static int fake_PLs(args_t *args, bcf_hdr_t *hdr, bcf1_t *line)
{
// PLs not present, use GTs instead.
int fake_PL = args->no_PLs ? args->no_PLs : 99; // with 1, discordance is the number of non-matching GTs
int nsm_gt, i;
if ( (nsm_gt=bcf_get_genotypes(hdr, line, &args->tmp_arr, &args->ntmp_arr)) <= 0 )
error("GT not present at %s:%d?\n", hdr->id[BCF_DT_CTG][line->rid].key, line->pos+1);
nsm_gt /= bcf_hdr_nsamples(hdr);
int npl = line->n_allele*(line->n_allele+1)/2;
hts_expand(int,npl*bcf_hdr_nsamples(hdr),args->npl_arr,args->pl_arr);
for (i=0; i<bcf_hdr_nsamples(hdr); i++)
{
int *gt_ptr = args->tmp_arr + i*nsm_gt;
int a = bcf_gt_allele(gt_ptr[0]);
int b = bcf_gt_allele(gt_ptr[1]);
int j, *pl_ptr = args->pl_arr + i*npl;
if ( a<0 || b<0 ) // missing genotype
{
for (j=0; j<npl; j++) pl_ptr[j] = -1;
}
else
{
for (j=0; j<npl; j++) pl_ptr[j] = fake_PL;
int idx = bcf_alleles2gt(a,b);
pl_ptr[idx] = 0;
}
}
return npl;
}
int process_GT(args_t *args, bcf1_t *line, uint32_t *ntot, uint32_t *ndif)
{
int ngt = bcf_get_genotypes(args->sm_hdr, line, &args->tmp_arr, &args->ntmp_arr);
if ( ngt<=0 ) return 1; // GT not present
if ( ngt!=args->nsmpl*2 ) return 2; // not diploid
ngt /= args->nsmpl;
int i,j, idx = 0;
for (i=1; i<args->nsmpl; i++)
{
int32_t *a = args->tmp_arr + i*ngt;
if ( bcf_gt_is_missing(a[0]) || bcf_gt_is_missing(a[1]) || a[1]==bcf_int32_vector_end ) { idx+=i; continue; }
int agt = 1<<bcf_gt_allele(a[0]) | 1<<bcf_gt_allele(a[1]);
for (j=0; j<i; j++)
{
int32_t *b = args->tmp_arr + j*ngt;
if ( bcf_gt_is_missing(b[0]) || bcf_gt_is_missing(b[1]) || b[1]==bcf_int32_vector_end ) { idx++; continue; }
int bgt = 1<<bcf_gt_allele(b[0]) | 1<<bcf_gt_allele(b[1]);
ntot[idx]++;
if ( agt!=bgt ) ndif[idx]++;
idx++;
}
}
return 0;
}
int estimate_AF(args_t *args, bcf1_t *line, double *alt_freq)
{
if ( !args->nitmp )
{
args->nitmp = bcf_get_genotypes(args->hdr, line, &args->itmp, &args->mitmp);
if ( args->nitmp != 2*args->nsmpl ) return -1; // not diploid?
args->nitmp /= args->nsmpl;
}
int i, nalt = 0, nref = 0;
for (i=0; i<args->nsmpl; i++)
{
int32_t *gt = &args->itmp[i*args->nitmp];
if ( bcf_gt_is_missing(gt[0]) || bcf_gt_is_missing(gt[1]) ) continue;
if ( bcf_gt_allele(gt[0]) ) nalt++;
else nref++;
if ( bcf_gt_allele(gt[1]) ) nalt++;
else nref++;
}
if ( !nalt && !nref ) return -1;
*alt_freq = (double)nalt / (nalt + nref);
return 0;
}
int process_region_precise(args_t *args, char *seq, regitr_t *itr)
{
int k = 1;
uint32_t start = itr->reg[itr->i].start, end = itr->reg[itr->i].end;
while ( itr->i+k<itr->n && start==itr->reg[itr->i+k].start && end==itr->reg[itr->i+k].end ) k++;
int ret = ploidy_query(args->ploidy, seq, start, args->sex2ploidy, NULL, NULL);
assert(ret);
memset(args->counts,0,args->ncounts*sizeof(int));
// Select 'nsites' sites spaced so that they evenly cover the whole region
// to get a representative sample. We index-jump as we should be checking
// a few sites only.
int i, rid = -1, pos, prev_pos = -1, ismpl;
for (i=0; i<args->nsites; i++)
{
rid = -1;
pos = ((i+1.0)/(args->nsites+1))*(end - start) + start;
if ( i>0 && pos <= prev_pos ) continue; // the vcf is too sparse
if ( bcf_sr_seek(args->sr,seq,pos)!=0 ) return k; // sequence not present
if ( !bcf_sr_next_line(args->sr) ) return k; // no sites found
bcf1_t *rec = bcf_sr_get_line(args->sr,0);
if ( rid==-1 ) rid = rec->rid;
if ( rid!=rec->rid || rec->pos > end ) break;
prev_pos = rec->pos;
int ngts = bcf_get_genotypes(args->hdr,rec,&args->gts,&args->ngts);
ngts /= args->nsample;
for (ismpl=0; ismpl<args->nsample; ismpl++)
{
int32_t *gts = args->gts + ngts*ismpl;
int igt, ploidy = 0;
for (igt=0; igt<ngts; igt++)
{
if ( gts[igt]==bcf_int32_vector_end || bcf_gt_is_missing(gts[igt]) ) break;
else ploidy++;
}
args->counts[ismpl*(args->max_ploidy+1) + ploidy]++;
if ( args->verbose )
fprintf(stderr,"%s:%d\t%s\tploidy=%d\n", seq,rec->pos+1,args->hdr->samples[ismpl],ploidy);
}
}
for (ismpl=0; ismpl<args->nsample; ismpl++)
{
float sum = 0, *probs = args->sex2prob + ismpl*args->nsex;
int *counts = args->counts + ismpl*(args->max_ploidy+1);
for (i=0; i<args->max_ploidy+1; i++) sum += counts[i];
if ( !sum ) continue;
for (i=0; i<args->nsex; i++)
{
int ploidy = args->sex2ploidy[i];
probs[i] *= counts[ploidy]/sum;
}
}
return k;
}
static void phase_update(args_t *args, bcf_hdr_t *hdr, bcf1_t *rec)
{
int i, nGTs = bcf_get_genotypes(hdr, rec, &args->GTa, &args->mGTa);
for (i=0; i<bcf_hdr_nsamples(hdr); i++)
{
if ( !args->swap_phase[i] ) continue;
int *gt = &args->GTa[i*2];
if ( gt[0]==bcf_gt_missing || gt[1]==bcf_int32_vector_end ) continue;
SWAP(int, gt[0], gt[1]);
gt[1] |= 1;
}
bcf_update_genotypes(hdr,rec,args->GTa,nGTs);
}
static void set_observed_prob_trio(bcf1_t *rec)
{
int ngt = bcf_get_genotypes(args.hdr, rec, &args.gt_arr, &args.ngt_arr);
if ( ngt<0 ) return;
if ( ngt!=6 ) return; // chrX
int32_t a,b,c,d,e,f;
a = args.gt_arr[2*args.imother];
b = args.gt_arr[2*args.imother+1];
c = args.gt_arr[2*args.ifather];
d = args.gt_arr[2*args.ifather+1];
e = args.gt_arr[2*args.ichild];
f = args.gt_arr[2*args.ichild+1];
if ( bcf_gt_is_missing(a) || bcf_gt_is_missing(b) ) return;
if ( bcf_gt_is_missing(c) || bcf_gt_is_missing(d) ) return;
if ( bcf_gt_is_missing(e) || bcf_gt_is_missing(f) ) return;
if ( !bcf_gt_is_phased(a) && !bcf_gt_is_phased(b) ) return; // only the second allele should be set when phased
if ( !bcf_gt_is_phased(c) && !bcf_gt_is_phased(d) ) return;
if ( !bcf_gt_is_phased(e) && !bcf_gt_is_phased(f) ) return;
a = bcf_gt_allele(a);
b = bcf_gt_allele(b);
c = bcf_gt_allele(c);
d = bcf_gt_allele(d);
e = bcf_gt_allele(e);
f = bcf_gt_allele(f);
int mother = (1<<a) | (1<<b);
int father = (1<<c) | (1<<d);
int child = (1<<e) | (1<<f);
if ( !(mother&child) || !(father&child) ) return; // Mendelian-inconsistent site, skip
if ( a!=b ) args.nhet_mother++;
if ( c!=d ) args.nhet_father++;
int m = args.msites;
args.nsites++;
hts_expand(uint32_t,args.nsites,args.msites,args.sites);
if ( m!=args.msites ) args.eprob = (double*) realloc(args.eprob, sizeof(double)*args.msites*args.nstates);
args.sites[args.nsites-1] = rec->pos;
double *prob = args.eprob + args.nstates*(args.nsites-1);
prob[TRIO_AC] = prob_shared(0,e,a) * prob_shared(0,f,c);
prob[TRIO_AD] = prob_shared(0,e,a) * prob_shared(0,f,d);
prob[TRIO_BC] = prob_shared(0,e,b) * prob_shared(0,f,c);
prob[TRIO_BD] = prob_shared(0,e,b) * prob_shared(0,f,d);
prob[TRIO_CA] = prob_shared(0,e,c) * prob_shared(0,f,a);
prob[TRIO_DA] = prob_shared(0,e,d) * prob_shared(0,f,a);
prob[TRIO_CB] = prob_shared(0,e,c) * prob_shared(0,f,b);
prob[TRIO_DB] = prob_shared(0,e,d) * prob_shared(0,f,b);
}
static void set_observed_prob_unrelated(bcf1_t *rec)
{
float af = 0.5; // alternate allele frequency
int ngt = bcf_get_genotypes(args.hdr, rec, &args.gt_arr, &args.ngt_arr);
if ( ngt<0 ) return;
if ( ngt!=4 ) return; // chrX
int32_t a,b,c,d;
