cram_io.c

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/*
Copyright (c) 2012-2014 Genome Research Ltd.
Author: James Bonfield <jkb@sanger.ac.uk>

Redistribution and use in source and binary forms, with or without 
modification, are permitted provided that the following conditions are met:

   1. Redistributions of source code must retain the above copyright notice, 
this list of conditions and the following disclaimer.

   2. Redistributions in binary form must reproduce the above copyright notice, 
this list of conditions and the following disclaimer in the documentation 
and/or other materials provided with the distribution.

   3. Neither the names Genome Research Ltd and Wellcome Trust Sanger
Institute nor the names of its contributors may be used to endorse or promote
products derived from this software without specific prior written permission.

THIS SOFTWARE IS PROVIDED BY GENOME RESEARCH LTD AND CONTRIBUTORS "AS IS" AND 
ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE IMPLIED 
WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE 
DISCLAIMED. IN NO EVENT SHALL GENOME RESEARCH LTD OR CONTRIBUTORS BE LIABLE
FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR CONSEQUENTIAL
DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR
SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER
CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY,
OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE
OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
*/

/*
 * CRAM I/O primitives.
 *
 * - ITF8 encoding and decoding.
 * - Block based I/O
 * - Zlib inflating and deflating (memory)
 * - CRAM basic data structure reading and writing
 * - File opening / closing
 * - Reference sequence handling
 */

/*
 * TODO: BLOCK_GROW, BLOCK_RESIZE, BLOCK_APPEND and itf8_put_blk all need
 * a way to return errors for when malloc fails.
 */

#ifdef HAVE_CONFIG_H
#include "io_lib_config.h"
#endif

#include <stdio.h>
#include <errno.h>
#include <assert.h>
#include <stdlib.h>
#include <string.h>
#include <zlib.h>
#ifdef HAVE_LIBBZ2
#include <bzlib.h>
#endif
#include <sys/types.h>
#include <sys/stat.h>
#include <math.h>
#include <ctype.h>

#include "cram/cram.h"
#include "cram/os.h"
#include "cram/md5.h"
#include "cram/open_trace_file.h"

//#define REF_DEBUG

#ifdef REF_DEBUG
#include <sys/syscall.h>
#define gettid() (int)syscall(SYS_gettid)

#define RP(...) fprintf (stderr, __VA_ARGS__)
#else
#define RP(...) 
#endif

#ifdef SAMTOOLS
#include "htslib/hfile.h"
#define paranoid_hclose(fp) (hclose(fp))
#else
#define hclose_abruptly(fp) (fclose(fp))
#define hflush(fp)   (fflush(fp))
#define hgetc(fp)    (getc(fp))
#define hputc(c, fp) (putc((c), (fp)))
#define hread(fp, buffer, nbytes)  (fread((buffer), 1, (nbytes), (fp)))
#define hseek(fp, offset, whence)  (fseeko((fp), (offset), (whence)))
#define hwrite(fp, buffer, nbytes) (fwrite((buffer), 1, (nbytes), (fp)))
#define paranoid_hclose(fp)        (paranoid_fclose(fp))
#endif

/* ----------------------------------------------------------------------
 * ITF8 encoding and decoding.
 *
* Also see the itf8_get and itf8_put macros in cram_io.h
 */

/*
 * Reads an integer in ITF-8 encoding from 'cp' and stores it in
 * *val.
 *
 * Returns the number of bytes read on success
 *        -1 on failure
 */
int itf8_decode(cram_fd *fd, int32_t *val_p) {
    static int nbytes[16] = {
        0,0,0,0, 0,0,0,0,                               // 0000xxxx - 0111xxxx
        1,1,1,1,                                        // 1000xxxx - 1011xxxx
        2,2,                                            // 1100xxxx - 1101xxxx
        3,                                              // 1110xxxx
        4,                                              // 1111xxxx
    };

    static int nbits[16] = {
        0x7f, 0x7f, 0x7f, 0x7f, 0x7f, 0x7f, 0x7f, 0x7f, // 0000xxxx - 0111xxxx
        0x3f, 0x3f, 0x3f, 0x3f,                         // 1000xxxx - 1011xxxx
        0x1f, 0x1f,                                     // 1100xxxx - 1101xxxx
        0x0f,                                           // 1110xxxx
        0x0f,                                           // 1111xxxx
    };

    int32_t val = hgetc(fd->fp);
    if (val == -1)
        return -1;

    int i = nbytes[val>>4];
    val &= nbits[val>>4];

    switch(i) {
    case 0:
        *val_p = val;
        return 1;

    case 1:
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        *val_p = val;
        return 2;

    case 2:
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        *val_p = val;
        return 3;

    case 3:
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        *val_p = val;
        return 4;

    case 4: // really 3.5 more, why make it different?
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<4) | (((unsigned char)hgetc(fd->fp)) & 0x0f);
        *val_p = val;
    }

    return 5;
}

/*
 * Encodes and writes a single integer in ITF-8 format.
 * Returns 0 on success
 *        -1 on failure
 */
int itf8_encode(cram_fd *fd, int32_t val) {
    char buf[5];
    int len = itf8_put(buf, val);
    return hwrite(fd->fp, buf, len) == len ? 0 : -1;
}

#ifndef ITF8_MACROS
/*
 * As above, but decoding from memory
 */
int itf8_get(char *cp, int32_t *val_p) {
    unsigned char *up = (unsigned char *)cp;
    
    if (up[0] < 0x80) {
        *val_p =   up[0];
        return 1;
    } else if (up[0] < 0xc0) {
        *val_p = ((up[0] <<8) |  up[1])                           & 0x3fff;
        return 2;
    } else if (up[0] < 0xe0) {
        *val_p = ((up[0]<<16) | (up[1]<< 8) |  up[2])             & 0x1fffff;
        return 3;
    } else if (up[0] < 0xf0) {
        *val_p = ((up[0]<<24) | (up[1]<<16) | (up[2]<<8) | up[3]) & 0x0fffffff;
        return 4;
    } else {
        *val_p = ((up[0] & 0x0f)<<28) | (up[1]<<20) | (up[2]<<12) | (up[3]<<4) | (up[4] & 0x0f);
        return 5;
    }
}

/*
 * Stores a value to memory in ITF-8 format.
 *
 * Returns the number of bytes required to store the number.
 * This is a maximum of 5 bytes.
 */
int itf8_put(char *cp, int32_t val) {
    if        (!(val & ~0x00000007f)) { // 1 byte
        *cp = val;
        return 1;
    } else if (!(val & ~0x00003fff)) { // 2 byte
        *cp++ = (val >> 8 ) | 0x80;
        *cp   = val & 0xff;
        return 2;
    } else if (!(val & ~0x01fffff)) { // 3 byte
        *cp++ = (val >> 16) | 0xc0;
        *cp++ = (val >> 8 ) & 0xff;
        *cp   = val & 0xff;
        return 3;
    } else if (!(val & ~0x0fffffff)) { // 4 byte
        *cp++ = (val >> 24) | 0xe0;
        *cp++ = (val >> 16) & 0xff;
        *cp++ = (val >> 8 ) & 0xff;
        *cp   = val & 0xff;
        return 4;
    } else {                           // 5 byte
        *cp++ = 0xf0 | ((val>>28) & 0xff);
        *cp++ = (val >> 20) & 0xff;
        *cp++ = (val >> 12) & 0xff;
        *cp++ = (val >> 4 ) & 0xff;
        *cp = val & 0x0f;
        return 5;
    }
}
#endif

/* 64-bit itf8 variant */
int ltf8_put(char *cp, int64_t val) {
    if        (!(val & ~((1LL<<7)-1))) {
        *cp = val;
        return 1;
    } else if (!(val & ~((1LL<<(6+8))-1))) {
        *cp++ = (val >> 8 ) | 0x80;
        *cp   = val & 0xff;
        return 2;
    } else if (!(val & ~((1LL<<(5+2*8))-1))) {
        *cp++ = (val >> 16) | 0xc0;
        *cp++ = (val >> 8 ) & 0xff;
        *cp   = val & 0xff;
        return 3;
    } else if (!(val & ~((1LL<<(4+3*8))-1))) {
        *cp++ = (val >> 24) | 0xe0;
        *cp++ = (val >> 16) & 0xff;
        *cp++ = (val >> 8 ) & 0xff;
        *cp   = val & 0xff;
        return 4;
    } else if (!(val & ~((1LL<<(3+4*8))-1))) {
        *cp++ = (val >> 32) | 0xf0;
        *cp++ = (val >> 24) & 0xff;
        *cp++ = (val >> 16) & 0xff;
        *cp++ = (val >> 8 ) & 0xff;
        *cp   = val & 0xff;
        return 5;
    } else if (!(val & ~((1LL<<(2+5*8))-1))) {
        *cp++ = (val >> 40) | 0xf8;
        *cp++ = (val >> 32) & 0xff;
        *cp++ = (val >> 24) & 0xff;
        *cp++ = (val >> 16) & 0xff;
        *cp++ = (val >> 8 ) & 0xff;
        *cp   = val & 0xff;
        return 6;
    } else if (!(val & ~((1LL<<(1+6*8))-1))) {
        *cp++ = (val >> 48) | 0xfc;
        *cp++ = (val >> 40) & 0xff;
        *cp++ = (val >> 32) & 0xff;
        *cp++ = (val >> 24) & 0xff;
        *cp++ = (val >> 16) & 0xff;
        *cp++ = (val >> 8 ) & 0xff;
        *cp   = val & 0xff;
        return 7;
    } else if (!(val & ~((1LL<<(7*8))-1))) {
        *cp++ = (val >> 56) | 0xfe;
        *cp++ = (val >> 48) & 0xff;
        *cp++ = (val >> 40) & 0xff;
        *cp++ = (val >> 32) & 0xff;
        *cp++ = (val >> 24) & 0xff;
        *cp++ = (val >> 16) & 0xff;
        *cp++ = (val >> 8 ) & 0xff;
        *cp   = val & 0xff;
        return 8;
    } else {
        *cp++ = 0xff;
        *cp++ = (val >> 56) & 0xff;
        *cp++ = (val >> 48) & 0xff;
        *cp++ = (val >> 40) & 0xff;
        *cp++ = (val >> 32) & 0xff;
        *cp++ = (val >> 24) & 0xff;
        *cp++ = (val >> 16) & 0xff;
        *cp++ = (val >> 8 ) & 0xff;
        *cp   = val & 0xff;
        return 9;
    }
}

int ltf8_get(char *cp, int64_t *val_p) {
    unsigned char *up = (unsigned char *)cp;
    
    if (up[0] < 0x80) {
        *val_p =   up[0];
        return 1;
    } else if (up[0] < 0xc0) {
        *val_p = (((uint64_t)up[0]<< 8) |
                   (uint64_t)up[1]) & (((1LL<<(6+8)))-1);
        return 2;
    } else if (up[0] < 0xe0) {
        *val_p = (((uint64_t)up[0]<<16) |
                  ((uint64_t)up[1]<< 8) |
                   (uint64_t)up[2]) & ((1LL<<(5+2*8))-1);
        return 3;
    } else if (up[0] < 0xf0) {
        *val_p = (((uint64_t)up[0]<<24) |
                  ((uint64_t)up[1]<<16) |
                  ((uint64_t)up[2]<< 8) |
                   (uint64_t)up[3]) & ((1LL<<(4+3*8))-1);
        return 4;
    } else if (up[0] < 0xf8) {
        *val_p = (((uint64_t)up[0]<<32) |
                  ((uint64_t)up[1]<<24) |
                  ((uint64_t)up[2]<<16) |
                  ((uint64_t)up[3]<< 8) |
                   (uint64_t)up[4]) & ((1LL<<(3+4*8))-1);
        return 5;
    } else if (up[0] < 0xfc) {
        *val_p = (((uint64_t)up[0]<<40) |
                  ((uint64_t)up[1]<<32) |
                  ((uint64_t)up[2]<<24) |
                  ((uint64_t)up[3]<<16) |
                  ((uint64_t)up[4]<< 8) |
                   (uint64_t)up[5]) & ((1LL<<(2+5*8))-1);
        return 6;
    } else if (up[0] < 0xfe) {
        *val_p = (((uint64_t)up[0]<<48) |
                  ((uint64_t)up[1]<<40) |
                  ((uint64_t)up[2]<<32) |
                  ((uint64_t)up[3]<<24) |
                  ((uint64_t)up[4]<<16) |
                  ((uint64_t)up[5]<< 8) |
                   (uint64_t)up[6]) & ((1LL<<(1+6*8))-1);
        return 7;
    } else if (up[0] < 0xff) {
        *val_p = (((uint64_t)up[1]<<48) |
                  ((uint64_t)up[2]<<40) |
                  ((uint64_t)up[3]<<32) |
                  ((uint64_t)up[4]<<24) |
                  ((uint64_t)up[5]<<16) |
                  ((uint64_t)up[6]<< 8) |
                   (uint64_t)up[7]) & ((1LL<<(7*8))-1);
        return 8;
    } else {
        *val_p = (((uint64_t)up[1]<<56) |
                  ((uint64_t)up[2]<<48) |
                  ((uint64_t)up[3]<<40) |
                  ((uint64_t)up[4]<<32) |
                  ((uint64_t)up[5]<<24) |
                  ((uint64_t)up[6]<<16) |
                  ((uint64_t)up[7]<< 8) |
                   (uint64_t)up[8]);
        return 9;
    }
}

int ltf8_decode(cram_fd *fd, int64_t *val_p) {
    int c = hgetc(fd->fp);
    int64_t val = (unsigned char)c;
    if (c == -1)
        return -1;

    if (val < 0x80) {
        *val_p =   val;
        return 1;

    } else if (val < 0xc0) {
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        *val_p = val & (((1LL<<(6+8)))-1);
        return 2;

    } else if (val < 0xe0) {
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        *val_p = val & ((1LL<<(5+2*8))-1);
        return 3;

