libhts-dev 1.7-2 / usr / include / htslib / vcf.h

/// @file htslib/vcf.h
/// High-level VCF/BCF variant calling file operations.
/*
    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"
#include "hts_defs.h"
#include "hts_endian.h"

#ifdef __cplusplus
extern "C" {
#endif

/*****************
 * 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 in info[0..2]
                       // for BCF_HL_FLT,INFO,FMT and contig length in info[0] for BCF_HL_CTG
    bcf_hrec_t *hrec[3];
    int id;
} bcf_idinfo_t;

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

// Note that bcf_hdr_t structs must always be created via bcf_hdr_init()
typedef struct {
    int32_t n[3];           // n:the size of the dictionary block in use, (allocated size, m, is below to preserve ABI)
    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;
    int32_t m[3];          // m: allocated size of the dictionary block in use (see n above)
} 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
#define VCF_BND   16    // breakend

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
#define BCF_ERR_LIMITS    8
#define BCF_ERR_CHAR     16
#define BCF_ERR_CTG_INVALID   32
#define BCF_ERR_TAG_INVALID   64

/*
    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 *
 *******/

    /***********************************************************************
     *  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.
     *
     ***********************************************************************/

    /** These macros are defined only for consistency with other parts of htslib */
    #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 bcf_empty1(v)       bcf_empty(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_init() - create an empty BCF header.
     *  @param mode    "r" or "w"
     *
     *  When opened for writing, the mandatory fileFormat and
     *  FILTER=PASS lines are added automatically.
     */
    bcf_hdr_t *bcf_hdr_init(const char *mode);

    /** Destroy a BCF header struct */
    void bcf_hdr_destroy(bcf_hdr_t *h);

    /** Initialize a bcf1_t object; equivalent to calloc(1, sizeof(bcf1_t)) */
    bcf1_t *bcf_init(void);

    /** Deallocate a bcf1_t object */
    void bcf_destroy(bcf1_t *v);

    /**
     *  Same as bcf_destroy() but frees only the memory allocated by bcf1_t,
     *  not the bcf1_t object itself.
     */
    void bcf_empty(bcf1_t *v);

    /**
     *  Make the bcf1_t object ready for next read. Intended mostly for
     *  internal use, the user should rarely need to call this function
     *  directly.
     */
    void bcf_clear(bcf1_t *v);


    /** bcf_open and vcf_open mode: please see hts_open() in hts.h */
    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)

    /** Reads VCF or BCF header */
    bcf_hdr_t *bcf_hdr_read(htsFile *fp);

    /**
     *  bcf_hdr_set_samples() - for more efficient VCF parsing when only one/few samples are needed
     *  @samples: samples to include or exclude from file or as a comma-separated string.
     *              LIST|FILE   .. select samples in list/file
     *              ^LIST|FILE  .. exclude samples from list/file
     *              -           .. include all samples
     *              NULL        .. exclude all samples
     *  @is_file: @samples is a file (1) or a comma-separated list (0)
     *
     *  The bottleneck of VCF reading is parsing of genotype fields. If the
     *  reader knows in advance that only subset of samples is needed (possibly
     *  no samples at all), the performance of bcf_read() can be significantly
     *  improved by calling bcf_hdr_set_samples after bcf_hdr_read().
     *  The function bcf_read() will subset the VCF/BCF records automatically
     *  with the notable exception when reading records via bcf_itr_next().
     *  In this case, bcf_subset_format() must be called explicitly, because
     *  bcf_readrec() does not see the header.
     *
     *  Returns 0 on success, -1 on error or a positive integer if the list
     *  contains samples not present in the VCF header. In such a case, the
     *  return value is the index of the offending sample.
     */
    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);


    /** Writes VCF or BCF header */
    int bcf_hdr_write(htsFile *fp, bcf_hdr_t *h);

    /**
     * Parse VCF line contained in kstring and populate the bcf1_t struct
     * The line must not end with \n or \r characters.
     */
    int vcf_parse(kstring_t *s, const bcf_hdr_t *h, bcf1_t *v);

    /** The opposite of vcf_parse. It should rarely be called directly, see vcf_write */
    int vcf_format(const bcf_hdr_t *h, const bcf1_t *v, kstring_t *s);

