vcf.h

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/*  vcf.h -- VCF/BCF API functions.

    Copyright (C) 2012, 2013 Broad Institute.
    Copyright (C) 2012-2014 Genome Research Ltd.

    Author: Heng Li <lh3@sanger.ac.uk>

Permission is hereby granted, free of charge, to any person obtaining a copy
of this software and associated documentation files (the "Software"), to deal
in the Software without restriction, including without limitation the rights
to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
copies of the Software, and to permit persons to whom the Software is
furnished to do so, subject to the following conditions:

The above copyright notice and this permission notice shall be included in
all copies or substantial portions of the Software.

THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL
THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING
FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER
DEALINGS IN THE SOFTWARE.  */

/*
    todo:
        - make the function names consistent
        - provide calls to abstract away structs as much as possible
 */

#ifndef HTSLIB_VCF_H
#define HTSLIB_VCF_H

#include <stdint.h>
#include <limits.h>
#include <assert.h>
#include "hts.h"
#include "kstring.h"


/*****************
 * Header struct *
 *****************/

#define BCF_HL_FLT  0 // header line
#define BCF_HL_INFO 1
#define BCF_HL_FMT  2
#define BCF_HL_CTG  3
#define BCF_HL_STR  4 // structured header line TAG=<A=..,B=..>
#define BCF_HL_GEN  5 // generic header line

#define BCF_HT_FLAG 0 // header type
#define BCF_HT_INT  1
#define BCF_HT_REAL 2
#define BCF_HT_STR  3

#define BCF_VL_FIXED 0 // variable length
#define BCF_VL_VAR   1
#define BCF_VL_A     2
#define BCF_VL_G     3
#define BCF_VL_R     4

/* === Dictionary ===

   The header keeps three dictonaries. The first keeps IDs in the
   "FILTER/INFO/FORMAT" lines, the second keeps the sequence names and lengths
   in the "contig" lines and the last keeps the sample names. bcf_hdr_t::dict[]
   is the actual hash table, which is opaque to the end users. In the hash
   table, the key is the ID or sample name as a C string and the value is a
   bcf_idinfo_t struct. bcf_hdr_t::id[] points to key-value pairs in the hash
   table in the order that they appear in the VCF header. bcf_hdr_t::n[] is the
   size of the hash table or, equivalently, the length of the id[] arrays.
*/

#define BCF_DT_ID       0 // dictionary type
#define BCF_DT_CTG      1
#define BCF_DT_SAMPLE   2

// Complete textual representation of a header line
typedef struct {
    int type;       // One of the BCF_HL_* type
    char *key;      // The part before '=', i.e. FILTER/INFO/FORMAT/contig/fileformat etc.
    char *value;    // Set only for generic lines, NULL for FILTER/INFO, etc.
    int nkeys;              // Number of structured fields
    char **keys, **vals;    // The key=value pairs
} bcf_hrec_t;

typedef struct {
    uint32_t info[3];  // stores Number:20, var:4, Type:4, ColType:4 for BCF_HL_FLT,INFO,FMT
    bcf_hrec_t *hrec[3];
    int id;
} bcf_idinfo_t;

typedef struct {
    const char *key;
    const bcf_idinfo_t *val;
} bcf_idpair_t;

typedef struct {
    int32_t n[3];
    bcf_idpair_t *id[3];
    void *dict[3]; // ID dictionary, contig dict and sample dict
    char **samples;
    bcf_hrec_t **hrec;
    int nhrec, dirty;
    int ntransl, *transl[2];    // for bcf_translate()
    int nsamples_ori;           // for bcf_hdr_set_samples()
    uint8_t *keep_samples;
    kstring_t mem;
} bcf_hdr_t;

extern uint8_t bcf_type_shift[];

/**************
 * VCF record *
 **************/

#define BCF_BT_NULL     0
#define BCF_BT_INT8     1
#define BCF_BT_INT16    2
#define BCF_BT_INT32    3
#define BCF_BT_FLOAT    5
#define BCF_BT_CHAR     7

