int run_association_test(shared_options_data_t* shared_options_data, assoc_options_data_t* options_data) {
list_t *output_list = (list_t*) malloc (sizeof(list_t));
list_init("output", shared_options_data->num_threads, INT_MAX, output_list);
int ret_code = 0;
vcf_file_t *vcf_file = vcf_open(shared_options_data->vcf_filename, shared_options_data->max_batches);
if (!vcf_file) {
LOG_FATAL("VCF file does not exist!\n");
}
ped_file_t *ped_file = ped_open(shared_options_data->ped_filename);
if (!ped_file) {
LOG_FATAL("PED file does not exist!\n");
}
LOG_INFO("About to read PED file...\n");
// Read PED file before doing any processing
ret_code = ped_read(ped_file);
if (ret_code != 0) {
LOG_FATAL_F("Can't read PED file: %s\n", ped_file->filename);
}
// Try to create the directory where the output files will be stored
ret_code = create_directory(shared_options_data->output_directory);
if (ret_code != 0 && errno != EEXIST) {
LOG_FATAL_F("Can't create output directory: %s\n", shared_options_data->output_directory);
}
LOG_INFO("About to perform basic association test...\n");
#pragma omp parallel sections private(ret_code)
{
#pragma omp section
{
LOG_DEBUG_F("Level %d: number of threads in the team - %d\n", 0, omp_get_num_threads());
double start = omp_get_wtime();
ret_code = vcf_read(vcf_file, 0,
(shared_options_data->batch_bytes > 0) ? shared_options_data->batch_bytes : shared_options_data->batch_lines,
shared_options_data->batch_bytes <= 0);
double stop = omp_get_wtime();
double total = stop - start;
if (ret_code) {
LOG_FATAL_F("Error %d while reading the file %s\n", ret_code, vcf_file->filename);
}
LOG_INFO_F("[%dR] Time elapsed = %f s\n", omp_get_thread_num(), total);
LOG_INFO_F("[%dR] Time elapsed = %e ms\n", omp_get_thread_num(), total*1000);
notify_end_reading(vcf_file);
}
#pragma omp section
{
LOG_DEBUG_F("Level %d: number of threads in the team - %d\n", 10, omp_get_num_threads());
// Enable nested parallelism
omp_set_nested(1);
volatile int initialization_done = 0;
// Pedigree information
individual_t **individuals = NULL;
khash_t(ids) *sample_ids = NULL;
// Create chain of filters for the VCF file
filter_t **filters = NULL;
int num_filters = 0;
if (shared_options_data->chain != NULL) {
filters = sort_filter_chain(shared_options_data->chain, &num_filters);
}
FILE *passed_file = NULL, *failed_file = NULL;
get_filtering_output_files(shared_options_data, &passed_file, &failed_file);
double start = omp_get_wtime();
double *factorial_logarithms = NULL;
int i = 0;
#pragma omp parallel num_threads(shared_options_data->num_threads) shared(initialization_done, factorial_logarithms, filters, individuals)
{
LOG_DEBUG_F("Level %d: number of threads in the team - %d\n", 11, omp_get_num_threads());
char *text_begin, *text_end;
vcf_reader_status *status;
while(text_begin = fetch_vcf_text_batch(vcf_file)) {
text_end = text_begin + strlen(text_begin);
if (text_begin == text_end) { // EOF
free(text_begin);
break;
}
# pragma omp critical
{
status = vcf_reader_status_new(shared_options_data->batch_lines, i);
i++;
}
if (shared_options_data->batch_bytes > 0) {
ret_code = run_vcf_parser(text_begin, text_end, 0, vcf_file, status);
} else if (shared_options_data->batch_lines > 0) {
ret_code = run_vcf_parser(text_begin, text_end, shared_options_data->batch_lines, vcf_file, status);
}
// Initialize structures needed for association tests and write headers of output files
if (!initialization_done && vcf_file->samples_names->size > 0) {
# pragma omp critical
{
// Guarantee that just one thread performs this operation
if (!initialization_done) {
// Create map to associate the position of individuals in the list of samples defined in the VCF file
sample_ids = associate_samples_and_positions(vcf_file);
// Sort individuals in PED as defined in the VCF file
individuals = sort_individuals(vcf_file, ped_file);
/*
printf("num samples = %zu\n", get_num_vcf_samples(file));
printf("pos = { ");
for (int j = 0; j < get_num_vcf_samples(file); j++) {
assert(individuals[j]);
printf("%s ", individuals[j]->id);
}
printf("}\n");
*/
// Add headers associated to the defined filters
vcf_header_entry_t **filter_headers = get_filters_as_vcf_headers(filters, num_filters);
for (int j = 0; j < num_filters; j++) {
add_vcf_header_entry(filter_headers[j], vcf_file);
}
// Write file format, header entries and delimiter
if (passed_file != NULL) { write_vcf_header(vcf_file, passed_file); }
