str_as_int(lst_get_ptr(tmplist, 1), &(pf->window_shift)) != 0)
die("ERROR: illegal arguments to --windows.\n");
lst_free_strings(tmplist);
lst_free(tmplist);
break;
case 'v':
tmplist = get_arg_list(optarg);
if (lst_size(tmplist) % 2 != 0)
die("ERROR: argument to --windows-explicit must be a list of even length.\n");
pf->window_coords = str_list_as_int(tmplist);
lst_free(tmplist);
break;
case 'E':
pf->use_em = TRUE;
break;
case 'e':
pf->error_fname=optarg;
break;
case 'p':
if (!strcmp(optarg, "LOW")) pf->precision = OPT_LOW_PREC;
else if (!strcmp(optarg, "MED")) pf->precision = OPT_MED_PREC;
else if (!strcmp(optarg, "HIGH")) pf->precision = OPT_HIGH_PREC;
else if (!strcmp(optarg, "VERY_HIGH")) pf->precision = OPT_VERY_HIGH_PREC;
else die("ERROR: --precision must be LOW, MED, or HIGH.\n\n");
break;
case 'M':
pf->input_mod = tm_new_from_file(phast_fopen(optarg, "r"), 1);
break;
case 'r':
pf->random_init = TRUE;
break;
case 'y':
pf->init_parsimony = TRUE;
break;
case 'Y':
pf->init_parsimony = TRUE;
pf->parsimony_cost_fname = optarg;
pf->parsimony_only=TRUE;
break;
case 'L':
pf->likelihood_only = TRUE;
break;
case 'q':
pf->quiet = TRUE;
break;
case 'P':
pf->do_bases = TRUE;
break;
case 'X':
pf->do_expected_nsubst = TRUE;
break;
case 'Z':
pf->do_expected_nsubst_tot = TRUE;
break;
case 'J':
pf->do_expected_nsubst_col = TRUE;
break;
case 'U':
pf->likelihood_only = TRUE; /* force -L */
pf->nsites_threshold = 0; /* also force this; typical use is
with small number of tuples, no
tuple_idx */
pf->do_column_probs = TRUE;
break;
case 'A':
pf->root_seqname = optarg;
break;
case 'I':
pf->nsites_threshold = get_arg_int(optarg);
break;
case 'G':
pf->gaps_as_bases = TRUE;
alph = "ACGT-";
break;
case 'B':
pf->estimate_scale_only = TRUE;
break;
case 'S':
pf->subtree_name = optarg;
break;
case 'F':
pf->estimate_backgd = TRUE;
break;
case 'W':
pf->estimate_backgd = TRUE;
pf->symfreq = TRUE;
break;
case 'f':
pf->no_freqs = TRUE;
break;
case 'n':
pf->no_rates = TRUE;
break;
case 'K':
tmplist = get_arg_list(optarg);
pf->rate_consts = str_list_as_dbl(tmplist);
pf->nratecats = lst_size(pf->rate_consts);
pf->use_em = 1;
lst_free_strings(tmplist); lst_free(tmplist);
break;
case 'b':
pf->ignore_branches = get_arg_list(optarg);
break;
case 'z':
pf->assume_clock = TRUE;
break;
case 'O':
if (pf->nooptstr == NULL)
pf->nooptstr = str_new_charstr(optarg);
else die("ERROR: no-opt argument can only be used once! parameters can be comma-separated list.");
break;
case 'd':
if (pf->alt_mod_str == NULL) {
pf->alt_mod_str = lst_new_ptr(1);
}
optstr = str_new_charstr(optarg);
lst_push_ptr(pf->alt_mod_str, optstr);
break;
case 0:
if (strcmp(long_opts[opt_idx].name, "label-branches") == 0 ||
strcmp(long_opts[opt_idx].name, "label-subtree") == 0) {
optstr = str_new_charstr(optarg);
if (pf->label_str == NULL) {
pf->label_str = lst_new_ptr(3);
pf->label_type = lst_new_int(3);
}
lst_push_ptr(pf->label_str, optstr);
lst_push_int(pf->label_type,
strcmp(long_opts[opt_idx].name, "label-branches") == 0 ?
BRANCH_TYPE : SUBTREE_TYPE);
}
else if (strcmp(long_opts[opt_idx].name, "selection") == 0) {
pf->selection = get_arg_dbl(optarg);
pf->use_selection = TRUE;
}
else {
die("ERROR: unknown option. Type 'phyloFit -h' for usage.\n");
}
break;
case 'u':
if (pf->bound_arg == NULL)
pf->bound_arg = lst_new_ptr(1);
optstr = str_new_charstr(optarg);
lst_push_ptr(pf->bound_arg, optstr);
break;
case 'D':
seed = get_arg_int_bounds(optarg, 1, INFTY);
break;
case 'h':
printf("%s", HELP);
exit(0);
case '?':
die("ERROR: illegal argument. Type 'phyloFit -h' for usage.\n");
}
}
set_seed(seed);
if (msa_fname == NULL) {
if (optind >= argc)
die("ERROR: missing alignment filename. Type 'phyloFit -h' for usage.\n");
msa_fname = argv[optind];
pf->msa_fname = msa_fname;
}
infile = phast_fopen(msa_fname, "r");
if (input_format == UNKNOWN_FORMAT)
input_format = msa_format_for_content(infile, 1);
if (pf->nonoverlapping && (pf->use_conditionals || pf->gff != NULL ||
pf->cats_to_do_str || input_format == SS))
die("ERROR: cannot use --non-overlapping with --markov, --features,\n--msa-format SS, or --do-cats.\n");
/* read alignment */
if (!pf->quiet) fprintf(stderr, "Reading alignment from %s ...\n", msa_fname);
if (input_format == MAF) {
pf->msa = maf_read(infile, NULL,
tm_order(pf->subst_mod) + 1,
NULL, pf->gff, pf->cm,
pf->nonoverlapping ? tm_order(pf->subst_mod) + 1 : -1,
FALSE, pf->reverse_group_tag, NO_STRIP, FALSE);
if (pf->gaps_as_bases)
msa_reset_alphabet(pf->msa, alph);
}
else
pf->msa = msa_new_from_file_define_format(infile,
input_format, alph);
/* set up for categories */
/* first label sites, if necessary */
pf->label_categories = (input_format != MAF);
run_phyloFit(pf);
if (pf->logf != NULL && pf->logf != stderr && pf->logf != stdout)
phast_fclose(pf->logf);
if (!pf->quiet) fprintf(stderr, "Done.\n");
sfree(pf);
return 0;
}
int main(int argc, char *argv[]) {
List *pruned_names = lst_new_ptr(5);
TreeModel *source_mod;
MSA *msa = NULL, *out_msa;
IndelHistory *ih;
char *read_hist_fname = NULL;
char c;
int opt_idx, old_nnodes, i;
msa_format_type msa_format = UNKNOWN_FORMAT;
int output_alignment = FALSE, ia_names = FALSE;
struct option long_opts[] = {
{"msa-format", 1, 0, 'i'},
{"output-alignment", 0, 0, 'A'},
{"read-history", 1, 0, 'H'},
{"ia-names", 0, 0, 'I'},
{"help", 0, 0, 'h'},
{0, 0, 0, 0}
};
while ((c = getopt_long(argc, argv, "i:H:AIh", long_opts, &opt_idx)) != -1) {
switch (c) {
case 'i':
msa_format = msa_str_to_format(optarg);
if (msa_format == -1)
die("ERROR: unrecognized alignment format.\n");
break;
case 'A':
output_alignment = TRUE;
break;
case 'H':
read_hist_fname = optarg;
break;
case 'I':
ia_names = TRUE;
break;
case 'h':
printf("%s", HELP);
exit(0);
case '?':
die("Bad argument. Try 'indelHistory -h'.\n");
}
}
set_seed(-1);
if (read_hist_fname != NULL) {
fprintf(stderr, "Reading indel history from %s...\n", read_hist_fname);
ih = ih_new_from_file(phast_fopen(read_hist_fname, "r"));
}
else {
FILE *mfile;
if (optind != argc - 2)
die("Two arguments required. Try 'indelHistory -h'.\n");
fprintf(stderr, "Reading alignment from %s...\n", argv[optind]);
mfile = phast_fopen(argv[optind], "r");
if (msa_format == UNKNOWN_FORMAT)
msa_format = msa_format_for_content(mfile, 1);
msa = msa_new_from_file_define_format(mfile, msa_format, "ACGTNB^.-");
phast_fclose(mfile);
if (msa->seqs == NULL && (msa->ss == NULL || msa->ss->tuple_idx == NULL))
die("ERROR: ordered representation of alignment required.\n");
fprintf(stderr, "Reading tree from %s...\n", argv[optind+1]);