    } else if (val < 0xf0) {
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        *val_p = val & ((1LL<<(4+3*8))-1);
        return 4;

    } else if (val < 0xf8) {
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        *val_p = val & ((1LL<<(3+4*8))-1);
        return 5;

    } else if (val < 0xfc) {
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        *val_p = val & ((1LL<<(2+5*8))-1);
        return 6;

    } else if (val < 0xfe) {
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        *val_p = val & ((1LL<<(1+6*8))-1);
        return 7;

    } else if (val < 0xff) {
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        *val_p = val & ((1LL<<(7*8))-1);
        return 8;

    } else {
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        val = (val<<8) | (unsigned char)hgetc(fd->fp);
        *val_p = val;
    }

    return 9;
}

/*
 * Pushes a value in ITF8 format onto the end of a block.
 * This shouldn't be used for high-volume data as it is not the fastest
 * method.
 *
 * Returns the number of bytes written
 */
int itf8_put_blk(cram_block *blk, int val) {
    char buf[5];
    int sz;

    sz = itf8_put(buf, val);
    BLOCK_APPEND(blk, buf, sz);
    return sz;
}

/*
 * Decodes a 32-bit little endian value from fd and stores in val.
 *
 * Returns the number of bytes read on success
 *         -1 on failure
 */
int int32_decode(cram_fd *fd, int32_t *val) {
    int32_t i;
    if (4 != hread(fd->fp, &i, 4))
        return -1;

    *val = le_int4(i);
    return 4;
}

/*
 * Encodes a 32-bit little endian value 'val' and writes to fd.
 *
 * Returns the number of bytes written on success
 *         -1 on failure
 */
int int32_encode(cram_fd *fd, int32_t val) {
    val = le_int4(val);
    if (4 != hwrite(fd->fp, &val, 4))
        return -1;

    return 4;
}

/* As int32_decoded/encode, but from/to blocks instead of cram_fd */
int int32_get(cram_block *b, int32_t *val) {
    if (b->uncomp_size - BLOCK_SIZE(b) < 4)
        return -1;

    *val =
         b->data[b->byte  ]        |
        (b->data[b->byte+1] <<  8) |
        (b->data[b->byte+2] << 16) |
        (b->data[b->byte+3] << 24);
    BLOCK_SIZE(b) += 4;
    return 4;
}

/* As int32_decoded/encode, but from/to blocks instead of cram_fd */
int int32_put(cram_block *b, int32_t val) {
    unsigned char cp[4];
    cp[0] = ( val      & 0xff);
    cp[1] = ((val>>8)  & 0xff);
    cp[2] = ((val>>16) & 0xff);
    cp[3] = ((val>>24) & 0xff);

    BLOCK_APPEND(b, cp, 4);
    return b->data ? 0 : -1;
}

/* ----------------------------------------------------------------------
 * zlib compression code - from Gap5's tg_iface_g.c
 * They're static here as they're only used within the cram_compress_block
 * and cram_uncompress_block functions, which are the external interface.
 */
char *zlib_mem_inflate(char *cdata, size_t csize, size_t *size) {
    z_stream s;
    unsigned char *data = NULL; /* Uncompressed output */
    int data_alloc = 0;
    int err;

    /* Starting point at uncompressed size, and scale after that */
    data = malloc(data_alloc = csize*1.2+100);
    if (!data)
        return NULL;

    /* Initialise zlib stream */
    s.zalloc = Z_NULL; /* use default allocation functions */
    s.zfree  = Z_NULL;
    s.opaque = Z_NULL;
    s.next_in  = (unsigned char *)cdata;
    s.avail_in = csize;
    s.total_in = 0;
    s.next_out  = data;
    s.avail_out = data_alloc;
    s.total_out = 0;

    //err = inflateInit(&s);
    err = inflateInit2(&s, 15 + 32);
    if (err != Z_OK) {
        fprintf(stderr, "zlib inflateInit error: %s\n", s.msg);
        free(data);
        return NULL;
    }

    /* Decode to 'data' array */
    for (;s.avail_in;) {
        unsigned char *data_tmp;
        int alloc_inc;

        s.next_out = &data[s.total_out];
        err = inflate(&s, Z_NO_FLUSH);
        if (err == Z_STREAM_END)
            break;

        if (err != Z_OK) {
            fprintf(stderr, "zlib inflate error: %s\n", s.msg);
            break;
        }

        /* More to come, so realloc based on growth so far */
        alloc_inc = (double)s.avail_in/s.total_in * s.total_out + 100;
        data = realloc((data_tmp = data), data_alloc += alloc_inc);
        if (!data) {
            free(data_tmp);
            return NULL;
        }
        s.avail_out += alloc_inc;
    }
    inflateEnd(&s);

    *size = s.total_out;
    return (char *)data;
}

static char *zlib_mem_deflate(char *data, size_t size, size_t *cdata_size,
                              int level, int strat) {
    z_stream s;
    unsigned char *cdata = NULL; /* Compressed output */
    int cdata_alloc = 0;
    int cdata_pos = 0;
    int err;

    cdata = malloc(cdata_alloc = size*1.05+100);
    if (!cdata)
        return NULL;
    cdata_pos = 0;

    /* Initialise zlib stream */
    s.zalloc = Z_NULL; /* use default allocation functions */
    s.zfree  = Z_NULL;
    s.opaque = Z_NULL;
    s.next_in  = (unsigned char *)data;
    s.avail_in = size;
    s.total_in = 0;
    s.next_out  = cdata;
    s.avail_out = cdata_alloc;
    s.total_out = 0;
    s.data_type = Z_BINARY;

    err = deflateInit2(&s, level, Z_DEFLATED, 15|16, 9, strat);
    if (err != Z_OK) {
        fprintf(stderr, "zlib deflateInit2 error: %s\n", s.msg);
        return NULL;
    }

    /* Encode to 'cdata' array */
    for (;s.avail_in;) {
        s.next_out = &cdata[cdata_pos];
        s.avail_out = cdata_alloc - cdata_pos;
        if (cdata_alloc - cdata_pos <= 0) {
            fprintf(stderr, "Deflate produced larger output than expected. Abort\n"); 
            return NULL;
        }
        err = deflate(&s, Z_NO_FLUSH);
        cdata_pos = cdata_alloc - s.avail_out;
        if (err != Z_OK) {
            fprintf(stderr, "zlib deflate error: %s\n", s.msg);
            break;
        }
    }
    if (deflate(&s, Z_FINISH) != Z_STREAM_END) {
        fprintf(stderr, "zlib deflate error: %s\n", s.msg);
    }
    *cdata_size = s.total_out;

    if (deflateEnd(&s) != Z_OK) {
        fprintf(stderr, "zlib deflate error: %s\n", s.msg);
    }
    return (char *)cdata;
}

/* ----------------------------------------------------------------------
 * CRAM blocks - the dynamically growable data block. We have code to
 * create, update, (un)compress and read/write.
 *
 * These are derived from the deflate_interlaced.c blocks, but with the
 * CRAM extension of content types and IDs.
 */

/*
 * Allocates a new cram_block structure with a specified content_type and
 * id.
 *
 * Returns block pointer on success
 *         NULL on failure
 */
cram_block *cram_new_block(enum cram_content_type content_type,
                           int content_id) {
    cram_block *b = malloc(sizeof(*b));
    if (!b)
        return NULL;
    b->method = b->orig_method = RAW;
    b->content_type = content_type;
    b->content_id = content_id;
    b->comp_size = 0;
    b->uncomp_size = 0;
    b->data = NULL;
    b->alloc = 0;
    b->byte = 0;
    b->bit = 7; // MSB

    return b;
}

/*
 * Reads a block from a cram file.
 * Returns cram_block pointer on success.
 *         NULL on failure
 */
cram_block *cram_read_block(cram_fd *fd) {
    cram_block *b = malloc(sizeof(*b));
    if (!b)
        return NULL;

    //fprintf(stderr, "Block at %d\n", (int)ftell(fd->fp));

    if (-1 == (b->method      = hgetc(fd->fp))) { free(b); return NULL; }
    if (-1 == (b->content_type= hgetc(fd->fp))) { free(b); return NULL; }
    if (-1 == itf8_decode(fd, &b->content_id))  { free(b); return NULL; }
    if (-1 == itf8_decode(fd, &b->comp_size))   { free(b); return NULL; }
    if (-1 == itf8_decode(fd, &b->uncomp_size)) { free(b); return NULL; }

    //    fprintf(stderr, "  method %d, ctype %d, cid %d, csize %d, ucsize %d\n",
    //      b->method, b->content_type, b->content_id, b->comp_size, b->uncomp_size);

    if (b->method == RAW) {
        b->alloc = b->uncomp_size;
        if (!(b->data = malloc(b->uncomp_size))){ free(b); return NULL; }
        if (b->uncomp_size != hread(fd->fp, b->data, b->uncomp_size)) {
            free(b->data);
            free(b);
            return NULL;
        }
    } else {
        b->alloc = b->comp_size;
        if (!(b->data = malloc(b->comp_size)))  { free(b); return NULL; }
        if (b->comp_size != hread(fd->fp, b->data, b->comp_size)) {
            free(b->data);
            free(b);
            return NULL;
        }
    }

    b->orig_method = b->method;
    b->idx = 0;
    b->byte = 0;
    b->bit = 7; // MSB

    return b;
}

/*
 * Writes a CRAM block.
 * Returns 0 on success
 *        -1 on failure
 */
int cram_write_block(cram_fd *fd, cram_block *b) {
    assert(b->method != RAW || (b->comp_size == b->uncomp_size));

    if (hputc(b->method,       fd->fp)  == EOF) return -1;
    if (hputc(b->content_type, fd->fp)  == EOF) return -1;
    if (itf8_encode(fd, b->content_id)  ==  -1) return -1;
    if (itf8_encode(fd, b->comp_size)   ==  -1) return -1;
    if (itf8_encode(fd, b->uncomp_size) ==  -1) return -1;

    if (b->method == RAW) {
        if (b->uncomp_size != hwrite(fd->fp, b->data, b->uncomp_size))
            return -1;
    } else {
        if (b->comp_size != hwrite(fd->fp, b->data, b->comp_size))
            return -1;
    }

    return 0;
}

/*
 * Frees a CRAM block, deallocating internal data too.
 */
void cram_free_block(cram_block *b) {
    if (!b)
        return;
    if (b->data)
        free(b->data);
    free(b);
}

/*
 * Uncompresses a CRAM block, if compressed.
 */
int cram_uncompress_block(cram_block *b) {
    char *uncomp;
    size_t uncomp_size = 0;

    if (b->uncomp_size == 0) {
        // blank block
        b->method = RAW;
        return 0;
    }

    switch (b->method) {
    case RAW:
        b->uncomp_size = b->comp_size;
        return 0;

    case GZIP:
        uncomp = zlib_mem_inflate((char *)b->data, b->comp_size, &uncomp_size);
        if (!uncomp)
            return -1;
        if ((int)uncomp_size != b->uncomp_size)
            return -1;
        free(b->data);
        b->data = (unsigned char *)uncomp;
        b->alloc = uncomp_size;
        b->method = RAW;
        break;

#ifdef HAVE_LIBBZ2
    case BZIP2: {
        unsigned int usize = b->uncomp_size;
        if (!(uncomp = malloc(usize)))
            return -1;
        if (BZ_OK != BZ2_bzBuffToBuffDecompress(uncomp, &usize,
                                                (char *)b->data, b->comp_size,
                                                0, 0)) {
            free(uncomp);
            return -1;
        }
        b->data = (unsigned char *)uncomp;
        b->alloc = usize;
        b->method = RAW;
        b->uncomp_size = usize; // Just incase it differs
        break;
    }
#else
    case BZIP2:
        fprintf(stderr, "Bzip2 compression is not compiled into this "
                "version.\nPlease rebuild and try again.\n");
        return -1;
#endif

    case BM_ERROR:
    default:
        return -1;
    }

    return 0;
}

#ifdef HAVE_LIBBZ2
static int cram_compress_block_bzip2(cram_fd *fd, cram_block *b,
                                     cram_metrics *metrics, int level) {
    unsigned int comp_size = b->uncomp_size*1.01 + 600;
    char *comp = malloc(comp_size);
    char *data = (char *)b->data;

    if (!comp)
        return -1;

    if (!data)
        data = "";

    if (BZ_OK != BZ2_bzBuffToBuffCompress(comp, &comp_size,
                                          data, b->uncomp_size,
                                          level, 0, 30)) {
        free(comp);
        return -1;
    }

    free(b->data);
    b->data = (unsigned char *)comp;
    b->method = BZIP2;
    b->comp_size = comp_size;

    if (fd->verbose)
        fprintf(stderr, "Compressed block ID %d from %d to %d\n",
                b->content_id, b->uncomp_size, b->comp_size);

    return 0;
}
#endif

/*
 * Compresses a block using one of two different zlib strategies. If we only
 * want one choice set strat2 to be -1.
 *
 * The logic here is that sometimes Z_RLE does a better job than Z_FILTERED
 * or Z_DEFAULT_STRATEGY on quality data. If so, we'd rather use it as it is
 * significantly faster.
 */
int cram_compress_block(cram_fd *fd, cram_block *b, cram_metrics *metrics,
                        int level,  int strat,
                        int level2, int strat2) {
    char *comp = NULL;
    size_t comp_size = 0;

    if (level == 0) {
        b->method = RAW;
        b->comp_size = b->uncomp_size;
        return 0;
    }

    if (b->method != RAW) {
        fprintf(stderr, "Attempt to compress an already compressed block.\n");
        return 0;
    }

