/* vcfmerge.c -- Merge multiple VCF/BCF files to create one multi-sample file. Copyright (C) 2012-2023 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 #include #include #include #include #include #include #include "bcftools.h" #include "regidx.h" #include "vcmp.h" #define DBG 0 #define COLLAPSE_SNP_INS_DEL (1<<10) #include KHASH_MAP_INIT_STR(strdict, int) typedef khash_t(strdict) strdict_t; #define FLT_LOGIC_ADD 0 #define FLT_LOGIC_REMOVE 1 #define SKIP_DONE 1 // the record was processed #define SKIP_DIFF 2 // not compatible, merge later #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) #define SWAP(type_t,a,b) { type_t tmp = (a); (a) = (b); (b) = tmp; } #define PL2PROB_MAX 1024 // Rules for merging FORMAT Number=A,G,R vectors with missing values #define MERGE_MISSING_DOT 0 // leave as is, i.e. use a missing value "." #define MERGE_MISSING_CONST 1 // use a constant value #define MERGE_MISSING_MAX 2 // use the existing maximum value typedef struct _missing_rule_t { char *hdr_tag; int type; float value; } missing_rule_t; // 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 type_size; // size of the corresponding BCF_HT_* type 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; typedef struct { bcf1_t *line; int end, active; // end: 0-based INFO/END } gvcf_aux_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 array of output alleles (set by merge_alleles) int mmap; // size of map array (only buffer[i].n_allele is actually used) int als_differ; int var_types; // variant types in this record, shifted by <<1 to account for VCF_REF } maux1_t; // Buffered lines for a single reader typedef struct { int rid; // current rid int beg,end; // valid ranges in reader's buffer [beg,end). Maintained by maux_reset and gvcf_flush. int unkn_allele;// the index of the unknown allele (<*>, ) int cur; // current line or -1 if none int mrec; // allocated size of buf maux1_t *rec; // buffer to keep reader's lines bcf1_t **lines; // source buffer: either gvcf or readers' buffer int var_types; // reader's variant types in the active [beg,end] window } buffer_t; typedef struct { int n, pos, var_types; // number of readers; current position; variant types at this position across all available records int *als_types, // allele type of each output allele mals_types; char *chr; // current chromosome 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 *smpl_ploidy, *smpl_nGsize; // ploidy and derived number of values in Number=G tags, updated for each line (todo: cache for missing cases) const char **fmt_key;// temporary short-lived array to store output tag names 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, from src idxs to dst file idxs void *tmp_arr; size_t ntmp_arr; buffer_t *buf; AGR_info_t *AGR_info; int nAGR_info, mAGR_info; bcf_srs_t *files; int gvcf_min, // min buffered gvcf END position (NB: gvcf_min is 1-based) or 0 if no active lines are present gvcf_break; // 0-based position of a next record which breaks a gVCF block gvcf_aux_t *gvcf; // buffer of gVCF lines, for each reader one line int nout_smpl; kstring_t *str; int32_t *laa; // localized alternate alleles given as input-based indexes in per-sample blocks of (args->local_alleles+1) values, 0 is always first int nlaa, laa_dirty; // number of LAA alleles actually used at this site, and was any L* added? int32_t *tmpi, *k2k; double *tmpd, *pl2prob; // mapping from phred-score likelihoods (PL) to probability int ntmpi, ntmpd, nk2k; } maux_t; typedef struct { vcmp_t *vcmp; maux_t *maux; regidx_t *regs; // apply regions only after the blocks are expanded regitr_t *regs_itr; int header_only, collapse, output_type, force_samples, merge_by_id, do_gvcf, filter_logic, missing_to_ref, no_index; char *header_fname, *output_fname, *regions_list, *info_rules, *file_list; faidx_t *gvcf_fai; info_rule_t *rules; int nrules; char *missing_rules_str; missing_rule_t *missing_rules; // lookup for -M, --missing-rules int nmissing_rules; 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, n_threads, record_cmd_line, clevel; int local_alleles; // the value of -L option int keep_AC_AN; char *index_fn; int write_index; int trim_star_allele; // 0=don't trim; 1=trim at variant sites; 2=trim at all sites } args_t; static bcf1_t *maux_get_line(args_t *args, int i) { maux_t *ma = args->maux; int ibuf = ma->buf[i].cur; if ( ibuf >= 0 ) return ma->buf[i].lines[ibuf]; return NULL; } 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 { int isrc, idst = 0; #define BRANCH(type_t,is_missing,is_vector_end) { \ type_t *ptr = (type_t*) rule->vals; \ for (isrc=0; isrcnvals; isrc++) \ { \ if ( is_vector_end ) break; \ if ( is_missing ) continue; \ if ( idst!=isrc ) ptr[idst] = ptr[isrc]; \ idst++; \ } \ } switch (rule->type) { case BCF_HT_INT: BRANCH(int32_t, ptr[isrc]==bcf_int32_missing, ptr[isrc]==bcf_int32_vector_end); break; case BCF_HT_REAL: BRANCH(float, bcf_float_is_missing(ptr[isrc]), bcf_float_is_vector_end(ptr[isrc])); break; default: error("TODO: %s:%d .. type=%d\n", __FILE__,__LINE__, rule->type); } #undef BRANCH rule->nvals = idst; bcf_update_info(hdr,line,rule->hdr_tag,rule->vals,rule->nvals,rule->type); } } static int missing_rules_comp_key2(const void *a, const void *b) { missing_rule_t *rule1 = (missing_rule_t*) a; missing_rule_t *rule2 = (missing_rule_t*) b; return strcmp(rule1->hdr_tag, rule2->hdr_tag); } static int missing_rules_comp_key(const void *a, const void *b) { char *key = (char*) a; missing_rule_t *rule = (missing_rule_t*) b; return strcmp(key, rule->hdr_tag); } static void missing_rules_init(args_t *args) { kstring_t str = {0,0,0}; if ( args->missing_rules_str ) { if ( !strcmp("-",args->missing_rules_str) ) kputs("PL:.,AD:.",&str); else kputs(args->missing_rules_str,&str); } else if ( args->do_gvcf ) kputs("PL:max,AD:0",&str); else return; args->nmissing_rules = 1; char *ss = str.s, *tmp = ss; int n = 0; while ( *ss ) { if ( *ss==':' ) { *ss = 0; n++; if ( n%2==0 ) error("Could not parse --missing-rules: \"%s\"\n", args->missing_rules_str); } else if ( *ss==',' ) { *ss = 0; args->nmissing_rules++; n++; if ( n%2==1 ) error("Could not parse --missing-rules: \"%s\"\n", args->missing_rules_str); } ss++; } if ( n%2==0 ) error("Could not parse --missing-rules: \"%s\"\n", args->missing_rules_str); args->missing_rules = (missing_rule_t*) calloc(args->nmissing_rules,sizeof(missing_rule_t)); n = args->nmissing_rules; args->nmissing_rules = 0; ss = tmp; while ( args->nmissing_rules < n ) { missing_rule_t *rule = &args->missing_rules[args->nmissing_rules]; 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_FMT,id) ) { if ( args->missing_rules_str ) error("The FORMAT tag is not defined in the header: \"%s\"\n", rule->hdr_tag); free(rule->hdr_tag); n--; ss = strchr(ss, '\0'); ss++; if ( !*ss ) error("Could not parse --missing-rules, missing logic of \"%s\"\n", rule->hdr_tag); ss = strchr(ss, '\0'); ss++; continue; } ss = strchr(ss, '\0'); ss++; if ( !*ss ) error("Could not parse --missing-rules, missing logic of \"%s\"\n", rule->hdr_tag); if ( !strcasecmp(ss,".") ) rule->type = MERGE_MISSING_DOT; else if ( !strcasecmp(ss,"max") ) rule->type = MERGE_MISSING_MAX; else { char *tmp = ss; rule->value = strtod(ss, &tmp); if ( *tmp ) error("Could not parse --missing-rules: \"%s\"\n", args->missing_rules_str); rule->type = MERGE_MISSING_CONST; } ss = strchr(ss, '\0'); ss++; args->nmissing_rules++; } qsort(args->missing_rules, args->nmissing_rules, sizeof(*args->missing_rules), missing_rules_comp_key2); free(str.s); } static void missing_rules_destroy(args_t *args) { int i; for (i=0; inmissing_rules; i++) { missing_rule_t *rule = &args->missing_rules[i]; free(rule->hdr_tag); } free(args->missing_rules); } 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 ( args->do_gvcf && bcf_hdr_idinfo_exists(args->out_hdr,BCF_HL_INFO,bcf_hdr_id2int(args->out_hdr, BCF_DT_ID, "QS")) ) { if ( str.l ) kputc(',',&str); kputs("QS:sum",&str); } if ( args->do_gvcf && bcf_hdr_idinfo_exists(args->out_hdr,BCF_HL_INFO,bcf_hdr_id2int(args->out_hdr, BCF_DT_ID, "MIN_DP")) ) { if ( str.l ) kputc(',',&str); kputs("MIN_DP:min",&str); } if ( args->do_gvcf && bcf_hdr_idinfo_exists(args->out_hdr,BCF_HL_INFO,bcf_hdr_id2int(args->out_hdr, BCF_DT_ID, "MinDP")) ) { if ( str.l ) kputc(',',&str); kputs("MinDP:min",&str); } if ( args->do_gvcf && bcf_hdr_idinfo_exists(args->out_hdr,BCF_HL_INFO,bcf_hdr_id2int(args->out_hdr, BCF_DT_ID, "I16")) ) { if ( str.l ) kputc(',',&str); kputs("I16:sum",&str); } if ( args->do_gvcf && bcf_hdr_idinfo_exists(args->out_hdr,BCF_HL_INFO,bcf_hdr_id2int(args->out_hdr, BCF_DT_ID, "IDV")) ) { if ( str.l ) kputc(',',&str); kputs("IDV:max",&str); } if ( args->do_gvcf && bcf_hdr_idinfo_exists(args->out_hdr,BCF_HL_INFO,bcf_hdr_id2int(args->out_hdr, BCF_DT_ID, "IMF")) ) { if ( str.l ) kputc(',',&str); kputs("IMF:max",&str); } if ( !bcf_hdr_nsamples(args->out_hdr) ) { if ( bcf_hdr_idinfo_exists(args->out_hdr,BCF_HL_INFO,bcf_hdr_id2int(args->out_hdr, BCF_DT_ID, "AN")) ) { if ( str.l ) kputc(',',&str); kputs("AN:sum",&str); } if ( bcf_hdr_idinfo_exists(args->out_hdr,BCF_HL_INFO,bcf_hdr_id2int(args->out_hdr, BCF_DT_ID, "AC")) ) { if ( str.l ) kputc(',',&str); kputs("AC: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 INFO 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_size = sizeof(int32_t); else if ( rule->type==BCF_HT_REAL ) rule->type_size = sizeof(float); else if ( rule->type==BCF_HT_STR ) rule->type_size = sizeof(char); else error("The INFO rule \"%s\" is not supported; the tag \"%s\" type is %d\n", ss,rule->hdr_tag,rule->type); if ( !strcmp(rule->hdr_tag,"AC") || !strcmp(rule->hdr_tag,"AN") ) args->keep_AC_AN = 1; ss = strchr(ss, '\0'); 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 && bcf_hdr_id2length(args->out_hdr,BCF_HL_INFO,id)!=BCF_VL_VAR ) { bcf_hrec_t *hrec = bcf_hdr_get_hrec(args->out_hdr, BCF_HL_INFO, "ID", rule->hdr_tag, NULL); hrec = bcf_hrec_dup(hrec); int i = bcf_hrec_find_key(hrec, "Number"); if ( i<0 ) error("Uh, could not find the entry Number in the header record of %s\n",rule->hdr_tag); free(hrec->vals[i]); hrec->vals[i] = strdup("."); bcf_hdr_remove(args->out_hdr,BCF_HL_INFO, rule->hdr_tag); bcf_hdr_add_hrec(args->out_hdr, hrec); } if ( !is_join && !is_agr ) error("Only fixed-length vectors are supported with -i %s:%s\n", ss, rule->hdr_tag); } ss = strchr(ss, '\0'); 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 msize = args->maux->ntmp_arr / rule->type_size; int ret = bcf_get_info_values(hdr, line, rule->hdr_tag, &args->maux->tmp_arr, &msize, rule->type); if ( ret<=0 ) error("FIXME: error parsing %s at %s:%"PRId64" .. %d\n", rule->hdr_tag,bcf_seqname(hdr,line),(int64_t) line->pos+1,ret); args->maux->ntmp_arr = msize * rule->type_size; 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 ) { if ( ret!