if (failed_file != NULL) { write_vcf_header(vcf_file, failed_file); }
LOG_DEBUG("VCF header written\n");
if (options_data->task == FISHER) {
factorial_logarithms = init_logarithm_array(get_num_vcf_samples(vcf_file) * 10);
}
initialization_done = 1;
}
}
}
// If it has not been initialized it means that header is not fully read
if (!initialization_done) {
continue;
}
vcf_batch_t *batch = fetch_vcf_batch(vcf_file);
if (i % 100 == 0) {
LOG_INFO_F("Batch %d reached by thread %d - %zu/%zu records \n",
i, omp_get_thread_num(),
batch->records->size, batch->records->capacity);
}
assert(batch);
// Launch association test over records that passed the filters
array_list_t *failed_records = NULL;
int num_variables = ped_file? get_num_variables(ped_file): 0;
array_list_t *passed_records = filter_records(filters, num_filters, individuals, sample_ids, num_variables, batch->records, &failed_records);
if (passed_records->size > 0) {
assoc_test(options_data->task, (vcf_record_t**) passed_records->items, passed_records->size,
individuals, get_num_vcf_samples(vcf_file), factorial_logarithms, output_list);
}
// Write records that passed and failed filters to separate files, and free them
write_filtering_output_files(passed_records, failed_records, passed_file, failed_file);
free_filtered_records(passed_records, failed_records, batch->records);
// Free batch and its contents
vcf_reader_status_free(status);
vcf_batch_free(batch);
}
notify_end_parsing(vcf_file);
}
double stop = omp_get_wtime();
double total = stop - start;
LOG_INFO_F("[%d] Time elapsed = %f s\n", omp_get_thread_num(), total);
LOG_INFO_F("[%d] Time elapsed = %e ms\n", omp_get_thread_num(), total*1000);
// Free resources
for (int i = 0; i < num_filters; i++) {
filter_t *filter = filters[i];
filter->free_func(filter);
}
free(filters);
if (sample_ids) { kh_destroy(ids, sample_ids); }
if (individuals) { free(individuals); }
// Decrease list writers count
for (int i = 0; i < shared_options_data->num_threads; i++) {
list_decr_writers(output_list);
}
}
#pragma omp section
{
// Thread that writes the results to the output file
LOG_DEBUG_F("Level %d: number of threads in the team - %d\n", 20, omp_get_num_threads());
double start = omp_get_wtime();
// Get the file descriptor
char *path;
FILE *fd = get_assoc_output_file(options_data->task, shared_options_data, &path);
LOG_INFO_F("Association test output filename = %s\n", path);
// Write data: header + one line per variant
write_output_header(options_data->task, fd);
write_output_body(options_data->task, output_list, fd);
fclose(fd);
// Sort resulting file
char *cmd = calloc (40 + strlen(path) * 4, sizeof(char));
sprintf(cmd, "sort -k1,1h -k2,2n %s > %s.tmp && mv %s.tmp %s", path, path, path, path);
int sort_ret = system(cmd);
if (sort_ret) {
LOG_WARN("Association results could not be sorted by chromosome and position, will be shown unsorted\n");
}
double stop = omp_get_wtime();
double total = stop - start;
LOG_INFO_F("[%dW] Time elapsed = %f s\n", omp_get_thread_num(), total);
LOG_INFO_F("[%dW] Time elapsed = %e ms\n", omp_get_thread_num(), total*1000);
}
}
free(output_list);
vcf_close(vcf_file);
ped_close(ped_file, 1,1);
return ret_code;
}
int run_filter(shared_options_data_t *shared_options_data, filter_options_data_t *options_data) {
int ret_code;
double start, stop, total;
vcf_file_t *file = vcf_open(shared_options_data->vcf_filename, shared_options_data->max_batches);
if (!file) {
LOG_FATAL("VCF file does not exist!\n");
}
ret_code = create_directory(shared_options_data->output_directory);
if (ret_code != 0 && errno != EEXIST) {
LOG_FATAL_F("Can't create output directory: %s\n", shared_options_data->output_directory);
}
#pragma omp parallel sections private(start, stop, total)
{
#pragma omp section
{
LOG_DEBUG_F("Thread %d reads the VCF file\n", omp_get_thread_num());
// Reading
start = omp_get_wtime();
if (shared_options_data->batch_bytes > 0) {
ret_code = vcf_parse_batches_in_bytes(shared_options_data->batch_bytes, file);
} else if (shared_options_data->batch_lines > 0) {
ret_code = vcf_parse_batches(shared_options_data->batch_lines, file);
}
stop = omp_get_wtime();
total = stop - start;
if (ret_code) { LOG_FATAL_F("[%dR] Error code = %d\n", omp_get_thread_num(), ret_code); }
LOG_INFO_F("[%dR] Time elapsed = %f s\n", omp_get_thread_num(), total);
LOG_INFO_F("[%dR] Time elapsed = %e ms\n", omp_get_thread_num(), total*1000);
notify_end_parsing(file);
}