#ifdef HAVE_LIBBZ2
    if (fd->use_bz2)
        // metrics ignored for bzip2
        return cram_compress_block_bzip2(fd, b, metrics, level);
#endif

    pthread_mutex_lock(&fd->metrics_lock);
    if (strat2 >= 0)
        if (fd->verbose > 1)
            fprintf(stderr, "metrics trial %d, next_trial %d, m1 %d, m2 %d\n",
                    metrics->trial, metrics->next_trial,
                    metrics->m1, metrics->m2);

    if (strat2 >= 0 && (metrics->trial > 0 || --metrics->next_trial <= 0)) {
        char *c1, *c2;
        size_t s1, s2;

        if (metrics->next_trial == 0) {
            metrics->next_trial = 100;
            metrics->trial = 3;
            metrics->m1 = metrics->m2 = 0;
        }
        pthread_mutex_unlock(&fd->metrics_lock);

        c1 = zlib_mem_deflate((char *)b->data, b->uncomp_size,
                              &s1, level, strat);
        c2 = zlib_mem_deflate((char *)b->data, b->uncomp_size,
                              &s2, level2, strat2);
        if (!c1 || !c2)
            return -1;
        
        //fprintf(stderr, "1: %6d   2: %6d   %5.1f\n", s1, s2, 100.0*s1/s2);

        pthread_mutex_lock(&fd->metrics_lock);
        if (s1 < 0.98 * s2) { // 2nd one should be faster alternative
            if (fd->verbose > 1)
                fprintf(stderr, "M1 wins %d vs %d\n", (int)s1, (int)s2);
            comp = c1; comp_size = s1;
            free(c2);
            metrics->m1++;
        } else {
            if (fd->verbose > 1)
                fprintf(stderr, "M2 wins %d vs %d\n", (int)s1, (int)s2);
            comp = c2; comp_size = s2;
            free(c1);
            metrics->m2++;
        }
        metrics->trial--;
        pthread_mutex_unlock(&fd->metrics_lock);
    } else if (strat2 >= 0) {
        int xlevel = metrics->m1 > metrics->m2 ? level : level2;
        int xstrat = metrics->m1 > metrics->m2 ? strat : strat2;
        pthread_mutex_unlock(&fd->metrics_lock);
        comp = zlib_mem_deflate((char *)b->data, b->uncomp_size, &comp_size,
                                xlevel, xstrat);
    } else {
        pthread_mutex_unlock(&fd->metrics_lock);
        comp = zlib_mem_deflate((char *)b->data, b->uncomp_size, &comp_size,
                                level, strat);
    }

    if (!comp)
        return -1;

    free(b->data);
    b->data = (unsigned char *)comp;
    b->method = GZIP;
    b->comp_size = comp_size;

    if (fd->verbose)
        fprintf(stderr, "Compressed block ID %d from %d to %d\n",
                b->content_id, b->uncomp_size, b->comp_size);

    return 0;
}

cram_metrics *cram_new_metrics(void) {
    cram_metrics *m = malloc(sizeof(*m));
    if (!m)
        return NULL;
    m->m1 = m->m2 = 0;
    m->trial = 2;
    m->next_trial = 100;
    return m;
}

char *cram_block_method2str(enum cram_block_method m) {
    switch(m) {
    case RAW:   return "RAW";
    case GZIP:  return "GZIP";
    case BZIP2: return "BZIP2";
    case BM_ERROR: break;
    }
    return "?";
}

char *cram_content_type2str(enum cram_content_type t) {
    switch (t) {
    case FILE_HEADER:         return "FILE_HEADER";
    case COMPRESSION_HEADER:  return "COMPRESSION_HEADER";
    case MAPPED_SLICE:        return "MAPPED_SLICE";
    case UNMAPPED_SLICE:      return "UNMAPPED_SLICE";
    case EXTERNAL:            return "EXTERNAL";
    case CORE:                return "CORE";
    case CT_ERROR:            break;
    }
    return "?";
}

/*
 * Extra error checking on fclose to really ensure data is written.
 * Care needs to be taken to handle pipes vs real files.
 *
 * Returns 0 on success
 *        -1 on failure.
 */
int paranoid_fclose(FILE *fp) {
    if (-1 == fflush(fp) && errno != EBADF) {
        fclose(fp);
        return -1;
    }

    errno = 0;
    if (-1 == fsync(fileno(fp))) {
        if (errno != EINVAL) { // eg pipe
            fclose(fp);
            return -1;
        }
    }
    return fclose(fp);
}

/* ----------------------------------------------------------------------
 * Reference sequence handling
 *
 * These revolve around the refs_t structure, which may potentially be
 * shared between multiple cram_fd.
 *
 * We start with refs_create() to allocate an empty refs_t and then
 * populate it with @SQ line data using refs_from_header(). This is done on
 * cram_open().  Also at start up we can call cram_load_reference() which
 * is used with "scramble -r foo.fa". This replaces the fd->refs with the
 * new one specified. In either case refs2id() is then called which
 * maps ref_entry names to @SQ ids (refs_t->ref_id[]).
 *
 * Later, possibly within a thread, we will want to know the actual ref
 * seq itself, obtained by calling cram_get_ref().  This may use the
 * UR: or M5: fields or the filename specified in the original
 * cram_load_reference() call.
 *
 * Given the potential for multi-threaded reference usage, we have
 * reference counting (sorry for the confusing double use of "ref") to
 * track the number of callers interested in any specific reference.
 */

void refs_free(refs_t *r) {
    RP("refs_free()\n");

    if (--r->count > 0)
        return;

    if (!r)
        return;

    if (r->pool)
        string_pool_destroy(r->pool);

    if (r->h_meta) {
        khint_t k;

        for (k = kh_begin(r->h_meta); k != kh_end(r->h_meta); k++) {
            ref_entry *e;

            if (!kh_exist(r->h_meta, k))
                continue;
            if (!(e = kh_val(r->h_meta, k)))
                continue;
            if (e->seq)
                free(e->seq);
            free(e);
        }

        kh_destroy(refs, r->h_meta);
    }
    
    if (r->ref_id)
        free(r->ref_id);

    if (r->fp)
        fclose(r->fp);

    pthread_mutex_destroy(&r->lock);

    free(r);
}

static refs_t *refs_create(void) {
    refs_t *r = calloc(1, sizeof(*r));

    RP("refs_create()\n");

    if (!r)
        return NULL;

    if (!(r->pool = string_pool_create(8192)))
        goto err;

    r->ref_id = NULL; // see refs2id() to populate.
    r->count = 1;
    r->last = NULL;
    r->last_id = -1;

    if (!(r->h_meta = kh_init(refs)))
        goto err;

    pthread_mutex_init(&r->lock, NULL);

    return r;

 err:
    refs_free(r);
    return NULL;
}

/*
 * Loads a FAI file for a reference.fasta.
 * "is_err" indicates whether failure to load is worthy of emitting an
 * error message. In some cases (eg with embedded references) we
 * speculatively load, just incase, and silently ignore errors.
 *
 * Returns the refs_t struct on success (maybe newly allocated);
 *         NULL on failure
 */
static refs_t *refs_load_fai(refs_t *r_orig, char *fn, int is_err) {
    struct stat sb;
    FILE *fp = NULL;
    char fai_fn[PATH_MAX];
    char line[8192];
    refs_t *r = r_orig;
    size_t fn_l = strlen(fn);

    RP("refs_load_fai %s\n", fn);

    if (!r)
        if (!(r = refs_create()))
            goto err;

    /* Open reference, for later use */
    if (stat(fn, &sb) != 0) {
        if (is_err)
            perror(fn);
        goto err;
    }

    if (r->fp)
        fclose(r->fp);
    r->fp = NULL;

    if (!(r->fn = string_dup(r->pool, fn)))
        goto err;
        
    if (fn_l > 4 && strcmp(&fn[fn_l-4], ".fai") == 0)
        r->fn[fn_l-4] = 0;

    if (!(r->fp = fopen(r->fn, "r"))) {
        if (is_err)
            perror(fn);
        goto err;
    }

    /* Parse .fai file and load meta-data */
    sprintf(fai_fn, "%.*s.fai", PATH_MAX-5, r->fn);

    if (stat(fai_fn, &sb) != 0) {
        if (is_err)
            perror(fai_fn);
        goto err;
    }
    if (!(fp = fopen(fai_fn, "r"))) {
        if (is_err)
            perror(fai_fn);
        goto err;
    }
    while (fgets(line, 8192, fp) != NULL) {
        ref_entry *e = malloc(sizeof(*e));
        char *cp;
        int n;
        khint_t k;

        if (!e)
            return NULL;

        // id
        for (cp = line; *cp && !isspace(*cp); cp++)
            ;
        *cp++ = 0;
        e->name = string_dup(r->pool, line);
        
        // length
        while (*cp && isspace(*cp))
            cp++;
        e->length = strtoll(cp, &cp, 10);

        // offset
        while (*cp && isspace(*cp))
            cp++;
        e->offset = strtoll(cp, &cp, 10);

        // bases per line
        while (*cp && isspace(*cp))
            cp++;
        e->bases_per_line = strtol(cp, &cp, 10);

        // line length
        while (*cp && isspace(*cp))
            cp++;
        e->line_length = strtol(cp, &cp, 10);

        // filename
        e->fn = r->fn;

        e->count = 0;
        e->seq = NULL;

        k = kh_put(refs, r->h_meta, e->name, &n);
        if (-1 == n)  {
            free(e);
            return NULL;
        }

        if (n) {
            kh_val(r->h_meta, k) = e;
        } else {
            ref_entry *re = kh_val(r->h_meta, k);
            if (re && (re->count != 0 || re->length != 0)) {
                /* Keep old */
                free(e);
            } else {
                /* Replace old */
                if (re)
                    free(re);
                kh_val(r->h_meta, k) = e;
            }
        }
    }

    return r;

 err:
    if (fp)
        fclose(fp);

    if (!r_orig)
        refs_free(r);
    
    return NULL;
}

/*
 * Indexes references by the order they appear in a BAM file. This may not
 * necessarily be the same order they appear in the fasta reference file.
 *
 * Returns 0 on success
 *        -1 on failure
 */
int refs2id(refs_t *r, SAM_hdr *h) {
    int i;

    if (r->ref_id)
        free(r->ref_id);
    if (r->last)
        r->last = NULL;

    r->ref_id = calloc(h->nref, sizeof(*r->ref_id));
    if (!r->ref_id)
        return -1;

    r->nref = h->nref;
    for (i = 0; i < h->nref; i++) {
        khint_t k = kh_get(refs, r->h_meta, h->ref[i].name);
        if (k != kh_end(r->h_meta)) {
            r->ref_id[i] = kh_val(r->h_meta, k);
        } else {
            fprintf(stderr, "Unable to find ref name '%s'\n",
                    h->ref[i].name);
        }
    }

    return 0;
}

/*
 * Generates refs_t entries based on @SQ lines in the header.
 * Returns 0 on success
 *         -1 on failure
 */
static int refs_from_header(refs_t *r, cram_fd *fd, SAM_hdr *h) {
    int i;

    if (!h || h->nref == 0)
        return 0;

    //fprintf(stderr, "refs_from_header for %p mode %c\n", fd, fd->mode);

    /* Existing refs are fine, as long as they're compatible with the hdr. */
    i = r->nref;
    if (r->nref < h->nref)
        r->nref = h->nref;

    if (!(r->ref_id = realloc(r->ref_id, r->nref * sizeof(*r->ref_id))))
        return -1;

    for (; i < r->nref; i++)
        r->ref_id[i] = NULL;

    /* Copy info from h->ref[i] over to r */
    for (i = 0; i < h->nref; i++) {
        SAM_hdr_type *ty;
        SAM_hdr_tag *tag;
        khint_t k;
        int n;

        if (r->ref_id[i] && 0 == strcmp(r->ref_id[i]->name, h->ref[i].name))
            continue;

        if (!(r->ref_id[i] = calloc(1, sizeof(ref_entry))))
            return -1;

        if (!h->ref[i].name)
            return -1;

        r->ref_id[i]->name = string_dup(r->pool, h->ref[i].name);
        r->ref_id[i]->length = 0; // marker for not yet loaded

        /* Initialise likely filename if known */
        if ((ty = sam_hdr_find(h, "SQ", "SN", h->ref[i].name))) {
            if ((tag = sam_hdr_find_key(h, ty, "M5", NULL))) {
                r->ref_id[i]->fn = string_dup(r->pool, tag->str+3);
                //fprintf(stderr, "Tagging @SQ %s / %s\n", r->ref_id[i]->name, r->ref_id[i]->fn);
            }
        }

        k = kh_put(refs, r->h_meta, r->ref_id[i]->name, &n);
        if (n <= 0) // already exists or error
            return -1;
        kh_val(r->h_meta, k) = r->ref_id[i];
    }

    return 0;
}

/*
 * Attaches a header to a cram_fd.
 *
 * This should be used when creating a new cram_fd for writing where
 * we have an SAM_hdr already constructed (eg from a file we've read
 * in).
 */
int cram_set_header(cram_fd *fd, SAM_hdr *hdr) {
    fd->header = hdr;
    return refs_from_header(fd->refs, fd, hdr);
}

/*
 * Converts a directory and a filename into an expanded path, replacing %s
 * in directory with the filename and %[0-9]+s with portions of the filename
 * Any remaining parts of filename are added to the end with /%s.
 */
void expand_cache_path(char *path, char *dir, char *fn) {
    char *cp;

    while ((cp = strchr(dir, '%'))) {
        strncpy(path, dir, cp-dir);
        path += cp-dir;

        if (*++cp == 's') {
            strcpy(path, fn);
            path += strlen(fn);
            fn += strlen(fn);
            cp++;
        } else if (*cp >= '0' && *cp <= '9') {
            char *endp;
            long l;

            l = strtol(cp, &endp, 10);
            l = MIN(l, strlen(fn));
            if (*endp == 's') {
                strncpy(path, fn, l);
                path += l;
                fn += l;
                *path = 0;
                cp = endp+1;
            } else {
                *path++ = '%';
                *path++ = *cp++;
            }
        } else {
            *path++ = '%';
            *path++ = *cp++;
        }
        dir = cp;
    }
    strcpy(path, dir);
    path += strlen(dir);
    if (*fn && path[-1] != '/')
        *path++ = '/';
    strcpy(path, fn);
}