a = args.gt_arr[2*args.isample];
b = args.gt_arr[2*args.isample+1];
c = args.gt_arr[2*args.jsample];
d = args.gt_arr[2*args.jsample+1];
if ( bcf_gt_is_missing(a) || bcf_gt_is_missing(b) ) return;
if ( bcf_gt_is_missing(c) || bcf_gt_is_missing(d) ) return;
if ( !bcf_gt_is_phased(a) && !bcf_gt_is_phased(b) ) return; // only the second allele should be set when phased
if ( !bcf_gt_is_phased(c) && !bcf_gt_is_phased(d) ) return;
a = bcf_gt_allele(a);
b = bcf_gt_allele(b);
c = bcf_gt_allele(c);
d = bcf_gt_allele(d);
int m = args.msites;
args.nsites++;
hts_expand(uint32_t,args.nsites,args.msites,args.sites);
if ( m!=args.msites ) args.eprob = (double*) realloc(args.eprob, sizeof(double)*args.msites*args.nstates);
args.sites[args.nsites-1] = rec->pos;
double *prob = args.eprob + args.nstates*(args.nsites-1);
prob[UNRL_xxxx] = prob_not_shared(af,a,c) * prob_not_shared(af,a,d) * prob_not_shared(af,b,c) * prob_not_shared(af,b,d);
prob[UNRL_0x0x] = prob_shared(af,a,c) * prob_not_shared(af,b,d);
prob[UNRL_0xx0] = prob_shared(af,a,d) * prob_not_shared(af,b,c);
prob[UNRL_x00x] = prob_shared(af,b,c) * prob_not_shared(af,a,d);
prob[UNRL_x0x0] = prob_shared(af,b,d) * prob_not_shared(af,a,c);
prob[UNRL_0101] = prob_shared(af,a,c) * prob_shared(af,b,d);
prob[UNRL_0110] = prob_shared(af,a,d) * prob_shared(af,b,c);
#if 0
static int x = 0;
if ( !x++)
{
printf("p(0==0) .. %f\n", prob_shared(af,0,0));
printf("p(0!=0) .. %f\n", prob_not_shared(af,0,0));
printf("p(0==1) .. %f\n", prob_shared(af,0,1));
printf("p(0!=1) .. %f\n", prob_not_shared(af,0,1));
}
printf("%d|%d %d|%d x:%f 11:%f 12:%f 21:%f 22:%f 11,22:%f 12,21:%f %d\n", a,b,c,d,
prob[UNRL_xxxx], prob[UNRL_0x0x], prob[UNRL_0xx0], prob[UNRL_x00x], prob[UNRL_x0x0], prob[UNRL_0101], prob[UNRL_0110], rec->pos+1);
#endif
}
bcf1_t *process(bcf1_t *rec)
{
int ngts = bcf_get_genotypes(in_hdr, rec, >s, &mgts);
int i, changed = 0;
for (i=0; i<ngts; i++)
{
if ( gts[i]==bcf_gt_missing )
{
gts[i] = new_gt;
changed++;
}
}
nchanged += changed;
if ( changed ) bcf_update_genotypes(out_hdr, rec, gts, ngts);
return rec;
}
int calc_dosage_GT(bcf1_t *rec)
{
int i, j, nret = bcf_get_genotypes(in_hdr,rec,(void**)&buf,&nbuf);
if ( nret<0 ) return -1;
nret /= rec->n_sample;
int32_t *ptr = (int32_t*) buf;
for (i=0; i<rec->n_sample; i++)
{
float dsg = 0;
for (j=0; j<nret; j++)
{
if ( ptr[j]==bcf_int32_missing || ptr[j]==bcf_int32_vector_end || ptr[j]==bcf_gt_missing ) break;
if ( bcf_gt_allele(ptr[j]) ) dsg += 1;
}
printf("\t%.1f", j>0 ? dsg : -1);
ptr += nret;
}
return 0;
}
void union_data::readGenotypesVCF(string fvcf,string region) {
int n_includedG = 0;
int n_excludedG_mult = 0;
int n_excludedG_void = 0;
int n_excludedG_user = 0;
int n_includedS = 0;
vector < int > mappingS;
genotype_id.clear();
genotype_chr.clear();
genotype_start.clear();
genotype_end.clear();
genotype_val.clear();
genotype_count=0;
genotype_id_to_idx.clear();
//Opening files
bcf_srs_t * sr = bcf_sr_init();
//vrb.bullet("target region [" + regionGenotype.get() + "]");
//if (bcf_sr_set_regions(sr, regionGenotype.get().c_str(), 0) == -1) vrb.error("Cannot jump to region!");
bcf_sr_set_regions(sr, region.c_str(), 0);
if(!(bcf_sr_add_reader (sr, fvcf.c_str()))) {
switch (sr->errnum) {
case not_bgzf: vrb.error("File not compressed with bgzip!");
case idx_load_failed: vrb.error("Impossible to load index file!");
case file_type_error: vrb.error("File format not detected by htslib!");
default : vrb.error("Unknown error!");
}
}
//Sample processing
int n_samples = bcf_hdr_nsamples(sr->readers[0].header);
for (int i0 = 0 ; i0 < n_samples ; i0 ++) {
mappingS.push_back(findSample(string(sr->readers[0].header->samples[i0])));
if (mappingS.back() >= 0) n_includedS++;
}
//Read genotype data
int ngt, ngt_arr = 0, nds, nds_arr = 0, * gt_arr = NULL, nsl, nsl_arr = 0, * sl_arr = NULL;
float * ds_arr = NULL;
bcf1_t * line;
unsigned int linecount = 0;
while(bcf_sr_next_line (sr)) {
linecount ++;
if (linecount % 100000 == 0) vrb.bullet("Read " + stb.str(linecount) + " lines");
line = bcf_sr_get_line(sr, 0);
if (line->n_allele == 2) {
ngt = bcf_get_genotypes(sr->readers[0].header, line, >_arr, &ngt_arr);
nds = bcf_get_format_float(sr->readers[0].header, line,"DS", &ds_arr, &nds_arr);
if (nds == n_samples || ngt == 2*n_samples) {
bcf_unpack(line, BCF_UN_STR);
string sid = string(line->d.id);
if (filter_genotype.check(sid)) {
genotype_id.push_back(sid);
genotype_chr.push_back(string(bcf_hdr_id2name(sr->readers[0].header, line->rid)));
string genotype_ref = string(line->d.allele[0]);
genotype_start.push_back(line->pos + 1);
nsl = bcf_get_info_int32(sr->readers[0].header, line, "END", &sl_arr, &nsl_arr);
if (nsl >= 0 && nsl_arr == 1) genotype_end.push_back(sl_arr[0]);
else genotype_end.push_back(genotype_start.back() + genotype_ref.size() - 1);
genotype_val.push_back(vector < float > (sample_count, 0.0));
for(int i = 0 ; i < n_samples ; i ++) {
if (mappingS[i] >= 0) {
if (nds > 0) genotype_val.back()[mappingS[i]] = ds_arr[i];
else {
if (gt_arr[2*i+0] == bcf_gt_missing || gt_arr[2*i+1] == bcf_gt_missing) genotype_val.back()[mappingS[i]] = bcf_float_missing;
else genotype_val.back()[mappingS[i]] = bcf_gt_allele(gt_arr[2*i+0]) + bcf_gt_allele(gt_arr[2*i+1]);
}
}
}
pair < string, int > temp (sid,n_includedG);
genotype_id_to_idx.insert(temp);
n_includedG++;
} else n_excludedG_user ++;
} else n_excludedG_void ++;
} else n_excludedG_mult ++;
}
//Finalize
free(gt_arr);
free(ds_arr);
bcf_sr_destroy(sr);
genotype_count = n_includedG;
//vrb.bullet(stb.str(n_includedG) + " variants included");
//if (n_excludedG_user > 0) vrb.bullet(stb.str(n_excludedG_user) + " variants excluded by user");
//if (n_excludedG_mult > 0) vrb.bullet(stb.str(n_excludedG_mult) + " multi-allelic variants excluded");
//if (n_excludedG_void > 0) vrb.bullet(stb.str(n_excludedG_void) + " uninformative variants excluded [no GT/DS]");
//if (genotype_count == 0) vrb.leave("Cannot find genotypes in target region!");
}
void bcf_remove_alleles(const bcf_hdr_t *header, bcf1_t *line, int rm_mask)
{
int *map = (int*) calloc(line->n_allele, sizeof(int));
// create map of indexes from old to new ALT numbering and modify ALT
kstring_t str = {0,0,0};
kputs(line->d.allele[0], &str);
int nrm = 0, i,j; // i: ori alleles, j: new alleles
for (i=1, j=1; i<line->n_allele; i++)
{
if ( rm_mask & 1<<i )
{
// remove this allele
line->d.allele[i] = NULL;
nrm++;
continue;
}
kputc(',', &str);
kputs(line->d.allele[i], &str);
map[i] = j;
j++;
}
if ( !nrm ) { free(map); free(str.s); return; }
int nR_ori = line->n_allele;
int nR_new = line->n_allele-nrm;
assert(nR_new > 0); // should not be able to remove reference allele
int nA_ori = nR_ori-1;
int nA_new = nR_new-1;
int nG_ori = nR_ori*(nR_ori + 1)/2;
int nG_new = nR_new*(nR_new + 1)/2;
bcf_update_alleles_str(header, line, str.s);
// remove from Number=G, Number=R and Number=A INFO fields.
