/* vcfmerge.c -- Merge multiple VCF/BCF files to create one multi-sample file. Copyright (C) 2012-2014 Genome Research Ltd. Author: Petr Danecek 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 #include #include #include #include #include #include #include #include #include #include "bcftools.h" #include "vcmp.h" #include KHASH_MAP_INIT_STR(strdict, int) typedef khash_t(strdict) strdict_t; #define SKIP_DONE 1 #define SKIP_DIFF 2 #define IS_VL_G(hdr,id) (bcf_hdr_id2length(hdr,BCF_HL_FMT,id) == BCF_VL_G) #define IS_VL_A(hdr,id) (bcf_hdr_id2length(hdr,BCF_HL_FMT,id) == BCF_VL_A) #define IS_VL_R(hdr,id) (bcf_hdr_id2length(hdr,BCF_HL_FMT,id) == BCF_VL_R) // For merging INFO Number=A,G,R tags typedef struct { const char *hdr_tag; int type, nvals; int nbuf, mbuf; uint8_t *buf; } AGR_info_t; // Rules for merging arbitrary INFO tags typedef struct _info_rule_t { char *hdr_tag; void (*merger)(bcf_hdr_t *hdr, bcf1_t *line, struct _info_rule_t *rule); int type; // one of BCF_HT_* int block_size; // number of values in a block int nblocks; // number of blocks in nvals (the number of merged files) int nvals, mvals; // used and total size of vals array void *vals; // the info tag values } info_rule_t; // Auxiliary merge data for selecting the right combination // of buffered records across multiple readers. maux1_t // corresponds to one buffered line. typedef struct { int skip; int *map; // mapping from input alleles to the output array int mmap; // size of map array (only buffer[i].n_allele is actually used) int als_differ; } maux1_t; typedef struct { int n; // number of readers char **als, **out_als; // merged alleles (temp, may contain empty records) and merged alleles ready for output int nals, mals, nout_als, mout_als; // size of the output array int *cnt, ncnt; // number of records that refer to the alleles int *nbuf; // readers have buffers of varying lengths int *smpl_ploidy, *smpl_nGsize; // ploidy and derived number of values in Number=G tags, updated for each line (todo: cache for missing cases) int *flt, mflt, minf; bcf_info_t *inf;// out_line's INFO fields bcf_fmt_t **fmt_map; // i-th output FORMAT field corresponds in j-th reader to i*nreader+j, first row is reserved for GT int nfmt_map; // number of rows in the fmt_map array int *agr_map, nagr_map, magr_map; // mapping between Number=AGR element indexes void *tmp_arr; int ntmp_arr; maux1_t **d; // d[i][j] i-th reader, j-th buffer line AGR_info_t *AGR_info; int nAGR_info, mAGR_info; bcf_srs_t *files; int *has_line; // which files are being merged } maux_t; typedef struct { vcmp_t *vcmp; maux_t *maux; int header_only, collapse, output_type, force_samples, merge_by_id; char *header_fname, *output_fname, *regions_list, *info_rules, *file_list; info_rule_t *rules; int nrules; strdict_t *tmph; kstring_t tmps; bcf_srs_t *files; bcf1_t *out_line; htsFile *out_fh; bcf_hdr_t *out_hdr; char **argv; int argc; } args_t; static void info_rules_merge_sum(bcf_hdr_t *hdr, bcf1_t *line, info_rule_t *rule) { if ( !rule->nvals ) return; int i, j, ndim = rule->block_size; #define BRANCH(type_t,is_missing) { \ type_t *ptr = (type_t*) rule->vals; \ for (i=0; invals; i++) if ( is_missing ) ptr[i] = 0; \ for (i=1; inblocks; i++) \ { \ for (j=0; jtype) { case BCF_HT_INT: BRANCH(int32_t, ptr[i]==bcf_int32_missing); break; case BCF_HT_REAL: BRANCH(float, bcf_float_is_missing(ptr[i])); break; default: error("TODO: %s:%d .. type=%d\n", __FILE__,__LINE__, rule->type); } #undef BRANCH bcf_update_info(hdr,line,rule->hdr_tag,rule->vals,ndim,rule->type); } static void info_rules_merge_avg(bcf_hdr_t *hdr, bcf1_t *line, info_rule_t *rule) { if ( !rule->nvals ) return; int i, j, ndim = rule->block_size; #define BRANCH(type_t,is_missing) { \ type_t *ptr = (type_t*) rule->vals; \ for (i=0; invals; i++) if ( is_missing ) ptr[i] = 0; \ for (j=0; jnblocks; i++) sum += ptr[j+i*ndim]; \ ptr[j] = sum / rule->nblocks; \ } \ } switch (rule->type) { case BCF_HT_INT: BRANCH(int32_t, ptr[i]==bcf_int32_missing); break; case BCF_HT_REAL: BRANCH(float, bcf_float_is_missing(ptr[i])); break; default: error("TODO: %s:%d .. type=%d\n", __FILE__,__LINE__, rule->type); } #undef BRANCH bcf_update_info(hdr,line,rule->hdr_tag,rule->vals,ndim,rule->type); } static void info_rules_merge_min(bcf_hdr_t *hdr, bcf1_t *line, info_rule_t *rule) { if ( !rule->nvals ) return; int i, j, ndim = rule->block_size; #define BRANCH(type_t,is_missing,set_missing,huge_val) { \ type_t *ptr = (type_t*) rule->vals; \ for (i=0; invals; i++) if ( is_missing ) ptr[i] = huge_val; \ for (i=1; inblocks; i++) \ { \ for (j=0; j ptr[j+i*ndim] ) ptr[j] = ptr[j+i*ndim]; \ } \ for (i=0; invals; i++) if ( ptr[i]==huge_val ) set_missing; \ } switch (rule->type) { case BCF_HT_INT: BRANCH(int32_t, ptr[i]==bcf_int32_missing, ptr[i]=bcf_int32_missing, INT32_MAX); break; case BCF_HT_REAL: BRANCH(float, bcf_float_is_missing(ptr[i]), bcf_float_set_missing(ptr[i]), HUGE_VAL); break; default: error("TODO: %s:%d .. type=%d\n", __FILE__,__LINE__, rule->type); } #undef BRANCH bcf_update_info(hdr,line,rule->hdr_tag,rule->vals,ndim,rule->type); } static void info_rules_merge_max(bcf_hdr_t *hdr, bcf1_t *line, info_rule_t *rule) { if ( !rule->nvals ) return; int i, j, ndim = rule->block_size; #define BRANCH(type_t,is_missing,set_missing,huge_val) { \ type_t *ptr = (type_t*) rule->vals; \ for (i=0; invals; i++) if ( is_missing ) ptr[i] = huge_val; \ for (i=1; inblocks; i++) \ { \ for (j=0; jnvals; i++) if ( ptr[i]==huge_val ) set_missing; \ } switch (rule->type) { case BCF_HT_INT: BRANCH(int32_t, ptr[i]==bcf_int32_missing, ptr[i]=bcf_int32_missing, INT32_MIN); break; case BCF_HT_REAL: BRANCH(float, bcf_float_is_missing(ptr[i]), bcf_float_set_missing(ptr[i]), -HUGE_VAL); break; default: error("TODO: %s:%d .. type=%d\n", __FILE__,__LINE__, rule->type); } #undef BRANCH bcf_update_info(hdr,line,rule->hdr_tag,rule->vals,ndim,rule->type); } static void info_rules_merge_join(bcf_hdr_t *hdr, bcf1_t *line, info_rule_t *rule) { if ( !rule->nvals ) return; if ( rule->type==BCF_HT_STR ) { ((char*)rule->vals)[rule->nvals] = 0; bcf_update_info_string(hdr,line,rule->hdr_tag,rule->vals); } else bcf_update_info(hdr,line,rule->hdr_tag,rule->vals,rule->nvals,rule->type); } static int info_rules_comp_key2(const void *a, const void *b) { info_rule_t *rule1 = (info_rule_t*) a; info_rule_t *rule2 = (info_rule_t*) b; return strcmp(rule1->hdr_tag, rule2->hdr_tag); } static int info_rules_comp_key(const void *a, const void *b) { char *key = (char*) a; info_rule_t *rule = (info_rule_t*) b; return strcmp(key, rule->hdr_tag); } static void info_rules_init(args_t *args) { if ( args->info_rules && !strcmp("-",args->info_rules) ) return; kstring_t str = {0,0,0}; if ( !args->info_rules ) { if ( bcf_hdr_idinfo_exists(args->out_hdr,BCF_HL_INFO,bcf_hdr_id2int(args->out_hdr, BCF_DT_ID, "DP")) ) kputs("DP:sum",&str); if ( bcf_hdr_idinfo_exists(args->out_hdr,BCF_HL_INFO,bcf_hdr_id2int(args->out_hdr, BCF_DT_ID, "DP4")) ) { if ( str.l ) kputc(',',&str); kputs("DP4:sum",&str); } if ( !str.l ) return; args->info_rules = str.s; } args->nrules = 1; char *ss = strdup(args->info_rules), *tmp = ss; int n = 0; while ( *ss ) { if ( *ss==':' ) { *ss = 0; n++; if ( n%2==0 ) error("Could not parse INFO rules: \"%s\"\n", args->info_rules); } else if ( *ss==',' ) { *ss = 0; args->nrules++; n++; if ( n%2==1 ) error("Could not parse INFO rules: \"%s\"\n", args->info_rules); } ss++; } if ( n%2==0 ) error("Could not parse INFO rules: \"%s\"\n", args->info_rules); args->rules = (info_rule_t*) calloc(args->nrules,sizeof(info_rule_t)); n = 0; ss = tmp; while ( n < args->nrules ) { info_rule_t *rule = &args->rules[n]; rule->hdr_tag = strdup(ss); int id = bcf_hdr_id2int(args->out_hdr, BCF_DT_ID, rule->hdr_tag); if ( !bcf_hdr_idinfo_exists(args->out_hdr,BCF_HL_INFO,id) ) error("The tag is not defined in the header: \"%s\"\n", rule->hdr_tag); rule->type = bcf_hdr_id2type(args->out_hdr,BCF_HL_INFO,id); if ( rule->type!