/*
 * Make the directory containing path and any prefix directories.
 */
void mkdir_prefix(char *path, int mode) {
    char *cp = strrchr(path, '/');
    if (!cp)
        return;

    *cp = 0;
    if (is_directory(path)) {
        *cp = '/';
        return;
    }

    if (mkdir(path, mode) == 0) {
        chmod(path, mode);
        *cp = '/';
        return;
    }

    mkdir_prefix(path, mode);
    mkdir(path, mode);
    chmod(path, mode);
    *cp = '/';
}

/*
 * Queries the M5 string from the header and attempts to populate the
 * reference from this using the REF_PATH environment.
 *
 * Returns 0 on sucess
 *        -1 on failure
 */
static int cram_populate_ref(cram_fd *fd, int id, ref_entry *r) {
    char *ref_path = getenv("REF_PATH");
    SAM_hdr_type *ty;
    SAM_hdr_tag *tag;
    char path[PATH_MAX], path_tmp[PATH_MAX];
    char *local_cache = getenv("REF_CACHE");
    mFILE *mf;

    if (fd->verbose)
        fprintf(stderr, "cram_populate_ref on fd %p, id %d\n", fd, id);

    if (!ref_path)
        ref_path = ".";

    if (!r->name)
        return -1;

    if (!(ty = sam_hdr_find(fd->header, "SQ", "SN", r->name)))
        return -1;

    if (!(tag = sam_hdr_find_key(fd->header, ty, "M5", NULL)))
        goto no_M5;

    if (fd->verbose)
        fprintf(stderr, "Querying ref %s\n", tag->str+3);

    /* Use cache if available */
    if (local_cache && *local_cache) {
        struct stat sb;
        FILE *fp;

        expand_cache_path(path, local_cache, tag->str+3);

        if (0 == stat(path, &sb) && (fp = fopen(path, "r"))) {
            r->length = sb.st_size;
            r->offset = r->line_length = r->bases_per_line = 0;

            r->fn = string_dup(fd->refs->pool, path);

            if (fd->refs->fp)
                fclose(fd->refs->fp);
            fd->refs->fp = fp;
            fd->refs->fn = r->fn;

            // Fall back to cram_get_ref() where it'll do the actual
            // reading of the file.
            return 0;
        }
    }

    /* Otherwise search */
    if ((mf = open_path_mfile(tag->str+3, ref_path, NULL))) {
        size_t sz;
        r->seq = mfsteal(mf, &sz);
        r->length = sz;
    } else {
        refs_t *refs;
        char *fn;

    no_M5:
        /* Failed to find in search path or M5 cache, see if @SQ UR: tag? */
        if (!(tag = sam_hdr_find_key(fd->header, ty, "UR", NULL)))
            return -1;

        fn = (strncmp(tag->str+3, "file:", 5) == 0)
            ? tag->str+8
            : tag->str+3;

        if (fd->refs->fp) {
            fclose(fd->refs->fp);
            fd->refs->fp = NULL;
        }
        if (!(refs = refs_load_fai(fd->refs, fn, 0)))
            return -1;
        fd->refs = refs;
        if (fd->refs->fp) {
            fclose(fd->refs->fp);
            fd->refs->fp = NULL;
        }

        if (!fd->refs->fn)
            return -1;

        if (-1 == refs2id(fd->refs, fd->header))
            return -1;
        if (!fd->refs->ref_id || !fd->refs->ref_id[id])
            return -1;

        // Local copy already, so fall back to cram_get_ref().
        return 0;
    }

    /* Populate the local disk cache if required */
    if (local_cache && *local_cache) {
        FILE *fp;
        int i;

        expand_cache_path(path, local_cache, tag->str+3);
        if (fd->verbose)
            fprintf(stderr, "Path='%s'\n", path);
        mkdir_prefix(path, 01777);

        i = 0;
        do {
            sprintf(path_tmp, "%s.tmp_%d", path, /*getpid(),*/ i);
            i++;
            fp = fopen(path_tmp, "wx");
        } while (fp == NULL && errno == EEXIST);
        if (!fp) {
            perror(path_tmp);

            // Not fatal - we have the data already so keep going.
            return 0;
        }

        if (r->length != fwrite(r->seq, 1, r->length, fp)) {
            perror(path);
        }
        if (-1 == paranoid_fclose(fp)) {
            unlink(path_tmp);
        } else {
            if (0 == chmod(path_tmp, 0444))
                rename(path_tmp, path);
            else
                unlink(path_tmp);
        }
    }

    return 0;
}

static void cram_ref_incr_locked(refs_t *r, int id) {
    RP("%d INC REF %d, %d %p\n", gettid(), id, (int)(id>=0?r->ref_id[id]->count+1:-999), id>=0?r->ref_id[id]->seq:(char *)1);

    if (id < 0 || !r->ref_id[id]->seq)
        return;

    if (r->last_id == id)
        r->last_id = -1;

    ++r->ref_id[id]->count;
}

void cram_ref_incr(refs_t *r, int id) {
    pthread_mutex_lock(&r->lock);
    cram_ref_incr_locked(r, id);
    pthread_mutex_unlock(&r->lock);
}

static void cram_ref_decr_locked(refs_t *r, int id) {
    RP("%d DEC REF %d, %d %p\n", gettid(), id, (int)(id>=0?r->ref_id[id]->count-1:-999), id>=0?r->ref_id[id]->seq:(char *)1);

    if (id < 0 || !r->ref_id[id]->seq) {
        assert(r->ref_id[id]->count >= 0);
        return;
    }

    if (--r->ref_id[id]->count <= 0) {
        assert(r->ref_id[id]->count == 0);
        if (r->last_id >= 0) {
            if (r->ref_id[r->last_id]->count <= 0 &&
                r->ref_id[r->last_id]->seq) {
                RP("%d FREE REF %d (%p)\n", gettid(),
                   r->last_id, r->ref_id[r->last_id]->seq);
                free(r->ref_id[r->last_id]->seq);
                r->ref_id[r->last_id]->seq = NULL;
                r->ref_id[r->last_id]->length = 0;
            }
            r->last_id = -1;
        } else {
            r->last_id = id;
        }
    }
}

void cram_ref_decr(refs_t *r, int id) {
    pthread_mutex_lock(&r->lock);
    cram_ref_decr_locked(r, id);
    pthread_mutex_unlock(&r->lock);
}

/*
 * Used by cram_ref_load and cram_ref_get. The file handle will have
 * already been opened, so we can catch it. The ref_entry *e informs us
 * of whether this is a multi-line fasta file or a raw MD5 style file.
 * Either way we create a single contiguous sequence.
 *
 * Returns all or part of a reference sequence on success (malloced);
 *         NULL on failure.
 */
static char *load_ref_portion(FILE *fp, ref_entry *e, int start, int end) {
    off_t offset, len;
    char *seq;

    if (end < start)
        end = start;

    /*
     * Compute locations in file. This is trivial for the MD5 files, but
     * is still necessary for the fasta variants.
     */
    offset = e->line_length
        ? e->offset + (start-1)/e->bases_per_line * e->line_length +
          (start-1) % e->bases_per_line
        : start-1;

    len = (e->line_length
           ? e->offset + (end-1)/e->bases_per_line * e->line_length + 
             (end-1) % e->bases_per_line
           : end-1) - offset + 1;

    if (0 != fseeko(fp, offset, SEEK_SET)) {
        perror("fseeko() on reference file");
        return NULL;
    }

    if (len == 0 || !(seq = malloc(len))) {
        return NULL;
    }

    if (len != fread(seq, 1, len, fp)) {
        perror("fread() on reference file");
        free(seq);
        return NULL;
    }

    /* Strip white-space if required. */
    if (len != end-start+1) {
        int i, j;
        char *cp = seq;
        char *cp_to;

        for (i = j = 0; i < len; i++) {
            if (cp[i] >= '!' && cp[i] <= '~')
                cp[j++] = cp[i] & ~0x20;
        }
        cp_to = cp+j;

        if (cp_to - seq != end-start+1) {
            fprintf(stderr, "Malformed reference file?\n");
            free(seq);
            return NULL;
        }
    } else {
        int i;
        for (i = 0; i < len; i++) {
            seq[i] = seq[i] & ~0x20; // uppercase in ASCII
        }
    }

    return seq;
}

/*
 * Load the entire reference 'id'.
 * This also increments the reference count by 1.
 *
 * Returns ref_entry on success;
 *         NULL on failure
 */
ref_entry *cram_ref_load(refs_t *r, int id) {
    ref_entry *e = r->ref_id[id];
    int start = 1, end = e->length;
    char *seq;

    if (e->seq) {
        return e;
    }

    assert(e->count == 0);

    if (r->last) {
#ifdef REF_DEBUG
        int idx = 0;
        for (idx = 0; idx < r->nref; idx++)
            if (r->last == r->ref_id[idx])
                break;
        RP("%d cram_ref_load DECR %d\n", gettid(), idx);
#endif
        assert(r->last->count > 0);
        if (--r->last->count <= 0) {
            RP("%d FREE REF %d (%p)\n", gettid(), id, r->ref_id[id]->seq);
            if (r->last->seq) {
                free(r->last->seq);
                r->last->seq = NULL;
            }
        }
    }

    /* Open file if it's not already the current open reference */
    if (strcmp(r->fn, e->fn) || r->fp == NULL) {
        if (r->fp)
            fclose(r->fp);
        r->fn = e->fn;
        if (!(r->fp = fopen(r->fn, "r"))) {
            perror(r->fn);
            return NULL;
        }
    }

    RP("%d Loading ref %d (%d..%d)\n", gettid(), id, start, end);

    if (!(seq = load_ref_portion(r->fp, e, start, end))) {
        return NULL;
    }

    RP("%d Loaded ref %d (%d..%d) = %p\n", gettid(), id, start, end, seq);

    RP("%d INC REF %d, %d\n", gettid(), id, (int)(e->count+1));
    e->seq = seq;
    e->count++;

    /*
     * Also keep track of last used ref so incr/decr loops on the same
     * sequence don't cause load/free loops.
     */
    RP("%d cram_ref_load INCR %d => %d\n", gettid(), id, e->count+1);
    r->last = e;
    e->count++; 

    return e;
}

/*
 * Returns a portion of a reference sequence from start to end inclusive.
 * The returned pointer is owned by either the cram_file fd or by the
 * internal refs_t structure and should not be freed  by the caller.
 *
 * The difference is whether or not this refs_t is in use by just the one
 * cram_fd or by multiples, or whether we have multiple threads accessing
 * references. In either case fd->shared will be true and we start using
 * reference counting to track the number of users of a specific reference
 * sequence.
 *
 * Otherwise the ref seq returned is allocated as part of cram_fd itself
 * and will be freed up on the next call to cram_get_ref or cram_close.
 *
 * To return the entire reference sequence, specify start as 1 and end
 * as 0.
 *
 * To cease using a reference, call cram_ref_decr().
 *
 * Returns reference on success,
 *         NULL on failure
 */
char *cram_get_ref(cram_fd *fd, int id, int start, int end) {
    ref_entry *r;
    char *seq;
    int ostart = start;

    if (id == -1)
        return NULL;

    /* FIXME: axiomatic query of r->seq being true?
     * Or shortcut for unsorted data where we load once and never free?
     */

    //fd->shared_ref = 1; // hard code for now to simplify things

    pthread_mutex_lock(&fd->ref_lock);

    RP("%d cram_get_ref on fd %p, id %d, range %d..%d\n", gettid(), fd, id, start, end);

    /*
     * Unsorted data implies we want to fetch an entire reference at a time.
     * We just deal with this at the moment by claiming we're sharing
     * references instead, which has the same requirement.
     */
    if (fd->unsorted)
        fd->shared_ref = 1;


    /* Sanity checking: does this ID exist? */
    if (id >= fd->refs->nref) {
        fprintf(stderr, "No reference found for id %d\n", id);
        pthread_mutex_unlock(&fd->ref_lock);
        return NULL;
    }

    if (!fd->refs || !fd->refs->ref_id[id]) {
        fprintf(stderr, "No reference found for id %d\n", id);
        pthread_mutex_unlock(&fd->ref_lock);
        return NULL;
    }

    if (!(r = fd->refs->ref_id[id])) {
        fprintf(stderr, "No reference found for id %d\n", id);
        pthread_mutex_unlock(&fd->ref_lock);
        return NULL;
    }


    /*
     * It has an entry, but may not have been populated yet.
     * Any manually loaded .fai files have their lengths known.
     * A ref entry computed from @SQ lines (M5 or UR field) will have
     * r->length == 0 unless it's been loaded once and verified that we have
     * an on-disk filename for it.
     *
     * 19 Sep 2013: Moved the lock here as the cram_populate_ref code calls
     * open_path_mfile and libcurl, which isn't multi-thread safe unless I
     * rewrite my code to have one curl handle per thread.
     */
    pthread_mutex_lock(&fd->refs->lock);
    if (r->length == 0) {
        if (cram_populate_ref(fd, id, r) == -1) {
            fprintf(stderr, "Failed to populate reference for id %d\n", id);
            pthread_mutex_unlock(&fd->refs->lock);
            pthread_mutex_unlock(&fd->ref_lock);
            return NULL;
        }
        r = fd->refs->ref_id[id];
    }


    /*
     * We now know that we the filename containing the reference, so check
     * for limits. If it's over half the reference we'll load all of it in
     * memory as this will speed up subsequent calls.
     */
    if (end < 1)
        end = r->length;
    if (end >= r->length)
        end  = r->length; 
    assert(start >= 1);

    if (end - start >= 0.5*r->length || fd->shared_ref) {
        start = 1;
        end = r->length;
    }
    