source_mod = tm_new_from_file(phast_fopen(argv[optind+1], "r"), 1);
/* prune tree, if necessary */
old_nnodes = source_mod->tree->nnodes;
tm_prune(source_mod, msa, pruned_names);
if (lst_size(pruned_names) == (old_nnodes + 1) / 2)
die("ERROR: no match for leaves of tree in alignment (leaf names must match alignment names).\n");
if (lst_size(pruned_names) > 0) {
fprintf(stderr, "WARNING: pruned away leaves of tree with no match in alignment (");
for (i = 0; i < lst_size(pruned_names); i++)
fprintf(stderr, "%s%s", ((String*)lst_get_ptr(pruned_names, i))->chars,
i < lst_size(pruned_names) - 1 ? ", " : ").\n");
}
lst_free(pruned_names);
tr_name_ancestors(source_mod->tree);
if (msa->nseqs > (source_mod->tree->nnodes + 1) / 2) { /* assume ancestral
seqs specified
in this case */
if (ia_names) {
fprintf(stderr, "Converting sequence names...\n");
ih_convert_ia_names(msa, source_mod->tree);
}
fprintf(stderr, "Extracting indel history from alignment...\n");
ih = ih_extract_from_alignment(msa, source_mod->tree);
}
else { /* infer by parsimony */
if (msa->ss == NULL) {
fprintf(stderr, "Extracting sufficient statistics...\n");
ss_from_msas(msa, 1, TRUE, NULL, NULL, NULL, -1, 0);
}
fprintf(stderr, "Inferring indel history by parsimony...\n");
ih = ih_reconstruct(msa, source_mod->tree);
}
}
if (output_alignment) {
out_msa = ih_as_alignment(ih, msa);
msa_print(stdout, out_msa, FASTA, FALSE);
}
else
ih_print(ih, stdout,
read_hist_fname != NULL ? read_hist_fname : argv[optind],
"indelHistory");
fprintf(stderr, "Done.\n");
return 0;
}
int main(int argc, char *argv[]) {
char c;
List *l;
int i, j, strand, bed_output = 0, backgd_nmods = -1, feat_nmods = -1,
winsize = -1, verbose = 0, max_nmods, memblocksize, old_nleaves,
refidx = 1, base_by_base = FALSE, windowWig = FALSE;
TreeModel **backgd_mods = NULL, **feat_mods = NULL;
HMM *backgd_hmm = NULL, *feat_hmm = NULL;
msa_format_type inform = UNKNOWN_FORMAT;
GFF_Set *features = NULL;
MSA *msa, *msa_compl=NULL;
double **backgd_emissions, **feat_emissions, **mem, **dummy_emissions,
*winscore_pos=NULL, *winscore_neg=NULL;
int *no_alignment=NULL;
List *pruned_names;
char *msa_fname;
FILE *infile;
int opt_idx;
struct option long_opts[] = {
{"background-mods", 1, 0, 'b'},
{"background-hmm", 1, 0, 'B'},
{"feature-mods", 1, 0, 'f'},
{"feature-hmm", 1, 0, 'F'},
{"features", 1, 0, 'g'},
{"window", 1, 0, 'w'},
{"window-wig", 1, 0, 'W'},
{"base-by-base", 0, 0, 'y'},
{"msa-format", 1, 0, 'i'},
{"refidx", 1, 0, 'r'},
{"output-bed", 0, 0, 'd'},
{"verbose", 0, 0, 'v'},
{"help", 0, 0, 'h'},
{0, 0, 0, 0}
};
while ((c = getopt_long(argc, argv, "B:b:F:f:r:g:w:W:i:ydvh", long_opts, &opt_idx)) != -1) {
switch (c) {
case 'B':
backgd_hmm = hmm_new_from_file(phast_fopen(optarg, "r"));
break;
case 'b':
l = get_arg_list(optarg);
backgd_nmods = lst_size(l);
backgd_mods = smalloc(backgd_nmods * sizeof(void*));
for (i = 0; i < backgd_nmods; i++)
backgd_mods[i] = tm_new_from_file(phast_fopen(((String*)lst_get_ptr(l, i))->chars, "r"), 1);
lst_free_strings(l);
lst_free(l);
break;
case 'F':
feat_hmm = hmm_new_from_file(phast_fopen(optarg, "r"));
break;
case 'f':
l = get_arg_list(optarg);
feat_nmods = lst_size(l);
feat_mods = smalloc(feat_nmods * sizeof(void*));
for (i = 0; i < feat_nmods; i++)
feat_mods[i] = tm_new_from_file(phast_fopen(((String*)lst_get_ptr(l, i))->chars, "r"), 1);
lst_free_strings(l);
lst_free(l);
break;
case 'g':
features = gff_read_set(phast_fopen(optarg, "r"));
break;
case 'w':
winsize = get_arg_int(optarg);
if (winsize <= 0) die("ERROR: window size must be positive.\n");
break;
case 'W':
winsize = get_arg_int(optarg);
if (winsize <= 0) die("ERROR: window size must be positive.\n");
windowWig = TRUE;
break;
case 'y':
base_by_base = TRUE;
break;
case 'i':
inform = msa_str_to_format(optarg);
if (inform == UNKNOWN_FORMAT) die("Bad argument to -i.\n");
break;
case 'r':
refidx = get_arg_int_bounds(optarg, 0, INFTY);
break;
case 'd':
bed_output = 1;
break;
case 'h':
printf("%s", HELP);
exit(0);
case 'v':
verbose = 1;
break;
case '?':
die("Bad argument. Try '%s -h'.\n", argv[0]);
}
}
set_seed(-1);
if (backgd_mods == NULL || feat_mods == NULL)
die("ERROR: -b and -f required. Try '%s -h'.\n", argv[0]);
if (backgd_nmods == 1 && backgd_hmm == NULL)
backgd_hmm = hmm_create_trivial();
else if (backgd_hmm == NULL)
die("ERROR: -B required. Try '%s -h'.\n", argv[0]);
if (feat_nmods == 1 && feat_hmm == NULL)
feat_hmm = hmm_create_trivial();
else if (feat_hmm == NULL)
die("ERROR: -F required. Try '%s -h'.\n", argv[0]);
if ((winsize == -1 && features == NULL && !base_by_base) ||
(winsize != -1 && features != NULL) ||
(winsize != -1 && base_by_base) ||
(features != NULL && base_by_base))
die("ERROR: must specify exactly one of -g, -w, and -y. Try '%s -h'.\n", argv[0]);
if (backgd_hmm->nstates != backgd_nmods)
die("ERROR: number of states must equal number of tree models for background.\n");
if (feat_hmm->nstates != feat_nmods)
die("ERROR: number of states must equal number of tree models for features.\n");
if (features != NULL && lst_size(features->features) == 0)
die("ERROR: empty features file.\n");
if (base_by_base && (backgd_nmods > 1 || feat_nmods > 1))
die("ERROR: only single phylogenetic models (not HMMs) are supported with --base-by-base.\n");
if (optind != argc - 1)
die("ERROR: too few arguments. Try '%s -h'.\n", argv[0]);
if (verbose) fprintf(stderr, "Reading alignment ...\n");
msa_fname = argv[optind];
infile = phast_fopen(msa_fname, "r");
if (inform == UNKNOWN_FORMAT)
inform = msa_format_for_content(infile, 1);
if (inform == MAF)
msa = maf_read(infile, NULL, 1, NULL, NULL,
NULL, -1, TRUE, NULL, NO_STRIP, FALSE);
else
msa = msa_new_from_file_define_format(infile, inform, NULL);
if (msa_alph_has_lowercase(msa)) msa_toupper(msa);
msa_remove_N_from_alph(msa);
/* need ordered representation of alignment */
if (msa->seqs == NULL && (msa->ss == NULL || msa->ss->tuple_idx == NULL) )
die("ERROR: ordered sufficient statistics are required.\n");
pruned_names = lst_new_ptr(msa->nseqs);
for (i = 0; i < backgd_nmods; i++) {
old_nleaves = (backgd_mods[i]->tree->nnodes + 1) / 2;
tm_prune(backgd_mods[i], msa, pruned_names);
if (lst_size(pruned_names) >= old_nleaves)
die("ERROR: no match for leaves of tree in alignment (background model #%d)\n", i+1);
else if (lst_size(pruned_names) > 0) {
fprintf(stderr, "WARNING: pruned away leaves in background model (#%d) with no match in alignment (", i+1);
for (j = 0; j < lst_size(pruned_names); j++)
fprintf(stderr, "%s%s", ((String*)lst_get_ptr(pruned_names, j))->chars,
