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#include "bcftools.pysam.h"
/* The MIT License
Copyright (c) 2016 Genome Research Ltd.
Author: Petr Danecek <pd3@sanger.ac.uk>
Permission is hereby granted, free of charge, to any person obtaining a copy
of this software and associated documentation files (the "Software"), to deal
in the Software without restriction, including without limitation the rights
to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
copies of the Software, and to permit persons to whom the Software is
furnished to do so, subject to the following conditions:
The above copyright notice and this permission notice shall be included in
all copies or substantial portions of the Software.
THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN
THE SOFTWARE.
*/
#include <stdio.h>
#include <stdlib.h>
#include <getopt.h>
#include <math.h>
#include <htslib/hts.h>
#include <htslib/vcf.h>
#include <htslib/kstring.h>
#include <htslib/kseq.h>
#include <htslib/khash_str2int.h>
#include "bcftools.h"
typedef struct
{
int father, mother, child; // VCF sample index
int prev, ipop;
uint32_t err, nswitch, ntest;
}
trio_t;
typedef struct
{
char *name;
uint32_t err, nswitch, ntest, ntrio;
float pswitch;
}
pop_t;
typedef struct
{
int argc;
char **argv;
bcf_hdr_t *hdr;
trio_t *trio;
int ntrio, mtrio;
int32_t *gt_arr;
int npop;
pop_t *pop;
int mgt_arr, prev_rid;
}
args_t;
args_t args;
const char *about(void)
{
return "Calculate phase switch rate in trio samples, children samples must have phased GTs.\n";
}
const char *usage(void)
{
return
"\n"
"About: Calculate phase switch rate in trio children.\n"
"Usage: bcftools +trio-swich-rate [General Options] -- [Plugin Options]\n"
"Options:\n"
" run \"bcftools plugin\" for a list of common options\n"
"\n"
"Plugin options:\n"
" -p, --ped <file> PED file with optional 7th column to group\n"
" results by population\n"
"\n"
"Example:\n"
" bcftools +trio-switch-rate file.bcf -- -p file.ped\n"
"\n";
}
void parse_ped(args_t *args, char *fname)
{
htsFile *fp = hts_open(fname, "r");
if ( !fp ) error("Could not read: %s\n", fname);
kstring_t str = {0,0,0};
if ( hts_getline(fp, KS_SEP_LINE, &str) <= 0 ) error("Empty file: %s\n", fname);
void *pop2i = khash_str2int_init();
int moff = 0, *off = NULL;
do
{
// familyID sampleID paternalID maternalID sex phenotype population relationship siblings secondOrder thirdOrder children comment
// BB03 HG01884 HG01885 HG01956 2 0 ACB child 0 0 0 0
int ncols = ksplit_core(str.s,0,&moff,&off);
if ( ncols<4 ) error("Could not parse the ped file: %s\n", str.s);
int father = bcf_hdr_id2int(args->hdr,BCF_DT_SAMPLE,&str.s[off[2]]);
if ( father<0 ) continue;
int mother = bcf_hdr_id2int(args->hdr,BCF_DT_SAMPLE,&str.s[off[3]]);
if ( mother<0 ) continue;
int child = bcf_hdr_id2int(args->hdr,BCF_DT_SAMPLE,&str.s[off[1]]);
if ( child<0 ) continue;
args->ntrio++;
hts_expand0(trio_t,args->ntrio,args->mtrio,args->trio);
trio_t *trio = &args->trio[args->ntrio-1];
trio->father = father;
trio->mother = mother;
trio->child = child;
if (ncols>6) {
char *pop_name = &str.s[off[6]];
if ( !khash_str2int_has_key(pop2i,pop_name) )
{
pop_name = strdup(&str.s[off[6]]);
khash_str2int_set(pop2i,pop_name,args->npop);
args->npop++;
args->pop = (pop_t*) realloc(args->pop,args->npop*sizeof(*args->pop));
memset(args->pop+args->npop-1,0,sizeof(*args->pop));
args->pop[args->npop-1].name = pop_name;
}
khash_str2int_get(pop2i,pop_name,&trio->ipop);
args->pop[trio->ipop].ntrio++;
}
} while ( hts_getline(fp, KS_SEP_LINE, &str)>=0 );
khash_str2int_destroy(pop2i);
free(str.s);
free(off);
hts_close(fp);
}
int init(int argc, char **argv, bcf_hdr_t *in, bcf_hdr_t *out)
{
memset(&args,0,sizeof(args_t));
args.argc = argc; args.argv = argv;
args.prev_rid = -1;
args.hdr = in;
char *ped_fname = NULL;