=BCF_HT_INT && rule->type!=BCF_HT_REAL && rule->type!=BCF_HT_STR ) error("The type is not supported: \"%s\"\n", rule->hdr_tag); while ( *ss ) ss++; ss++; if ( !*ss ) error("Could not parse INFO rules, missing logic of \"%s\"\n", rule->hdr_tag); int is_join = 0; if ( !strcasecmp(ss,"sum") ) rule->merger = info_rules_merge_sum; else if ( !strcasecmp(ss,"avg") ) rule->merger = info_rules_merge_avg; else if ( !strcasecmp(ss,"min") ) rule->merger = info_rules_merge_min; else if ( !strcasecmp(ss,"max") ) rule->merger = info_rules_merge_max; else if ( !strcasecmp(ss,"join") ) { rule->merger = info_rules_merge_join; is_join = 1; } else error("The rule logic \"%s\" not recognised\n", ss); if ( !is_join && rule->type==BCF_HT_STR ) error("Numeric operation \"%s\" requested on non-numeric field: %s\n", ss, rule->hdr_tag); if ( bcf_hdr_id2number(args->out_hdr,BCF_HL_INFO,id)==0xfffff ) { int is_agr = ( bcf_hdr_id2length(args->out_hdr,BCF_HL_INFO,id)==BCF_VL_A || bcf_hdr_id2length(args->out_hdr,BCF_HL_INFO,id)==BCF_VL_G || bcf_hdr_id2length(args->out_hdr,BCF_HL_INFO,id)==BCF_VL_R ) ? 1 : 0; if ( is_join && is_agr ) error("Cannot -i %s:join on Number=[AGR] tags is not supported.\n", rule->hdr_tag); if ( !is_join && !is_agr ) error("Only fixed-length vectors are supported with -i %s:%s\n", ss, rule->hdr_tag); } while ( *ss ) ss++; ss++; n++; } free(str.s); free(tmp); qsort(args->rules, args->nrules, sizeof(*args->rules), info_rules_comp_key2); } static void info_rules_destroy(args_t *args) { int i; for (i=0; inrules; i++) { info_rule_t *rule = &args->rules[i]; free(rule->hdr_tag); free(rule->vals); } free(args->rules); } static void info_rules_reset(args_t *args) { int i; for (i=0; inrules; i++) args->rules[i].nblocks = args->rules[i].nvals = args->rules[i].block_size = 0; } static int info_rules_add_values(args_t *args, bcf_hdr_t *hdr, bcf1_t *line, info_rule_t *rule, maux1_t *als, int var_len) { int ret = bcf_get_info_values(hdr, line, rule->hdr_tag, &args->maux->tmp_arr, &args->maux->ntmp_arr, rule->type); if ( ret<=0 ) error("FIXME: error parsing %s at %s:%d .. %d\n", rule->hdr_tag,bcf_seqname(hdr,line),line->pos+1,ret); rule->nblocks++; if ( rule->type==BCF_HT_STR ) { int need_comma = rule->nblocks==1 ? 0 : 1; hts_expand(char,rule->nvals+ret+need_comma+1,rule->mvals,rule->vals); // 1 for null-termination char *tmp = (char*) rule->vals + rule->nvals; if ( rule->nvals>0 ) { *tmp = ','; tmp++; } strncpy(tmp,(char*)args->maux->tmp_arr,ret); rule->nvals += ret + need_comma; return 1; } int i, j; if ( var_len==BCF_VL_A ) { assert( ret==line->n_allele-1 ); args->maux->nagr_map = ret; hts_expand(int,args->maux->nagr_map,args->maux->magr_map,args->maux->agr_map); // create mapping from source file ALT indexes to dst file indexes for (i=0; imaux->agr_map[i] = als->map[i+1] - 1; rule->block_size = args->maux->nout_als - 1; } else if ( var_len==BCF_VL_R ) { assert( ret==line->n_allele ); args->maux->nagr_map = ret; hts_expand(int,args->maux->nagr_map,args->maux->magr_map,args->maux->agr_map); for (i=0; imaux->agr_map[i] = als->map[i]; rule->block_size = args->maux->nout_als; } else if ( var_len==BCF_VL_G ) { args->maux->nagr_map = bcf_alleles2gt(line->n_allele-1,line->n_allele-1)+1; assert( ret==line->n_allele || ret==args->maux->nagr_map ); if ( ret==line->n_allele ) // haploid { args->maux->nagr_map = line->n_allele; hts_expand(int,args->maux->nagr_map,args->maux->magr_map,args->maux->agr_map); for (i=0; imaux->agr_map[i] = als->map[i]; rule->block_size = args->maux->nout_als; } else { hts_expand(int,args->maux->nagr_map,args->maux->magr_map,args->maux->agr_map); int k_src = 0; for (i=0; in_allele; i++) { for (j=0; j<=i; j++) { args->maux->agr_map[k_src] = bcf_alleles2gt(als->map[i],als->map[j]); k_src++; } } rule->block_size = bcf_alleles2gt(args->maux->nout_als-1,args->maux->nout_als-1)+1; } } else { if ( rule->nblocks>1 && ret!=rule->block_size ) error("Mismatch in number of values for INFO/%s at %s:%d\n", rule->hdr_tag,bcf_seqname(hdr,line),line->pos+1); rule->block_size = ret; args->maux->nagr_map = 0; } #define BRANCH(src_type_t,dst_type_t,set_missing) { \ src_type_t *src = (src_type_t *) args->maux->tmp_arr; \ hts_expand0(dst_type_t,(rule->nvals+rule->block_size),rule->mvals,rule->vals); \ dst_type_t *dst = (dst_type_t *) rule->vals + rule->nvals; \ rule->nvals += rule->block_size; \ if ( !args->maux->nagr_map ) \ { \ for (i=0; iblock_size; i++) set_missing; \ for (i=0; imaux->agr_map[i]] = src[i]; \ } \ } switch (rule->type) { case BCF_HT_INT: BRANCH(int, int32_t, dst[i] = bcf_int32_missing); break; case BCF_HT_REAL: BRANCH(float, float, bcf_float_set_missing(dst[i])); break; default: error("TODO: %s:%d .. type=%d\n", __FILE__,__LINE__, rule->type); } #undef BRANCH return 1; } int bcf_hdr_sync(bcf_hdr_t *h); void bcf_hdr_merge(bcf_hdr_t *hw, const bcf_hdr_t *hr, const char *clash_prefix, int force_samples) { // header lines int ret = bcf_hdr_combine(hw, hr); if ( ret!=0 ) error("Error occurred while merging the headers.\n"); // samples int i; for (i=0; isamples[i]; if ( bcf_hdr_id2int(hw, BCF_DT_SAMPLE, name)!=-1 ) { // there is a sample with the same name if ( !force_samples ) error("Error: Duplicate sample names (%s), use --force-samples to proceed anyway.\n", name); int len = strlen(hr->samples[i]) + strlen(clash_prefix) + 1; name = (char*) malloc(sizeof(char)*(len+1)); sprintf(name,"%s:%s",clash_prefix,hr->samples[i]); bcf_hdr_add_sample(hw,name); free(name); } else bcf_hdr_add_sample(hw,name); } } void debug_als(char **als, int nals) { int k; for (k=0; k=lens[j] ) done = 1; if ( als[j][lens[j]-i] != als[0][lens[0]-i] ) { done = 1; break; } } if ( done ) break; i++; } if ( i>1 ) { i--; als[0][lens[0]-i] = 0; for (j=1; j0, * 1->2, and 2->3. */ char **merge_alleles(char **a, int na, int *map, char **b, int *nb, int *mb) { // reference allele never changes map[0] = 0; int i,j; int rla = !a[0][1] ? 1 : strlen(a[0]); int rlb = !b[0][1] ? 