    /*
     * Maybe we have it cached already? If so use it.
     *
     * Alternatively if we don't have the sequence but we're sharing
     * references and/or are asking for the entire length of it, then
     * load the full reference into the refs structure and return
     * a pointer to that one instead.
     */
    if (fd->shared_ref || r->seq || (start == 1 && end == r->length)) {
        char *cp;

        if (id >= 0) {
            if (r->seq) {
                cram_ref_incr_locked(fd->refs, id);
            } else {
                ref_entry *e;
                if (!(e = cram_ref_load(fd->refs, id))) {
                    pthread_mutex_unlock(&fd->refs->lock);
                    pthread_mutex_unlock(&fd->ref_lock);
                    return NULL;
                }

                /* unsorted data implies cache ref indefinitely, to avoid
                 * continually loading and unloading.
                 */
                if (fd->unsorted)
                    cram_ref_incr_locked(fd->refs, id);
            }       

            fd->ref = NULL; /* We never access it directly */
            fd->ref_start = 1;
            fd->ref_end   = r->length;
            fd->ref_id    = id;

            cp = fd->refs->ref_id[id]->seq + ostart-1;
        } else {
            fd->ref = NULL;
            cp = NULL;
        }

        RP("%d cram_get_ref returning for id %d, count %d\n", gettid(), id, (int)r->count);

        pthread_mutex_unlock(&fd->refs->lock);
        pthread_mutex_unlock(&fd->ref_lock);
        return cp;
    }

    /*
     * Otherwise we're not sharing, we don't have a copy of it already and
     * we're only asking for a small portion of it.
     *
     * In this case load up just that segment ourselves, freeing any old
     * small segments in the process.
     */

    /* Unmapped ref ID */
    if (id < 0) {
        if (fd->ref_free) {
            free(fd->ref_free);
            fd->ref_free = NULL;
        }
        fd->ref = NULL;
        fd->ref_id = id;
        pthread_mutex_unlock(&fd->refs->lock);
        pthread_mutex_unlock(&fd->ref_lock);
        return NULL;
    }

    /* Open file if it's not already the current open reference */
    if (strcmp(fd->refs->fn, r->fn) || fd->refs->fp == NULL) {
        if (fd->refs->fp)
            fclose(fd->refs->fp);
        fd->refs->fn = r->fn;
        if (!(fd->refs->fp = fopen(fd->refs->fn, "r"))) {
            perror(fd->refs->fn);
            pthread_mutex_unlock(&fd->refs->lock);
            pthread_mutex_unlock(&fd->ref_lock);
            return NULL;
        }
    }

    if (!(fd->ref = load_ref_portion(fd->refs->fp, r, start, end))) {
        pthread_mutex_unlock(&fd->refs->lock);
        pthread_mutex_unlock(&fd->ref_lock);
        return NULL;
    }

    if (fd->ref_free)
        free(fd->ref_free);

    fd->ref_id    = id;
    fd->ref_start = start;
    fd->ref_end   = end;
    fd->ref_free = fd->ref;
    seq = fd->ref;

    pthread_mutex_unlock(&fd->refs->lock);
    pthread_mutex_unlock(&fd->ref_lock);

    return seq + ostart - start;
}

/*
 * If fd has been opened for reading, it may be permitted to specify 'fn'
 * as NULL and let the code auto-detect the reference by parsing the
 * SAM header @SQ lines.
 */
int cram_load_reference(cram_fd *fd, char *fn) {
    if (fn) {
        fd->refs = refs_load_fai(fd->refs, fn,
                                 !(fd->embed_ref && fd->mode == 'r'));
        fn = fd->refs ? fd->refs->fn : NULL;
    }
    fd->ref_fn = fn;

    if ((!fd->refs || (fd->refs->nref == 0 && !fn)) && fd->header) {
        if (!(fd->refs = refs_create()))
            return -1;
        if (-1 == refs_from_header(fd->refs, fd, fd->header))
            return -1;
    }

    if (-1 == refs2id(fd->refs, fd->header))
        return -1;

    return fn ? 0 : -1;
}

/* ----------------------------------------------------------------------
 * Containers
 */

/*
 * Creates a new container, specifying the maximum number of slices
 * and records permitted.
 *
 * Returns cram_container ptr on success
 *         NULL on failure
 */
cram_container *cram_new_container(int nrec, int nslice) {
    cram_container *c = calloc(1, sizeof(*c));
    if (!c)
        return NULL;

    c->curr_ref = -2;

    c->max_c_rec = nrec * nslice;
    c->curr_c_rec = 0;

    c->max_rec = nrec;
    c->record_counter = 0;
    c->num_bases = 0;

    c->max_slice = nslice;
    c->curr_slice = 0;

    c->pos_sorted = 1;
    c->max_apos   = 0;
    c->multi_seq  = 0;

    c->bams = NULL;

    if (!(c->slices = (cram_slice **)calloc(nslice, sizeof(cram_slice *))))
        goto err;
    c->slice = NULL;

    if (!(c->comp_hdr = cram_new_compression_header()))
        goto err;
    c->comp_hdr_block = NULL;

    if (!(c->BF_stats = cram_stats_create())) goto err;
    if (!(c->CF_stats = cram_stats_create())) goto err;
    if (!(c->RN_stats = cram_stats_create())) goto err;
    if (!(c->AP_stats = cram_stats_create())) goto err;
    if (!(c->RG_stats = cram_stats_create())) goto err;
    if (!(c->MQ_stats = cram_stats_create())) goto err;
    if (!(c->NS_stats = cram_stats_create())) goto err;
    if (!(c->NP_stats = cram_stats_create())) goto err;
    if (!(c->TS_stats = cram_stats_create())) goto err;
    if (!(c->MF_stats = cram_stats_create())) goto err;
    if (!(c->NF_stats = cram_stats_create())) goto err;
    if (!(c->RL_stats = cram_stats_create())) goto err;
    if (!(c->FN_stats = cram_stats_create())) goto err;
    if (!(c->FC_stats = cram_stats_create())) goto err;
    if (!(c->FP_stats = cram_stats_create())) goto err;
    if (!(c->DL_stats = cram_stats_create())) goto err;
    if (!(c->BA_stats = cram_stats_create())) goto err;
    if (!(c->QS_stats = cram_stats_create())) goto err;
    if (!(c->BS_stats = cram_stats_create())) goto err;
    if (!(c->TC_stats = cram_stats_create())) goto err;
    if (!(c->TN_stats = cram_stats_create())) goto err;
    if (!(c->TL_stats = cram_stats_create())) goto err;
    if (!(c->RI_stats = cram_stats_create())) goto err;
    if (!(c->RS_stats = cram_stats_create())) goto err;
    if (!(c->PD_stats = cram_stats_create())) goto err;
    if (!(c->HC_stats = cram_stats_create())) goto err;
    
    //c->aux_B_stats = cram_stats_create();

    if (!(c->tags_used = kh_init(s_i2i)))
        goto err;
    c->refs_used = 0;

    return c;

 err:
    if (c) {
        if (c->slices)
            free(c->slices);
        free(c);
    }
    return NULL;
}

void cram_free_container(cram_container *c) {
    int i;

    if (!c)
        return;

    if (c->refs_used)
        free(c->refs_used);

    if (c->landmark)
        free(c->landmark);

    if (c->comp_hdr)
        cram_free_compression_header(c->comp_hdr);

    if (c->comp_hdr_block)
        cram_free_block(c->comp_hdr_block);

    if (c->slices) {
        for (i = 0; i < c->max_slice; i++)
            if (c->slices[i])
                cram_free_slice(c->slices[i]);
        free(c->slices);
    }

    if (c->TS_stats) cram_stats_free(c->TS_stats);
    if (c->RG_stats) cram_stats_free(c->RG_stats);
    if (c->FP_stats) cram_stats_free(c->FP_stats);
    if (c->NS_stats) cram_stats_free(c->NS_stats);
    if (c->RN_stats) cram_stats_free(c->RN_stats);
    if (c->CF_stats) cram_stats_free(c->CF_stats);
    if (c->TN_stats) cram_stats_free(c->TN_stats);
    if (c->BA_stats) cram_stats_free(c->BA_stats);
    if (c->TV_stats) cram_stats_free(c->TV_stats);
    if (c->BS_stats) cram_stats_free(c->BS_stats);
    if (c->FC_stats) cram_stats_free(c->FC_stats);
    if (c->BF_stats) cram_stats_free(c->BF_stats);
    if (c->AP_stats) cram_stats_free(c->AP_stats);
    if (c->NF_stats) cram_stats_free(c->NF_stats);
    if (c->MF_stats) cram_stats_free(c->MF_stats);
    if (c->FN_stats) cram_stats_free(c->FN_stats);
    if (c->RL_stats) cram_stats_free(c->RL_stats);
    if (c->DL_stats) cram_stats_free(c->DL_stats);
    if (c->TC_stats) cram_stats_free(c->TC_stats);
    if (c->TL_stats) cram_stats_free(c->TL_stats);
    if (c->MQ_stats) cram_stats_free(c->MQ_stats);
    if (c->TM_stats) cram_stats_free(c->TM_stats);
    if (c->QS_stats) cram_stats_free(c->QS_stats);
    if (c->NP_stats) cram_stats_free(c->NP_stats);
    if (c->RI_stats) cram_stats_free(c->RI_stats);
    if (c->RS_stats) cram_stats_free(c->RS_stats);
    if (c->PD_stats) cram_stats_free(c->PD_stats);
    if (c->HC_stats) cram_stats_free(c->HC_stats);

    //if (c->aux_B_stats) cram_stats_free(c->aux_B_stats);
    
    if (c->tags_used) kh_destroy(s_i2i, c->tags_used);

    free(c);
}

/*
 * Reads a container header.
 *
 * Returns cram_container on success
 *         NULL on failure or no container left (fd->err == 0).
 */
cram_container *cram_read_container(cram_fd *fd) {
    cram_container c2, *c;
    int i, s;
    size_t rd = 0;
    
    fd->err = 0;

    memset(&c2, 0, sizeof(c2));
    if (fd->version == CRAM_1_VERS) {
        if ((s = itf8_decode(fd, &c2.length)) == -1) {
            fd->eof = fd->empty_container ? 1 : 2;
            return NULL;
        } else {
            rd+=s;
        }
    } else {
        if ((s = int32_decode(fd, &c2.length)) == -1) {
            fd->eof = fd->empty_container ? 1 : 2;
            return NULL;
        } else {
            rd+=s;
        }
    }
    if ((s = itf8_decode(fd, &c2.ref_seq_id))   == -1) return NULL; else rd+=s;
    if ((s = itf8_decode(fd, &c2.ref_seq_start))== -1) return NULL; else rd+=s;
    if ((s = itf8_decode(fd, &c2.ref_seq_span)) == -1) return NULL; else rd+=s;
    if ((s = itf8_decode(fd, &c2.num_records))  == -1) return NULL; else rd+=s;

    if (fd->version == CRAM_1_VERS) {
        c2.record_counter = 0;
        c2.num_bases = 0;
    } else {
        if ((s = itf8_decode(fd, &c2.record_counter)) == -1)
            return NULL;
        else
            rd += s;

        if ((s = ltf8_decode(fd, &c2.num_bases))== -1)
            return NULL;
        else
            rd += s;
    }
    if ((s = itf8_decode(fd, &c2.num_blocks))   == -1) return NULL; else rd+=s;
    if ((s = itf8_decode(fd, &c2.num_landmarks))== -1) return NULL; else rd+=s;

    if (!(c = calloc(1, sizeof(*c))))
        return NULL;

    *c = c2;

    if (!(c->landmark = malloc(c->num_landmarks * sizeof(int32_t))) &&
        c->num_landmarks) {
        fd->err = errno;
        cram_free_container(c);
        return NULL;
    }  
    for (i = 0; i < c->num_landmarks; i++) {
        if ((s = itf8_decode(fd, &c->landmark[i])) == -1) {
            cram_free_container(c);
            return NULL;
        } else {
            rd += s;
        }
    }
    c->offset = rd;

    c->slices = NULL;
    c->curr_slice = 0;
    c->max_slice = c->num_landmarks;
    c->slice_rec = 0;
    c->curr_rec = 0;
    c->max_rec = 0;

    if (c->ref_seq_id == -2) {
        c->multi_seq = 1;
        fd->multi_seq = 1;
    }

    fd->empty_container =
        (c->num_records == 0 &&
         c->ref_seq_id == -1 &&
         c->ref_seq_start == 0x454f46 /* EOF */) ? 1 : 0;

    return c;
}

/*
 * Writes a container structure.
 *
 * Returns 0 on success
 *        -1 on failure
 */
int cram_write_container(cram_fd *fd, cram_container *c) {
    char buf_a[1024], *buf = buf_a, *cp;
    int i;

    if (50 + c->num_landmarks * 5 >= 1024)
        buf = malloc(50 + c->num_landmarks * 5);
    cp = buf;

    if (fd->version == CRAM_1_VERS) {
        cp += itf8_put(cp, c->length);
    } else {
        *(int32_t *)cp = le_int4(c->length);
        cp += 4;
    }
    if (c->multi_seq) {
        cp += itf8_put(cp, -2);
        cp += itf8_put(cp, 0);
        cp += itf8_put(cp, 0);
    } else {
        cp += itf8_put(cp, c->ref_seq_id);
        cp += itf8_put(cp, c->ref_seq_start);
        cp += itf8_put(cp, c->ref_seq_span);
    }
    cp += itf8_put(cp, c->num_records);
    if (fd->version != CRAM_1_VERS) {
        cp += itf8_put(cp, c->record_counter);
        cp += ltf8_put(cp, c->num_bases);
    }
    cp += itf8_put(cp, c->num_blocks);
    cp += itf8_put(cp, c->num_landmarks);
    for (i = 0; i < c->num_landmarks; i++)
        cp += itf8_put(cp, c->landmark[i]);
    if (cp-buf != hwrite(fd->fp, buf, cp-buf)) {
        if (buf != buf_a)
            free(buf);
        return -1;
    }

    if (buf != buf_a)
        free(buf);

    return 0;
}

// common component shared by cram_flush_container{,_mt}
static int cram_flush_container2(cram_fd *fd, cram_container *c) {
    int i, j;