=line->n_allele-1 ) error("Wrong number of %s fields at %s:%"PRId64"\n",rule->hdr_tag,bcf_seqname(hdr,line),(int64_t) line->pos+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 ) { if ( ret!=line->n_allele ) error("Wrong number of %s fields at %s:%"PRId64"\n",rule->hdr_tag,bcf_seqname(hdr,line),(int64_t) line->pos+1); 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; if ( ret!=line->n_allele && ret!=args->maux->nagr_map ) error("Wrong number of %s fields at %s:%"PRId64"\n",rule->hdr_tag,bcf_seqname(hdr,line),(int64_t) line->pos+1); 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:%"PRId64"\n", rule->hdr_tag,bcf_seqname(hdr,line),(int64_t) 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 merge_headers(bcf_hdr_t *hw, const bcf_hdr_t *hr, const char *clash_prefix, int force_samples) { // header lines hw = bcf_hdr_merge(hw, hr); // samples int i; for (i=0; isamples[i]; while ( 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); // Resolve conflicting samples names. For example, replace: // A + A with A,2:A // A,2:A + A with A,2:A,2:2:A int len = strlen(name) + strlen(clash_prefix) + 1; char *tmp = (char*) malloc(sizeof(char)*(len+1)); sprintf(tmp,"%s:%s",clash_prefix,name); free(rmme); rmme = name = tmp; } bcf_hdr_add_sample(hw,name); free(rmme); } } 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++) { if ( b[i][0]=='<' ) continue; // symbolic allele, do not modify if ( b[i][0]=='*' ) continue; // overlapping deletion (*), do not modify 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[i][0]!='<' && a[i][0]!='*' ) // $a alleles need expanding and not a symbolic allele or * { 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); const_ai = 0; } else ai = a[i]; for (j=1; j<*nb; j++) if ( !strcasecmp(ai,b[j]) ) break; if ( j<*nb ) // $b already has the same allele { map[i] = j; if ( !const_ai ) free(ai); continue; } // new allele map[i] = *nb; b[*nb] = const_ai ? strdup(ai) : ai; (*nb)++; } return b; } maux_t *maux_init(args_t *args) { bcf_srs_t *files = args->files; maux_t *ma = (maux_t*) calloc(1,sizeof(maux_t)); ma->n = files->nreaders; ma->files = files; int i, n_smpl = 0; for (i=0; in; i++) n_smpl += bcf_hdr_nsamples(files->readers[i].header); ma->nout_smpl = n_smpl; assert( n_smpl==bcf_hdr_nsamples(args->out_hdr) ); if ( args->do_gvcf ) { ma->gvcf = (gvcf_aux_t*) calloc(ma->n,sizeof(gvcf_aux_t)); // -Walloc-size-larger-than gives a harmless warning caused by signed integer ma->n for (i=0; in; i++) ma->gvcf[i].line = bcf_init1(); } ma->smpl_ploidy = (int*) calloc(n_smpl,sizeof(int)); ma->smpl_nGsize = (int*) malloc(n_smpl*sizeof(int)); ma->buf = (buffer_t*) calloc(ma->n,sizeof(buffer_t)); for (i=0; in; i++) ma->buf[i].rid = -1; ma->str = (kstring_t*) calloc(n_smpl,sizeof(kstring_t)); if ( args->local_alleles ) { ma->laa = (int32_t*)malloc(sizeof(*ma->laa)*ma->nout_smpl*(1+args->local_alleles)); ma->pl2prob = (double*)malloc(PL2PROB_MAX*sizeof(*ma->pl2prob)); for (i=0; ipl2prob[i] = pow(10,-0.1*i); } return ma; } void maux_destroy(maux_t *ma) { int i,j; for (i=0; inout_smpl; i++) free(ma->str[i].s); free(ma->str); free(ma->als_types); for (i=0; imals; i++) { free(ma->als[i]); ma->als[i] = NULL; } for (i=0; in; i++) // for each reader { for (j=0; jbuf[i].mrec; j++) // for each buffered line free(ma->buf[i].rec[j].map); free(ma->buf[i].rec); } free(ma->buf); if ( ma->gvcf ) { for (i=0; in; i++) bcf_destroy(ma->gvcf[i].line); free(ma->gvcf); } 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); free(ma->fmt_key); // ma->inf freed in bcf_destroy1 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->chr); free(ma->laa); free(ma->tmpi); free(ma->k2k); free(ma->tmpd); free(ma->pl2prob); free(ma); } void maux_expand1(buffer_t *buf, int size) { if ( buf->mrec < size ) { hts_expand0(maux1_t,size,buf->mrec,buf->rec); buf->mrec = size; } } void maux_reset(maux_t *ma, int *rid_tab) { int i,j; for (i=0; in; i++) maux_expand1(&ma->buf[i],ma->files->readers[i].nbuffer+1); for (i=0; imals; i++) { free(ma->als[i]); ma->als[i] = NULL; } const char *chr = NULL; ma->nals = 0; ma->pos = -1; for (i=0; in; i++) { if ( !bcf_sr_has_line(ma->files,i) ) continue; bcf1_t *line = bcf_sr_get_line(ma->files,i); bcf_hdr_t *hdr = bcf_sr_get_header(ma->files,i); chr = bcf_seqname(hdr,line); ma->pos = line->pos; break; } int new_chr = 0; if ( chr && (!ma->chr || strcmp(ma->chr,chr)) ) { free(ma->chr); ma->chr = strdup(chr); new_chr = 1; } for (i=0; in; i++) { bcf_hdr_t *hdr = bcf_sr_get_header(ma->files,i); if (new_chr) rid_tab[i] = bcf_hdr_name2id(hdr,chr); ma->buf[i].rid = rid_tab[i]; ma->buf[i].beg = bcf_sr_has_line(ma->files,i) ? 0 : 1; for (j=ma->buf[i].beg; j<=ma->files->readers[i].nbuffer; j++) { ma->buf[i].rec[j].skip = 0; ma->buf[i].rec[j].var_types = 0; bcf1_t *line = ma->files->readers[i].buffer[j]; if ( line->rid!=ma->buf[i].rid || line->pos!=ma->pos ) break; } ma->buf[i].end = j; ma->buf[i].cur = -1; if ( ma->buf[i].beg < ma->buf[i].end ) { ma->buf[i].lines = ma->files->readers[i].buffer; if ( ma->gvcf ) ma->gvcf[i].active = 0; // gvcf block cannot overlap with the next record } if ( new_chr && ma->gvcf ) ma->gvcf[i].active = 0; // make sure to close active gvcf block on new chr } } 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++) { bcf1_t *line = maux_get_line(args, i); if ( !line ) continue; bcf_unpack(line, BCF_UN_ALL); bcf_sr_t *reader = &files->readers[i]; bcf_hdr_t *hdr = reader->header; // not all maux alleles are always used, mark the ones we'll need int j; for (j=1; jn_allele; j++) { int irec = ma->buf[i].cur; al_idxs[ ma->buf[i].rec[irec].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(line->qual) ) { if ( bcf_float_is_missing(out->qual) || out->qual < line->qual ) out->qual = line->qual; } } // set ID if ( !tmps->l ) kputs(".", tmps); bcf_update_id(out_hdr, out, 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++) { ma->buf[ir].unkn_allele = 0; bcf1_t *line = maux_get_line(args,ir); if ( !line ) continue; for (j=1; jn_allele; j++) { int irec = ma->buf[ir].cur; if ( ma->buf[ir].rec[irec].map[j]==i ) ma->buf[ir].rec[irec].map[j] = ma->nout_als; if ( bcf_has_variant_type(line,j,VCF_REF) && line->d.allele[j][0]=='<' ) ma->buf[ir].unkn_allele = j; } } } // 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]); if ( k!=ma->nout_als ) error("Error: could not merge alleles at %s:%"PRId64", sanity check failed: %d!=%d\n",bcf_seqname(out_hdr,out),out->pos+1,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; if ( args->filter_logic == FLT_LOGIC_REMOVE ) { for (i=0; inreaders; i++) { bcf1_t *line = maux_get_line(args, i); if ( !line ) continue; bcf_sr_t *reader = &files->readers[i]; bcf_hdr_t *hdr = reader->header; if ( bcf_has_filter(hdr, line, "PASS") ) break; } if ( inreaders ) { int flt_id = bcf_hdr_id2int(out_hdr, BCF_DT_ID, "PASS"); bcf_add_filter(out_hdr, out, flt_id); return; } } khiter_t kitr; strdict_t *tmph = args->tmph; kh_clear(strdict, tmph); out->d.n_flt = 0; for (i=0; inreaders; i++) { bcf1_t *line = maux_get_line(args, i); if ( !line ) continue; bcf_sr_t *reader = &files->readers[i]; bcf_hdr_t *hdr = reader->header; 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("Error: The filter is not defined in the header: %s\n", flt); hts_expand(int,out->d.n_flt+1,out->d.m_flt,out->d.flt); out->d.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 ( out->d.flt[i]==id ) break; if ( id.n_flt ) { out->d.n_flt--; for (; id.n_flt; i++) out->d.flt[i] = out->d.flt[i+1]; } } } static void bcf_info_set_id(bcf1_t *line, bcf_info_t *info, int id, kstring_t *tmp_str) { 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; 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 with missing values, e.g. as ".") * @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 %"PRId64"\n", info->type,agr->hdr_tag,(int64_t) 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, convert, is_missing, is_vector_end, out_type_t) { \ uint8_t *src = info->vptr; \ out_type_t *tgt = (out_type_t *) agr->buf; \ int iori, inew; \ for (iori=ifrom; iorin_allele; iori++, src += sizeof(type_t)) \ { \ type_t val = convert(src); \ if ( is_vector_end ) break; \ if ( is_missing ) continue; \ inew = als->map[iori] - ifrom; \ tgt[inew] = val; \ } \ } switch (info->type) { case BCF_BT_INT8: BRANCH(int8_t, le_to_i8, val==bcf_int8_missing, val==bcf_int8_vector_end, int); break; case BCF_BT_INT16: BRANCH(int16_t, le_to_i16, val==bcf_int16_missing, val==bcf_int16_vector_end, int); break; case BCF_BT_INT32: BRANCH(int32_t, le_to_i32, val==bcf_int32_missing, val==bcf_int32_vector_end, int); break; case BCF_BT_FLOAT: BRANCH(float, le_to_float, bcf_float_is_missing(val), bcf_float_is_vector_end(val), 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, convert, is_missing, is_vector_end, out_type_t) { \ uint8_t *src = 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; \ type_t val = convert(&src[kori * sizeof(type_t)]); \ 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] = val; \ } \ if ( jori<=iori ) break; \ } \ } switch (info->type) { case BCF_BT_INT8: BRANCH(int8_t, le_to_i8, val==bcf_int8_missing, val==bcf_int8_vector_end, int); break; case BCF_BT_INT16: BRANCH(int16_t, le_to_i16, val==bcf_int16_missing, val==bcf_int16_vector_end, int); break; case BCF_BT_INT32: BRANCH(int32_t, le_to_i32, val==bcf_int32_missing, val==bcf_int32_vector_end, int); break; case BCF_BT_FLOAT: BRANCH(float, le_to_float, bcf_float_is_missing(val), bcf_float_is_vector_end(val), 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:%"PRId64": wrong number of fields in %s?\n", bcf_seqname(hdr,line),(int64_t) 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:%"PRId64": wrong number of fields in %s?\n", bcf_seqname(hdr,line),(int64_t) 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++) { bcf1_t *line = maux_get_line(args,i); if ( !line ) continue; int irec = ma->buf[i].cur; bcf_sr_t *reader = &files->readers[i]; 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; // AC and AN are done in merge_format() after genotypes are done if (!args->keep_AC_AN && (key[0] == 'A' && (key[1] == 'C' || key[1] == 'N') && key[2] == 0)) continue; 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->buf[i].rec[irec] : 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) ) { // seeing this key for the first time 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:%"PRId64"\n", key,bcf_seqname(hdr,line),(int64_t) line->pos+1); merge_AGR_info_tag(hdr, line,inf,len,&ma->buf[i].rec[irec],&ma->AGR_info[idx]); continue; } if ( kitr == kh_end(tmph) ) { // Seeing this key for the first time. Although quite hacky, // this is faster than anything else given the data structures.. hts_expand0(bcf_info_t,out->n_info+1,out->d.m_info,out->d.info); out->d.info[out->n_info].key = id; out->d.info[out->n_info].type = inf->type; out->d.info[out->n_info].len = inf->len; out->d.info[out->n_info].v1.i = inf->v1.i; out->d.info[out->n_info].v1.f = inf->v1.f; out->d.info[out->n_info].vptr_off = inf->vptr_off; out->d.info[out->n_info].vptr_len = inf->vptr_len; out->d.info[out->n_info].vptr_free = 1; out->d.info[out->n_info].vptr = (uint8_t*) malloc(inf->vptr_len+inf->vptr_off); memcpy(out->d.info[out->n_info].vptr,inf->vptr-inf->vptr_off, inf->vptr_len+inf->vptr_off); out->d.info[out->n_info].vptr += inf->vptr_off; if ( (args->output_type & FT_BCF) && id!