#pragma omp section
{
filter_t **filters = NULL;
int num_filters = 0;
if (shared_options_data->chain != NULL) {
filters = sort_filter_chain(shared_options_data->chain, &num_filters);
}
FILE *passed_file = NULL, *failed_file = NULL;
get_filtering_output_files(shared_options_data, &passed_file, &failed_file);
if (!options_data->save_rejected) {
fclose(failed_file);
}
LOG_DEBUG("File streams created\n");
start = omp_get_wtime();
int i = 0;
vcf_batch_t *batch = NULL;
while ((batch = fetch_vcf_batch(file)) != NULL) {
if (i == 0) {
// Add headers associated to the defined filters
vcf_header_entry_t **filter_headers = get_filters_as_vcf_headers(filters, num_filters);
for (int j = 0; j < num_filters; j++) {
add_vcf_header_entry(filter_headers[j], file);
}
// Write file format, header entries and delimiter
write_vcf_header(file, passed_file);
if (options_data->save_rejected) {
write_vcf_header(file, failed_file);
}
LOG_DEBUG("VCF header written created\n");
}
array_list_t *input_records = batch->records;
array_list_t *passed_records, *failed_records;
if (i % 100 == 0) {
LOG_INFO_F("Batch %d reached by thread %d - %zu/%zu records \n",
i, omp_get_thread_num(),
batch->records->size, batch->records->capacity);
}
if (filters == NULL) {
passed_records = input_records;
} else {
failed_records = array_list_new(input_records->size + 1, 1, COLLECTION_MODE_ASYNCHRONIZED);
passed_records = run_filter_chain(input_records, failed_records, filters, num_filters);
}
// Write records that passed and failed to 2 new separated files
if (passed_records != NULL && passed_records->size > 0) {
LOG_DEBUG_F("[batch %d] %zu passed records\n", i, passed_records->size);
#pragma omp critical
{
for (int r = 0; r < passed_records->size; r++) {
write_vcf_record(passed_records->items[r], passed_file);
}
// write_batch(passed_records, passed_file);
}
}
if (options_data->save_rejected && failed_records != NULL && failed_records->size > 0) {
LOG_DEBUG_F("[batch %d] %zu failed records\n", i, failed_records->size);
#pragma omp critical
{
for (int r = 0; r < failed_records->size; r++) {
write_vcf_record(failed_records->items[r], failed_file);
}
// write_batch(failed_records, failed_file);
}
}
// Free batch and its contents
vcf_batch_free(batch);
// Free items in both lists (not their internal data)
if (passed_records != input_records) {
array_list_free(passed_records, NULL);
}
if (failed_records) {
array_list_free(failed_records, NULL);
}
i++;
}
stop = omp_get_wtime();
total = stop - start;
LOG_INFO_F("[%d] Time elapsed = %f s\n", omp_get_thread_num(), total);
LOG_INFO_F("[%d] Time elapsed = %e ms\n", omp_get_thread_num(), total*1000);
// Free resources
if (passed_file) {
fclose(passed_file);
}
if (options_data->save_rejected && failed_file) {
fclose(failed_file);
}
free_filters(filters, num_filters);
}
}
vcf_close(file);
return 0;
}
int run_effect(char **urls, shared_options_data_t *shared_options_data, effect_options_data_t *options_data) {
int ret_code = 0;
double start, stop, total;
vcf_file_t *vcf_file = vcf_open(shared_options_data->vcf_filename, shared_options_data->max_batches);
if (!vcf_file) {
LOG_FATAL("VCF file does not exist!\n");
}
ped_file_t *ped_file = NULL;
if (shared_options_data->ped_filename) {
ped_file = ped_open(shared_options_data->ped_filename);
if (!ped_file) {
LOG_FATAL("PED file does not exist!\n");
}
LOG_INFO("About to read PED file...\n");
// Read PED file before doing any processing
ret_code = ped_read(ped_file);
if (ret_code != 0) {
LOG_FATAL_F("Can't read PED file: %s\n", ped_file->filename);
}
}
char *output_directory = shared_options_data->output_directory;
size_t output_directory_len = strlen(output_directory);
ret_code = create_directory(output_directory);
if (ret_code != 0 && errno != EEXIST) {
LOG_FATAL_F("Can't create output directory: %s\n", output_directory);
}
// Remove all .txt files in folder
ret_code = delete_files_by_extension(output_directory, "txt");
if (ret_code != 0) {
return ret_code;
}
// Initialize environment for connecting to the web service
ret_code = init_http_environment(0);
if (ret_code != 0) {
return ret_code;
}
// Output file descriptors
static cp_hashtable *output_files = NULL;
// Lines of the output data in the main .txt files
static list_t *output_list = NULL;
// Consequence type counters (for summary, must be kept between web service calls)
static cp_hashtable *summary_count = NULL;
// Gene list (for genes-with-variants, must be kept between web service calls)