    //fprintf(stderr, "Writing container %d, sum %u\n", c->record_counter, sum);

    /* Write the container struct itself */
    if (0 != cram_write_container(fd, c))
        return -1;

    /* And the compression header */
    if (0 != cram_write_block(fd, c->comp_hdr_block))
        return -1;

    /* Followed by the slice blocks */
    for (i = 0; i < c->curr_slice; i++) {
        cram_slice *s = c->slices[i];

        if (0 != cram_write_block(fd, s->hdr_block))
            return -1;

        for (j = 0; j < s->hdr->num_blocks; j++) {
            if (0 != cram_write_block(fd, s->block[j]))
                return -1;
        }
    }

    return hflush(fd->fp) == 0 ? 0 : -1;
}

/*
 * Flushes a completely or partially full container to disk, writing
 * container structure, header and blocks. This also calls the encoder
 * functions.
 *
 * Returns 0 on success
 *        -1 on failure
 */
int cram_flush_container(cram_fd *fd, cram_container *c) {
    /* Encode the container blocks and generate compression header */
    if (0 != cram_encode_container(fd, c))
        return -1;

    return cram_flush_container2(fd, c);
}

typedef struct {
    cram_fd *fd;
    cram_container *c;
} cram_job;

void *cram_flush_thread(void *arg) {
    cram_job *j = (cram_job *)arg;

    /* Encode the container blocks and generate compression header */
    if (0 != cram_encode_container(j->fd, j->c)) {
        fprintf(stderr, "cram_encode_container failed\n");
        return NULL;
    }

    return arg;
}

static int cram_flush_result(cram_fd *fd) {
    int i, ret = 0;
    t_pool_result *r;

    while ((r = t_pool_next_result(fd->rqueue))) {
        cram_job *j = (cram_job *)r->data;
        cram_container *c;

        if (!j) {
            t_pool_delete_result(r, 0);
            return -1;
        }

        fd = j->fd;
        c = j->c;

        if (0 != cram_flush_container2(fd, c))
            return -1;

        /* Free the container */
        for (i = 0; i < c->max_slice; i++) {
            cram_free_slice(c->slices[i]);
            c->slices[i] = NULL;
        }

        c->slice = NULL;
        c->curr_slice = 0;

        cram_free_container(c);

        ret |= hflush(fd->fp) == 0 ? 0 : -1;

        t_pool_delete_result(r, 1);
    }

    return ret;
}

int cram_flush_container_mt(cram_fd *fd, cram_container *c) {
    cram_job *j;

    if (!fd->pool)
        return cram_flush_container(fd, c);

    if (!(j = malloc(sizeof(*j))))
        return -1;
    j->fd = fd;
    j->c = c;
    
    t_pool_dispatch(fd->pool, fd->rqueue, cram_flush_thread, j);

    return cram_flush_result(fd);
}

/* ----------------------------------------------------------------------
 * Compression headers; the first part of the container
 */

/*
 * Creates a new blank container compression header
 *
 * Returns header ptr on success
 *         NULL on failure
 */
cram_block_compression_hdr *cram_new_compression_header(void) {
    cram_block_compression_hdr *hdr = calloc(1, sizeof(*hdr));
    if (!hdr)
        return NULL;

    if (!(hdr->TD_blk = cram_new_block(CORE, 0))) {
        free(hdr);
        return NULL;
    }

    if (!(hdr->TD_hash = kh_init(m_s2i))) {
        cram_free_block(hdr->TD_blk);
        free(hdr);
        return NULL;
    }

    if (!(hdr->TD_keys = string_pool_create(8192))) {
        kh_destroy(m_s2i, hdr->TD_hash);
        cram_free_block(hdr->TD_blk);
        free(hdr);
        return NULL;
    }

    return hdr;
}

void cram_free_compression_header(cram_block_compression_hdr *hdr) {
    int i;

    if (hdr->landmark)
        free(hdr->landmark);

    if (hdr->preservation_map)
        kh_destroy(map, hdr->preservation_map);

    for (i = 0; i < CRAM_MAP_HASH; i++) {
        cram_map *m, *m2;
        for (m = hdr->rec_encoding_map[i]; m; m = m2) {
            m2 = m->next;
            if (m->codec)
                m->codec->free(m->codec);
            free(m);
        }
    }

    for (i = 0; i < CRAM_MAP_HASH; i++) {
        cram_map *m, *m2;
        for (m = hdr->tag_encoding_map[i]; m; m = m2) {
            m2 = m->next;
            if (m->codec)
                m->codec->free(m->codec);
            free(m);
        }
    }

    if (hdr->BF_codec) hdr->BF_codec->free(hdr->BF_codec);
    if (hdr->CF_codec) hdr->CF_codec->free(hdr->CF_codec);
    if (hdr->RL_codec) hdr->RL_codec->free(hdr->RL_codec);
    if (hdr->AP_codec) hdr->AP_codec->free(hdr->AP_codec);
    if (hdr->RG_codec) hdr->RG_codec->free(hdr->RG_codec);
    if (hdr->MF_codec) hdr->MF_codec->free(hdr->MF_codec);
    if (hdr->NS_codec) hdr->NS_codec->free(hdr->NS_codec);
    if (hdr->NP_codec) hdr->NP_codec->free(hdr->NP_codec);
    if (hdr->TS_codec) hdr->TS_codec->free(hdr->TS_codec);
    if (hdr->NF_codec) hdr->NF_codec->free(hdr->NF_codec);
    if (hdr->TC_codec) hdr->TC_codec->free(hdr->TC_codec);
    if (hdr->TN_codec) hdr->TN_codec->free(hdr->TN_codec);
    if (hdr->TL_codec) hdr->TL_codec->free(hdr->TL_codec);
    if (hdr->FN_codec) hdr->FN_codec->free(hdr->FN_codec);
    if (hdr->FC_codec) hdr->FC_codec->free(hdr->FC_codec);
    if (hdr->FP_codec) hdr->FP_codec->free(hdr->FP_codec);
    if (hdr->BS_codec) hdr->BS_codec->free(hdr->BS_codec);
    if (hdr->IN_codec) hdr->IN_codec->free(hdr->IN_codec);
    if (hdr->SC_codec) hdr->SC_codec->free(hdr->SC_codec);
    if (hdr->DL_codec) hdr->DL_codec->free(hdr->DL_codec);
    if (hdr->BA_codec) hdr->BA_codec->free(hdr->BA_codec);
    if (hdr->MQ_codec) hdr->MQ_codec->free(hdr->MQ_codec);
    if (hdr->RN_codec) hdr->RN_codec->free(hdr->RN_codec);
    if (hdr->QS_codec) hdr->QS_codec->free(hdr->QS_codec);
    if (hdr->Qs_codec) hdr->Qs_codec->free(hdr->Qs_codec);
    if (hdr->RI_codec) hdr->RI_codec->free(hdr->RI_codec);
    if (hdr->RS_codec) hdr->RS_codec->free(hdr->RS_codec);
    if (hdr->PD_codec) hdr->PD_codec->free(hdr->PD_codec);
    if (hdr->HC_codec) hdr->HC_codec->free(hdr->HC_codec);

    if (hdr->TL)
        free(hdr->TL);
    if (hdr->TD_blk)
        cram_free_block(hdr->TD_blk);
    if (hdr->TD_hash)
        kh_destroy(m_s2i, hdr->TD_hash);
    if (hdr->TD_keys)
        string_pool_destroy(hdr->TD_keys);

    free(hdr);
}


/* ----------------------------------------------------------------------
 * Slices and slice headers
 */

void cram_free_slice_header(cram_block_slice_hdr *hdr) {
    if (!hdr)
        return;

    if (hdr->block_content_ids)
        free(hdr->block_content_ids);

    free(hdr);

    return;
}

void cram_free_slice(cram_slice *s) {
    if (!s)
        return;

    if (s->hdr_block)
        cram_free_block(s->hdr_block);

    if (s->block) {
        int i;

        if (s->hdr) {
            for (i = 0; i < s->hdr->num_blocks; i++) {
                cram_free_block(s->block[i]);
            }
        }
        free(s->block);
    }

    if (s->block_by_id)
        free(s->block_by_id);

    if (s->hdr)
        cram_free_slice_header(s->hdr);

    if (s->seqs_blk)
        cram_free_block(s->seqs_blk);

    if (s->qual_blk)
        cram_free_block(s->qual_blk);

    if (s->name_blk)
        cram_free_block(s->name_blk);

    if (s->aux_blk)
        cram_free_block(s->aux_blk);

    if (s->base_blk)
        cram_free_block(s->base_blk);

    if (s->soft_blk)
        cram_free_block(s->soft_blk);

#ifdef TN_external
    if (s->tn_blk)
        cram_free_block(s->tn_blk);
#endif

    if (s->cigar)
        free(s->cigar);

    if (s->crecs)
        free(s->crecs);

    if (s->features)
        free(s->features);

#ifndef TN_external
    if (s->TN)
        free(s->TN);
#endif
    
    if (s->pair_keys)
        string_pool_destroy(s->pair_keys);

    if (s->pair)
        kh_destroy(m_s2i, s->pair);

    free(s);
}

/*
 * Creates a new empty slice in memory, for subsequent writing to
 * disk.
 *
 * Returns cram_slice ptr on success
 *         NULL on failure
 */
cram_slice *cram_new_slice(enum cram_content_type type, int nrecs) {
    cram_slice *s = calloc(1, sizeof(*s));
    if (!s)
        return NULL;

    if (!(s->hdr = (cram_block_slice_hdr *)calloc(1, sizeof(*s->hdr))))
        goto err;
    s->hdr->content_type = type;

    s->hdr_block = NULL;
    s->block = NULL;
    s->block_by_id = NULL;
    s->last_apos = 0;
    s->id = 0;
    if (!(s->crecs = malloc(nrecs * sizeof(cram_record))))        goto err;
    s->cigar = NULL;
    s->cigar_alloc = 0;
    s->ncigar = 0;

    if (!(s->seqs_blk = cram_new_block(EXTERNAL, 0)))             goto err;
    if (!(s->qual_blk = cram_new_block(EXTERNAL, CRAM_EXT_QUAL))) goto err;
    if (!(s->name_blk = cram_new_block(EXTERNAL, CRAM_EXT_NAME))) goto err;
    if (!(s->aux_blk  = cram_new_block(EXTERNAL, CRAM_EXT_TAG)))  goto err;
    if (!(s->base_blk = cram_new_block(EXTERNAL, CRAM_EXT_IN)))   goto err;
    if (!(s->soft_blk = cram_new_block(EXTERNAL, CRAM_EXT_SC)))   goto err;
#ifdef TN_external
    if (!(s->tn_blk   = cram_new_block(EXTERNAL, CRAM_EXT_TN)))   goto err;
#endif

    s->features = NULL;
    s->nfeatures = s->afeatures = 0;

#ifndef TN_external
    s->TN = NULL;
    s->nTN = s->aTN = 0;
#endif

    // Volatile keys as we do realloc in dstring
    if (!(s->pair_keys = string_pool_create(8192))) goto err;
    if (!(s->pair = kh_init(m_s2i)))                goto err;
    
#ifdef BA_external
    s->BA_len = 0;
#endif

    return s;

 err:
    if (s)
        cram_free_slice(s);

    return NULL;
}

/*
 * Loads an entire slice.
 * FIXME: In 1.0 the native unit of slices within CRAM is broken
 * as slices contain references to objects in other slices.
 * To work around this while keeping the slice oriented outer loop
 * we read all slices and stitch them together into a fake large
 * slice instead.
 *
 * Returns cram_slice ptr on success
 *         NULL on failure
 */
cram_slice *cram_read_slice(cram_fd *fd) {
    cram_block *b = cram_read_block(fd);
    cram_slice *s = calloc(1, sizeof(*s));
    int i, n, max_id, min_id;

    if (!b || !s)
        goto err;

    s->hdr_block = b;
    switch (b->content_type) {
    case MAPPED_SLICE:
    case UNMAPPED_SLICE:
        if (!(s->hdr = cram_decode_slice_header(fd, b)))
            goto err;
        break;

    default:
        fprintf(stderr, "Unexpected block of type %s\n",
                cram_content_type2str(b->content_type));
        goto err;
    }

    s->block = calloc(n = s->hdr->num_blocks, sizeof(*s->block));
    if (!s->block)
        goto err;

    for (max_id = i = 0, min_id = INT_MAX; i < n; i++) {
        if (!(s->block[i] = cram_read_block(fd)))
            goto err;

        if (s->block[i]->content_type == EXTERNAL) {
            if (max_id < s->block[i]->content_id)
                max_id = s->block[i]->content_id;
            if (min_id > s->block[i]->content_id)
                min_id = s->block[i]->content_id;
        }
    }
    if (min_id >= 0 && max_id < 1024) {
        if (!(s->block_by_id = calloc(1024, sizeof(s->block[0]))))
            goto err;

        for (i = 0; i < n; i++) {
            if (s->block[i]->content_type != EXTERNAL)
                continue;
            s->block_by_id[s->block[i]->content_id] = s->block[i];
        }
    }

    /* Initialise encoding/decoding tables */
    s->cigar = NULL;
    s->cigar_alloc = 0;
    s->ncigar = 0;

    if (!(s->seqs_blk = cram_new_block(EXTERNAL, 0)))             goto err;
    if (!(s->qual_blk = cram_new_block(EXTERNAL, CRAM_EXT_QUAL))) goto err;
    if (!(s->name_blk = cram_new_block(EXTERNAL, CRAM_EXT_NAME))) goto err;
    if (!(s->aux_blk  = cram_new_block(EXTERNAL, CRAM_EXT_TAG)))  goto err;
    if (!(s->base_blk = cram_new_block(EXTERNAL, CRAM_EXT_IN)))   goto err;
    if (!(s->soft_blk = cram_new_block(EXTERNAL, CRAM_EXT_SC)))   goto err;
#ifdef TN_external
    if (!(s->tn_blk   = cram_new_block(EXTERNAL, CRAM_EXT_TN)))   goto err;
#endif


    s->crecs = NULL;

    s->last_apos = s->hdr->ref_seq_start;
    
    s->id = fd->slice_num++;

    return s;

 err:
    if (b)
        cram_free_block(b);
    if (s) {
        s->hdr_block = NULL;
        cram_free_slice(s);
    }
    return NULL;
}


/* ----------------------------------------------------------------------
 * CRAM file definition (header)
 */

/*
 * Reads a CRAM file definition structure.
 * Returns file_def ptr on success
 *         NULL on failure
 */
cram_file_def *cram_read_file_def(cram_fd *fd) {
    cram_file_def *def = malloc(sizeof(*def));
    if (!def)
        return NULL;

    if (26 != hread(fd->fp, &def->magic[0], 26)) {
        free(def);
        return NULL;
    }

    if (memcmp(def->magic, "CRAM", 4) != 0) {
        free(def);
        return NULL;
    }

    if (def->major_version > 2) {
        fprintf(stderr, "CRAM version number mismatch\n"
                "Expected 1.x or 2.x, got %d.%d\n",
                def->major_version, def->minor_version);
        free(def);
        return NULL;
    }

    fd->first_container += 26;
    fd->last_slice = 0;

    return def;
}

/*
 * Writes a cram_file_def structure to cram_fd.
 * Returns 0 on success
 *        -1 on failure
 */
int cram_write_file_def(cram_fd *fd, cram_file_def *def) {
    return (hwrite(fd->fp, &def->magic[0], 26) == 26) ? 0 : -1;
}

void cram_free_file_def(cram_file_def *def) {
    if (def) free(def);
}

/* ----------------------------------------------------------------------
 * SAM header I/O
 */


/*
 * Reads the SAM header from the first CRAM data block.
 * Also performs minimal parsing to extract read-group
 * and sample information.