#define VCF_REF   0
#define VCF_SNP   1
#define VCF_MNP   2
#define VCF_INDEL 4
#define VCF_OTHER 8

typedef struct {
    int type, n;    // variant type and the number of bases affected, negative for deletions
} variant_t;

typedef struct {
    int id;             // id: numeric tag id, the corresponding string is bcf_hdr_t::id[BCF_DT_ID][$id].key
    int n, size, type;  // n: number of values per-sample; size: number of bytes per-sample; type: one of BCF_BT_* types
    uint8_t *p;         // same as vptr and vptr_* in bcf_info_t below
    uint32_t p_len;
    uint32_t p_off:31, p_free:1;
} bcf_fmt_t;

typedef struct {
    int key;        // key: numeric tag id, the corresponding string is bcf_hdr_t::id[BCF_DT_ID][$key].key
    int type, len;  // type: one of BCF_BT_* types; len: vector length, 1 for scalars
    union {
        int32_t i; // integer value
        float f;   // float value
    } v1; // only set if $len==1; for easier access
    uint8_t *vptr;          // pointer to data array in bcf1_t->shared.s, excluding the size+type and tag id bytes
    uint32_t vptr_len;      // length of the vptr block or, when set, of the vptr_mod block, excluding offset
    uint32_t vptr_off:31,   // vptr offset, i.e., the size of the INFO key plus size+type bytes
            vptr_free:1;    // indicates that vptr-vptr_off must be freed; set only when modified and the new
                            //    data block is bigger than the original
} bcf_info_t;


#define BCF1_DIRTY_ID  1
#define BCF1_DIRTY_ALS 2
#define BCF1_DIRTY_FLT 4
#define BCF1_DIRTY_INF 8

typedef struct {
    int m_fmt, m_info, m_id, m_als, m_allele, m_flt; // allocated size (high-water mark); do not change
    int n_flt;  // Number of FILTER fields
    int *flt;   // FILTER keys in the dictionary
    char *id, *als;     // ID and REF+ALT block (\0-seperated)
    char **allele;      // allele[0] is the REF (allele[] pointers to the als block); all null terminated
    bcf_info_t *info;   // INFO
    bcf_fmt_t *fmt;     // FORMAT and individual sample
    variant_t *var;     // $var and $var_type set only when set_variant_types called
    int n_var, var_type;
    int shared_dirty;   // if set, shared.s must be recreated on BCF output
    int indiv_dirty;    // if set, indiv.s must be recreated on BCF output
} bcf_dec_t;


#define BCF_ERR_CTG_UNDEF 1
#define BCF_ERR_TAG_UNDEF 2
#define BCF_ERR_NCOLS     4

/*
    The bcf1_t structure corresponds to one VCF/BCF line. Reading from VCF file
    is slower because the string is first to be parsed, packed into BCF line
    (done in vcf_parse), then unpacked into internal bcf1_t structure. If it
    is known in advance that some of the fields will not be required (notably
    the sample columns), parsing of these can be skipped by setting max_unpack
    appropriately.
    Similarly, it is fast to output a BCF line because the columns (kept in
    shared.s, indiv.s, etc.) are written directly by bcf_write, whereas a VCF
    line must be formatted in vcf_format.
 */
typedef struct {
    int32_t rid;  // CHROM
    int32_t pos;  // POS
    int32_t rlen; // length of REF
    float qual;   // QUAL
    uint32_t n_info:16, n_allele:16;
    uint32_t n_fmt:8, n_sample:24;
    kstring_t shared, indiv;
    bcf_dec_t d; // lazy evaluation: $d is not generated by bcf_read(), but by explicitly calling bcf_unpack()
    int max_unpack;         // Set to BCF_UN_STR, BCF_UN_FLT, or BCF_UN_INFO to boost performance of vcf_parse when some of the fields won't be needed
    int unpacked;           // remember what has been unpacked to allow calling bcf_unpack() repeatedly without redoing the work
    int unpack_size[3];     // the original block size of ID, REF+ALT and FILTER
    int errcode;    // one of BCF_ERR_* codes
} bcf1_t;