1 : strlen(b[0]); // the most common case: same SNPs if ( na==2 && *nb==2 && rla==1 && rlb==1 && a[1][0]==b[1][0] && !a[1][1] && !b[1][1] ) { map[1] = 1; return b; } // Sanity check: reference prefixes must be identical if ( strncmp(a[0],b[0],rlarlb ) { for (i=0; i<*nb; i++) { int l = strlen(b[i]); b[i] = (char*) realloc(b[i],l+rla-rlb+1); memcpy(b[i]+l,a[0]+rlb,rla-rlb+1); } } // now check if the $a alleles are present and if not add them for (i=1; irla ) // $a alleles need expanding { int l = strlen(a[i]); ai = (char*) malloc(l+rlb-rla+1); memcpy(ai,a[i],l); memcpy(ai+l,b[0]+rla,rlb-rla+1); } else ai = a[i]; for (j=1; j<*nb; j++) if ( !strcmp(ai,b[j]) ) break; if ( j<*nb ) // $b already has the same allele { map[i] = j; if ( rlb>rla ) free(ai); continue; } // new allele map[i] = *nb; b[*nb] = rlb>rla ? ai : strdup(ai); (*nb)++; } return b; } maux_t *maux_init(bcf_srs_t *files) { maux_t *ma = (maux_t*) calloc(1,sizeof(maux_t)); ma->n = files->nreaders; ma->nbuf = (int *) calloc(ma->n,sizeof(int)); ma->d = (maux1_t**) calloc(ma->n,sizeof(maux1_t*)); ma->files = files; int i, n_smpl = 0; for (i=0; in; i++) n_smpl += bcf_hdr_nsamples(files->readers[i].header); ma->smpl_ploidy = (int*) calloc(n_smpl,sizeof(int)); ma->smpl_nGsize = (int*) malloc(n_smpl*sizeof(int)); ma->has_line = (int*) malloc(ma->n*sizeof(int)); return ma; } void maux_destroy(maux_t *ma) { int i; for (i=0; in; i++) // for each reader { if ( !ma->d[i] ) continue; int j; for (j=0; jnbuf[i]; j++) // for each buffered line if ( ma->d[i][j].map ) free(ma->d[i][j].map); free(ma->d[i]); } for (i=0; imAGR_info; i++) free(ma->AGR_info[i].buf); free(ma->agr_map); free(ma->AGR_info); if (ma->ntmp_arr) free(ma->tmp_arr); if (ma->nfmt_map) free(ma->fmt_map); // ma->inf freed in bcf_destroy1 free(ma->d); free(ma->nbuf); for (i=0; imals; i++) free(ma->als[i]); if (ma->mout_als) free(ma->out_als); free(ma->als); free(ma->cnt); free(ma->smpl_ploidy); free(ma->smpl_nGsize); free(ma->has_line); free(ma); } void maux_expand1(maux_t *ma, int i) { if ( ma->nbuf[i] <= ma->files->readers[i].nbuffer ) { int n = ma->files->readers[i].nbuffer + 1; ma->d[i] = (maux1_t*) realloc(ma->d[i], sizeof(maux1_t)*n); memset(ma->d[i]+ma->nbuf[i],0,sizeof(maux1_t)*(n-ma->nbuf[i])); ma->nbuf[i] = n; } } void maux_reset(maux_t *ma) { int i; for (i=0; in; i++) maux_expand1(ma, i); for (i=1; incnt; i++) ma->cnt[i] = 0; } void maux_debug(maux_t *ma, int ir, int ib) { printf("[%d,%d]\t", ir,ib); int i; for (i=0; inals; i++) { printf(" %s [%d]", ma->als[i], ma->cnt[i]); } printf("\n"); } void merge_chrom2qual(args_t *args, bcf1_t *out) { bcf_srs_t *files = args->files; bcf_hdr_t *out_hdr = args->out_hdr; int i, ret; khiter_t kitr; strdict_t *tmph = args->tmph; kh_clear(strdict, tmph); kstring_t *tmps = &args->tmps; tmps->l = 0; maux_t *ma = args->maux; int *al_idxs = (int*) calloc(ma->nals,sizeof(int)); bcf_float_set_missing(out->qual); // CHROM, POS, ID, QUAL out->pos = -1; for (i=0; inreaders; i++) { if ( !ma->has_line[i] ) continue; bcf_sr_t *reader = &files->readers[i]; bcf1_t *line = reader->buffer[0]; bcf_hdr_t *hdr = reader->header; // alleles int j; for (j=1; jn_allele; j++) al_idxs[ ma->d[i][0].map[j] ] = 1; // position if ( out->pos==-1 ) { const char *chr = hdr->id[BCF_DT_CTG][line->rid].key; out->rid = bcf_hdr_name2id(out_hdr, chr); if ( strcmp(chr,out_hdr->id[BCF_DT_CTG][out->rid].key) ) error("Uh\n"); out->pos = line->pos; } // ID if ( line->d.id[0]!='.' || line->d.id[1] ) { kitr = kh_get(strdict, tmph, line->d.id); if ( kitr == kh_end(tmph) ) { if ( tmps->l ) kputc(';', tmps); kputs(line->d.id, tmps); kh_put(strdict, tmph, line->d.id, &ret); } } // set QUAL to the max qual value. Not exactly correct, but good enough for now if ( !bcf_float_is_missing(files->readers[i].buffer[0]->qual) ) { if ( bcf_float_is_missing(out->qual) || out->qual < files->readers[i].buffer[0]->qual ) out->qual = files->readers[i].buffer[0]->qual; } } // set ID if ( !tmps->l ) kputs(".", tmps); if ( out->d.id ) free(out->d.id); out->d.id = strdup(tmps->s); // set alleles ma->nout_als = 0; for (i=1; inals; i++) { if ( !al_idxs[i] ) continue; ma->nout_als++; // Adjust the indexes, the allele map could be created for multiple collapsed records, // some of which might be unused for this output line int ir, j; for (ir=0; irnreaders; ir++) { if ( !ma->has_line[ir] ) continue; bcf1_t *line = files->readers[ir].buffer[0]; for (j=1; jn_allele; j++) if ( ma->d[ir][0].map[j]==i ) ma->d[ir][0].map[j] = ma->nout_als; } } // Expand the arrays and realloc the alleles string. Note that all alleles are in a single allocated block. ma->nout_als++; hts_expand0(char*, ma->nout_als, ma->mout_als, ma->out_als); int k = 0; for (i=0; inals; i++) if ( i==0 || al_idxs[i] ) ma->out_als[k++] = strdup(ma->als[i]); assert( k==ma->nout_als ); normalize_alleles(ma->out_als, ma->nout_als); bcf_update_alleles(out_hdr, out, (const char**) ma->out_als, ma->nout_als); free(al_idxs); for (i=0; inout_als; i++) free(ma->out_als[i]); } void merge_filter(args_t *args, bcf1_t *out) { bcf_srs_t *files = args->files; bcf_hdr_t *out_hdr = args->out_hdr; int i, ret; khiter_t kitr; strdict_t *tmph = args->tmph; kh_clear(strdict, tmph); maux_t *ma = args->maux; out->d.n_flt = 0; for (i=0; inreaders; i++) { if ( !ma->has_line[i]) continue; bcf_sr_t *reader = &files->readers[i]; bcf1_t *line = reader->buffer[0]; bcf_hdr_t *hdr = reader->header; bcf_unpack(line, BCF_UN_ALL); int k; for (k=0; kd.n_flt; k++) { const char *flt = hdr->id[BCF_DT_ID][line->d.flt[k]].key; kitr = kh_get(strdict, tmph, flt); if ( kitr == kh_end(tmph) ) { int id = bcf_hdr_id2int(out_hdr, BCF_DT_ID, flt); if ( id==-1 ) error("The filter not defined: %s\n", flt); hts_expand(int,out->d.n_flt+1,ma->mflt,ma->flt); ma->flt[out->d.n_flt] = id; out->d.n_flt++; kh_put(strdict, tmph, flt, &ret); } } } // Check if PASS is not mixed with other filters if ( out->d.n_flt>1 ) { int id = bcf_hdr_id2int(out_hdr, BCF_DT_ID, "PASS"); for (i=0; id.n_flt; i++) if ( ma->flt[i]==id ) break; if ( id.n_flt ) { out->d.n_flt--; for (; id.n_flt; i++) ma->flt[i] = ma->flt[i+1]; } } out->d.flt = ma->flt; } static void bcf_info_set_id(bcf1_t *line, bcf_info_t *info, int id, kstring_t *tmp_str) { assert( !info->vptr_free ); uint8_t *ptr = info->vptr - info->vptr_off; bcf_dec_typed_int1(ptr, &ptr); tmp_str->l = 0; bcf_enc_int1(tmp_str, id); if ( tmp_str->l == ptr - info->vptr + info->vptr_off ) { // the new id is represented with the same number of bytes memcpy(info->vptr - info->vptr_off, tmp_str->s, tmp_str->l); return; } kputsn_(ptr, info->vptr - ptr, tmp_str); info->vptr_off = tmp_str->l; kputsn_(info->vptr, info->len << bcf_type_shift[info->type], tmp_str); info->vptr = (uint8_t*) tmp_str->s + info->vptr_off; info->vptr_free = 1; line->d.shared_dirty |= BCF1_DIRTY_INF; tmp_str->s = NULL; tmp_str->m = 0; tmp_str->l = 0; } /* * copy_string_field() - copy a comma-separated field * @param src: source string * @param isrc: index of the field to copy * @param src_len: length of source string (excluding the terminating \0) * @param dst: destination kstring (must be initialized) * @param idst: index of the destination field */ int copy_string_field(char *src, int isrc, int src_len, kstring_t *dst, int idst) { int ith_src = 0, start_src = 0; // i-th field in src string while ( ith_srcl ) { if ( dst->s[start_dst]==',' ) { ith_dst++; } start_dst++; } if ( ith_dst!