/src/htslib/cram/cram_encode.c

Source
/*
Copyright (c) 2012-2020, 2022-2025 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.
*/

#define HTS_BUILDING_LIBRARY // Enables HTSLIB_EXPORT, see htslib/hts_defs.h
#include <config.h>

#include <stdio.h>
#include <errno.h>
#include <assert.h>
#include <stdlib.h>
#include <string.h>
#include <strings.h>
#include <zlib.h>
#include <sys/types.h>
#include <sys/stat.h>
#include <math.h>
#include <inttypes.h>
#include <ctype.h>

#include "cram.h"
#include "os.h"
#include "../sam_internal.h" // for nibble2base
#include "../htslib/hts.h"
#include "../htslib/hts_endian.h"
#include "../textutils_internal.h"

KHASH_MAP_INIT_STR(m_s2u64, uint64_t)

#define Z_CRAM_STRAT Z_FILTERED
//#define Z_CRAM_STRAT Z_RLE
//#define Z_CRAM_STRAT Z_HUFFMAN_ONLY
//#define Z_CRAM_STRAT Z_DEFAULT_STRATEGY

static int process_one_read(cram_fd *fd, cram_container *c,
                            cram_slice *s, cram_record *cr,
                            bam_seq_t *b, int rnum, kstring_t *MD,
                            int embed_ref, int no_ref);

/*
 * Returns index of val into key.
 * Basically strchr(key, val)-key;
 */
static int sub_idx(char *key, char val) {
    int i;

    for (i = 0; i < 4 && *key++ != val; i++);
    return i;
}

/*
 * Encodes a compression header block into a generic cram_block structure.
 *
 * Returns cram_block ptr on success
 *         NULL on failure
 */
cram_block *cram_encode_compression_header(cram_fd *fd, cram_container *c,
                                           cram_block_compression_hdr *h,
                                           int embed_ref) {
    cram_block *cb  = cram_new_block(COMPRESSION_HEADER, 0);
    cram_block *map = cram_new_block(COMPRESSION_HEADER, 0);
    int i, mc, r = 0;

    int no_ref = c->no_ref;

    if (!cb || !map)
        return NULL;

    /*
     * This is a concatenation of several blocks of data:
     * header + landmarks, preservation map, read encoding map, and the tag
     * encoding map.
     * All 4 are variable sized and we need to know how large these are
     * before creating the compression header itself as this starts with
     * the total size (stored as a variable length string).
     */

    // Duplicated from container itself, and removed in 1.1
    if (CRAM_MAJOR_VERS(fd->version) == 1) {
        r |= itf8_put_blk(cb, h->ref_seq_id);
        r |= itf8_put_blk(cb, h->ref_seq_start);
        r |= itf8_put_blk(cb, h->ref_seq_span);
        r |= itf8_put_blk(cb, h->num_records);
        r |= itf8_put_blk(cb, h->num_landmarks);
        for (i = 0; i < h->num_landmarks; i++) {
            r |= itf8_put_blk(cb, h->landmark[i]);
        }
    }

    if (h->preservation_map) {
        kh_destroy(map, h->preservation_map);
        h->preservation_map = NULL;
    }

    /* Create in-memory preservation map */
    /* FIXME: should create this when we create the container */
    if (c->num_records > 0) {
        khint_t k;
        int r;

        if (!(h->preservation_map = kh_init(map)))
            return NULL;

        k = kh_put(map, h->preservation_map, "RN", &r);
        if (-1 == r) return NULL;
        kh_val(h->preservation_map, k).i = !fd->lossy_read_names;

        if (CRAM_MAJOR_VERS(fd->version) == 1) {
            k = kh_put(map, h->preservation_map, "PI", &r);
            if (-1 == r) return NULL;
            kh_val(h->preservation_map, k).i = 0;

            k = kh_put(map, h->preservation_map, "UI", &r);
            if (-1 == r) return NULL;
            kh_val(h->preservation_map, k).i = 1;

            k = kh_put(map, h->preservation_map, "MI", &r);
            if (-1 == r) return NULL;
            kh_val(h->preservation_map, k).i = 1;

        } else {
            // Technically SM was in 1.0, but wasn't in Java impl.
            k = kh_put(map, h->preservation_map, "SM", &r);
            if (-1 == r) return NULL;
            kh_val(h->preservation_map, k).i = 0;

            k = kh_put(map, h->preservation_map, "TD", &r);
            if (-1 == r) return NULL;
            kh_val(h->preservation_map, k).i = 0;

            k = kh_put(map, h->preservation_map, "AP", &r);
            if (-1 == r) return NULL;
            kh_val(h->preservation_map, k).i = h->AP_delta;

            if (CRAM_MAJOR_VERS(fd->version) >= 4) {
                k = kh_put(map, h->preservation_map, "QO", &r);
                if (-1 == r) return NULL;
                kh_val(h->preservation_map, k).i = h->qs_seq_orient;
            }

            if (no_ref || embed_ref>0) {
                // Reference Required == No
                k = kh_put(map, h->preservation_map, "RR", &r);
                if (-1 == r) return NULL;
                kh_val(h->preservation_map, k).i = 0;
            }
        }
    }

    /* Encode preservation map; could collapse this and above into one */
    mc = 0;
    BLOCK_SIZE(map) = 0;
    if (h->preservation_map) {
        khint_t k;

        for (k = kh_begin(h->preservation_map);
             k != kh_end(h->preservation_map);
             k++) {
            const char *key;
            khash_t(map) *pmap = h->preservation_map;


            if (!kh_exist(pmap, k))
                continue;

            key = kh_key(pmap, k);
            BLOCK_APPEND(map, key, 2);

            switch(CRAM_KEY(key[0], key[1])) {
            case CRAM_KEY('M','I'):
            case CRAM_KEY('U','I'):
            case CRAM_KEY('P','I'):
            case CRAM_KEY('A','P'):
            case CRAM_KEY('R','N'):
            case CRAM_KEY('R','R'):
            case CRAM_KEY('Q','O'):
                BLOCK_APPEND_CHAR(map, kh_val(pmap, k).i);
                break;

            case CRAM_KEY('S','M'): {
                char smat[5], *mp = smat;
                // Output format is for order ACGTN (minus ref base)
                // to store the code value 0-3 for each symbol.
                //
                // Note this is different to storing the symbols in order
                // that the codes occur from 0-3, which is what we used to
                // do.  (It didn't matter as we always had a fixed table in
                // the order.)
                *mp++ =
                    (sub_idx(h->substitution_matrix[0], 'C') << 6) |
                    (sub_idx(h->substitution_matrix[0], 'G') << 4) |
                    (sub_idx(h->substitution_matrix[0], 'T') << 2) |
                    (sub_idx(h->substitution_matrix[0], 'N') << 0);
                *mp++ =
                    (sub_idx(h->substitution_matrix[1], 'A') << 6) |
                    (sub_idx(h->substitution_matrix[1], 'G') << 4) |
                    (sub_idx(h->substitution_matrix[1], 'T') << 2) |
                    (sub_idx(h->substitution_matrix[1], 'N') << 0);
                *mp++ =
                    (sub_idx(h->substitution_matrix[2], 'A') << 6) |
                    (sub_idx(h->substitution_matrix[2], 'C') << 4) |
                    (sub_idx(h->substitution_matrix[2], 'T') << 2) |
                    (sub_idx(h->substitution_matrix[2], 'N') << 0);
                *mp++ =
                    (sub_idx(h->substitution_matrix[3], 'A') << 6) |
                    (sub_idx(h->substitution_matrix[3], 'C') << 4) |
                    (sub_idx(h->substitution_matrix[3], 'G') << 2) |
                    (sub_idx(h->substitution_matrix[3], 'N') << 0);
                *mp++ =
                    (sub_idx(h->substitution_matrix[4], 'A') << 6) |
                    (sub_idx(h->substitution_matrix[4], 'C') << 4) |
                    (sub_idx(h->substitution_matrix[4], 'G') << 2) |
                    (sub_idx(h->substitution_matrix[4], 'T') << 0);
                BLOCK_APPEND(map, smat, 5);
                break;
            }

            case CRAM_KEY('T','D'): {
                r |= (fd->vv.varint_put32_blk(map, BLOCK_SIZE(h->TD_blk)) <= 0);
                BLOCK_APPEND(map,
                             BLOCK_DATA(h->TD_blk),
                             BLOCK_SIZE(h->TD_blk));
                break;
            }

            default:
                hts_log_warning("Unknown preservation key '%.2s'", key);
                break;
            }

            mc++;
        }
    }
    r |= (fd->vv.varint_put32_blk(cb, BLOCK_SIZE(map) + fd->vv.varint_size(mc)) <= 0);
    r |= (fd->vv.varint_put32_blk(cb, mc) <= 0);
    BLOCK_APPEND(cb, BLOCK_DATA(map), BLOCK_SIZE(map));

    /* rec encoding map */
    mc = 0;
    BLOCK_SIZE(map) = 0;
    if (h->codecs[DS_BF]) {
        if (-1 == h->codecs[DS_BF]->store(h->codecs[DS_BF], map, "BF",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_CF]) {
        if (-1 == h->codecs[DS_CF]->store(h->codecs[DS_CF], map, "CF",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_RL]) {
        if (-1 == h->codecs[DS_RL]->store(h->codecs[DS_RL], map, "RL",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_AP]) {
        if (-1 == h->codecs[DS_AP]->store(h->codecs[DS_AP], map, "AP",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_RG]) {
        if (-1 == h->codecs[DS_RG]->store(h->codecs[DS_RG], map, "RG",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_MF]) {
        if (-1 == h->codecs[DS_MF]->store(h->codecs[DS_MF], map, "MF",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_NS]) {
        if (-1 == h->codecs[DS_NS]->store(h->codecs[DS_NS], map, "NS",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_NP]) {
        if (-1 == h->codecs[DS_NP]->store(h->codecs[DS_NP], map, "NP",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_TS]) {
        if (-1 == h->codecs[DS_TS]->store(h->codecs[DS_TS], map, "TS",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_NF]) {
        if (-1 == h->codecs[DS_NF]->store(h->codecs[DS_NF], map, "NF",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_TC]) {
        if (-1 == h->codecs[DS_TC]->store(h->codecs[DS_TC], map, "TC",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_TN]) {
        if (-1 == h->codecs[DS_TN]->store(h->codecs[DS_TN], map, "TN",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_TL]) {
        if (-1 == h->codecs[DS_TL]->store(h->codecs[DS_TL], map, "TL",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_FN]) {
        if (-1 == h->codecs[DS_FN]->store(h->codecs[DS_FN], map, "FN",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_FC]) {
        if (-1 == h->codecs[DS_FC]->store(h->codecs[DS_FC], map, "FC",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_FP]) {
        if (-1 == h->codecs[DS_FP]->store(h->codecs[DS_FP], map, "FP",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_BS]) {
        if (-1 == h->codecs[DS_BS]->store(h->codecs[DS_BS], map, "BS",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_IN]) {
        if (-1 == h->codecs[DS_IN]->store(h->codecs[DS_IN], map, "IN",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_DL]) {
        if (-1 == h->codecs[DS_DL]->store(h->codecs[DS_DL], map, "DL",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_BA]) {
        if (-1 == h->codecs[DS_BA]->store(h->codecs[DS_BA], map, "BA",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_BB]) {
        if (-1 == h->codecs[DS_BB]->store(h->codecs[DS_BB], map, "BB",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_MQ]) {
        if (-1 == h->codecs[DS_MQ]->store(h->codecs[DS_MQ], map, "MQ",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_RN]) {
        if (-1 == h->codecs[DS_RN]->store(h->codecs[DS_RN], map, "RN",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_QS]) {
        if (-1 == h->codecs[DS_QS]->store(h->codecs[DS_QS], map, "QS",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_QQ]) {
        if (-1 == h->codecs[DS_QQ]->store(h->codecs[DS_QQ], map, "QQ",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_RI]) {
        if (-1 == h->codecs[DS_RI]->store(h->codecs[DS_RI], map, "RI",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (CRAM_MAJOR_VERS(fd->version) != 1) {
        if (h->codecs[DS_SC]) {
            if (-1 == h->codecs[DS_SC]->store(h->codecs[DS_SC], map, "SC",
                                              fd->version))
                return NULL;
            mc++;
        }
        if (h->codecs[DS_RS]) {
            if (-1 == h->codecs[DS_RS]->store(h->codecs[DS_RS], map, "RS",
                                              fd->version))
                return NULL;
            mc++;
        }
        if (h->codecs[DS_PD]) {
            if (-1 == h->codecs[DS_PD]->store(h->codecs[DS_PD], map, "PD",
                                              fd->version))
                return NULL;
            mc++;
        }
        if (h->codecs[DS_HC]) {
            if (-1 == h->codecs[DS_HC]->store(h->codecs[DS_HC], map, "HC",
                                              fd->version))
                return NULL;
            mc++;
        }
    }
    if (h->codecs[DS_TM]) {
        if (-1 == h->codecs[DS_TM]->store(h->codecs[DS_TM], map, "TM",
                                          fd->version))
            return NULL;
        mc++;
    }
    if (h->codecs[DS_TV]) {
        if (-1 == h->codecs[DS_TV]->store(h->codecs[DS_TV], map, "TV",
                                          fd->version))
            return NULL;
        mc++;
    }
    r |= (fd->vv.varint_put32_blk(cb, BLOCK_SIZE(map) + fd->vv.varint_size(mc)) <= 0);
    r |= (fd->vv.varint_put32_blk(cb, mc) <= 0);
    BLOCK_APPEND(cb, BLOCK_DATA(map), BLOCK_SIZE(map));