j < lst_size(pruned_names) - 1 ? ", " : ").\n");
}
lst_free_strings(pruned_names);
}
for (i = 0; i < feat_nmods; i++) {
old_nleaves = (feat_mods[i]->tree->nnodes + 1) / 2;
tm_prune(feat_mods[i], msa, pruned_names);
if (lst_size(pruned_names) >= old_nleaves)
die("ERROR: no match for leaves of tree in alignment (features model #%d)\n", i+1);
else if (lst_size(pruned_names) > 0) {
fprintf(stderr, "WARNING: pruned away leaves in features model (#%d) with no match in alignment (", i+1);
for (j = 0; j < lst_size(pruned_names); j++)
fprintf(stderr, "%s%s", ((String*)lst_get_ptr(pruned_names, j))->chars,
j < lst_size(pruned_names) - 1 ? ", " : ").\n");
}
lst_free_strings(pruned_names);
}
lst_free(pruned_names);
/* first have to subtract offset from features, if necessary */
if (msa->idx_offset != 0 && features != NULL) {
for (i = 0; i < lst_size(features->features); i++) {
GFF_Feature *f = lst_get_ptr(features->features, i);
f->start -= msa->idx_offset;
f->end -= msa->idx_offset;
}
}
/* convert to coord frame of alignment */
if (features != NULL && refidx != 0) {
if (verbose) fprintf(stderr, "Mapping coordinates ...\n");
msa_map_gff_coords(msa, features, refidx, 0, 0);
if (lst_size(features->features) == 0)
die("ERROR: no features within coordinate range of alignment.\n");
}
/* Make a reverse complemented copy of the alignment. The two
strands will be processed separately, to avoid problems with
overlapping features, etc. */
if (!base_by_base) { /* skip in base by base case */
if (verbose) fprintf(stderr, "Creating reverse complemented alignment ...\n");
msa_compl = msa_create_copy(msa, 0);
/* temporary workaround: make sure reverse complement not based on
sufficient stats */
if (msa_compl->seqs == NULL) ss_to_msa(msa_compl);
if (msa_compl->ss != NULL) {
ss_free(msa_compl->ss);
msa_compl->ss = NULL;
}
msa_reverse_compl(msa_compl);
}
/* allocate memory for computing scores */
backgd_emissions = smalloc(backgd_nmods * sizeof(void*));
for (i = 0; i < backgd_nmods; i++)
backgd_emissions[i] = smalloc(msa->length * sizeof(double));
feat_emissions = smalloc(feat_nmods * sizeof(void*));
for (i = 0; i < feat_nmods; i++)
feat_emissions[i] = smalloc(msa->length * sizeof(double));
max_nmods = max(backgd_nmods, feat_nmods);
dummy_emissions = smalloc(max_nmods * sizeof(void*));
mem = smalloc(max_nmods * sizeof(void*));
/* memory for forward algorithm -- each block must be as large as
the largest feature */
if (features != NULL) {
for (i = 0, memblocksize = -1; i < lst_size(features->features); i++) {
GFF_Feature *f = lst_get_ptr(features->features, i);
if (f->end - f->start + 1 > memblocksize)
memblocksize = f->end - f->start + 1;
}
}
else memblocksize = winsize; /* -1 if base-by-base mode */
if (memblocksize > 0)
for (i = 0; i < max_nmods; i++)
mem[i] = smalloc(memblocksize * sizeof(double));
if (winsize != -1) {
winscore_pos = smalloc(msa->length * sizeof(double));
winscore_neg = smalloc(msa->length * sizeof(double));
no_alignment = smalloc(msa->length * sizeof(int));
for (i = 0; i < msa->length; i++) {
winscore_pos[i] = winscore_neg[i] = NEGINFTY;
if (refidx == 0)
no_alignment[i] = FALSE;
else
no_alignment[i] = msa_missing_col(msa, refidx, i);
}
}
/* the rest will be repeated for each strand */
for (strand = 1; strand <= 2; strand++) {
MSA *thismsa = strand == 1 ? msa : msa_compl;
double *winscore = strand == 1 ? winscore_pos : winscore_neg;
if (base_by_base && strand == 2) break; /* don't do second pass in
base_by_base case */
if (verbose) fprintf(stderr, "Processing %c strand ...\n",
strand == 1 ? '+' : '-');
/* set up dummy categories array, so that emissions are only
computed where needed */
thismsa->categories = smalloc(thismsa->length * sizeof(int));
thismsa->ncats = 1;
if (winsize != -1) {
if (strand == 1)
for (i = 0; i < thismsa->length; i++)
thismsa->categories[i] = no_alignment[i] ? 0 : 1;
else
for (i = 0; i < thismsa->length; i++)
thismsa->categories[i] = no_alignment[thismsa->length - i - 1] ? 0 : 1;
}
else if (features != NULL) {
for (i = 0; i < thismsa->length; i++) thismsa->categories[i] = 0;
for (i = 0; i < lst_size(features->features); i++) {
GFF_Feature *f = lst_get_ptr(features->features, i);
if (f->start <= 0 || f->end <= 0) {
fprintf(stderr, "WARNING: feature out of range ('");
gff_print_feat(stderr, f);
fprintf(stderr, "')\n");
continue;
}
if (strand == 1 && f->strand != '-')
for (j = f->start - 1; j < f->end; j++)
thismsa->categories[j] = 1;
else if (strand == 2 && f->strand == '-')
for (j = thismsa->length - f->end;
j < thismsa->length - f->start + 1; j++)
thismsa->categories[j] = 1;
}
}
else { /* base-by-base scores */
for (i = 0; i < thismsa->length; i++) thismsa->categories[i] = 1;
}
if (thismsa->ss != NULL) ss_update_categories(thismsa);
/* compute emissions */
for (i = 0; i < backgd_nmods; i++) {
if (verbose)
fprintf(stderr, "Computing emissions for background model #%d ...\n", i+1);
tl_compute_log_likelihood(backgd_mods[i], thismsa,
backgd_emissions[i], NULL, 1, NULL);
}
for (i = 0; i < feat_nmods; i++) {
if (verbose)
fprintf(stderr, "Computing emissions for features model #%d ...\n", i+1);
tl_compute_log_likelihood(feat_mods[i], thismsa,
feat_emissions[i], NULL, 1, NULL);
}
/* now compute scores */
if (winsize != -1) { /* windows case */
int winstart;
if (verbose) fprintf(stderr, "Computing scores ...\n");
for (winstart = 0; winstart <= thismsa->length - winsize; winstart++) {
int centeridx = winstart + winsize/2;
if (strand == 2) centeridx = thismsa->length - centeridx - 1;
if (no_alignment[centeridx]) continue;
for (j = 0; j < feat_nmods; j++)
dummy_emissions[j] = &(feat_emissions[j][winstart]);
winscore[centeridx] = hmm_forward(feat_hmm, dummy_emissions,
winsize, mem);
if (winscore[centeridx] <= NEGINFTY) {
winscore[centeridx] = NEGINFTY;
continue;
}
for (j = 0; j < backgd_nmods; j++)
dummy_emissions[j] = &(backgd_emissions[j][winstart]);
winscore[centeridx] -= hmm_forward(backgd_hmm, dummy_emissions,
winsize, mem);
if (winscore[centeridx] < NEGINFTY) winscore[centeridx] = NEGINFTY;
}
}
else if (features != NULL) { /* features case */
if (verbose) fprintf(stderr, "Computing scores ...\n");
for (i = 0; i < lst_size(features->features); i++) {
GFF_Feature *f = lst_get_ptr(features->features, i);
int s, e;
if ((strand == 1 && f->strand == '-') ||
(strand == 2 && f->strand != '-') ||
f->start <= 0 || f->end <= 0 || f->end - f->start < 0)
continue;
/* effective coords */
if (f->strand == '-') {
s = thismsa->length - f->end + 1;
e = thismsa->length - f->start + 1;
}
else {
s = f->start;