=idst ) return -2; int end_dst = start_dst; while ( end_dstl && dst->s[end_dst]!=',' ) end_dst++; if ( end_dst - start_dst>1 || dst->s[start_dst]!='.' ) return 0; // do not overwrite non-empty values // Now start_dst and end_dst are indexes to the destination memory area // which needs to be replaced with nsrc_cpy // source bytes, end_dst points just after. int ndst_shift = nsrc_cpy - (end_dst - start_dst); int ndst_move = dst->l - end_dst + 1; // how many bytes must be moved (including \0) if ( ndst_shift ) { ks_resize(dst, dst->l + ndst_shift + 1); // plus \0 memmove(dst->s+end_dst+ndst_shift, dst->s+end_dst, ndst_move); } memcpy(dst->s+start_dst, src+start_src, nsrc_cpy); dst->l += ndst_shift; return 0; } static void merge_AGR_info_tag(bcf_hdr_t *hdr, bcf1_t *line, bcf_info_t *info, int len, maux1_t *als, AGR_info_t *agr) { int i; if ( !agr->nbuf ) { if ( info->type==BCF_BT_INT8 || info->type==BCF_BT_INT16 || info->type==BCF_BT_INT32 || info->type==BCF_BT_FLOAT ) { agr->nbuf = 4 * agr->nvals; hts_expand(uint8_t,agr->nbuf,agr->mbuf,agr->buf); if ( info->type!=BCF_BT_FLOAT ) { int32_t *tmp = (int32_t*) agr->buf; for (i=0; invals; i++) tmp[i] = bcf_int32_missing; } else { float *tmp = (float*) agr->buf; for (i=0; invals; i++) bcf_float_set_missing(tmp[i]); } } else if ( info->type==BCF_BT_CHAR ) { kstring_t tmp; tmp.l = 0; tmp.m = agr->mbuf; tmp.s = (char*)agr->buf; kputc('.',&tmp); for (i=1; invals; i++) kputs(",.",&tmp); agr->mbuf = tmp.m; agr->nbuf = tmp.l; agr->buf = (uint8_t*)tmp.s; } else error("Not ready for type [%d]: %s at %d\n", info->type,agr->hdr_tag,line->pos+1); } if ( info->type==BCF_BT_INT8 || info->type==BCF_BT_INT16 || info->type==BCF_BT_INT32 || info->type==BCF_BT_FLOAT ) { if ( len==BCF_VL_A || len==BCF_VL_R ) { int ifrom = len==BCF_VL_A ? 1 : 0; #define BRANCH(type_t, is_missing, is_vector_end, out_type_t) { \ type_t *src = (type_t *) info->vptr; \ out_type_t *tgt = (out_type_t *) agr->buf; \ int iori, inew; \ for (iori=ifrom; iorin_allele; iori++) \ { \ if ( is_vector_end ) break; \ if ( is_missing ) continue; \ inew = als->map[iori] - ifrom; \ tgt[inew] = *src; \ src++; \ } \ } switch (info->type) { case BCF_BT_INT8: BRANCH(int8_t, *src==bcf_int8_missing, *src==bcf_int8_vector_end, int); break; case BCF_BT_INT16: BRANCH(int16_t, *src==bcf_int16_missing, *src==bcf_int16_vector_end, int); break; case BCF_BT_INT32: BRANCH(int32_t, *src==bcf_int32_missing, *src==bcf_int32_vector_end, int); break; case BCF_BT_FLOAT: BRANCH(float, bcf_float_is_missing(*src), bcf_float_is_vector_end(*src), float); break; default: fprintf(stderr,"TODO: %s:%d .. info->type=%d\n", __FILE__,__LINE__, info->type); exit(1); } #undef BRANCH } else { #define BRANCH(type_t, is_missing, is_vector_end, out_type_t) { \ type_t *src = (type_t *) info->vptr; \ out_type_t *tgt = (out_type_t *) agr->buf; \ int iori,jori, inew,jnew; \ for (iori=0; iorin_allele; iori++) \ { \ inew = als->map[iori]; \ for (jori=0; jori<=iori; jori++) \ { \ jnew = als->map[jori]; \ int kori = iori*(iori+1)/2 + jori; \ if ( is_vector_end ) break; \ if ( is_missing ) continue; \ int knew = inew>jnew ? inew*(inew+1)/2 + jnew : jnew*(jnew+1)/2 + inew; \ tgt[knew] = src[kori]; \ } \ if ( jori<=iori ) break; \ } \ } switch (info->type) { case BCF_BT_INT8: BRANCH(int8_t, src[kori]==bcf_int8_missing, src[kori]==bcf_int8_vector_end, int); break; case BCF_BT_INT16: BRANCH(int16_t, src[kori]==bcf_int16_missing, src[kori]==bcf_int16_vector_end, int); break; case BCF_BT_INT32: BRANCH(int32_t, src[kori]==bcf_int32_missing, src[kori]==bcf_int32_vector_end, int); break; case BCF_BT_FLOAT: BRANCH(float, bcf_float_is_missing(src[kori]), bcf_float_is_vector_end(src[kori]), float); break; default: fprintf(stderr,"TODO: %s:%d .. info->type=%d\n", __FILE__,__LINE__, info->type); exit(1); } #undef BRANCH } } else { kstring_t tmp; tmp.l = agr->nbuf; tmp.m = agr->mbuf; tmp.s = (char*)agr->buf; if ( len==BCF_VL_A || len==BCF_VL_R ) { int iori, ifrom = len==BCF_VL_A ? 1 : 0; for (iori=ifrom; iorin_allele; iori++) { int ret = copy_string_field((char*)info->vptr, iori-ifrom, info->len, &tmp, als->map[iori]-ifrom); if ( ret ) error("Error at %s:%d: wrong number of fields in %s?\n", bcf_seqname(hdr,line),line->pos+1,agr->hdr_tag); } } else { int iori,jori, inew,jnew; for (iori=0; iorin_allele; iori++) { inew = als->map[iori]; for (jori=0; jori<=iori; jori++) { jnew = als->map[jori]; int kori = iori*(iori+1)/2 + jori; int knew = bcf_alleles2gt(inew,jnew); int ret = copy_string_field((char*)info->vptr, kori, info->len, &tmp, knew); if ( ret ) error("Error at %s:%d: wrong number of fields in %s?\n", bcf_seqname(hdr,line),line->pos+1,agr->hdr_tag); } } } agr->mbuf = tmp.m; agr->nbuf = tmp.l; agr->buf = (uint8_t*)tmp.s; } } void merge_info(args_t *args, bcf1_t *out) { bcf_srs_t *files = args->files; bcf_hdr_t *out_hdr = args->out_hdr; int i, j, ret; khiter_t kitr; strdict_t *tmph = args->tmph; kh_clear(strdict, tmph); maux_t *ma = args->maux; ma->nAGR_info = 0; out->n_info = 0; info_rules_reset(args); for (i=0; inreaders; i++) { if ( !ma->has_line[i] ) continue; bcf_sr_t *reader = &files->readers[i]; bcf1_t *line = reader->buffer[0]; bcf_hdr_t *hdr = reader->header; for (j=0; jn_info; j++) { bcf_info_t *inf = &line->d.info[j]; const char *key = hdr->id[BCF_DT_ID][inf->key].key; if ( !strcmp("AC",key) || !strcmp("AN",key) ) continue; // AC and AN are done in merge_format() after genotypes are done int id = bcf_hdr_id2int(out_hdr, BCF_DT_ID, key); if ( id==-1 ) error("Error: The INFO field is not defined in the header: %s\n", key); kitr = kh_get(strdict, tmph, key); // have we seen the tag in one of the readers? int len = bcf_hdr_id2length(hdr,BCF_HL_INFO,inf->key); if ( args->nrules ) { info_rule_t *rule = (info_rule_t*) bsearch(key, args->rules, args->nrules, sizeof(*args->rules), info_rules_comp_key); if ( rule ) { maux1_t *als = ( len==BCF_VL_A || len==BCF_VL_G || len==BCF_VL_R ) ? &ma->d[i][0] : NULL; if ( info_rules_add_values(args, hdr, line, rule, als, len) ) continue; } } // Todo: Number=AGR tags should use the newer info_rules_* functions (info_rules_merge_first to be added) // and merge_AGR_info_tag to be made obsolete. if ( len==BCF_VL_A || len==BCF_VL_G || len==BCF_VL_R ) // Number=R,G,A requires special treatment { if ( kitr == kh_end(tmph) ) { // first occurance in this reader, alloc arrays ma->nAGR_info++; hts_expand0(AGR_info_t,ma->nAGR_info,ma->mAGR_info,ma->AGR_info); kitr = kh_put(strdict, tmph, key, &ret); kh_val(tmph,kitr) = ma->nAGR_info - 1; ma->AGR_info[ma->nAGR_info-1].hdr_tag = key; ma->AGR_info[ma->nAGR_info-1].type = bcf_hdr_id2type(hdr,BCF_HL_INFO,inf->key); ma->AGR_info[ma->nAGR_info-1].nbuf = 0; // size of the buffer switch (len) { case BCF_VL_A: ma->AGR_info[ma->nAGR_info-1].nvals = ma->nout_als - 1; break; case BCF_VL_G: ma->AGR_info[ma->nAGR_info-1].nvals = bcf_alleles2gt(ma->nout_als-1,ma->nout_als-1)+1; break; case BCF_VL_R: ma->AGR_info[ma->nAGR_info-1].nvals = ma->nout_als; break; } } kitr = kh_get(strdict, tmph, key); int idx = kh_val(tmph, kitr); if ( idx<0 ) error("Error occurred while processing INFO tag \"%s\" at %s:%d\n", key,bcf_seqname(hdr,line),line->pos+1); merge_AGR_info_tag(hdr, line,inf,len,&ma->d[i][0],&ma->AGR_info[idx]); continue; } if ( kitr == kh_end(tmph) ) { hts_expand0(bcf_info_t,out->n_info+1,ma->minf,ma->inf); ma->inf[out->n_info].key = id; ma->inf[out->n_info].type = inf->type; ma->inf[out->n_info].len = inf->len; ma->inf[out->n_info].vptr = inf->vptr; ma->inf[out->n_info].v1.i = inf->v1.i; ma->inf[out->n_info].v1.f = inf->v1.f; ma->inf[out->n_info].vptr_off = inf->vptr_off; ma->inf[out->n_info].vptr_len = inf->vptr_len; ma->inf[out->n_info].vptr_free = inf->vptr_free; if ( (args->output_type & FT_BCF) && id!