    /* tag encoding map */
    mc = 0;
    BLOCK_SIZE(map) = 0;
    if (c->tags_used) {
        khint_t k;

        for (k = kh_begin(c->tags_used); k != kh_end(c->tags_used); k++) {
            int key;
            if (!kh_exist(c->tags_used, k))
                continue;

            key = kh_key(c->tags_used, k);
            cram_codec *cd = kh_val(c->tags_used, k)->codec;

            r |= (fd->vv.varint_put32_blk(map, key) <= 0);
            if (-1 == cd->store(cd, map, NULL, fd->version))
                return NULL;

            mc++;
        }
    }

    r |= (fd->vv.varint_put32_blk(cb, BLOCK_SIZE(map) + fd->vv.varint_size(mc)) <= 0);
    r |= (fd->vv.varint_put32_blk(cb, mc) <= 0);
    BLOCK_APPEND(cb, BLOCK_DATA(map), BLOCK_SIZE(map));

    hts_log_info("Wrote compression block header in %d bytes", (int)BLOCK_SIZE(cb));

    BLOCK_UPLEN(cb);

    cram_free_block(map);

    if (r >= 0)
        return cb;

 block_err:
    return NULL;
}


/*
 * Encodes a slice compression header.
 *
 * Returns cram_block on success
 *         NULL on failure
 */
cram_block *cram_encode_slice_header(cram_fd *fd, cram_slice *s) {
    char *buf;
    char *cp;
    cram_block *b = cram_new_block(MAPPED_SLICE, 0);
    int j;

    if (!b)
        return NULL;

    cp = buf = malloc(22+16+5*(8+s->hdr->num_blocks));
    if (NULL == buf) {
        cram_free_block(b);
        return NULL;
    }

    cp += fd->vv.varint_put32s(cp, NULL, s->hdr->ref_seq_id);
    if (CRAM_MAJOR_VERS(fd->version) >= 4) {
        cp += fd->vv.varint_put64(cp, NULL, s->hdr->ref_seq_start);
        cp += fd->vv.varint_put64(cp, NULL, s->hdr->ref_seq_span);
    } else {
        if (s->hdr->ref_seq_start < 0 || s->hdr->ref_seq_start > INT_MAX) {
            hts_log_error("Reference position too large for CRAM 3");
            cram_free_block(b);
            free(buf);
            return NULL;
        }
        cp += fd->vv.varint_put32(cp, NULL, s->hdr->ref_seq_start);
        cp += fd->vv.varint_put32(cp, NULL, s->hdr->ref_seq_span);
    }
    cp += fd->vv.varint_put32(cp, NULL, s->hdr->num_records);
    if (CRAM_MAJOR_VERS(fd->version) == 2)
        cp += fd->vv.varint_put32(cp, NULL, s->hdr->record_counter);
    else if (CRAM_MAJOR_VERS(fd->version) >= 3)
        cp += fd->vv.varint_put64(cp, NULL, s->hdr->record_counter);
    cp += fd->vv.varint_put32(cp, NULL, s->hdr->num_blocks);
    cp += fd->vv.varint_put32(cp, NULL, s->hdr->num_content_ids);
    for (j = 0; j < s->hdr->num_content_ids; j++) {
        cp += fd->vv.varint_put32(cp, NULL, s->hdr->block_content_ids[j]);
    }
    if (s->hdr->content_type == MAPPED_SLICE)
        cp += fd->vv.varint_put32(cp, NULL, s->hdr->ref_base_id);

    if (CRAM_MAJOR_VERS(fd->version) != 1) {
        memcpy(cp, s->hdr->md5, 16); cp += 16;
    }

    assert(cp-buf <= 22+16+5*(8+s->hdr->num_blocks));

    b->data = (unsigned char *)buf;
    b->comp_size = b->uncomp_size = cp-buf;

    return b;
}


/*
 * Encodes a single read.
 *
 * Returns 0 on success
 *        -1 on failure
 */
static int cram_encode_slice_read(cram_fd *fd,
                                  cram_container *c,
                                  cram_block_compression_hdr *h,
                                  cram_slice *s,
                                  cram_record *cr,
                                  int64_t *last_pos) {
    int r = 0;
    int32_t i32;
    int64_t i64;
    unsigned char uc;

    //fprintf(stderr, "Encode seq %d, %d/%d FN=%d, %s\n", rec, core->byte, core->bit, cr->nfeature, s->name_ds->str + cr->name);

    //printf("BF=0x%x\n", cr->flags);
    //      bf = cram_flag_swap[cr->flags];
    i32 = fd->cram_flag_swap[cr->flags & 0xfff];
    r |= h->codecs[DS_BF]->encode(s, h->codecs[DS_BF], (char *)&i32, 1);

    i32 = cr->cram_flags & CRAM_FLAG_MASK;
    r |= h->codecs[DS_CF]->encode(s, h->codecs[DS_CF], (char *)&i32, 1);

    if (CRAM_MAJOR_VERS(fd->version) != 1 && s->hdr->ref_seq_id == -2)
        r |= h->codecs[DS_RI]->encode(s, h->codecs[DS_RI], (char *)&cr->ref_id, 1);

    r |= h->codecs[DS_RL]->encode(s, h->codecs[DS_RL], (char *)&cr->len, 1);

    if (c->pos_sorted) {
        if (CRAM_MAJOR_VERS(fd->version) >= 4) {
            i64 = cr->apos - *last_pos;
            r |= h->codecs[DS_AP]->encode(s, h->codecs[DS_AP], (char *)&i64, 1);
        } else {
            i32 = cr->apos - *last_pos;
            r |= h->codecs[DS_AP]->encode(s, h->codecs[DS_AP], (char *)&i32, 1);
        }
        *last_pos = cr->apos;
    } else {
        if (CRAM_MAJOR_VERS(fd->version) >= 4) {
            i64 = cr->apos;
            r |= h->codecs[DS_AP]->encode(s, h->codecs[DS_AP], (char *)&i64, 1);
        } else {
            i32 = cr->apos;
            r |= h->codecs[DS_AP]->encode(s, h->codecs[DS_AP], (char *)&i32, 1);
        }
    }

    r |= h->codecs[DS_RG]->encode(s, h->codecs[DS_RG], (char *)&cr->rg, 1);

    if (cr->cram_flags & CRAM_FLAG_DETACHED) {
        i32 = cr->mate_flags;
        r |= h->codecs[DS_MF]->encode(s, h->codecs[DS_MF], (char *)&i32, 1);

        r |= h->codecs[DS_NS]->encode(s, h->codecs[DS_NS],
                                      (char *)&cr->mate_ref_id, 1);

        if (CRAM_MAJOR_VERS(fd->version) >= 4) {
            r |= h->codecs[DS_NP]->encode(s, h->codecs[DS_NP],
                                          (char *)&cr->mate_pos, 1);
            r |= h->codecs[DS_TS]->encode(s, h->codecs[DS_TS],
                                          (char *)&cr->tlen, 1);
        } else {
            i32 = cr->mate_pos;
            r |= h->codecs[DS_NP]->encode(s, h->codecs[DS_NP],
                                          (char *)&i32, 1);
            i32 = cr->tlen;
            r |= h->codecs[DS_TS]->encode(s, h->codecs[DS_TS],
                                          (char *)&i32, 1);
        }
    } else {
        if (cr->cram_flags & CRAM_FLAG_MATE_DOWNSTREAM) {
            r |= h->codecs[DS_NF]->encode(s, h->codecs[DS_NF],
                                          (char *)&cr->mate_line, 1);
        }
        if (cr->cram_flags & CRAM_FLAG_EXPLICIT_TLEN) {
            if (CRAM_MAJOR_VERS(fd->version) >= 4) {
                r |= h->codecs[DS_TS]->encode(s, h->codecs[DS_TS],
                                              (char *)&cr->tlen, 1);
            }
        }
    }

    /* Aux tags */
    if (CRAM_MAJOR_VERS(fd->version) == 1) {
        int j;
        uc = cr->ntags;
        r |= h->codecs[DS_TC]->encode(s, h->codecs[DS_TC], (char *)&uc, 1);

        for (j = 0; j < cr->ntags; j++) {
            uint32_t i32 = s->TN[cr->TN_idx + j]; // id
            r |= h->codecs[DS_TN]->encode(s, h->codecs[DS_TN], (char *)&i32, 1);
        }
    } else {
        r |= h->codecs[DS_TL]->encode(s, h->codecs[DS_TL], (char *)&cr->TL, 1);
    }

    // qual
    // QS codec : Already stored in block[2].

    // features (diffs)
    if (!(cr->flags & BAM_FUNMAP)) {
        int prev_pos = 0, j;

        r |= h->codecs[DS_FN]->encode(s, h->codecs[DS_FN],
                                      (char *)&cr->nfeature, 1);
        for (j = 0; j < cr->nfeature; j++) {
            cram_feature *f = &s->features[cr->feature + j];

            uc = f->X.code;
            r |= h->codecs[DS_FC]->encode(s, h->codecs[DS_FC], (char *)&uc, 1);
            i32 = f->X.pos - prev_pos;
            r |= h->codecs[DS_FP]->encode(s, h->codecs[DS_FP], (char *)&i32, 1);
            prev_pos = f->X.pos;

            switch(f->X.code) {
                //char *seq;

            case 'X':
                //fprintf(stderr, "    FC=%c FP=%d base=%d\n", f->X.code, i32, f->X.base);

                uc = f->X.base;
                r |= h->codecs[DS_BS]->encode(s, h->codecs[DS_BS],
                                              (char *)&uc, 1);
                break;
            case 'S':
                // Already done
                //r |= h->codecs[DS_SC]->encode(s, h->codecs[DS_SC],
                //                              BLOCK_DATA(s->soft_blk) + f->S.seq_idx,
                //                              f->S.len);

                //if (CRAM_MAJOR_VERS(fd->version) >= 3) {
                //    r |= h->codecs[DS_BB]->encode(s, h->codecs[DS_BB],
                //                                  BLOCK_DATA(s->seqs_blk) + f->S.seq_idx,
                //                                  f->S.len);
                //}
                break;
            case 'I':
                //seq = DSTRING_STR(s->seqs_ds) + f->S.seq_idx;
                //r |= h->codecs[DS_IN]->encode(s, h->codecs[DS_IN],
                //                           seq, f->S.len);
                //if (CRAM_MAJOR_VERS(fd->version) >= 3) {
                //    r |= h->codecs[DS_BB]->encode(s, h->codecs[DS_BB],
                //                                  BLOCK_DATA(s->seqs_blk) + f->I.seq_idx,
                //                                  f->I.len);
                //}
                break;
            case 'i':
                uc = f->i.base;
                r |= h->codecs[DS_BA]->encode(s, h->codecs[DS_BA],
                                              (char *)&uc, 1);
                //seq = DSTRING_STR(s->seqs_ds) + f->S.seq_idx;
                //r |= h->codecs[DS_IN]->encode(s, h->codecs[DS_IN],
                //                           seq, 1);
                break;
            case 'D':
                i32 = f->D.len;
                r |= h->codecs[DS_DL]->encode(s, h->codecs[DS_DL],
                                              (char *)&i32, 1);
                break;

            case 'B':
                //                  // Used when we try to store a non ACGTN base or an N
                //                  // that aligns against a non ACGTN reference

                uc  = f->B.base;
                r |= h->codecs[DS_BA]->encode(s, h->codecs[DS_BA],
                                              (char *)&uc, 1);