static cp_hashtable *gene_list = NULL;
// Initialize collections of file descriptors and summary counters
ret_code = initialize_output_files(output_directory, output_directory_len, &output_files);
if (ret_code != 0) {
return ret_code;
}
initialize_output_data_structures(shared_options_data, &output_list, &summary_count, &gene_list);
initialize_ws_buffers(shared_options_data->num_threads);
// Create job.status file
char job_status_filename[output_directory_len + 10];
sprintf(job_status_filename, "%s/job.status", output_directory);
FILE *job_status = new_job_status_file(job_status_filename);
if (!job_status) {
LOG_FATAL("Can't create job status file\n");
} else {
update_job_status_file(0, job_status);
}
#pragma omp parallel sections private(start, stop, total)
{
#pragma omp section
{
LOG_DEBUG_F("Thread %d reads the VCF file\n", omp_get_thread_num());
start = omp_get_wtime();
ret_code = vcf_read(vcf_file, 1,
(shared_options_data->batch_bytes > 0) ? shared_options_data->batch_bytes : shared_options_data->batch_lines,
shared_options_data->batch_bytes <= 0);
stop = omp_get_wtime();
total = stop - start;
if (ret_code) {
LOG_ERROR_F("Error %d while reading the file %s\n", ret_code, vcf_file->filename);
}
LOG_INFO_F("[%dR] Time elapsed = %f s\n", omp_get_thread_num(), total);
LOG_INFO_F("[%dR] Time elapsed = %e ms\n", omp_get_thread_num(), total*1000);
notify_end_parsing(vcf_file);
}
#pragma omp section
{
// Enable nested parallelism and set the number of threads the user has chosen
omp_set_nested(1);
LOG_DEBUG_F("Thread %d processes data\n", omp_get_thread_num());
// Filters and files for filtering output
filter_t **filters = NULL;
int num_filters = 0;
if (shared_options_data->chain != NULL) {
filters = sort_filter_chain(shared_options_data->chain, &num_filters);
}
FILE *passed_file = NULL, *failed_file = NULL, *non_processed_file = NULL;
get_filtering_output_files(shared_options_data, &passed_file, &failed_file);
// Pedigree information (used in some filters)
individual_t **individuals = NULL;
khash_t(ids) *sample_ids = NULL;
// Filename structure outdir/vcfname.errors
char *prefix_filename = calloc(strlen(shared_options_data->vcf_filename), sizeof(char));
get_filename_from_path(shared_options_data->vcf_filename, prefix_filename);
char *non_processed_filename = malloc((strlen(shared_options_data->output_directory) + strlen(prefix_filename) + 9) * sizeof(char));
sprintf(non_processed_filename, "%s/%s.errors", shared_options_data->output_directory, prefix_filename);
non_processed_file = fopen(non_processed_filename, "w");
free(non_processed_filename);
// Maximum size processed by each thread (never allow more than 1000 variants per query)
if (shared_options_data->batch_lines > 0) {
shared_options_data->entries_per_thread = MIN(MAX_VARIANTS_PER_QUERY,
ceil((float) shared_options_data->batch_lines / shared_options_data->num_threads));
} else {
shared_options_data->entries_per_thread = MAX_VARIANTS_PER_QUERY;
}
LOG_DEBUG_F("entries-per-thread = %d\n", shared_options_data->entries_per_thread);
int i = 0;
vcf_batch_t *batch = NULL;
int ret_ws_0 = 0, ret_ws_1 = 0, ret_ws_2 = 0;
start = omp_get_wtime();
while (batch = fetch_vcf_batch(vcf_file)) {
if (i == 0) {
// Add headers associated to the defined filters
vcf_header_entry_t **filter_headers = get_filters_as_vcf_headers(filters, num_filters);
for (int j = 0; j < num_filters; j++) {
add_vcf_header_entry(filter_headers[j], vcf_file);
}
// Write file format, header entries and delimiter
if (passed_file != NULL) { write_vcf_header(vcf_file, passed_file); }
if (failed_file != NULL) { write_vcf_header(vcf_file, failed_file); }
if (non_processed_file != NULL) { write_vcf_header(vcf_file, non_processed_file); }
LOG_DEBUG("VCF header written\n");
if (ped_file) {
// Create map to associate the position of individuals in the list of samples defined in the VCF file
sample_ids = associate_samples_and_positions(vcf_file);
// Sort individuals in PED as defined in the VCF file
individuals = sort_individuals(vcf_file, ped_file);
}
}
// printf("batch loaded = '%.*s'\n", 50, batch->text);
// printf("batch text len = %zu\n", strlen(batch->text));
// if (i % 10 == 0) {
LOG_INFO_F("Batch %d reached by thread %d - %zu/%zu records \n",
i, omp_get_thread_num(),
batch->records->size, batch->records->capacity);
// }
int reconnections = 0;
int max_reconnections = 3; // TODO allow to configure?