uint8_t *dat = NULL;
int mdat = 0, ndat = 0, mdat_bytes = 0, nret;
for (i=0; i<line->n_info; i++)
{
bcf_info_t *info = &line->d.info[i];
int vlen = bcf_hdr_id2length(header,BCF_HL_INFO,info->key);
if ( vlen!=BCF_VL_A && vlen!=BCF_VL_G && vlen!=BCF_VL_R ) continue; // no need to change
int type = bcf_hdr_id2type(header,BCF_HL_INFO,info->key);
if ( type==BCF_HT_FLAG ) continue;
int size = 1;
if ( type==BCF_HT_REAL || type==BCF_HT_INT ) size = 4;
mdat = mdat_bytes / size;
nret = bcf_get_info_values(header, line, bcf_hdr_int2id(header,BCF_DT_ID,info->key), (void**)&dat, &mdat, type);
mdat_bytes = mdat * size;
if ( nret<0 )
{
fprintf(stderr,"[%s:%d %s] Could not access INFO/%s at %s:%d [%d]\n", __FILE__,__LINE__,__FUNCTION__,
bcf_hdr_int2id(header,BCF_DT_ID,info->key), bcf_seqname(header,line), line->pos+1, nret);
exit(1);
}
if ( type==BCF_HT_STR )
{
str.l = 0;
char *ss = (char*) dat, *se = (char*) dat;
if ( vlen==BCF_VL_A || vlen==BCF_VL_R )
{
int nexp, inc = 0;
if ( vlen==BCF_VL_A )
{
nexp = nA_ori;
inc = 1;
}
else
nexp = nR_ori;
for (j=0; j<nexp; j++)
{
if ( !*se ) break;
while ( *se && *se!=',' ) se++;
if ( rm_mask & 1<<(j+inc) )
{
if ( *se ) se++;
ss = se;
continue;
}
if ( str.l ) kputc(',',&str);
kputsn(ss,se-ss,&str);
if ( *se ) se++;
ss = se;
}
assert( j==nexp );
}
else // Number=G, assuming diploid genotype
{
int k = 0, n = 0;
for (j=0; j<nR_ori; j++)
{
for (k=0; k<=j; k++)
{
if ( !*se ) break;
while ( *se && *se!=',' ) se++;
n++;
if ( rm_mask & 1<<j || rm_mask & 1<<k )
{
if ( *se ) se++;
ss = se;
continue;
}
if ( str.l ) kputc(',',&str);
kputsn(ss,se-ss,&str);
if ( *se ) se++;
ss = se;
}
if ( !*se ) break;
}
assert( n=nG_ori );
}
nret = bcf_update_info(header, line, bcf_hdr_int2id(header,BCF_DT_ID,info->key), (void*)str.s, str.l, type);
if ( nret<0 )
{
fprintf(stderr,"[%s:%d %s] Could not update INFO/%s at %s:%d [%d]\n", __FILE__,__LINE__,__FUNCTION__,
bcf_hdr_int2id(header,BCF_DT_ID,info->key), bcf_seqname(header,line), line->pos+1, nret);
exit(1);
}
continue;
}
if ( vlen==BCF_VL_A || vlen==BCF_VL_R )
{
int inc = 0, ntop;
if ( vlen==BCF_VL_A )
{
assert( nret==nA_ori );
ntop = nA_ori;
ndat = nA_new;
inc = 1;
}
else
{
assert( nret==nR_ori );
ntop = nR_ori;
ndat = nR_new;
}
int k = 0;
#define BRANCH(type_t,is_vector_end) \
{ \
type_t *ptr = (type_t*) dat; \
int size = sizeof(type_t); \
for (j=0; j<ntop; j++) /* j:ori, k:new */ \
{ \
if ( is_vector_end ) { memcpy(dat+k*size, dat+j*size, size); break; } \
if ( rm_mask & 1<<(j+inc) ) continue; \
if ( j!=k ) memcpy(dat+k*size, dat+j*size, size); \
k++; \
} \
}
switch (type)
{
case BCF_HT_INT: BRANCH(int32_t,ptr[j]==bcf_int32_vector_end); break;
case BCF_HT_REAL: BRANCH(float,bcf_float_is_vector_end(ptr[j])); break;
}
#undef BRANCH
}
else // Number=G
{
assert( nret==nG_ori );
int k, l_ori = -1, l_new = 0;
ndat = nG_new;
#define BRANCH(type_t,is_vector_end) \
{ \
type_t *ptr = (type_t*) dat; \
int size = sizeof(type_t); \
for (j=0; j<nR_ori; j++) \
{ \
for (k=0; k<=j; k++) \
{ \
l_ori++; \
if ( is_vector_end ) { memcpy(dat+l_new*size, dat+l_ori*size, size); break; } \
if ( rm_mask & 1<<j || rm_mask & 1<<k ) continue; \
if ( l_ori!=l_new ) memcpy(dat+l_new*size, dat+l_ori*size, size); \
l_new++; \
} \
} \
}
switch (type)
{
case BCF_HT_INT: BRANCH(int32_t,ptr[l_ori]==bcf_int32_vector_end); break;
case BCF_HT_REAL: BRANCH(float,bcf_float_is_vector_end(ptr[l_ori])); break;
}
#undef BRANCH
}
nret = bcf_update_info(header, line, bcf_hdr_int2id(header,BCF_DT_ID,info->key), (void*)dat, ndat, type);
if ( nret<0 )
{
fprintf(stderr,"[%s:%d %s] Could not update INFO/%s at %s:%d [%d]\n", __FILE__,__LINE__,__FUNCTION__,
bcf_hdr_int2id(header,BCF_DT_ID,info->key), bcf_seqname(header,line), line->pos+1, nret);
exit(1);
}
}
// Update GT fields, the allele indexes might have changed
for (i=1; i<line->n_allele; i++) if ( map[i]!=i ) break;
if ( i<line->n_allele )
{
mdat = mdat_bytes / 4; // sizeof(int32_t)
nret = bcf_get_genotypes(header,line,(void**)&dat,&mdat);
mdat_bytes = mdat * 4;
if ( nret>0 )
{
nret /= line->n_sample;
int32_t *ptr = (int32_t*) dat;
for (i=0; i<line->n_sample; i++)
{
for (j=0; j<nret; j++)
{
if ( ptr[j]==bcf_gt_missing ) continue;
if ( ptr[j]==bcf_int32_vector_end ) break;
int al = bcf_gt_allele(ptr[j]);
assert( al<nR_ori && map[al]>=0 );
ptr[j] = (map[al]+1)<<1 | (ptr[j]&1);
}
ptr += nret;
}
bcf_update_genotypes(header, line, (void*)dat, nret*line->n_sample);
}
}
// Remove from Number=G, Number=R and Number=A FORMAT fields.
