int gff_write_to_file(gff_file_t *gff_file, FILE *fd) {
if(gff_file == NULL || fd == NULL) {
return -1;
}
// Write header entries
cp_list_iterator *headers_iter = cp_list_create_iterator(gff_file->header_entries, COLLECTION_LOCK_READ);
// cp_list_iterator_init(headers_iter, gff_file->header_entries, COLLECTION_LOCK_READ);
gff_header_entry_t *entry = NULL;
while ((entry = cp_list_iterator_next(headers_iter)) != NULL) {
write_gff_header_entry(entry, fd);
}
// Write records
cp_list_iterator *records_iter = cp_list_create_iterator(gff_file->records, COLLECTION_LOCK_READ);
// cp_list_iterator_init(records_iter, gff_file->records, COLLECTION_LOCK_READ);
gff_record_t *record = NULL;
while ((record = cp_list_iterator_next(records_iter)) != NULL) {
write_gff_record(record, fd);
}
return 0;
}
int cp_thread_pool_stop(cp_thread_pool *pool)
{
cp_hashlist_iterator *i;
cp_list_iterator *j;
cp_pooled_thread *pt;
pool->running = 0;
i = cp_hashlist_create_iterator(pool->in_use, COLLECTION_LOCK_READ);
while ((pt = (cp_pooled_thread *) cp_hashlist_iterator_next_value(i)))
cp_pooled_thread_stop(pt);
cp_hashlist_iterator_destroy(i);
j = cp_list_create_iterator(pool->free_pool, COLLECTION_LOCK_READ);
while ((pt = (cp_pooled_thread *) cp_list_iterator_next(j)))
cp_pooled_thread_stop(pt);
cp_list_iterator_destroy(j);
return 0;
}
int tdt_test(vcf_record_t **variants, int num_variants, family_t **families, int num_families, cp_hashtable *sample_ids, list_t *output_list) {
double start = omp_get_wtime();
int ret_code = 0;
int tid = omp_get_thread_num();
int num_samples = cp_hashtable_count(sample_ids);
tdt_result_t *result;
char **sample_data;
int gt_position;
int father_allele1, father_allele2;
int mother_allele1, mother_allele2;
int child_allele1, child_allele2;
///////////////////////////////////
// Perform analysis for each variant
vcf_record_t *record;
for (int i = 0; i < num_variants; i++) {
record = variants[i];
LOG_DEBUG_F("[%d] Checking variant %.*s:%ld\n", tid, record->chromosome_len, record->chromosome, record->position);
sample_data = (char**) record->samples->items;
gt_position = get_field_position_in_format("GT", strndup(record->format, record->format_len));
// Transmission counts
int t1 = 0;
int t2 = 0;
// Count over families
family_t *family;
for (int f = 0; f < num_families; f++) {
family = families[f];
individual_t *father = family->father;
individual_t *mother = family->mother;
cp_list *children = family->children;
// LOG_DEBUG_F("[%d] Checking suitability of family %s\n", tid, family->id);
if (father == NULL || mother == NULL) {
continue;
}
int *father_pos = cp_hashtable_get(sample_ids, father->id);
if (father_pos != NULL) {
// LOG_DEBUG_F("[%d] Father %s is in position %d\n", tid, father->id, *father_pos);
} else {
// LOG_DEBUG_F("[%d] Father %s is not positioned\n", tid, father->id);
continue;
}
int *mother_pos = cp_hashtable_get(sample_ids, mother->id);
if (mother_pos != NULL) {
// LOG_DEBUG_F("[%d] Mother %s is in position %d\n", tid, mother->id, *mother_pos);
} else {
// LOG_DEBUG_F("[%d] Mother %s is not positioned\n", tid, mother->id);
continue;
}
char *father_sample = strdup(sample_data[*father_pos]);
char *mother_sample = strdup(sample_data[*mother_pos]);
// LOG_DEBUG_F("[%d] Samples: Father = %s\tMother = %s\n", tid, father_sample, mother_sample);
// If any parent's alleles can't be read or is missing, go to next family
if (get_alleles(father_sample, gt_position, &father_allele1, &father_allele2) ||
get_alleles(mother_sample, gt_position, &mother_allele1, &mother_allele2)) {
free(father_sample);
free(mother_sample);
continue;
}
// LOG_DEBUG_F("[%d] Alleles: Father = %d/%d\tMother = %d/%d\n", tid, father_allele1, father_allele2, mother_allele1, mother_allele2);
// We need two genotyped parents, with at least one het
if (father_allele1 == father_allele2 && mother_allele1 == mother_allele2) {
free(father_sample);
free(mother_sample);
continue;
}
if ((father_allele1 && !father_allele2) || (mother_allele1 && !mother_allele2)) {