    /**
     *  bcf_read() - read next VCF or BCF record
     *
     *  Returns -1 on critical errors, 0 otherwise. On errors which are not
     *  critical for reading, such as missing header definitions, v->errcode is
     *  set to one of BCF_ERR* code and must be checked before calling
     *  vcf_write().
     */
    int bcf_read(htsFile *fp, const bcf_hdr_t *h, bcf1_t *v);

    /**
     *  bcf_unpack() - unpack/decode a BCF record (fills the bcf1_t::d field)
     *
     *  Note that bcf_unpack() must be called even when reading VCF. It is safe
     *  to call the function repeatedly, it will not unpack the same field
     *  twice.
     */
    #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);

    /**
     *  bcf_write() - write one VCF or BCF record. The type is determined at the open() call.
     */
    int bcf_write(htsFile *fp, bcf_hdr_t *h, bcf1_t *v);

    /**
     *  The following functions work only with VCFs and should rarely be called
     *  directly. Usually one wants to use their bcf_* alternatives, which work
     *  transparently with both VCFs and BCFs.
     */
    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);

    /** Helper function for the bcf_itr_next() macro; internal use, ignore it */
    int bcf_readrec(BGZF *fp, void *null, void *v, int *tid, int *beg, int *end);



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

    /** Create a new header using the supplied template */
    bcf_hdr_t *bcf_hdr_dup(const bcf_hdr_t *hdr);

    /**
     *  Copy header lines from src to dst if not already present in dst. See also bcf_translate().
     *  Returns 0 on success or sets a bit on error:
     *      1 .. conflicting definitions of tag length
     *      // todo
     */
    int bcf_hdr_combine(bcf_hdr_t *dst, const bcf_hdr_t *src) HTS_DEPRECATED("Please use bcf_hdr_merge instead");

    /**
     *  bcf_hdr_merge() - copy header lines from src to dst, see also bcf_translate()
     *  @param dst: the destination header to be merged into, NULL on the first pass
     *  @param src: the source header
     *
     *  Notes:
     *      - use as:
     *          bcf_hdr_t *dst = NULL;
     *          for (i=0; i<nsrc; i++) dst = bcf_hdr_merge(dst,src[i]);
     *
     *      - bcf_hdr_merge() replaces bcf_hdr_combine() which had a problem when
     *      combining multiple BCF headers. The current bcf_hdr_combine()
     *      does not have this problem, but became slow when used for many files.
     */
    bcf_hdr_t *bcf_hdr_merge(bcf_hdr_t *dst, const bcf_hdr_t *src);

    /**
     *  bcf_hdr_add_sample() - add a new sample.
     *  @param sample:  sample name to be added
     */
    int bcf_hdr_add_sample(bcf_hdr_t *hdr, const char *sample);

    /** Read VCF header from a file and update the header */
    int bcf_hdr_set(bcf_hdr_t *hdr, const char *fname);

    /// Appends formatted header text to _str_.
    /** If _is_bcf_ is zero, `IDX` fields are discarded.
     *  @return 0 if successful, or negative if an error occurred
     *  @since 1.4
     */
    int bcf_hdr_format(const bcf_hdr_t *hdr, int is_bcf, kstring_t *str);

    /** Returns formatted header (newly allocated string) and its length,
     *  excluding the terminating \0. If is_bcf parameter is unset, IDX
     *  fields are discarded.
     *  @deprecated Use bcf_hdr_format() instead as it can handle huge headers.
     */
    char *bcf_hdr_fmt_text(const bcf_hdr_t *hdr, int is_bcf, int *len)
        HTS_DEPRECATED("use bcf_hdr_format() instead");

    /** Append new VCF header line, returns 0 on success */
    int bcf_hdr_append(bcf_hdr_t *h, const char *line);
    int bcf_hdr_printf(bcf_hdr_t *h, const char *format, ...);

    /** VCF version, e.g. VCFv4.2 */
    const char *bcf_hdr_get_version(const bcf_hdr_t *hdr);
    void bcf_hdr_set_version(bcf_hdr_t *hdr, const char *version);

