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vcfnorm.c
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/* vcfnorm.c -- Left-align and normalize indels.
Copyright (C) 2013-2016 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 <strings.h>
#include <unistd.h>
#include <getopt.h>
#include <ctype.h>
#include <string.h>
#include <errno.h>
#include <sys/stat.h>
#include <sys/types.h>
#include <htslib/vcf.h>
#include <htslib/synced_bcf_reader.h>
#include <htslib/faidx.h>
#include "bcftools.h"
#include "rbuf.h"
#define CHECK_REF_EXIT 0
#define CHECK_REF_WARN 1
#define CHECK_REF_SKIP 2
#define CHECK_REF_FIX 4
#define MROWS_SPLIT 1
#define MROWS_MERGE 2
// for -m+, mapping from allele indexes of a single input record
// to allele indexes of output record
typedef struct
{
int nals, mals, *map;
}
map_t;
typedef struct
{
char *tseq, *seq;
int mseq;
bcf1_t **lines, **tmp_lines, **alines, **blines, *mrow_out;
int ntmp_lines, mtmp_lines, nalines, malines, nblines, mblines;
map_t *maps; // mrow map for each buffered record
char **als;
int mmaps, nals, mals;
uint8_t *tmp_arr1, *tmp_arr2, *diploid;
int ntmp_arr1, ntmp_arr2;
kstring_t *tmp_str;
kstring_t *tmp_als, tmp_als_str;
int ntmp_als;
rbuf_t rbuf;
int buf_win; // maximum distance between two records to consider
int aln_win; // the realignment window size (maximum repeat size)
bcf_srs_t *files; // using the synced reader only for -r option
bcf_hdr_t *hdr;
faidx_t *fai;
struct { int tot, set, swap; } nref;
char **argv, *output_fname, *ref_fname, *vcf_fname, *region, *targets;
int argc, rmdup, output_type, n_threads, check_ref, strict_filter, do_indels;
int nchanged, nskipped, nsplit, ntotal, mrows_op, mrows_collapse, parsimonious;
int record_cmd_line;
}
args_t;
static inline int replace_iupac_codes(char *seq, int nseq)
{
// Replace ambiguity codes with N for now, it awaits to be seen what the VCF spec codifies in the end
int i, n = 0;
for (i=0; i<nseq; i++)
{
char c = toupper(seq[i]);
if ( c!='A' && c!='C' && c!='G' && c!='T' && c!='N' ) { seq[i] = 'N'; n++; }
}
return n;
}
static inline int has_non_acgtn(char *seq, int nseq)
{
char *end = nseq ? seq + nseq : seq + UINT32_MAX; // arbitrary large number
while ( *seq && seq<end )
{
char c = toupper(*seq);
if ( c!='A' && c!='C' && c!='G' && c!='T' && c!='N' ) return 1;
seq++;
}
return 0;
}
static void seq_to_upper(char *seq, int len)
{
int i;
if ( len )
for (i=0; i<len; i++) seq[i] = nt_to_upper(seq[i]);
else
for (i=0; seq[i]; i++) seq[i] = nt_to_upper(seq[i]);
}
static void fix_ref(args_t *args, bcf1_t *line)
{
int reflen = strlen(line->d.allele[0]);
int i, maxlen = reflen, len;
for (i=1; i<line->n_allele; i++)
{
int len = strlen(line->d.allele[i]);
if ( maxlen < len ) maxlen = len;
}
char *ref = faidx_fetch_seq(args->fai, (char*)bcf_seqname(args->hdr,line), line->pos, line->pos+maxlen-1, &len);
if ( !ref ) error("faidx_fetch_seq failed at %s:%d\n", bcf_seqname(args->hdr,line),line->pos+1);
replace_iupac_codes(ref,len);
args->nref.tot++;
// is the REF different?
if ( !strncasecmp(line->d.allele[0],ref,reflen) ) { free(ref); return; }
// is the REF allele missing or N?
if ( reflen==1 && (line->d.allele[0][0]=='.' || line->d.allele[0][0]=='N' || line->d.allele[0][0]=='n') )
{
line->d.allele[0][0] = ref[0];
args->nref.set++;
free(ref);
bcf_update_alleles(args->hdr,line,(const char**)line->d.allele,line->n_allele);
return;
}
// does REF contain non-standard bases?
if ( replace_iupac_codes(line->d.allele[0],strlen(line->d.allele[0])) )
{
args->nref.set++;
bcf_update_alleles(args->hdr,line,(const char**)line->d.allele,line->n_allele);
if ( !strncasecmp(line->d.allele[0],ref,reflen) ) { free(ref); return; }
}
// is it swapped?