                //                  Already added
                //                  uc  = f->B.qual;
                //                  r |= h->codecs[DS_QS]->encode(s, h->codecs[DS_QS],
                //                                           (char *)&uc, 1);
                break;

            case 'b':
                // string of bases
                r |= h->codecs[DS_BB]->encode(s, h->codecs[DS_BB],
                                              (char *)BLOCK_DATA(s->seqs_blk)
                                                      + f->b.seq_idx,
                                              f->b.len);
                break;

            case 'Q':
                //                  Already added
                //                  uc  = f->B.qual;
                //                  r |= h->codecs[DS_QS]->encode(s, h->codecs[DS_QS],
                //                                           (char *)&uc, 1);
                break;

            case 'N':
                i32 = f->N.len;
                r |= h->codecs[DS_RS]->encode(s, h->codecs[DS_RS],
                                              (char *)&i32, 1);
                break;

            case 'P':
                i32 = f->P.len;
                r |= h->codecs[DS_PD]->encode(s, h->codecs[DS_PD],
                                              (char *)&i32, 1);
                break;

            case 'H':
                i32 = f->H.len;
                r |= h->codecs[DS_HC]->encode(s, h->codecs[DS_HC],
                                              (char *)&i32, 1);
                break;


            default:
                hts_log_error("Unhandled feature code %c", f->X.code);
                return -1;
            }
        }

        r |= h->codecs[DS_MQ]->encode(s, h->codecs[DS_MQ],
                                      (char *)&cr->mqual, 1);
    } else {
        char *seq = (char *)BLOCK_DATA(s->seqs_blk) + cr->seq;
        if (cr->len)
            r |= h->codecs[DS_BA]->encode(s, h->codecs[DS_BA], seq, cr->len);
    }

    return r ? -1 : 0;
}


/*
 * Applies various compression methods to specific blocks, depending on
 * known observations of how data series compress.
 *
 * Returns 0 on success
 *        -1 on failure
 */
static int cram_compress_slice(cram_fd *fd, cram_container *c, cram_slice *s) {
    int level = fd->level, i;
    int method = 1<<GZIP | 1<<GZIP_RLE, methodF = method;
    int v31_or_above = (fd->version >= (3<<8)+1);

    /* Compress the CORE Block too, with minimal zlib level */
    if (level > 5 && s->block[0]->uncomp_size > 500)
        cram_compress_block2(fd, s, s->block[0], NULL, 1<<GZIP, 1);

    if (fd->use_bz2)
        method |= 1<<BZIP2;

    int method_rans   = (1<<RANS0) | (1<<RANS1);
    int method_ranspr = method_rans;

    if (fd->use_rans) {
        method_ranspr = (1<<RANS_PR0)   | (1<<RANS_PR1);
        if (level > 1)
            method_ranspr |=
                  (1<<RANS_PR64)  | (1<<RANS_PR9)
                | (1<<RANS_PR128) | (1<<RANS_PR193);
        if (level > 5)
            method_ranspr |= (1<<RANS_PR129) | (1<<RANS_PR192);
    }

    if (fd->use_rans) {
        methodF |= v31_or_above ? method_ranspr : method_rans;
        method  |= v31_or_above ? method_ranspr : method_rans;
    }

    int method_arith   = 0;
    if (fd->use_arith) {
        method_arith = (1<<ARITH_PR0)   | (1<<ARITH_PR1);
        if (level > 1)
            method_arith |=
                  (1<<ARITH_PR64)  | (1<<ARITH_PR9)
                | (1<<ARITH_PR128) | (1<<ARITH_PR129)
                | (1<<ARITH_PR192) | (1u<<ARITH_PR193);
    }
    if (fd->use_arith && v31_or_above) {
        methodF |= method_arith;
        method  |= method_arith;
    }

    if (fd->use_lzma)
        method |= (1<<LZMA);

    /* Faster method for data series we only need entropy encoding on */
    methodF = method & ~(1<<GZIP | 1<<BZIP2 | 1<<LZMA);
    if (level >= 5) {
        method |= 1<<GZIP_1;
        methodF = method;
    }
    if (level == 1) {
        method &= ~(1<<GZIP);
        method |=   1<<GZIP_1;
        methodF = method;
    }

    int qmethod  = method;
    int qmethodF = method;
    if (v31_or_above && fd->use_fqz) {
        qmethod  |= 1<<FQZ;
        qmethodF |= 1<<FQZ;
        if (fd->level > 4) {
            qmethod  |= 1<<FQZ_b;
            qmethodF |= 1<<FQZ_b;
        }
        if (fd->level > 6) {
            qmethod  |= (1<<FQZ_c) | (1<<FQZ_d);
            qmethodF |= (1<<FQZ_c) | (1<<FQZ_d);
        }
    }

    pthread_mutex_lock(&fd->metrics_lock);
    for (i = 0; i < DS_END; i++)
        if (c->stats[i] && c->stats[i]->nvals > 16)
            fd->m[i]->unpackable = 1;
    pthread_mutex_unlock(&fd->metrics_lock);

    /* Specific compression methods for certain block types */
    if (cram_compress_block2(fd, s, s->block[DS_IN], fd->m[DS_IN], //IN (seq)
                             method, level))
        return -1;

    if (fd->level == 0) {
        /* Do nothing */
    } else if (fd->level == 1) {
        if (cram_compress_block2(fd, s, s->block[DS_QS], fd->m[DS_QS],
                                 qmethodF, 1))
            return -1;
        for (i = DS_aux; i <= DS_aux_oz; i++) {
            if (s->block[i])
                if (cram_compress_block2(fd, s, s->block[i], fd->m[i],
                                         method, 1))
                    return -1;
        }
    } else if (fd->level < 3) {
        if (cram_compress_block2(fd, s, s->block[DS_QS], fd->m[DS_QS],
                                 qmethod, 1))
            return -1;
        if (cram_compress_block2(fd, s, s->block[DS_BA], fd->m[DS_BA],
                                 method, 1))
            return -1;
        if (s->block[DS_BB])
            if (cram_compress_block2(fd, s, s->block[DS_BB], fd->m[DS_BB],
                                     method, 1))
                return -1;
        for (i = DS_aux; i <= DS_aux_oz; i++) {
            if (s->block[i])
                if (cram_compress_block2(fd, s, s->block[i], fd->m[i],
                                         method, level))
                    return -1;
        }
    } else {
        if (cram_compress_block2(fd, s, s->block[DS_QS], fd->m[DS_QS],
                                 qmethod, level))
            return -1;
        if (cram_compress_block2(fd, s, s->block[DS_BA], fd->m[DS_BA],
                                 method, level))
            return -1;
        if (s->block[DS_BB])
            if (cram_compress_block2(fd, s, s->block[DS_BB], fd->m[DS_BB],
                                     method, level))
                return -1;
        for (i = DS_aux; i <= DS_aux_oz; i++) {
            if (s->block[i])
                if (cram_compress_block2(fd, s, s->block[i], fd->m[i],
                                         method, level))
                    return -1;
        }
    }

    // NAME: best is generally xz, bzip2, zlib then rans1
    int method_rn = method & ~(method_rans | method_ranspr | 1<<GZIP_RLE);
    if (fd->version >= (3<<8)+1 && fd->use_tok)
        method_rn |= fd->use_arith ? (1<<TOKA) : (1<<TOK3);
    if (cram_compress_block2(fd, s, s->block[DS_RN], fd->m[DS_RN],
                             method_rn, level))
        return -1;

    // NS shows strong local correlation as rearrangements are localised
    if (s->block[DS_NS] && s->block[DS_NS] != s->block[0])
        if (cram_compress_block2(fd, s, s->block[DS_NS], fd->m[DS_NS],
                                 method, level))
            return -1;


    /*
     * Compress any auxiliary tags with their own per-tag metrics
     */
    {
        int i;
        for (i = DS_END /*num_blk - naux_blk*/; i < s->hdr->num_blocks; i++) {
            if (!s->block[i] || s->block[i] == s->block[0])
                continue;

            if (s->block[i]->method != RAW)
                continue;

            if (cram_compress_block2(fd, s, s->block[i], s->block[i]->m,
                                     method, level))
                return -1;
        }
    }

    /*
     * Minimal compression of any block still uncompressed, bar CORE
     */
    {
        int i;
        for (i = 1; i < s->hdr->num_blocks && i < DS_END; i++) {
            if (!s->block[i] || s->block[i] == s->block[0])
                continue;

            if (s->block[i]->method != RAW)
                continue;

            if (cram_compress_block2(fd, s, s->block[i], fd->m[i],
                                    methodF, level))
                return -1;
        }
    }

    return 0;
}

/*
 * Allocates a block associated with the cram codec associated with
 * data series ds_id or the internal codec_id (depending on codec
 * type).
 *
 * The ds_ids are what end up written to disk as an external block.
 * The c_ids are internal and used when daisy-chaining transforms
 * such as MAP and RLE.  These blocks are also allocated, but
 * are ephemeral in nature.  (The codecs themselves cannot allocate
 * these as the same codec pointer may be operating on multiple slices
 * if we're using a multi-slice container.)
 *
 * Returns 0 on success
 *        -1 on failure
 */
static int cram_allocate_block(cram_codec *codec, cram_slice *s, int ds_id) {
    if (!codec)
        return 0;

    switch(codec->codec) {
    // Codecs which are hard-coded to use the CORE block
    case E_GOLOMB:
    case E_HUFFMAN:
    case E_BETA:
    case E_SUBEXP:
    case E_GOLOMB_RICE:
    case E_GAMMA:
        codec->out = s->block[0];
        break;

    // Codecs which don't use external blocks
    case E_CONST_BYTE:
    case E_CONST_INT:
       codec->out = NULL;
       break;

    // Codecs that emit directly to external blocks
    case E_EXTERNAL:
    case E_VARINT_UNSIGNED:
    case E_VARINT_SIGNED:
        if (!(s->block[ds_id] = cram_new_block(EXTERNAL, ds_id)))
            return -1;
        codec->u.external.content_id = ds_id;
        codec->out = s->block[ds_id];
        break;

    case E_BYTE_ARRAY_STOP: // Why no sub-codec?
        if (!(s->block[ds_id] = cram_new_block(EXTERNAL, ds_id)))
            return -1;
        codec->u.byte_array_stop.content_id = ds_id;
        codec->out = s->block[ds_id];
        break;


    // Codecs that contain sub-codecs which may in turn emit to external blocks
    case E_BYTE_ARRAY_LEN: {
        cram_codec *bal = codec->u.e_byte_array_len.len_codec;
        if (cram_allocate_block(bal, s, bal->u.external.content_id))
            return -1;
        bal = codec->u.e_byte_array_len.val_codec;
        if (cram_allocate_block(bal, s, bal->u.external.content_id))
            return -1;

        break;
    }

    case E_XRLE:
        if (cram_allocate_block(codec->u.e_xrle.len_codec, s, ds_id))
                                //ds_id == DS_QS ? DS_QS_len : ds_id))
            return -1;
        if (cram_allocate_block(codec->u.e_xrle.lit_codec, s, ds_id))
            return -1;

        break;

    case E_XPACK:
        if (cram_allocate_block(codec->u.e_xpack.sub_codec, s, ds_id))
            return -1;
        codec->out = cram_new_block(0, 0); // ephemeral
        if (!codec->out)
            return -1;

        break;

    case E_XDELTA:
        if (cram_allocate_block(codec->u.e_xdelta.sub_codec, s, ds_id))
            return -1;
        codec->out = cram_new_block(0, 0); // ephemeral
        if (!codec->out)
            return -1;

        break;

    default:
        break;
    }

    return 0;
}

/*
 * Encodes a single slice from a container
 *
 * Returns 0 on success
 *        -1 on failure
 */
static int cram_encode_slice(cram_fd *fd, cram_container *c,
                             cram_block_compression_hdr *h, cram_slice *s,
                             int embed_ref) {
    int rec, r = 0;
    int64_t last_pos;
    enum cram_DS_ID id;