static struct option loptions[] =
{
{"ped",required_argument,NULL,'p'},
{0,0,0,0}
};
int c;
while ((c = getopt_long(argc, argv, "?hp:",loptions,NULL)) >= 0)
{
switch (c)
{
case 'p': ped_fname = optarg; break;
case 'h':
case '?':
default: error("%s", usage()); break;
}
}
if ( !ped_fname ) error("Expected the -p option\n");
parse_ped(&args, ped_fname);
return 1;
}
typedef struct
{
int a, b, phased;
}
gt_t;
int parse_genotype(gt_t *gt, int32_t *ptr);
inline int parse_genotype(gt_t *gt, int32_t *ptr)
{
if ( ptr[0]==bcf_gt_missing ) return 0;
if ( ptr[1]==bcf_gt_missing ) return 0;
if ( ptr[1]==bcf_int32_vector_end ) return 0;
gt->phased = bcf_gt_is_phased(ptr[1]) ? 1 : 0;
gt->a = bcf_gt_allele(ptr[0]); if ( gt->a > 1 ) return 0; // consider only the first two alleles at biallelic sites
gt->b = bcf_gt_allele(ptr[1]); if ( gt->b > 1 ) return 0;
return 1;
}
bcf1_t *process(bcf1_t *rec)
{
int ngt = bcf_get_genotypes(args.hdr, rec, &args.gt_arr, &args.mgt_arr);
if ( ngt<0 ) return NULL;
ngt /= bcf_hdr_nsamples(args.hdr);
if ( ngt!=2 ) return NULL;
int i;
if ( rec->rid!=args.prev_rid )
{
args.prev_rid = rec->rid;
for (i=0; i<args.ntrio; i++) args.trio[i].prev = 0;
}
gt_t child, father, mother;
for (i=0; i<args.ntrio; i++)
{
trio_t *trio = &args.trio[i];
if ( !parse_genotype(&child, args.gt_arr + ngt*trio->child) ) continue;
if ( !child.phased ) continue;
if ( child.a+child.b != 1 ) continue; // child is not a het
if ( !parse_genotype(&father, args.gt_arr + ngt*trio->father) ) continue;
if ( !parse_genotype(&mother, args.gt_arr + ngt*trio->mother) ) continue;
if ( father.a+father.b == 1 && mother.a+mother.b == 1 ) continue; // both parents are hets
if ( father.a+father.b == mother.a+mother.b ) { trio->err++; continue; } // mendelian error
int test_phase = 0;
if ( father.a==father.b ) test_phase = 1 + (child.a==father.a);
else if ( mother.a==mother.b ) test_phase = 1 + (child.b==mother.a);
if ( trio->prev > 0 )
{
if ( trio->prev!=test_phase ) trio->nswitch++;
}
trio->ntest++;
trio->prev = test_phase;
}
return NULL;
}
void destroy(void)
{
int i;
fprintf(bcftools_stdout, "# This file was produced by: bcftools +trio-switch-rate(%s+htslib-%s)\n", bcftools_version(),hts_version());
fprintf(bcftools_stdout, "# The command line was:\tbcftools +trio-switch-rate %s", args.argv[0]);
for (i=1; i<args.argc; i++) fprintf(bcftools_stdout, " %s",args.argv[i]);
fprintf(bcftools_stdout, "\n#\n");
fprintf(bcftools_stdout, "# TRIO\t[2]Father\t[3]Mother\t[4]Child\t[5]nTested\t[6]nMendelian Errors\t[7]nSwitch\t[8]nSwitch (%%)\n");
for (i=0; i<args.ntrio; i++)
{
trio_t *trio = &args.trio[i];
fprintf(bcftools_stdout, "TRIO\t%s\t%s\t%s\t%d\t%d\t%d\t%.2f\n",
bcf_hdr_int2id(args.hdr,BCF_DT_SAMPLE,trio->father),
bcf_hdr_int2id(args.hdr,BCF_DT_SAMPLE,trio->mother),
bcf_hdr_int2id(args.hdr,BCF_DT_SAMPLE,trio->child),
trio->ntest, trio->err, trio->nswitch, trio->ntest ? trio->nswitch*100./trio->ntest : 0
);
if (args.npop) {
pop_t *pop = &args.pop[trio->ipop];
pop->err += trio->err;
pop->nswitch += trio->nswitch;
pop->ntest += trio->ntest;
pop->pswitch += trio->ntest ? trio->nswitch*100./trio->ntest : 0;
}
}
fprintf(bcftools_stdout, "# POP\tpopulation or other grouping defined by an optional 7-th column of the PED file\n");
fprintf(bcftools_stdout, "# POP\t[2]Name\t[3]Number of trios\t[4]avgTested\t[5]avgMendelian Errors\t[6]avgSwitch\t[7]avgSwitch (%%)\n");
for (i=0; i<args.npop; i++)
{
pop_t *pop = &args.pop[i];
fprintf(bcftools_stdout, "POP\t%s\t%d\t%.0f\t%.0f\t%.0f\t%.2f\n", pop->name,pop->ntrio,
(float)pop->ntest/pop->ntrio,(float)pop->err/pop->ntrio,(float)pop->nswitch/pop->ntrio,
pop->pswitch/pop->ntrio);
}
for (i=0; i<args.npop; i++) free(args.pop[i].name);
free(args.pop);
free(args.trio);
free(args.gt_arr);
}
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