/*******
 * API *
 *******/

#ifdef __cplusplus
extern "C" {
#endif

    /***********************************************************************
     *  BCF and VCF I/O
     *
     *  A note about naming conventions: htslib internally represents VCF
     *  records as bcf1_t data structures, therefore most functions are
     *  prefixed with bcf_. There are a few exceptions where the functions must
     *  be aware of both BCF and VCF worlds, such as bcf_parse vs vcf_parse. In
     *  these cases, functions prefixed with bcf_ are more general and work
     *  with both BCF and VCF.
     *
     ***********************************************************************/

    #define bcf_init1()         bcf_init()
    #define bcf_read1(fp,h,v)   bcf_read((fp),(h),(v))
    #define vcf_read1(fp,h,v)   vcf_read((fp),(h),(v))
    #define bcf_write1(fp,h,v)  bcf_write((fp),(h),(v))
    #define vcf_write1(fp,h,v)  vcf_write((fp),(h),(v))
    #define bcf_destroy1(v)     bcf_destroy(v)
    #define vcf_parse1(s,h,v)   vcf_parse((s),(h),(v))
    #define bcf_clear1(v)       bcf_clear(v)
    #define vcf_format1(h,v,s)  vcf_format((h),(v),(s))

    bcf_hdr_t *bcf_hdr_init(const char *mode);

    void bcf_hdr_destroy(bcf_hdr_t *h);

    bcf1_t *bcf_init(void);

    void bcf_destroy(bcf1_t *v);

    void bcf_empty(bcf1_t *v);

    void bcf_clear(bcf1_t *v);


    typedef htsFile vcfFile;
    #define bcf_open(fn, mode) hts_open((fn), (mode))
    #define vcf_open(fn, mode) hts_open((fn), (mode))
    #define bcf_close(fp) hts_close(fp)
    #define vcf_close(fp) hts_close(fp)

    bcf_hdr_t *bcf_hdr_read(htsFile *fp);

    int bcf_hdr_set_samples(bcf_hdr_t *hdr, const char *samples, int is_file);
    int bcf_subset_format(const bcf_hdr_t *hdr, bcf1_t *rec);


    int bcf_hdr_write(htsFile *fp, bcf_hdr_t *h);

    int vcf_parse(kstring_t *s, const bcf_hdr_t *h, bcf1_t *v);

    int vcf_format(const bcf_hdr_t *h, const bcf1_t *v, kstring_t *s);

    int bcf_read(htsFile *fp, const bcf_hdr_t *h, bcf1_t *v);

    #define BCF_UN_STR  1       // up to ALT inclusive
    #define BCF_UN_FLT  2       // up to FILTER
    #define BCF_UN_INFO 4       // up to INFO
    #define BCF_UN_SHR  (BCF_UN_STR|BCF_UN_FLT|BCF_UN_INFO) // all shared information
    #define BCF_UN_FMT  8                           // unpack format and each sample
    #define BCF_UN_IND  BCF_UN_FMT                  // a synonymo of BCF_UN_FMT
    #define BCF_UN_ALL  (BCF_UN_SHR|BCF_UN_FMT)     // everything
    int bcf_unpack(bcf1_t *b, int which);

    /*
     *  bcf_dup() - create a copy of BCF record.
     *
     *  Note that bcf_unpack() must be called on the returned copy as if it was
     *  obtained from bcf_read(). Also note that bcf_dup() calls bcf_sync1(src)
     *  internally to reflect any changes made by bcf_update_* functions.
     */
    bcf1_t *bcf_dup(bcf1_t *src);
    bcf1_t *bcf_copy(bcf1_t *dst, bcf1_t *src);

    int bcf_write(htsFile *fp, const bcf_hdr_t *h, bcf1_t *v);

    bcf_hdr_t *vcf_hdr_read(htsFile *fp);
    int vcf_hdr_write(htsFile *fp, const bcf_hdr_t *h);
    int vcf_read(htsFile *fp, const bcf_hdr_t *h, bcf1_t *v);
    int vcf_write(htsFile *fp, const bcf_hdr_t *h, bcf1_t *v);

    int bcf_readrec(BGZF *fp, void *null, void *v, int *tid, int *beg, int *end);