=bcf_hdr_id2int(hdr, BCF_DT_ID, key) ) bcf_info_set_id(out, &out->d.info[out->n_info], id, &args->tmps); out->d.shared_dirty |= BCF1_DIRTY_INF; out->n_info++; kitr = kh_put(strdict, tmph, key, &ret); kh_val(tmph,kitr) = -(out->n_info-1); // arbitrary negative value } } } 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); } static inline int max_used_gt_ploidy(bcf_fmt_t *fmt, int nsmpl) { int i,j, max_ploidy = 0; #define BRANCH(type_t, convert, vector_end) { \ uint8_t *ptr = fmt->p; \ for (i=0; in; j++) \ if ( convert(&ptr[j * sizeof(type_t)])==vector_end ) break; \ if ( j==fmt->n ) \ { \ /* all fields were used */ \ if ( max_ploidy < j ) max_ploidy = j; \ break; \ } \ if ( max_ploidy < j ) max_ploidy = j; \ ptr += fmt->n * sizeof(type_t); \ } \ } switch (fmt->type) { case BCF_BT_INT8: BRANCH(int8_t, le_to_i8, bcf_int8_vector_end); break; case BCF_BT_INT16: BRANCH(int16_t, le_to_i16, bcf_int16_vector_end); break; case BCF_BT_INT32: BRANCH(int32_t, le_to_i32, bcf_int32_vector_end); break; default: error("Unexpected case: %d\n", fmt->type); } #undef BRANCH return max_ploidy; } // Sets ma->laa to local indexes relevant for each sample or missing/vector_end. // The indexes are with respect to the source indexes and must be translated as // the very last step. void init_local_alleles(args_t *args, bcf1_t *out, int ifmt_PL) { bcf_srs_t *files = args->files; maux_t *ma = args->maux; int i,j,k,l, ismpl = 0, nlaa = 0; static int warned = 0; hts_expand(double,out->n_allele,ma->ntmpd,ma->tmpd); // allele probabilities hts_expand(int,out->n_allele,ma->ntmpi,ma->tmpi); // indexes of the sorted probabilities // Let map[] be the mapping from src to output idx. Then k2k[] is mapping from src allele idxs to src allele idxs // reordered so that if in_allele,ma->nk2k,ma->k2k); // Determine local alleles: either take all that are present in the reader or use PL to determine the best // subset for each sample. The alleles must be listed in the order of the alleles in the output file. for (i=0; inreaders; i++) { bcf_sr_t *reader = &files->readers[i]; bcf_hdr_t *hdr = reader->header; bcf_fmt_t *fmt_ori = ma->fmt_map[files->nreaders*ifmt_PL+i]; bcf1_t *line = maux_get_line(args, i); int nsmpl = bcf_hdr_nsamples(hdr); if ( line ) { if ( nlaa < line->n_allele - 1 ) nlaa = line->n_allele - 1 <= args->local_alleles ? line->n_allele - 1 : args->local_alleles; for (j=0; jn_allele; j++) ma->k2k[j] = j; if ( line->n_allele <= args->local_alleles + 1 ) { // sort to the output order, insertion sort, ascending int *map = ma->buf[i].rec[ma->buf[i].cur].map; int *k2k = ma->k2k; int tmp; for (k=1; kn_allele; k++) for (l=k; l>0 && map[k2k[l]] < map[k2k[l-1]]; l--) tmp = k2k[l], k2k[l] = k2k[l-1], k2k[l-1] = tmp; // fewer than the allowed number of alleles, use all alleles from this file for (j=0; jlaa + (1+args->local_alleles)*ismpl; for (k=0; kn_allele; k++) ptr[k] = k2k[k]; for (; k<=args->local_alleles; k++) ptr[k] = bcf_int32_vector_end; ismpl++; } continue; } } if ( !line || !fmt_ori ) { // no values, fill in missing values for (j=0; jlaa + (1+args->local_alleles)*ismpl; ptr[0] = bcf_int32_missing; for (k=1; k<=args->local_alleles; k++) ptr[k] = bcf_int32_vector_end; ismpl++; } continue; } // there are more alternate alleles in the input files than is allowed on output, need to subset if ( ifmt_PL==-1 ) { if ( !warned ) fprintf(stderr,"Warning: local alleles are determined from FORMAT/PL but the tag is missing, cannot apply --local-alleles\n"); warned = 1; ma->nlaa = 0; return; } if ( !IS_VL_G(hdr, fmt_ori->id) ) error("FORMAT/PL must be defined as Number=G\n"); if ( 2*fmt_ori->n != line->n_allele*(line->n_allele+1) ) error("Todo: haploid PL to LPL\n"); int *map = ma->buf[i].rec[ma->buf[i].cur].map; double *allele_prob = ma->tmpd; int *idx = ma->tmpi; #define BRANCH(src_type_t, convert, src_is_missing, src_is_vector_end, pl2prob_idx) { \ uint8_t *src = fmt_ori->p; \ for (j=0; jn_allele; k++) allele_prob[k] = 0; \ for (k=0; kn_allele; k++) \ for (l=0; l<=k; l++) \ { \ src_type_t val = convert(src); \ if ( !(src_is_missing) && !(src_is_vector_end) ) \ { \ double prob = ma->pl2prob[pl2prob_idx]; \ allele_prob[k] += prob; \ allele_prob[l] += prob; \ } \ src += sizeof(src_type_t); \ } \ /* insertion sort by allele probability, descending order, with the twist that REF (idx=0) always comes first */ \ allele_prob++; idx[0] = -1; idx++; /* keep REF first */ \ int si,sj,tmp; \ for (si=0; sin_allele-1; si++) idx[si] = si; \ for (si=1; sin_allele-1; si++) \ for (sj=si; sj>0 && allele_prob[idx[sj]] > allele_prob[idx[sj-1]]; sj--) \ tmp = idx[sj], idx[sj] = idx[sj-1], idx[sj-1] = tmp; \ /*for debugging only: test order*/ \ for (si=1; sin_allele-1; si++) \ assert( allele_prob[idx[si-1]] >= allele_prob[idx[si]] ); \ allele_prob--; idx--; /* this was to keep REF first */ \ int32_t *ptr = ma->laa + (1+args->local_alleles)*ismpl; \ ptr[0] = 0; \ for (k=1; k<=args->local_alleles && kn_allele; k++) ptr[k] = idx[k]+1; \ int kmax = k; \ for (; k<=args->local_alleles; k++) ptr[k] = bcf_int32_vector_end; \ /* insertion sort by indexes to the output order, ascending */ \ for (k=1; k0 && map[ptr[l]] < map[ptr[l-1]]; l--) \ tmp = ptr[l], ptr[l] = ptr[l-1], ptr[l-1] = tmp; \ ismpl++; \ } \ } switch (fmt_ori->type) { case BCF_BT_INT8: BRANCH( int8_t, le_to_i8, val==bcf_int8_missing, val==bcf_int8_vector_end, val); break; case BCF_BT_INT16: BRANCH(int16_t, le_to_i16, val==bcf_int16_missing, val==bcf_int16_vector_end, val>=0 && val=0 && valtype); } #undef BRANCH } ma->nlaa = nlaa; } void update_local_alleles(args_t *args, bcf1_t *out) { bcf_srs_t *files = args->files; maux_t *ma = args->maux; int i,j,k,ismpl=0,nsamples = bcf_hdr_nsamples(args->out_hdr); for (i=0; inreaders; i++) { int irec = ma->buf[i].cur; bcf_sr_t *reader = &files->readers[i]; int nsmpl = bcf_hdr_nsamples(reader->header); for (k=0; klaa + ismpl*(1+args->local_alleles); int32_t *dst = ma->laa + ismpl*ma->nlaa; j = 0; if ( irec>=0 ) { for (; jnlaa; j++) { if ( src[j+1]==bcf_int32_missing ) dst[j] = bcf_int32_missing; else if ( src[j+1]==bcf_int32_vector_end ) break; else dst[j] = ma->buf[i].rec[irec].map[src[j+1]]; } } if ( j==0 ) dst[j++] = bcf_int32_missing; for (; jnlaa; j++) src[j] = bcf_int32_vector_end; ismpl++; } } bcf_update_format_int32(args->out_hdr, out, "LAA", ma->laa, nsamples*ma->nlaa); } 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); static int warned = 0; int nsize = 0; for (i=0; inreaders; i++) { bcf_fmt_t *fmt = fmt_map[i]; if ( !fmt ) continue; int pld = max_used_gt_ploidy(fmt_map[i], bcf_hdr_nsamples(bcf_sr_get_header(args->files,i))); if ( nsize < pld ) nsize = pld; } if ( nsize==0 ) nsize = 1; size_t msize = sizeof(int32_t)*nsize*nsamples; if ( msize > 2147483647 ) { if ( !warned ) fprintf(stderr,"Warning: Too many genotypes at %s:%"PRId64", requires %zu bytes, skipping.\n", bcf_seqname(out_hdr,out),(int64_t) out->pos+1,msize); warned = 1; return; } if ( ma->ntmp_arr < msize ) { ma->tmp_arr = realloc(ma->tmp_arr, msize); if ( !ma->tmp_arr ) error("Could not allocate %zu bytes\n",msize); ma->ntmp_arr = msize; } memset(ma->smpl_ploidy,0,nsamples*sizeof(int)); int default_gt = args->missing_to_ref ? bcf_gt_unphased(0) : bcf_gt_missing; 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 irec = ma->buf[i].cur; 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, convert, vector_end) { \ uint8_t *p_ori = fmt_ori->p; \ if ( !ma->buf[i].rec[irec].als_differ ) \ { \ /* the allele numbering is unchanged */ \ for (j=0; jn; k++) \ { \ type_t val = convert(&p_ori[k * sizeof(type_t)]); \ if ( val==vector_end ) break; /* smaller ploidy */ \ ma->smpl_ploidy[ismpl+j]++; \ if ( bcf_gt_is_missing(val) ) tmp[k] = 0; /* missing allele */ \ else tmp[k] = val; \ } \ for (; kn * sizeof(type_t); \ } \ ismpl += bcf_hdr_nsamples(hdr); \ continue; \ } \ /* allele numbering needs to be changed */ \ for (j=0; jn; k++) \ { \ type_t val = convert(&p_ori[k * sizeof(type_t)]); \ if ( val==vector_end ) break; /* smaller ploidy */ \ ma->smpl_ploidy[ismpl+j]++; \ if ( bcf_gt_is_missing(val) ) tmp[k] = 0; /* missing allele */ \ else \ { \ int al = (val>>1) - 1; \ al = al<=0 ? al + 1 : ma->buf[i].rec[irec].map[al] + 1; \ tmp[k] = (al << 1) | ((val)&1); \ } \ } \ for (; kn * sizeof(type_t); \ } \ ismpl += bcf_hdr_nsamples(hdr); \ } switch (fmt_ori->type) { case BCF_BT_INT8: BRANCH(int8_t, le_to_i8, bcf_int8_vector_end); break; case BCF_BT_INT16: BRANCH(int16_t, le_to_i16, bcf_int16_vector_end); break; case BCF_BT_INT32: BRANCH(int32_t, le_to_i32, 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_string(args_t *args, const char *key, bcf_fmt_t **fmt_map, bcf1_t *out, int length, int nsize) { bcf_srs_t *files = args->files; bcf_hdr_t *out_hdr = args->out_hdr; maux_t *ma = args->maux; int i,j, nsamples = bcf_hdr_nsamples(out_hdr); static int warned = 0; // initialize empty strings, a dot for each value, e.g. ".,.,." int nmax = 0; for (i=0; istr[i]; if ( length==BCF_VL_FIXED || length==BCF_VL_VAR ) { str->l = 1; ks_resize(str, str->l+1); str->s[0] = '.'; } else { str->l = nsize*2 - 1; ks_resize(str, str->l+1); str->s[0] = '.'; for (j=1; js[j*2-1] = ',', str->s[j*2] = '.'; } str->s[str->l] = 0; if ( nmax < str->l ) nmax = str->l; } // fill in values for each sample int ismpl = 0; 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 ) { // the field is not present in this file ismpl += bcf_hdr_nsamples(hdr); continue; } bcf1_t *line = maux_get_line(args, i); int irec = ma->buf[i].cur; char *src = (char*) fmt_ori->p; if ( length==BCF_VL_FIXED || length==BCF_VL_VAR || (line->n_allele==out->n_allele && !ma->buf[i].rec[irec].als_differ) ) { // alleles unchanged, copy over for (j=0; jstr[ismpl++]; str->l = 0; kputsn(src, fmt_ori->n, str); if ( nmax < str->l ) nmax = str->l; src += fmt_ori->n; } continue; } // NB, what is below is not the fastest way, copy_string_field() keeps // finding the indexes repeatedly at multiallelic sites if ( length==BCF_VL_A || length==BCF_VL_R ) { int ifrom = length==BCF_VL_A ? 