    /**
     *  bcf_hdr_remove() - remove VCF header tag
     *  @param type:      one of BCF_HL_*
     *  @param key:       tag name or NULL to remove all tags of the given type
     */
    void bcf_hdr_remove(bcf_hdr_t *h, int type, const char *key);

    /**
     *  bcf_hdr_subset() - creates a new copy of the header removing unwanted samples
     *  @param n:        number of samples to keep
     *  @param samples:  names of the samples to keep
     *  @param imap:     mapping from index in @samples to the sample index in the original file
     *
     *  Sample names not present in h0 are ignored. The number of unmatched samples can be checked
     *  by comparing n and bcf_hdr_nsamples(out_hdr).
     *  This function can be used to reorder samples.
     *  See also bcf_subset() which subsets individual records.
     */
    bcf_hdr_t *bcf_hdr_subset(const bcf_hdr_t *h0, int n, char *const* samples, int *imap);

    /** Creates a list of sequence names. It is up to the caller to free the list (but not the sequence names) */
    const char **bcf_hdr_seqnames(const bcf_hdr_t *h, int *nseqs);

    /** Get number of samples */
    #define bcf_hdr_nsamples(hdr) (hdr)->n[BCF_DT_SAMPLE]


    /** The following functions are for internal use and should rarely be called directly */
    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_hdr_get_hrec() - get header line info
     *  @param type:  one of the BCF_HL_* types: FLT,INFO,FMT,CTG,STR,GEN
     *  @param key:   the header key for generic lines (e.g. "fileformat"), any field
     *                  for structured lines, typically "ID".
     *  @param value: the value which pairs with key. Can be be NULL for BCF_HL_GEN
     *  @param str_class: the class of BCF_HL_STR line (e.g. "ALT" or "SAMPLE"), otherwise NULL
     */
    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
     **************************************************************************/

    /** See the description of bcf_hdr_subset() */
    int bcf_subset(const bcf_hdr_t *h, bcf1_t *v, int n, int *imap);

    /**
     *  bcf_translate() - translate tags ids to be consistent with different header. This function
     *                    is useful when lines from multiple VCF need to be combined.
     *  @dst_hdr:   the destination header, to be used in bcf_write(), see also bcf_hdr_combine()
     *  @src_hdr:   the source header, used in bcf_read()
     *  @src_line:  line obtained by bcf_read()
     */
    int bcf_translate(const bcf_hdr_t *dst_hdr, bcf_hdr_t *src_hdr, bcf1_t *src_line);

    /**
     *  bcf_get_variant_type[s]()  - returns one of VCF_REF, VCF_SNP, etc
     */
    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);

    /**
     *  bcf_update_filter() - sets the FILTER column
     *  @flt_ids:  The filter IDs to set, numeric IDs returned by bcf_hdr_id2int(hdr, BCF_DT_ID, "PASS")
     *  @n:        Number of filters. If n==0, all filters are removed
     */
    int bcf_update_filter(const bcf_hdr_t *hdr, bcf1_t *line, int *flt_ids, int n);
    /**
     *  bcf_add_filter() - adds to the FILTER column
     *  @flt_id:   filter ID to add, numeric ID returned by bcf_hdr_id2int(hdr, BCF_DT_ID, "PASS")
     *
     *  If flt_id is PASS, all existing filters are removed first. If other than PASS, existing PASS is removed.
     */
    int bcf_add_filter(const bcf_hdr_t *hdr, bcf1_t *line, int flt_id);
    /**
     *  bcf_remove_filter() - removes from the FILTER column
     *  @flt_id:   filter ID to remove, numeric ID returned by bcf_hdr_id2int(hdr, BCF_DT_ID, "PASS")
     *  @pass:     when set to 1 and no filters are present, set to PASS
     */
    int bcf_remove_filter(const bcf_hdr_t *hdr, bcf1_t *line, int flt_id, int pass);
    /**
     *  Returns 1 if present, 0 if absent, or -1 if filter does not exist. "PASS" and "." can be used interchangeably.
     */
    int bcf_has_filter(const bcf_hdr_t *hdr, bcf1_t *line, char *filter);
    /**
     *  bcf_update_alleles() and bcf_update_alleles_str() - update REF and ALLT column
     *  @alleles:           Array of alleles
     *  @nals:              Number of alleles
     *  @alleles_string:    Comma-separated alleles, starting with the REF allele
     */
    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);