// Write records that passed to a separate file, and query the WS with them as args
array_list_t *failed_records = NULL;
int num_variables = ped_file? get_num_variables(ped_file): 0;
array_list_t *passed_records = filter_records(filters, num_filters, individuals, sample_ids, num_variables, batch->records, &failed_records);
if (passed_records->size > 0) {
// Divide the list of passed records in ranges of size defined in config file
int num_chunks;
int *chunk_sizes;
int *chunk_starts = create_chunks(passed_records->size, shared_options_data->entries_per_thread, &num_chunks, &chunk_sizes);
do {
// OpenMP: Launch a thread for each range
#pragma omp parallel for num_threads(shared_options_data->num_threads)
for (int j = 0; j < num_chunks; j++) {
int tid = omp_get_thread_num();
LOG_DEBUG_F("[%d] WS invocation\n", tid);
LOG_DEBUG_F("[%d] -- effect WS\n", tid);
if (!reconnections || ret_ws_0) {
ret_ws_0 = invoke_effect_ws(urls[0], (vcf_record_t**) (passed_records->items + chunk_starts[j]),
chunk_sizes[j], options_data->excludes);
parse_effect_response(tid, output_directory, output_directory_len, output_files, output_list, summary_count, gene_list);
free(effect_line[tid]);
effect_line[tid] = (char*) calloc (max_line_size[tid], sizeof(char));
}
if (!options_data->no_phenotypes) {
if (!reconnections || ret_ws_1) {
LOG_DEBUG_F("[%d] -- snp WS\n", omp_get_thread_num());
ret_ws_1 = invoke_snp_phenotype_ws(urls[1], (vcf_record_t**) (passed_records->items + chunk_starts[j]), chunk_sizes[j]);
parse_snp_phenotype_response(tid, output_list);
free(snp_line[tid]);
snp_line[tid] = (char*) calloc (snp_max_line_size[tid], sizeof(char));
}
if (!reconnections || ret_ws_2) {
LOG_DEBUG_F("[%d] -- mutation WS\n", omp_get_thread_num());
ret_ws_2 = invoke_mutation_phenotype_ws(urls[2], (vcf_record_t**) (passed_records->items + chunk_starts[j]), chunk_sizes[j]);
parse_mutation_phenotype_response(tid, output_list);
free(mutation_line[tid]);
mutation_line[tid] = (char*) calloc (mutation_max_line_size[tid], sizeof(char));
}
}
}
LOG_DEBUG_F("*** %dth web services invocation finished\n", i);
if (ret_ws_0 || ret_ws_1 || ret_ws_2) {
if (ret_ws_0) {
LOG_ERROR_F("Effect web service error: %s\n", get_last_http_error(ret_ws_0));
}
if (ret_ws_1) {
LOG_ERROR_F("SNP phenotype web service error: %s\n", get_last_http_error(ret_ws_1));
}
if (ret_ws_2) {
LOG_ERROR_F("Mutations phenotype web service error: %s\n", get_last_http_error(ret_ws_2));
}
// In presence of errors, wait 4 seconds before retrying
reconnections++;
LOG_ERROR_F("Some errors ocurred, reconnection #%d\n", reconnections);
sleep(4);
} else {
free(chunk_starts);
free(chunk_sizes);
}
} while (reconnections < max_reconnections && (ret_ws_0 || ret_ws_1 || ret_ws_2));
}
// If the maximum number of reconnections was reached still with errors,
// write the non-processed batch to the corresponding file
if (reconnections == max_reconnections && (ret_ws_0 || ret_ws_1 || ret_ws_2)) {
#pragma omp critical
{
write_vcf_batch(batch, non_processed_file);
}
}
// Write records that passed and failed filters to separate files, and free them
write_filtering_output_files(passed_records, failed_records, passed_file, failed_file);
free_filtered_records(passed_records, failed_records, batch->records);
// Free batch and its contents
vcf_batch_free(batch);
i++;
}
stop = omp_get_wtime();
total = stop - start;
LOG_INFO_F("[%d] Time elapsed = %f s\n", omp_get_thread_num(), total);
LOG_INFO_F("[%d] Time elapsed = %e ms\n", omp_get_thread_num(), total*1000);
// Free resources
if (passed_file) { fclose(passed_file); }
if (failed_file) { fclose(failed_file); }
if (non_processed_file) { fclose(non_processed_file); }
// Free filters
for (i = 0; i < num_filters; i++) {
filter_t *filter = filters[i];
filter->free_func(filter);
}
free(filters);
// Decrease list writers count
for (i = 0; i < shared_options_data->num_threads; i++) {
list_decr_writers(output_list);
}
}
#pragma omp section
{
// Thread which writes the results to all_variants, summary and one file per consequence type
int ret = 0;
char *line;
list_item_t* item = NULL;
FILE *fd = NULL;
FILE *all_variants_file = cp_hashtable_get(output_files, "all_variants");
FILE *snp_phenotype_file = cp_hashtable_get(output_files, "snp_phenotypes");
FILE *mutation_phenotype_file = cp_hashtable_get(output_files, "mutation_phenotypes");
while ((item = list_remove_item(output_list)) != NULL) {
line = item->data_p;
// Type greater than 0: consequence type identified by its SO code