    /**************************************************************************
     *  Header querying and manipulation routines
     **************************************************************************/

    bcf_hdr_t *bcf_hdr_dup(const bcf_hdr_t *hdr);
    int bcf_hdr_combine(bcf_hdr_t *dst, const bcf_hdr_t *src);

    int bcf_hdr_add_sample(bcf_hdr_t *hdr, const char *sample);

    int bcf_hdr_set(bcf_hdr_t *hdr, const char *fname);

    char *bcf_hdr_fmt_text(const bcf_hdr_t *hdr, int is_bcf, int *len);

    int bcf_hdr_append(bcf_hdr_t *h, const char *line);
    int bcf_hdr_printf(bcf_hdr_t *h, const char *format, ...);

    const char *bcf_hdr_get_version(const bcf_hdr_t *hdr);
    void bcf_hdr_set_version(bcf_hdr_t *hdr, const char *version);

    void bcf_hdr_remove(bcf_hdr_t *h, int type, const char *key);

    bcf_hdr_t *bcf_hdr_subset(const bcf_hdr_t *h0, int n, char *const* samples, int *imap);

    const char **bcf_hdr_seqnames(const bcf_hdr_t *h, int *nseqs);

    #define bcf_hdr_nsamples(hdr) (hdr)->n[BCF_DT_SAMPLE]


    int bcf_hdr_parse(bcf_hdr_t *hdr, char *htxt);
    int bcf_hdr_sync(bcf_hdr_t *h);
    bcf_hrec_t *bcf_hdr_parse_line(const bcf_hdr_t *h, const char *line, int *len);
    void bcf_hrec_format(const bcf_hrec_t *hrec, kstring_t *str);
    int bcf_hdr_add_hrec(bcf_hdr_t *hdr, bcf_hrec_t *hrec);
    bcf_hrec_t *bcf_hdr_get_hrec(const bcf_hdr_t *hdr, int type, const char *key, const char *value, const char *str_class);
    bcf_hrec_t *bcf_hrec_dup(bcf_hrec_t *hrec);
    void bcf_hrec_add_key(bcf_hrec_t *hrec, const char *str, int len);
    void bcf_hrec_set_val(bcf_hrec_t *hrec, int i, const char *str, int len, int is_quoted);
    int bcf_hrec_find_key(bcf_hrec_t *hrec, const char *key);
    void hrec_add_idx(bcf_hrec_t *hrec, int idx);
    void bcf_hrec_destroy(bcf_hrec_t *hrec);



    /**************************************************************************
     *  Individual record querying and manipulation routines
     **************************************************************************/

    int bcf_subset(const bcf_hdr_t *h, bcf1_t *v, int n, int *imap);

    int bcf_translate(const bcf_hdr_t *dst_hdr, bcf_hdr_t *src_hdr, bcf1_t *src_line);

    int bcf_get_variant_types(bcf1_t *rec);
    int bcf_get_variant_type(bcf1_t *rec, int ith_allele);
    int bcf_is_snp(bcf1_t *v);

    int bcf_update_filter(const bcf_hdr_t *hdr, bcf1_t *line, int *flt_ids, int n);
    int bcf_add_filter(const bcf_hdr_t *hdr, bcf1_t *line, int flt_id);
    int bcf_remove_filter(const bcf_hdr_t *hdr, bcf1_t *line, int flt_id, int pass);
    int bcf_has_filter(const bcf_hdr_t *hdr, bcf1_t *line, char *filter);
    int bcf_update_alleles(const bcf_hdr_t *hdr, bcf1_t *line, const char **alleles, int nals);
    int bcf_update_alleles_str(const bcf_hdr_t *hdr, bcf1_t *line, const char *alleles_string);
    int bcf_update_id(const bcf_hdr_t *hdr, bcf1_t *line, const char *id);