    /*
     * Slice external blocks:
     * ID 0 => base calls (insertions, soft-clip)
     * ID 1 => qualities
     * ID 2 => names
     * ID 3 => TS (insert size), NP (next frag)
     * ID 4 => tag values
     * ID 6 => tag IDs (TN), if CRAM_V1.0
     * ID 7 => TD tag dictionary, if !CRAM_V1.0
     */

    /* Create cram slice header */
    s->hdr->ref_base_id = embed_ref>0 && s->hdr->ref_seq_span > 0
        ? DS_ref
        : (CRAM_MAJOR_VERS(fd->version) >= 4 ? 0 : -1);
    s->hdr->record_counter = c->num_records + c->record_counter;
    c->num_records += s->hdr->num_records;

    int ntags = c->tags_used ? c->tags_used->n_occupied : 0;
    s->block = calloc(DS_END + ntags*2, sizeof(s->block[0]));
    s->hdr->block_content_ids = malloc(DS_END * sizeof(int32_t));
    if (!s->block || !s->hdr->block_content_ids)
        return -1;

    // Create first fixed blocks, always external.
    // CORE
    if (!(s->block[0] = cram_new_block(CORE, 0)))
        return -1;

    // TN block for CRAM v1
    if (CRAM_MAJOR_VERS(fd->version) == 1) {
        if (h->codecs[DS_TN]->codec == E_EXTERNAL) {
            if (!(s->block[DS_TN] = cram_new_block(EXTERNAL,DS_TN))) return -1;
            h->codecs[DS_TN]->u.external.content_id = DS_TN;
        } else {
            s->block[DS_TN] = s->block[0];
        }
    }

    // Embedded reference
    if (embed_ref>0) {
        if (!(s->block[DS_ref] = cram_new_block(EXTERNAL, DS_ref)))
            return -1;
        s->ref_id = DS_ref; // needed?
        BLOCK_APPEND(s->block[DS_ref],
                     c->ref + s->hdr->ref_seq_start - c->ref_start,
                     s->hdr->ref_seq_span);
    }

    /*
     * All the data-series blocks if appropriate.
     */
    for (id = DS_QS; id < DS_TN; id++) {
        if (cram_allocate_block(h->codecs[id], s, id) < 0)
            return -1;
    }

    /*
     * Add in the external tag blocks too.
     */
    if (c->tags_used) {
        int n;
        s->hdr->num_blocks = DS_END;
        for (n = 0; n < s->naux_block; n++) {
            s->block[s->hdr->num_blocks++] = s->aux_block[n];
            s->aux_block[n] = NULL;
        }
    }

    /* Encode reads */
    last_pos = s->hdr->ref_seq_start;
    for (rec = 0; rec < s->hdr->num_records; rec++) {
        cram_record *cr = &s->crecs[rec];
        if (cram_encode_slice_read(fd, c, h, s, cr, &last_pos) == -1)
            return -1;
    }

    s->block[0]->uncomp_size = s->block[0]->byte + (s->block[0]->bit < 7);
    s->block[0]->comp_size = s->block[0]->uncomp_size;

    // Make sure the fixed blocks point to the correct sources
    if (s->block[DS_IN]) cram_free_block(s->block[DS_IN]);
    s->block[DS_IN] = s->base_blk; s->base_blk = NULL;
    if (s->block[DS_QS]) cram_free_block(s->block[DS_QS]);
    s->block[DS_QS] = s->qual_blk; s->qual_blk = NULL;
    if (s->block[DS_RN]) cram_free_block(s->block[DS_RN]);
    s->block[DS_RN] = s->name_blk; s->name_blk = NULL;
    if (s->block[DS_SC]) cram_free_block(s->block[DS_SC]);
    s->block[DS_SC] = s->soft_blk; s->soft_blk = NULL;

    // Finalise any data transforms.
    for (id = DS_QS; id < DS_TN; id++) {
       if (h->codecs[id] && h->codecs[id]->flush)
           h->codecs[id]->flush(h->codecs[id]);
    }

    // Ensure block sizes are up to date.
    for (id = 1; id < s->hdr->num_blocks; id++) {
        if (!s->block[id] || s->block[id] == s->block[0])
            continue;

        if (s->block[id]->uncomp_size == 0)
            BLOCK_UPLEN(s->block[id]);
    }

    // Compress it all
    if (cram_compress_slice(fd, c, s) == -1)
        return -1;

    // Collapse empty blocks and create hdr_block
    {
        int i, j;

        s->hdr->block_content_ids = realloc(s->hdr->block_content_ids,
                                            s->hdr->num_blocks * sizeof(int32_t));
        if (!s->hdr->block_content_ids)
            return -1;

        for (i = j = 1; i < s->hdr->num_blocks; i++) {
            if (!s->block[i] || s->block[i] == s->block[0])
                continue;
            if (s->block[i]->uncomp_size == 0) {
                cram_free_block(s->block[i]);
                s->block[i] = NULL;
                continue;
            }
            s->block[j] = s->block[i];
            s->hdr->block_content_ids[j-1] = s->block[i]->content_id;
            j++;
        }
        s->hdr->num_content_ids = j-1;
        s->hdr->num_blocks = j;

        if (!(s->hdr_block = cram_encode_slice_header(fd, s)))
            return -1;
    }

    return r ? -1 : 0;

 block_err:
    return -1;
}

static inline const char *bam_data_end(bam1_t *b) {
    return (const char *)b->data + b->l_data;
}

/*
 * A bounds checking version of bam_aux2i.
 */
static inline int bam_aux2i_end(const uint8_t *aux, const uint8_t *aux_end) {
    int type = *aux++;
    switch (type) {
        case 'c':
            if (aux_end - aux < 1) {
                errno = EINVAL;
                return 0;
            }
            return *(int8_t *)aux;
        case 'C':
            if (aux_end - aux < 1) {
                errno = EINVAL;
                return 0;
            }
            return *aux;
        case 's':
            if (aux_end - aux < 2) {
                errno = EINVAL;
                return 0;
            }
            return le_to_i16(aux);
        case 'S':
            if (aux_end - aux < 2) {
                errno = EINVAL;
                return 0;
            }
            return le_to_u16(aux);
        case 'i':
            if (aux_end - aux < 4) {
                errno = EINVAL;
                return 0;
            }
            return le_to_i32(aux);
        case 'I':
            if (aux_end - aux < 4) {
                errno = EINVAL;
                return 0;
            }
            return le_to_u32(aux);
        default:
            errno = EINVAL;
    }
    return 0;
}

/*
 * Returns the number of expected read names for this record.
 */
static int expected_template_count(bam_seq_t *b) {
    int expected = bam_flag(b) & BAM_FPAIRED ? 2 : 1;

    uint8_t *TC = (uint8_t *)bam_aux_get(b, "TC");
    if (TC) {
        int n = bam_aux2i_end(TC, (uint8_t *)bam_data_end(b));
        if (expected < n)
            expected = n;
    }

    if (!TC && bam_aux_get(b, "SA")) {
        // We could count the semicolons, but we'd have to do this for
        // read1, read2 and read(not-1-or-2) combining the results
        // together.  This is a cheap and safe alternative for now.
        expected = INT_MAX;
    }

    return expected;
}

/*
 * Lossily reject read names.
 *
 * The rule here is that if all reads for this template reside in the
 * same slice then we can lose the name.  Otherwise we keep them as we
 * do not know when (or if) the other reads will turn up.
 *
 * Note there may be only 1 read (non-paired library) or more than 2
 * reads (paired library with supplementary reads), or other weird
 * setups.  We need to know how many are expected.  Ways to guess:
 *
 * - Flags (0x1 - has > 1 read)
 * - TC aux field (not mandatory)
 * - SA tags (count semicolons, NB per fragment so sum - hard)
 * - RNEXT/PNEXT uniqueness count. (not implemented, tricky)
 *
 * Returns 0 on success
 *        -1 on failure
 */
static int lossy_read_names(cram_fd *fd, cram_container *c, cram_slice *s,
                            int bam_start) {
    int r1, r2, ret = -1;

    // Initialise cram_flags
    for (r2 = 0; r2 < s->hdr->num_records; r2++)
        s->crecs[r2].cram_flags = 0;

    if (!fd->lossy_read_names)
        return 0;

    khash_t(m_s2u64) *names = kh_init(m_s2u64);
    if (!names)
        goto fail;

    // 1: Iterate through names to count frequency
    for (r1 = bam_start, r2 = 0; r2 < s->hdr->num_records; r1++, r2++) {
        //cram_record *cr = &s->crecs[r2];
        bam_seq_t *b = c->bams[r1];
        khint_t k;
        int n;
        uint64_t e;
        union {
            uint64_t i64;
            struct {
                int32_t e,c; // expected & observed counts.
            } counts;
        } u;

        e = expected_template_count(b);
        u.counts.e = e; u.counts.c = 1;

        k = kh_put(m_s2u64, names, bam_name(b), &n);
        if (n == -1)
            goto fail;

        if (n == 0) {
            // not a new name
            u.i64 = kh_val(names, k);
            if (u.counts.e != e) {
                // different expectation or already hit the max
                //fprintf(stderr, "Err computing no. %s recs\n", bam_name(b));
                kh_val(names, k) = 0;
            } else {
                u.counts.c++;
                if (u.counts.e == u.counts.c) {
                    // Reached expected count.
                    kh_val(names, k) = -1;
                } else {
                    kh_val(names, k) = u.i64;
                }
            }
        } else {
            // new name
            kh_val(names, k) = u.i64;
        }
    }

    // 2: Remove names if all present (hd.i == -1)
    for (r1 = bam_start, r2 = 0; r2 < s->hdr->num_records; r1++, r2++) {
        cram_record *cr = &s->crecs[r2];
        bam_seq_t *b = c->bams[r1];
        khint_t k;

        k = kh_get(m_s2u64, names, bam_name(b));

        if (k == kh_end(names))
            goto fail;

        if (kh_val(names, k) == -1)
            cr->cram_flags = CRAM_FLAG_DISCARD_NAME;
    }

    ret = 0;
 fail: // ret==-1

    if (names)
        kh_destroy(m_s2u64, names);

    return ret;
}

/*
 * Adds the reading names.  We do this here as a separate pass rather
 * than per record in the process_one_read calls as that function can
 * go back and change the CRAM_FLAG_DETACHED status of a previously
 * processed read if it subsequently determines the TLEN field is
 * incorrect.  Given DETACHED reads always try to decode read names,
 * we need to know their status before generating the read-name block.
 *
 * Output is an update s->name_blk, and cr->name / cr->name_len
 * fields.
 */
static int add_read_names(cram_fd *fd, cram_container *c, cram_slice *s,
                          int bam_start) {
    int r1, r2;
    int keep_names = !fd->lossy_read_names;

    for (r1 = bam_start, r2 = 0;
         r1 < c->curr_c_rec && r2 < s->hdr->num_records;
         r1++, r2++) {
        cram_record *cr = &s->crecs[r2];
        bam_seq_t *b = c->bams[r1];

        cr->name        = BLOCK_SIZE(s->name_blk);
        if ((cr->cram_flags & CRAM_FLAG_DETACHED) || keep_names) {
            if (CRAM_MAJOR_VERS(fd->version) >= 4
                && (cr->cram_flags & CRAM_FLAG_MATE_DOWNSTREAM)
                && cr->mate_line) {
                // Dedup read names in V4
                BLOCK_APPEND(s->name_blk, "\0", 1);
                cr->name_len    = 1;
            } else {
                BLOCK_APPEND(s->name_blk, bam_name(b), bam_name_len(b));
                cr->name_len    = bam_name_len(b);
            }
        } else {
            // Can only discard duplicate names if not detached
            cr->name_len = 0;
        }

        if (cram_stats_add(c->stats[DS_RN], cr->name_len) < 0)
            goto block_err;
    }

    return 0;

 block_err:
    return -1;
}

// CRAM version >= 3.1
#define CRAM_ge31(v) ((v) >= 0x301)