// Type equals to -1: SNP phenotype
// Type equals to -2: mutation phenotype
if (item->type > 0) {
// Write entry in the consequence type file
fd = cp_hashtable_get(output_files, &(item->type));
int ret = fprintf(fd, "%s\n", line);
if (ret < 0) {
LOG_ERROR_F("Error writing to file: '%s'\n", line);
}
// Write in all_variants
ret = fprintf(all_variants_file, "%s\n", line);
if (ret < 0) {
LOG_ERROR_F("Error writing to all_variants: '%s'\n", line);
}
} else if (item->type == SNP_PHENOTYPE) {
ret = fprintf(snp_phenotype_file, "%s\n", line);
if (ret < 0) {
LOG_ERROR_F("Error writing to snp_phenotypes: '%s'\n", line);
}
} else if (item->type == MUTATION_PHENOTYPE) {
ret = fprintf(mutation_phenotype_file, "%s\n", line);
if (ret < 0) {
LOG_ERROR_F("Error writing to mutation_phenotypes: '%s'\n", line);
}
}
free(line);
list_item_free(item);
}
}
}
write_summary_file(summary_count, cp_hashtable_get(output_files, "summary"));
write_genes_with_variants_file(gene_list, output_directory);
write_result_file(shared_options_data, options_data, summary_count, output_directory);
free_output_data_structures(output_files, summary_count, gene_list);
free_ws_buffers(shared_options_data->num_threads);
free(output_list);
vcf_close(vcf_file);
update_job_status_file(100, job_status);
close_job_status_file(job_status);
return ret_code;
}
int run_stats(shared_options_data_t *shared_options_data, stats_options_data_t *options_data) {
file_stats_t *file_stats = file_stats_new();
sample_stats_t **sample_stats;
// List that stores the batches of records filtered by each thread
list_t *output_list[shared_options_data->num_threads];
// List that stores which thread filtered the next batch to save
list_t *next_token_list = malloc(sizeof(list_t));
int ret_code;
double start, stop, total;
vcf_file_t *vcf_file = vcf_open(shared_options_data->vcf_filename, shared_options_data->max_batches);
if (!vcf_file) {
LOG_FATAL("VCF file does not exist!\n");
}
ped_file_t *ped_file = NULL;
if (shared_options_data->ped_filename) {
ped_file = ped_open(shared_options_data->ped_filename);
if (!ped_file) {
LOG_FATAL("PED file does not exist!\n");
}
if(options_data->variable) {
set_variable_field(options_data->variable, 0, ped_file);
} else {
set_variable_field("PHENO", 6, ped_file);
}
if(options_data->variable_groups) {
int n, m;
char *variable_groups = strdup(options_data->variable_groups);
char **groups;
char **phenos_in_group;
groups = split(variable_groups, ":", &n);
for(int i = 0; i < n; i++){
phenos_in_group = split(groups[i], ",", &m);
if(set_phenotype_group(phenos_in_group, m, ped_file) < 0) {
LOG_ERROR("Variable can't appear in two groups\n");
return DUPLICATED_VARIABLE;
}
free(phenos_in_group);
}
ped_file->accept_new_values = 0;
free(variable_groups);
free(groups);
} else {
ped_file->accept_new_values = 1;
}
if(options_data->phenotype) {
int n;
char* phenotypes = strdup(options_data->phenotype);
char** pheno_values = split(phenotypes, ",", &n);
if(n != 2) {
LOG_ERROR("To handle case-control test, only two phenotypes are supported\n");
return MORE_THAN_TWO_PHENOTYPES;
} else {
set_unaffected_phenotype(pheno_values[0],ped_file);
set_affected_phenotype(pheno_values[1],ped_file);
}
} else {
set_unaffected_phenotype("1", ped_file);
set_affected_phenotype("2", ped_file);
}
LOG_INFO("About to read PED file...\n");
// Read PED file before doing any processing
ret_code = ped_read(ped_file);
if (ret_code != 0) {
LOG_FATAL_F("Can't read PED file: %s\n", ped_file->filename);
}
if(!ped_file->num_field) {
LOG_ERROR_F("Can't find the specified field \"%s\" in file: %s \n", options_data->variable, ped_file->filename);
return VARIABLE_FIELD_NOT_FOUND;
}
}
ret_code = create_directory(shared_options_data->output_directory);
if (ret_code != 0 && errno != EEXIST) {
LOG_FATAL_F("Can't create output directory: %s\n", shared_options_data->output_directory);
}
// Initialize variables related to the different threads
for (int i = 0; i < shared_options_data->num_threads; i++) {
output_list[i] = (list_t*) malloc(sizeof(list_t));
list_init("input", 1, shared_options_data->num_threads * shared_options_data->batch_lines, output_list[i]);
}
list_init("next_token", shared_options_data->num_threads, INT_MAX, next_token_list);
LOG_INFO("About to retrieve statistics from VCF file...\n");
#pragma omp parallel sections private(start, stop, total)
{
#pragma omp section
{
LOG_DEBUG_F("Thread %d reads the VCF file\n", omp_get_thread_num());
// Reading
start = omp_get_wtime();
if (shared_options_data->batch_bytes > 0) {