free(father_sample);
free(mother_sample);
continue;
}
// LOG_DEBUG_F("[%d] Proceeding to analyse family %s...\n", tid, family->id);
int trA = 0; // transmitted allele from first het parent
int unA = 0; // untransmitted allele from first het parent
int trB = 0; // transmitted allele from second het parent
int unB = 0; // untransmitted allele from second het parent
// Consider all offspring in nuclear family
cp_list_iterator *children_iterator = cp_list_create_iterator(family->children, COLLECTION_LOCK_READ);
individual_t *child = NULL;
while ((child = cp_list_iterator_next(children_iterator)) != NULL) {
// Only consider affected children
if (child->condition != AFFECTED) { continue; }
int *child_pos = cp_hashtable_get(sample_ids, child->id);
if (child_pos != NULL) {
// LOG_DEBUG_F("[%d] Child %s is in position %d\n", tid, child->id, *child_pos);
} else {
// LOG_DEBUG_F("[%d] Child %s is not positioned\n", tid, child->id);
continue;
}
char *child_sample = strdup(sample_data[*child_pos]);
// LOG_DEBUG_F("[%d] Samples: Child = %s\n", tid, child_sample);
// Skip if offspring has missing genotype
if (get_alleles(child_sample, gt_position, &child_allele1, &child_allele2)) {
free(child_sample);
continue;
}
// Exclude mendelian errors
char *aux_chromosome = strndup(record->chromosome, record->chromosome_len);
if (check_mendel(aux_chromosome, father_allele1, father_allele2, mother_allele1, mother_allele2,
child_allele1, child_allele2, child->sex)) {
free(child_sample);
free(aux_chromosome);
continue;
}
free(aux_chromosome);
// We've now established: no missing genotypes
// and at least one heterozygous parent
// Kid is 00
if (!child_allele1 && !child_allele2) {
if ( ( (!father_allele1) && father_allele2 ) &&
( (!mother_allele1) && mother_allele2 ) )
{ trA=1; unA=2; trB=1; unB=2; }
else
{ trA=1; unA=2; }
}
else if ( (!child_allele1) && child_allele2 ) // Kid is 01
{
// het dad
if (father_allele1 != father_allele2 )
{
// het mum
if ( mother_allele1 != mother_allele2 )
{ trA=1; trB=2; unA=2; unB=1; }
else if ( !mother_allele1 )
{ trA=2; unA=1; }
else { trA=1; unA=2; }
}
else if ( !father_allele1 )
{
trA=2; unA=1;
}
else
{
trA=1; unA=2;
}
}
else // kid is 1/1
{
if ( ( (!father_allele1) && father_allele2 ) &&
( (!mother_allele1) && mother_allele2 ) )
{ trA=2; unA=1; trB=2; unB=1; }
else
{
trA=2; unA=1;
}
}
// We have now populated trA (first transmission)
// and possibly trB also
////////////////////////////////////////
// Permutation? 50:50 flip (precomputed)
// if (permute) {
// if (flipA[f])
// {
// int t = trA;
// trA = unA;
// unA = t;
//
// t = trB;
// trB = unB;
// unB = t;
// }
// }
// Increment transmission counts
if (trA==1) { t1++; }
else if (trA==2) { t2++; }
if (trB==1) { t1++; }
else if (trB==2) { t2++; }
// // LOG_DEBUG_F("TDT\t%.*s %s : %d %d - %d %d - %d %d - F %d/%d - M %d/%d - C %d/%d\n",
// record->id_len, record->id, family->id, trA, unA, trB, unB, t1, t2,
// father_allele1, father_allele2, mother_allele1, mother_allele2, child_allele1, child_allele2);
free(child_sample);
} // next offspring in family
cp_list_iterator_destroy(children_iterator);
free(father_sample);
free(mother_sample);
} // next nuclear family
/////////////////////////////
// Finished counting: now compute
// the statistics
double tdt_chisq = -1;
// Basic TDT test
if (t1+t2 > 0) {
tdt_chisq = ((double) ((t1-t2) * (t1-t2))) / (t1+t2);
}
// LOG_DEBUG_F("[%d] before adding %s:%ld\n", tid, record->chromosome, record->position);
result = tdt_result_new(record->chromosome, record->chromosome_len,
record->position,
record->reference, record->reference_len,
record->alternate, record->alternate_len,
t1, t2, tdt_chisq);
list_item_t *output_item = list_item_new(tid, 0, result);
list_insert_item(output_item, output_list);
// LOG_DEBUG_F("[%d] after adding %.*s:%ld\n", tid, record->chromosome_len, record->chromosome, record->position);
} // next variant
double end = omp_get_wtime();
return ret_code;
}