// Returns the next cigar op code: one of the BAM_C* codes,
// or -1 if no more are present.
static inline
int next_cigar_op(uint32_t *cigar, uint32_t ncigar, int *skip, int *spos,
                  uint32_t *cig_ind, uint32_t *cig_op, uint32_t *cig_len) {
    for(;;) {
        while (*cig_len == 0) {
            if (*cig_ind < ncigar) {
                *cig_op  = cigar[*cig_ind] & BAM_CIGAR_MASK;
                *cig_len = cigar[*cig_ind] >> BAM_CIGAR_SHIFT;
                (*cig_ind)++;
            } else {
                return -1;
            }
        }

        if (skip[*cig_op]) {
            *spos += (bam_cigar_type(*cig_op)&1) * *cig_len;
            *cig_len = 0;
            continue;
        }

        (*cig_len)--;
        break;
    }

    return *cig_op;
}

// Ensure ref and hist are large enough.
static inline int extend_ref(char **ref, uint32_t (**hist)[5], hts_pos_t pos,
                             hts_pos_t ref_start, hts_pos_t *ref_end) {
    if (pos < ref_start)
        return -1;
    if (pos < *ref_end)
        return 0;

    // realloc
    if (pos - ref_start > UINT_MAX)
        return -2; // protect overflow in new_end calculation

    hts_pos_t old_end = *ref_end ? *ref_end : ref_start;
    hts_pos_t new_end = ref_start + 1000 + (pos-ref_start)*1.5;

    // Refuse to work on excessively large blocks.
    // We'll just switch to referenceless encoding, which is probably better
    // here as this must be very sparse data anyway.
    if (new_end - ref_start > UINT_MAX/sizeof(**hist)/2)
        return -2;

    char *tmp = realloc(*ref, new_end-ref_start+1);
    if (!tmp)
        return -1;
    *ref = tmp;

    uint32_t (*tmp5)[5] = realloc(**hist,
                                  (new_end - ref_start)*sizeof(**hist));
    if (!tmp5)
        return -1;
    *hist = tmp5;
    *ref_end = new_end;

    // initialise
    old_end -= ref_start;
    new_end -= ref_start;
    memset(&(*ref)[old_end],  0,  new_end-old_end);
    memset(&(*hist)[old_end], 0, (new_end-old_end)*sizeof(**hist));

    return 0;
}

// Walk through MD + seq to generate ref
// Returns 1 on success, <0 on failure
static int cram_add_to_ref_MD(bam1_t *b, char **ref, uint32_t (**hist)[5],
                              hts_pos_t ref_start, hts_pos_t *ref_end,
                              const uint8_t *MD) {
    uint8_t *seq = bam_get_seq(b);
    uint32_t *cigar = bam_get_cigar(b);
    uint32_t ncigar = b->core.n_cigar;
    uint32_t cig_op = 0, cig_len = 0, cig_ind = 0;

    // End position of the sequence on the reference.
    hts_pos_t rlen = bam_cigar2rlen(b->core.n_cigar, bam_get_cigar(b));
    hts_pos_t rseq_end = b->core.pos + (rlen ? rlen : b->core.l_qseq);

    // No sequence means extend based on CIGAR instead
    if (!b->core.l_qseq && extend_ref(ref, hist, rseq_end,
                                      ref_start, ref_end) < 0)
        return -1;

    int iseq = 0, next_op;
    hts_pos_t iref = b->core.pos - ref_start;

    // Skip INS, REF_SKIP, *CLIP, PAD. and BACK.
    static int cig_skip[16] = {0,1,0,1,1,1,1,0,0,1,1,1,1,1,1,1};
    while (iseq < b->core.l_qseq && *MD) {
        if (isdigit(*MD)) {
            // match
            int overflow = 0;
            int len = hts_str2uint((char *)MD, (char **)&MD, 31, &overflow);
            if (overflow ||
                extend_ref(ref, hist, iref+ref_start + len,
                           ref_start, ref_end) < 0)
                return -1;
            while (iseq < b->core.l_qseq && len) {
                // rewrite to have internal loops?
                if ((next_op = next_cigar_op(cigar, ncigar, cig_skip,
                                             &iseq, &cig_ind, &cig_op,
                                             &cig_len)) < 0)
                    return -1;

                if (next_op != BAM_CMATCH &&
                    next_op != BAM_CEQUAL) {
                    hts_log_info("MD:Z and CIGAR are incompatible for "
                                 "record %s", bam_get_qname(b));
                    return -1;
                }

                // Short-cut loop over same cigar op for efficiency
                cig_len++;
                do {
                    cig_len--;
                    (*ref)[iref++] = seq_nt16_str[bam_seqi(seq, iseq)];
                    iseq++;
                    len--;
                } while (cig_len && iseq < b->core.l_qseq && len);
            }
            if (len > 0)
                return -1; // MD is longer than seq
        } else if (*MD == '^') {
            // deletion
            MD++;
            while (isalpha(*MD)) {
                if (extend_ref(ref, hist, iref+ref_start, ref_start,
                               ref_end) < 0)
                    return -1;
                if ((next_op = next_cigar_op(cigar, ncigar, cig_skip,
                                             &iseq, &cig_ind, &cig_op,
                                             &cig_len)) < 0)
                    return -1;

                if (next_op != BAM_CDEL) {
                    hts_log_info("MD:Z and CIGAR are incompatible");
                    return -1;
                }

                (*ref)[iref++] = *MD++ & ~0x20;
            }
        } else {
            // substitution
            if (extend_ref(ref, hist, iref+ref_start, ref_start, ref_end) < 0)
                return -1;
            if ((next_op = next_cigar_op(cigar, ncigar, cig_skip,
                                         &iseq, &cig_ind, &cig_op,
                                         &cig_len)) < 0)
                return -1;

            if (next_op != BAM_CMATCH && next_op != BAM_CDIFF) {
                hts_log_info("MD:Z and CIGAR are incompatible");
                return -1;
            }

            (*ref)[iref++] = *MD++ & ~0x20;
            iseq++;
        }
    }

    return 1;
}

// Append a sequence to a ref/consensus structure.
// We maintain both an absolute refefence (ACGTN where MD:Z is
// present) and a 5-way frequency array for when no MD:Z is known.
// We then subsequently convert the 5-way frequencies to a consensus
// ref in a second pass.
//
// Returns >=0 on success,
//         -1 on failure (eg inconsistent data)
static int cram_add_to_ref(bam1_t *b, char **ref, uint32_t (**hist)[5],
                           hts_pos_t ref_start, hts_pos_t *ref_end) {
    const uint8_t *MD = bam_aux_get(b, "MD");
    int ret = 0;
    if (MD && *MD == 'Z') {
        // We can use MD to directly compute the reference
        int ret = cram_add_to_ref_MD(b, ref, hist, ref_start, ref_end, MD+1);

        if (ret > 0)
            return ret;
    }

    // Otherwise we just use SEQ+CIGAR and build a consensus which we later
    // turn into a fake reference
    uint32_t *cigar = bam_get_cigar(b);
    uint32_t ncigar = b->core.n_cigar;
    uint32_t i, j;
    hts_pos_t iseq = 0, iref = b->core.pos - ref_start;
    uint8_t *seq = bam_get_seq(b);
    for (i = 0; i < ncigar; i++) {
        switch (bam_cigar_op(cigar[i])) {
        case BAM_CSOFT_CLIP:
        case BAM_CINS:
            iseq += bam_cigar_oplen(cigar[i]);
            break;

        case BAM_CMATCH:
        case BAM_CEQUAL:
        case BAM_CDIFF: {
            int len = bam_cigar_oplen(cigar[i]);
            // Maps an nt16 (A=1 C=2 G=4 T=8 bits) to 0123 plus N=4
            static uint8_t L16[16] = {4,0,1,4, 2,4,4,4, 3,4,4,4, 4,4,4,4};

            if (extend_ref(ref, hist, iref+ref_start + len,
                           ref_start, ref_end) < 0)
                return -1;
            if (iseq + len <= b->core.l_qseq) {
                // Nullify failed MD:Z if appropriate
                if (ret < 0)
                    memset(&(*ref)[iref], 0, len);

                for (j = 0; j < len; j++, iref++, iseq++)
                    (*hist)[iref][L16[bam_seqi(seq, iseq)]]++;
            } else {
                // Probably a 2ndary read with seq "*"
                iseq += len;
                iref += len;
            }
            break;
        }

        case BAM_CDEL:
        case BAM_CREF_SKIP:
            iref += bam_cigar_oplen(cigar[i]);
        }
    }

    return 1;
}

// Automatically generates the reference and stashed it in c->ref, also
// setting c->ref_start and c->ref_end.
//
// If we have MD:Z tags then we use them to directly infer the reference,
// along with SEQ + CIGAR.  Otherwise we use SEQ/CIGAR only to build up
// a consensus and then assume the reference as the majority rule.
//
// In this latter scenario we need to be wary of auto-generating MD and NM
// during decode, but that's handled elsewhere via an additional aux tag.
//
// Returns 0 on success,
//        -1 on failure
static int cram_generate_reference(cram_container *c, cram_slice *s, int r1) {
    // TODO: if we can find an external reference then use it, even if the
    // user told us to do embed_ref=2.
    char *ref = NULL;
    uint32_t (*hist)[5] = NULL;
    hts_pos_t ref_start = c->bams[r1]->core.pos, ref_end = 0;
    if (ref_start < 0)
        return -1; // cannot build consensus from unmapped data

    // initial allocation
    if (extend_ref(&ref, &hist,
                   c->bams[r1 + s->hdr->num_records-1]->core.pos +
                   c->bams[r1 + s->hdr->num_records-1]->core.l_qseq,
                   ref_start, &ref_end) < 0)
        return -1;

    // Add each bam file to the reference/consensus arrays
    int r2;
    hts_pos_t last_pos = -1;
    for (r2 = 0; r1 < c->curr_c_rec && r2 < s->hdr->num_records; r1++, r2++) {
        if (c->bams[r1]->core.pos < last_pos) {
            hts_log_error("Cannot build reference with unsorted data");
            goto err;
        }
        last_pos = c->bams[r1]->core.pos;
        if (cram_add_to_ref(c->bams[r1], &ref, &hist, ref_start, &ref_end) < 0)
            goto err;
    }

    // Compute the consensus
    hts_pos_t i;
    for (i = 0; i < ref_end-ref_start; i++) {
        if (!ref[i]) {
            int max_v = 0, max_j = 4, j;
            for (j = 0; j < 4; j++)
                // don't call N (j==4) unless no coverage
                if (max_v < hist[i][j])
                    max_v = hist[i][j], max_j = j;
            ref[i] = "ACGTN"[max_j];
        }
    }
    free(hist);

    // Put the reference in place so it appears to be an external
    // ref file.
    c->ref       = ref;
    c->ref_start = ref_start+1;
    c->ref_end   = ref_end+1;
    c->ref_free  = 1;
    return 0;

 err:
    free(ref);
    free(hist);
    return -1;
}

// Check if the SQ M5 tag matches the reference we've loaded.
static int validate_md5(cram_fd *fd, int ref_id) {
    if (fd->ignore_md5 || ref_id < 0 || ref_id >= fd->refs->nref)
        return 0;

    // Have we already checked this ref?
    if (fd->refs->ref_id[ref_id]->validated_md5)
        return 0;

    // Check if we have the MD5 known.
    // We should, but maybe we're using embedded references?
    sam_hrecs_t *hrecs = fd->header->hrecs;
    sam_hrec_type_t *ty = sam_hrecs_find_type_id(hrecs, "SQ", "SN",
                                                 hrecs->ref[ref_id].name);
    if (!ty)
        return 0;

    sam_hrec_tag_t *m5tag = sam_hrecs_find_key(ty, "M5", NULL);
    if (!m5tag)
        return 0;