e = f->end;
}
f->score_is_null = 0;
for (j = 0; j < feat_nmods; j++)
dummy_emissions[j] = &(feat_emissions[j][s-1]);
f->score = hmm_forward(feat_hmm, dummy_emissions, e - s + 1, mem);
if (f->score <= NEGINFTY) {
f->score = NEGINFTY;
continue;
}
for (j = 0; j < backgd_nmods; j++)
dummy_emissions[j] = &(backgd_emissions[j][s-1]);
f->score -= hmm_forward(backgd_hmm, dummy_emissions, e - s + 1, mem);
if (f->score < NEGINFTY) f->score = NEGINFTY;
}
}
}
if (verbose) fprintf(stderr, "Generating output ...\n");
if (winsize != -1 && windowWig == FALSE) { /* standard windows output */
for (i = 0, j = 0; i < msa->length; i++) {
if (no_alignment[i] == FALSE)
printf("%d\t%.3f\t%.3f\n", j + msa->idx_offset + 1, winscore_pos[i],
winscore_neg[i]);
if (ss_get_char_pos(msa, i, 0, 0) != GAP_CHAR) j++;
}
}
else if (windowWig == TRUE) { /* windows with wig output */
int last = NEGINFTY;
for (i = 0, j = 0; i < msa->length; i++) {
if (refidx == 0 || msa_get_char(msa, refidx-1, i) != GAP_CHAR) {
if (no_alignment[i] == FALSE && winscore_pos[i] > NEGINFTY) {
if (j > last + 1)
printf("fixedStep chrom=%s start=%d step=1\n",
refidx > 0 ? msa->names[refidx-1] : "alignment",
j + msa->idx_offset + 1);
printf("%.3f\n", winscore_pos[i]);
last = j;
}
j++;
}
}
}
else if (features != NULL) { /* features output */
/* return to coord frame of reference seq (also, replace offset) */
if (refidx != 0)
msa_map_gff_coords(msa, features, 0, refidx, msa->idx_offset);
else if (msa->idx_offset != 0) {
for (i = 0; i < lst_size(features->features); i++) {
GFF_Feature *f = lst_get_ptr(features->features, i);
f->start += msa->idx_offset;
f->end += msa->idx_offset;
}
}
if (bed_output)
gff_print_bed(stdout, features, FALSE);
else
gff_print_set(stdout, features);
}
else { /* base-by-base scores */
/* in this case, we can just output the difference between the emissions */
printf("fixedStep chrom=%s start=%d step=1\n",
refidx > 0 ? msa->names[refidx-1] : "alignment",
msa->idx_offset + 1);
for (i = 0, j = 0; i < msa->length; i++) {
if (refidx == 0 || msa_get_char(msa, refidx-1, i) != GAP_CHAR) {
printf("%.3f\n", feat_emissions[0][i] - backgd_emissions[0][i]);
j++;
}
}
}
if (verbose) fprintf(stderr, "\nDone.\n");
return 0;
}
int main(int argc, char *argv[]) {
char c;
char *msa_fname = NULL;
int opt_idx, i, old_nnodes;
MSA *msa;
List *pruned_names = lst_new_ptr(5), *tmpl;
BDPhyloHmm *bdphmm;
GFF_Set *predictions;
int found = FALSE;
List *ignore_types = lst_new_ptr(1);
struct option long_opts[] = {
{"refseq", 1, 0, 'M'},
{"msa-format", 1, 0, 'i'},
{"refidx", 1, 0, 'r'},
{"rho", 1, 0, 'R'},
{"phi", 1, 0, 'p'},
{"transitions", 1, 0, 't'},
{"expected-length", 1, 0, 'E'},
{"target-coverage", 1, 0, 'C'},
{"seqname", 1, 0, 'N'},
{"idpref", 1, 0, 'P'},
{"indel-model", 1, 0, 'I'},
{"indel-history", 1, 0, 'H'},
{"help", 0, 0, 'h'},
{0, 0, 0, 0}
};
/* arguments and defaults for options */
FILE *refseq_f = NULL, *msa_f = NULL;
msa_format_type msa_format = UNKNOWN_FORMAT;
TreeModel *source_mod;
double rho = DEFAULT_RHO, mu = DEFAULT_MU, nu = DEFAULT_NU,
phi = DEFAULT_PHI, gamma = -1, omega = -1,
alpha_c = -1, beta_c = -1, tau_c = -1,
alpha_n = -1, beta_n = -1, tau_n = -1;
int set_transitions = FALSE, refidx = 1, estim_phi = TRUE,
estim_gamma = TRUE, estim_omega = TRUE;
char *seqname = NULL, *idpref = NULL;
IndelHistory *ih = NULL;
while ((c = getopt_long(argc, argv, "R:t:p:E:C:r:M:i:N:P:I:H:h", long_opts, &opt_idx)) != -1) {
switch (c) {
case 'R':
rho = get_arg_dbl_bounds(optarg, 0, 1);
break;
case 't':
if (optarg[0] != '~') estim_gamma = estim_omega = FALSE;
else optarg = &optarg[1];
set_transitions = TRUE;
tmpl = get_arg_list_dbl(optarg);
if (lst_size(tmpl) != 2)
die("ERROR: bad argument to --transitions.\n");
mu = lst_get_dbl(tmpl, 0);
nu = lst_get_dbl(tmpl, 1);
if (mu <= 0 || mu >= 1 || nu <= 0 || nu >= 1)
die("ERROR: bad argument to --transitions.\n");
lst_free(tmpl);
break;
case 'p':
if (optarg[0] != '~') estim_phi = FALSE;
else optarg = &optarg[1];
phi = get_arg_dbl_bounds(optarg, 0, 1);
break;
case 'E':
if (optarg[0] != '~') estim_omega = FALSE;
else optarg = &optarg[1];
omega = get_arg_dbl_bounds(optarg, 1, INFTY);
mu = 1/omega;
break;
case 'C':
if (optarg[0] != '~') estim_gamma = FALSE;
else optarg = &optarg[1];
gamma = get_arg_dbl_bounds(optarg, 0, 1);
break;
case 'r':
refidx = get_arg_int_bounds(optarg, 0, INFTY);
break;
case 'M':
refseq_f = phast_fopen(optarg, "r");
break;
case 'i':
msa_format = msa_str_to_format(optarg);
if (msa_format == UNKNOWN_FORMAT)
die("ERROR: unrecognized alignment format.\n");
break;
case 'N':
seqname = optarg;
break;
case 'P':
idpref = optarg;
break;
case 'I':
tmpl = get_arg_list_dbl(optarg);
if (lst_size(tmpl) != 3 && lst_size(tmpl) != 6)
die("ERROR: bad argument to --indel-model.\n");
alpha_n = lst_get_dbl(tmpl, 0);
beta_n = lst_get_dbl(tmpl, 1);
tau_n = lst_get_dbl(tmpl, 2);
if (lst_size(tmpl) == 6) {
alpha_c = lst_get_dbl(tmpl, 3);
beta_c = lst_get_dbl(tmpl, 4);
tau_c = lst_get_dbl(tmpl, 5);
}
else {
alpha_c = alpha_n; beta_c = beta_n; tau_c = tau_n;
}
if (alpha_c <= 0 || alpha_c >= 1 || beta_c <= 0 || beta_c >= 1 ||
tau_c <= 0 || tau_c >= 1 || alpha_n <= 0 || alpha_n >= 1 ||
beta_n <= 0 || beta_n >= 1 || tau_n <= 0 || tau_n >= 1)
die("ERROR: bad argument to --indel-model.\n");
break;
case 'H':
fprintf(stderr, "Reading indel history from %s...\n", optarg);
ih = ih_new_from_file(phast_fopen(optarg, "r"));
break;
case 'h':
printf("%s", HELP);
exit(0);
case '?':
die("Bad argument. Try 'dless -h'.\n");
}
}
if (optind != argc - 1)
die("Missing alignment file or model file. Try 'dless -h'.\n");
if (set_transitions && (gamma != -1 || omega != -1))
die("ERROR: --transitions and --target-coverage/--expected-length cannot be used together.\n");
if ((gamma != -1 && omega == -1) || (gamma == -1 && omega != -1))
die("ERROR: --target-coverage and --expecteed-length must be used together.\n");
set_seed(-1);
if (gamma != -1)
nu = gamma/(1-gamma) * mu;
fprintf(stderr, "Reading tree model from %s...\n", argv[optind]);
source_mod = tm_new_from_file(phast_fopen(argv[optind], "r"), 1);
if (source_mod->nratecats > 1)
die("ERROR: rate variation not currently supported.\n");
if (source_mod->order > 0)
die("ERROR: only single nucleotide models are currently supported.\n");
if (!tm_is_reversible(source_mod))
phast_warning("WARNING: p-value computation assumes reversibility and your model is non-reversible.\n");
/* read alignment */
msa_f = phast_fopen(argv[optind], "r");
fprintf(stderr, "Reading alignment from %s...\n", argv[optind]);