1 : 0; for (j=0; jstr[ismpl++]; int iori,inew; for (iori=ifrom; iorin_allele; iori++) { inew = ma->buf[i].rec[irec].map[iori] - ifrom; int ret = copy_string_field(src, iori - ifrom, fmt_ori->size, str, inew); if ( ret<-1 ) error("[E::%s] fixme: internal error at %s:%"PRId64" .. %d\n",__func__,bcf_seqname(hdr,line),(int64_t) line->pos+1,ret); } if ( nmax < str->l ) nmax = str->l; src += fmt_ori->size; } continue; } assert( length==BCF_VL_G ); error("[E::%s] Merging of Number=G FORMAT strings (in your case FORMAT/%s) is not supported yet, sorry!\n" "Please open an issue on github if this feature is essential for you. However, note that using FORMAT strings is not\n" "a good idea in general - it is slow to parse and does not compress well, it is better to use integer codes instead.\n" "If you don't really need it, use `bcftools annotate -x` to remove the annotation before merging.\n", __func__,key); } // update the record size_t msize = nsamples*nmax; if ( msize > 2147483647 ) { if ( !warned ) fprintf(stderr,"Warning: The row size is too big for FORMAT/%s at %s:%"PRId64", requires %zu bytes, skipping.\n", key,bcf_seqname(out_hdr,out),(int64_t) out->pos+1,msize); warned = 1; return; } if ( ma->ntmp_arr < msize ) { ma->tmp_arr = realloc(ma->tmp_arr, msize); if ( !ma->tmp_arr ) error("Could not allocate %zu bytes\n",msize); ma->ntmp_arr = msize; } char *tgt = (char*) ma->tmp_arr; for (i=0; istr[i].s, ma->str[i].l); if ( ma->str[i].l < nmax ) memset(tgt + ma->str[i].l, 0, nmax - ma->str[i].l); tgt += nmax; } bcf_update_format_char(out_hdr, out, key, (float*)ma->tmp_arr, nsamples*nmax); } // Note: only diploid Number=G tags only for now void merge_localized_numberG_format_field(args_t *args, bcf_fmt_t **fmt_map, bcf1_t *out, int irdr) { int i,j,k, nsamples = bcf_hdr_nsamples(args->out_hdr); bcf_srs_t *files = args->files; maux_t *ma = args->maux; bcf_fmt_t *fmt = fmt_map[irdr]; const char *key = files->readers[irdr].header->id[BCF_DT_ID][fmt_map[irdr]->id].key; size_t nsize = (ma->nlaa+1)*(ma->nlaa+2)/2; // max number of Number=G localized fields size_t msize = sizeof(float)>sizeof(int32_t) ? sizeof(float) : sizeof(int32_t); msize *= nsamples*nsize; if ( msize > 2147483647 ) { static int warned = 0; if ( !warned ) fprintf(stderr,"Warning: The row size is too big for FORMAT/%s at %s:%"PRId64", requires %zu bytes, skipping.\n", key,bcf_seqname(args->out_hdr,out),(int64_t) out->pos+1,msize); warned = 1; return; } if ( ma->ntmp_arr < msize ) { ma->tmp_arr = realloc(ma->tmp_arr, msize); if ( !ma->tmp_arr ) error("Failed to allocate %zu bytes at %s:%"PRId64" for FORMAT/%s\n", msize,bcf_seqname(args->out_hdr,out),(int64_t) out->pos+1,key); ma->ntmp_arr = msize; } int ismpl = 0; 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]; bcf1_t *line = maux_get_line(args, i); int nsmpl = bcf_hdr_nsamples(hdr); if ( !fmt_ori ) { // fill missing values #define BRANCH(tgt_type_t, tgt_set_missing, tgt_set_vector_end) { \ for (j=0; jtmp_arr + ismpl*nsize; \ tgt_set_missing; \ for (k=1; ktype) { case BCF_BT_INT8: BRANCH(int32_t, *tgt=bcf_int32_missing, *tgt=bcf_int32_vector_end); break; case BCF_BT_INT16: BRANCH(int32_t, *tgt=bcf_int32_missing, *tgt=bcf_int32_vector_end); break; case BCF_BT_INT32: BRANCH(int32_t, *tgt=bcf_int32_missing, *tgt=bcf_int32_vector_end); break; case BCF_BT_FLOAT: BRANCH(float, bcf_float_set_missing(*tgt), bcf_float_set_vector_end(*tgt)); break; default: error("Unexpected case: %d, %s\n", fmt->type, key); } #undef BRANCH continue; } if ( 2*fmt_ori->n!=line->n_allele*(line->n_allele+1) ) error("Todo: localization of missing or haploid Number=G tags\n"); // localize #define BRANCH(tgt_type_t, src_type_t, convert, src_is_missing, src_is_vector_end, tgt_set_missing, tgt_set_vector_end) { \ for (j=0; jp + sizeof(src_type_t)*j*fmt_ori->n; \ tgt_type_t *tgt = (tgt_type_t *) ma->tmp_arr + ismpl*nsize; \ int *laa = ma->laa + (1+args->local_alleles)*ismpl; \ int ii,ij,tgt_idx = 0; \ for (ii=0; ii<=ma->nlaa; ii++) \ { \ if ( laa[ii]==bcf_int32_missing || laa[ii]==bcf_int32_vector_end ) break; \ for (ij=0; ij<=ii; ij++) \ { \ int src_idx = bcf_alleles2gt(laa[ii],laa[ij]); \ src_type_t val = convert(&src[src_idx * sizeof(src_type_t)]); \ if ( src_is_missing ) tgt_set_missing; \ else if ( src_is_vector_end ) break; \ else tgt[tgt_idx] = val; \ tgt_idx++; \ } \ } \ if ( !tgt_idx ) { tgt_set_missing; tgt_idx++; } \ for (; tgt_idxtype) { case BCF_BT_INT8: BRANCH(int32_t, int8_t, le_to_i8, val==bcf_int8_missing, val==bcf_int8_vector_end, tgt[tgt_idx]=bcf_int32_missing, tgt[tgt_idx]=bcf_int32_vector_end); break; case BCF_BT_INT16: BRANCH(int32_t, int16_t, le_to_i16, val==bcf_int16_missing, val==bcf_int16_vector_end, tgt[tgt_idx]=bcf_int32_missing, tgt[tgt_idx]=bcf_int32_vector_end); break; case BCF_BT_INT32: BRANCH(int32_t, int32_t, le_to_i16, val==bcf_int32_missing, val==bcf_int32_vector_end, tgt[tgt_idx]=bcf_int32_missing, tgt[tgt_idx]=bcf_int32_vector_end); break; case BCF_BT_FLOAT: BRANCH(float, float, le_to_float, bcf_float_is_missing(val), bcf_float_is_vector_end(val), bcf_float_set_missing(tgt[tgt_idx]), bcf_float_set_vector_end(tgt[tgt_idx])); break; default: error("Unexpected case: %d, %s\n", fmt_ori->type, key); } #undef BRANCH } args->tmps.l = 0; kputc('L',&args->tmps); kputs(key,&args->tmps); if ( fmt_map[irdr]->type==BCF_BT_FLOAT ) bcf_update_format_float(args->out_hdr, out, args->tmps.s, (float*)ma->tmp_arr, nsamples*nsize); else bcf_update_format_int32(args->out_hdr, out, args->tmps.s, (int32_t*)ma->tmp_arr, nsamples*nsize); ma->laa_dirty = 1; } void merge_localized_numberAR_format_field(args_t *args, bcf_fmt_t **fmt_map, bcf1_t *out, int irdr) { int i,j,k, nsamples = bcf_hdr_nsamples(args->out_hdr); bcf_srs_t *files = args->files; maux_t *ma = args->maux; bcf_fmt_t *fmt = fmt_map[irdr]; const char *key = files->readers[irdr].header->id[BCF_DT_ID][fmt->id].key; size_t nsize = IS_VL_R(files->readers[irdr].header, fmt->id) ? ma->nlaa + 1 : ma->nlaa; size_t msize = sizeof(float)>sizeof(int32_t) ? sizeof(float) : sizeof(int32_t); msize *= nsamples*nsize; if ( msize > 2147483647 ) { static int warned = 0; if ( !warned ) fprintf(stderr,"Warning: The row size is too big for FORMAT/%s at %s:%"PRId64", requires %zu bytes, skipping.\n", key,bcf_seqname(args->out_hdr,out),(int64_t) out->pos+1,msize); warned = 1; return; } if ( ma->ntmp_arr < msize ) { ma->tmp_arr = realloc(ma->tmp_arr, msize); if ( !ma->tmp_arr ) error("Failed to allocate %zu bytes at %s:%"PRId64" for FORMAT/%s\n", msize,bcf_seqname(args->out_hdr,out),(int64_t) out->pos+1,key); ma->ntmp_arr = msize; } int ismpl = 0, ibeg = IS_VL_R(files->readers[irdr].header, fmt->id) ? 0 : 1;; 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]; int nsmpl = bcf_hdr_nsamples(hdr); if ( !fmt_ori ) { // fill missing values #define BRANCH(tgt_type_t, tgt_set_missing, tgt_set_vector_end) { \ for (j=0; jtmp_arr + ismpl*nsize; \ tgt_set_missing; \ for (k=1; ktype) { case BCF_BT_INT8: BRANCH(int32_t, *tgt=bcf_int32_missing, *tgt=bcf_int32_vector_end); break; case BCF_BT_INT16: BRANCH(int32_t, *tgt=bcf_int32_missing, *tgt=bcf_int32_vector_end); break; case BCF_BT_INT32: BRANCH(int32_t, *tgt=bcf_int32_missing, *tgt=bcf_int32_vector_end); break; case BCF_BT_FLOAT: BRANCH(float, bcf_float_set_missing(*tgt), bcf_float_set_vector_end(*tgt)); break; default: error("Unexpected case: %d, %s\n", fmt->type, key); } #undef BRANCH continue; } // localize #define BRANCH(tgt_type_t, src_type_t, convert, src_is_missing, src_is_vector_end, tgt_set_missing, tgt_set_vector_end) { \ for (j=0; jp + sizeof(src_type_t)*j*fmt_ori->n; \ tgt_type_t *tgt = (tgt_type_t *) ma->tmp_arr + ismpl*nsize; \ int *laa = ma->laa + (1+args->local_alleles)*ismpl; \ int ii,tgt_idx = 0; \ for (ii=ibeg; ii<=ma->nlaa; ii++) \ { \ if ( laa[ii]==bcf_int32_missing || laa[ii]==bcf_int32_vector_end ) break; \ int src_idx = laa[ii] - ibeg; \ src_type_t val = convert(&src[src_idx * sizeof(src_type_t)]); \ if ( src_is_missing ) tgt_set_missing; \ else if ( src_is_vector_end ) break; \ else tgt[tgt_idx] = val; \ tgt_idx++; \ } \ if ( !tgt_idx ) { tgt_set_missing; tgt_idx++; } \ for (; tgt_idxtype) { case BCF_BT_INT8: BRANCH(int32_t, int8_t, le_to_i8, val==bcf_int8_missing, val==bcf_int8_vector_end, tgt[tgt_idx]=bcf_int32_missing, tgt[tgt_idx]=bcf_int32_vector_end); break; case BCF_BT_INT16: BRANCH(int32_t, int16_t, le_to_i16, val==bcf_int16_missing, val==bcf_int16_vector_end, tgt[tgt_idx]=bcf_int32_missing, tgt[tgt_idx]=bcf_int32_vector_end); break; case BCF_BT_INT32: BRANCH(int32_t, int32_t, le_to_i32, val==bcf_int32_missing, val==bcf_int32_vector_end, tgt[tgt_idx]=bcf_int32_missing, tgt[tgt_idx]=bcf_int32_vector_end); break; case BCF_BT_FLOAT: BRANCH(float, float, le_to_float, bcf_float_is_missing(val), bcf_float_is_vector_end(val), bcf_float_set_missing(tgt[tgt_idx]), bcf_float_set_vector_end(tgt[tgt_idx])); break; default: error("Unexpected case: %d, %s\n", fmt_ori->type, key); } #undef BRANCH } args->tmps.l = 0; kputc('L',&args->tmps); kputs(key,&args->tmps); if ( fmt_map[irdr]->type==BCF_BT_FLOAT ) bcf_update_format_float(args->out_hdr, out, args->tmps.s, (float*)ma->tmp_arr, nsamples*nsize); else bcf_update_format_int32(args->out_hdr, out, args->tmps.s, (int32_t*)ma->tmp_arr, nsamples*nsize); ma->laa_dirty = 1; } void merge_format_field(args_t *args, bcf_fmt_t **fmt_map, missing_rule_t *mrule, 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); static int warned = 0; const char *key = NULL; size_t nsize = 0, length = BCF_VL_FIXED; int type = -1; for (i=0; inreaders; i++) { if ( !maux_get_line(args,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; } if ( ma->nlaa && length!=BCF_VL_FIXED ) { if ( length==BCF_VL_G ) merge_localized_numberG_format_field(args,fmt_map,out,i); else if ( length==BCF_VL_A || length==BCF_VL_R ) merge_localized_numberAR_format_field(args,fmt_map,out,i); return; } if ( type==BCF_BT_CHAR ) { merge_format_string(args, key, fmt_map, out, length, nsize); return; } size_t msize = sizeof(float)>sizeof(int32_t) ? sizeof(float) : sizeof(int32_t); msize *= nsamples*nsize; if ( msize > 2147483647 ) { if ( !warned ) fprintf(stderr,"Warning: The row size is too big for FORMAT/%s at %s:%"PRId64", requires %zu bytes, skipping.