for (i=1; i<line->n_allele; i++)
{
int len = strlen(line->d.allele[i]);
if ( !strncasecmp(line->d.allele[i],ref,len) ) break;
}
kstring_t str = {0,0,0};
if ( i==line->n_allele )
{
// none of the alternate alleles matches the reference
if ( line->n_allele>1 )
args->nref.set++;
else
args->nref.swap++;
kputs(line->d.allele[0],&str);
kputc(',',&str);
for (i=1; i<line->n_allele; i++)
{
kputs(line->d.allele[i],&str);
kputc(',',&str);
}
kputc(ref[0],&str);
bcf_update_alleles_str(args->hdr,line,str.s);
str.l = 0;
}
else
args->nref.swap++;
free(ref);
// swap the alleles
int j;
kputs(line->d.allele[i],&str);
for (j=1; j<i; j++)
{
kputc(',',&str);
kputs(line->d.allele[j],&str);
}
kputc(',',&str);
kputs(line->d.allele[0],&str);
for (j=i+1; j<line->n_allele; j++)
{
kputc(',',&str);
kputs(line->d.allele[j],&str);
}
bcf_update_alleles_str(args->hdr,line,str.s);
// swap genotypes
int ntmp = args->ntmp_arr1 / sizeof(int32_t); // reuse tmp_arr declared as uint8_t
int ngts = bcf_get_genotypes(args->hdr, line, &args->tmp_arr1, &ntmp);
args->ntmp_arr1 = ntmp * sizeof(int32_t);
int32_t *gts = (int32_t*) args->tmp_arr1;
int ni = 0;
for (j=0; j<ngts; j++)
{
if ( gts[j]==bcf_gt_unphased(0) ) { gts[j] = bcf_gt_unphased(i); ni++; }
else if ( gts[j]==bcf_gt_phased(0) ) { gts[j] = bcf_gt_phased(i); ni++; }
else if ( gts[j]==bcf_gt_unphased(i) ) gts[j] = bcf_gt_unphased(0);
else if ( gts[j]==bcf_gt_phased(i) ) gts[j] = bcf_gt_phased(0);
}
bcf_update_genotypes(args->hdr,line,gts,ngts);
// update AC
int nac = bcf_get_info_int32(args->hdr, line, "AC", &args->tmp_arr1, &ntmp);
args->ntmp_arr1 = ntmp * sizeof(int32_t);
if ( i <= nac )
{
int32_t *ac = (int32_t*)args->tmp_arr1;
ac[i-1] = ni;
bcf_update_info_int32(args->hdr, line, "AC", ac, nac);
}
free(str.s);
}
static void fix_dup_alt(args_t *args, bcf1_t *line)
{
// update alleles, create a mapping between old and new indexes
hts_expand(uint8_t,line->n_allele,args->ntmp_arr1,args->tmp_arr1);
args->tmp_arr1[0] = 0; // ref always unchanged
int i, j, nals = line->n_allele, nals_ori = line->n_allele;
for (i=1, j=1; i<line->n_allele; i++)
{
if ( strcmp(line->d.allele[0],line->d.allele[i]) )
{
args->tmp_arr1[i] = j++;
continue;
}
args->tmp_arr1[i] = 0;
nals--;
}
for (i=1, j=1; i<line->n_allele; i++)
{
if ( !args->tmp_arr1[i] ) continue;
line->d.allele[j++] = line->d.allele[i];
}
bcf_update_alleles(args->hdr, line, (const char**)line->d.allele, nals);
// update genotypes
int ntmp = args->ntmp_arr2 / sizeof(int32_t); // reuse tmp_arr declared as uint8_t
int ngts = bcf_get_genotypes(args->hdr, line, &args->tmp_arr2, &ntmp);
args->ntmp_arr2 = ntmp * sizeof(int32_t);
int32_t *gts = (int32_t*) args->tmp_arr2;
int changed = 0;
for (i=0; i<ngts; i++)
{
if ( bcf_gt_is_missing(gts[i]) || gts[i]==bcf_int32_vector_end ) continue;
int ial = bcf_gt_allele(gts[i]);
if ( ial<nals_ori && ial==args->tmp_arr1[ial] ) continue;
int ial_new = ial<nals_ori ? args->tmp_arr1[ial] : 0;
gts[i] = bcf_gt_is_phased(gts[i]) ? bcf_gt_phased(ial_new) : bcf_gt_unphased(ial_new);
changed = 1;
}
if ( changed ) bcf_update_genotypes(args->hdr,line,gts,ngts);
}
#define ERR_DUP_ALLELE -2
#define ERR_REF_MISMATCH -1
#define ERR_OK 0
#define ERR_SYMBOLIC 1
#define ERR_SPANNING_DELETION 2
static int realign(args_t *args, bcf1_t *line)
{
bcf_unpack(line, BCF_UN_STR);
// Sanity check REF
int i, nref, reflen = strlen(line->d.allele[0]);
char *ref = faidx_fetch_seq(args->fai, (char*)args->hdr->id[BCF_DT_CTG][line->rid].key, line->pos, line->pos+reflen-1, &nref);
if ( !ref ) error("faidx_fetch_seq failed at %s:%d\n", args->hdr->id[BCF_DT_CTG][line->rid].key, line->pos+1);
seq_to_upper(ref,0);
replace_iupac_codes(ref,nref); // any non-ACGT character in fasta ref is replaced with N
// does VCF REF contain non-standard bases?