if (msa_format == UNKNOWN_FORMAT)
msa_format = msa_format_for_content(msa_f, 1);
if (msa_format == MAF) {
msa = maf_read(msa_f, refseq_f, 1, NULL, NULL, NULL, -1, TRUE, NULL,
NO_STRIP, FALSE);
}
else
msa = msa_new_from_file_define_format(msa_f, msa_format, NULL);
if (msa_alph_has_lowercase(msa)) msa_toupper(msa);
msa_remove_N_from_alph(msa);
if (msa->ss == NULL) {
fprintf(stderr, "Extracting sufficient statistics...\n");
ss_from_msas(msa, 1, TRUE, NULL, NULL, NULL, -1, 0);
}
else if (msa->ss->tuple_idx == NULL)
die("ERROR: ordered representation of alignment required unless --suff-stats.\n");
/* prune tree, if necessary */
old_nnodes = source_mod->tree->nnodes;
tm_prune(source_mod, msa, pruned_names);
if (lst_size(pruned_names) == (old_nnodes + 1) / 2)
die("ERROR: no match for leaves of tree in alignment (leaf names must match alignment names).\n");
if (lst_size(pruned_names) > 0) {
fprintf(stderr, "WARNING: pruned away leaves of tree with no match in alignment (");
for (i = 0; i < lst_size(pruned_names); i++)
fprintf(stderr, "%s%s", ((String*)lst_get_ptr(pruned_names, i))->chars,
i < lst_size(pruned_names) - 1 ? ", " : ").\n");
}
/* this has to be done after pruning tree */
tr_name_ancestors(source_mod->tree);
/* also make sure match for reference sequence in tree */
if (refidx > 0) {
for (i = 0, found = FALSE; !found && i < source_mod->tree->nnodes; i++) {
TreeNode *n = lst_get_ptr(source_mod->tree->nodes, i);
if (!strcmp(n->name, msa->names[refidx-1]))
found = TRUE;
}
if (!found) die("ERROR: no match for reference sequence in tree.\n");
}
/* checks for indel model */
if (alpha_c > 0) {
if (ih == NULL) {
fprintf(stderr, "Reconstructing indel history by parsimony...\n");
ih = ih_reconstruct(msa, source_mod->tree);
}
else {
if (ih->ncols != msa->length)
die("ERROR: indel history doesn't seem to match alignment.\n");
if (ih->tree->nnodes != source_mod->tree->nnodes)
die("ERROR: indel history doesn't seem to match tree model.\n");
}
}
bdphmm = bd_new(source_mod, rho, mu, nu, phi, alpha_c, beta_c, tau_c,
alpha_n, beta_n, tau_n, estim_gamma, estim_omega,
estim_phi);
/* compute emissions */
phmm_compute_emissions(bdphmm->phmm, msa, FALSE);
/* add emissions for indel model, if necessary */
if (alpha_c > 0) {
fprintf(stderr, "Adjusting emissions for indels...\n");
bd_add_indel_emissions(bdphmm, ih);
}
/* postprocess for missing data (requires special handling) */
fprintf(stderr, "Adjusting emissions for missing data...\n");
bd_handle_missing_data(bdphmm, msa);
if (estim_gamma || estim_omega || estim_phi) {
fprintf(stderr, "Estimating free parameters...\n");
bd_estimate_transitions(bdphmm, msa);
}
/* set seqname and idpref, if necessary */
if (seqname == NULL || idpref == NULL) {
/* derive default from file name root */
String *tmp = str_new_charstr(msa_fname);
if (!str_equals_charstr(tmp, "-")) {
str_remove_path(tmp);
str_root(tmp, '.');
if (idpref == NULL) idpref = copy_charstr(tmp->chars);
str_root(tmp, '.'); /* apply one more time for double suffix */
if (seqname == NULL) seqname = tmp->chars;
}
else if (seqname == NULL) seqname = "refseq";
}
/* obtain predictions */
fprintf(stderr, "Running Viterbi algorithm...\n");
predictions = phmm_predict_viterbi(bdphmm->phmm, seqname, NULL, idpref, NULL);
lst_push_ptr(ignore_types, str_new_charstr("nonconserved"));
gff_filter_by_type(predictions, ignore_types, TRUE, NULL);
/* score predictions */
fprintf(stderr, "Scoring predictions...\n");
bd_score_predictions(bdphmm, predictions);
/* can free emissions now */
for (i = 0; i < bdphmm->phmm->hmm->nstates; i++)
sfree(bdphmm->phmm->emissions[i]);
sfree(bdphmm->phmm->emissions);
bdphmm->phmm->emissions = NULL;
/* convert GFF to coord frame of reference sequence and adjust
coords by idx_offset, if necessary */
if (refidx != 0 || msa->idx_offset != 0)
msa_map_gff_coords(msa, predictions, 0, refidx, msa->idx_offset);
if (refidx != 0)
gff_flatten(predictions);
/* necessary because coord conversion might create overlapping
features (can happen in deletions in reference sequence) */
/* now output predictions */
fprintf(stderr, "Writing GFF to stdout...\n");
gff_print_set(stdout, predictions);
fprintf(stderr, "Done.\n");
return 0;
}
int main(int argc, char* argv[]) {
FILE* F;
TreeModel *model;
int i, j, k, alph_size, nstates, do_eqfreqs = 0, exch_mode = 0,
list_mode = 0, latex_mode = 0, suppress_diag = 0, ti_tv = 0,
scientific_mode = 0,
induced_aa = 0, do_stop_codons = 0, do_zeroes = 0, symmetric = 0,
context_ti_tv = 0, all_branches = 0;
int startcol, endcol, ncols, branch_no = 0, matrix_idx = 0;
/* int aa_inv[256]; */
double t = -1, total_ti = 0, total_tv = 0, rho_s = 0, cpg_ti = 0,
cpg_tv = 0, non_cpg_ti = 0, non_cpg_tv = 0, cpg_eqfreq = 0;
char *rate_format_string = "%8.6f";
MarkovMatrix *M;
char c;
char tuple[5], tuple2[5]; /* , aa_alph[50]; */
char *subst_mat_fname = NULL, *subst_score_fname = NULL,
*subst_mat_fname_paml = NULL, *order1_mod_fname = NULL;
Matrix *subst_mat = NULL;
List *matrix_list = lst_new_ptr(20), *traversal = NULL;
while ((c = (char)getopt(argc, argv, "t:fedlLiM:N:A:B:aszSECh")) != -1) {
switch(c) {
case 't':
if (optarg[0] == 'A') all_branches = 1;
else t = get_arg_dbl_bounds(optarg, 0, INFTY);
break;
case 'f':
do_eqfreqs = 1;
break;
case 'e':
exch_mode = 1;
break;
case 'd':
suppress_diag = 1;
break;
case 'l':
list_mode = 1;
break;
case 'L':
latex_mode = 1;
break;
case 'i':
ti_tv = 1;
break;
case 'M':
subst_mat_fname = optarg;
induced_aa = 1;
break;
case 'N':
subst_mat_fname_paml = optarg;
induced_aa = 1;
break;
case 'A':
subst_score_fname = optarg;
break;
case 'B':
order1_mod_fname = optarg;
break;
case 'a':
induced_aa = 1;
do_zeroes = 1;
break;
case 's':
do_stop_codons = 1;
break;
case 'z':
do_zeroes = 1;
break;
case 'S':
symmetric = 1;
break;
case 'E':
scientific_mode = 1;
rate_format_string = "%13.6e";
break;
case 'C':
context_ti_tv = 1;
break;
case 'h':
print_usage();
exit(0);
case '?':
die("Unrecognized option. Try \"display_rate_matrix -h\" for help.\n");
}
}
set_seed(-1);
if ((t >= 0 && exch_mode) || (latex_mode && list_mode) ||
((ti_tv || subst_mat_fname != NULL || subst_score_fname != NULL ||
subst_mat_fname_paml != NULL || scientific_mode) && !list_mode) ||
(subst_mat_fname != NULL && subst_score_fname != NULL) ||
(subst_score_fname != NULL && subst_mat_fname_paml != NULL) ||
(subst_mat_fname != NULL && subst_mat_fname_paml != NULL) ||
optind != argc - 1) {
die("ERROR: missing required arguments or illegal combination of arguments.\nTry \"display_rate_matrix -h\" for help.\n");
}