// Assuming haploid or diploid GTs
for (i=0; i<line->n_fmt; i++)
{
bcf_fmt_t *fmt = &line->d.fmt[i];
int vlen = bcf_hdr_id2length(header,BCF_HL_FMT,fmt->id);
if ( vlen!=BCF_VL_A && vlen!=BCF_VL_G && vlen!=BCF_VL_R ) continue; // no need to change
int type = bcf_hdr_id2type(header,BCF_HL_FMT,fmt->id);
if ( type==BCF_HT_FLAG ) continue;
int size = 1;
if ( type==BCF_HT_REAL || type==BCF_HT_INT ) size = 4;
mdat = mdat_bytes / size;
nret = bcf_get_format_values(header, line, bcf_hdr_int2id(header,BCF_DT_ID,fmt->id), (void**)&dat, &mdat, type);
mdat_bytes = mdat * size;
if ( nret<0 )
{
fprintf(stderr,"[%s:%d %s] Could not access FORMAT/%s at %s:%d [%d]\n", __FILE__,__LINE__,__FUNCTION__,
bcf_hdr_int2id(header,BCF_DT_ID,fmt->id), bcf_seqname(header,line), line->pos+1, nret);
exit(1);
}
if ( type==BCF_HT_STR )
{
int size = nret/line->n_sample; // number of bytes per sample
str.l = 0;
if ( vlen==BCF_VL_A || vlen==BCF_VL_R )
{
int nexp, inc = 0;
if ( vlen==BCF_VL_A )
{
nexp = nA_ori;
inc = 1;
}
else
nexp = nR_ori;
for (j=0; j<line->n_sample; j++)
{
char *ss = ((char*)dat) + j*size, *se = ss + size, *ptr = ss;
int k_src = 0, k_dst = 0, l = str.l;
for (k_src=0; k_src<nexp; k_src++)
{
if ( ptr>=se || !*ptr) break;
while ( ptr<se && *ptr && *ptr!=',' ) ptr++;
if ( rm_mask & 1<<(k_src+inc) )
{
ss = ++ptr;
continue;
}
if ( k_dst ) kputc(',',&str);
kputsn(ss,ptr-ss,&str);
ss = ++ptr;
k_dst++;
}
assert( k_src==nexp );
l = str.l - l;
for (; l<size; l++) kputc(0, &str);
}
}
else // Number=G, diploid or haploid
{
for (j=0; j<line->n_sample; j++)
{
char *ss = ((char*)dat) + j*size, *se = ss + size, *ptr = ss;
int k_src = 0, k_dst = 0, l = str.l;
int nexp = 0; // diploid or haploid?
while ( ptr<se )
{
if ( !*ptr ) break;
if ( *ptr==',' ) nexp++;
ptr++;
}
if ( ptr!=ss ) nexp++;
assert( nexp==nG_ori || nexp==nR_ori );
ptr = ss;
if ( nexp==nG_ori ) // diploid
{
int ia, ib;
for (ia=0; ia<nR_ori; ia++)
{
for (ib=0; ib<=ia; ib++)
{
if ( ptr>=se || !*ptr ) break;
while ( ptr<se && *ptr && *ptr!=',' ) ptr++;
if ( rm_mask & 1<<ia || rm_mask & 1<<ib )
{
ss = ++ptr;
continue;
}
if ( k_dst ) kputc(',',&str);
kputsn(ss,ptr-ss,&str);
ss = ++ptr;
k_dst++;
}
if ( ptr>=se || !*ptr ) break;
}
}
else // haploid
{
for (k_src=0; k_src<nR_ori; k_src++)
{
if ( ptr>=se || !*ptr ) break;
while ( ptr<se && *ptr && *ptr!=',' ) ptr++;
if ( rm_mask & 1<<k_src )
{
ss = ++ptr;
continue;
}
if ( k_dst ) kputc(',',&str);
kputsn(ss,ptr-ss,&str);
ss = ++ptr;
k_dst++;
}
assert( k_src==nR_ori );
l = str.l - l;
for (; l<size; l++) kputc(0, &str);
}
}
}
nret = bcf_update_format(header, line, bcf_hdr_int2id(header,BCF_DT_ID,fmt->id), (void*)str.s, str.l, type);
if ( nret<0 )
{
fprintf(stderr,"[%s:%d %s] Could not update FORMAT/%s at %s:%d [%d]\n", __FILE__,__LINE__,__FUNCTION__,
bcf_hdr_int2id(header,BCF_DT_ID,fmt->id), bcf_seqname(header,line), line->pos+1, nret);
exit(1);
}
continue;
}
int nori = nret / line->n_sample;
if ( vlen==BCF_VL_A || vlen==BCF_VL_R || (vlen==BCF_VL_G && nori==nR_ori) ) // Number=A, R or haploid Number=G
{
int ntop, inc = 0;
if ( vlen==BCF_VL_A )
{
assert( nori==nA_ori ); // todo: will fail if all values are missing
ntop = nA_ori;
ndat = nA_new*line->n_sample;
inc = 1;
}
else
{
assert( nori==nR_ori ); // todo: will fail if all values are missing
ntop = nR_ori;
ndat = nR_new*line->n_sample;
}
#define BRANCH(type_t,is_vector_end) \
{ \
for (j=0; j<line->n_sample; j++) \
{ \
type_t *ptr_src = ((type_t*)dat) + j*nori; \
type_t *ptr_dst = ((type_t*)dat) + j*nA_new; \
int size = sizeof(type_t); \
int k_src, k_dst = 0; \
for (k_src=0; k_src<ntop; k_src++) \
{ \
if ( is_vector_end ) { memcpy(ptr_dst+k_dst, ptr_src+k_src, size); break; } \
if ( rm_mask & 1<<(k_src+inc) ) continue; \
if ( k_src!=k_dst ) memcpy(ptr_dst+k_dst, ptr_src+k_src, size); \
k_dst++; \
} \
} \
}
switch (type)
{
case BCF_HT_INT: BRANCH(int32_t,ptr_src[k_src]==bcf_int32_vector_end); break;
case BCF_HT_REAL: BRANCH(float,bcf_float_is_vector_end(ptr_src[k_src])); break;
}
#undef BRANCH
}
else // Number=G, diploid or mixture of haploid+diploid
{
assert( nori==nG_ori );
ndat = nG_new*line->n_sample;
#define BRANCH(type_t,is_vector_end) \
{ \
for (j=0; j<line->n_sample; j++) \
{ \
type_t *ptr_src = ((type_t*)dat) + j*nori; \
type_t *ptr_dst = ((type_t*)dat) + j*nG_new; \
int size = sizeof(type_t); \
int ia, ib, k_dst = 0, k_src; \
int nset = 0; /* haploid or diploid? */ \
for (k_src=0; k_src<nG_ori; k_src++) { if ( is_vector_end ) break; nset++; } \
if ( nset==nR_ori ) /* haploid */ \
{ \
for (k_src=0; k_src<nR_ori; k_src++) \
{ \
if ( rm_mask & 1<<k_src ) continue; \
if ( k_src!=k_dst ) memcpy(ptr_dst+k_dst, ptr_src+k_src, size); \
k_dst++; \
} \
memcpy(ptr_dst+k_dst, ptr_src+k_src, size); \
} \
else /* diploid */ \
{ \
k_src = -1; \
for (ia=0; ia<nR_ori; ia++) \
{ \
for (ib=0; ib<=ia; ib++) \
{ \
k_src++; \
if ( is_vector_end ) { memcpy(ptr_dst+k_dst, ptr_src+k_src, size); ia = nR_ori; break; } \
if ( rm_mask & 1<<ia || rm_mask & 1<<ib ) continue; \
if ( k_src!=k_dst ) memcpy(ptr_dst+k_dst, ptr_src+k_src, size); \
k_dst++; \
} \
} \
} \
} \
}
switch (type)
{
case BCF_HT_INT: BRANCH(int32_t,ptr_src[k_src]==bcf_int32_vector_end); break;
case BCF_HT_REAL: BRANCH(float,bcf_float_is_vector_end(ptr_src[k_src])); break;
}
#undef BRANCH
}
nret = bcf_update_format(header, line, bcf_hdr_int2id(header,BCF_DT_ID,fmt->id), (void*)dat, ndat, type);
if ( nret<0 )
{
fprintf(stderr,"[%s:%d %s] Could not update FORMAT/%s at %s:%d [%d]\n", __FILE__,__LINE__,__FUNCTION__,
bcf_hdr_int2id(header,BCF_DT_ID,fmt->id), bcf_seqname(header,line), line->pos+1, nret);
exit(1);
}
}
free(dat);
free(str.s);
free(map);
}
bcf1_t *process(bcf1_t *rec)
{
bcf1_t *dflt = args.mode&MODE_LIST_GOOD ? rec : NULL;
args.nrec++;
if ( rec->n_allele > 63 ) return dflt; // we use 64bit bitmask below
int ngt = bcf_get_genotypes(args.hdr, rec, &args.gt_arr, &args.ngt_arr);
if ( ngt<0 ) return dflt;
if ( ngt!=2*bcf_hdr_nsamples(args.hdr) && ngt!=bcf_hdr_nsamples(args.hdr) ) return dflt;
ngt /= bcf_hdr_nsamples(args.hdr);
int itr_set = regidx_overlap(args.rules, bcf_seqname(args.hdr,rec),rec->pos,rec->pos, args.itr_ori);
int i, has_bad = 0, needs_update = 0;
for (i=0; i<args.ntrios; i++)
{
int32_t a,b,c,d,e,f;
trio_t *trio = &args.trios[i];
a = args.gt_arr[ngt*trio->imother];
b = ngt==2 ? args.gt_arr[ngt*trio->imother+1] : bcf_int32_vector_end;
c = args.gt_arr[ngt*trio->ifather];
d = ngt==2 ? args.gt_arr[ngt*trio->ifather+1] : bcf_int32_vector_end;
e = args.gt_arr[ngt*trio->ichild];
f = ngt==2 ? args.gt_arr[ngt*trio->ichild+1] : bcf_int32_vector_end;
// skip sites with missing data in child
if ( bcf_gt_is_missing(e) || bcf_gt_is_missing(f) ) continue;
uint64_t mother = 0, father = 0,child1,child2;
int is_ok = 0;
if ( !itr_set )
{
if ( f==bcf_int32_vector_end ) { warn_ploidy(rec); continue; }
// All M,F,C genotypes are diploid. Missing data are considered consistent.