if ( has_non_acgtn(line->d.allele[0],reflen) )
{
if ( args->check_ref==CHECK_REF_EXIT )
error("Non-ACGTN reference allele at %s:%d .. REF_SEQ:'%s' vs VCF:'%s'\n", bcf_seqname(args->hdr,line),line->pos+1,ref,line->d.allele[0]);
if ( args->check_ref & CHECK_REF_WARN )
fprintf(stderr,"NON_ACGTN_REF\t%s\t%d\t%s\n", bcf_seqname(args->hdr,line),line->pos+1,line->d.allele[0]);
free(ref);
return ERR_REF_MISMATCH;
}
if ( strcasecmp(ref,line->d.allele[0]) )
{
if ( args->check_ref==CHECK_REF_EXIT )
error("Reference allele mismatch at %s:%d .. REF_SEQ:'%s' vs VCF:'%s'\n", bcf_seqname(args->hdr,line),line->pos+1,ref,line->d.allele[0]);
if ( args->check_ref & CHECK_REF_WARN )
fprintf(stderr,"REF_MISMATCH\t%s\t%d\t%s\n", bcf_seqname(args->hdr,line),line->pos+1,line->d.allele[0]);
free(ref);
return ERR_REF_MISMATCH;
}
free(ref);
ref = NULL;
if ( line->n_allele == 1 ) // a REF
{
if ( line->rlen > 1 )
{
line->d.allele[0][1] = 0;
bcf_update_alleles(args->hdr,line,(const char**)line->d.allele,line->n_allele);
}
return ERR_OK;
}
if ( bcf_get_variant_types(line)==VCF_BND ) return ERR_SYMBOLIC; // breakend, not an error
// make a copy of each allele for trimming
hts_expand0(kstring_t,line->n_allele,args->ntmp_als,args->tmp_als);
kstring_t *als = args->tmp_als;
for (i=0; i<line->n_allele; i++)
{
if ( line->d.allele[i][0]=='<' ) return ERR_SYMBOLIC; // symbolic allele
if ( line->d.allele[i][0]=='*' ) return ERR_SPANNING_DELETION; // spanning deletion
if ( has_non_acgtn(line->d.allele[i],0) )
{
if ( args->check_ref==CHECK_REF_EXIT )
error("Non-ACGTN alternate allele at %s:%d .. REF_SEQ:'%s' vs VCF:'%s'\n", bcf_seqname(args->hdr,line),line->pos+1,ref,line->d.allele[i]);
if ( args->check_ref & CHECK_REF_WARN )
fprintf(stderr,"NON_ACGTN_ALT\t%s\t%d\t%s\n", bcf_seqname(args->hdr,line),line->pos+1,line->d.allele[i]);
return ERR_REF_MISMATCH;
}
als[i].l = 0;
kputs(line->d.allele[i], &als[i]);
seq_to_upper(als[i].s,0);
if ( i>0 && als[i].l==als[0].l && !strcmp(als[0].s,als[i].s) ) return ERR_DUP_ALLELE;
}
// trim from right
int ori_pos = line->pos;
while (1)
{
// is the rightmost base identical in all alleles?
int min_len = als[0].l;
for (i=1; i<line->n_allele; i++)
{
if ( als[0].s[ als[0].l-1 ]!=als[i].s[ als[i].l-1 ] ) break;
if ( als[i].l < min_len ) min_len = als[i].l;
}
if ( i!=line->n_allele ) break; // there are differences, cannot be trimmed
if ( min_len<=1 && line->pos==0 ) break;
int pad_from_left = 0;
for (i=0; i<line->n_allele; i++) // trim all alleles
{
als[i].l--;
if ( !als[i].l ) pad_from_left = 1;
}
if ( pad_from_left )
{
int npad = line->pos >= args->aln_win ? args->aln_win : line->pos;
free(ref);
ref = faidx_fetch_seq(args->fai, (char*)args->hdr->id[BCF_DT_CTG][line->rid].key, line->pos-npad, line->pos-1, &nref);
if ( !ref ) error("faidx_fetch_seq failed at %s:%d\n", args->hdr->id[BCF_DT_CTG][line->rid].key, line->pos-npad+1);
replace_iupac_codes(ref,nref);
for (i=0; i<line->n_allele; i++)
{
ks_resize(&als[i], als[i].l + npad);
if ( als[i].l ) memmove(als[i].s+npad,als[i].s,als[i].l);
memcpy(als[i].s,ref,npad);
als[i].l += npad;
}
line->pos -= npad;
}
}
free(ref);
// trim from left
int ntrim_left = 0;
while (1)
{
// is the first base identical in all alleles?
int min_len = als[0].l - ntrim_left;
for (i=1; i<line->n_allele; i++)
{
if ( als[0].s[ntrim_left]!=als[i].s[ntrim_left] ) break;
if ( min_len > als[i].l - ntrim_left ) min_len = als[i].l - ntrim_left;
}
if ( i!=line->n_allele || min_len<=1 ) break; // there are differences, cannot be trimmed
ntrim_left++;
}
if ( ntrim_left )
{
for (i=0; i<line->n_allele; i++)
{
memmove(als[i].s,als[i].s+ntrim_left,als[i].l-ntrim_left);
als[i].l -= ntrim_left;
}
line->pos += ntrim_left;
}
// Have the alleles changed?