    /*
     *  bcf_update_info_*() - functions for updating INFO fields
     *  @hdr:       the BCF header
     *  @line:      VCF line to be edited
     *  @key:       the INFO tag to be updated
     *  @values:    pointer to the array of values. Pass NULL to remove the tag.
     *  @n:         number of values in the array. When set to 0, the INFO tag is removed
     *
     *  The @string in bcf_update_info_flag() is optional, @n indicates whether
     *  the flag is set or removed.
     *
     *  Returns 0 on success or negative value on error.
     */
    #define bcf_update_info_int32(hdr,line,key,values,n)   bcf_update_info((hdr),(line),(key),(values),(n),BCF_HT_INT)
    #define bcf_update_info_float(hdr,line,key,values,n)   bcf_update_info((hdr),(line),(key),(values),(n),BCF_HT_REAL)
    #define bcf_update_info_flag(hdr,line,key,string,n)    bcf_update_info((hdr),(line),(key),(string),(n),BCF_HT_FLAG)
    #define bcf_update_info_string(hdr,line,key,string)    bcf_update_info((hdr),(line),(key),(string),1,BCF_HT_STR)
    int bcf_update_info(const bcf_hdr_t *hdr, bcf1_t *line, const char *key, const void *values, int n, int type);

    /*
     *  bcf_update_format_*() - functions for updating FORMAT fields
     *  @values:    pointer to the array of values, the same number of elements
     *              is expected for each sample. Missing values must be padded
     *              with bcf_*_missing or bcf_*_vector_end values.
     *  @n:         number of values in the array. If n==0, existing tag is removed.
     *
     *  The function bcf_update_format_string() is a higher-level (slower) variant of
     *  bcf_update_format_char(). The former accepts array of \0-terminated strings
     *  whereas the latter requires that the strings are collapsed into a single array
     *  of fixed-length strings. In case of strings with variable length, shorter strings
     *  can be \0-padded. Note that the collapsed strings passed to bcf_update_format_char()
     *  are not \0-terminated.
     *
     *  Returns 0 on success or negative value on error.
     */
    #define bcf_update_format_int32(hdr,line,key,values,n) bcf_update_format((hdr),(line),(key),(values),(n),BCF_HT_INT)
    #define bcf_update_format_float(hdr,line,key,values,n) bcf_update_format((hdr),(line),(key),(values),(n),BCF_HT_REAL)
    #define bcf_update_format_char(hdr,line,key,values,n) bcf_update_format((hdr),(line),(key),(values),(n),BCF_HT_STR)
    #define bcf_update_genotypes(hdr,line,gts,n) bcf_update_format((hdr),(line),"GT",(gts),(n),BCF_HT_INT)     // See bcf_gt_ macros below
    int bcf_update_format_string(const bcf_hdr_t *hdr, bcf1_t *line, const char *key, const char **values, int n);
    int bcf_update_format(const bcf_hdr_t *hdr, bcf1_t *line, const char *key, const void *values, int n, int type);

    // Macros for setting genotypes correctly, for use with bcf_update_genotypes only; idx corresponds
    // to VCF's GT (1-based index to ALT or 0 for the reference allele) and val is the opposite, obtained
    // from bcf_get_genotypes() below.
    #define bcf_gt_phased(idx)      ((idx+1)<<1|1)
    #define bcf_gt_unphased(idx)    ((idx+1)<<1)
    #define bcf_gt_missing          0 
    #define bcf_gt_is_missing(val)  ((val)>>1 ? 0 : 1)
    #define bcf_gt_is_phased(idx)   ((idx)&1)
    #define bcf_gt_allele(val)      (((val)>>1)-1)

