static void _prune_sites(vcfbuf_t *buf, int flush_all)
{
int nbuf = flush_all ? buf->rbuf.n : buf->rbuf.n - 1;
if ( nbuf > buf->prune.mvrec )
{
buf->prune.idx = (int*) realloc(buf->prune.idx, nbuf*sizeof(int));
buf->prune.vrec = (vcfrec_t**) realloc(buf->prune.vrec, nbuf*sizeof(vcfrec_t*));
buf->prune.mvrec = nbuf;
}
// set allele frequency and prepare buffer for sorting
int i,k,irec = 0;
for (i=-1; rbuf_next(&buf->rbuf,&i) && irec<nbuf; )
{
bcf1_t *line = buf->vcf[i].rec;
if ( line->n_allele > buf->prune.mac )
{
buf->prune.ac = (int*) realloc(buf->prune.ac, line->n_allele*sizeof(*buf->prune.ac));
buf->prune.mac = line->n_allele;
}
if ( !buf->vcf[i].af_set )
{
buf->vcf[i].af = 0;
if ( buf->prune.af_tag )
{
if ( bcf_get_info_float(buf->hdr,line,buf->prune.af_tag,&buf->prune.farr, &buf->prune.mfarr) > 0 ) buf->vcf[i].af = buf->prune.farr[0];
}
else if ( bcf_calc_ac(buf->hdr, line, buf->prune.ac, BCF_UN_INFO|BCF_UN_FMT) )
{
int ntot = buf->prune.ac[0], nalt = 0;
for (k=1; k<line->n_allele; k++) nalt += buf->prune.ac[k];
buf->vcf[i].af = ntot ? (float)nalt/ntot : 0;
}
buf->vcf[i].af_set = 1;
}
buf->vcf[i].idx = irec;
buf->prune.vrec[irec++] = &buf->vcf[i];
}
// sort by allele frequency, low AF will be removed preferentially
qsort(buf->prune.vrec, nbuf, sizeof(*buf->prune.vrec), cmpvrec);
// sort the rbuf indexes to be pruned descendently so that j-th rbuf index
// is removed before i-th index if i<j
int nprune = nbuf - buf->prune.max_sites;
for (i=0; i<nprune; i++)
buf->prune.idx[i] = buf->prune.vrec[i]->idx;
qsort(buf->prune.idx, nprune, sizeof(int), cmpint_desc);
for (i=0; i<nprune; i++)
rbuf_remove_kth(&buf->rbuf, vcfrec_t, buf->prune.idx[i], buf->vcf);
}
int process(bcf1_t *rec)
{
hts_expand(int,rec->n_allele,marr,arr);
int ret = bcf_calc_ac(in_hdr,rec,arr,BCF_UN_FMT);
if ( ret>0 )
{
int i, an = 0;
for (i=0; i<rec->n_allele; i++) an += arr[i];
bcf_update_info_int32(out_hdr, rec, "AN", &an, 1);
bcf_update_info_int32(out_hdr, rec, "AC", arr+1, rec->n_allele-1);
}
return 0;
}
static void buffered_filters(args_t *args, bcf1_t *line)
{
/**
* The logic of SnpGap=3. The SNPs at positions 1 and 7 are filtered,
* positions 0 and 8 are not:
* 0123456789
* ref .G.GT..G..
* del .A.G-..A..
* Here the positions 1 and 6 are filtered, 0 and 7 are not:
* 0123-456789
* ref .G.G-..G..
* ins .A.GT..A..
*
* The logic of IndelGap=2. The second indel is filtered:
* 012345678901
* ref .GT.GT..GT..
* del .G-.G-..G-..
* And similarly here, the second is filtered:
* 01 23 456 78
* ref .A-.A-..A-..
* ins .AT.AT..AT..
*/
// To avoid additional data structure, we abuse bcf1_t's var and var_type records.
const int SnpGap_set = VCF_OTHER<<1;
const int IndelGap_set = VCF_OTHER<<2;
const int IndelGap_flush = VCF_OTHER<<3;
int var_type = 0, i;
if ( line )
{
// Still on the same chromosome?
int ilast = rbuf_last(&args->rbuf);
if ( ilast>=0 && line->rid != args->rbuf_lines[ilast]->rid )
flush_buffer(args, args->rbuf.n); // new chromosome, flush everything
rbuf_expand0(&args->rbuf,bcf1_t*,args->rbuf.n,args->rbuf_lines);
// Insert the new record in the buffer. The line would be overwritten in
// the next bcf_sr_next_line call, therefore we need to swap it with an
// unused one
ilast = rbuf_append(&args->rbuf);
if ( !args->rbuf_lines[ilast] ) args->rbuf_lines[ilast] = bcf_init1();
SWAP(bcf1_t*, args->files->readers[0].buffer[0], args->rbuf_lines[ilast]);
var_type = bcf_get_variant_types(line);
// Find out the size of an indel. The indel boundaries are based on REF
// (POS+1,POS+rlen-1). This is not entirely correct: mpileup likes to
// output REF=CAGAGAGAGA, ALT=CAGAGAGAGAGA where REF=C,ALT=CGA could be
// used. This filter is therefore more strict and may remove some valid
// SNPs.