\n", key,bcf_seqname(out_hdr,out),(int64_t) out->pos+1,msize); warned = 1; return; } if ( ma->ntmp_arr < msize ) { ma->tmp_arr = realloc(ma->tmp_arr, msize); if ( !ma->tmp_arr ) error("Failed to allocate %zu bytes at %s:%"PRId64" for FORMAT/%s\n", msize,bcf_seqname(args->out_hdr,out),(int64_t) out->pos+1,key); ma->ntmp_arr = msize; } // 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]; bcf1_t *line = maux_get_line(args, i); int irec = ma->buf[i].cur; if ( fmt_ori ) { type = fmt_ori->type; int nals_ori = line->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 FORMAT/%s values at %s:%"PRId64", cannot merge. The tag is defined as Number=G, but found\n" "%d values and %d alleles. See also http://samtools.github.io/bcftools/howtos/FAQ.html#incorrect-nfields\n", key,bcf_seqname(args->out_hdr,out),(int64_t) out->pos+1,fmt_ori->n,nals_ori); } else if ( length==BCF_VL_A ) { if ( fmt_ori->n!=1 && fmt_ori->n != nals_ori-1 ) error("Incorrect number of FORMAT/%s values at %s:%"PRId64", cannot merge. The tag is defined as Number=A, but found\n" "%d values and %d alleles. See also http://samtools.github.io/bcftools/howtos/FAQ.html#incorrect-nfields\n", key,bcf_seqname(args->out_hdr,out),(int64_t) out->pos+1,fmt_ori->n,nals_ori); } else if ( length==BCF_VL_R ) { if ( fmt_ori->n!=1 && fmt_ori->n != nals_ori ) error("Incorrect number of FORMAT/%s values at %s:%"PRId64", cannot merge. The tag is defined as Number=R, but found\n" "%d values and %d alleles. See also http://samtools.github.io/bcftools/howtos/FAQ.html#incorrect-nfields\n", key,bcf_seqname(args->out_hdr,out),(int64_t) out->pos+1,fmt_ori->n,nals_ori); } } // set the values #define BRANCH(tgt_type_t, src_type_t, convert, 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; jp; \ if ( (length!=BCF_VL_G && length!=BCF_VL_A && length!=BCF_VL_R) || (line->n_allele==out->n_allele && !ma->buf[i].rec[irec].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 = convert(src); \ tgt++; src += sizeof(src_type_t); \ } \ 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 = fmt_ori->p + sizeof(src_type_t) * j * fmt_ori->n; \ int tag_missing = src_is_missing && fmt_ori->n==1; \ if (!tag_missing) \ { \ src += sizeof(src_type_t); \ tag_missing = src_is_vector_end ; \ } \ if ( tag_missing ) \ { \ /* tag with missing value "." */ \ tgt_set_missing; \ for (l=1; lsmpl_ploidy[ismpl+j]==1 ? 1 : 0; \ int ngsize = haploid ? out->n_allele : out->n_allele*(out->n_allele + 1)/2; \ if ( ma->buf[i].unkn_allele ) /* Use value from the unknown allele when available */ \ { \ src = fmt_ori->p + sizeof(src_type_t)*j*fmt_ori->n; \ int iunkn = haploid ? ma->buf[i].unkn_allele : (ma->buf[i].unkn_allele+1)*(ma->buf[i].unkn_allele + 2)/2 - 1; \ src_type_t val = convert(&src[iunkn * sizeof(src_type_t)]); \ for (l=0; ltype==MERGE_MISSING_CONST ) \ { \ for (l=0; lvalue; tgt++; } \ } \ else if ( mrule && mrule->type==MERGE_MISSING_MAX ) \ { \ src = fmt_ori->p + sizeof(src_type_t)*j*fmt_ori->n; \ src_type_t max = convert(src); \ for (l=1; ln; l++) \ { \ src_type_t val = convert(&src[l * sizeof(src_type_t)]); \ if ( max < val ) max = val; \ } \ for (l=0; ln_allele; iori++) \ { \ inew = ma->buf[i].rec[irec].map[iori]; \ src = fmt_ori->p + (j*fmt_ori->n + iori) * sizeof(src_type_t); \ 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 = convert(src); \ } \ } \ else \ { \ /* Diploid */ \ int iori,jori, inew,jnew; \ for (iori=0; iorin_allele; iori++) \ { \ inew = ma->buf[i].rec[irec].map[iori]; \ for (jori=0; jori<=iori; jori++) \ { \ jnew = ma->buf[i].rec[irec].map[jori]; \ int kori = iori*(iori+1)/2 + jori; \ int knew = inew>jnew ? inew*(inew+1)/2 + jnew : jnew*(jnew+1)/2 + inew; \ src = fmt_ori->p + (j*fmt_ori->n + kori) * sizeof(src_type_t); \ 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 = convert(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 = fmt_ori->p + sizeof(src_type_t) * j * fmt_ori->size; \ int tag_missing = src_is_missing && fmt_ori->n==1; \ if (!tag_missing) { \ src += sizeof(src_type_t); \ tag_missing = src_is_vector_end ; \ } \ if ( tag_missing ) \ { \ /* tag with missing value "." */ \ tgt_set_missing; \ for (l=1; lp + sizeof(src_type_t) * j *fmt_ori->size; \ if ( ma->buf[i].unkn_allele ) /* Use value from the unknown allele when available */ \ { \ int iunkn = ma->buf[i].unkn_allele; \ src_type_t val = convert(&src[iunkn * sizeof(src_type_t)]); \ for (l=0; ltype==MERGE_MISSING_CONST ) \ { \ for (l=0; lvalue; tgt++; } \ } \ else if ( mrule && mrule->type==MERGE_MISSING_MAX ) \ { \ src = fmt_ori->p + sizeof(src_type_t)*j*fmt_ori->n; \ src_type_t max = convert(src); \ for (l=1; ln; l++) \ { \ src_type_t val = convert(&src[l * sizeof(src_type_t)]); \ if ( max < val ) max = val; \ } \ for (l=0; ln_allele; iori++) \ { \ inew = ma->buf[i].rec[irec].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 = convert(src); \ src += sizeof(src_type_t); \ } \ } \ } \ ismpl += bcf_hdr_nsamples(hdr); \ } switch (type) { case BCF_BT_INT8: BRANCH(int32_t, int8_t, le_to_i8, le_to_i8(src)==bcf_int8_missing, le_to_i8(src)==bcf_int8_vector_end, *tgt=bcf_int32_missing, *tgt=bcf_int32_vector_end); break; case BCF_BT_INT16: BRANCH(int32_t, int16_t, le_to_i16, le_to_i16(src)==bcf_int16_missing, le_to_i16(src)==bcf_int16_vector_end, *tgt=bcf_int32_missing, *tgt=bcf_int32_vector_end); break; case BCF_BT_INT32: BRANCH(int32_t, int32_t, le_to_i32, le_to_i32(src)==bcf_int32_missing, le_to_i32(src)==bcf_int32_vector_end, *tgt=bcf_int32_missing, *tgt=bcf_int32_vector_end); break; case BCF_BT_FLOAT: BRANCH(float, float, le_to_float, bcf_float_is_missing(le_to_float(src)), bcf_float_is_vector_end(le_to_float(src)), bcf_float_set_missing(*tgt), bcf_float_set_vector_end(*tgt)); 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 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*)); ma->fmt_key = (const char**) malloc(ma->nfmt_map*sizeof(*ma->fmt_key)); } 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, has_PL = -1, max_ifmt = 0; // max fmt index for (i=0; inreaders; i++) { bcf1_t *line = maux_get_line(args,i); if ( !line ) continue; bcf_sr_t *reader = &files->readers[i]; bcf_hdr_t *hdr = reader->header; for (j=0; jn_fmt; j++) { // Was 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->fmt_key = (const char**) realloc(ma->fmt_key, sizeof(*ma->fmt_key)*(max_ifmt+1)); ma->nfmt_map = max_ifmt+1; } if ( key[0]=='P' && key[1]=='L' && key[2]==0 ) { has_PL = ifmt; } ma->fmt_key[max_ifmt] = key; } 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 int irec = ma->buf[i].cur; for (j=1; jn_allele; j++) if ( ma->buf[i].rec[irec].map[j]!=j ) break; ma->buf[i].rec[irec].als_differ = j==line->n_allele ? 0 : 1; } if ( args->local_alleles ) { ma->laa_dirty = ma->nlaa = 0; if ( out->n_allele > args->local_alleles + 1 ) init_local_alleles(args, out, has_PL); } out->n_sample = bcf_hdr_nsamples(out_hdr); if ( has_GT ) merge_GT(args, ma->fmt_map, out); if ( !args->keep_AC_AN ) update_AN_AC(out_hdr, out); for (i=1; i<=max_ifmt; i++) { missing_rule_t *rule = (missing_rule_t*) bsearch(ma->fmt_key[i], args->missing_rules, args->nmissing_rules, sizeof(*args->missing_rules), missing_rules_comp_key); merge_format_field(args, &ma->fmt_map[i*files->nreaders], rule, out); } if ( ma->laa_dirty ) update_local_alleles(args, out); out->d.indiv_dirty = 1; } void gvcf_set_alleles(args_t *args) { int i,k; bcf_srs_t *files = args->files; maux_t *maux = args->maux; gvcf_aux_t *gaux = maux->gvcf; for (i=0; inals; i++) { free(maux->als[i]); maux->als[i] = NULL; } maux->nals = 0; for (i=0; inreaders; i++) { if ( !gaux[i].active ) continue; bcf1_t *line = maux_get_line(args, i); if ( !line ) continue; int irec = maux->buf[i].cur; hts_expand(int, line->n_allele, maux->buf[i].rec[irec].mmap, maux->buf[i].rec[irec].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++) { if ( maux->als[k] ) free(maux->als[k]); maux->als[k] = strdup(line->d.allele[k]); maux->buf[i].rec[irec].map[k] = k; } } else { maux->als = merge_alleles(line->d.allele, line->n_allele, maux->buf[i].rec[irec].map, maux->als, &maux->nals, &maux->mals); if ( !maux->als ) { bcf_hdr_t *hdr = bcf_sr_get_header(args->files,i); error("Failed to merge alleles at %s:%"PRId64"\n",bcf_seqname(hdr,line),(int64_t) line->pos+1); } } } } /* Output staged gVCF blocks, end is the last position of the block. Assuming gaux[i].active flags are set and maux_get_line returns correct lines. Both start,end coordinates are 0-based. */ void gvcf_write_block(args_t *args, int start, int end) { int i; maux_t *maux = args->maux; gvcf_aux_t *gaux = maux->gvcf; assert(gaux); // Update POS int min = INT_MAX; // the minimum active gVCF INFO/END (0-based) char ref = 'N'; for (i=0; ifiles->nreaders; i++) { if ( !gaux[i].active ) continue; if ( ref=='N' && gaux[i].line->pos==start ) ref = gaux[i].line->d.allele[0][0]; gaux[i].line->pos = start; } for (i=0; ifiles->nreaders; i++) { if ( !gaux[i].active ) continue; if ( gaux[i].end < start ) { gaux[i].active = 0; maux->buf[i].cur = -1; continue; } gaux[i].line->d.allele[0][0] = ref; if ( min > gaux[i].end ) min = gaux[i].end; } // Check for valid gVCF blocks in this region if ( min==INT_MAX ) // this probably should not happen { assert(0); maux->gvcf_min = 0; return; } bcf1_t *out = args->out_line; gvcf_set_alleles(args); // Merge the staged lines merge_chrom2qual(args, out); merge_filter(args, out); merge_info(args, out); merge_format(args, out); if ( args->gvcf_fai && out->d.allele[0][0]=='N' ) { int slen = 0; char *seq = faidx_fetch_seq(args->gvcf_fai,maux->chr,out->pos,out->pos,&slen); if (!seq) exit(1); // faidx_fetch_seq has already reported the error. if (slen) { out->d.allele[0][0] = seq[0]; free(seq); } } // Update END boundary if ( end > start ) { end++; bcf_update_info_int32(args->out_hdr, out, "END", &end, 1); } else bcf_update_info_int32(args->out_hdr, out, "END", NULL, 0); int iunseen; if ( args->trim_star_allele && (out->n_allele > 2 || args->trim_star_allele > 1) && (iunseen=get_unseen_allele(out)) && iunseen>0 ) { // the unobserved star allele should be trimmed, either it is variant site or trimming of all sites was requested kbitset_t *rm_set = kbs_init(out->n_allele); kbs_insert(rm_set, iunseen); if ( bcf_remove_allele_set(args->out_hdr,out,rm_set) ) error("[%s] Error: failed to trim the unobserved allele at %s:%"PRIhts_pos"\n",__func__,bcf_seqname(args->out_hdr,out),out->pos+1); kbs_destroy(rm_set); } if ( bcf_write1(args->out_fh, args->out_hdr, out)!=0 ) error("[%s] Error: cannot write to %s\n", __func__,args->output_fname); bcf_clear1(out); // Inactivate blocks which do not extend beyond END and find new gvcf_min min = INT_MAX; for (i=0; ifiles->nreaders; i++) { if ( !gaux[i].active ) continue; if ( gaux[i].end < end ) { gaux[i].active = 0; maux->buf[i].cur = -1; continue; } // next min END position bigger than the current one if ( maux->gvcf_min < gaux[i].end+1 && min > gaux[i].end+1 ) min = gaux[i].end + 1; } maux->gvcf_min = min==INT_MAX ? 