F = phast_fopen(argv[optind], "r");
model = tm_new_from_file(F, 1);
if (context_ti_tv) {
/* this option requires completely different handling from the others */
if (model->order != 2) {
die("ERROR: -C requires a model of order 3.\n");
}
do_context_dependent_ti_tv(model);
exit(0);
}
if (induced_aa) {
TreeModel *aa_model = tm_induced_aa(model);
char *codon_to_aa = get_codon_mapping(model->rate_matrix->states);
/* before freeing model, grab the expected rate of synonymous
subst, rho_s */
for (i = 0; i < model->rate_matrix->size; i++)
for (j = 0; j < model->rate_matrix->size; j++)
if (i != j && codon_to_aa[i] == codon_to_aa[j])
rho_s += mm_get(model->rate_matrix, i, j) *
vec_get(model->backgd_freqs, i);
sfree(codon_to_aa);
tm_free(model);
model = aa_model;
}
if (all_branches) {
traversal = tr_inorder(model->tree);
for (matrix_idx = 0; matrix_idx < lst_size(traversal); matrix_idx++) {
TreeNode *n = lst_get_ptr(traversal, matrix_idx);
if (n->parent == NULL) { lst_push_ptr(matrix_list, NULL); continue; }
M = mm_new(model->rate_matrix->size, model->rate_matrix->states, DISCRETE);
mm_exp(M, model->rate_matrix, n->dparent);
lst_push_ptr(matrix_list, M);
}
}
else if (t >= 0) {
M = mm_new(model->rate_matrix->size, model->rate_matrix->states, DISCRETE);
mm_exp(M, model->rate_matrix, t);
lst_push_ptr(matrix_list, M);
}
else
lst_push_ptr(matrix_list, model->rate_matrix);
alph_size = (int)strlen(model->rate_matrix->states);
nstates = model->rate_matrix->size;
if (subst_mat_fname != NULL) {
if ((F = fopen(subst_mat_fname, "r")) == NULL) {
die("ERROR: Can't open %s.\n", subst_mat_fname);
}
subst_mat = read_subst_mat(F, AA_ALPHABET);
}
else if (subst_mat_fname_paml != NULL) {
if ((F = fopen(subst_mat_fname_paml, "r")) == NULL) {
die("ERROR: Can't open %s.\n", subst_mat_fname_paml);
}
subst_mat = read_paml_matrix(F, AA_ALPHABET);
}
else if (subst_score_fname != NULL) {
if ((F = fopen(subst_score_fname, "r")) == NULL) {
die("ERROR: Can't open %s.\n", subst_score_fname);
}
subst_mat = read_subst_scores(model, F);
}
else if (order1_mod_fname != NULL) {
if ((F = fopen(order1_mod_fname, "r")) == NULL) {
die("ERROR: Can't open %s.\n", order1_mod_fname);
}
subst_mat = unproject_rates(model, tm_new_from_file(F, 1));
}
/* loop through matrices to print */
for (matrix_idx = 0; matrix_idx < lst_size(matrix_list); matrix_idx++) {
M = lst_get_ptr(matrix_list, matrix_idx);
if (all_branches) {
if (M == NULL) continue; /* root */
printf("BRANCH %d (t = %.6f)\n", ++branch_no,
((TreeNode*)lst_get_ptr(traversal, matrix_idx))->dparent);
}
/* print no more than 16 columns at a time (except with -a) */
ncols = (induced_aa ? nstates : 16);
for (startcol = 0; startcol < nstates; startcol += ncols) {
endcol = min(nstates, startcol+ncols);
/* table header */
if (! list_mode) {
if (latex_mode) {
printf("\\begin{tabular}{|c|");
for (i = startcol; i < endcol; i++) printf("r");
printf("|}\n\\hline\n");
}
printf("%-5s ", "");
if (latex_mode) printf("& ");
for (i = startcol; i < endcol; i++) {
get_state_tuple(model, tuple, i);
if (latex_mode) {
printf("{\\bf %s}", tuple);
if (i < endcol-1) printf("& ");
}
else printf("%8s ", tuple);
}
if (latex_mode) printf("\\\\\n\\hline\n");
else printf("\n");
}
/* table or list contents */
for (i = 0; i < nstates; i++) {
if (induced_aa && AA_ALPHABET[i] == '$' && !do_stop_codons) continue;
get_state_tuple(model, tuple, i);
/* get total eq freq of tuples containing CpG dinucs */
for (k = 0; k < model->order; k++) {
if (tuple[k] == 'C' && tuple[k+1] == 'G') {
cpg_eqfreq += vec_get(model->backgd_freqs, i);
/* printf("***CPG***"); */
break;
}
}
if (latex_mode) printf("{\\bf %s}& ", tuple);
else if (!list_mode) printf("%-5s ", tuple);
for (j = startcol; j < endcol; j++) {
if (induced_aa && AA_ALPHABET[j] == '$' && !do_stop_codons) continue;
if (latex_mode) printf("$");
if (list_mode) {
if (symmetric && j <= i) continue;
else if ((t < 0 && ! all_branches)
&& (i == j || (!do_zeroes && mm_get(M, i, j) == 0)))
continue;
get_state_tuple(model, tuple2, j);
printf("%-5s %-5s ", tuple, tuple2);
}
if (i == j && suppress_diag && !list_mode) printf("%-7s", "-");
else {
/* get rate or probability */
double val = exch_mode == 0 ? mm_get(M, i, j) :
safediv(mm_get(M, i, j), vec_get(model->backgd_freqs,j));
/* print value in format %8.6f or %13.6e */
printf(rate_format_string, val);
printf(" ");
}
if (latex_mode) {
printf("$");
if (j < endcol-1) printf("& ");
}
else if (list_mode) {
int ti, is_cpg;
if (ti_tv) {
ti = -1;
is_cpg = 0;
for (k = 0; k <= model->order; k++) {
int dig_i = (i % int_pow(alph_size, k+1)) / int_pow(alph_size, k);
int dig_j = (j % int_pow(alph_size, k+1)) / int_pow(alph_size, k);
char next_char = '\0', prev_char = '\0';
if (dig_i != dig_j) {
ti = is_transition(M->states[dig_i], M->states[dig_j]);
if (k != model->order)
prev_char = M->states[(i % int_pow(alph_size, k+2)) /
int_pow(alph_size, k+1)];
if (k != 0)
next_char = M->states[(i % int_pow(alph_size, k)) /
int_pow(alph_size, k-1)];
if ((M->states[dig_i] == 'C' && next_char == 'G') ||
(M->states[dig_i] == 'G' && prev_char == 'C'))
is_cpg = 1;
}
}
if (ti == -1)
die("ERROR ti=-1\n");
printf("%5s ", ti ? "ti" : "tv");
/* printf("%5s ", is_cpg ? "CPG" : "-"); */
if (ti) {
total_ti += mm_get(M, i, j) *
vec_get(model->backgd_freqs, i);
if (is_cpg)
cpg_ti += mm_get(M, i, j) *
vec_get(model->backgd_freqs, i);
else non_cpg_ti += mm_get(M, i, j) *
vec_get(model->backgd_freqs, i);
}
else {
total_tv += mm_get(M, i, j) *
vec_get(model->backgd_freqs, i);
if (is_cpg)
cpg_tv += mm_get(M, i, j) *
vec_get(model->backgd_freqs, i);
else non_cpg_tv += mm_get(M, i, j) *
vec_get(model->backgd_freqs, i);
}
}
if (subst_mat != NULL) {
if (mat_get(subst_mat, i, j) == NEGINFTY)
printf("%8s", "-");
else printf("%8.4f", mat_get(subst_mat, i, j));
}
printf("\n");
}
}
if (latex_mode) printf("\\\\\n");
else if (!list_mode) printf("\n");
}
/* equilibrium freqs (table case only) */
if (do_eqfreqs && ! list_mode) {
if (latex_mode)
printf("\\hline\n$\\boldsymbol{\\mathbf{\\pi}}$&");
else
printf("%-5s ", "pi");
for (i = startcol; i < endcol; i++) {
if (latex_mode)
printf("$%8.4f$ ", vec_get(model->backgd_freqs, i));
else
printf("%8.4f ", vec_get(model->backgd_freqs, i));
if (latex_mode && i < endcol-1) printf("& ");
}
if (latex_mode) printf("\\\\\n");
else printf("\n");
}
if (latex_mode) printf("\\hline\n\\end{tabular}\n\n");
}
/* equilibrium freqs (list case only) */
if (do_eqfreqs && list_mode) {
for (i = 0; i < nstates; i++) {
get_state_tuple(model, tuple, i);
printf("%-5s %-5s ", "-", tuple); //!!