child1 = 1<<bcf_gt_allele(e);
child2 = 1<<bcf_gt_allele(f);
mother = bcf_gt_is_missing(a) ? child1|child2 : 1<<bcf_gt_allele(a);
mother |= bcf_gt_is_missing(b) || b==bcf_int32_vector_end ? child1|child2 : 1<<bcf_gt_allele(b);
father = bcf_gt_is_missing(c) ? child1|child2 : 1<<bcf_gt_allele(c);
father |= bcf_gt_is_missing(d) || d==bcf_int32_vector_end ? child1|child2 : 1<<bcf_gt_allele(d);
if ( (mother&child1 && father&child2) || (mother&child2 && father&child1) ) is_ok = 1;
}
else
{
child1 = 1<<bcf_gt_allele(e);
child2 = bcf_gt_is_missing(f) || f==bcf_int32_vector_end ? 0 : 1<<bcf_gt_allele(f);
mother |= bcf_gt_is_missing(a) ? 0 : 1<<bcf_gt_allele(a);
mother |= bcf_gt_is_missing(b) || b==bcf_int32_vector_end ? 0 : 1<<bcf_gt_allele(b);
father |= bcf_gt_is_missing(c) ? 0 : 1<<bcf_gt_allele(c);
father |= bcf_gt_is_missing(d) || d==bcf_int32_vector_end ? 0 : 1<<bcf_gt_allele(d);
regitr_copy(args.itr, args.itr_ori);
while ( !is_ok && regitr_overlap(args.itr) )
{
rule_t *rule = ®itr_payload(args.itr,rule_t);
if ( child1 && child2 )
{
if ( !rule->mal || !rule->fal ) continue; // wrong rule (haploid), but this is a diploid GT
if ( !mother ) mother = child1|child2;
if ( !father ) father = child1|child2;
if ( (mother&child1 && father&child2) || (mother&child2 && father&child1) ) is_ok = 1;
continue;
}
if ( rule->mal )
{
if ( mother && !(child1&mother) ) continue;
}
if ( rule->fal )
{
if ( father && !(child1&father) ) continue;
}
is_ok = 1;
}
}
if ( is_ok )
{
trio->nok++;
}
else
{
trio->nbad++;
has_bad = 1;
if ( args.mode&MODE_DELETE )
{
args.gt_arr[ngt*trio->imother] = bcf_gt_missing;
if ( b!=bcf_int32_vector_end ) args.gt_arr[ngt*trio->imother+1] = bcf_gt_missing; // should be always true
args.gt_arr[ngt*trio->ifather] = bcf_gt_missing;
if ( d!=bcf_int32_vector_end ) args.gt_arr[ngt*trio->ifather+1] = bcf_gt_missing;
args.gt_arr[ngt*trio->ichild] = bcf_gt_missing;
if ( f!=bcf_int32_vector_end ) args.gt_arr[ngt*trio->ichild+1] = bcf_gt_missing;
needs_update = 1;
}
}
}
if ( needs_update && bcf_update_genotypes(args.hdr,rec,args.gt_arr,ngt*bcf_hdr_nsamples(args.hdr)) )
error("Could not update GT field at %s:%d\n", bcf_seqname(args.hdr,rec),rec->pos+1);
if ( args.mode&MODE_DELETE ) return rec;
if ( args.mode&MODE_LIST_GOOD ) return has_bad ? NULL : rec;
if ( args.mode&MODE_LIST_BAD ) return has_bad ? rec : NULL;
return NULL;
}
/*
* GT field (genotype) comparison function.
*/
bcf1_t *process(bcf1_t *rec)
{
uint64_t i;
bcf_unpack(rec, BCF_UN_FMT); // unpack the Format fields, including the GT field
int gte_smp = 0; // number GT array entries per sample (should be 2, one entry per allele)
args.ngt_arr = 0; /*! hold the number of current GT array entries */
if ( (gte_smp = bcf_get_genotypes(args.hdr, rec, &(args.gt_arr), &(args.ngt_arr) ) ) <= 0 )
{
error("GT not present at %s: %d\n", args.hdr->id[BCF_DT_CTG][rec->rid].key, rec->pos+1);
}
gte_smp /= args.nsmp; // divide total number of genotypes array entries (= args.ngt_arr) by number of samples
// initialize with missing genotype
int a1 = 0;
int a2 = 0;
// initialize with first selected sample genotype that is not missing
int gt = -1;
while ( (a1 == 0) || (a2 == 0) )
{
gt++;
if (gt == args.nsmp) break;
if (args.selected_smps[gt] == 0) continue;
a1 = (args.gt_arr + gte_smp * gt)[0];
if ( gte_smp == 2 ) a2 = (args.gt_arr + gte_smp * gt)[1];
else if ( gte_smp == 1 ) a2 = bcf_int32_vector_end;
else error("GTsubset does not support ploidy higher than 2.\n");
}
// fprintf(stderr, "a1: %i a2: %i\n", a1, a2);
// check all genotypes if they match (for included samples) or disagree (for samples not included)
gt = 0;
for ( i = 0; i < args.nsmp; i++ )
{
int *gt_ptr = args.gt_arr + gte_smp * i;
int b1 = gt_ptr[0];
int b2;
if ( gte_smp == 2 ) // two entries available per sample, padded with missing values for haploid genotypes
{
b2 = gt_ptr[1];
}
else if (gte_smp == 1 ) // use vector end value for second entry, if only one is available
{
b2 = bcf_int32_vector_end;
}
else
{
error("GTsubset does not support ploidy higher than 2.\n");
}
// fprintf(stderr, "b1: %i b2: %i\n", b1, b2);
/* missing genotypes are counted as always passing, as they neither
* mismatch the initial selected genotype for a selected sample, nor
* do they match the initial selected genotype for an excluded sample's
* genotype */
if ( (b1 == 0) || (b2 == 0) )
{
gt++;
// fprintf(stderr, "missing => pass\n");
continue;
}
else if ( args.selected_smps[i] == 1 )
{
if ( (b1 == a1) && (b2 == a2) )
{
gt++;
// fprintf(stderr, "match => pass\n");
continue;
}
else
{
// fprintf(stderr, "no match => fail\n");
break;
}
}
else if ( args.selected_smps[i] == 0 )
{
if ( (b1 != a1 ) || (b2 != a2) )
{
gt++;
// fprintf(stderr, "no match => pass\n");
continue;
}
else
{
// fprintf(stderr, "match => fail\n");
break;
}
}
}
if ( gt == args.nsmp )
{
return rec;
}
else
{
return NULL;
}
}
int parse_line(args_t *args, bcf1_t *line, double *alt_freq, double *pdg)
{
args->nitmp = 0;
// Set allele frequency
int ret;
if ( args->af_tag )
{
// Use an INFO tag provided by the user
ret = bcf_get_info_float(args->hdr, line, args->af_tag, &args->AFs, &args->mAFs);
if ( ret==1 )
*alt_freq = args->AFs[0];
if ( ret==-2 )
error("Type mismatch for INFO/%s tag at %s:%d\n", args->af_tag, bcf_seqname(args->hdr,line), line->pos+1);
}
else if ( args->af_fname )
{
// Read AF from a file
ret = read_AF(args->files->targets, line, alt_freq);
}
else
{
// Use GTs or AC/AN: GTs when AC/AN not present or when GTs explicitly requested by --estimate-AF
ret = -1;
if ( !args->estimate_AF )
{
int AC = -1, AN = 0;
ret = bcf_get_info_int32(args->hdr, line, "AN", &args->itmp, &args->mitmp);
if ( ret==1 )
{
AN = args->itmp[0];
ret = bcf_get_info_int32(args->hdr, line, "AC", &args->itmp, &args->mitmp);
if ( ret>0 )
AC = args->itmp[0];
}
if ( AN<=0 || AC<0 )
ret = -1;
else
*alt_freq = (double) AC/AN;
}
if ( ret==-1 )
ret = estimate_AF(args, line, alt_freq); // reads GTs into args->itmp
}
if ( ret<0 ) return ret;
if ( *alt_freq==0.0 )
{
if ( args->dflt_AF==0 ) return -1; // we skip sites with AF=0
*alt_freq = args->dflt_AF;
}
// Set P(D|G)
if ( args->fake_PLs )
{
if ( !args->nitmp )
{
args->nitmp = bcf_get_genotypes(args->hdr, line, &args->itmp, &args->mitmp);
if ( args->nitmp != 2*args->nsmpl ) return -1; // not diploid?
args->nitmp /= args->nsmpl;
}
int32_t *gt = &args->itmp[args->ismpl*args->nitmp];
if ( bcf_gt_is_missing(gt[0]) || bcf_gt_is_missing(gt[1]) ) return -1;
int a = bcf_gt_allele(gt[0]);
int b = bcf_gt_allele(gt[1]);
if ( a!=b )
{
pdg[0] = pdg[2] = args->unseen_PL;
pdg[1] = 1 - 2*args->unseen_PL;
}
else if ( a==0 )
{
pdg[0] = 1 - 2*args->unseen_PL;
pdg[1] = pdg[2] = args->unseen_PL;
}
else
{
pdg[0] = pdg[1] = args->unseen_PL;
pdg[2] = 1 - 2*args->unseen_PL;
}
}
else
{
args->nitmp = bcf_get_format_int32(args->hdr, line, "PL", &args->itmp, &args->mitmp);
if ( args->nitmp != args->nsmpl*line->n_allele*(line->n_allele+1)/2. ) return -1; // not diploid?