    /**
      *  bcf_update_id() - sets new ID string
      *  bcf_add_id() - adds to the ID string checking for duplicates
      */
    int bcf_update_id(const bcf_hdr_t *hdr, bcf1_t *line, const char *id);
    int bcf_add_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)

    /** Conversion between alleles indexes to Number=G genotype index (assuming diploid, all 0-based) */
    #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_get_fmt() - returns pointer to FORMAT's field data
     * @header: for access to BCF_DT_ID dictionary
     * @line:   VCF line obtained from vcf_parse1
     * @fmt:    one of GT,PL,...
     *
     * Returns bcf_fmt_t* if the call succeeded, or returns NULL when the field
     * is not available.
     */
    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_get_*_id() - returns pointer to FORMAT/INFO field data given the header index instead of the string ID
     * @line: VCF line obtained from vcf_parse1
     * @id:  The header index for the tag, obtained from bcf_hdr_id2int()
     *
     * Returns bcf_fmt_t* / bcf_info_t*. These functions do not check if the index is valid
     * as their goal is to avoid the header lookup.
     */
    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);

    /**
     *  bcf_get_info_*() - get INFO values, integers or floats
     *  @hdr:       BCF header
     *  @line:      BCF record
     *  @tag:       INFO tag to retrieve
     *  @dst:       *dst is pointer to a memory location, can point to NULL
     *  @ndst:      pointer to the size of allocated memory
     *
     *  Returns negative value on error or the number of written values
     *  (including missing values) on success. bcf_get_info_string() returns
     *  on success the number of characters written excluding the null-
     *  terminating byte. bcf_get_info_flag() returns 1 when flag is set or 0
     *  if not.
     *
     *  List of return codes:
     *      -1 .. no such INFO tag defined in the header
     *      -2 .. clash between types defined in the header and encountered in the VCF record
     *      -3 .. tag is not present in the VCF record
     */
    #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);

    /**
     *  bcf_get_format_*() - same as bcf_get_info*() above
     *
     *  The function bcf_get_format_string() is a higher-level (slower) variant of bcf_get_format_char().
     *  see the description of bcf_update_format_string() and bcf_update_format_char() above.
     *  Unlike other bcf_get_format__*() functions, bcf_get_format_string() allocates two arrays:
     *  a single block of \0-terminated strings collapsed into a single array and an array of pointers
     *  to these strings. Both arrays must be cleaned by the user.
     *
     *  Returns negative value on error or the number of written values on success.
     *
     *  Use the returned number of written values for accessing valid entries of dst, as ndst is only a
     *  watermark that can be higher than the returned value, i.e. the end of dst can contain carry-over
     *  values from previous calls to bcf_get_format_*() on lines with more values per sample.
     *
     *  Example:
     *      int ndst = 0; char **dst = NULL;
     *      if ( bcf_get_format_string(hdr, line, "XX", &dst, &ndst) > 0 )
     *          for (i=0; i<bcf_hdr_nsamples(hdr); i++) printf("%s\n", dst[i]);
     *      free(dst[0]); free(dst);
     *
     *  Example:
     *      int i, j, ngt, nsmpl = bcf_hdr_nsamples(hdr);
     *      int32_t *gt_arr = NULL, ngt_arr = 0;
     *
     *      ngt = bcf_get_genotypes(hdr, line, &gt_arr, &ngt_arr);
     *      if ( ngt<=0 ) return; // GT not present
     *
     *      int max_ploidy = ngt/nsmpl;
     *      for (i=0; i<nsmpl; i++)
     *      {
     *        int32_t *ptr = gt + i*max_ploidy;
     *        for (j=0; j<max_ploidy; j++)
     *        {
     *           // if true, the sample has smaller ploidy
     *           if ( ptr[j]==bcf_int32_vector_end ) break;
     *
     *           // missing allele
     *           if ( bcf_gt_is_missing(ptr[j]) ) continue;
     *
     *           // the VCF 0-based allele index
     *           int allele_index = bcf_gt_allele(ptr[j]);
     *
     *           // is phased?
     *           int is_phased = bcf_gt_is_phased(ptr[j]);
     *
     *           // .. do something ..
     *         }
     *      }
     *      free(gt_arr);
     *
     */
    #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
     **************************************************************************/