ret_code = vcf_parse_batches_in_bytes(shared_options_data->batch_bytes, vcf_file);
} else if (shared_options_data->batch_lines > 0) {
ret_code = vcf_parse_batches(shared_options_data->batch_lines, vcf_file);
}
stop = omp_get_wtime();
total = stop - start;
if (ret_code) { LOG_FATAL_F("[%dR] Error code = %d\n", omp_get_thread_num(), ret_code); }
LOG_INFO_F("[%dR] Time elapsed = %f s\n", omp_get_thread_num(), total);
LOG_INFO_F("[%dR] Time elapsed = %e ms\n", omp_get_thread_num(), total*1000);
notify_end_parsing(vcf_file);
}
#pragma omp section
{
// Enable nested parallelism and set the number of threads the user has chosen
omp_set_nested(1);
LOG_DEBUG_F("Thread %d processes data\n", omp_get_thread_num());
individual_t **individuals = NULL;
khash_t(ids) *sample_ids = NULL;
khash_t(str) *phenotype_ids = NULL;
int num_phenotypes;
start = omp_get_wtime();
int i = 0;
vcf_batch_t *batch = NULL;
while ((batch = fetch_vcf_batch(vcf_file)) != NULL) {
if (i == 0) {
sample_stats = malloc (get_num_vcf_samples(vcf_file) * sizeof(sample_stats_t*));
for (int j = 0; j < get_num_vcf_samples(vcf_file); j++) {
sample_stats[j] = sample_stats_new(array_list_get(j, vcf_file->samples_names));
}
if (ped_file) {
// Create map to associate the position of individuals in the list of samples defined in the VCF file
sample_ids = associate_samples_and_positions(vcf_file);
// Sort individuals in PED as defined in the VCF file
individuals = sort_individuals(vcf_file, ped_file);
// Get the khash of the phenotypes in PED file
phenotype_ids = get_phenotypes(ped_file);
num_phenotypes = get_num_variables(ped_file);
}
}
if (i % 50 == 0) {
LOG_INFO_F("Batch %d reached by thread %d - %zu/%zu records \n",
i, omp_get_thread_num(),
batch->records->size, batch->records->capacity);
}
// Divide the list of passed records in ranges of size defined in config file
int num_chunks;
int *chunk_sizes = NULL;
array_list_t *input_records = batch->records;
int *chunk_starts = create_chunks(input_records->size,
ceil((float) shared_options_data->batch_lines / shared_options_data->num_threads),
&num_chunks, &chunk_sizes);
// OpenMP: Launch a thread for each range
#pragma omp parallel for num_threads(shared_options_data->num_threads)
for (int j = 0; j < num_chunks; j++) {
LOG_DEBUG_F("[%d] Stats invocation\n", omp_get_thread_num());
// Invoke variant stats and/or sample stats when applies
if (options_data->variant_stats) {
int index = omp_get_thread_num() % shared_options_data->num_threads;
ret_code = get_variants_stats((vcf_record_t**) (input_records->items + chunk_starts[j]),
chunk_sizes[j], individuals, sample_ids,num_phenotypes, output_list[index], file_stats);
}
if (options_data->sample_stats) {
ret_code |= get_sample_stats((vcf_record_t**) (input_records->items + chunk_starts[j]),
chunk_sizes[j], individuals, sample_ids, sample_stats, file_stats);
}
}
if (options_data->variant_stats) {
// Insert as many tokens as elements correspond to each thread
for (int t = 0; t < num_chunks; t++) {
for (int s = 0; s < chunk_sizes[t]; s++) {
list_item_t *token_item = list_item_new(t, 0, NULL);
list_insert_item(token_item, next_token_list);
}
}
}
free(chunk_starts);
free(chunk_sizes);
vcf_batch_free(batch);
i++;
}
stop = omp_get_wtime();
total = stop - start;
LOG_INFO_F("[%d] Time elapsed = %f s\n", omp_get_thread_num(), total);
LOG_INFO_F("[%d] Time elapsed = %e ms\n", omp_get_thread_num(), total*1000);
// Decrease list writers count
for (i = 0; i < shared_options_data->num_threads; i++) {
list_decr_writers(next_token_list);
list_decr_writers(output_list[i]);
}
if (sample_ids) { kh_destroy(ids, sample_ids); }
if (individuals) { free(individuals); }
}
#pragma omp section
{
LOG_DEBUG_F("Thread %d writes the output\n", omp_get_thread_num());
char *stats_prefix = get_vcf_stats_filename_prefix(shared_options_data->vcf_filename,
shared_options_data->output_filename,
shared_options_data->output_directory);
// File names and descriptors for output to plain text files
char *stats_filename, *summary_filename, *phenotype_filename;
FILE *stats_fd, *summary_fd, **phenotype_fd;
char *stats_db_name;
sqlite3 *db = NULL;
khash_t(stats_chunks) *hash;
khash_t(str) *phenotype_ids;
int num_phenotypes;
if(ped_file){
phenotype_ids = get_phenotypes(ped_file);
num_phenotypes = get_num_variables(ped_file);
}
if (options_data->save_db) {
delete_files_by_extension(shared_options_data->output_directory, "db");
stats_db_name = calloc(strlen(stats_prefix) + strlen(".db") + 2, sizeof(char));