args->nitmp /= args->nsmpl;
int32_t *pl = &args->itmp[args->ismpl*args->nitmp];
pdg[0] = pl[0] < 256 ? args->pl2p[ pl[0] ] : 1.0;
pdg[1] = pl[1] < 256 ? args->pl2p[ pl[1] ] : 1.0;
pdg[2] = pl[2] < 256 ? args->pl2p[ pl[2] ] : 1.0;
double sum = pdg[0] + pdg[1] + pdg[2];
if ( !sum ) return -1;
pdg[0] /= sum;
pdg[1] /= sum;
pdg[2] /= sum;
}
return 0;
}
void genrich_data::readReferenceGenotypes(string fvcf) {
vector < int > mappingS;
//Opening files
vrb.title("Reading variant list in [" + fvcf + "] MAF=" + stb.str(threshold_maf));
bcf_srs_t * sr = bcf_sr_init();
if(!(bcf_sr_add_reader (sr, fvcf.c_str()))) {
switch (sr->errnum) {
case not_bgzf: vrb.error("File not compressed with bgzip!");
case idx_load_failed: vrb.error("Impossible to load index file!");
case file_type_error: vrb.error("File format not detected by htslib!");
default : vrb.error("Unknown error!");
}
}
//Sample processing
int included_sample = 0;
int n_samples = bcf_hdr_nsamples(sr->readers[0].header);
for (int i = 0 ; i < n_samples ; i ++) {
mappingS.push_back(findSample(string(sr->readers[0].header->samples[i])));
if (mappingS.back() >= 0) included_sample ++;
}
vrb.bullet("#samples = " + stb.str(included_sample));
//Variant processing
unsigned int n_excludedV_mult = 0, n_excludedV_void = 0, n_excludedV_rare = 0, n_excludedV_uchr = 0, n_line = 0, n_excludedV_toofar = 0;
int ngt, ngt_arr = 0, *gt_arr = NULL;
bcf1_t * line;
while(bcf_sr_next_line (sr)) {
line = bcf_sr_get_line(sr, 0);
if (line->n_allele == 2) {
bcf_unpack(line, BCF_UN_STR);
string sid = string(line->d.id);
string chr = string(bcf_hdr_id2name(sr->readers[0].header, line->rid));
int chr_idx = findCHR(chr);
if (chr_idx >= 0) {
unsigned int pos = line->pos + 1;
ngt = bcf_get_genotypes(sr->readers[0].header, line, >_arr, &ngt_arr);
if (ngt == 2*n_samples) {
double freq = 0.0, tot = 0.0;
for(int i = 0 ; i < n_samples ; i ++) {
assert(gt_arr[2*i+0] != bcf_gt_missing && gt_arr[2*i+1] != bcf_gt_missing);
if (mappingS[i] >= 0) {
freq += bcf_gt_allele(gt_arr[2*i+0]) + bcf_gt_allele(gt_arr[2*i+1]);
tot += 2.0;
}
}
double maf = freq / tot;
if (maf > 0.5) maf = 1.0 - maf;
if (maf >= threshold_maf) {
int dist_tss = getDistance(chr_idx, pos);
if (dist_tss < 1e6) {
string tmp_id = chr + "_" + stb.str(pos);
genotype_uuid.insert(pair < string, unsigned int > (tmp_id, genotype_pos.size()));
genotype_chr.push_back(chr_idx);
genotype_pos.push_back(pos);
genotype_maf.push_back(maf);
genotype_dist.push_back(dist_tss);
genotype_haps.push_back(vector < bool > (2 * included_sample, false));
for(int i = 0 ; i < n_samples ; i ++) {
if (mappingS[i] >= 0) {
genotype_haps.back()[2 * mappingS[i] + 0] = bcf_gt_allele(gt_arr[2 * i + 0]);
genotype_haps.back()[2 * mappingS[i] + 1] = bcf_gt_allele(gt_arr[2 * i + 1]);
}
}
} else n_excludedV_toofar++;
} else n_excludedV_rare ++;
} else n_excludedV_void ++;
} else n_excludedV_uchr ++;
} else n_excludedV_mult ++;
if (n_line % 100000 == 0) vrb.bullet("#lines = " + stb.str(n_line));
n_line ++;
}
genotype_qtl = vector < bool > (genotype_pos.size(), false);
genotype_gwas = vector < bool > (genotype_pos.size(), false);
genotype_bin = vector < int > (genotype_pos.size(), -1);
//Finalize
bcf_sr_destroy(sr);
vrb.bullet(stb.str(genotype_pos.size()) + " variants included");
if (n_excludedV_mult > 0) vrb.bullet(stb.str(n_excludedV_mult) + " multi-allelic variants excluded");
if (n_excludedV_uchr > 0) vrb.bullet(stb.str(n_excludedV_uchr) + " variants with unreferenced chromosome in --tss");
if (n_excludedV_rare > 0) vrb.bullet(stb.str(n_excludedV_rare) + " maf filtered variants");
if (n_excludedV_toofar > 0) vrb.bullet(stb.str(n_excludedV_toofar) + " too far variants");
}
static void check_gt(args_t *args)
{
int i,ret, *gt2ipl = NULL, m_gt2ipl = 0, *gt_arr = NULL, ngt_arr = 0;
int fake_pls = args->no_PLs;
// Initialize things: check which tags are defined in the header, sample names etc.
if ( bcf_hdr_id2int(args->gt_hdr, BCF_DT_ID, "GT")<0 ) error("[E::%s] GT not present in the header of %s?\n", __func__, args->files->readers[1].fname);
if ( bcf_hdr_id2int(args->sm_hdr, BCF_DT_ID, "PL")<0 )
{
if ( bcf_hdr_id2int(args->sm_hdr, BCF_DT_ID, "GT")<0 )
error("[E::%s] Neither PL nor GT present in the header of %s\n", __func__, args->files->readers[0].fname);
fprintf(stderr,"Warning: PL not present in the header of %s, using GT instead\n", args->files->readers[0].fname);
fake_pls = 1;
}
FILE *fp = args->plot ? open_file(NULL, "w", "%s.tab", args->plot) : stdout;
print_header(args, fp);
int tgt_isample = -1, query_isample = 0;
if ( args->target_sample )
{
tgt_isample = bcf_hdr_id2int(args->gt_hdr, BCF_DT_SAMPLE, args->target_sample);
if ( tgt_isample<0 ) error("No such sample in %s: [%s]\n", args->files->readers[1].fname, args->target_sample);
}
if ( args->all_sites )
{
if ( tgt_isample==-1 )
{
fprintf(stderr,"No target sample selected for comparison, using the first sample in %s: %s\n", args->gt_fname,args->gt_hdr->samples[0]);
tgt_isample = 0;
}
}
if ( args->query_sample )
{
query_isample = bcf_hdr_id2int(args->sm_hdr, BCF_DT_SAMPLE, args->query_sample);
if ( query_isample<0 ) error("No such sample in %s: [%s]\n", args->files->readers[0].fname, args->query_sample);
}
if ( args->all_sites )
fprintf(fp, "# [1]SC, Site by Site Comparison\t[2]Chromosome\t[3]Position\t[4]-g alleles\t[5]-g GT (%s)\t[6]Coverage\t[7]Query alleles\t[8-]Query PLs (%s)\n", args->gt_hdr->samples[tgt_isample],args->sm_hdr->samples[query_isample]);
// Main loop
while ( (ret=bcf_sr_next_line(args->files)) )
{
if ( ret!=2 ) continue;
bcf1_t *sm_line = args->files->readers[0].buffer[0]; // the query file
bcf1_t *gt_line = args->files->readers[1].buffer[0]; // the -g target file
bcf_unpack(sm_line, BCF_UN_FMT);
bcf_unpack(gt_line, BCF_UN_FMT);
// Init mapping from target genotype index to the sample's PL fields
int n_gt2ipl = gt_line->n_allele*(gt_line->n_allele + 1)/2;
if ( n_gt2ipl > m_gt2ipl )
{
m_gt2ipl = n_gt2ipl;
gt2ipl = (int*) realloc(gt2ipl, sizeof(int)*m_gt2ipl);
}
if ( !init_gt2ipl(args, gt_line, sm_line, gt2ipl, n_gt2ipl) ) continue;
// Target genotypes
int ngt, npl;
if ( (ngt=bcf_get_genotypes(args->gt_hdr, gt_line, >_arr, &ngt_arr)) <= 0 )
error("GT not present at %s:%d?", args->gt_hdr->id[BCF_DT_CTG][gt_line->rid].key, gt_line->pos+1);
ngt /= bcf_hdr_nsamples(args->gt_hdr);
if ( ngt!=2 ) continue; // checking only diploid genotypes
// Sample PLs
if ( !fake_pls )
{
if ( (npl=bcf_get_format_int32(args->sm_hdr, sm_line, "PL", &args->pl_arr, &args->npl_arr)) <= 0 )