als[0].s[ als[0].l ] = 0; // in order for strcmp to work
if ( ori_pos==line->pos && !strcmp(line->d.allele[0],als[0].s) ) return ERR_OK;
// Create new block of alleles and update
args->tmp_als_str.l = 0;
for (i=0; i<line->n_allele; i++)
{
if (i>0) kputc(',',&args->tmp_als_str);
kputsn(als[i].s,als[i].l,&args->tmp_als_str);
}
args->tmp_als_str.s[ args->tmp_als_str.l ] = 0;
bcf_update_alleles_str(args->hdr,line,args->tmp_als_str.s);
args->nchanged++;
return ERR_OK;
}
static void split_info_numeric(args_t *args, bcf1_t *src, bcf_info_t *info, int ialt, bcf1_t *dst)
{
#define BRANCH_NUMERIC(type,type_t) \
{ \
const char *tag = bcf_hdr_int2id(args->hdr,BCF_DT_ID,info->key); \
int ntmp = args->ntmp_arr1 / sizeof(type_t); \
int ret = bcf_get_info_##type(args->hdr,src,tag,&args->tmp_arr1,&ntmp); \
args->ntmp_arr1 = ntmp * sizeof(type_t); \
assert( ret>0 ); \
type_t *vals = (type_t*) args->tmp_arr1; \
int len = bcf_hdr_id2length(args->hdr,BCF_HL_INFO,info->key); \
if ( len==BCF_VL_A ) \
{ \
if ( ret!=src->n_allele-1 ) \
error("Error: wrong number of fields in INFO/%s at %s:%d, expected %d, found %d\n", \
tag,bcf_seqname(args->hdr,src),src->pos+1,src->n_allele-1,ret); \
bcf_update_info_##type(args->hdr,dst,tag,vals+ialt,1); \
} \
else if ( len==BCF_VL_R ) \
{ \
if ( ret!=src->n_allele ) \
error("Error: wrong number of fields in INFO/%s at %s:%d, expected %d, found %d\n", \
tag,bcf_seqname(args->hdr,src),src->pos+1,src->n_allele,ret); \
if ( ialt!=0 ) vals[1] = vals[ialt+1]; \
bcf_update_info_##type(args->hdr,dst,tag,vals,2); \
} \
else if ( len==BCF_VL_G ) \
{ \
if ( ret!=src->n_allele*(src->n_allele+1)/2 ) \
error("Error: wrong number of fields in INFO/%s at %s:%d, expected %d, found %d\n", \
tag,bcf_seqname(args->hdr,src),src->pos+1,src->n_allele*(src->n_allele+1)/2,ret); \
if ( ialt!=0 ) \
{ \
vals[1] = vals[bcf_alleles2gt(0,ialt+1)]; \
vals[2] = vals[bcf_alleles2gt(ialt+1,ialt+1)]; \
} \
bcf_update_info_##type(args->hdr,dst,tag,vals,3); \
} \
else \
bcf_update_info_##type(args->hdr,dst,tag,vals,ret); \
}
switch (bcf_hdr_id2type(args->hdr,BCF_HL_INFO,info->key))
{
case BCF_HT_INT: BRANCH_NUMERIC(int32, int32_t); break;
case BCF_HT_REAL: BRANCH_NUMERIC(float, float); break;
}
#undef BRANCH_NUMERIC
}
// Find n-th field in a comma-separated list and move it to dst.
// The memory areas may overlap.
#define STR_MOVE_NTH(dst,src,end,nth,len) \
{ \
char *ss = src, *se = src; \
int j = 0; \
while ( *se && se<(end) ) \
{ \
if ( *se==',' ) \
{ \
if ( j==nth ) break; \
j++; \
ss = se+1; \
} \
se++; \
} \
if ( j==nth ) \
{ \
int n = se - ss; \
memmove((dst),ss,n); \
src = se; \
len += n; \
} \
else len = -1; \
}
static void split_info_string(args_t *args, bcf1_t *src, bcf_info_t *info, int ialt, bcf1_t *dst)
{
const char *tag = bcf_hdr_int2id(args->hdr,BCF_DT_ID,info->key);
int ret = bcf_get_info_string(args->hdr,src,tag,&args->tmp_arr1,&args->ntmp_arr1);
assert( ret>0 );
kstring_t str;
str.m = args->ntmp_arr1;
str.l = ret;
str.s = (char*) args->tmp_arr1;
int len = bcf_hdr_id2length(args->hdr,BCF_HL_INFO,info->key);
if ( len==BCF_VL_A )
{
char *tmp = str.s;
int len = 0;
STR_MOVE_NTH(str.s,tmp,str.s+str.l,ialt,len);
if ( len<0 ) return; // wrong number of fields: skip
str.s[len] = 0;
bcf_update_info_string(args->hdr,dst,tag,str.s);
}
else if ( len==BCF_VL_R )
{
char *tmp = str.s;
int len = 0;
STR_MOVE_NTH(str.s,tmp,str.s+str.l,0,len);
str.s[len]=','; tmp++; len++;
STR_MOVE_NTH(&str.s[len],tmp,str.s+str.l,ialt,len);
if ( len<0 ) return; // wrong number of fields: skip
str.s[len] = 0;
bcf_update_info_string(args->hdr,dst,tag,str.s);
}
else if ( len==BCF_VL_G )
{
int i0a = bcf_alleles2gt(0,ialt+1), iaa = bcf_alleles2gt(ialt+1,ialt+1);
char *tmp = str.s;
int len = 0;
STR_MOVE_NTH(str.s,tmp,str.s+str.l,0,len);
str.s[len]=','; tmp++; len++;
STR_MOVE_NTH(&str.s[len],tmp,str.s+str.l,i0a-1,len);
if ( len<0 ) return; // wrong number of fields: skip
str.s[len]=','; tmp++; len++;
STR_MOVE_NTH(&str.s[len],tmp,str.s+str.l,iaa-i0a-1,len);
if ( len<0 ) return; // wrong number of fields: skip
str.s[len] = 0;
