/*********************************************************************** * Discard motifs that are not connected. ***********************************************************************/ static void throw_out_unused_motifs (MATRIX_T* transp_freq, MATRIX_T* spacer_ave, int* num_motifs, MOTIF_T* motifs) { int i_motif, j_motif; ARRAY_T* row_sums; ARRAY_T* col_sums; // Extract the margins of the transition matrix. row_sums = get_matrix_row_sums(transp_freq); col_sums = get_matrix_col_sums(transp_freq); for (i_motif = 0; i_motif < *num_motifs; i_motif++) { // Is this row or column empty? if ((get_array_item(i_motif + 1, row_sums) == 0.0) || (get_array_item(i_motif + 1, col_sums) == 0.0)) { if (verbosity >= NORMAL_VERBOSE) { fprintf(stderr, "Removing unused motif %s. No occurrences of this motif were found.\n", get_motif_id(&(motifs[i_motif]))); } // Remove the row and column from the transition matrix. remove_matrix_row(i_motif + 1, transp_freq); remove_matrix_col(i_motif + 1, transp_freq); assert(get_num_rows(transp_freq) == get_num_cols(transp_freq)); remove_matrix_row(i_motif + 1, spacer_ave); remove_matrix_col(i_motif + 1, spacer_ave); assert(get_num_rows(spacer_ave) == get_num_cols(spacer_ave)); // Remove the motif from the array. for (j_motif = i_motif + 1; j_motif < *num_motifs; j_motif++) { free_motif(&(motifs[j_motif - 1])); copy_motif(&(motifs[j_motif]), &(motifs[j_motif - 1])); } free_motif(&(motifs[j_motif - 1])); (*num_motifs)--; i_motif--; // Recalculate the row and column sums. free_array(row_sums); free_array(col_sums); row_sums = get_matrix_row_sums(transp_freq); col_sums = get_matrix_col_sums(transp_freq); } } free_array(row_sums); free_array(col_sums); }
/************************************************************************* * Entry point for pmp_bf *************************************************************************/ int main(int argc, char *argv[]) { char* bg_filename = NULL; char* motif_name = "motif"; // Use this motif name in the output. STRING_LIST_T* selected_motifs = NULL; double fg_rate = 1.0; double bg_rate = 1.0; double purine_pyrimidine = 1.0; // r double transition_transversion = 0.5; // R double pseudocount = 0.1; GAP_SUPPORT_T gap_support = SKIP_GAPS; MODEL_TYPE_T model_type = F81_MODEL; BOOLEAN_T use_halpern_bruno = FALSE; char* ustar_label = NULL; // TLB; create uniform star tree int i; program_name = "pmp_bf"; /********************************************** * COMMAND LINE PROCESSING **********************************************/ // Define command line options. (FIXME: Repeated code) // FIXME: Note that if you add or remove options you // must change n_options. int n_options = 12; cmdoption const pmp_options[] = { {"hb", NO_VALUE}, {"ustar", REQUIRED_VALUE}, {"model", REQUIRED_VALUE}, {"pur-pyr", REQUIRED_VALUE}, {"transition-transversion", REQUIRED_VALUE}, {"bg", REQUIRED_VALUE}, {"fg", REQUIRED_VALUE}, {"motif", REQUIRED_VALUE}, {"motif-name", REQUIRED_VALUE}, {"bgfile", REQUIRED_VALUE}, {"pseudocount", REQUIRED_VALUE}, {"verbosity", REQUIRED_VALUE} }; int option_index = 0; // Define the usage message. char usage[1000] = ""; strcat(usage, "USAGE: pmp [options] <tree file> <MEME file>\n"); strcat(usage, "\n"); strcat(usage, " Options:\n"); // Evolutionary model parameters. strcat(usage, " --hb\n"); strcat(usage, " --model single|average|jc|k2|f81|f84|hky|tn"); strcat(usage, " (default=f81)\n"); strcat(usage, " --pur-pyr <float> (default=1.0)\n"); strcat(usage, " --transition-transversion <float> (default=0.5)\n"); strcat(usage, " --bg <float> (default=1.0)\n"); strcat(usage, " --fg <float> (default=1.0)\n"); // Motif parameters. strcat(usage, " --motif <id> (default=all)\n"); strcat(usage, " --motif-name <string> (default from motif file)\n"); // Miscellaneous parameters strcat(usage, " --bgfile <background> (default from motif file)\n"); strcat(usage, " --pseudocount <float> (default=0.1)\n"); strcat(usage, " --ustar <label>\n"); // TLB; create uniform star tree strcat(usage, " --verbosity [1|2|3|4] (default 2)\n"); strcat(usage, "\n Prints the FP and FN rate at each of 10000 score values.\n"); strcat(usage, "\n Output format: [<motif_id> score <score> FPR <fpr> TPR <tpr>]+\n"); // Parse the command line. if (simple_setopt(argc, argv, n_options, pmp_options) != NO_ERROR) { die("Error processing command line options: option name too long.