=bcf_hdr_id2int(hdr, BCF_DT_ID, key) ) { // The existing packed info cannot be reused. Change the id. // Although quite hacky, it's faster than anything else given // the data structures bcf_info_set_id(out, &ma->inf[out->n_info], id, &args->tmps); } out->n_info++; kitr = kh_put(strdict, tmph, key, &ret); kh_val(tmph,kitr) = -(out->n_info-1); // arbitrary negative value } } } out->d.info = ma->inf; out->d.m_info = ma->minf; for (i=0; inrules; i++) args->rules[i].merger(args->out_hdr, out, &args->rules[i]); for (i=0; inAGR_info; i++) { AGR_info_t *agr = &ma->AGR_info[i]; bcf_update_info(out_hdr,out,agr->hdr_tag,agr->buf,agr->nvals,agr->type); } } void update_AN_AC(bcf_hdr_t *hdr, bcf1_t *line) { int32_t an = 0, *tmp = (int32_t*) malloc(sizeof(int)*line->n_allele); int ret = bcf_calc_ac(hdr, line, tmp, BCF_UN_FMT); if ( ret>0 ) { int i; for (i=0; in_allele; i++) an += tmp[i]; bcf_update_info_int32(hdr, line, "AN", &an, 1); bcf_update_info_int32(hdr, line, "AC", tmp+1, line->n_allele-1); } free(tmp); } void merge_GT(args_t *args, bcf_fmt_t **fmt_map, bcf1_t *out) { bcf_srs_t *files = args->files; bcf_hdr_t *out_hdr = args->out_hdr; maux_t *ma = args->maux; int i, ismpl = 0, nsamples = bcf_hdr_nsamples(out_hdr); int nsize = 0, msize = sizeof(int32_t); for (i=0; inreaders; i++) { if ( !fmt_map[i] ) continue; if ( fmt_map[i]->n > nsize ) nsize = fmt_map[i]->n; } if ( ma->ntmp_arr < nsamples*nsize*msize ) { ma->ntmp_arr = nsamples*nsize*msize; ma->tmp_arr = realloc(ma->tmp_arr, ma->ntmp_arr); } memset(ma->smpl_ploidy,0,nsamples*sizeof(int)); for (i=0; inreaders; i++) { bcf_sr_t *reader = &files->readers[i]; bcf_hdr_t *hdr = reader->header; bcf_fmt_t *fmt_ori = fmt_map[i]; int32_t *tmp = (int32_t *) ma->tmp_arr + ismpl*nsize; int j, k; if ( !fmt_ori ) { // missing values: assume maximum ploidy for (j=0; jsmpl_ploidy[ismpl+j]++; } tmp += nsize; } ismpl += bcf_hdr_nsamples(hdr); continue; } #define BRANCH(type_t, vector_end) { \ type_t *p_ori = (type_t*) fmt_ori->p; \ if ( !ma->d[i][0].als_differ ) \ { \ /* the allele numbering is unchanged */ \ for (j=0; jn; k++) \ { \ if ( p_ori[k]==vector_end ) break; /* smaller ploidy */ \ ma->smpl_ploidy[ismpl+j]++; \ if ( bcf_gt_is_missing(p_ori[k]) ) tmp[k] = 0; /* missing allele */ \ else tmp[k] = p_ori[k]; \ } \ for (; kn; \ } \ ismpl += bcf_hdr_nsamples(hdr); \ continue; \ } \ /* allele numbering needs to be changed */ \ for (j=0; jn; k++) \ { \ if ( p_ori[k]==vector_end ) break; /* smaller ploidy */ \ ma->smpl_ploidy[ismpl+j]++; \ if ( bcf_gt_is_missing(p_ori[k]) ) tmp[k] = 0; /* missing allele */ \ else \ { \ int al = (p_ori[k]>>1) - 1; \ al = al<=0 ? al + 1 : ma->d[i][0].map[al] + 1; \ tmp[k] = (al << 1) | ((p_ori[k])&1); \ } \ } \ for (; kn; \ } \ ismpl += bcf_hdr_nsamples(hdr); \ } switch (fmt_ori->type) { case BCF_BT_INT8: BRANCH(int8_t, bcf_int8_vector_end); break; case BCF_BT_INT16: BRANCH(int16_t, bcf_int16_vector_end); break; case BCF_BT_INT32: BRANCH(int32_t, bcf_int32_vector_end); break; default: error("Unexpected case: %d\n", fmt_ori->type); } #undef BRANCH } bcf_update_format_int32(out_hdr, out, "GT", (int32_t*)ma->tmp_arr, nsamples*nsize); } void merge_format_field(args_t *args, bcf_fmt_t **fmt_map, bcf1_t *out) { bcf_srs_t *files = args->files; bcf_hdr_t *out_hdr = args->out_hdr; maux_t *ma = args->maux; int i, ismpl = 0, nsamples = bcf_hdr_nsamples(out_hdr); const char *key = NULL; int nsize = 0, length = BCF_VL_FIXED, type = -1; for (i=0; inreaders; i++) { if ( !ma->has_line[i] ) continue; if ( !fmt_map[i] ) continue; if ( !key ) key = files->readers[i].header->id[BCF_DT_ID][fmt_map[i]->id].key; type = fmt_map[i]->type; if ( IS_VL_G(files->readers[i].header, fmt_map[i]->id) ) { length = BCF_VL_G; nsize = out->n_allele*(out->n_allele + 1)/2; break; } if ( IS_VL_A(files->readers[i].header, fmt_map[i]->id) ) { length = BCF_VL_A; nsize = out->n_allele - 1; break; } if ( IS_VL_R(files->readers[i].header, fmt_map[i]->id) ) { length = BCF_VL_R; nsize = out->n_allele; break; } if ( fmt_map[i]->n > nsize ) nsize = fmt_map[i]->n; } int msize = sizeof(float)>sizeof(int32_t) ? sizeof(float) : sizeof(int32_t); if ( ma->ntmp_arr < nsamples*nsize*msize ) { ma->ntmp_arr = nsamples*nsize*msize; ma->tmp_arr = realloc(ma->tmp_arr, ma->ntmp_arr); } // Fill the temp array for all samples by collecting values from all files for (i=0; inreaders; i++) { bcf_sr_t *reader = &files->readers[i]; bcf_hdr_t *hdr = reader->header; bcf_fmt_t *fmt_ori = fmt_map[i]; if ( fmt_ori ) { type = fmt_ori->type; int nals_ori = reader->buffer[0]->n_allele; if ( length==BCF_VL_G ) { // if all fields are missing then n==1 is valid if ( fmt_ori->n!=1 && fmt_ori->n != nals_ori*(nals_ori+1)/2 && fmt_map[i]->n != nals_ori ) error("Incorrect number of %s fields (%d) at %s:%d, cannot merge.\n", key,fmt_ori->n,bcf_seqname(args->out_hdr,out),out->pos+1); } else if ( length==BCF_VL_A ) { if ( fmt_ori->n!=1 && fmt_ori->n != nals_ori-1 ) error("Incorrect number of %s fields (%d) at %s:%d, cannot merge.\n", key,fmt_ori->n,bcf_seqname(args->out_hdr,out),out->pos+1); } else if ( length==BCF_VL_R ) { if ( fmt_ori->n!=1 && fmt_ori->n != nals_ori ) error("Incorrect number of %s fields (%d) at %s:%d, cannot merge.\n", key,fmt_ori->n,bcf_seqname(args->out_hdr,out),out->pos+1); } } // set the values #define BRANCH(tgt_type_t, src_type_t, src_is_missing, src_is_vector_end, tgt_set_missing, tgt_set_vector_end) { \ int j, l, k; \ tgt_type_t *tgt = (tgt_type_t *) ma->tmp_arr + ismpl*nsize; \ if ( !fmt_ori ) \ { \ /* the field is not present in this file, set missing values */ \ for (j=0; jhas_line[i] ); \ bcf1_t *line = reader->buffer[0]; \ src_type_t *src = (src_type_t*) fmt_ori->p; \ if ( (length!=BCF_VL_G && length!=BCF_VL_A && length!