    /**
     *  bcf_hdr_id2int() - Translates string into numeric ID
     *  bcf_hdr_int2id() - Translates numeric ID into string
     *  @type:     one of BCF_DT_ID, BCF_DT_CTG, BCF_DT_SAMPLE
     *  @id:       tag name, such as: PL, DP, GT, etc.
     *
     *  Returns -1 if string is not in dictionary, otherwise numeric ID which identifies
     *  fields in BCF records.
     */
    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)

    /**
     *  bcf_hdr_name2id() - Translates sequence names (chromosomes) into numeric ID
     *  bcf_hdr_id2name() - Translates numeric ID to sequence name
     */
    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; }

    /**
     *  bcf_hdr_id2*() - Macros for accessing bcf_idinfo_t
     *  @type:      one of BCF_HL_FLT, BCF_HL_INFO, BCF_HL_FMT
     *  @int_id:    return value of bcf_hdr_id2int, must be >=0
     *
     *  The returned values are:
     *     bcf_hdr_id2length   ..  whether the number of values is fixed or variable, one of BCF_VL_*
     *     bcf_hdr_id2number   ..  the number of values, 0xfffff for variable length fields
     *     bcf_hdr_id2type     ..  the field type, one of BCF_HT_*
     *     bcf_hdr_id2coltype  ..  the column type, one of BCF_HL_*
     *
     *  Notes: Prior to using the macros, the presence of the info should be
     *  tested with bcf_hdr_idinfo_exists().
     */
    #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))

    hts_idx_t *bcf_index_load2(const char *fn, const char *fnidx);

    /**
     *  bcf_index_build() - Generate and save an index file
     *  @fn:         Input VCF/BCF filename
     *  @min_shift:  Positive to generate CSI, or 0 to generate TBI
     *
     *  Returns 0 if successful, or negative if an error occurred.
     *
     *  List of error codes:
     *      -1 .. indexing failed
     *      -2 .. opening @fn failed
     *      -3 .. format not indexable
     *      -4 .. failed to create and/or save the index
     */
    int bcf_index_build(const char *fn, int min_shift);

    /**
     *  bcf_index_build2() - Generate and save an index to a specific file
     *  @fn:         Input VCF/BCF filename
     *  @fnidx:      Output filename, or NULL to add .csi/.tbi to @fn
     *  @min_shift:  Positive to generate CSI, or 0 to generate TBI
     *
     *  Returns 0 if successful, or negative if an error occurred.
     *
     *  List of error codes:
     *      -1 .. indexing failed
     *      -2 .. opening @fn failed
     *      -3 .. format not indexable
     *      -4 .. failed to create and/or save the index
     */
    int bcf_index_build2(const char *fn, const char *fnidx, int min_shift);

    /**
     *  bcf_index_build3() - Generate and save an index to a specific file
     *  @fn:         Input VCF/BCF filename
     *  @fnidx:      Output filename, or NULL to add .csi/.tbi to @fn
     *  @min_shift:  Positive to generate CSI, or 0 to generate TBI
     *  @n_threads:  Number of VCF/BCF decoder threads
     *
     *  Returns 0 if successful, or negative if an error occurred.
     *
     *  List of error codes:
     *      -1 .. indexing failed
     *      -2 .. opening @fn failed
     *      -3 .. format not indexable
     *      -4 .. failed to create and/or save the index
     */
     int bcf_index_build3(const char *fn, const char *fnidx, int min_shift, int n_threads);

/*******************
 * 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;
        case BCF_BT_NULL:  kputc('.', str); break;
        default: hts_log_error("Unexpected type %d", 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 le_to_i8(p);
    } else if (type == BCF_BT_INT16) {
        *q = (uint8_t*)p + 2;
        return le_to_i16(p);
    } else {
        *q = (uint8_t*)p + 4;
        return le_to_i32(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);
}

#ifdef __cplusplus
}
#endif

#endif