\n"); } while (TRUE) { int c = 0; char* option_name = NULL; char* option_value = NULL; const char * message = NULL; // Read the next option, and break if we're done. c = simple_getopt(&option_name, &option_value, &option_index); if (c == 0) { break; } else if (c < 0) { (void) simple_getopterror(&message); die("Error processing command line options (%s)\n", message); } if (strcmp(option_name, "model") == 0) { if (strcmp(option_value, "jc") == 0) { model_type = JC_MODEL; } else if (strcmp(option_value, "k2") == 0) { model_type = K2_MODEL; } else if (strcmp(option_value, "f81") == 0) { model_type = F81_MODEL; } else if (strcmp(option_value, "f84") == 0) { model_type = F84_MODEL; } else if (strcmp(option_value, "hky") == 0) { model_type = HKY_MODEL; } else if (strcmp(option_value, "tn") == 0) { model_type = TAMURA_NEI_MODEL; } else if (strcmp(option_value, "single") == 0) { model_type = SINGLE_MODEL; } else if (strcmp(option_value, "average") == 0) { model_type = AVERAGE_MODEL; } else { die("Unknown model: %s\n", option_value); } } else if (strcmp(option_name, "hb") == 0){ use_halpern_bruno = TRUE; } else if (strcmp(option_name, "ustar") == 0){ // TLB; create uniform star tree ustar_label = option_value; } else if (strcmp(option_name, "pur-pyr") == 0){ purine_pyrimidine = atof(option_value); } else if (strcmp(option_name, "transition-transversion") == 0){ transition_transversion = atof(option_value); } else if (strcmp(option_name, "bg") == 0){ bg_rate = atof(option_value); } else if (strcmp(option_name, "fg") == 0){ fg_rate = atof(option_value); } else if (strcmp(option_name, "motif") == 0){ if (selected_motifs == NULL) { selected_motifs = new_string_list(); } add_string(option_value, selected_motifs); } else if (strcmp(option_name, "motif-name") == 0){ motif_name = option_value; } else if (strcmp(option_name, "bgfile") == 0){ bg_filename = option_value; } else if (strcmp(option_name, "pseudocount") == 0){ pseudocount = atof(option_value); } else if (strcmp(option_name, "verbosity") == 0){ verbosity = atoi(option_value); } } // Must have tree and motif file names if (argc != option_index + 2) { fprintf(stderr, "%s", usage); exit(EXIT_FAILURE); } /********************************************** * Read the phylogenetic tree. **********************************************/ char* tree_filename = NULL; TREE_T* tree = NULL; tree_filename = argv[option_index]; option_index++; tree = read_tree_from_file(tree_filename); // get the species names STRING_LIST_T* alignment_species = make_leaf_list(tree); char *root_label = get_label(tree); // in case target in center if (strlen(root_label)>0) add_string(root_label, alignment_species); //write_string_list(" ", alignment_species, stderr); // TLB; Convert the tree to a uniform star tree with // the target sequence at its center. if (ustar_label != NULL) { tree = convert_to_uniform_star_tree(tree, ustar_label); if (tree == NULL) die("Tree or alignment missing target %s\n", ustar_label); if (verbosity >= NORMAL_VERBOSE) { fprintf(stderr, "Target %s placed at center of uniform (d=%.3f) star tree:\n", ustar_label, get_total_length(tree) / get_num_children(tree) ); write_tree(tree, stderr); } } /********************************************** * Read the motifs. **********************************************/ char* meme_filename = argv[option_index]; option_index++; int num_motifs = 0; MREAD_T *mread; ALPH_T alph; ARRAYLST_T *motifs; ARRAY_T *bg_freqs; mread = mread_create(meme_filename, OPEN_MFILE); mread_set_bg_source(mread, bg_filename); mread_set_pseudocount(mread, pseudocount); // read motifs motifs = mread_load(mread, NULL); alph = mread_get_alphabet(mread); bg_freqs = mread_get_background(mread); // check if (arraylst_size(motifs) == 0) die("No motifs in %s.", meme_filename); // TLB; need to resize bg_freqs array to ALPH_SIZE items // or copy array breaks in HB mode. This throws away // the freqs for the ambiguous characters; int asize = alph_size(alph, ALPH_SIZE); resize_array(bg_freqs, asize); /************************************************************** * Compute probability distributions for each of the selected motifs. **************************************************************/ int motif_index; for (motif_index = 0; motif_index < arraylst_size(motifs); motif_index++) { MOTIF_T* motif = (MOTIF_T*)arraylst_get(motif_index, motifs); char* motif_id = get_motif_id(motif); char* bare_motif_id = motif_id; // We may have specified on the command line that // only certain motifs were to be used. if (selected_motifs != NULL) { if (*bare_motif_id == '+' || *bare_motif_id == '-') { // The selected motif id won't included a strand indicator. bare_motif_id++; } if (have_string(bare_motif_id, selected_motifs) == FALSE) { continue; } } if (verbosity >= NORMAL_VERBOSE) { fprintf( stderr, "Using motif %s of width %d.\n", motif_id, get_motif_length(motif) ); } // Build an array of evolutionary models for each position in the motif. EVOMODEL_T** models = make_motif_models( motif, bg_freqs, model_type, fg_rate, bg_rate, purine_pyrimidine, transition_transversion, use_halpern_bruno ); // Get the frequencies under the background model (row 0) // and position-dependent scores (rows 1..w) // for each possible alignment column. MATRIX_T* pssm_matrix = build_alignment_pssm_matrix( alph, alignment_species, get_motif_length(motif) + 1, models, tree, gap_support ); ARRAY_T* alignment_col_freqs = allocate_array(get_num_cols(pssm_matrix)); copy_array(get_matrix_row(0, pssm_matrix), alignment_col_freqs); remove_matrix_row(0, pssm_matrix); // throw away first row //print_col_frequencies(alph, alignment_col_freqs); // // Get the position-dependent null model alignment column frequencies // int w = get_motif_length(motif); int ncols = get_num_cols(pssm_matrix); MATRIX_T* pos_dep_bkg = allocate_matrix(w, ncols); for (i=0; i<w; i++) { // get the evo model corresponding to this column of the motif // and store it as the first evolutionary model. myfree(models[0]); // Use motif PSFM for equilibrium freqs. for model. ARRAY_T* site_specific_freqs = allocate_array(asize); int j = 0; for(j = 0; j < asize; j++) { double value = get_matrix_cell(i, j, get_motif_freqs(motif)); set_array_item(j, value, site_specific_freqs); } if (use_halpern_bruno == FALSE) { models[0] = make_model( model_type, fg_rate, transition_transversion, purine_pyrimidine, site_specific_freqs, NULL ); } else { models[0] = make_model( model_type, fg_rate, transition_transversion, purine_pyrimidine, bg_freqs, site_specific_freqs ); } // get the alignment column frequencies using this model MATRIX_T* tmp_pssm_matrix = build_alignment_pssm_matrix( alph, alignment_species, 2, // only interested in freqs under bkg models, tree, gap_support ); // assemble the position-dependent background alignment column freqs. set_matrix_row(i, get_matrix_row(0, tmp_pssm_matrix), pos_dep_bkg); // chuck the pssm (not his real name) free_matrix(tmp_pssm_matrix); } // // Compute and print the score distribution under the background model // and under the (position-dependent) motif model. // int range = 10000; // 10^4 gives same result as 10^5, but 10^3 differs // under background model PSSM_T* pssm = build_matrix_pssm(alph, pssm_matrix, alignment_col_freqs, range); // under position-dependent background (motif) model PSSM_T* pssm_pos_dep = build_matrix_pssm(alph, pssm_matrix, alignment_col_freqs, range); get_pv_lookup_pos_dep( pssm_pos_dep, pos_dep_bkg, NULL // no priors used ); // print FP and FN distributions int num_items = get_pssm_pv_length(pssm_pos_dep); for (i=0; i<num_items; i++) { double pvf = get_pssm_pv(i, pssm); double pvt = get_pssm_pv(i, pssm_pos_dep); double fpr = pvf; double fnr = 1 - pvt; if (fpr >= 0.99999 || fnr == 0) continue; printf("%s score %d FPR %.3g FNR %.3g\n", motif_id, i, fpr, fnr); } // free stuff free_pssm(pssm); free_pssm(pssm_pos_dep); if (models != NULL) { int model_index; int num_models = get_motif_length(motif) + 1; for (model_index = 0; model_index < num_models; model_index++) { free_model(models[model_index]); } myfree(models); } } // motif arraylst_destroy(destroy_motif, motifs); /********************************************** * Clean up. **********************************************/ // TLB may have encountered a memory corruption bug here // CEG has not been able to reproduce it. valgrind says all is well. free_array(bg_freqs); free_tree(TRUE, tree); free_string_list(selected_motifs); return(0); } // main