=BCF_VL_R) || (line->n_allele==out->n_allele && !ma->d[i][0].als_differ) ) \ { \ /* alleles unchanged, copy over */ \ for (j=0; jn; l++) \ { \ if ( src_is_vector_end ) break; \ else if ( src_is_missing ) tgt_set_missing; \ else *tgt = *src; \ tgt++; src++; \ } \ for (k=l; kn - l; \ } \ ismpl += bcf_hdr_nsamples(hdr); \ continue; \ } \ /* allele numbering needs to be changed */ \ if ( length==BCF_VL_G ) \ { \ /* Number=G tags */ \ for (j=0; jtmp_arr + (ismpl+j)*nsize; \ src = (src_type_t*) fmt_ori->p + j*fmt_ori->n; \ if ( (src_is_missing && fmt_ori->n==1) || (++src && src_is_vector_end) ) \ { \ /* tag with missing value "." */ \ tgt_set_missing; \ for (l=1; lsmpl_ploidy[ismpl+j]==1 ? out->n_allele : out->n_allele*(out->n_allele + 1)/2; \ for (l=0; lsmpl_ploidy[ismpl+j]==1 ) \ { \ /* Haploid */ \ int iori, inew; \ for (iori=0; iorin_allele; iori++) \ { \ inew = ma->d[i][0].map[iori]; \ src = (src_type_t*) fmt_ori->p + j*fmt_ori->n + iori; \ tgt = (tgt_type_t *) ma->tmp_arr + (ismpl+j)*nsize + inew; \ if ( src_is_vector_end ) break; \ if ( src_is_missing ) tgt_set_missing; \ else *tgt = *src; \ } \ } \ else \ { \ /* Diploid */ \ int iori,jori, inew,jnew; \ for (iori=0; iorin_allele; iori++) \ { \ inew = ma->d[i][0].map[iori]; \ for (jori=0; jori<=iori; jori++) \ { \ jnew = ma->d[i][0].map[jori]; \ int kori = iori*(iori+1)/2 + jori; \ int knew = inew>jnew ? inew*(inew+1)/2 + jnew : jnew*(jnew+1)/2 + inew; \ src = (src_type_t*) fmt_ori->p + j*fmt_ori->n + kori; \ tgt = (tgt_type_t *) ma->tmp_arr + (ismpl+j)*nsize + knew; \ if ( src_is_vector_end ) \ { \ iori = line->n_allele; \ break; \ } \ if ( src_is_missing ) tgt_set_missing; \ else *tgt = *src; \ } \ } \ } \ } \ } \ else \ { \ /* Number=A or Number=R tags */ \ int ifrom = length==BCF_VL_A ? 1 : 0; \ for (j=0; jtmp_arr + (ismpl+j)*nsize; \ src = (src_type_t*) (fmt_ori->p + j*fmt_ori->size); \ if ( (src_is_missing && fmt_ori->n==1) || (++src && src_is_vector_end) ) \ { \ /* tag with missing value "." */ \ tgt_set_missing; \ for (l=1; lp + j*fmt_ori->size); \ for (l=0; ln_allele; iori++) \ { \ inew = ma->d[i][0].map[iori] - ifrom; \ tgt = (tgt_type_t *) ma->tmp_arr + (ismpl+j)*nsize + inew; \ if ( src_is_vector_end ) break; \ if ( src_is_missing ) tgt_set_missing; \ else *tgt = *src; \ src++; \ } \ } \ } \ ismpl += bcf_hdr_nsamples(hdr); \ } switch (type) { case BCF_BT_INT8: BRANCH(int32_t, int8_t, *src==bcf_int8_missing, *src==bcf_int8_vector_end, *tgt=bcf_int32_missing, *tgt=bcf_int32_vector_end); break; case BCF_BT_INT16: BRANCH(int32_t, int16_t, *src==bcf_int16_missing, *src==bcf_int16_vector_end, *tgt=bcf_int32_missing, *tgt=bcf_int32_vector_end); break; case BCF_BT_INT32: BRANCH(int32_t, int32_t, *src==bcf_int32_missing, *src==bcf_int32_vector_end, *tgt=bcf_int32_missing, *tgt=bcf_int32_vector_end); break; case BCF_BT_FLOAT: BRANCH(float, float, bcf_float_is_missing(*src), bcf_float_is_vector_end(*src), bcf_float_set_missing(*tgt), bcf_float_set_vector_end(*tgt)); break; case BCF_BT_CHAR: BRANCH(uint8_t, uint8_t, *src==bcf_str_missing, *src==bcf_str_vector_end, *tgt=bcf_str_missing, *tgt=bcf_str_vector_end); break; default: error("Unexpected case: %d, %s\n", type, key); } #undef BRANCH } if ( type==BCF_BT_FLOAT ) bcf_update_format_float(out_hdr, out, key, (float*)ma->tmp_arr, nsamples*nsize); else if ( type==BCF_BT_CHAR ) bcf_update_format_char(out_hdr, out, key, (float*)ma->tmp_arr, nsamples*nsize); else bcf_update_format_int32(out_hdr, out, key, (int32_t*)ma->tmp_arr, nsamples*nsize); } void merge_format(args_t *args, bcf1_t *out) { bcf_srs_t *files = args->files; bcf_hdr_t *out_hdr = args->out_hdr; maux_t *ma = args->maux; if ( !ma->nfmt_map ) { ma->nfmt_map = 2; ma->fmt_map = (bcf_fmt_t**) calloc(ma->nfmt_map*files->nreaders, sizeof(bcf_fmt_t*)); } else memset(ma->fmt_map, 0, ma->nfmt_map*files->nreaders*sizeof(bcf_fmt_t**)); khiter_t kitr; strdict_t *tmph = args->tmph; kh_clear(strdict, tmph); int i, j, ret, has_GT = 0, max_ifmt = 0; // max fmt index for (i=0; inreaders; i++) { if ( !ma->has_line[i] ) continue; bcf_sr_t *reader = &files->readers[i]; bcf1_t *line = reader->buffer[0]; bcf_hdr_t *hdr = reader->header; for (j=0; jn_fmt; j++) { // Wat this tag already seen? bcf_fmt_t *fmt = &line->d.fmt[j]; const char *key = hdr->id[BCF_DT_ID][fmt->id].key; kitr = kh_get(strdict, tmph, key); int ifmt; if ( kitr != kh_end(tmph) ) ifmt = kh_value(tmph, kitr); // seen else { // new FORMAT tag if ( key[0]=='G' && key[1]=='T' && key[2]==0 ) { has_GT = 1; ifmt = 0; } else { ifmt = ++max_ifmt; if ( max_ifmt >= ma->nfmt_map ) { ma->fmt_map = (bcf_fmt_t**) realloc(ma->fmt_map, sizeof(bcf_fmt_t*)*(max_ifmt+1)*files->nreaders); memset(ma->fmt_map+ma->nfmt_map*files->nreaders, 0, (max_ifmt-ma->nfmt_map+1)*files->nreaders*sizeof(bcf_fmt_t*)); ma->nfmt_map = max_ifmt+1; } } kitr = kh_put(strdict, tmph, key, &ret); kh_value(tmph, kitr) = ifmt; } ma->fmt_map[ifmt*files->nreaders+i] = fmt; } // Check if the allele numbering must be changed for (j=1; jbuffer[0]->n_allele; j++) if ( ma->d[i][0].map[j]!=j ) break; ma->d[i][0].als_differ = j==reader->buffer[0]->n_allele ? 0 : 1; } out->n_sample = bcf_hdr_nsamples(out_hdr); if ( has_GT ) merge_GT(args, ma->fmt_map, out); update_AN_AC(out_hdr, out); if ( out->d.info!=ma->inf ) { // hacky, we rely on htslib internals: bcf_update_info() reallocated the info ma->inf = out->d.info; ma->minf = out->d.m_info; } for (i=1; i<=max_ifmt; i++) merge_format_field(args, &ma->fmt_map[i*files->nreaders], out); out->d.indiv_dirty = 1; } // The core merging function, one or none line from each reader void merge_line(args_t *args) { bcf1_t *out = args->out_line; bcf_clear1(out); out->unpacked = BCF_UN_ALL; merge_chrom2qual(args, out); merge_filter(args, out); merge_info(args, out); merge_format(args, out); bcf_write1(args->out_fh, args->out_hdr, out); } void debug_buffers(FILE *fp, bcf_srs_t *files); void debug_buffer(FILE *fp, bcf_sr_t *reader); #define SWAP(type_t,a,b) { type_t tmp = (a); (a) = (b); (b) = tmp; } // Clean the reader's buffer to and make it ready for the next next_line() call. // Moves finished records (SKIP_DONE flag set) at the end of the buffer and put // the rest to the beggining. Then shorten the buffer so that the last element // points to the last unfinished record. There are two special cases: the last // line of the buffer typically has a different position and must stay at the // end; next, the first record of the buffer must be one of those already // printed, as it will be discarded by next_line(). // void shake_buffer(maux_t *maux, int ir, int pos) { bcf_sr_t *reader = &maux->files->readers[ir]; maux1_t *m = maux->d[ir]; if ( !reader->buffer ) return; int i; // FILE *fp = stdout; // fprintf(fp," nbuf=%d\t", reader->nbuffer); for (i=0; inbuffer; i++) fprintf(fp," %d", skip[i]); fprintf(fp,"\n"); // debug_buffer(fp,reader); // fprintf(fp,"--\n"); int a = 1, b = reader->nbuffer; if ( reader->buffer[b]->pos != pos ) b--; // move the last line separately afterwards while ( abuffer[a], reader->buffer[b]); SWAP(maux1_t, m[a], m[b]); a++; b--; } // position $a to the after the first unfinished record while ( a<=reader->nbuffer && !(m[a].skip&SKIP_DONE) ) a++; if ( anbuffer ) { // there is a gap between the unfinished lines at the beggining and the // last line. The last line must be brought forward to fill the gap if ( reader->buffer[reader->nbuffer]->pos != pos ) { SWAP(bcf1_t*, reader->buffer[a], reader->buffer[reader->nbuffer]); SWAP(maux1_t, m[a], m[reader->nbuffer]); reader->nbuffer = a; } } if ( !