0 : min; } /* Flush staged gVCF blocks. Flush everything if there are no more lines (done=1) or if there is a new chromosome. If still on the same chromosome, all hanging blocks must be ended by creating new records: A 1 END=10 B 3 END=7 C 3 END=5 out 1 END=2 A . . 3 END=5 A B C 6 END=7 A B . 8 END=10 A . . */ void gvcf_flush(args_t *args, int done) { int i; maux_t *maux = args->maux; if ( !maux->chr ) return; // first time here, nothing to flush int flush_until = INT_MAX; if ( !done ) { // Get current position and chromosome for (i=0; in; i++) if ( bcf_sr_has_line(maux->files,i) ) break; bcf1_t *line = bcf_sr_get_line(maux->files,i); bcf_hdr_t *hdr = bcf_sr_get_header(maux->files,i); if ( !strcmp(maux->chr,bcf_seqname(hdr,line)) ) flush_until = line->pos; // still on the same chr } // When called on a region, trim the blocks accordingly int start = maux->gvcf_break>=0 ? maux->gvcf_break + 1 : maux->pos; // the start of a new gvcf block to output if ( args->regs ) { int rstart = -1, rend = -1; if ( regidx_overlap(args->regs,maux->chr,start,flush_until,args->regs_itr) ) { // In case there are multiple regions, we treat them as one rstart = args->regs_itr->beg; while ( regitr_overlap(args->regs_itr) ) rend = args->regs_itr->end; } if ( rstart > start ) start = rstart; if ( rend < flush_until ) flush_until = rend+1; } // output all finished blocks while ( maux->gvcf_min && start < flush_until ) { // does the block end before the new line or is it interrupted? int tmp = maux->gvcf_min < flush_until ? maux->gvcf_min : flush_until; if ( start > tmp-1 ) break; gvcf_write_block(args,start,tmp-1); // gvcf_min is 1-based, passing 0-based coordinates start = tmp; } } static inline int is_gvcf_block(bcf1_t *line) { if ( line->rlen<=1 ) return 0; if ( strlen(line->d.allele[0])==line->rlen ) return 0; if ( line->n_allele==1 ) return 1; int i; for (i=1; in_allele; i++) { if ( !strcmp(line->d.allele[i],"<*>") ) return 1; if ( !strcmp(line->d.allele[i],"") ) return 1; if ( !strcmp(line->d.allele[i],"") ) return 1; } return 0; } /* Check incoming lines for new gVCF blocks, set pointer to the current source buffer (gvcf or readers). In contrast to gvcf_flush, this function can be called only after maux_reset as it relies on updated maux buffers. The coordinate is 0-based */ void gvcf_stage(args_t *args, int pos) { maux_t *maux = args->maux; gvcf_aux_t *gaux = maux->gvcf; bcf_srs_t *files = args->files; int32_t *end = (int32_t*) maux->tmp_arr; int i, nend = maux->ntmp_arr / sizeof(int32_t); maux->gvcf_break = -1; maux->gvcf_min = INT_MAX; for (i=0; inreaders; i++) { if ( gaux[i].active && gaux[i].end < pos ) gaux[i].active = 0; if ( gaux[i].active ) { // gvcf block should not overlap with another record if ( maux->gvcf_min > gaux[i].end+1 ) maux->gvcf_min = gaux[i].end + 1; maux->buf[i].beg = 0; maux->buf[i].end = 1; maux->buf[i].cur = 0; continue; } // Does any of the lines have END set? It is enough to check only the // first line, there should be no duplicate records with END in gVCF if ( maux->buf[i].beg==maux->buf[i].end ) continue; // no new record int irec = maux->buf[i].beg; bcf_hdr_t *hdr = bcf_sr_get_header(files, i); bcf1_t *line = args->files->readers[i].buffer[irec]; int ret = is_gvcf_block(line) ? bcf_get_info_int32(hdr,line,"END",&end,&nend) : 0; if ( ret==1 ) { if ( end[0] == line->pos + 1 ) // POS and INFO/END are identical, treat as if a normal w/o INFO/END { maux->gvcf_break = line->pos; continue; } if ( end[0] <= line->pos ) error("Error: Incorrect END at %s:%"PRId64" .. END=%d\n", bcf_seqname(hdr,line),(int64_t) line->pos+1,end[0]); // END is set, this is a new gVCF block. Cache this line in gaux[i] and swap with // an empty record: the gaux line must be kept until we reach its END. gaux[i].active = 1; gaux[i].end = end[0] - 1; SWAP(bcf1_t*,args->files->readers[i].buffer[irec],gaux[i].line); gaux[i].line->pos = pos; maux->buf[i].lines = &gaux[i].line; maux->buf[i].beg = 0; maux->buf[i].end = 1; maux->buf[i].cur = 0; // Set the rid,pos of the swapped line in the buffer or else the // synced reader will have a problem with the next line // args->files->readers[i].buffer[irec]->rid = maux->buf[i].rid; args->files->readers[i].buffer[irec]->pos = maux->pos; // Update block offsets if ( maux->gvcf_min > gaux[i].end+1 ) maux->gvcf_min = gaux[i].end + 1; } else maux->gvcf_break = line->pos; // must break the gvcf block } maux->ntmp_arr = nend * sizeof(int32_t); maux->tmp_arr = end; if ( maux->gvcf_min==INT_MAX ) maux->gvcf_min = 0; } void debug_buffers(FILE *fp, bcf_srs_t *files); void debug_buffer(FILE *fp, bcf_srs_t *files, int reader); /* Flush all buffered and processed records with the same coordinate. Note that synced reader discards buffer[0], so that needs to stay untouched. */ void clean_buffer(args_t *args) { maux_t *ma = args->maux; int ir; for (ir=0; irn; ir++) { // Invalidate pointer to reader's buffer or else gvcf_flush will attempt // to use the old lines via maux_get_line() if ( ma->gvcf ) { if ( ma->gvcf[ir].active ) { if ( ma->pos > ma->gvcf[ir].end ) ma->gvcf[ir].active = 0; else if ( ma->buf[ir].cur==-1 ) ma->buf[ir].cur = ma->buf[ir].beg; // re-activate interrupted gVCF block } if ( !ma->gvcf[ir].active ) ma->buf[ir].cur = -1; } bcf_sr_t *reader = bcf_sr_get_reader(args->files,ir); if ( !reader->nbuffer ) continue; // nothing to clean bcf1_t **buf = reader->buffer; if ( buf[1]->rid!=ma->buf[ir].rid || buf[1]->pos!=ma->pos ) continue; // nothing to flush int a = 1, b = 2; while ( b<=reader->nbuffer && buf[b]->rid==ma->buf[ir].rid && buf[b]->pos==ma->pos ) b++; // b now points to the first line we want to preserve while ( b<=reader->nbuffer ) { SWAP(bcf1_t*, buf[a], buf[b]); a++; b++; } reader->nbuffer -= b-a; } } void debug_maux(args_t *args) { bcf_srs_t *files = args->files; maux_t *maux = args->maux; int j,k,l; fprintf(stderr,"Alleles to merge at %d, nals=%d\n", maux->pos+1,maux->nals); for (j=0; jnreaders; j++) { bcf_sr_t *reader = &files->readers[j]; buffer_t *buf = &maux->buf[j]; fprintf(stderr," reader %d (k=%d-%d): ", j,buf->beg,buf->end); for (k=buf->beg; kend; k++) { if ( buf->rec[k].skip & SKIP_DONE ) { fprintf(stderr," DONE"); continue; } bcf1_t *line = reader->buffer[k]; // selected for merging by can_merge fprintf(stderr,"\t"); if ( buf->cur==k ) fprintf(stderr,"!"); // selected for merging by stage_line if ( buf->rec[k].skip ) fprintf(stderr,"["); // this record cannot be merged in this round if ( !line->n_allele && maux->gvcf[j].active ) fprintf(stderr,"<*>"); for (l=0; ln_allele; l++) fprintf(stderr,"%s%s", l==0?"":",", line->d.allele[l]); if ( buf->rec[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\n"); } void debug_state(args_t *args) { maux_t *maux = args->maux; int i,j; fprintf(stderr,"State after position=%d done:\n",maux->pos+1); for (i=0; ifiles->nreaders; i++) { fprintf(stderr,"\treader %d:\tcur,beg,end=% d,%d,%d", i,maux->buf[i].cur,maux->buf[i].beg,maux->buf[i].end); if ( maux->buf[i].cur >=0 ) { bcf_hdr_t *hdr = bcf_sr_get_header(args->files,i); const char *chr = bcf_hdr_id2name(hdr, maux->buf[i].rid); fprintf(stderr,"\t"); for (j=maux->buf[i].beg; jbuf[i].end; j++) fprintf(stderr," %s:%"PRId64,chr,(int64_t) maux->buf[i].lines[j]->pos+1); } fprintf(stderr,"\n"); } fprintf(stderr,"\tgvcf_min=%d\n", args->maux->gvcf_min); for (i=0; ifiles->nreaders; i++) { fprintf(stderr,"\t\treader %d:\tgvcf_active=%d", i,maux->gvcf[i].active); if ( maux->gvcf[i].active ) fprintf(stderr,"\tpos,end=%"PRId64",%"PRId64, (int64_t) maux->gvcf[i].line->pos+1,(int64_t) maux->gvcf[i].end+1); fprintf(stderr,"\n"); } fprintf(stderr,"\n"); } // Lines can come with any combination of variant types. We use a subset of types defined in vcf.h // but shift by two bits to account for VCF_REF defined as 0 (design flaw in vcf.h, my fault) static const int snp_mask = (VCF_SNP<<1)|(VCF_MNP<<1), indel_mask = (VCF_INDEL<<1), ins_mask = VCF_INS<<1, del_mask = VCF_DEL<<1, ref_mask = 1; // Can these types be merged given the -m settings? Despite the function's name, its focus is on // excluding incompatible records, there will be a finer matching later in stage_line() static inline int types_compatible(args_t *args, int selected_types, buffer_t *buf, int irec) { int k; maux_t *maux = args->maux; bcf1_t *rec = buf->lines[irec]; int rec_types = buf->rec[irec].var_types; assert( selected_types ); // this is trivially true, set in can_merge() if ( args->collapse & COLLAPSE_ANY ) return 1; // can merge anything with anything // REF and gVCF_REF with no other alleles present can be merged with anything if ( (selected_types&ref_mask) && !(selected_types&(~ref_mask)) ) return 1; if ( (rec_types&ref_mask) && !(rec_types&(~ref_mask)) ) return 1; if ( args->collapse!=COLLAPSE_NONE ) { // If we are here, one the following modes must have been set: both,snps,indels,snp-ins-del // Include the new record if // - rec has SNV, we already have SNV, and -m is both,snps,snp-ins-del // - rec has indel, we already have an indel, and -m both,indels,snp-ins-del if ( args->collapse&(COLLAPSE_SNPS|COLLAPSE_SNP_INS_DEL) ) { if ( (rec_types&snp_mask) && (selected_types&snp_mask) ) return 1; } if ( args->collapse&COLLAPSE_INDELS ) { if ( (rec_types&indel_mask) && (selected_types&indel_mask) ) return 1; } if ( args->collapse&COLLAPSE_SNP_INS_DEL ) { if ( (rec_types&ins_mask) && (selected_types&ins_mask) ) return 1; if ( (rec_types&del_mask) && (selected_types&del_mask) ) return 1; } // Whatever is left, allow to match if the alleles match exactly } // The -m none mode or exact matching requested // Simple test first: are the variants of the same type? int x = selected_types >> 1; // remove REF int y = rec_types >> 1; // remove REF while ( x && y ) { x>>=1; y>>=1; } if ( x || y ) return 0; // the types differ if ( vcmp_set_ref(args->vcmp,maux->als[0],rec->d.allele[0]) < 0 ) return 0; // refs are not compatible for (k=1; kn_allele; k++) { if ( bcf_has_variant_type(rec,k,VCF_REF) ) continue; // this must be gVCF_REF (<*> or ) if ( vcmp_find_allele(args->vcmp,maux->als+1,maux->nals-1,rec->d.allele[k])>=0 ) break; } if ( k==rec->n_allele ) return 0; // this record has a new allele rec->d.allele[k] return 1; // all alleles in rec are also in the records selected thus far, perhaps save for gVCF_REF } static void maux_update_alleles(args_t *args, int ireader, int irec) { int k; bcf_sr_t *reader = &args->files->readers[ireader]; maux_t *maux = args->maux; buffer_t *buf = &maux->buf[ireader]; maux1_t *ma1 = &buf->rec[irec]; bcf1_t *line = buf->lines[irec]; hts_expand(int, line->n_allele, ma1->mmap, ma1->map); if ( !maux->nals ) // first record to be merged, 