int len = 1;
if ( var_type & VCF_INDEL )
{
for (i=1; i<line->n_allele; i++)
if ( len < 1-line->d.var[i].n ) len = 1-line->d.var[i].n;
}
// Set the REF allele's length to max deletion length or to 1 if a SNP or an insertion.
line->d.var[0].n = len;
}
int k_flush = 1;
if ( args->indel_gap )
{
k_flush = 0;
// Find indels which are too close to each other
int last_to = -1;
for (i=-1; rbuf_next(&args->rbuf,&i); )
{
bcf1_t *rec = args->rbuf_lines[i];
int rec_from = rec->pos;
if ( last_to!=-1 && last_to < rec_from ) break;
k_flush++;
if ( !(rec->d.var_type & VCF_INDEL) ) continue;
rec->d.var_type |= IndelGap_set;
last_to = args->indel_gap + rec->pos + rec->d.var[0].n - 1;
}
if ( i==args->rbuf.f && line && last_to!=-1 ) k_flush = 0;
if ( k_flush || !line )
{
// Select the best indel from the cluster of k_flush indels
int k = 0, max_ac = -1, imax_ac = -1;
for (i=-1; rbuf_next(&args->rbuf,&i) && k<k_flush; )
{
k++;
bcf1_t *rec = args->rbuf_lines[i];
if ( !(rec->d.var_type & IndelGap_set) ) continue;
hts_expand(int, rec->n_allele, args->ntmpi, args->tmpi);
int ret = bcf_calc_ac(args->hdr, rec, args->tmpi, BCF_UN_ALL);
if ( imax_ac==-1 || (ret && max_ac < args->tmpi[1]) ) { max_ac = args->tmpi[1]; imax_ac = i; }
}
// Filter all but the best indel (with max AF or first if AF not available)
k = 0;
for (i=-1; rbuf_next(&args->rbuf,&i) && k<k_flush; )
{
k++;
bcf1_t *rec = args->rbuf_lines[i];
if ( !(rec->d.var_type & IndelGap_set) ) continue;
rec->d.var_type |= IndelGap_flush;
if ( i!=imax_ac ) bcf_add_filter(args->hdr, args->rbuf_lines[i], args->IndelGap_id);
}
}
int subset_vcf(args_t *args, bcf1_t *line)
{
if ( args->min_alleles && line->n_allele < args->min_alleles ) return 0; // min alleles
if ( args->max_alleles && line->n_allele > args->max_alleles ) return 0; // max alleles
if (args->novel || args->known)
{
if ( args->novel && (line->d.id[0]!='.' || line->d.id[1]!=0) ) return 0; // skip sites which are known, ID != '.'
if ( args->known && line->d.id[0]=='.' && line->d.id[1]==0 ) return 0; // skip sites which are novel, ID == '.'
}
if (args->include || args->exclude)
{
int line_type = bcf_get_variant_types(line);
if ( args->include && !(line_type&args->include) ) return 0; // include only given variant types
if ( args->exclude && line_type&args->exclude ) return 0; // exclude given variant types
}
if ( args->filter )
{
int ret = filter_test(args->filter, line, NULL);
if ( args->filter_logic==FLT_INCLUDE ) { if ( !ret ) return 0; }
else if ( ret ) return 0;
}
hts_expand(int, line->n_allele, args->mac, args->ac);
int i, an = 0, non_ref_ac = 0;
if (args->calc_ac) {
bcf_calc_ac(args->hdr, line, args->ac, BCF_UN_INFO|BCF_UN_FMT); // get original AC and AN values from INFO field if available, otherwise calculate
for (i=1; i<line->n_allele; i++)
non_ref_ac += args->ac[i];
for (i=0; i<line->n_allele; i++)
an += args->ac[i];
}
if (args->n_samples)
{
int non_ref_ac_sub = 0, *ac_sub = (int*) calloc(line->n_allele,sizeof(int));
bcf_subset(args->hdr, line, args->n_samples, args->imap);
if (args->calc_ac) {
bcf_calc_ac(args->hsub, line, ac_sub, BCF_UN_FMT); // recalculate AC and AN
an = 0;
for (i=0; i<line->n_allele; i++) {
args->ac[i] = ac_sub[i];
an += ac_sub[i];
}
for (i=1; i<line->n_allele; i++)
non_ref_ac_sub += ac_sub[i];
if (args->private_vars) {
if (args->private_vars == FLT_INCLUDE && !(non_ref_ac_sub > 0 && non_ref_ac == non_ref_ac_sub)) { free(ac_sub); return 0; } // select private sites
if (args->private_vars == FLT_EXCLUDE && non_ref_ac_sub > 0 && non_ref_ac == non_ref_ac_sub) { free(ac_sub); return 0; } // exclude private sites
}
non_ref_ac = non_ref_ac_sub;
}
free(ac_sub);
}
bcf_fmt_t *gt_fmt;
if ( args->gt_type && (gt_fmt=bcf_get_fmt(args->hdr,line,"GT")) )
{
int nhet = 0, nhom = 0, nmiss = 0;
for (i=0; i<bcf_hdr_nsamples(args->hdr); i++)
{
int type = bcf_gt_type(gt_fmt,i,NULL,NULL);