    #define bcf_alleles2gt(a,b) ((a)>(b)?((a)*((a)+1)/2+(b)):((b)*((b)+1)/2+(a)))
    static inline void bcf_gt2alleles(int igt, int *a, int *b)
    {
        int k = 0, dk = 1;
        while ( k<igt ) { dk++; k += dk; }
        *b = dk - 1; *a = igt - k + *b;
    }

    bcf_fmt_t *bcf_get_fmt(const bcf_hdr_t *hdr, bcf1_t *line, const char *key);
    bcf_info_t *bcf_get_info(const bcf_hdr_t *hdr, bcf1_t *line, const char *key);

    bcf_fmt_t *bcf_get_fmt_id(bcf1_t *line, const int id);
    bcf_info_t *bcf_get_info_id(bcf1_t *line, const int id);

    #define bcf_get_info_int32(hdr,line,tag,dst,ndst)  bcf_get_info_values(hdr,line,tag,(void**)(dst),ndst,BCF_HT_INT)
    #define bcf_get_info_float(hdr,line,tag,dst,ndst)  bcf_get_info_values(hdr,line,tag,(void**)(dst),ndst,BCF_HT_REAL)
    #define bcf_get_info_string(hdr,line,tag,dst,ndst) bcf_get_info_values(hdr,line,tag,(void**)(dst),ndst,BCF_HT_STR)
    #define bcf_get_info_flag(hdr,line,tag,dst,ndst)   bcf_get_info_values(hdr,line,tag,(void**)(dst),ndst,BCF_HT_FLAG)
    int bcf_get_info_values(const bcf_hdr_t *hdr, bcf1_t *line, const char *tag, void **dst, int *ndst, int type);

    #define bcf_get_format_int32(hdr,line,tag,dst,ndst)  bcf_get_format_values(hdr,line,tag,(void**)(dst),ndst,BCF_HT_INT)
    #define bcf_get_format_float(hdr,line,tag,dst,ndst)  bcf_get_format_values(hdr,line,tag,(void**)(dst),ndst,BCF_HT_REAL)
    #define bcf_get_format_char(hdr,line,tag,dst,ndst)   bcf_get_format_values(hdr,line,tag,(void**)(dst),ndst,BCF_HT_STR)
    #define bcf_get_genotypes(hdr,line,dst,ndst)         bcf_get_format_values(hdr,line,"GT",(void**)(dst),ndst,BCF_HT_INT)
    int bcf_get_format_string(const bcf_hdr_t *hdr, bcf1_t *line, const char *tag, char ***dst, int *ndst);
    int bcf_get_format_values(const bcf_hdr_t *hdr, bcf1_t *line, const char *tag, void **dst, int *ndst, int type);



    /**************************************************************************
     *  Helper functions
     **************************************************************************/

    int bcf_hdr_id2int(const bcf_hdr_t *hdr, int type, const char *id);
    #define bcf_hdr_int2id(hdr,type,int_id) ((hdr)->id[type][int_id].key)

    static inline int bcf_hdr_name2id(const bcf_hdr_t *hdr, const char *id) { return bcf_hdr_id2int(hdr, BCF_DT_CTG, id); }
    static inline const char *bcf_hdr_id2name(const bcf_hdr_t *hdr, int rid) { return hdr->id[BCF_DT_CTG][rid].key; }
    static inline const char *bcf_seqname(const bcf_hdr_t *hdr, bcf1_t *rec) { return hdr->id[BCF_DT_CTG][rec->rid].key; }

    #define bcf_hdr_id2length(hdr,type,int_id)  ((hdr)->id[BCF_DT_ID][int_id].val->info[type]>>8 & 0xf)
    #define bcf_hdr_id2number(hdr,type,int_id)  ((hdr)->id[BCF_DT_ID][int_id].val->info[type]>>12)
    #define bcf_hdr_id2type(hdr,type,int_id)    ((hdr)->id[BCF_DT_ID][int_id].val->info[type]>>4 & 0xf)
    #define bcf_hdr_id2coltype(hdr,type,int_id) ((hdr)->id[BCF_DT_ID][int_id].val->info[type] & 0xf)
    #define bcf_hdr_idinfo_exists(hdr,type,int_id)  ((int_id<0 || bcf_hdr_id2coltype(hdr,type,int_id)==0xf) ? 0 : 1)
    #define bcf_hdr_id2hrec(hdr,dict_type,col_type,int_id)    ((hdr)->id[(dict_type)==BCF_DT_CTG?BCF_DT_CTG:BCF_DT_ID][int_id].val->hrec[(dict_type)==BCF_DT_CTG?0:(col_type)])