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); hts_expand0(int, maux->nals, maux->mals_types, maux->als_types); for (k=0; knals; k++) { free(maux->als[k]); maux->als[k] = strdup(line->d.allele[k]); ma1->map[k] = k; maux->cnt[k] = 1; int var_type = bcf_has_variant_type(line, k, VCF_ANY); if ( args->collapse==COLLAPSE_SNP_INS_DEL ) var_type &= ~VCF_INDEL; maux->als_types[k] = var_type ? var_type<<1 : ref_mask; } return; } // normalize alleles maux->als = merge_alleles(line->d.allele, line->n_allele, ma1->map, maux->als, &maux->nals, &maux->mals); if ( !maux->als ) error("Failed to merge alleles at %s:%"PRId64" in %s\n",maux->chr,(int64_t) line->pos+1,reader->fname); hts_expand0(int, maux->nals, maux->ncnt, maux->cnt); hts_expand0(int, maux->nals, maux->mals_types, maux->als_types); for (k=1; kn_allele; k++) { int ik = ma1->map[k]; int var_type = bcf_has_variant_type(line, k, VCF_ANY); if ( args->collapse==COLLAPSE_SNP_INS_DEL ) var_type &= ~VCF_INDEL; maux->als_types[ik] = var_type ? var_type<<1 : ref_mask; maux->cnt[ik]++; // how many times an allele appears in the files } maux->cnt[0]++; } /* Determine which lines remain to be merged across readers at the current position and are compatible given the -m criteria. This is indicated by maux1_t.skip: 0=compatible, SKIP_DONE=the record is done, SKIP_DIFF=not compatible and will be included next time. At the same time count how many times is each allele present across the readers and records so that we can prioritize the records with the same alleles to come first. In the end maximum one record at a time can be selected from each reader and that witll be done in stage_line(). The function maux_reset already initialized structures for this position, so here each reader comes with the beg,end indexes that point to records with the same maux_t.pos position. */ int can_merge(args_t *args) { bcf_srs_t *files = args->files; maux_t *maux = args->maux; gvcf_aux_t *gaux = maux->gvcf; char *id = NULL, ref = 'N'; int i,j, ntodo = 0; for (i=0; inals; i++) { free(maux->als[i]); maux->als[i] = NULL; maux->cnt[i] = 0; } maux->var_types = maux->nals = 0; // In this loop we do the following: // - remember the first encountered ID if matching by ID // - count the number of unprocessed records at this position // - collect all variant types at this position. This is to be able to perform -m matching and // print SNVs first, then indels, then gVCF blocks // - init the 'skip' variable to SKIP_DIFF for each record that has not been used yet for (i=0; inreaders; i++) { buffer_t *buf = &maux->buf[i]; buf->var_types = 0; if ( gaux && gaux[i].active ) // active gvcf block { buf->rec[buf->beg].skip = SKIP_DIFF; maux->var_types |= ref_mask; buf->var_types |= ref_mask; buf->rec[buf->beg].var_types = ref_mask; continue; } // for gvcf: find out REF at this position if ( buf->beg < buf->end && ref=='N' ) ref = buf->lines[buf->beg]->d.allele[0][0]; for (j=buf->beg; jend; j++) { if ( buf->rec[j].skip & SKIP_DONE ) continue; buf->rec[j].skip = SKIP_DIFF; ntodo++; bcf1_t *line = buf->lines[j]; if ( args->merge_by_id && !id ) { id = line->d.id; continue; } // set ID when merging by id if ( !buf->rec[j].var_types ) { int var_type = bcf_has_variant_types(line, VCF_ANY, bcf_match_overlap); if ( var_type < 0 ) error("bcf_has_variant_types() failed."); if ( args->collapse==COLLAPSE_SNP_INS_DEL ) { // need to distinguish between ins and del so strip the VCF_INDEL flag var_type &= ~VCF_INDEL; } var_type = var_type ? var_type<<1 : ref_mask; if ( args->do_gvcf && is_gvcf_block(line) ) var_type |= ref_mask; buf->rec[j].var_types = var_type; } maux->var_types |= buf->rec[j].var_types; buf->var_types |= buf->rec[j].var_types; } } if ( !ntodo ) return 0; int selected_types = 0; // 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++) { buffer_t *buf = &maux->buf[i]; if ( gaux && gaux[i].active ) { // gVCF records inherited from an upstream gVCF block have incorrect or missing allele and position gaux[i].line->d.allele[0][0] = ref; gaux[i].line->pos = maux->pos; maux_update_alleles(args, i, buf->beg); selected_types |= ref_mask; continue; } for (j=buf->beg; jend; j++) { if ( buf->rec[j].skip & SKIP_DONE ) continue; bcf1_t *line = buf->lines[j]; // ptr to reader's buffer or gvcf buffer int line_types = buf->rec[j].var_types; // select relevant lines if ( args->merge_by_id ) { if ( strcmp(id,line->d.id) ) continue; // matching by ID and it does not match the selected record } else if ( selected_types && !types_compatible(args,selected_types,buf,j) ) continue; else { // First time here, choosing the first line: prioritize SNPs when available in the -m snps,both modes if ( (args->collapse&COLLAPSE_SNPS || args->collapse==COLLAPSE_NONE) // asked to merge SNVs into multiallelics && (maux->var_types&snp_mask) // there are SNVs at the current position && !(buf->rec[j].var_types&(snp_mask|ref_mask)) // and this record is not a SNV nor ref ) continue; } selected_types |= line_types; buf->rec[j].skip = 0; // the j-th record from i-th reader can be included. Final decision will be made in stage_line maux_update_alleles(args, i, j); } } return 1; } /* 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. */ void stage_line(args_t *args) { bcf_srs_t *files = args->files; maux_t *maux = args->maux; // Take the most frequent allele present in multiple files, REF and gVCF_REF is skipped. int i,j,k,icnt = -1; for (i=1; inals; i++) { if ( maux->als_types[i] & ref_mask ) continue; if ( icnt==-1 || maux->cnt[icnt] < maux->cnt[i] ) icnt = i; } int selected_type = icnt>0 ? maux->als_types[icnt] : ref_mask; int nout = 0; for (i=0; inreaders; i++) { buffer_t *buf = &maux->buf[i]; buf->cur = -1; if ( buf->beg >= buf->end ) continue; // No lines in the buffer at this site // find lines with the same allele for (j=buf->beg; jend; j++) { if ( buf->rec[j].skip ) { int is_gvcf = maux->gvcf && maux->gvcf[i].active ? 1 : 0; if ( !is_gvcf && is_gvcf_block(buf->lines[j]) ) is_gvcf = 1; if ( !is_gvcf ) continue; // done or not compatible } if ( args->merge_by_id ) break; // if merging by ID and the line is compatible, the this is THE line // skip if the reader has a record that matches the most frequent allele and this record is not it if ( (selected_type & buf->var_types) && !(selected_type & buf->rec[j].var_types) ) continue; // if the reader does not have the most frequent allele type but is a ref, accept if ( !(selected_type & buf->var_types) && (buf->rec[j].var_types & ref_mask) ) break; if ( selected_type==ref_mask ) break; // accept if the record has the most frequent allele for (k=0; klines[j]->n_allele; k++) if ( icnt==buf->rec[j].map[k] ) break; if ( klines[j]->n_allele ) break; } if ( j>=buf->end ) { // no matching allele found in this file if ( args->collapse==COLLAPSE_NONE ) continue; // exact matching requested, skip // choose something compatible to create a multiallelic site given the -m criteria for (j=buf->beg; jend; j++) { if ( buf->rec[j].skip ) continue; // done or not compatible if ( args->collapse&COLLAPSE_ANY ) break; // anything can be merged int line_type = buf->rec[j].var_types; if ( maux->var_types&snp_mask && line_type&snp_mask && (args->collapse&COLLAPSE_SNPS) ) break; if ( maux->var_types&indel_mask && line_type&indel_mask && (args->collapse&COLLAPSE_INDELS) ) break; if ( maux->var_types&ins_mask && line_type&ins_mask && (args->collapse&COLLAPSE_SNP_INS_DEL) ) break; if ( maux->var_types&del_mask && line_type&del_mask && (args->collapse&COLLAPSE_SNP_INS_DEL) ) break; if ( line_type&ref_mask ) { if ( maux->var_types&snp_mask && (args->collapse&COLLAPSE_SNPS) ) break; if ( maux->var_types&indel_mask && (args->collapse&COLLAPSE_INDELS) ) break; if ( maux->var_types&ins_mask && (args->collapse&COLLAPSE_SNP_INS_DEL) ) break; if ( maux->var_types&del_mask && (args->collapse&COLLAPSE_SNP_INS_DEL) ) break; if ( maux->var_types&ref_mask ) break; } else if ( maux->var_types&ref_mask ) { if ( line_type&snp_mask && (args->collapse&COLLAPSE_SNPS) ) break; if ( line_type&indel_mask && (args->collapse&COLLAPSE_INDELS) ) break; if ( line_type&ins_mask && (args->collapse&COLLAPSE_SNP_INS_DEL) ) break; if ( line_type&del_mask && (args->collapse&COLLAPSE_SNP_INS_DEL) ) break; } } } if ( jend ) { // found a suitable line for merging buf->cur = j; } } // debug_maux(args); // Mark lines staged for merging as finished so that they are ignored next time for (i=0; inreaders; i++) { buffer_t *buf = &maux->buf[i]; if ( buf->cur == -1 ) continue; buf->rec[buf->cur].skip = SKIP_DONE; nout++; } assert( nout ); } void merge_line(args_t *args) { bcf1_t *out = args->out_line; merge_chrom2qual(args, out); if ( args->regs && !regidx_overlap(args->regs,args->maux->chr,out->pos,out->pos+out->rlen-1,NULL) ) return; merge_filter(args, out); merge_info(args, out); if ( args->do_gvcf ) bcf_update_info_int32(args->out_hdr, out, "END", NULL, 0); merge_format(args, out); int iunseen; if ( args->trim_star_allele && (out->n_allele > 2 || args->trim_star_allele > 1) && (iunseen=get_unseen_allele(out)) && iunseen>0 ) { // the unobserved star allele should be trimmed, either it is variant site or trimming of all sites was requested kbitset_t *rm_set = kbs_init(out->n_allele); kbs_insert(rm_set, iunseen); if ( bcf_remove_allele_set(args->out_hdr,out,rm_set) ) error("[%s] Error: failed to trim the unobserved allele at %s:%"PRIhts_pos"\n",__func__,bcf_seqname(args->out_hdr,out),out->pos+1); kbs_destroy(rm_set); } if ( bcf_write1(args->out_fh, args->out_hdr, out)!=0 ) error("[%s] Error: cannot write to %s\n", __func__,args->output_fname); bcf_clear1(out); } void bcf_hdr_append_version(bcf_hdr_t *hdr, int argc, char **argv, const char *cmd) { kstring_t str = {0,0,0}; int e = 0; if (ksprintf(&str,"##%sVersion=%s+htslib-%s\n", cmd, bcftools_version(), hts_version()) < 0) goto fail; if (bcf_hdr_append(hdr,str.s) < 0) goto fail; str.l = 0; e |= ksprintf(&str,"##%sCommand=%s", cmd, argv[0]) < 0; int i; for (i=1; inhrec; i++) { if ( hdr->hrec[i]->type!