error("PL not present at %s:%d?", args->sm_hdr->id[BCF_DT_CTG][sm_line->rid].key, sm_line->pos+1);
npl /= bcf_hdr_nsamples(args->sm_hdr);
}
else
npl = fake_PLs(args, args->sm_hdr, sm_line);
// Calculate likelihoods for all samples, assuming diploid genotypes
// For faster access to genotype likelihoods (PLs) of the query sample
int max_ipl, *pl_ptr = args->pl_arr + query_isample*npl;
double sum_pl = 0; // for converting PLs to probs
for (max_ipl=0; max_ipl<npl; max_ipl++)
{
if ( pl_ptr[max_ipl]==bcf_int32_vector_end ) break;
if ( pl_ptr[max_ipl]==bcf_int32_missing ) continue;
sum_pl += pow(10, -0.1*pl_ptr[max_ipl]);
}
if ( sum_pl==0 ) continue; // no PLs present
// The main stats: concordance of the query sample with the target -g samples
for (i=0; i<bcf_hdr_nsamples(args->gt_hdr); i++)
{
int *gt_ptr = gt_arr + i*ngt;
if ( gt_ptr[1]==bcf_int32_vector_end ) continue; // skip haploid genotypes
int a = bcf_gt_allele(gt_ptr[0]);
int b = bcf_gt_allele(gt_ptr[1]);
if ( a<0 || b<0 ) continue; // missing genotypes
if ( args->hom_only && a!=b ) continue; // heterozygous genotype
int igt_tgt = igt_tgt = bcf_alleles2gt(a,b); // genotype index in the target file
int igt_qry = gt2ipl[igt_tgt]; // corresponding genotype in query file
if ( igt_qry>=max_ipl || pl_ptr[igt_qry]<0 ) continue; // genotype not present in query sample: haploid or missing
args->lks[i] += log(pow(10, -0.1*pl_ptr[igt_qry])/sum_pl);
args->sites[i]++;
}
if ( args->all_sites )
{
// Print LKs at all sites for debugging
int *gt_ptr = gt_arr + tgt_isample*ngt;
if ( gt_ptr[1]==bcf_int32_vector_end ) continue; // skip haploid genotypes
int a = bcf_gt_allele(gt_ptr[0]);
int b = bcf_gt_allele(gt_ptr[1]);
if ( args->hom_only && a!=b ) continue; // heterozygous genotype
fprintf(fp, "SC\t%s\t%d", args->gt_hdr->id[BCF_DT_CTG][gt_line->rid].key, gt_line->pos+1);
for (i=0; i<gt_line->n_allele; i++) fprintf(fp, "%c%s", i==0?'\t':',', gt_line->d.allele[i]);
fprintf(fp, "\t%s/%s", a>=0 ? gt_line->d.allele[a] : ".", b>=0 ? gt_line->d.allele[b] : ".");
int igt, *pl_ptr = args->pl_arr + query_isample*npl; // PLs of the query sample
for (i=0; i<sm_line->n_allele; i++) fprintf(fp, "%c%s", i==0?'\t':',', sm_line->d.allele[i]);
for (igt=0; igt<npl; igt++)
if ( pl_ptr[igt]==bcf_int32_vector_end ) break;
else if ( pl_ptr[igt]==bcf_int32_missing ) fprintf(fp, ".");
else fprintf(fp, "\t%d", pl_ptr[igt]);
fprintf(fp, "\n");
}
}
free(gt2ipl);
free(gt_arr);
free(args->pl_arr);
free(args->tmp_arr);
// Scale LKs and certainties
int nsamples = bcf_hdr_nsamples(args->gt_hdr);
double min = args->lks[0];
for (i=1; i<nsamples; i++) if ( min>args->lks[i] ) min = args->lks[i];
for (i=0; i<nsamples; i++) args->lks[i] = min ? args->lks[i] / min : 0;
double max_avg = args->sites[0] ? args->lks[0]/args->sites[0] : 0;
for (i=1; i<nsamples; i++)
{
double val = args->sites[i] ? args->lks[i]/args->sites[i] : 0;
if ( max_avg<val ) max_avg = val;
}
// Sorted output
double **p = (double**) malloc(sizeof(double*)*nsamples);
for (i=0; i<nsamples; i++) p[i] = &args->lks[i];
qsort(p, nsamples, sizeof(int*), cmp_doubleptr);
fprintf(fp, "# [1]CN\t[2]Concordance with %s (total)\t[3]Concordance (average)\t[4]Number of sites compared\t[5]Sample\t[6]Sample ID\n", args->sm_hdr->samples[query_isample]);
for (i=0; i<nsamples; i++)
{
int idx = p[i] - args->lks;
double avg = args->sites[idx] ? args->lks[idx]/args->sites[idx] : 0;
fprintf(fp, "CN\t%e\t%e\t%.0f\t%s\t%d\n", 1-args->lks[idx], 1-avg/max_avg, args->sites[idx], args->gt_hdr->samples[idx], i);
}
if ( args->plot )
{
fclose(fp);
plot_check(args, args->target_sample ? args->target_sample : "", args->sm_hdr->samples[query_isample]);
}
}
static void phased_flush(args_t *args)
{
if ( !args->nbuf ) return;
bcf_hdr_t *ahdr = args->files->readers[0].header;
bcf_hdr_t *bhdr = args->files->readers[1].header;
int i, j, nsmpl = bcf_hdr_nsamples(args->out_hdr);
static int gt_absent_warned = 0;
for (i=0; i<args->nbuf; i+=2)
{
bcf1_t *arec = args->buf[i];
bcf1_t *brec = args->buf[i+1];
int nGTs = bcf_get_genotypes(ahdr, arec, &args->GTa, &args->mGTa);
if ( nGTs < 0 )
{
if ( !gt_absent_warned )
{
fprintf(stderr,"GT is not present at %s:%d. (This warning is printed only once.)\n", bcf_seqname(ahdr,arec), arec->pos+1);
gt_absent_warned = 1;
}
continue;
}
if ( nGTs != 2*nsmpl ) continue; // not diploid
nGTs = bcf_get_genotypes(bhdr, brec, &args->GTb, &args->mGTb);
if ( nGTs < 0 )
{
if ( !gt_absent_warned )
{
fprintf(stderr,"GT is not present at %s:%d. (This warning is printed only once.)\n", bcf_seqname(bhdr,brec), brec->pos+1);
gt_absent_warned = 1;
}
continue;
}
if ( nGTs != 2*nsmpl ) continue; // not diploid
for (j=0; j<nsmpl; j++)
{
int *gta = &args->GTa[j*2];
int *gtb = &args->GTb[j*2];
if ( gta[1]==bcf_int32_vector_end || gtb[1]==bcf_int32_vector_end ) continue;
if ( bcf_gt_is_missing(gta[0]) || bcf_gt_is_missing(gta[1]) || bcf_gt_is_missing(gtb[0]) || bcf_gt_is_missing(gtb[1]) ) continue;
if ( !bcf_gt_is_phased(gta[1]) || !bcf_gt_is_phased(gtb[1]) ) continue;
if ( bcf_gt_allele(gta[0])==bcf_gt_allele(gta[1]) || bcf_gt_allele(gtb[0])==bcf_gt_allele(gtb[1]) ) continue;
if ( bcf_gt_allele(gta[0])==bcf_gt_allele(gtb[0]) && bcf_gt_allele(gta[1])==bcf_gt_allele(gtb[1]) )
{
if ( args->swap_phase[j] ) args->nmism[j]++; else args->nmatch[j]++;
}
if ( bcf_gt_allele(gta[0])==bcf_gt_allele(gtb[1]) && bcf_gt_allele(gta[1])==bcf_gt_allele(gtb[0]) )
{
if ( args->swap_phase[j] ) args->nmatch[j]++; else args->nmism[j]++;
}
}
}
for (i=0; i<args->nbuf/2; i+=2)
{
bcf1_t *arec = args->buf[i];
bcf_translate(args->out_hdr, args->files->readers[0].header, arec);
if ( args->nswap )
phase_update(args, args->out_hdr, arec);
if ( !args->compact_PS || args->phase_set_changed )
{
bcf_update_format_int32(args->out_hdr,arec,"PS",args->phase_set,nsmpl);
args->phase_set_changed = 0;
}
bcf_write(args->out_fh, args->out_hdr, arec);
if ( arec->pos < args->prev_pos_check ) error("FIXME, disorder: %s:%d vs %d [1]\n", bcf_seqname(args->files->readers[0].header,arec),arec->pos+1,args->prev_pos_check+1);
args->prev_pos_check = arec->pos;
}
args->nswap = 0;
for (j=0; j<nsmpl; j++)
{
if ( args->nmatch[j] >= args->nmism[j] )
args->swap_phase[j] = 0;
else
{
args->swap_phase[j] = 1;
args->nswap++;
}
if ( args->nmatch[j] && args->nmism[j] )
{
// Entropy-inspired quality. The factor 0.7 shifts and scales to (0,1)
double f = (double)args->nmatch[j]/(args->nmatch[j]+args->nmism[j]);
args->phase_qual[j] = 99*(0.7 + f*log(f) + (1-f)*log(1-f))/0.7;
}
else
args->phase_qual[j] = 99;
args->nmatch[j] = 0;
args->nmism[j] = 0;
}
int PQ_printed = 0;