    void bcf_fmt_array(kstring_t *s, int n, int type, void *data);
    uint8_t *bcf_fmt_sized_array(kstring_t *s, uint8_t *ptr);

    void bcf_enc_vchar(kstring_t *s, int l, const char *a);
    void bcf_enc_vint(kstring_t *s, int n, int32_t *a, int wsize);
    void bcf_enc_vfloat(kstring_t *s, int n, float *a);


    /**************************************************************************
     *  BCF index
     *
     *  Note that these functions work with BCFs only. See synced_bcf_reader.h
     *  which provides (amongst other things) an API to work transparently with
     *  both indexed BCFs and VCFs.
     **************************************************************************/

    #define bcf_itr_destroy(iter) hts_itr_destroy(iter)
    #define bcf_itr_queryi(idx, tid, beg, end) hts_itr_query((idx), (tid), (beg), (end), bcf_readrec)
    #define bcf_itr_querys(idx, hdr, s) hts_itr_querys((idx), (s), (hts_name2id_f)(bcf_hdr_name2id), (hdr), hts_itr_query, bcf_readrec)
    #define bcf_itr_next(htsfp, itr, r) hts_itr_next((htsfp)->fp.bgzf, (itr), (r), 0)
    #define bcf_index_load(fn) hts_idx_load(fn, HTS_FMT_CSI)
    #define bcf_index_seqnames(idx, hdr, nptr) hts_idx_seqnames((idx),(nptr),(hts_id2name_f)(bcf_hdr_id2name),(hdr))

    int bcf_index_build(const char *fn, int min_shift);

#ifdef __cplusplus
}
#endif

/*******************
 * Typed value I/O *
 *******************/

/*
    Note that in contrast with BCFv2.1 specification, HTSlib implementation
    allows missing values in vectors. For integer types, the values 0x80,
    0x8000, 0x80000000 are interpreted as missing values and 0x81, 0x8001,
    0x80000001 as end-of-vector indicators.  Similarly for floats, the value of
    0x7F800001 is interpreted as a missing value and 0x7F800002 as an
    end-of-vector indicator.
    Note that the end-of-vector byte is not part of the vector.

    This trial BCF version (v2.2) is compatible with the VCF specification and
    enables to handle correctly vectors with different ploidy in presence of
    missing values.
 */
#define bcf_int8_vector_end  (INT8_MIN+1)
#define bcf_int16_vector_end (INT16_MIN+1)
#define bcf_int32_vector_end (INT32_MIN+1)
#define bcf_str_vector_end   0
#define bcf_int8_missing     INT8_MIN
#define bcf_int16_missing    INT16_MIN
#define bcf_int32_missing    INT32_MIN
#define bcf_str_missing      0x07
extern uint32_t bcf_float_vector_end;
extern uint32_t bcf_float_missing;
static inline void bcf_float_set(float *ptr, uint32_t value)
{
    union { uint32_t i; float f; } u;
    u.i = value;
    *ptr = u.f;
}
#define bcf_float_set_vector_end(x) bcf_float_set(&(x),bcf_float_vector_end)
#define bcf_float_set_missing(x)    bcf_float_set(&(x),bcf_float_missing)
static inline int bcf_float_is_missing(float f)
{
    union { uint32_t i; float f; } u;
    u.f = f;
    return u.i==bcf_float_missing ? 1 : 0;
}
static inline int bcf_float_is_vector_end(float f)
{
    union { uint32_t i; float f; } u;
    u.f = f;
    return u.i==bcf_float_vector_end ? 1 : 0;
}