bcf_update_info_string(args->hdr,dst,tag,str.s);
}
else
bcf_update_info_string(args->hdr,dst,tag,str.s);
}
static void split_info_flag(args_t *args, bcf1_t *src, bcf_info_t *info, int ialt, bcf1_t *dst)
{
const char *tag = bcf_hdr_int2id(args->hdr,BCF_DT_ID,info->key);
int ret = bcf_get_info_flag(args->hdr,src,tag,&args->tmp_arr1,&args->ntmp_arr1);
bcf_update_info_flag(args->hdr,dst,tag,NULL,ret);
}
static void split_format_genotype(args_t *args, bcf1_t *src, bcf_fmt_t *fmt, int ialt, bcf1_t *dst)
{
int ntmp = args->ntmp_arr1 / 4;
int ngts = bcf_get_genotypes(args->hdr,src,&args->tmp_arr1,&ntmp);
args->ntmp_arr1 = ntmp * 4;
assert( ngts >0 );
int32_t *gt = (int32_t*) args->tmp_arr1;
int i, j, nsmpl = bcf_hdr_nsamples(args->hdr);
ngts /= nsmpl;
for (i=0; i<nsmpl; i++)
{
for (j=0; j<ngts; j++)
{
if ( gt[j]==bcf_int32_vector_end ) break;
if ( bcf_gt_is_missing(gt[j]) || bcf_gt_allele(gt[j])==0 ) continue; // missing allele or ref: leave as is
if ( bcf_gt_allele(gt[j])==ialt+1 )
gt[j] = bcf_gt_unphased(1) | bcf_gt_is_phased(gt[j]); // set to first ALT
else
gt[j] = bcf_gt_unphased(0) | bcf_gt_is_phased(gt[j]); // set to REF
}
gt += ngts;
}
bcf_update_genotypes(args->hdr,dst,args->tmp_arr1,ngts*nsmpl);
}
static void split_format_numeric(args_t *args, bcf1_t *src, bcf_fmt_t *fmt, int ialt, bcf1_t *dst)
{
#define BRANCH_NUMERIC(type,type_t,is_vector_end,set_vector_end) \
{ \
const char *tag = bcf_hdr_int2id(args->hdr,BCF_DT_ID,fmt->id); \
int ntmp = args->ntmp_arr1 / sizeof(type_t); \
int nvals = bcf_get_format_##type(args->hdr,src,tag,&args->tmp_arr1,&ntmp); \
args->ntmp_arr1 = ntmp * sizeof(type_t); \
assert( nvals>0 ); \
type_t *vals = (type_t *) args->tmp_arr1; \
int len = bcf_hdr_id2length(args->hdr,BCF_HL_FMT,fmt->id); \
int i, nsmpl = bcf_hdr_nsamples(args->hdr); \
if ( nvals==nsmpl ) /* all values are missing */ \
{ \
bcf_update_format_##type(args->hdr,dst,tag,vals,nsmpl); \
return; \
} \
if ( len==BCF_VL_A ) \
{ \
if ( nvals!=(src->n_allele-1)*nsmpl ) \
error("Error: wrong number of fields in FMT/%s at %s:%d, expected %d, found %d\n", \
tag,bcf_seqname(args->hdr,src),src->pos+1,(src->n_allele-1)*nsmpl,nvals); \
nvals /= nsmpl; \
type_t *src_vals = vals, *dst_vals = vals; \
for (i=0; i<nsmpl; i++) \
{ \
dst_vals[0] = src_vals[ialt]; \
dst_vals += 1; \
src_vals += nvals; \
} \
bcf_update_format_##type(args->hdr,dst,tag,vals,nsmpl); \
} \
else if ( len==BCF_VL_R ) \
{ \
if ( nvals!=src->n_allele*nsmpl ) \
error("Error: wrong number of fields in FMT/%s at %s:%d, expected %d, found %d\n", \
tag,bcf_seqname(args->hdr,src),src->pos+1,src->n_allele*nsmpl,nvals); \
nvals /= nsmpl; \
type_t *src_vals = vals, *dst_vals = vals; \
for (i=0; i<nsmpl; i++) \
{ \
dst_vals[0] = src_vals[0]; \
dst_vals[1] = src_vals[ialt+1]; \
dst_vals += 2; \
src_vals += nvals; \
} \
bcf_update_format_##type(args->hdr,dst,tag,vals,nsmpl*2); \
} \
else if ( len==BCF_VL_G ) \
{ \
if ( nvals!=src->n_allele*(src->n_allele+1)/2*nsmpl && nvals!=src->n_allele*nsmpl ) \
error("Error at %s:%d, the tag %s has wrong number of fields\n", bcf_seqname(args->hdr,src),src->pos+1,bcf_hdr_int2id(args->hdr,BCF_DT_ID,fmt->id)); \
nvals /= nsmpl; \
int all_haploid = nvals==src->n_allele ? 1 : 0; \
type_t *src_vals = vals, *dst_vals = vals; \
for (i=0; i<nsmpl; i++) \
{ \
int haploid = all_haploid; \
if ( !haploid ) \
{ \
int j; \
for (j=0; j<nvals; j++) if ( is_vector_end ) break; \
if ( j!=nvals ) haploid = 1; \
} \
dst_vals[0] = src_vals[0]; \
if ( haploid ) \
{ \
dst_vals[1] = src_vals[ialt+1]; \
if ( !all_haploid ) set_vector_end; \
} \
else \
{ \
dst_vals[1] = src_vals[bcf_alleles2gt(0,ialt+1)]; \
dst_vals[2] = src_vals[bcf_alleles2gt(ialt+1,ialt+1)]; \
} \
dst_vals += all_haploid ? 2 : 3; \
src_vals += nvals; \
} \
bcf_update_format_##type(args->hdr,dst,tag,vals,all_haploid ? nsmpl*2 : nsmpl*3); \
} \
else \
bcf_update_format_##type(args->hdr,dst,tag,vals,nvals); \
}
switch (bcf_hdr_id2type(args->hdr,BCF_HL_FMT,fmt->id))
{
case BCF_HT_INT: BRANCH_NUMERIC(int32, int32_t, src_vals[j]==bcf_int32_vector_end, dst_vals[2]=bcf_int32_vector_end); break;