    // It's known, so compute md5 on the loaded reference sequence.
    char *ref = fd->refs->ref_id[ref_id]->seq;
    int64_t len = fd->refs->ref_id[ref_id]->length;
    hts_md5_context *md5;
    char unsigned buf[16];
    char buf2[33];

    if (!(md5 = hts_md5_init()))
        return -1;
    hts_md5_update(md5, ref, len);
    hts_md5_final(buf, md5);
    hts_md5_destroy(md5);
    hts_md5_hex(buf2, buf);

    // Compare it to header @SQ M5 tag
    if (strcmp(m5tag->str+3, buf2)) {
        hts_log_error("SQ header M5 tag discrepancy for reference '%s'",
                      hrecs->ref[ref_id].name);
        hts_log_error("Please use the correct reference, or "
                      "consider using embed_ref=2");
        return -1;
    }
    fd->refs->ref_id[ref_id]->validated_md5 = 1;

    return 0;
}

/*
 * Encodes all slices in a container into blocks.
 * Returns 0 on success
 *        -1 on failure
 */
int cram_encode_container(cram_fd *fd, cram_container *c) {
    int i, j, slice_offset;
    cram_block_compression_hdr *h = c->comp_hdr;
    cram_block *c_hdr;
    int multi_ref = 0;
    int r1, r2, sn, nref, embed_ref, no_ref;
    spare_bams *spares;

    if (!c->bams)
        goto err;

    if (CRAM_MAJOR_VERS(fd->version) == 1)
        goto err;

//#define goto_err {fprintf(stderr, "ERR at %s:%d\n", __FILE__, __LINE__);goto err;}
#define goto_err goto err

    // Don't try embed ref if we repeatedly fail
    pthread_mutex_lock(&fd->ref_lock);
    int failed_embed = (fd->no_ref_counter >= 5); // maximum 5 tries
    if (!failed_embed && c->embed_ref == -2 && c->ref_id >= 0) {
        hts_log_warning("Retrying embed_ref=2 mode for #%d/5", fd->no_ref_counter);
        fd->no_ref = c->no_ref = 0;
        fd->embed_ref = c->embed_ref = 2;
    } else if (failed_embed && c->embed_ref == -2) {
        // We've tried several times, so this time give up for good
        hts_log_warning("Keeping non-ref mode from now on");
        fd->embed_ref = c->embed_ref = 0;
    }
    pthread_mutex_unlock(&fd->ref_lock);

 restart:
    /* Cache references up-front if we have unsorted access patterns */
    pthread_mutex_lock(&fd->ref_lock);
    nref = fd->refs->nref;
    pthread_mutex_unlock(&fd->ref_lock);
    embed_ref = c->embed_ref;
    no_ref = c->no_ref;

    /* To create M5 strings */
    /* Fetch reference sequence */
    if (!no_ref) {
        if (!c->bams || !c->curr_c_rec || !c->bams[0])
            goto_err;
        bam_seq_t *b = c->bams[0];

        if (embed_ref <= 1) {
            char *ref = cram_get_ref(fd, bam_ref(b), 1, 0);
            if (!ref && bam_ref(b) >= 0) {
                if (!c->pos_sorted) {
                    // TODO: maybe also check fd->no_ref?
                    hts_log_warning("Failed to load reference #%d",
                                    bam_ref(b));
                    hts_log_warning("Switching to non-ref mode");

                    pthread_mutex_lock(&fd->ref_lock);
                    c->embed_ref = fd->embed_ref = 0;
                    c->no_ref = fd->no_ref = 1;
                    pthread_mutex_unlock(&fd->ref_lock);
                    goto restart;
                }

                if (c->multi_seq || embed_ref == 0) {
                    hts_log_error("Failed to load reference #%d", bam_ref(b));
                    return -1;
                }
                hts_log_warning("Failed to load reference #%d", bam_ref(b));
                hts_log_warning("Enabling embed_ref=2 mode to auto-generate"
                                " reference");
                if (embed_ref <= 0)
                    hts_log_warning("NOTE: the CRAM file will be bigger than"
                                    " using an external reference");
                pthread_mutex_lock(&fd->ref_lock);
                embed_ref = c->embed_ref = fd->embed_ref = 2;
                pthread_mutex_unlock(&fd->ref_lock);
                goto auto_ref;
            } else if (ref) {
                if (validate_md5(fd, c->ref_seq_id) < 0)
                    goto_err;
            }
            if ((c->ref_id = bam_ref(b)) >= 0) {
                c->ref_seq_id = c->ref_id;
                c->ref       = fd->refs->ref_id[c->ref_seq_id]->seq;
                c->ref_start = 1;
                c->ref_end   = fd->refs->ref_id[c->ref_seq_id]->length;
            }
        } else {
        auto_ref:
            // Auto-embed ref.
            // This starts as 'N' and is amended on-the-fly as we go
            // based on MD:Z tags.
            if ((c->ref_id = bam_ref(b)) >= 0) {
                c->ref = NULL;
                // c->ref_free is boolean; whether to free c->ref.  In this
                // case c->ref will be our auto-embedded sequence instead of
                // a "global" portion of reference from fd->refs.
                // Do not confuse with fd->ref_free which is a pointer to a
                // reference string to free.
                c->ref_free = 1;
            } else {
                // Double check for broken input.  We shouldn't have
                // embedded references enabled for unmapped data, but our
                // data could be broken.
                embed_ref = 0;
                no_ref = c->no_ref = 1;
            }
        }
        c->ref_seq_id = c->ref_id;
    } else {
        c->ref_id = bam_ref(c->bams[0]);
        cram_ref_incr(fd->refs, c->ref_id);
        c->ref_seq_id = c->ref_id;
    }

    if (!no_ref && c->refs_used) {
        for (i = 0; i < nref; i++) {
            if (c->refs_used[i]) {
                if (cram_get_ref(fd, i, 1, 0)) {
                    if (validate_md5(fd, i) < 0)
                        goto_err;
                } else {
                    hts_log_warning("Failed to find reference, "
                                    "switching to non-ref mode");
                    no_ref = c->no_ref = 1;
                }
            }
        }
    }

    /* Turn bams into cram_records and gather basic stats */
    for (r1 = sn = 0; r1 < c->curr_c_rec; sn++) {
        cram_slice *s = c->slices[sn];
        int64_t first_base = INT64_MAX, last_base = INT64_MIN;

        int r1_start = r1;

        assert(sn < c->curr_slice);

        // Discover which read names *may* be safely removed.
        // Ie which ones have all their records in this slice.
        if (lossy_read_names(fd, c, s, r1_start) != 0)
            return -1;

        // Tracking of MD tags so we can spot when the auto-generated values
        // will differ from the current stored ones.  The kstring here is
        // simply to avoid excessive malloc and free calls.  All initialisation
        // is done within process_one_read().
        kstring_t MD = {0};

        // Embed consensus / MD-generated ref
        if (embed_ref == 2) {
            if (c->ref_id < 0 || cram_generate_reference(c, s, r1) < 0) {
                // Should this be a permanent thing via fd->no_ref?
                // Doing so means we cannot easily switch back again should
                // things fix themselves later on.  This is likely not a
                // concern though as failure to generate a reference implies
                // unsorted data which is rarely recovered from.

                // Only if sn == 0.  We're hosed if we're on the 2nd slice and
                // the first worked, as no-ref is a container global param.
                if (sn > 0) {
                    hts_log_error("Failed to build reference, "
                                  "switching to non-ref mode");
                    return -1;
                } else {
                    hts_log_warning("Failed to build reference, "
                                    "switching to non-ref mode");
                }
                pthread_mutex_lock(&fd->ref_lock);
                c->embed_ref = fd->embed_ref = -2; // was previously embed_ref
                c->no_ref = fd->no_ref = 1;
                fd->no_ref_counter++; // more likely to keep permanent action
                pthread_mutex_unlock(&fd->ref_lock);
                failed_embed = 1;
                goto restart;
            } else {
                pthread_mutex_lock(&fd->ref_lock);
                fd->no_ref_counter -= (fd->no_ref_counter > 0);
                pthread_mutex_unlock(&fd->ref_lock);
            }

            if (c->ref_end > fd->refs->ref_id[c->ref_id]->LN_length)
                c->ref_end = fd->refs->ref_id[c->ref_id]->LN_length;
        }

        // Iterate through records creating the cram blocks for some
        // fields and just gathering stats for others.
        for (r2 = 0; r1 < c->curr_c_rec && r2 < s->hdr->num_records; r1++, r2++) {
            cram_record *cr = &s->crecs[r2];
            bam_seq_t *b = c->bams[r1];

            /* If multi-ref we need to cope with changing reference per seq */
            if (c->multi_seq && !no_ref) {
                if (bam_ref(b) != c->ref_seq_id && bam_ref(b) >= 0) {
                    if (c->ref_seq_id >= 0)
                        cram_ref_decr(fd->refs, c->ref_seq_id);

                    if (!cram_get_ref(fd, bam_ref(b), 1, 0)) {
                        hts_log_error("Failed to load reference #%d", bam_ref(b));
                        free(MD.s);
                        return -1;
                    }
                    if (validate_md5(fd, bam_ref(b)) < 0)
                        return -1;

                    c->ref_seq_id = bam_ref(b); // overwritten later by -2
                    if (!fd->refs->ref_id[c->ref_seq_id]->seq)
                        return -1;
                    c->ref       = fd->refs->ref_id[c->ref_seq_id]->seq;
                    c->ref_start = 1;
                    c->ref_end   = fd->refs->ref_id[c->ref_seq_id]->length;
                }
            }

            if (process_one_read(fd, c, s, cr, b, r2, &MD, embed_ref,
                                 no_ref) != 0) {
                free(MD.s);
                return -1;
            }

            if (first_base > cr->apos)
                first_base = cr->apos;

            if (last_base < cr->aend)
                last_base = cr->aend;
        }

        free(MD.s);

        // Process_one_read doesn't add read names as it can change
        // its mind during the loop on the CRAM_FLAG_DETACHED setting
        // of earlier records (if it detects the auto-generation of
        // TLEN is incorrect).  This affects which read-names can be
        // lossily compressed, so we do these in another pass.
        if (add_read_names(fd, c, s, r1_start) < 0)
            return -1;

        if (c->multi_seq) {
            s->hdr->ref_seq_id    = -2;
            s->hdr->ref_seq_start = 0;
            s->hdr->ref_seq_span  = 0;
        } else if (c->ref_id == -1 && CRAM_ge31(fd->version)) {
            // Spec states span=0, but it broke our range queries.
            // See commit message for this and prior.
            s->hdr->ref_seq_id    = -1;
            s->hdr->ref_seq_start = 0;
            s->hdr->ref_seq_span  = 0;
        } else {
            s->hdr->ref_seq_id    = c->ref_id;
            s->hdr->ref_seq_start = first_base;
            s->hdr->ref_seq_span  = MAX(0, last_base - first_base + 1);
        }
        s->hdr->num_records = r2;

        // Processed a slice, now stash the aux blocks so the next
        // slice can start aggregating them from the start again.
        if (c->tags_used->n_occupied) {
            int ntags = c->tags_used->n_occupied;
            s->aux_block = calloc(ntags*2, sizeof(*s->aux_block));
            if (!s->aux_block)
                return -1;

            khint_t k;

            s->naux_block = 0;
            for (k = kh_begin(c->tags_used); k != kh_end(c->tags_used); k++) {
                if (!kh_exist(c->tags_used, k))
                    continue;

                cram_tag_map *tm = kh_val(c->tags_used, k);
                if (!tm) goto_err;
                if (!tm->blk) continue;
                s->aux_block[s->naux_block++] = tm->blk;
                tm->blk = NULL;
                if (!tm->blk2) continue;
                s->aux_block[s->naux_block++] = tm->blk2;
                tm->blk2 = NULL;
            }
            assert(s->naux_block <= 2*c->tags_used->n_occupied);
        }
    }

    if (c->multi_seq && !no_ref) {
        if (c->ref_seq_id >= 0)
            cram_ref_decr(fd->refs, c->ref_seq_id);
    }