static inline void bcf_format_gt(bcf_fmt_t *fmt, int isample, kstring_t *str)
{
    #define BRANCH(type_t, missing, vector_end) { \
        type_t *ptr = (type_t*) (fmt->p + isample*fmt->size); \
        int i; \
        for (i=0; i<fmt->n && ptr[i]!=vector_end; i++) \
        { \
            if ( i ) kputc("/|"[ptr[i]&1], str); \
            if ( !(ptr[i]>>1) ) kputc('.', str); \
            else kputw((ptr[i]>>1) - 1, str); \
        } \
        if (i == 0) kputc('.', str); \
    }
    switch (fmt->type) {
        case BCF_BT_INT8:  BRANCH(int8_t,  bcf_int8_missing, bcf_int8_vector_end); break;
        case BCF_BT_INT16: BRANCH(int16_t, bcf_int16_missing, bcf_int16_vector_end); break;
        case BCF_BT_INT32: BRANCH(int32_t, bcf_int32_missing, bcf_int32_vector_end); break;
        default: fprintf(stderr,"FIXME: type %d in bcf_format_gt?\n", fmt->type); abort(); break;
    }
    #undef BRANCH
}

static inline void bcf_enc_size(kstring_t *s, int size, int type)
{
    if (size >= 15) {
        kputc(15<<4|type, s);
        if (size >= 128) {
            if (size >= 32768) {
                int32_t x = size;
                kputc(1<<4|BCF_BT_INT32, s);
                kputsn((char*)&x, 4, s);
            } else {
                int16_t x = size;
                kputc(1<<4|BCF_BT_INT16, s);
                kputsn((char*)&x, 2, s);
            }
        } else {
            kputc(1<<4|BCF_BT_INT8, s);
            kputc(size, s);
        }
    } else kputc(size<<4|type, s);
}

static inline int bcf_enc_inttype(long x)
{
    if (x <= INT8_MAX && x > bcf_int8_missing) return BCF_BT_INT8;
    if (x <= INT16_MAX && x > bcf_int16_missing) return BCF_BT_INT16;
    return BCF_BT_INT32;
}

static inline void bcf_enc_int1(kstring_t *s, int32_t x)
{
    if (x == bcf_int32_vector_end) {
        bcf_enc_size(s, 1, BCF_BT_INT8);
        kputc(bcf_int8_vector_end, s);
    } else if (x == bcf_int32_missing) {
        bcf_enc_size(s, 1, BCF_BT_INT8);
        kputc(bcf_int8_missing, s);
    } else if (x <= INT8_MAX && x > bcf_int8_missing) {
        bcf_enc_size(s, 1, BCF_BT_INT8);
        kputc(x, s);
    } else if (x <= INT16_MAX && x > bcf_int16_missing) {
        int16_t z = x;
        bcf_enc_size(s, 1, BCF_BT_INT16);
        kputsn((char*)&z, 2, s);
    } else {
        int32_t z = x;
        bcf_enc_size(s, 1, BCF_BT_INT32);
        kputsn((char*)&z, 4, s);
    }
}

static inline int32_t bcf_dec_int1(const uint8_t *p, int type, uint8_t **q)
{
    if (type == BCF_BT_INT8) {
        *q = (uint8_t*)p + 1;
        return *(int8_t*)p;
    } else if (type == BCF_BT_INT16) {
        *q = (uint8_t*)p + 2;
        return *(int16_t*)p;
    } else {
        *q = (uint8_t*)p + 4;
        return *(int32_t*)p;
    }
}

static inline int32_t bcf_dec_typed_int1(const uint8_t *p, uint8_t **q)
{
    return bcf_dec_int1(p + 1, *p&0xf, q);
}

static inline int32_t bcf_dec_size(const uint8_t *p, uint8_t **q, int *type)
{
    *type = *p & 0xf;
    if (*p>>4 != 15) {
        *q = (uint8_t*)p + 1;
        return *p>>4;
    } else return bcf_dec_typed_int1(p + 1, q);
}

#endif