 * Returns SAM hdr ptr on success
 *         NULL on failure
 */
SAM_hdr *cram_read_SAM_hdr(cram_fd *fd) {
    int32_t header_len;
    char *header;
    SAM_hdr *hdr;

    /* 1.1 onwards stores the header in the first block of a container */
    if (fd->version == CRAM_1_VERS) {
        /* Length */
        if (-1 == int32_decode(fd, &header_len))
            return NULL;

        /* Alloc and read */
        if (NULL == (header = malloc(header_len+1)))
            return NULL;

        *header = 0;
        if (header_len != hread(fd->fp, header, header_len))
            return NULL;

        fd->first_container += 4 + header_len;
    } else {
        cram_container *c = cram_read_container(fd);
        cram_block *b;
        int i, len;

        if (!c)
            return NULL;

        if (c->num_blocks < 1) {
            cram_free_container(c);
            return NULL;
        }

        if (!(b = cram_read_block(fd))) {
            cram_free_container(c);
            return NULL;
        }

        len = b->comp_size + 2 +
            itf8_size(b->content_id) + 
            itf8_size(b->uncomp_size) + 
            itf8_size(b->comp_size);

        /* Extract header from 1st block */
        if (-1 == int32_get(b, &header_len) ||
            b->uncomp_size - 4 < header_len) {
            cram_free_container(c);
            cram_free_block(b);
            return NULL;
        }
        if (NULL == (header = malloc(header_len))) {
            cram_free_container(c);
            cram_free_block(b);
            return NULL;
        }
        memcpy(header, BLOCK_END(b), header_len);
        cram_free_block(b);

        /* Consume any remaining blocks */
        for (i = 1; i < c->num_blocks; i++) {
            if (!(b = cram_read_block(fd))) {
                cram_free_container(c);
                return NULL;
            }
            len += b->comp_size + 2 + 
                itf8_size(b->content_id) + 
                itf8_size(b->uncomp_size) + 
                itf8_size(b->comp_size);
            cram_free_block(b);
        }

        if (c->length && c->length > len) {
            // Consume padding
            char *pads = malloc(c->length - len);
            if (!pads) {
                cram_free_container(c);
                return NULL;
            }

            if (c->length - len != hread(fd->fp, pads, c->length - len)) {
                cram_free_container(c);
                return NULL;
            }
            free(pads);
        }

        cram_free_container(c);
    }

    /* Parse */
#ifdef SAMTOOLS
    hdr = sam_hdr_parse_(header, header_len);
#else
    hdr = sam_hdr_parse(header, header_len);
#endif
    free(header);

    return hdr;
}

/*
 * Converts 'in' to a full pathname to store in out.
 * Out must be at least PATH_MAX bytes long.
 */
static void full_path(char *out, char *in) {
    if (*in == '/') {
        strncpy(out, in, PATH_MAX);
        out[PATH_MAX-1] = 0;
    } else {
        int len;

        // unable to get dir or out+in is too long
        if (!getcwd(out, PATH_MAX) ||
            (len = strlen(out))+1+strlen(in) >= PATH_MAX) {
            strncpy(out, in, PATH_MAX);
            out[PATH_MAX-1] = 0;
            return;
        }

        sprintf(out+len, "/%.*s", PATH_MAX - len, in);

        // FIXME: cope with `pwd`/../../../foo.fa ?
    }
}

/*
 * Writes a CRAM SAM header.
 * Returns 0 on success
 *        -1 on failure
 */
//#define BLANK_BLOCK
//#define PADDED_CONTAINER
#define PADDED_BLOCK
int cram_write_SAM_hdr(cram_fd *fd, SAM_hdr *hdr) {
    int header_len;

    /* 1.0 requires and UNKNOWN read-group */
    if (fd->version == CRAM_1_VERS) {
        if (!sam_hdr_find_rg(hdr, "UNKNOWN"))
            if (sam_hdr_add(hdr, "RG",
                            "ID", "UNKNOWN", "SM", "UNKNOWN", NULL))
                return -1;
    }

    /* Fix M5 strings */
    if (fd->refs && !fd->no_ref) {
        int i;
        for (i = 0; i < hdr->nref; i++) {
            SAM_hdr_type *ty;
            char *ref;

            if (!(ty = sam_hdr_find(hdr, "SQ", "SN", hdr->ref[i].name)))
                return -1;

            if (!sam_hdr_find_key(hdr, ty, "M5", NULL)) {
                char unsigned buf[16], buf2[33];
                int j, rlen;
                MD5_CTX md5;

                if (!fd->refs ||
                    !fd->refs->ref_id ||
                    !fd->refs->ref_id[i]) {
                    return -1;
                }
                rlen = fd->refs->ref_id[i]->length;
                MD5_Init(&md5);
                ref = cram_get_ref(fd, i, 1, rlen);
                if (NULL == ref) return -1;
                rlen = fd->refs->ref_id[i]->length; /* In case it just loaded */
                MD5_Update(&md5, ref, rlen);
                MD5_Final(buf, &md5);
                cram_ref_decr(fd->refs, i);

                for (j = 0; j < 16; j++) {
                    buf2[j*2+0] = "0123456789abcdef"[buf[j]>>4];
                    buf2[j*2+1] = "0123456789abcdef"[buf[j]&15];
                }
                buf2[32] = 0;
                if (sam_hdr_update(hdr, ty, "M5", buf2, NULL))
                    return -1;
            }

            if (fd->ref_fn) {
                char ref_fn[PATH_MAX];
                full_path(ref_fn, fd->ref_fn);
                if (sam_hdr_update(hdr, ty, "UR", ref_fn, NULL))
                    return -1;
            }
        }
    }

    if (sam_hdr_rebuild(hdr))
        return -1;

    /* Length */
    header_len = sam_hdr_length(hdr);
    if (fd->version == CRAM_1_VERS) {
        if (-1 == int32_encode(fd, header_len))
            return -1;

        /* Text data */
        if (header_len != hwrite(fd->fp, sam_hdr_str(hdr), header_len))
            return -1;
    } else {
        /* Create a block inside a container */
        cram_block *b = cram_new_block(FILE_HEADER, 0);
        cram_container *c = cram_new_container(0, 0);
        int padded_length;
        char *pads;

        if (!b || !c) {
            if (b) cram_free_block(b);
            if (c) cram_free_container(c);
            return -1;
        }

        int32_put(b, header_len);
        BLOCK_APPEND(b, sam_hdr_str(hdr), header_len);
        BLOCK_UPLEN(b);

#ifndef BLANK_BLOCK
        c->num_blocks = 1;
        c->num_landmarks = 1;
        if (!(c->landmark = malloc(sizeof(*c->landmark)))) {
            cram_free_block(b);
            cram_free_container(c);
            return -1;
        }
        c->landmark[0] = 0;

        c->length = b->uncomp_size + 2 +
            itf8_size(b->content_id)   + 
            itf8_size(b->uncomp_size)  +
            itf8_size(b->comp_size);
#else
        c->length = b->uncomp_size + 2 +
            itf8_size(b->content_id)   + 
            itf8_size(b->uncomp_size)  +
            itf8_size(b->comp_size);

        c->num_blocks = 2;
        c->num_landmarks = 2;
        if (!(c->landmark = malloc(2*sizeof(*c->landmark))))
            return -1;
        c->landmark[0] = 0;
        c->landmark[1] = c->length;

        c->length *= 2;
#endif

#ifdef PADDED_BLOCK
        padded_length = MAX(c->length*1.5, 10000) - c->length;
        c->length += padded_length;
        if (NULL == (pads = calloc(1, padded_length))) {
            cram_free_block(b);
            cram_free_container(c);
            return -1;
        }
        BLOCK_APPEND(b, pads, padded_length);
        BLOCK_UPLEN(b);
        free(pads);
#endif

#ifdef PADDED_CONTAINER
        padded_length = MAX(c->length*2, 10000) - c->length;
        c->length += padded_length;
#endif

        if (-1 == cram_write_container(fd, c)) {
            cram_free_block(b);
            cram_free_container(c);
            return -1;
        }

        // Keep it uncompressed
        if (-1 == cram_write_block(fd, b)) {
            cram_free_block(b);
            cram_free_container(c);
            return -1;
        }

#ifdef BLANK_BLOCK
        if (-1 == cram_write_block(fd, b)) {
            cram_free_block(b);
            cram_free_container(c);
            return -1;
        }
#endif

        cram_free_block(b);
        cram_free_container(c);

#ifdef PADDED_CONTAINER
        // Write out padding to allow for in-line SAM header editing
        if (NULL == (pads = calloc(1, padded_length)))
            return -1;
        if (padded_length != hwrite(fd->fp, pads, padded_length))
            return -1;
        free(pads);
#endif
    }

    if (-1 == refs_from_header(fd->refs, fd, fd->header))
        return -1;
    if (-1 == refs2id(fd->refs, fd->header))
        return -1;

    if (0 != hflush(fd->fp))
        return -1;

    RP("=== Finishing saving header ===\n");

    return 0;
}

/* ----------------------------------------------------------------------
 * The top-level cram opening, closing and option handling
 */

/*
 * Initialises the lookup tables. These could be global statics, but they're
 * clumsy to setup in a multi-threaded environment unless we generate
 * verbatim code and include that.
 */
static void cram_init_tables(cram_fd *fd) {
    int i;

    memset(fd->L1, 4, 256);
    fd->L1['A'] = 0; fd->L1['a'] = 0;
    fd->L1['C'] = 1; fd->L1['c'] = 1;
    fd->L1['G'] = 2; fd->L1['g'] = 2;
    fd->L1['T'] = 3; fd->L1['t'] = 3;

    memset(fd->L2, 5, 256);
    fd->L2['A'] = 0; fd->L2['a'] = 0;
    fd->L2['C'] = 1; fd->L2['c'] = 1;
    fd->L2['G'] = 2; fd->L2['g'] = 2;
    fd->L2['T'] = 3; fd->L2['t'] = 3;
    fd->L2['N'] = 4; fd->L2['n'] = 4;

    if (fd->version == CRAM_1_VERS) {
        for (i = 0; i < 0x200; i++) {
            int f = 0;

            if (i & CRAM_FPAIRED)      f |= BAM_FPAIRED;
            if (i & CRAM_FPROPER_PAIR) f |= BAM_FPROPER_PAIR;
            if (i & CRAM_FUNMAP)       f |= BAM_FUNMAP;
            if (i & CRAM_FREVERSE)     f |= BAM_FREVERSE;
            if (i & CRAM_FREAD1)       f |= BAM_FREAD1;
            if (i & CRAM_FREAD2)       f |= BAM_FREAD2;
            if (i & CRAM_FSECONDARY)   f |= BAM_FSECONDARY;
            if (i & CRAM_FQCFAIL)      f |= BAM_FQCFAIL;
            if (i & CRAM_FDUP)         f |= BAM_FDUP;

            fd->bam_flag_swap[i]  = f;
        }
    
        for (i = 0; i < 0x1000; i++) {
            int g = 0;

            if (i & BAM_FPAIRED)           g |= CRAM_FPAIRED;
            if (i & BAM_FPROPER_PAIR)  g |= CRAM_FPROPER_PAIR;
            if (i & BAM_FUNMAP)        g |= CRAM_FUNMAP;
            if (i & BAM_FREVERSE)      g |= CRAM_FREVERSE;
            if (i & BAM_FREAD1)        g |= CRAM_FREAD1;
            if (i & BAM_FREAD2)        g |= CRAM_FREAD2;
            if (i & BAM_FSECONDARY)    g |= CRAM_FSECONDARY;
            if (i & BAM_FQCFAIL)       g |= CRAM_FQCFAIL;
            if (i & BAM_FDUP)          g |= CRAM_FDUP;

            fd->cram_flag_swap[i] = g;
        }
    } else {
        /* NOP */
        for (i = 0; i < 0x1000; i++)
            fd->bam_flag_swap[i] = i;
        for (i = 0; i < 0x1000; i++)
            fd->cram_flag_swap[i] = i;
    }

    memset(fd->cram_sub_matrix, 4, 32*32);
    for (i = 0; i < 32; i++) {
        fd->cram_sub_matrix[i]['A'&0x1f]=0;
        fd->cram_sub_matrix[i]['C'&0x1f]=1;
        fd->cram_sub_matrix[i]['G'&0x1f]=2;
        fd->cram_sub_matrix[i]['T'&0x1f]=3;
        fd->cram_sub_matrix[i]['N'&0x1f]=4;
    }
    for (i = 0; i < 20; i+=4) {
        int j;
        for (j = 0; j < 20; j++) {
            fd->cram_sub_matrix["ACGTN"[i>>2]&0x1f][j]=3;
            fd->cram_sub_matrix["ACGTN"[i>>2]&0x1f][j]=3;
            fd->cram_sub_matrix["ACGTN"[i>>2]&0x1f][j]=3;
            fd->cram_sub_matrix["ACGTN"[i>>2]&0x1f][j]=3;
        }
        fd->cram_sub_matrix["ACGTN"[i>>2]&0x1f][CRAM_SUBST_MATRIX[i+0]&0x1f]=0;
        fd->cram_sub_matrix["ACGTN"[i>>2]&0x1f][CRAM_SUBST_MATRIX[i+1]&0x1f]=1;
        fd->cram_sub_matrix["ACGTN"[i>>2]&0x1f][CRAM_SUBST_MATRIX[i+2]&0x1f]=2;
        fd->cram_sub_matrix["ACGTN"[i>>2]&0x1f][CRAM_SUBST_MATRIX[i+3]&0x1f]=3;
    }
}