printf(rate_format_string, vec_get(model->backgd_freqs, i));
printf("\n");
}
}
if (ti_tv && list_mode) {
printf("\n#Total ti/tv = %.4f\n", total_ti/total_tv);
printf("#CpG ti ratio = %.4f, CpG tv ratio = %.4f\n",
cpg_ti/non_cpg_ti /* * (1 - cpg_eqfreq) */ / cpg_eqfreq,
cpg_tv/non_cpg_tv /* * (1 - cpg_eqfreq) */ / cpg_eqfreq);
}
else if (induced_aa)
printf("\n#Total rho_s/rho_v = %.4f\n", rho_s/(3-rho_s));
if (all_branches == 1) printf("\n\n");
}
tm_free(model);
lst_free(matrix_list);
return 0;
}
int main(int argc, char *argv[]) {
/* variables for options, with defaults */
TreeNode *tree = NULL, *merge_tree = NULL, *extrapolate_tree = NULL;
Hashtable *rename_hash = NULL;
double scale_factor = 1;
List *prune_names = NULL, *label = NULL, *labelType = NULL;
int prune_all_but = FALSE, tree_only = FALSE, dissect = FALSE,
name_ancestors = FALSE, with_branch = FALSE, print_branchlen=FALSE,
inNewick=FALSE, no_branchlen = FALSE, print_distance_to_root = FALSE;
TreeModel *mod = NULL, *merge_mod = NULL;
char *reroot_name = NULL, *subtree_name =NULL, *get_subtree_name = NULL,
*node_distance_name = NULL;
/* other variables */
String *suffix, *optstr;
char c;
int i, opt_idx;
TreeNode *n;
struct option long_opts[] = {
{"scale", 1, 0, 's'},
{"extrapolate", 1, 0, 'e'},
{"prune", 1, 0, 'p'},
{"prune-all-but", 1, 0, 'P'},
{"get-subtree", 1, 0, 'g'},
{"merge", 1, 0, 'm'},
{"rename", 1, 0, 'r'},
{"tree-only", 0, 0, 't'},
{"no-branchlen", 0, 0, 'N'},
{"dissect", 0, 0, 'd'},
{"name-ancestors", 0, 0, 'a'},
{"reroot", 1, 0, 'R'},
{"with-branch", 1, 0, 'B'},
{"subtree", 1, 0, 'S'},
{"branchlen", 0, 0, 'b'},
{"newick", 0, 0, 'n'},
{"label-subtree", 1, 0, 'L'},
{"label-branches", 1, 0, 'l'},
{"help", 0, 0, 'h'},
{0, 0, 0, 0}
};
while ((c = getopt_long(argc, argv, "s:p:P:g:m:r:R:B:S:D:l:L:adtNbnh",
long_opts, &opt_idx)) != -1) {
switch (c) {
case 's':
scale_factor = get_arg_dbl_bounds(optarg, 0, INFTY);
break;
case 'e':
if (!strcmp(optarg, "default")) {
optarg = smalloc(1000 * sizeof(char));
#if defined(__MINGW32__)
sprintf(optarg, "%s\\data\\exoniphy\\mammals\\cftr25_hybrid.nh",
PHAST_HOME);
#else
sprintf(optarg, "%s/data/exoniphy/mammals/cftr25_hybrid.nh",
PHAST_HOME);
#endif
}
extrapolate_tree = tr_new_from_file(phast_fopen(optarg, "r"));
break;
case 'p':
prune_names = get_arg_list(optarg);
break;
case 'P':
prune_names = get_arg_list(optarg);
prune_all_but = TRUE;
break;
case 'g':
get_subtree_name = optarg;
break;
case 'm':
suffix = str_new_charstr(optarg);
str_suffix(suffix, '.');
if (str_equals_charstr(suffix, "nh"))
merge_tree = tr_new_from_file(phast_fopen(optarg, "r"));
else {
merge_mod = tm_new_from_file(phast_fopen(optarg, "r"), 1);
merge_tree = merge_mod->tree;
}
break;
case 'r':
rename_hash = make_name_hash(optarg);
break;
case 't':
tree_only = TRUE;
break;
case 'N':
no_branchlen = TRUE;
tree_only = TRUE;
break;
case 'd':
dissect = TRUE;
break;
case 'b':
print_branchlen = TRUE;
break;
case 'D':
print_distance_to_root = TRUE;
node_distance_name = optarg;
break;
case 'R':
reroot_name = optarg;
break;
case 'B':
with_branch = TRUE;
break;
case 'a':
name_ancestors = TRUE;
break;
case 'S':
subtree_name = optarg;
break;
case 'n':
inNewick=TRUE;
break;
case 'L': //do the same for --label--subtree and --label-branches
case 'l':
if (label == NULL) {
label = lst_new_ptr(1);
labelType = lst_new_int(1);
}
optstr = str_new_charstr(optarg);
lst_push_ptr(label, optstr);
lst_push_int(labelType, (int)c);
break;
case 'h':
usage(argv[0]);
case '?':
die("Bad argument. Try '%s -h'.\n", argv[0]);
}
}
if (optind != argc - 1)
die("Input filename required. Try '%s -h'.\n", argv[0]);
if (merge_tree != NULL && extrapolate_tree != NULL)
die("ERROR: Can't use --merge and --extrapolate together");
set_seed(-1);
suffix = str_new_charstr(argv[optind]);
str_suffix(suffix, '.');
if (inNewick || str_equals_charstr(suffix, "nh")) {
tree = tr_new_from_file(phast_fopen(argv[optind], "r"));
tree_only = TRUE; /* can't output tree model in this case */
}
else {
mod = tm_new_from_file(phast_fopen(argv[optind], "r"), 1);
tree = mod->tree;
}
if (prune_names != NULL) {
tr_prune(&tree, prune_names, prune_all_but, NULL);
if (mod != NULL) mod->tree = tree; /* root may have changed */
}
if (get_subtree_name != NULL) {
n = tr_get_node(tree, get_subtree_name);
if (n == NULL) {
tr_name_ancestors(tree);
n = tr_get_node(tree, get_subtree_name);
if (n == NULL) {
die("ERROR: no node named '%s'.\n", subtree_name);
}
}
tr_prune_supertree(&tree, n);
if (mod != NULL) mod->tree = tree;
}
if (merge_tree != NULL) {
tree = tr_hybrid(tree, merge_tree);
if (mod != NULL) mod->tree = tree;
}
else if (extrapolate_tree != NULL) {
tr_scale_by_subtree(extrapolate_tree, tree);
tree = extrapolate_tree;
if (mod != NULL) mod->tree = tree;
}
if (scale_factor != 1) {
if (subtree_name == NULL)
tr_scale(tree, scale_factor);
else {
n = tr_get_node(tree, subtree_name);
if (n == NULL) die("ERROR: no node named '%s'.\n", subtree_name);
tr_scale_subtree(tree, n, scale_factor, with_branch);
}
}
if (name_ancestors)
tr_name_ancestors(tree);
if (rename_hash != NULL) {
char *newname;
for (i = 0; i < tree->nnodes; i++) {
n = lst_get_ptr(tree->nodes, i);
if (n->name != NULL && n->name[0] != '\0' &&
(newname = hsh_get(rename_hash, n->name)) != (char*)-1) {
strcpy(n->name, newname);
}
}
}
if (reroot_name != NULL) {
n = tr_get_node(tree, reroot_name);
if (n == NULL) die("ERROR: no node named '%s'.\n", reroot_name);
tr_reroot(tree, n, with_branch);
if (mod != NULL) mod->tree = with_branch ? n->parent : n;
tree = with_branch ? n->parent : n;
}
if (label != NULL) {
for (i=0; i < lst_size(label); i++) {
String *currstr = (String*)lst_get_ptr(label, i), *arg1, *labelVal;
List *tmplst = lst_new_ptr(10);
String *nodename;
int j;
str_split(currstr, ":", tmplst);
if (lst_size(tmplst) != 2)
die("ERROR: bad argument to --label-branches or --label-subtree.\n");
arg1 = lst_get_ptr(tmplst, 0);
labelVal = lst_get_ptr(tmplst, 1);
lst_clear(tmplst);
if (lst_get_int(labelType, i) == (int)'l') {
str_split(arg1, ",", tmplst);
for (j=0; j < lst_size(tmplst); j++) {
nodename = (String*)lst_get_ptr(tmplst, j);
tr_label_node(tree, nodename->chars, labelVal->chars);
}
lst_free_strings(tmplst);
} else if (lst_get_int(labelType, i) == (int)'L') {
int include_leading_branch = FALSE;
TreeNode *node;
nodename = arg1;
node = tr_get_node(tree, nodename->chars);
if (node == NULL && nodename->chars[nodename->length-1] == '+') {
nodename->chars[--nodename->length] = '\0';
node = tr_get_node(tree, nodename->chars);
include_leading_branch = TRUE;
}
tr_label_subtree(tree, nodename->chars, include_leading_branch,
labelVal->chars);
} else die("ERROR got label_type %c\n", lst_get_int(labelType, (char)i));
str_free(arg1);
str_free(labelVal);
lst_free(tmplst);
str_free(currstr);
}
lst_free(label);
lst_free(labelType);
}
if (dissect)
tr_print_nodes(stdout, tree);
if (print_branchlen)
printf("TOTAL_TREE_LEN: %f\n", tr_total_len(tree));
if (print_distance_to_root) {
TreeNode *node = tr_get_node(tree, node_distance_name);
if (node == NULL)
die("ERROR: no node named '%s'.\n", node_distance_name);
printf("length(root-%s): %f\n", node_distance_name,
tr_distance_to_root(node));
}
if (dissect==0 && print_branchlen==0 && print_distance_to_root==0) {
if (tree_only)
tr_print(stdout, tree, no_branchlen==FALSE);
else
tm_print(stdout, mod);
}
return 0;
}
int main(int argc, char *argv[]) {
TreeNode *tree = NULL;
TreeModel *backgd_mod = NULL;
int i, j,
size = DEFAULT_SIZE, meme_mode = 0, profile_mode = 0,
nrestarts = 10, npseudocounts = 5, nsamples = -1,
nmostprevalent = -1, tuple_size = -1, nbest = -1, sample_parms = 0,
nmotifs = DEFAULT_NUMBER, nseqs = -1, do_html = 0, do_bed = 0,