if ( type==GT_HET_RA || type==GT_HET_AA )
{
if ( args->gt_type==GT_NO_HET ) return 0;
nhet = 1;
}
else if ( type==GT_UNKN )
{
if ( args->gt_type==GT_NO_MISSING ) return 0;
nmiss = 1;
}
else
{
if ( args->gt_type==GT_NO_HOM ) return 0;
nhom = 1;
}
}
if ( args->gt_type==GT_NEED_HOM && !nhom ) return 0;
else if ( args->gt_type==GT_NEED_HET && !nhet ) return 0;
else if ( args->gt_type==GT_NEED_MISSING && !nmiss ) return 0;
}
int minor_ac = 0;
int major_ac = 0;
if ( args->calc_ac )
{
minor_ac = args->ac[0];
major_ac = args->ac[0];
for (i=1; i<line->n_allele; i++){
if (args->ac[i] < minor_ac) { minor_ac = args->ac[i]; }
if (args->ac[i] > major_ac) { major_ac = args->ac[i]; }
}
}
if (args->min_ac)
{
if (args->min_ac_type == ALLELE_NONREF && args->min_ac>non_ref_ac) return 0; // min AC
else if (args->min_ac_type == ALLELE_MINOR && args->min_ac>minor_ac) return 0; // min minor AC
else if (args->min_ac_type == ALLELE_ALT1 && args->min_ac>args->ac[1]) return 0; // min 1st alternate AC
else if (args->min_ac_type == ALLELE_MAJOR && args->min_ac > major_ac) return 0; // min major AC
else if (args->min_ac_type == ALLELE_NONMAJOR && args->min_ac > an-major_ac) return 0; // min non-major AC
}
if (args->max_ac)
{
if (args->max_ac_type == ALLELE_NONREF && args->max_ac<non_ref_ac) return 0; // max AC
else if (args->max_ac_type == ALLELE_MINOR && args->max_ac<minor_ac) return 0; // max minor AC
else if (args->max_ac_type == ALLELE_ALT1 && args->max_ac<args->ac[1]) return 0; // max 1st alternate AC
else if (args->max_ac_type == ALLELE_MAJOR && args->max_ac < major_ac) return 0; // max major AC
else if (args->max_ac_type == ALLELE_NONMAJOR && args->max_ac < an-major_ac) return 0; // max non-major AC
}
if (args->min_af)
{
if (an == 0) return 0; // freq not defined, skip site
if (args->min_af_type == ALLELE_NONREF && args->min_af>non_ref_ac/(double)an) return 0; // min AF
else if (args->min_af_type == ALLELE_MINOR && args->min_af>minor_ac/(double)an) return 0; // min minor AF
else if (args->min_af_type == ALLELE_ALT1 && args->min_af>args->ac[1]/(double)an) return 0; // min 1st alternate AF
else if (args->min_af_type == ALLELE_MAJOR && args->min_af > major_ac/(double)an) return 0; // min major AF
else if (args->min_af_type == ALLELE_NONMAJOR && args->min_af > (an-major_ac)/(double)an) return 0; // min non-major AF
}
if (args->max_af)
{
if (an == 0) return 0; // freq not defined, skip site
if (args->max_af_type == ALLELE_NONREF && args->max_af<non_ref_ac/(double)an) return 0; // max AF
else if (args->max_af_type == ALLELE_MINOR && args->max_af<minor_ac/(double)an) return 0; // max minor AF
else if (args->max_af_type == ALLELE_ALT1 && args->max_af<args->ac[1]/(double)an) return 0; // max 1st alternate AF
else if (args->max_af_type == ALLELE_MAJOR && args->max_af < major_ac/(double)an) return 0; // max major AF
else if (args->max_af_type == ALLELE_NONMAJOR && args->max_af < (an-major_ac)/(double)an) return 0; // max non-major AF
}
if (args->uncalled) {
if (args->uncalled == FLT_INCLUDE && an > 0) return 0; // select uncalled
if (args->uncalled == FLT_EXCLUDE && an == 0) return 0; // skip if uncalled
}
if (args->calc_ac && args->update_info) {
bcf_update_info_int32(args->hdr, line, "AC", &args->ac[1], line->n_allele-1);
bcf_update_info_int32(args->hdr, line, "AN", &an, 1);
}
if (args->trim_alts)
{
int ret = bcf_trim_alleles(args->hsub ? args->hsub : args->hdr, line);
if ( ret==-1 ) error("Error: some GT index is out of bounds at %s:%d\n", bcf_seqname(args->hsub ? args->hsub : args->hdr, line), line->pos+1);
}
if (args->phased) {
int phased = bcf_all_phased(args->hdr, line);
if (args->phased == FLT_INCLUDE && !phased) { return 0; } // skip unphased
if (args->phased == FLT_EXCLUDE && phased) { return 0; } // skip phased
}
if (args->sites_only) bcf_subset(args->hsub ? args->hsub : args->hdr, line, 0, 0);
return 1;
}