=BCF_HL_FMT ) continue; j = bcf_hrec_find_key(hdr->hrec[i],"ID"); if ( j<0 ) continue; char *key = hdr->hrec[i]->vals[j]; int id = bcf_hdr_id2int(hdr, BCF_DT_ID, key); assert( id>=0 ); int localize = 0; if ( bcf_hdr_id2length(hdr,BCF_HL_FMT,id) == BCF_VL_G ) localize = 1; if ( bcf_hdr_id2length(hdr,BCF_HL_FMT,id) == BCF_VL_A ) localize = 1; if ( bcf_hdr_id2length(hdr,BCF_HL_FMT,id) == BCF_VL_R ) localize = 1; if ( !localize ) continue; args->tmps.l = 0; uint32_t e = 0, nout = 0; e |= ksprintf(&args->tmps, "##%s=<", hdr->hrec[i]->key) < 0; for (j=0; jhrec[i]->nkeys; j++) { if ( !strcmp("IDX",hdr->hrec[i]->keys[j]) ) continue; if ( nout ) e |= kputc(',',&args->tmps) < 0; if ( !strcmp("ID",hdr->hrec[i]->keys[j]) ) e |= ksprintf(&args->tmps,"%s=L%s", hdr->hrec[i]->keys[j], hdr->hrec[i]->vals[j]) < 0; else if ( !strcmp("Number",hdr->hrec[i]->keys[j]) ) e |= ksprintf(&args->tmps,"Number=.") < 0; else if ( !strcmp("Description",hdr->hrec[i]->keys[j]) && hdr->hrec[i]->vals[j][0]=='"' ) e |= ksprintf(&args->tmps,"Description=\"Localized field: %s", hdr->hrec[i]->vals[j]+1) < 0; else e |= ksprintf(&args->tmps,"%s=%s", hdr->hrec[i]->keys[j], hdr->hrec[i]->vals[j]) < 0; nout++; } e |= ksprintf(&args->tmps,">\n") < 0; if ( e ) error("Failed to format the header line for %s\n", key); nstr++; hts_expand(char*,nstr,mstr,str); str[nstr-1] = strdup(args->tmps.s); } if ( !nstr ) return; bcf_hdr_append(hdr,"##FORMAT="); for (i=0; ioutput_type,args->output_fname,args->clevel); args->out_fh = hts_open(args->output_fname ? args->output_fname : "-", wmode); if ( args->out_fh == NULL ) error("Can't write to \"%s\": %s\n", args->output_fname, strerror(errno)); if ( args->n_threads ) hts_set_opt(args->out_fh, HTS_OPT_THREAD_POOL, args->files->p); //hts_set_threads(args->out_fh, args->n_threads); 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[24]; snprintf(buf,sizeof buf,"%d",i+1); merge_headers(args->out_hdr, args->files->readers[i].header,buf,args->force_samples); } if ( args->local_alleles ) hdr_add_localized_tags(args, args->out_hdr); if (args->record_cmd_line) bcf_hdr_append_version(args->out_hdr, args->argc, args->argv, "bcftools_merge"); if (bcf_hdr_sync(args->out_hdr) < 0) error_errno("[%s] Failed to update header", __func__); } info_rules_init(args); missing_rules_init(args); bcf_hdr_set_version(args->out_hdr, bcf_hdr_get_version(args->files->readers[0].header)); if ( bcf_hdr_write(args->out_fh, args->out_hdr)!=0 ) error("[%s] Error: cannot write to %s\n", __func__,args->output_fname); if ( args->header_only ) { bcf_hdr_destroy(args->out_hdr); if ( hts_close(args->out_fh)!=0 ) error("[%s] Error: close failed .. %s\n", __func__,args->output_fname); return; } else if ( args->write_index && init_index(args->out_fh,args->out_hdr,args->output_fname,&args->index_fn)<0 ) error("Error: failed to initialise index for %s\n",args->output_fname); args->vcmp = vcmp_init(); args->maux = maux_init(args); args->out_line = bcf_init1(); args->tmph = kh_init(strdict); int *rid_tab = calloc(args->maux->n, sizeof(*rid_tab)); if (!rid_tab) error("[%s:%d] Could not allocate %zu bytes\n", __FILE__, __LINE__, args->maux->n*sizeof(*rid_tab)); while ( bcf_sr_next_line(args->files) ) { // output cached gVCF blocks which end before the new record if ( args->do_gvcf ) gvcf_flush(args,0); maux_reset(args->maux, rid_tab); // determine which of the new records are gvcf blocks if ( args->do_gvcf ) gvcf_stage(args, args->maux->pos); while ( can_merge(args) ) { stage_line(args); merge_line(args); } clean_buffer(args); // debug_state(args); } free(rid_tab); if ( args->do_gvcf ) gvcf_flush(args,1); info_rules_destroy(args); missing_rules_destroy(args); maux_destroy(args->maux); bcf_hdr_destroy(args->out_hdr); if ( args->write_index ) { if ( bcf_idx_save(args->out_fh)<0 ) { if ( hts_close(args->out_fh)!=0 ) error("Error: close failed .. %s\n", args->output_fname?args->output_fname:"stdout"); error("Error: cannot write to index %s\n", args->index_fn); } free(args->index_fn); } if ( hts_close(args->out_fh)!=0 ) error("[%s] Error: close failed .. %s\n", __func__,args->output_fname?args->output_fname:"stdout"); 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 FILE Use the provided header\n"); fprintf(stderr, " -0 --missing-to-ref Assume genotypes at missing sites are 0/0\n"); fprintf(stderr, " -f, --apply-filters LIST Require at least one of the listed FILTER strings (e.g. \"PASS,.\")\n"); fprintf(stderr, " -F, --filter-logic x|+ Remove filters if some input is PASS (\"x\"), or apply all filters (\"+\") [+]\n"); fprintf(stderr, " -g, --gvcf -|REF.FA Merge gVCF blocks, INFO/END tag is expected. Implies -i QS:sum,MinDP:min,MIN_DP:min,I16:sum,IDV:max,IMF:max -M PL:max,AD:0\n"); fprintf(stderr, " -i, --info-rules TAG:METHOD,.. 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 FILE Read file names from the file\n"); fprintf(stderr, " -L, --local-alleles INT If more than INT alt alleles are encountered, drop FMT/PL and output LAA+LPL instead; 0=unlimited [0]\n"); fprintf(stderr, " -m, --merge STRING[*|**] Allow multiallelic records for snps,indels,both,snp-ins-del,all,none,id,*,**; see man page for details [both]\n"); fprintf(stderr, " -M, --missing-rules TAG:METHOD Rules for replacing missing values in numeric vectors (.,0,max) when unknown allele <*> is not present [.]\n"); fprintf(stderr, " --no-index Merge unindexed files, the same chromosomal order is required and -r/-R are not allowed\n"); fprintf(stderr, " --no-version Do not append version and command line to the header\n"); fprintf(stderr, " -o, --output FILE Write output to a file [standard output]\n"); fprintf(stderr, " -O, --output-type u|b|v|z[0-9] u/b: un/compressed BCF, v/z: un/compressed VCF, 0-9: compression level [v]\n"); fprintf(stderr, " -r, --regions REGION Restrict to comma-separated list of regions\n"); fprintf(stderr, " -R, --regions-file FILE Restrict to regions listed in a file\n"); fprintf(stderr, " --regions-overlap 0|1|2 Include if POS in the region (0), record overlaps (1), variant overlaps (2) [1]\n"); fprintf(stderr, " --threads INT Use multithreading with INT worker threads [0]\n"); fprintf(stderr, " --write-index Automatically index the output files [off]\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->n_threads = 0; args->record_cmd_line = 1; args->collapse = COLLAPSE_BOTH; args->clevel = -1; int regions_is_file = 0; int regions_overlap = 1; static struct option loptions[] = { {"help",no_argument,NULL,'h'}, {"merge",required_argument,NULL,'m'}, {"local-alleles",required_argument,NULL,'L'}, {"gvcf",required_argument,NULL,'g'}, {"file-list",required_argument,NULL,'l'}, {"missing-to-ref",no_argument,NULL,'0'}, {"apply-filters",required_argument,NULL,'f'}, {"use-header",required_argument,NULL,1}, {"print-header",no_argument,NULL,2}, {"force-samples",no_argument,NULL,3}, {"output",required_argument,NULL,'o'}, {"output-type",required_argument,NULL,'O'}, {"threads",required_argument,NULL,9}, {"regions",required_argument,NULL,'r'}, {"regions-file",required_argument,NULL,'R'}, {"regions-overlap",required_argument,NULL,4}, {"info-rules",required_argument,NULL,'i'}, {"missing-rules",required_argument,NULL,'M'}, {"no-version",no_argument,NULL,8}, {"no-index",no_argument,NULL,10}, {"filter-logic",required_argument,NULL,'F'}, {"write-index",no_argument,NULL,11}, {NULL,0,NULL,0} }; char *tmp; while ((c = getopt_long(argc, argv, "hm:f:r:R:o:O:i:M:l:g:F:0L:",loptions,NULL)) >= 0) { switch (c) { case 'L': args->local_alleles = strtol(optarg,&tmp,10); if ( *tmp ) error("Could not parse argument: --local-alleles %s\n", optarg); if ( args->local_alleles < 1 ) error("Error: \"--local-alleles %s\" makes no sense, expected value bigger or equal than 1\n", optarg); break; case 'F': if ( !strcmp(optarg,"+") ) args->filter_logic = FLT_LOGIC_ADD; else if ( !strcmp(optarg,"x") ) args->filter_logic = FLT_LOGIC_REMOVE; else error("Filter logic not recognised: %s\n", optarg); break; case '0': args->missing_to_ref = 1; break; case 'g': args->do_gvcf = 1; if ( strcmp("-",optarg) ) { args->gvcf_fai = fai_load(optarg); if ( !args->gvcf_fai ) error("Failed to load the fai index: %s\n", optarg); } break; case 'l': args->file_list = optarg; break; case 'i': args->info_rules = optarg; break; case 'M': args->missing_rules_str = 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: { args->clevel = strtol(optarg,&tmp,10); if ( *tmp || args->clevel<0 || args->clevel>9 ) error("The output type \"%s\" not recognised\n", optarg); } } if ( optarg[1] ) { args->clevel = strtol(optarg+1,&tmp,10); if ( *tmp || args->clevel<0 || args->clevel>9 ) error("Could not parse argument: --compression-level %s\n", optarg+1); } break; case 'm': { int len = strlen(optarg); if ( optarg[len-1]=='*' ) { args->trim_star_allele++; len--; } if ( optarg[len-1]=='*' ) { args->trim_star_allele++; len--; } if ( optarg[len-1]==',' ) len--; args->collapse = COLLAPSE_NONE; if ( !strncmp(optarg,"snp-ins-del",len) ) args->collapse = COLLAPSE_SNP_INS_DEL|COLLAPSE_SNPS; else if ( !strncmp(optarg,"snps",len) ) args->collapse |= COLLAPSE_SNPS; else if ( !strncmp(optarg,"indels",len) ) args->collapse |= COLLAPSE_INDELS; else if ( !strncmp(optarg,"id",len) ) { args->collapse = COLLAPSE_NONE; args->merge_by_id = 1; } else if ( !strncmp(optarg,"any",len) ) args->collapse |= COLLAPSE_ANY; else if ( !strncmp(optarg,"all",len) ) args->collapse |= COLLAPSE_ANY; else if ( !strncmp(optarg,"both",len) ) args->collapse |= COLLAPSE_BOTH; else if ( !strncmp(optarg,"none",len) ) args->collapse = COLLAPSE_NONE; 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 4 : regions_overlap = parse_overlap_option(optarg); if ( regions_overlap < 0 ) error("Could not parse: --regions-overlap %s\n",optarg); break; case 9 : args->n_threads = strtol(optarg, 0, 0); break; case 8 : args->record_cmd_line = 0; break; case 10 : args->no_index = 1; break; case 11 : args->write_index = 1; break; case 'h': case '?': usage(); break; default: error("Unknown argument: %s\n", optarg); } } if ( argc==optind && !args->file_list ) usage(); if ( argc-optind<2 && !args->file_list ) usage(); if ( args->no_index ) { if ( args->regions_list ) error("Error: cannot combine --no-index with -r/-R\n"); bcf_sr_set_opt(args->files,BCF_SR_ALLOW_NO_IDX); } else bcf_sr_set_opt(args->files,BCF_SR_REQUIRE_IDX); if ( args->regions_list ) { bcf_sr_set_opt(args->files,BCF_SR_REGIONS_OVERLAP,regions_overlap); if ( bcf_sr_set_regions(args->files, args->regions_list, regions_is_file)<0 ) error("Failed to read the regions: %s\n", args->regions_list); if ( regions_is_file ) args->regs = regidx_init(args->regions_list,NULL,NULL,sizeof(char*),NULL); else { args->regs = regidx_init(NULL,regidx_parse_reg,NULL,sizeof(char*),NULL); if ( regidx_insert_list(args->regs,args->regions_list,',') !=0 ) error("Could not parse the regions: %s\n", args->regions_list); regidx_insert(args->regs,NULL); } if ( !args->regs ) error("Could not parse the regions: %s\n", args->regions_list); args->regs_itr = regitr_init(args->regs); } if ( bcf_sr_set_threads(args->files, args->n_threads)<0 ) error("Failed to create threads\n"); 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); if ( args->regs ) regidx_destroy(args->regs); if ( args->regs_itr ) regitr_destroy(args->regs_itr); if ( args->gvcf_fai ) fai_destroy(args->gvcf_fai); free(args); return 0; }