for (; i<args->nbuf; i+=2)
{
bcf1_t *brec = args->buf[i+1];
bcf_translate(args->out_hdr, args->files->readers[1].header, brec);
if ( !PQ_printed )
{
bcf_update_format_int32(args->out_hdr,brec,"PQ",args->phase_qual,nsmpl);
PQ_printed = 1;
for (j=0; j<nsmpl; j++)
if ( args->phase_qual[j] < args->min_PQ )
{
args->phase_set[j] = brec->pos+1;
args->phase_set_changed = 1;
}
else if ( args->compact_PS ) args->phase_set[j] = bcf_int32_missing;
}
if ( args->nswap )
phase_update(args, args->out_hdr, brec);
if ( !args->compact_PS || args->phase_set_changed )
{
bcf_update_format_int32(args->out_hdr,brec,"PS",args->phase_set,nsmpl);
args->phase_set_changed = 0;
}
bcf_write(args->out_fh, args->out_hdr, brec);
if ( brec->pos < args->prev_pos_check ) error("FIXME, disorder: %s:%d vs %d [2]\n", bcf_seqname(args->files->readers[1].header,brec),brec->pos+1,args->prev_pos_check+1);
args->prev_pos_check = brec->pos;
}
args->nbuf = 0;
}
int main(int argc, char **argv)
{
if (argc < 3) {
fprintf(stderr,"%s <bcf file> <num vars>\n", argv[0]);
return 1;
}
char *fname = argv[1];
uint32_t num_vars = atoi(argv[2]);
htsFile *fp = hts_open(fname,"rb");
bcf_hdr_t *hdr = bcf_hdr_read(fp);
bcf1_t *line = bcf_init1();
int32_t *gt_p = NULL;
uint32_t num_inds = bcf_hdr_nsamples(hdr);
int32_t i, j, k, ntmp = 0, int_i = 0, two_bit_i = 0, sum, t_sum = 0;
uint32_t num_ind_ints = 1 + ((num_inds - 1) / 16);
pri_queue q = priq_new(0);
priority p;
uint32_t *packed_ints = (uint32_t *) calloc(num_ind_ints,
sizeof(uint32_t));
FILE *gt_of = fopen("gt.tmp.packed","wb");
FILE *md_of = fopen("md.tmp.packed","w");
uint32_t *md_index = (uint32_t *) malloc(num_vars * sizeof(uint32_t));
uint32_t md_i = 0;
unsigned long t_bcf_read = 0,
t_bcf_dup = 0,
t_bcf_unpack = 0,
t_bcf_get_genotypes = 0,
t_bcf_hdr_nsamples = 0,
t_q = 0,
t_write = 0,
t_get_md = 0,
t_md_write = 0,
t_pack = 0;
for (i = 0; i < num_vars; ++i) {
sum = 0;
int_i = 0;
two_bit_i = 0;
int r = bcf_read(fp, hdr, line);
// Copy
bcf1_t *t_line = bcf_dup(line);
// Unpack
bcf_unpack(t_line, BCF_UN_ALL);
// Get metadata
size_t len = strlen(bcf_hdr_id2name(hdr, t_line->rid)) +
10 + // max length of pos
strlen(t_line->d.id) +
strlen(t_line->d.allele[0]) +
strlen(t_line->d.allele[1]) +
4; //tabs
char *md = (char *) malloc(len * sizeof(char));
sprintf(md, "%s\t%d\t%s\t%s\t%s",
bcf_hdr_id2name(hdr, t_line->rid),
t_line->pos + 1,
t_line->d.id,
t_line->d.allele[0],
t_line->d.allele[1]);
// Write metadata
md_i += strlen(md);
md_index[i] = md_i;
fprintf(md_of, "%s", md);
// Get gentotypes
uint32_t num_gts_per_sample = bcf_get_genotypes(hdr,
t_line,
>_p,
&ntmp);
num_gts_per_sample /= num_inds;
int32_t *gt_i = gt_p;
// Pack genotypes
for (j = 0; j < num_inds; ++j) {
uint32_t gt = 0;
for (k = 0; k < num_gts_per_sample; ++k) {
gt += bcf_gt_allele(gt_i[k]);
}
packed_ints[int_i] += gt << (30 - 2*two_bit_i);
two_bit_i += 1;
if (two_bit_i == 16) {
two_bit_i = 0;
int_i += 1;
}
sum += gt;
gt_i += num_gts_per_sample;
}
// Get a priority for the variant based on the sum and number of
// leading zeros
p.sum = sum;
uint32_t prefix_len = 0;
j = 0;
while ((j < num_ind_ints) && (packed_ints[j] == 0)){
prefix_len += 32;
j += 1;
}
if (j < num_ind_ints)
prefix_len += nlz1(packed_ints[j]);
// Push it into the q
p.len = prefix_len;
int *j = (int *) malloc (sizeof(int));
j[0] = i;
priq_push(q, j, p);
// Write to file
fwrite(packed_ints, sizeof(uint32_t), num_ind_ints,gt_of);
memset(packed_ints, 0, num_ind_ints*sizeof(uint32_t));
t_sum += sum;
bcf_destroy(t_line);
free(md);
}
fclose(gt_of);
fclose(md_of);
md_of = fopen("md.tmp.packed","r");
FILE *md_out = fopen("md.bim","w");
gt_of = fopen("gt.tmp.packed","rb");
FILE *s_gt_of = fopen("s.gt.tmp.packed","wb");
// Get variants in order and rewrite a variant-major sorted matrix
while ( priq_top(q, &p) != NULL ) {
int *d = priq_pop(q, &p);
uint32_t start = 0;
if (*d != 0)
start = md_index[*d - 1];
uint32_t len = md_index[*d] - start;
fseek(md_of, start*sizeof(char), SEEK_SET);
char buf[len+1];
fread(buf, sizeof(char), len, md_of);
buf[len] = '\0';
fseek(gt_of, (*d)*num_ind_ints*sizeof(uint32_t), SEEK_SET);
fread(packed_ints, sizeof(uint32_t), num_ind_ints, gt_of);
fwrite(packed_ints, sizeof(uint32_t), num_ind_ints,s_gt_of);
fprintf(md_out, "%s\n", buf);
}
fclose(md_out);
fclose(md_of);
fclose(gt_of);
fclose(s_gt_of);
/*
* In a packed-int variant-major matrix there will be a num_vars
* number of rows, and a num_inds number of values packed into
* num_inds_ints number of intergers. For examples, 16 rows of 16 values
* will be 16 ints, where each int encodes 16 values.
*
*/
uint32_t num_var_ints = 1 + ((num_vars - 1) / 16);
uint32_t *I_data = (uint32_t *)calloc(num_var_ints*16,sizeof(uint32_t));
uint32_t **I = (uint32_t **)malloc(16*sizeof(uint32_t*));
for (i = 0; i < 16; ++i)
I[i] = I_data + i*num_var_ints;
uint32_t I_i = 0, I_int_i = 0;
uint32_t v;
s_gt_of = fopen("s.gt.tmp.packed","rb");
FILE *rs_gt_of = fopen("r.s.gt.tmp.packed","wb");
// Write these to values to that this is a well-formed uncompressed
// packed int binary file (ubin) file
fwrite(&num_vars, sizeof(uint32_t), 1, rs_gt_of);
fwrite(&num_inds, sizeof(uint32_t), 1, rs_gt_of);
/*
* we need to loop over the columns in the v-major file.
* There are num_vars rows, and num_ind_ints 16-ind packed columns
*
* In this loop :
* i: cols in var-major form, rows in ind-major form
* j: rows in var-major form, cols in ind-major form
*/
uint32_t num_inds_to_write = num_inds;
for (i = 0; i < num_ind_ints; ++i) { // loop over each int col
for (j = 0; j < num_vars; ++j) { // loop over head row in that col
// skip to the value at the row/col
fseek(s_gt_of,
j*num_ind_ints*sizeof(uint32_t) + //row
i*sizeof(uint32_t), //col
SEEK_SET);
fread(&v, sizeof(uint32_t), 1, s_gt_of);
// one int corresponds to a col of 16 two-bit values
// two_bit_i will move across the cols
for (two_bit_i = 0; two_bit_i < 16; ++two_bit_i) {
I[two_bit_i][I_i] += ((v >> (30 - 2*two_bit_i)) & 3) <<
(30 - 2*I_int_i);
}
I_int_i += 1;
if (I_int_i == 16) {
I_i += 1;
I_int_i = 0;
}
}
// When we are at the end of the file, and the number of lines
// is not a factor of 16, only write out the lines that contain values
if (num_inds_to_write >= 16) {
fwrite(I_data,
sizeof(uint32_t),
num_var_ints*16,
rs_gt_of);
num_inds_to_write -= 16;
} else {
fwrite(I_data,
sizeof(uint32_t),
num_var_ints*num_inds_to_write,
rs_gt_of);
}
memset(I_data, 0, num_var_ints*16*sizeof(uint32_t));
I_int_i = 0;
I_i = 0;
}
fclose(s_gt_of);
fclose(rs_gt_of);
free(md_index);
free(packed_ints);
}