// Default version numbers for CRAM
static int major_version = 2;
static int minor_version = 1;

/*
 * Opens a CRAM file for read (mode "rb") or write ("wb").
 * The filename may be "-" to indicate stdin or stdout.
 *
 * Returns file handle on success
 *         NULL on failure.
 */
cram_fd *cram_open(const char *filename, const char *mode) {
    cram_FILE *fp;
    cram_fd *fd;
    char fmode[3]= { mode[0], '\0', '\0' };

    if (strlen(mode) > 1 && (mode[1] == 'b' || mode[1] == 'c')) {
        fmode[1] = 'b';
    }

#ifdef SAMTOOLS
    fp = hopen(filename, fmode);
#else
    if (strcmp(filename, "-") == 0) {
        fp = (*fmode == 'r') ? stdin : stdout;
    } else {
        fp = fopen(filename, fmode);
    }
#endif
    if (!fp)
        return NULL;

    fd = cram_dopen(fp, filename, mode);
    if (!fd)
        hclose_abruptly(fp);

    return fd;
}

/* Opens an existing stream for reading or writing.
 *
 * Returns file handle on success;
 *         NULL on failure.
 *
 * cram_FILE is either htslib's hFILE or stdio's FILE, depending on how
 * cram_structs.h has been configured.
 */
cram_fd *cram_dopen(cram_FILE *fp, const char *filename, const char *mode) {
    int i;
    char *cp;
    cram_fd *fd = calloc(1, sizeof(*fd));
    if (!fd)
        return NULL;

    fd->level = 5;
    if (strlen(mode) > 2 && mode[2] >= '0' && mode[2] <= '9')
        fd->level = mode[2] - '0';

    fd->fp = fp;
    fd->mode = *mode;
    fd->first_container = 0;

    if (fd->mode == 'r') {
        /* Reader */

        if (!(fd->file_def = cram_read_file_def(fd)))
            goto err;

        fd->version = fd->file_def->major_version * 100 +
            fd->file_def->minor_version;

        if (!(fd->header = cram_read_SAM_hdr(fd)))
            goto err;

    } else {
        /* Writer */
        cram_file_def def;

        def.magic[0] = 'C';
        def.magic[1] = 'R';
        def.magic[2] = 'A';
        def.magic[3] = 'M';
        def.major_version = major_version;
        def.minor_version = minor_version;
        memset(def.file_id, 0, 20);
        strncpy(def.file_id, filename, 20);
        if (0 != cram_write_file_def(fd, &def))
            goto err;

        fd->version = def.major_version * 100 + def.minor_version;

        /* SAM header written later */
    }

    cram_init_tables(fd);

    fd->prefix = strdup((cp = strrchr(filename, '/')) ? cp+1 : filename);
    if (!fd->prefix)
        goto err;
    fd->slice_num = 0;
    fd->first_base = fd->last_base = -1;
    fd->record_counter = 0;

    fd->ctr = NULL;
    fd->refs  = refs_create();
    if (!fd->refs)
        goto err;
    fd->ref_id = -2;
    fd->ref = NULL;

    fd->decode_md = 0;
    fd->verbose = 0;
    fd->seqs_per_slice = SEQS_PER_SLICE;
    fd->slices_per_container = SLICE_PER_CNT;
    fd->embed_ref = 0;
    fd->no_ref = 0;
    fd->ignore_md5 = 0;
    fd->use_bz2 = 0;
    fd->multi_seq = 0;
    fd->unsorted   = 0;
    fd->shared_ref = 0;

    fd->index       = NULL;
    fd->own_pool    = 0;
    fd->pool        = NULL;
    fd->rqueue      = NULL;
    fd->job_pending = NULL;
    fd->ooc         = 0;

    for (i = 0; i < 7; i++)
        fd->m[i] = cram_new_metrics();

    fd->range.refid = -2; // no ref.
    fd->eof = 1;          // See samtools issue #150
    fd->ref_fn = NULL;

    fd->bl = NULL;

    /* Initialise dummy refs from the @SQ headers */
    if (-1 == refs_from_header(fd->refs, fd, fd->header))
        goto err;

    return fd;

 err:
    if (fd)
        free(fd);

    return NULL;
}

/*
 * Seek within a CRAM file.
 *
 * Returns 0 on success
 *        -1 on failure
 */
int cram_seek(cram_fd *fd, off_t offset, int whence) {
    char buf[65536];

    if (hseek(fd->fp, offset, whence) >= 0)
        return 0;

    if (!(whence == SEEK_CUR && offset >= 0))
        return -1;

    /* Couldn't fseek, but we're in SEEK_CUR mode so read instead */
    while (offset > 0) {
        int len = MIN(65536, offset);
        if (len != hread(fd->fp, buf, len))
            return -1;
        offset -= len;
    }

    return 0;
}

/*
 * Flushes a CRAM file.
 * Useful for when writing to stdout without wishing to close the stream.
 *
 * Returns 0 on success
 *        -1 on failure
 */
int cram_flush(cram_fd *fd) {
    if (!fd)
        return -1;

    if (fd->mode == 'w' && fd->ctr) {
        if(fd->ctr->slice)
            fd->ctr->curr_slice++;
        if (-1 == cram_flush_container_mt(fd, fd->ctr))
            return -1;
    }

    return 0;
}

/*
 * Closes a CRAM file.
 * Returns 0 on success
 *        -1 on failure
 */
int cram_close(cram_fd *fd) {
    spare_bams *bl, *next;
    int i;
        
    if (!fd)
        return -1;

    if (fd->mode == 'w' && fd->ctr) {
        if(fd->ctr->slice)
            fd->ctr->curr_slice++;
        if (-1 == cram_flush_container_mt(fd, fd->ctr))
            return -1;
    }

    if (fd->pool) {
        t_pool_flush(fd->pool);

        if (0 != cram_flush_result(fd))
            return -1;

        pthread_mutex_destroy(&fd->metrics_lock);
        pthread_mutex_destroy(&fd->ref_lock);
        pthread_mutex_destroy(&fd->bam_list_lock);

        fd->ctr = NULL; // prevent double freeing

        //fprintf(stderr, "CRAM: destroy queue %p\n", fd->rqueue);

        t_results_queue_destroy(fd->rqueue);
    }

    if (fd->mode == 'w') {
        /* Write EOF block */
        if (30 != hwrite(fd->fp, "\x0b\x00\x00\x00\xff\xff\xff\xff"
                         "\xff\xe0\x45\x4f\x46\x00\x00\x00"
                         "\x00\x01\x00\x00\x01\x00\x06\x06"
                         "\x01\x00\x01\x00\x01\x00", 30))
            return -1;

//      if (1 != fwrite("\x00\x00\x00\x00\xff\xff\xff\xff"
//                      "\xff\xe0\x45\x4f\x46\x00\x00\x00"
//                      "\x00\x00\x00", 19, 1, fd->fp))
//          return -1;
    }

    for (bl = fd->bl; bl; bl = next) {
        int i, max_rec = fd->seqs_per_slice * fd->slices_per_container;

        next = bl->next;
        for (i = 0; i < max_rec; i++) {
            if (bl->bams[i])
                bam_free(bl->bams[i]);
        }
        free(bl->bams);
        free(bl);
    }

    if (paranoid_hclose(fd->fp) != 0)
        return -1;

    if (fd->file_def)
        cram_free_file_def(fd->file_def);

    if (fd->header)
        sam_hdr_free(fd->header);

    free(fd->prefix);

    if (fd->ctr)
        cram_free_container(fd->ctr);

    if (fd->refs)
        refs_free(fd->refs);
    if (fd->ref_free)
        free(fd->ref_free);

    for (i = 0; i < 7; i++)
        if (fd->m[i])
            free(fd->m[i]);

    if (fd->index)
        cram_index_free(fd);

    if (fd->own_pool && fd->pool)
        t_pool_destroy(fd->pool, 0);

    free(fd);
    return 0;
}

/*
 * Returns 1 if we hit an EOF while reading.
 */
int cram_eof(cram_fd *fd) {
    return fd->eof;
}


/* 
 * Sets options on the cram_fd. See CRAM_OPT_* definitions in cram_structs.h.
 * Use this immediately after opening.
 *
 * Returns 0 on success
 *        -1 on failure
 */
int cram_set_option(cram_fd *fd, enum cram_option opt, ...) {
    int r;
    va_list args;

    va_start(args, opt);
    r = cram_set_voption(fd, opt, args);
    va_end(args);

    return r;
}

/*
 * Sets options on the cram_fd. See CRAM_OPT_* definitions in cram_structs.h.
 * Use this immediately after opening.
 *
 * Returns 0 on success
 *        -1 on failure
 */
int cram_set_voption(cram_fd *fd, enum cram_option opt, va_list args) {
    refs_t *refs;

    switch (opt) {
    case CRAM_OPT_DECODE_MD:
        fd->decode_md = va_arg(args, int);
        break;

    case CRAM_OPT_PREFIX:
        if (fd->prefix)
            free(fd->prefix);
        if (!(fd->prefix = strdup(va_arg(args, char *))))
            return -1;
        break;

    case CRAM_OPT_VERBOSITY:
        fd->verbose = va_arg(args, int);
        break;

    case CRAM_OPT_SEQS_PER_SLICE:
        fd->seqs_per_slice = va_arg(args, int);
        break;

    case CRAM_OPT_SLICES_PER_CONTAINER:
        fd->slices_per_container = va_arg(args, int);
        break;

    case CRAM_OPT_EMBED_REF:
        fd->embed_ref = va_arg(args, int);
        break;

    case CRAM_OPT_NO_REF:
        fd->no_ref = va_arg(args, int);
        break;

    case CRAM_OPT_IGNORE_MD5:
        fd->ignore_md5 = va_arg(args, int);
        break;

    case CRAM_OPT_USE_BZIP2:
        fd->use_bz2 = va_arg(args, int);
        break;

    case CRAM_OPT_SHARED_REF:
        fd->shared_ref = 1;
        refs = va_arg(args, refs_t *);
        if (refs != fd->refs) {
            if (fd->refs)
                refs_free(fd->refs);
            fd->refs = refs;
            fd->refs->count++;
        }
        break;

    case CRAM_OPT_RANGE:
        fd->range = *va_arg(args, cram_range *);
        return cram_seek_to_refpos(fd, &fd->range);

    case CRAM_OPT_REFERENCE:
        return cram_load_reference(fd, va_arg(args, char *));

    case CRAM_OPT_VERSION: {
        int major, minor;
        char *s = va_arg(args, char *);
        if (2 != sscanf(s, "%d.%d", &major, &minor)) {
            fprintf(stderr, "Malformed version string %s\n", s);
            return -1;
        }
        if (!((major == 1 &&  minor == 0) ||
              (major == 2 && (minor == 0 || minor == 1)) ||
              (major == 3 &&  minor == 0))) {
            fprintf(stderr, "Unknown version string; "
                    "use 1.0, 2.0, 2.1 or 3.0\n");
            return -1;
        }
        break;
    }

    case CRAM_OPT_MULTI_SEQ_PER_SLICE:
        fd->multi_seq = va_arg(args, int);
        break;

    case CRAM_OPT_NTHREADS: {
        int nthreads =  va_arg(args, int);
        if (nthreads > 1) {
            if (!(fd->pool = t_pool_init(nthreads*2, nthreads)))
                return -1;

            fd->rqueue = t_results_queue_init();
            pthread_mutex_init(&fd->metrics_lock, NULL);
            pthread_mutex_init(&fd->ref_lock, NULL);
            pthread_mutex_init(&fd->bam_list_lock, NULL);
            fd->shared_ref = 1;
            fd->own_pool = 1;
        }
        break;
    }

    case CRAM_OPT_THREAD_POOL:
        fd->pool = va_arg(args, t_pool *);
        if (fd->pool) {
            fd->rqueue = t_results_queue_init();
            pthread_mutex_init(&fd->metrics_lock, NULL);
            pthread_mutex_init(&fd->ref_lock, NULL);
            pthread_mutex_init(&fd->bam_list_lock, NULL);
        }
        fd->shared_ref = 1; // Needed to avoid clobbering ref between threads
        fd->own_pool = 0;

        //fd->qsize = 1;
        //fd->decoded = calloc(fd->qsize, sizeof(cram_container *));
        //t_pool_dispatch(fd->pool, cram_decoder_thread, fd);
        break;

    default:
        fprintf(stderr, "Unknown CRAM option code %d\n", opt);
        return -1;
    }

    return 0;
}