case BCF_HT_REAL: BRANCH_NUMERIC(float, float, bcf_float_is_vector_end(src_vals[j]), bcf_float_set_vector_end(dst_vals[2])); break;
}
#undef BRANCH_NUMERIC
}
static void squeeze_format_char(char *str, int src_blen, int dst_blen, int n)
{
int i, isrc = 0, idst = 0;
for (i=0; i<n; i++)
{
memmove(str+idst,str+isrc,dst_blen);
idst += dst_blen;
isrc += src_blen;
}
}
static void split_format_string(args_t *args, bcf1_t *src, bcf_fmt_t *fmt, int ialt, bcf1_t *dst)
{
const char *tag = bcf_hdr_int2id(args->hdr,BCF_DT_ID,fmt->id);
int ret = bcf_get_format_char(args->hdr,src,tag,&args->tmp_arr1,&args->ntmp_arr1);
assert( ret>0 );
kstring_t str;
str.m = args->ntmp_arr1;
str.l = ret;
str.s = (char*) args->tmp_arr1;
int nsmpl = bcf_hdr_nsamples(args->hdr);
int len = bcf_hdr_id2length(args->hdr,BCF_HL_FMT,fmt->id);
if ( len==BCF_VL_A )
{
int i, blen = ret/nsmpl, maxlen = 0;
char *ptr = str.s;
for (i=0; i<nsmpl; i++)
{
char *tmp = ptr;
int len = 0;
STR_MOVE_NTH(tmp,tmp,ptr+blen,ialt,len);
if ( len<0 ) return; // wrong number of fields: skip
if ( maxlen < len ) maxlen = len;
ptr += blen;
}
if ( maxlen<blen ) squeeze_format_char(str.s,blen,maxlen,nsmpl);
bcf_update_format_char(args->hdr,dst,tag,str.s,nsmpl*maxlen);
}
else if ( len==BCF_VL_R )
{
int i, blen = ret/nsmpl, maxlen = 0;
char *ptr = str.s;
for (i=0; i<nsmpl; i++)
{
char *tmp = ptr;
int len = 0;
STR_MOVE_NTH(ptr,tmp,ptr+blen,0,len);
ptr[len]=','; tmp++; len++;
STR_MOVE_NTH(&ptr[len],tmp,ptr+blen,ialt,len);
if ( len<0 ) return; // wrong number of fields: skip
if ( maxlen < len ) maxlen = len;
ptr += blen;
}
if ( maxlen<blen ) squeeze_format_char(str.s,blen,maxlen,nsmpl);
bcf_update_format_char(args->hdr,dst,tag,str.s,nsmpl*maxlen);
}
else if ( len==BCF_VL_G )
{
int i, blen = ret/nsmpl, maxlen = 0, i0a = bcf_alleles2gt(0,ialt+1), iaa = bcf_alleles2gt(ialt+1,ialt+1);
char *ptr = str.s;
for (i=0; i<nsmpl; i++)
{
char *se = ptr, *sx = ptr+blen;
int nfields = 1;
while ( *se && se<sx )
{
if ( *se==',' ) nfields++;
se++;
}
if ( nfields!=src->n_allele*(src->n_allele+1)/2 && nfields!=src->n_allele )
error("Error: wrong number of fields in FMT/%s at %s:%d, expected %d or %d, found %d\n",
tag,bcf_seqname(args->hdr,src),src->pos+1,src->n_allele*(src->n_allele+1)/2,src->n_allele,nfields);
int len = 0;
if ( nfields==src->n_allele ) // haploid
{
char *tmp = ptr;
STR_MOVE_NTH(&ptr[len],tmp,ptr+blen,0,len);
ptr[len]=','; tmp++; len++;
STR_MOVE_NTH(&ptr[len],tmp,ptr+blen,ialt,len);
if ( len<0 ) return; // wrong number of fields: skip
}
else // diploid
{
char *tmp = ptr;
STR_MOVE_NTH(&ptr[len],tmp,ptr+blen,0,len);
ptr[len]=','; tmp++; len++;
STR_MOVE_NTH(&ptr[len],tmp,ptr+blen,i0a-1,len);
if ( len<0 ) return; // wrong number of fields: skip
ptr[len]=','; tmp++; len++;
STR_MOVE_NTH(&ptr[len],tmp,ptr+blen,iaa-i0a-1,len);
if ( len<0 ) return; // wrong number of fields: skip
}
if ( maxlen < len ) maxlen = len;
ptr += blen;
}
if ( maxlen<blen ) squeeze_format_char(str.s,blen,maxlen,nsmpl);
bcf_update_format_char(args->hdr,dst,tag,str.s,nsmpl*maxlen);
}
else
bcf_update_format_char(args->hdr,dst,tag,str.s,str.l);
}
static void split_multiallelic_to_biallelics(args_t *args, bcf1_t *line)
{
int i;
bcf_unpack(line, BCF_UN_ALL);
// Init the target biallelic lines
args->ntmp_lines = line->n_allele-1;
if ( args->mtmp_lines < args->ntmp_lines )
{
args->tmp_lines = (bcf1_t **)realloc(args->tmp_lines,sizeof(bcf1_t*)*args->ntmp_lines);
for (i=args->mtmp_lines; i<args->ntmp_lines; i++)
args->tmp_lines[i] = NULL;
args->mtmp_lines = args->ntmp_lines;
}
kstring_t tmp = {0,0,0};
kputs(line->d.allele[0], &tmp);
kputc(',', &tmp);
int rlen = tmp.l;
int gt_id = bcf_hdr_id2int(args->hdr,BCF_DT_ID,"GT");
for (i=0; i<args->ntmp_lines; i++) // for each ALT allele
{
if ( !args->tmp_lines[i] ) args->tmp_lines[i] = bcf_init1();
bcf1_t *dst = args->tmp_lines[i];
bcf_clear(dst);
dst->rid = line->rid;
dst->pos = line->pos;
dst->qual = line->qual;
// Not quite sure how to handle IDs, they can be assigned to a specific
// ALT. For now we leave the ID unchanged for all.