    /* Link our bams[] array onto the spare bam list for reuse */
    spares = malloc(sizeof(*spares));
    if (!spares) goto_err;
    pthread_mutex_lock(&fd->bam_list_lock);
    spares->bams = c->bams;
    spares->next = fd->bl;
    fd->bl = spares;
    pthread_mutex_unlock(&fd->bam_list_lock);
    c->bams = NULL;

    /* Detect if a multi-seq container */
    cram_stats_encoding(fd, c->stats[DS_RI]);
    multi_ref = c->stats[DS_RI]->nvals > 1;
    pthread_mutex_lock(&fd->metrics_lock);
    fd->last_RI_count = c->stats[DS_RI]->nvals;
    pthread_mutex_unlock(&fd->metrics_lock);


    if (multi_ref) {
        hts_log_info("Multi-ref container");
        c->ref_seq_id = -2;
        c->ref_seq_start = 0;
        c->ref_seq_span = 0;
    }


    /* Compute MD5s */
    no_ref = c->no_ref;
    int is_v4 = CRAM_MAJOR_VERS(fd->version) >= 4 ? 1 : 0;

    for (i = 0; i < c->curr_slice; i++) {
        cram_slice *s = c->slices[i];

        if (CRAM_MAJOR_VERS(fd->version) != 1) {
            if (s->hdr->ref_seq_id >= 0 && c->multi_seq == 0 && !no_ref) {
                hts_md5_context *md5 = hts_md5_init();
                if (!md5)
                    return -1;
                hts_md5_update(md5,
                               c->ref + s->hdr->ref_seq_start - c->ref_start,
                               s->hdr->ref_seq_span);
                hts_md5_final(s->hdr->md5, md5);
                hts_md5_destroy(md5);
            } else {
                memset(s->hdr->md5, 0, 16);
            }
        }
    }

    c->num_records = 0;
    c->num_blocks = 1; // cram_block_compression_hdr
    c->length = 0;

    //fprintf(stderr, "=== BF ===\n");
    h->codecs[DS_BF] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_BF]),
                                         c->stats[DS_BF], E_INT, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_BF]->nvals && !h->codecs[DS_BF]) goto_err;

    //fprintf(stderr, "=== CF ===\n");
    h->codecs[DS_CF] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_CF]),
                                         c->stats[DS_CF], E_INT, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_CF]->nvals && !h->codecs[DS_CF]) goto_err;

    //fprintf(stderr, "=== RN ===\n");
    //h->codecs[DS_RN] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_RN]),
    //                                     c->stats[DS_RN], E_BYTE_ARRAY, NULL,
    //                                     fd->version);

    //fprintf(stderr, "=== AP ===\n");
    if (c->pos_sorted || CRAM_MAJOR_VERS(fd->version) >= 4) {
        if (c->pos_sorted)
            h->codecs[DS_AP] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_AP]),
                                                 c->stats[DS_AP],
                                                 is_v4 ? E_LONG : E_INT,
                                                 NULL, fd->version, &fd->vv);
        else
            // Unsorted data has no stats, but hard-code VARINT_SIGNED / EXT.
            h->codecs[DS_AP] = cram_encoder_init(is_v4 ? E_VARINT_SIGNED
                                                       : E_EXTERNAL,
                                                 NULL,
                                                 is_v4 ? E_LONG : E_INT,
                                                 NULL, fd->version, &fd->vv);
    } else {
        // Removed BETA in v4.0.
        // Should we consider dropping use of it for 3.0 too?
        hts_pos_t p[2] = {0, c->max_apos};
        h->codecs[DS_AP] = cram_encoder_init(E_BETA, NULL,
                                             is_v4 ? E_LONG : E_INT,
                                             p, fd->version, &fd->vv);
//      cram_xdelta_encoder e;
//      e.word_size = is_v4 ? 8 : 4;
//      e.sub_encoding = E_EXTERNAL;
//      e.sub_codec_dat = (void *)DS_AP;
//
//      h->codecs[DS_AP] = cram_encoder_init(E_XDELTA, NULL,
//                                           is_v4 ? E_LONG : E_INT,
//                                           &e, fd->version, &fd->vv);
    }
    if (!h->codecs[DS_AP]) goto_err;

    //fprintf(stderr, "=== RG ===\n");
    h->codecs[DS_RG] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_RG]),
                                         c->stats[DS_RG],
                                         E_INT,
                                         NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_RG]->nvals && !h->codecs[DS_RG]) goto_err;

    //fprintf(stderr, "=== MQ ===\n");
    h->codecs[DS_MQ] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_MQ]),
                                         c->stats[DS_MQ], E_INT, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_MQ]->nvals && !h->codecs[DS_MQ]) goto_err;

    //fprintf(stderr, "=== NS ===\n");
    h->codecs[DS_NS] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_NS]),
                                         c->stats[DS_NS], E_INT, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_NS]->nvals && !h->codecs[DS_NS]) goto_err;

    //fprintf(stderr, "=== MF ===\n");
    h->codecs[DS_MF] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_MF]),
                                         c->stats[DS_MF], E_INT, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_MF]->nvals && !h->codecs[DS_MF]) goto_err;

    //fprintf(stderr, "=== TS ===\n");
    h->codecs[DS_TS] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_TS]),
                                         c->stats[DS_TS],
                                         is_v4 ? E_LONG : E_INT,
                                         NULL, fd->version, &fd->vv);
    if (c->stats[DS_TS]->nvals && !h->codecs[DS_TS]) goto_err;

    //fprintf(stderr, "=== NP ===\n");
    h->codecs[DS_NP] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_NP]),
                                         c->stats[DS_NP],
                                         is_v4 ? E_LONG : E_INT,
                                         NULL, fd->version, &fd->vv);
    if (c->stats[DS_NP]->nvals && !h->codecs[DS_NP]) goto_err;

    //fprintf(stderr, "=== NF ===\n");
    h->codecs[DS_NF] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_NF]),
                                         c->stats[DS_NF], E_INT, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_NF]->nvals && !h->codecs[DS_NF]) goto_err;

    //fprintf(stderr, "=== RL ===\n");
    h->codecs[DS_RL] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_RL]),
                                         c->stats[DS_RL], E_INT, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_RL]->nvals && !h->codecs[DS_RL]) goto_err;

    //fprintf(stderr, "=== FN ===\n");
    h->codecs[DS_FN] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_FN]),
                                         c->stats[DS_FN], E_INT, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_FN]->nvals && !h->codecs[DS_FN]) goto_err;

    //fprintf(stderr, "=== FC ===\n");
    h->codecs[DS_FC] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_FC]),
                                         c->stats[DS_FC], E_BYTE, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_FC]->nvals && !h->codecs[DS_FC]) goto_err;

    //fprintf(stderr, "=== FP ===\n");
    h->codecs[DS_FP] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_FP]),
                                         c->stats[DS_FP], E_INT, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_FP]->nvals && !h->codecs[DS_FP]) goto_err;

    //fprintf(stderr, "=== DL ===\n");
    h->codecs[DS_DL] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_DL]),
                                         c->stats[DS_DL], E_INT, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_DL]->nvals && !h->codecs[DS_DL]) goto_err;

    //fprintf(stderr, "=== BA ===\n");
    h->codecs[DS_BA] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_BA]),
                                         c->stats[DS_BA], E_BYTE, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_BA]->nvals && !h->codecs[DS_BA]) goto_err;

    if (CRAM_MAJOR_VERS(fd->version) >= 3) {
        cram_byte_array_len_encoder e;

        e.len_encoding = CRAM_MAJOR_VERS(fd->version) >= 4
            ? E_VARINT_UNSIGNED
            : E_EXTERNAL;
        e.len_dat = (void *)DS_BB_len;
        //e.len_dat = (void *)DS_BB;

        e.val_encoding = E_EXTERNAL;
        e.val_dat = (void *)DS_BB;

        h->codecs[DS_BB] = cram_encoder_init(E_BYTE_ARRAY_LEN, NULL,
                                             E_BYTE_ARRAY, (void *)&e,
                                             fd->version, &fd->vv);
        if (!h->codecs[DS_BB]) goto_err;
    } else {
        h->codecs[DS_BB] = NULL;
    }

    //fprintf(stderr, "=== BS ===\n");
    h->codecs[DS_BS] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_BS]),
                                         c->stats[DS_BS], E_BYTE, NULL,
                                         fd->version, &fd->vv);
    if (c->stats[DS_BS]->nvals && !h->codecs[DS_BS]) goto_err;

    if (CRAM_MAJOR_VERS(fd->version) == 1) {
        h->codecs[DS_TL] = NULL;
        h->codecs[DS_RI] = NULL;
        h->codecs[DS_RS] = NULL;
        h->codecs[DS_PD] = NULL;
        h->codecs[DS_HC] = NULL;
        h->codecs[DS_SC] = NULL;

        //fprintf(stderr, "=== TC ===\n");
        h->codecs[DS_TC] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_TC]),
                                             c->stats[DS_TC], E_BYTE, NULL,
                                             fd->version, &fd->vv);
        if (c->stats[DS_TC]->nvals && !h->codecs[DS_TC]) goto_err;

        //fprintf(stderr, "=== TN ===\n");
        h->codecs[DS_TN] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_TN]),
                                             c->stats[DS_TN], E_INT, NULL,
                                             fd->version, &fd->vv);
        if (c->stats[DS_TN]->nvals && !h->codecs[DS_TN]) goto_err;
    } else {
        h->codecs[DS_TC] = NULL;
        h->codecs[DS_TN] = NULL;

        //fprintf(stderr, "=== TL ===\n");
        h->codecs[DS_TL] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_TL]),
                                             c->stats[DS_TL], E_INT, NULL,
                                             fd->version, &fd->vv);
        if (c->stats[DS_TL]->nvals && !h->codecs[DS_TL]) goto_err;


        //fprintf(stderr, "=== RI ===\n");
        h->codecs[DS_RI] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_RI]),
                                             c->stats[DS_RI], E_INT, NULL,
                                             fd->version, &fd->vv);
        if (c->stats[DS_RI]->nvals && !h->codecs[DS_RI]) goto_err;

        //fprintf(stderr, "=== RS ===\n");
        h->codecs[DS_RS] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_RS]),
                                             c->stats[DS_RS], E_INT, NULL,
                                             fd->version, &fd->vv);
        if (c->stats[DS_RS]->nvals && !h->codecs[DS_RS]) goto_err;

        //fprintf(stderr, "=== PD ===\n");
        h->codecs[DS_PD] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_PD]),
                                             c->stats[DS_PD], E_INT, NULL,
                                             fd->version, &fd->vv);
        if (c->stats[DS_PD]->nvals && !h->codecs[DS_PD]) goto_err;

        //fprintf(stderr, "=== HC ===\n");
        h->codecs[DS_HC] = cram_encoder_init(cram_stats_encoding(fd, c->stats[DS_HC]),
                                             c->stats[DS_HC], E_INT, NULL,
                                             fd->version, &fd->vv);
        if (c->stats[DS_HC]->nvals && !h->codecs[DS_HC]) goto_err;

        //fprintf(stderr, "=== SC ===\n");
        if (1) {
            int i2[2] = {0, DS_SC};

            h->codecs[DS_SC] = cram_encoder_init(E_BYTE_ARRAY_STOP, NULL,
                                                 E_BYTE_ARRAY, (void *)i2,
                                                 fd->version, &fd->vv);
        } else {
            // Appears to be no practical benefit to using this method,
            // but it may work better if we start mixing SC, IN and BB
            // elements into the same external block.
            cram_byte_array_len_encoder e;

            e.len_encoding = CRAM_MAJOR_VERS(fd->version) >= 4
                ? E_VARINT_UNSIGNED
                : E_EXTERNAL;
            e.len_dat = (void *)DS_SC_len;

            e.val_encoding = E_EXTERNAL;
            e.val_dat = (void *)DS_SC;

            h->codecs[DS_SC] = cram_encoder_init(E_BYTE_ARRAY_LEN, NULL,
                                                 E_BYTE_ARRAY, (void *)&e,
                                                 fd->version, &fd->vv);
        }
        if (!h->codecs[DS_SC]) goto_err;
    }