(m[0].skip&SKIP_DONE) && reader->buffer[0]->pos==pos ) { // the first record is unfinished, replace it with an empty line // from the end of the buffer or else next_line will remove it if ( reader->nbuffer + 1 >= maux->nbuf[ir] ) { reader->nbuffer++; maux_expand1(maux, ir); reader->nbuffer--; m = maux->d[ir]; } if ( reader->nbuffer+1 >= reader->mbuffer ) error("Uh, did not expect this: %d vs %d\n", reader->nbuffer,reader->mbuffer); if ( reader->buffer[reader->nbuffer]->pos!=pos ) { // 4way swap bcf1_t *tmp = reader->buffer[0]; reader->buffer[0] = reader->buffer[reader->nbuffer+1]; reader->buffer[reader->nbuffer+1] = reader->buffer[reader->nbuffer]; reader->buffer[reader->nbuffer] = tmp; m[reader->nbuffer].skip = m[0].skip; m[reader->nbuffer+1].skip = SKIP_DIFF; reader->nbuffer++; } else { SWAP(bcf1_t*, reader->buffer[0], reader->buffer[reader->nbuffer+1]); SWAP(maux1_t, m[0], m[reader->nbuffer+1]); } } // debug_buffer(fp,reader); // fprintf(fp,"\t"); for (i=0; inbuffer; i++) fprintf(fp," %d", skip[i]); // fprintf(fp,"\n\n"); // set position of finished buffer[0] line to -1, otherwise swapping may // bring it back after next_line() reader->buffer[0]->pos = -1; // trim the buffer, remove finished lines from the end i = reader->nbuffer; while ( i>=1 && m[i--].skip&SKIP_DONE ) reader->nbuffer--; } void debug_maux(args_t *args, int pos, int var_type) { bcf_srs_t *files = args->files; maux_t *maux = args->maux; int j,k,l; fprintf(stderr,"Alleles to merge at %d\n", pos+1); for (j=0; jnreaders; j++) { bcf_sr_t *reader = &files->readers[j]; fprintf(stderr," reader %d: ", j); for (k=0; k<=reader->nbuffer; k++) { if ( maux->d[j][k].skip==SKIP_DONE ) continue; bcf1_t *line = reader->buffer[k]; if ( line->pos!=pos ) continue; fprintf(stderr,"\t"); if ( maux->d[j][k].skip ) fprintf(stderr,"["); // this record will not be merged in this round for (l=0; ln_allele; l++) fprintf(stderr,"%s%s", l==0?"":",", line->d.allele[l]); if ( maux->d[j][k].skip ) fprintf(stderr,"]"); } fprintf(stderr,"\n"); } fprintf(stderr," counts: "); for (j=0; jnals; j++) fprintf(stderr,"%s %dx %s", j==0?"":",",maux->cnt[j], maux->als[j]); fprintf(stderr,"\n"); for (j=0; jnreaders; j++) { bcf_sr_t *reader = &files->readers[j]; fprintf(stderr," out %d: ", j); for (k=0; k<=reader->nbuffer; k++) { if ( maux->d[j][k].skip==SKIP_DONE ) continue; bcf1_t *line = reader->buffer[k]; if ( line->pos!=pos ) continue; if ( maux->d[j][k].skip ) continue; fprintf(stderr,"\t"); for (l=0; ln_allele; l++) fprintf(stderr,"%s%s", l==0?"":",", maux->als[maux->d[j][k].map[l]]); } fprintf(stderr,"\n"); } fprintf(stderr,"\n"); } // Determine which line should be merged from which reader: go through all // readers and all buffered lines, expand REF,ALT and try to match lines with // the same ALTs. A step towards output independent on input ordering of the // lines. void merge_buffer(args_t *args) { bcf_srs_t *files = args->files; int i, pos = -1, var_type = 0; char *id = NULL; maux_t *maux = args->maux; maux_reset(maux); // set the current position for (i=0; inreaders; i++) { if ( bcf_sr_has_line(files,i) ) { bcf1_t *line = bcf_sr_get_line(files,i); pos = line->pos; var_type = bcf_get_variant_types(line); id = line->d.id; break; } } // In this loop we select from each reader compatible candidate lines. // (i.e. SNPs or indels). Go through all files and all lines at this // position and normalize relevant alleles. // REF-only sites may be associated with both SNPs and indels. for (i=0; inreaders; i++) { bcf_sr_t *reader = &files->readers[i]; if ( !reader->buffer ) continue; int j, k; for (j=0; j<=reader->nbuffer; j++) { bcf1_t *line = reader->buffer[j]; int line_type = bcf_get_variant_types(line); // select relevant lines maux->d[i][j].skip = SKIP_DIFF; if ( pos!=line->pos ) { if ( j==0 ) maux->d[i][j].skip |= SKIP_DONE; // left from previous run, force to ignore continue; } if ( args->merge_by_id ) { if ( strcmp(id,line->d.id) ) continue; } else { if ( args->collapse==COLLAPSE_NONE && maux->nals ) { // All alleles of the tested record must be present in the // selected maux record plus variant types must be the same if ( var_type!=line->d.var_type ) continue; if ( vcmp_set_ref(args->vcmp,maux->als[0],line->d.allele[0]) < 0 ) continue; // refs not compatible for (k=1; kn_allele; k++) { if ( vcmp_find_allele(args->vcmp,maux->als+1,maux->nals-1,line->d.allele[k])>=0 ) break; } if ( k==line->n_allele ) continue; // no matching allele } if ( !(args->collapse&COLLAPSE_ANY) ) { int compatible = 0; if ( line_type==var_type ) compatible = 1; else if ( line_type==VCF_REF ) compatible = 1; // REF can go with anything else if ( var_type&VCF_SNP && line_type&VCF_SNP ) compatible = 1; else if ( var_type&VCF_INDEL && line_type&VCF_INDEL ) compatible = 1; else if ( var_type&VCF_MNP && line_type&VCF_MNP ) compatible = 1; else if ( var_type&VCF_SNP && line_type&VCF_MNP ) compatible = 1; else if ( var_type&VCF_MNP && line_type&VCF_SNP ) compatible = 1; if ( !compatible ) continue; } } maux->d[i][j].skip = 0; hts_expand(int, line->n_allele, maux->d[i][j].mmap, maux->d[i][j].map); if ( !maux->nals ) // first record, copy the alleles to the output { maux->nals = line->n_allele; hts_expand0(char*, maux->nals, maux->mals, maux->als); hts_expand0(int, maux->nals, maux->ncnt, maux->cnt); for (k=0; knals; k++) { maux->als[k] = strdup(line->d.allele[k]); maux->d[i][j].map[k] = k; maux->cnt[k] = 1; } pos = line->pos; continue; } // normalize alleles maux->als = merge_alleles(line->d.allele, line->n_allele, maux->d[i][j].map, maux->als, &maux->nals, &maux->mals); if ( !maux->als ) error("Failed to merge alleles at %s:%d in %s\n",bcf_seqname(args->out_hdr,line),line->pos+1,reader->fname); hts_expand0(int, maux->nals, maux->ncnt, maux->cnt); for (k=1; kn_allele; k++) maux->cnt[ maux->d[i][j].map[k] ]++; // how many times an allele appears in the files maux->cnt[0]++; } } // debug_maux(args, pos, var_type); // Select records that have the same alleles; the input ordering of indels // must not matter. Multiple VCF lines can be emitted from this loop. // We expect only very few alleles and not many records with the same // position in the buffers, therefore the nested loops should not slow us // much. while (1) { // take the most frequent allele present in multiple files int icnt = 0; for (i=1; inals; i++) if ( maux->cnt[i] > maux->cnt[icnt] ) icnt = i; if ( maux->cnt[icnt]<0 ) break; int nmask = 0; for (i=0; inreaders; i++) { maux->has_line[i] = 0; bcf_sr_t *reader = &files->readers[i]; if ( !reader->buffer ) continue; // find lines with the same allele int j; for (j=0; j<=reader->nbuffer; j++) { if ( maux->d[i][j].skip ) continue; int k; for (k=0; kbuffer[j]->n_allele; k++) if ( icnt==maux->d[i][j].map[k] ) break; if ( kbuffer[j]->n_allele ) break; } if ( j>reader->nbuffer ) { // no matching allele found in this file if ( args->collapse==COLLAPSE_NONE ) continue; for (j=0; j<=reader->nbuffer; j++) { if ( maux->d[i][j].skip ) continue; if ( args->collapse&COLLAPSE_ANY ) break; int line_type = bcf_get_variant_types(reader->buffer[j]); if ( var_type&VCF_SNP && line_type&VCF_SNP && (args->collapse&COLLAPSE_SNPS) ) break; if ( var_type&VCF_INDEL && line_type&VCF_INDEL && (args->collapse&COLLAPSE_INDELS) ) break; if ( line_type==VCF_REF ) { if ( var_type&VCF_SNP && (args->collapse&COLLAPSE_SNPS) ) break; if ( var_type&VCF_INDEL && (args->collapse&COLLAPSE_INDELS) ) break; } else if ( var_type==VCF_REF ) { if ( line_type&VCF_SNP && (args->collapse&COLLAPSE_SNPS) ) break; if ( line_type&VCF_INDEL && (args->collapse&COLLAPSE_INDELS) ) break; } } } if ( j<=reader->nbuffer ) { // found a suitable line for merging, place it at the beggining if ( j>0 ) { SWAP(bcf1_t*, reader->buffer[0], reader->buffer[j]); SWAP(maux1_t, maux->d[i][0], maux->d[i][j]); } // mark as finished so that it's ignored next time maux->d[i][0].skip |= SKIP_DONE; maux->has_line[i] = 1; nmask++; } } if ( !nmask ) break; // done, no more lines suitable for merging found merge_line(args); // merge and output the line maux->cnt[icnt] = -1; // do not pick this allele again, mark it as finished } // clean the alleles for (i=0; inals; i++) { free(maux->als[i]); maux->als[i] = 0; } maux->nals = 0; // get the buffers ready for the next next_line() call for (i=0; inreaders; i++) shake_buffer(maux, i, pos); } void bcf_hdr_append_version(bcf_hdr_t *hdr, int argc, char **argv, const char *cmd) { kstring_t str = {0,0,0}; ksprintf(&str,"##%sVersion=%s+htslib-%s\n", cmd, bcftools_version(), hts_version()); bcf_hdr_append(hdr,str.s); str.l = 0; ksprintf(&str,"##%sCommand=%s", cmd, argv[0]); int i; for (i=1; iout_fh = hts_open(args->output_fname, hts_bcf_wmode(args->output_type)); if ( args->out_fh == NULL ) error("Can't write to \"%s\": %s\n", args->output_fname, strerror(errno)); args->out_hdr = bcf_hdr_init("w"); if ( args->header_fname ) { if ( bcf_hdr_set(args->out_hdr,args->header_fname) ) error("Could not read/parse the header: %s\n", args->header_fname); } else { int i; for (i=0; ifiles->nreaders; i++) { char buf[10]; snprintf(buf,10,"%d",i+1); bcf_hdr_merge(args->out_hdr, args->files->readers[i].header,buf,args->force_samples); } bcf_hdr_append_version(args->out_hdr, args->argc, args->argv, "bcftools_merge"); bcf_hdr_sync(args->out_hdr); } info_rules_init(args); bcf_hdr_set_version(args->out_hdr, bcf_hdr_get_version(args->files->readers[0].header)); bcf_hdr_write(args->out_fh, args->out_hdr); if ( args->header_only ) { bcf_hdr_destroy(args->out_hdr); hts_close(args->out_fh); return; } if ( args->collapse==COLLAPSE_NONE ) args->vcmp = vcmp_init(); args->maux = maux_init(args->files); args->out_line = bcf_init1(); args->tmph = kh_init(strdict); int ret; while ( (ret=bcf_sr_next_line(args->files)) ) { merge_buffer(args); } info_rules_destroy(args); maux_destroy(args->maux); bcf_hdr_destroy(args->out_hdr); hts_close(args->out_fh); bcf_destroy1(args->out_line); kh_destroy(strdict, args->tmph); if ( args->tmps.m ) free(args->tmps.s); if ( args->vcmp ) vcmp_destroy(args->vcmp); } static void usage(void) { fprintf(stderr, "\n"); fprintf(stderr, "About: Merge multiple VCF/BCF files from non-overlapping sample sets to create one multi-sample file.\n"); fprintf(stderr, " Note that only records from different files can be merged, never from the same file. For\n"); fprintf(stderr, " \"vertical\" merge take a look at \"bcftools norm\" instead.\n"); fprintf(stderr, "Usage: bcftools merge [options] [...]\n"); fprintf(stderr, "\n"); fprintf(stderr, "Options:\n"); fprintf(stderr, " --force-samples resolve duplicate sample names\n"); fprintf(stderr, " --print-header print only the merged header and exit\n"); fprintf(stderr, " --use-header use the provided header\n"); fprintf(stderr, " -f, --apply-filters require at least one of the listed FILTER strings (e.g. \"PASS,.\")\n"); fprintf(stderr, " -i, --info-rules rules for merging INFO fields (method is one of sum,avg,min,max,join) or \"-\" to turn off the default [DP:sum,DP4:sum]\n"); fprintf(stderr, " -l, --file-list read file names from the file\n"); fprintf(stderr, " -m, --merge allow multiallelic records for , see man page for details [both]\n"); fprintf(stderr, " -o, --output write output to a file [standard output]\n"); fprintf(stderr, " -O, --output-type 'b' compressed BCF; 'u' uncompressed BCF; 'z' compressed VCF; 'v' uncompressed VCF [v]\n"); fprintf(stderr, " -r, --regions restrict to comma-separated list of regions\n"); fprintf(stderr, " -R, --regions-file restrict to regions listed in a file\n"); fprintf(stderr, "\n"); exit(1); } int main_vcfmerge(int argc, char *argv[]) { int c; args_t *args = (args_t*) calloc(1,sizeof(args_t)); args->files = bcf_sr_init(); args->argc = argc; args->argv = argv; args->output_fname = "-"; args->output_type = FT_VCF; args->collapse = COLLAPSE_BOTH; int regions_is_file = 0; static struct option loptions[] = { {"help",0,0,'h'}, {"merge",1,0,'m'}, {"file-list",1,0,'l'}, {"apply-filters",1,0,'f'}, {"use-header",1,0,1}, {"print-header",0,0,2}, {"force-samples",0,0,3}, {"output",1,0,'o'}, {"output-type",1,0,'O'}, {"regions",1,0,'r'}, {"regions-file",1,0,'R'}, {"info-rules",1,0,'i'}, {0,0,0,0} }; while ((c = getopt_long(argc, argv, "hm:f:r:R:o:O:i:l:",loptions,NULL)) >= 0) { switch (c) { case 'l': args->file_list = optarg; break; case 'i': args->info_rules = optarg; break; case 'o': args->output_fname = optarg; break; case 'O': switch (optarg[0]) { case 'b': args->output_type = FT_BCF_GZ; break; case 'u': args->output_type = FT_BCF; break; case 'z': args->output_type = FT_VCF_GZ; break; case 'v': args->output_type = FT_VCF; break; default: error("The output type \"%s\" not recognised\n", optarg); } break; case 'm': args->collapse = COLLAPSE_NONE; if ( !strcmp(optarg,"snps") ) args->collapse |= COLLAPSE_SNPS; else if ( !strcmp(optarg,"indels") ) args->collapse |= COLLAPSE_INDELS; else if ( !strcmp(optarg,"both") ) args->collapse |= COLLAPSE_BOTH; else if ( !strcmp(optarg,"any") ) args->collapse |= COLLAPSE_ANY; else if ( !strcmp(optarg,"all") ) args->collapse |= COLLAPSE_ANY; else if ( !strcmp(optarg,"none") ) args->collapse = COLLAPSE_NONE; else if ( !strcmp(optarg,"id") ) { args->collapse = COLLAPSE_NONE; args->merge_by_id = 1; } else error("The -m type \"%s\" is not recognised.\n", optarg); break; case 'f': args->files->apply_filters = optarg; break; case 'r': args->regions_list = optarg; break; case 'R': args->regions_list = optarg; regions_is_file = 1; break; case 1 : args->header_fname = optarg; break; case 2 : args->header_only = 1; break; case 3 : args->force_samples = 1; break; case 'h': case '?': usage(); default: error("Unknown argument: %s\n", optarg); } } if ( argc==optind && !args->file_list ) usage(); if ( argc-optind<2 && !args->file_list ) usage(); args->files->require_index = 1; if ( args->regions_list && bcf_sr_set_regions(args->files, args->regions_list, regions_is_file)<0 ) error("Failed to read the regions: %s\n", args->regions_list); while (optindfiles, argv[optind]) ) error("Failed to open %s: %s\n", argv[optind],bcf_sr_strerror(args->files->errnum)); optind++; } if ( args->file_list ) { int nfiles, i; char **files = hts_readlines(args->file_list, &nfiles); if ( !files ) error("Failed to read from %s\n", args->file_list); for (i=0;ifiles, files[i]) ) error("Failed to open %s: %s\n", files[i],bcf_sr_strerror(args->files->errnum)); for (i=0; ifiles); free(args); return 0; }