bcf_update_id(args->hdr, dst, line->d.id ? line->d.id : ".");
tmp.l = rlen;
kputs(line->d.allele[i+1],&tmp);
bcf_update_alleles_str(args->hdr,dst,tmp.s);
if ( line->d.n_flt ) bcf_update_filter(args->hdr, dst, line->d.flt, line->d.n_flt);
int j;
for (j=0; j<line->n_info; j++)
{
bcf_info_t *info = &line->d.info[j];
int type = bcf_hdr_id2type(args->hdr,BCF_HL_INFO,info->key);
if ( type==BCF_HT_INT || type==BCF_HT_REAL ) split_info_numeric(args, line, info, i, dst);
else if ( type==BCF_HT_FLAG ) split_info_flag(args, line, info, i, dst);
else split_info_string(args, line, info, i, dst);
}
dst->n_sample = line->n_sample;
for (j=0; j<line->n_fmt; j++)
{
bcf_fmt_t *fmt = &line->d.fmt[j];
int type = bcf_hdr_id2type(args->hdr,BCF_HL_FMT,fmt->id);
if ( fmt->id==gt_id ) split_format_genotype(args, line, fmt, i, dst);
else if ( type==BCF_HT_INT || type==BCF_HT_REAL ) split_format_numeric(args, line, fmt, i, dst);
else split_format_string(args, line, fmt, i, dst);
}
}
free(tmp.s);
}
// Enlarge FORMAT array containing nsmpl samples each with nals_ori values
// to accommodate nvals values for each sample, filling the gaps with missing
// values. Works also for INFO arrays, with nsmpl set to 1.
#define ENLARGE_ARRAY(type_t,set_missing,arr,narr_bytes,nsmpl,nvals_ori,nvals) \
{ \
int nbytes_new = (nsmpl)*(nvals)*sizeof(type_t); \
hts_expand(uint8_t,nbytes_new,narr_bytes,arr); \
int ismpl, k; \
for (ismpl=nsmpl-1; ismpl>=0; ismpl--) \
{ \
type_t *dst_ptr = ((type_t*)arr) + ismpl*(nvals); \
type_t *src_ptr = ((type_t*)arr) + ismpl*nvals_ori; \
memmove(dst_ptr,src_ptr,sizeof(type_t)*nvals_ori); \
for (k=nvals_ori; k<nvals; k++) set_missing; \
} \
}
static void merge_info_numeric(args_t *args, bcf1_t **lines, int nlines, bcf_info_t *info, bcf1_t *dst)
{
#define BRANCH_NUMERIC(type,type_t,set_missing,is_vector_end) \
{ \
const char *tag = bcf_hdr_int2id(args->hdr,BCF_DT_ID,info->key); \
int ntmp = args->ntmp_arr1 / sizeof(type_t); \
int nvals_ori = bcf_get_info_##type(args->hdr,lines[0],tag,&args->tmp_arr1,&ntmp); \
args->ntmp_arr1 = ntmp * sizeof(type_t); \
assert( nvals_ori>0 ); \
type_t *vals = (type_t*) args->tmp_arr1, *vals2; \
int i,k,len = bcf_hdr_id2length(args->hdr,BCF_HL_INFO,info->key); \
if ( len==BCF_VL_A ) \
{ \
if (nvals_ori!=lines[0]->n_allele - 1) \
error("vcfnorm: number of fields in first record at position %s:%d for INFO tag %s not as expected [found: %d vs expected:%d]\n", bcf_seqname(args->hdr,lines[0]),lines[0]->pos+1, tag, nvals_ori, lines[0]->n_allele-1); \
int nvals = dst->n_allele - 1; \
ENLARGE_ARRAY(type_t,set_missing,args->tmp_arr1,args->ntmp_arr1,1,nvals_ori,nvals); \
vals = (type_t*) args->tmp_arr1; \
for (i=1; i<nlines; i++) \
{ \
int ntmp2 = args->ntmp_arr2 / sizeof(type_t); \
int nvals2 = bcf_get_info_##type(args->hdr,lines[i],tag,&args->tmp_arr2,&ntmp2); \
if (nvals2<0) continue; /* info tag does not exist in this record, skip */ \
args->ntmp_arr2 = ntmp2 * sizeof(type_t); \
if (nvals2!=lines[i]->n_allele-1) \
error("vcfnorm: could not merge INFO tag %s at position %s:%d\n", tag, bcf_seqname(args->hdr,lines[i]),lines[i]->pos+1); \
vals2 = (type_t*) args->tmp_arr2; \
for (k=0; k<nvals2; k++) \
{ \
if ( is_vector_end ) break; \
vals[ args->maps[i].map[k+1] - 1 ] = vals2[k]; \
} \
} \
bcf_update_info_##type(args->hdr,dst,tag,args->tmp_arr1,nvals); \
} \
else if ( len==BCF_VL_R ) \
{ \
if (nvals_ori!=lines[0]->n_allele) \
error("vcfnorm: number of fields in first record at position %s:%d for INFO tag %s not as expected [found: %d vs expected:%d]\n", bcf_seqname(args->hdr,lines[0]),lines[0]->pos+1, tag, nvals_ori, lines[0]->n_allele); \
int nvals = dst->n_allele; \
ENLARGE_ARRAY(type_t,set_missing,args->tmp_arr1,args->ntmp_arr1,1,nvals_ori,nvals); \
vals = (type_t*) args->tmp_arr1; \
for (i=1; i<nlines; i++) \
{ \
int ntmp2 = args->ntmp_arr2 / sizeof(type_t); \