sprintf(stats_db_name, "%s.db", stats_prefix);
create_stats_db(stats_db_name, VCF_CHUNKSIZE, create_vcf_query_fields, &db);
hash = kh_init(stats_chunks);
}
// Write variant (and global) statistics
if (options_data->variant_stats) {
stats_filename = get_variant_stats_output_filename(stats_prefix);
if (!(stats_fd = fopen(stats_filename, "w"))) {
LOG_FATAL_F("Can't open file for writing statistics of variants: %s\n", stats_filename);
}
//Open one file for each phenotype
if(ped_file){
phenotype_fd = malloc(sizeof(FILE*)*num_phenotypes);
if(options_data->variable_groups){
int n;
char *variable_groups = strdup(options_data->variable_groups);
char ** names = split(variable_groups, ":", &n);
for(int i = 0; i < n; i++) {
phenotype_filename = get_variant_phenotype_stats_output_filename(stats_prefix, names[i]);
if(!(phenotype_fd[i] = fopen(phenotype_filename, "w"))) {
LOG_FATAL_F("Can't open file for writing statistics of variants per phenotype: %s\n", stats_filename);
}
free(phenotype_filename);
}
free(names);
free(variable_groups);
} else {
for (khint_t i = kh_begin(phenotype_ids); i != kh_end(phenotype_ids); ++i) {
if (!kh_exist(phenotype_ids,i)) continue;
phenotype_filename = get_variant_phenotype_stats_output_filename(stats_prefix, kh_key(phenotype_ids,i));
if(!(phenotype_fd[kh_val(phenotype_ids,i)] = fopen(phenotype_filename, "w"))) {
LOG_FATAL_F("Can't open file for writing statistics of variants per phenotype: %s\n", stats_filename);
}
free(phenotype_filename);
}
}
}
// Write header
report_vcf_variant_stats_header(stats_fd);
if(ped_file){
for(int i = 0; i < num_phenotypes; i++)
report_vcf_variant_phenotype_stats_header(phenotype_fd[i]);
}
// For each variant, generate a new line
int avail_stats = 0;
variant_stats_t *var_stats_batch[VCF_CHUNKSIZE];
list_item_t *token_item = NULL, *output_item = NULL;
while ( token_item = list_remove_item(next_token_list) ) {
output_item = list_remove_item(output_list[token_item->id]);
assert(output_item);
var_stats_batch[avail_stats] = output_item->data_p;
avail_stats++;
// Run only when certain amount of stats is available
if (avail_stats >= VCF_CHUNKSIZE) {
report_vcf_variant_stats(stats_fd, db, hash, avail_stats, var_stats_batch);
if(ped_file)
for(int i = 0; i < num_phenotypes; i++)
report_vcf_variant_phenotype_stats(phenotype_fd[i], avail_stats, var_stats_batch, i);
// Free all stats from the "batch"
for (int i = 0; i < avail_stats; i++) {
variant_stats_free(var_stats_batch[i]);
}
avail_stats = 0;
}
// Free resources
list_item_free(output_item);
list_item_free(token_item);
}
if (avail_stats > 0) {
report_vcf_variant_stats(stats_fd, db, hash, avail_stats, var_stats_batch);
if(ped_file)
for(int i = 0; i < num_phenotypes; i++)
report_vcf_variant_phenotype_stats(phenotype_fd[i], avail_stats, var_stats_batch, i);
// Free all stats from the "batch"
for (int i = 0; i < avail_stats; i++) {
variant_stats_free(var_stats_batch[i]);
}
avail_stats = 0;
}
// Write whole file stats (data only got when launching variant stats)
summary_filename = get_vcf_file_stats_output_filename(stats_prefix);
if (!(summary_fd = fopen(summary_filename, "w"))) {
LOG_FATAL_F("Can't open file for writing statistics summary: %s\n", summary_filename);
}
report_vcf_summary_stats(summary_fd, db, file_stats);
free(stats_filename);
free(summary_filename);
// Close variant stats file
if (stats_fd) { fclose(stats_fd); }
if (summary_fd) { fclose(summary_fd); }
if(ped_file){
for(int i = 0; i < num_phenotypes; i++)
if(phenotype_fd[i]) fclose(phenotype_fd[i]);
free(phenotype_fd);
}
}
// Write sample statistics
if (options_data->sample_stats) {
stats_filename = get_sample_stats_output_filename(stats_prefix);
if (!(stats_fd = fopen(stats_filename, "w"))) {
LOG_FATAL_F("Can't open file for writing statistics of samples: %s\n", stats_filename);
}
report_vcf_sample_stats_header(stats_fd);
report_vcf_sample_stats(stats_fd, NULL, vcf_file->samples_names->size, sample_stats);
// Close sample stats file
free(stats_filename);
if (stats_fd) { fclose(stats_fd); }
}
free(stats_prefix);
if (db) {
insert_chunk_hash(VCF_CHUNKSIZE, hash, db);
create_stats_index(create_vcf_index, db);
close_stats_db(db, hash);
}
}
}
for (int i = 0; i < get_num_vcf_samples(vcf_file); i++) {
sample_stats_free(sample_stats[i]);
}
free(sample_stats);
free(file_stats);
free(next_token_list);
for (int i = 0; i < shared_options_data->num_threads; i++) {
free(output_list[i]);
}
vcf_close(vcf_file);
if (ped_file) { ped_close(ped_file, 1,1); }
return 0;
}