suppress_stdout = 0;
List *msa_name_list = NULL, *pos_examples = NULL, *init_list = NULL, *tmpl;
List *msas, *motifs;
SeqSet *seqset = NULL;
PooledMSA *pmsa = NULL;
msa_format_type msa_format = UNKNOWN_FORMAT;
Vector *backgd_mnmod = NULL;
Hashtable *hash=NULL;
String *output_prefix = str_new_charstr("phastm.");
double *has_motif = NULL;
double prior = PRIOR;
char c;
GFF_Set *bedfeats = NULL;
while ((c = getopt(argc, argv, "t:i:b:sk:md:pn:I:R:P:w:c:SB:o:HDxh")) != -1) {
switch (c) {
case 't':
tree = tr_new_from_file(phast_fopen(optarg, "r"));
break;
case 'i':
msa_format = msa_str_to_format(optarg);
if (msa_format == UNKNOWN_FORMAT)
die("ERROR: bad input format.\n");
break;
case 'b':
backgd_mod = tm_new_from_file(phast_fopen(optarg, "r"), 1);
break;
case 's':
break;
case 'k':
size = get_arg_int(optarg);
break;
case 'm':
meme_mode = 1;
break;
case 'd':
pos_examples = get_arg_list(optarg);
break;
case 'p':
profile_mode = 1;
break;
case 'n':
nrestarts = get_arg_int(optarg);
break;
case 'I':
init_list = get_arg_list(optarg);
break;
case 'P':
tmpl = str_list_as_int(get_arg_list(optarg));
if (lst_size(tmpl) != 2) die("ERROR: bad argument to -P.\n");
nmostprevalent = lst_get_int(tmpl, 0);
tuple_size = lst_get_int(tmpl, 1);
if (!(nmostprevalent > 0 && tuple_size > 0))
die("ERROR: bad argument nmostprevalent=%i tuple_size=%i\n",
nmostprevalent, tuple_size);
lst_free(tmpl);
break;
case 'R':
tmpl = str_list_as_int(get_arg_list(optarg));
if (lst_size(tmpl) != 2) die("ERROR: bad argument to -R.\n");
nsamples = lst_get_int(tmpl, 0);
tuple_size = lst_get_int(tmpl, 1);
if (!(nsamples > 0 && tuple_size > 0))
die("ERROR nsamples=%i tuple_sizse=%i\n", nsamples, tuple_size);
lst_free(tmpl);
break;
case 'c':
npseudocounts = get_arg_int(optarg);
break;
case 'w':
nbest = get_arg_int(optarg);
break;
case 'S':
sample_parms = 1;
break;
case 'B':
nmotifs = get_arg_int(optarg);
break;
case 'o':
str_free(output_prefix);
output_prefix = str_new_charstr(optarg);
str_append_char(output_prefix, '.');
break;
case 'H':
do_html = 1;
break;
case 'D':
do_bed = 1;
break;
case 'x':
suppress_stdout = 1;
break;
case 'h':
usage(argv[0]);
case '?':
die("Bad argument. Try '%s -h'.\n", argv[0]);
}
}
if (optind != argc - 1)
die("ERROR: List of alignment files required. Try '%s -h'.\n", argv[0]);
if ((nsamples > 0 && nmostprevalent > 0) ||
(nsamples > 0 && init_list != NULL) ||
(nmostprevalent > 0 && init_list != NULL))
die("ERROR: -I, -P, and -R are mutually exclusive.");
set_seed(-1);
msa_name_list = get_arg_list(argv[optind]);
if (backgd_mod != NULL && tree == NULL) tree = backgd_mod->tree;
if (tree == NULL && !meme_mode && !profile_mode)
die("ERROR: Must specify -t, -m, or -p.\n");
if ((init_list != NULL || nsamples > 0 || nmostprevalent > 0) &&
!sample_parms)
nrestarts = 1;
if (pos_examples != NULL) {
hash = hsh_new(lst_size(pos_examples));
for (i = 0; i < lst_size(pos_examples); i++)
hsh_put_int(hash, ((String*)lst_get_ptr(pos_examples, i))->chars, 1);
has_motif = smalloc(lst_size(msa_name_list) * sizeof(double));
}
/* open all MSAs */
msas = lst_new_ptr(lst_size(msa_name_list));
fprintf(stderr, "Reading alignment(s) ...\n");
for (i = 0, j = 0; i < lst_size(msa_name_list); i++) {
String *name = lst_get_ptr(msa_name_list, i);
FILE *mfile = phast_fopen(name->chars, "r");
msa_format_type temp_format;
MSA *msa;
if (msa_format == UNKNOWN_FORMAT)
temp_format = msa_format_for_content(mfile, 1);
else temp_format = msa_format;
msa = msa_new_from_file_define_format(mfile, temp_format, NULL);
phast_fclose(mfile);
if (nseqs == -1) nseqs = msa->nseqs;
if (!meme_mode &&
(msa->length - msa_num_gapped_cols(msa, STRIP_ANY_GAPS, -1, -1) < 300 ||
msa->nseqs != nseqs)) {
fprintf(stderr, "WARNING: ignoring alignment '%s' -- too few informative sites.\n", name->chars);
msa_free(msa);
continue;
}
if (msa_alph_has_lowercase(msa)) msa_toupper(msa);
msa_remove_N_from_alph(msa); /* Ns can be a problem */
lst_push_ptr(msas, msa);
if (has_motif != NULL) {
int k, hm = (hsh_get_int(hash, name->chars) == 1);
if (meme_mode) { /* here need to record at individ seq level */
has_motif = srealloc(has_motif,
(j + msa->nseqs + 1) * sizeof(double)); /* FIXME */
for (k = 0; k < msa->nseqs; k++) has_motif[j++] = hm;
}
else has_motif[j++] = hm;
}
}
if (!meme_mode) {
fprintf(stderr, "Extracting and pooling sufficient statistics ...\n");
pmsa = ss_pooled_from_msas(msas, 1, size, NULL, 0);
msa_remove_N_from_alph(pmsa->pooled_msa);
}
/* obtain individual sequences, if necessary */
if (nmostprevalent > 0 || nsamples > 0 || meme_mode) {
if (meme_mode) fprintf(stderr, "Converting to individual sequences ...\n");
else fprintf(stderr, "Obtaining reference sequences for pre-processing ...\n");
seqset = mtf_get_seqset(msas, meme_mode ? -1 : 1, 10 * size);
/* for now, assume 1st seq is reference */
msa_remove_N_from_alph(seqset->set);
}
if (nmostprevalent > 0) {
fprintf(stderr, "Obtaining %d most prevalent %d-tuples ...\n",
nmostprevalent, tuple_size);
init_list = lst_new_ptr(nmostprevalent);
mtf_get_common_ntuples(seqset, init_list, tuple_size, nmostprevalent);
}
else if (nsamples > 0) {
fprintf(stderr, "Sampling %d %d-tuples ...\n", nsamples, tuple_size);
init_list = lst_new_ptr(nsamples);
mtf_sample_ntuples(seqset, init_list, tuple_size, nsamples);
}
/* in meme_mode, backgd model can be specified as eq freqs in a .mod file */
if (meme_mode && backgd_mod != NULL && has_motif == NULL)
backgd_mnmod = backgd_mod->backgd_freqs;
/* estimate background model, if necessary */
else if (backgd_mod == NULL && (!meme_mode || has_motif == NULL)) {
fprintf(stderr, "Fitting background model%s ...\n",
has_motif == NULL ? "" : " (for use in initialization)");
/* if discriminative, be clear
backgd isn't really part of the
estimation procedure */
if (meme_mode) {
backgd_mnmod = vec_new(strlen(seqset->set->alphabet));
mtf_estim_backgd_mn(seqset, backgd_mnmod);
}
else {
backgd_mod = tm_new(tr_create_copy(tree), NULL, NULL, F81,
pmsa->pooled_msa->alphabet, 1, 0, NULL, -1);
tm_fit(backgd_mod, pmsa->pooled_msa,
tm_params_init(backgd_mod, .1, 5, 0),
-1, OPT_MED_PREC, NULL, 0, NULL);
}
}
/* select subset of init strings, if necessary */
if (nbest > 0 && init_list != NULL) {
fprintf(stderr, "Winnowing candidate start strings ...\n");
tmpl = lst_new_ptr(nbest);
mtf_winnow_starts(meme_mode ? (void*)seqset : (void*)pmsa,
init_list, nbest, tmpl, !meme_mode, size, tree,
meme_mode ? (void*)backgd_mnmod : (void*)backgd_mod,
has_motif);
lst_free(init_list);
init_list = tmpl;
}
/* Now find motifs */
motifs = mtf_find(meme_mode ? (void*)seqset : (void*)pmsa,
!meme_mode, size, nmotifs, tree,
meme_mode ? (void*)backgd_mnmod : (void*)backgd_mod,
has_motif, prior, nrestarts, init_list, sample_parms,
npseudocounts);
fprintf(stderr, "\n\n");
if (do_bed)
bedfeats = gff_new_set_init("phast_motif", "0.1b");
/* generate output */
for (i = 0; i < lst_size(motifs); i++) {
Motif *m = lst_get_ptr(motifs, i);
if (!suppress_stdout) {
if (lst_size(motifs) > 1)
printf("\n**********\nMOTIF #%d\n**********\n\n", i+1);
mtf_print(stdout, m);
}
if (do_html) {
String *fname = str_dup(output_prefix);
str_append_int(fname, i+1);
str_append_charstr(fname, ".html");
mtf_print_html(phast_fopen(fname->chars, "w+"), m);
str_free(fname);
}
if (do_bed)
mtf_add_features(m, bedfeats);
}
if (do_html) {
String *fname = str_dup(output_prefix);
str_append_charstr(fname, "index.html");
mtf_print_summary_html(phast_fopen(fname->chars, "w+"),
motifs, output_prefix);
str_free(fname);
}
if (do_bed) {
String *fname = str_dup(output_prefix);
str_append_charstr(fname, "bed");
gff_print_bed(phast_fopen(fname->chars, "w+"),
bedfeats, FALSE);
str_free(fname);
}
return 0;
}