int nvals2 = bcf_get_info_##type(args->hdr,lines[i],tag,&args->tmp_arr2,&ntmp2); \
if (nvals2<0) continue; /* info tag does not exist in this record, skip */ \
args->ntmp_arr2 = ntmp2 * sizeof(type_t); \
if (nvals2!=lines[i]->n_allele) \
error("vcfnorm: could not merge INFO tag %s at position %s:%d\n", tag, bcf_seqname(args->hdr,lines[i]),lines[i]->pos+1); \
vals2 = (type_t*) args->tmp_arr2; \
for (k=0; k<nvals2; k++) \
{ \
if ( is_vector_end ) break; \
vals[ args->maps[i].map[k] ] = vals2[k]; \
} \
} \
bcf_update_info_##type(args->hdr,dst,tag,args->tmp_arr1,nvals); \
} \
else if ( len==BCF_VL_G ) \
{ \
/* expecting diploid gt in INFO */ \
if (nvals_ori!=lines[0]->n_allele*(lines[0]->n_allele+1)/2) { \
fprintf(stderr, "todo: merge Number=G INFO fields for haploid sites\n"); \
error("vcfnorm: number of fields in first record at position %s:%d for INFO tag %s not as expected [found: %d vs expected:%d]\n", bcf_seqname(args->hdr,lines[0]),lines[0]->pos+1, tag, nvals_ori, lines[0]->n_allele*(lines[0]->n_allele+1)/2); \
} \
int nvals = dst->n_allele*(dst->n_allele+1)/2; \
ENLARGE_ARRAY(type_t,set_missing,args->tmp_arr1,args->ntmp_arr1,1,nvals_ori,nvals); \
vals = (type_t*) args->tmp_arr1; \
for (i=1; i<nlines; i++) \
{ \
int ntmp2 = args->ntmp_arr2 / sizeof(type_t); \
int nvals2 = bcf_get_info_##type(args->hdr,lines[i],tag,&args->tmp_arr2,&ntmp2); \
if (nvals2<0) continue; /* info tag does not exist in this record, skip */ \
args->ntmp_arr2 = ntmp2 * sizeof(type_t); \
if (nvals2!=lines[i]->n_allele*(lines[i]->n_allele+1)/2) \
error("vcfnorm: could not merge INFO tag %s at position %s:%d\n", tag, bcf_seqname(args->hdr,lines[i]),lines[i]->pos+1); \
vals2 = (type_t*) args->tmp_arr2; \
int ia,ib; \
k = 0; \
for (ia=0; ia<lines[i]->n_allele; ia++) \
{ \
for (ib=0; ib<=ia; ib++) \
{ \
if ( is_vector_end ) break; \
int l = bcf_alleles2gt(args->maps[i].map[ia],args->maps[i].map[ib]); \
vals[l] = vals2[k]; \
k++; \
} \
} \
} \
bcf_update_info_##type(args->hdr,dst,tag,args->tmp_arr1,nvals); \
} \
else \
bcf_update_info_##type(args->hdr,dst,tag,vals,nvals_ori); \
}
switch (bcf_hdr_id2type(args->hdr,BCF_HL_INFO,info->key))
{
case BCF_HT_INT: BRANCH_NUMERIC(int32, int32_t, dst_ptr[k]=bcf_int32_missing, vals2[k]==bcf_int32_vector_end); break;
case BCF_HT_REAL: BRANCH_NUMERIC(float, float, bcf_float_set_missing(dst_ptr[k]), bcf_float_is_vector_end(vals2[k])); break;
}
#undef BRANCH_NUMERIC
}
static void merge_info_flag(args_t *args, bcf1_t **lines, int nlines, bcf_info_t *info, bcf1_t *dst)
{
const char *tag = bcf_hdr_int2id(args->hdr,BCF_DT_ID,info->key);
int ret = bcf_get_info_flag(args->hdr,lines[0],tag,&args->tmp_arr1,&args->ntmp_arr1);
bcf_update_info_flag(args->hdr,dst,tag,NULL,ret);
}
int copy_string_field(char *src, int isrc, int src_len, kstring_t *dst, int idst); // see vcfmerge.c
static void merge_info_string(args_t *args, bcf1_t **lines, int nlines, bcf_info_t *info, bcf1_t *dst)
{
const char *tag = bcf_hdr_int2id(args->hdr,BCF_DT_ID,info->key);
kstring_t str;
str.m = args->ntmp_arr1;
str.l = 0;
str.s = (char*) args->tmp_arr1;
int i, j, len = bcf_hdr_id2length(args->hdr,BCF_HL_INFO,info->key);
if ( len==BCF_VL_A || len==BCF_VL_R )
{
int jfrom = len==BCF_VL_A ? 1 : 0;
kputc('.',&str);
for (i=jfrom+1; i<dst->n_allele; i++) kputs(",.",&str);
for (i=0; i<nlines; i++)
{
bcf_info_t *src = bcf_get_info(args->hdr,lines[i],tag);
if (!src) continue;
for (j=jfrom; j<lines[i]->n_allele; j++)
copy_string_field((char*)src->vptr, j-jfrom, src->len, &str, args->maps[i].map[j]-jfrom);
}
str.s[str.l] = 0;
args->tmp_arr1 = (uint8_t*) str.s;
args->ntmp_arr1 = str.m;
bcf_update_info_string(args->hdr,dst,tag,str.s);
}
else if ( len==BCF_VL_G )
{
int ngts = dst->n_allele*(dst->n_allele+1)/2;
kputc('.',&str);
for (i=1; i<ngts; i++) kputs(",.",&str);
for (i=0; i<nlines; i++)
{
bcf_info_t *src = bcf_get_info(args->hdr,lines[i],tag);
if (!src) continue;