    //fprintf(stderr, "=== IN ===\n");
    {
        int i2[2] = {0, DS_IN};
        h->codecs[DS_IN] = cram_encoder_init(E_BYTE_ARRAY_STOP, NULL,
                                             E_BYTE_ARRAY, (void *)i2,
                                             fd->version, &fd->vv);
        if (!h->codecs[DS_IN]) goto_err;
    }

    h->codecs[DS_QS] = cram_encoder_init(E_EXTERNAL, NULL, E_BYTE,
                                         (void *)DS_QS,
                                         fd->version, &fd->vv);
    if (!h->codecs[DS_QS]) goto_err;
    {
        int i2[2] = {0, DS_RN};
        h->codecs[DS_RN] = cram_encoder_init(E_BYTE_ARRAY_STOP, NULL,
                                             E_BYTE_ARRAY, (void *)i2,
                                             fd->version, &fd->vv);
        if (!h->codecs[DS_RN]) goto_err;
    }


    /* Encode slices */
    for (i = 0; i < c->curr_slice; i++) {
        hts_log_info("Encode slice %d", i);

        int local_embed_ref =
            embed_ref>0 && c->slices[i]->hdr->ref_seq_id != -1 ? 1 : 0;
        if (cram_encode_slice(fd, c, h, c->slices[i], local_embed_ref) != 0)
            return -1;
    }

    /* Create compression header */
    {
        h->ref_seq_id    = c->ref_seq_id;
        h->ref_seq_start = c->ref_seq_start;
        h->ref_seq_span  = c->ref_seq_span;
        h->num_records   = c->num_records;
        h->qs_seq_orient = c->qs_seq_orient;
        // slight misnomer - sorted or treat as-if sorted (ap_delta force to 1)
        h->AP_delta      = c->pos_sorted;
        memcpy(h->substitution_matrix, CRAM_SUBST_MATRIX, 20);

        if (!(c_hdr = cram_encode_compression_header(fd, c, h, embed_ref)))
            return -1;
    }

    /* Compute landmarks */
    /* Fill out slice landmarks */
    c->num_landmarks = c->curr_slice;
    c->landmark = malloc(c->num_landmarks * sizeof(*c->landmark));
    if (!c->landmark)
        return -1;

    /*
     * Slice offset starts after the first block, so we need to simulate
     * writing it to work out the correct offset
     */
    {
        slice_offset = c_hdr->method == RAW
            ? c_hdr->uncomp_size
            : c_hdr->comp_size;
        slice_offset += 2 + 4*(CRAM_MAJOR_VERS(fd->version) >= 3) +
            fd->vv.varint_size(c_hdr->content_id) +
            fd->vv.varint_size(c_hdr->comp_size) +
            fd->vv.varint_size(c_hdr->uncomp_size);
    }

    c->ref_seq_id    = c->slices[0]->hdr->ref_seq_id;
    if (c->ref_seq_id == -1 && CRAM_ge31(fd->version)) {
        // Spec states span=0, but it broke our range queries.
        // See commit message for this and prior.
        c->ref_seq_start = 0;
        c->ref_seq_span  = 0;
    } else {
        c->ref_seq_start = c->slices[0]->hdr->ref_seq_start;
        c->ref_seq_span  = c->slices[0]->hdr->ref_seq_span;
    }
    for (i = 0; i < c->curr_slice; i++) {
        cram_slice *s = c->slices[i];

        c->num_blocks += s->hdr->num_blocks + 1; // slice header
        c->landmark[i] = slice_offset;

        if (s->hdr->ref_seq_start + s->hdr->ref_seq_span >
            c->ref_seq_start + c->ref_seq_span) {
            c->ref_seq_span = s->hdr->ref_seq_start + s->hdr->ref_seq_span
                - c->ref_seq_start;
        }

        slice_offset += s->hdr_block->method == RAW
            ? s->hdr_block->uncomp_size
            : s->hdr_block->comp_size;

        slice_offset += 2 + 4*(CRAM_MAJOR_VERS(fd->version) >= 3) +
            fd->vv.varint_size(s->hdr_block->content_id) +
            fd->vv.varint_size(s->hdr_block->comp_size) +
            fd->vv.varint_size(s->hdr_block->uncomp_size);

        for (j = 0; j < s->hdr->num_blocks; j++) {
            slice_offset += 2 + 4*(CRAM_MAJOR_VERS(fd->version) >= 3) +
                fd->vv.varint_size(s->block[j]->content_id) +
                fd->vv.varint_size(s->block[j]->comp_size) +
                fd->vv.varint_size(s->block[j]->uncomp_size);

            slice_offset += s->block[j]->method == RAW
                ? s->block[j]->uncomp_size
                : s->block[j]->comp_size;
        }
    }
    c->length += slice_offset; // just past the final slice

    c->comp_hdr_block = c_hdr;

    if (c->ref_seq_id >= 0) {
        if (c->ref_free) {
            free(c->ref);
            c->ref = NULL;
        } else {
            cram_ref_decr(fd->refs, c->ref_seq_id);
        }
    }

    /* Cache references up-front if we have unsorted access patterns */
    if (!no_ref && c->refs_used) {
        for (i = 0; i < fd->refs->nref; i++) {
            if (c->refs_used[i])
                cram_ref_decr(fd->refs, i);
        }
    }

    return 0;

 err:
    return -1;
}


/*
 * Adds a feature code to a read within a slice. For purposes of minimising
 * memory allocations and fragmentation we have one array of features for all
 * reads within the slice. We return the index into this array for this new
 * feature.
 *
 * Returns feature index on success
 *         -1 on failure.
 */
static int cram_add_feature(cram_container *c, cram_slice *s,
                            cram_record *r, cram_feature *f) {
    if (s->nfeatures >= s->afeatures) {
        s->afeatures = s->afeatures ? s->afeatures*2 : 1024;
        s->features = realloc(s->features, s->afeatures*sizeof(*s->features));
        if (!s->features)
            return -1;
    }

    if (!r->nfeature++) {
        r->feature = s->nfeatures;
        if (cram_stats_add(c->stats[DS_FP], f->X.pos) < 0)
            return -1;
    } else {
        if (cram_stats_add(c->stats[DS_FP],
                           f->X.pos - s->features[r->feature + r->nfeature-2].X.pos) < 0)
            return -1;

    }
    if (cram_stats_add(c->stats[DS_FC], f->X.code) < 0)
        return -1;

    s->features[s->nfeatures++] = *f;

    return 0;
}

static int cram_add_substitution(cram_fd *fd, cram_container *c,
                                 cram_slice *s, cram_record *r,
                                 int pos, char base, char qual, char ref) {
    cram_feature f;

    // seq=ACGTN vs ref=ACGT or seq=ACGT vs ref=ACGTN
    if (fd->L2[(uc)base]<4 || (fd->L2[(uc)base]<5 && fd->L2[(uc)ref]<4)) {
        f.X.pos = pos+1;
        f.X.code = 'X';
        f.X.base = fd->cram_sub_matrix[ref&0x1f][base&0x1f];
        if (cram_stats_add(c->stats[DS_BS], f.X.base) < 0)
            return -1;
    } else {
        f.B.pos = pos+1;
        f.B.code = 'B';
        f.B.base = base;
        f.B.qual = qual;
        if (cram_stats_add(c->stats[DS_BA], f.B.base) < 0) return -1;
        if (cram_stats_add(c->stats[DS_QS], f.B.qual) < 0) return -1;
        BLOCK_APPEND_CHAR(s->qual_blk, qual);
    }
    return cram_add_feature(c, s, r, &f);

 block_err:
    return -1;
}

static int cram_add_bases(cram_fd *fd, cram_container *c,
                          cram_slice *s, cram_record *r,
                          int pos, int len, char *base) {
    cram_feature f;

    f.b.pos = pos+1;
    f.b.code = 'b';
    f.b.seq_idx = base - (char *)BLOCK_DATA(s->seqs_blk);
    f.b.len = len;

    return cram_add_feature(c, s, r, &f);
}

static int cram_add_base(cram_fd *fd, cram_container *c,
                         cram_slice *s, cram_record *r,
                         int pos, char base, char qual) {
    cram_feature f;
    f.B.pos = pos+1;
    f.B.code = 'B';
    f.B.base = base;
    f.B.qual = qual;
    if (cram_stats_add(c->stats[DS_BA], base) < 0) return -1;
    if (cram_stats_add(c->stats[DS_QS], qual) < 0) return -1;
    BLOCK_APPEND_CHAR(s->qual_blk, qual);
    return cram_add_feature(c, s, r, &f);

 block_err:
    return -1;
}

static int cram_add_quality(cram_fd *fd, cram_container *c,
                            cram_slice *s, cram_record *r,
                            int pos, char qual) {
    cram_feature f;
    f.Q.pos = pos+1;
    f.Q.code = 'Q';
    f.Q.qual = qual;
    if (cram_stats_add(c->stats[DS_QS], qual) < 0) return -1;
    BLOCK_APPEND_CHAR(s->qual_blk, qual);
    return cram_add_feature(c, s, r, &f);

 block_err:
    return -1;
}

static int cram_add_deletion(cram_container *c, cram_slice *s, cram_record *r,
                             int pos, int len, char *base) {
    cram_feature f;
    f.D.pos = pos+1;
    f.D.code = 'D';
    f.D.len = len;
    if (cram_stats_add(c->stats[DS_DL], len) < 0) return -1;
    return cram_add_feature(c, s, r, &f);
}

static int cram_add_softclip(cram_container *c, cram_slice *s, cram_record *r,
                             int pos, int len, char *base, int version) {
    cram_feature f;
    f.S.pos = pos+1;
    f.S.code = 'S';
    f.S.len = len;
    switch (CRAM_MAJOR_VERS(version)) {
    case 1:
        f.S.seq_idx = BLOCK_SIZE(s->base_blk);
        BLOCK_APPEND(s->base_blk, base, len);
        BLOCK_APPEND_CHAR(s->base_blk, '\0');
        break;

    case 2:
    default:
        f.S.seq_idx = BLOCK_SIZE(s->soft_blk);
        if (base) {
            BLOCK_APPEND(s->soft_blk, base, len);
        } else {
            int i;
            for (i = 0; i < len; i++)
                BLOCK_APPEND_CHAR(s->soft_blk, 'N');
        }
        BLOCK_APPEND_CHAR(s->soft_blk, '\0');
        break;

        //default:
        //    // v3.0 onwards uses BB data-series
        //    f.S.seq_idx = BLOCK_SIZE(s->soft_blk);
    }
    return cram_add_feature(c, s, r, &f);

 block_err:
    return -1;
}

static int cram_add_hardclip(cram_container *c, cram_slice *s, cram_record *r,
                             int pos, int len, char *base) {
    cram_feature f;
    f.S.pos = pos+1;
    f.S.code = 'H';
    f.S.len = len;
    if (cram_stats_add(c->stats[DS_HC], len) < 0) return -1;
    return cram_add_feature(c, s, r, &f);
}

static int cram_add_skip(cram_container *c, cram_slice *s, cram_record *r,
                         int pos, int len, char *base) {
    cram_feature f;
    f.S.pos = pos+1;
    f.S.code = 'N';
    f.S.len = len;
    if (cram_stats_add(c->stats[DS_RS], len) < 0) return -1;
    return cram_add_feature(c, s, r, &f);
}

static int cram_add_pad(cram_container *c, cram_slice *s, cram_record *r,
                        int pos, int len, char *base) {
    cram_feature f;
    f.S.pos = pos+1;
    f.S.code = 'P';
    f.S.len = len;
    if (cram_stats_add(c->stats[DS_PD], len) < 0) return -1;
    return cram_add_feature(c, s, r, &f);
}

static int cram_add_insertion(cram_container *c, cram_slice *s, cram_record *r,
                              int pos, int len, char *base) {
    cram_feature f;
    f.I.pos = pos+1;
    if (len == 1) {
        char b = base ? *base : 'N';
        f.i.code = 'i';
        f.i.base = b;
        if (cram_stats_add(c->stats[DS_BA], b) < 0) return -1;
    } else {
        f.I.code = 'I';
        f.I.len = len;
        f.S.seq_idx = BLOCK_SIZE(s->base_blk);
        if (base) {
            BLOCK_APPEND(s->base_blk, base, len);
        } else {
            int i;
            for (i = 0; i < len; i++)
                BLOCK_APPEND_CHAR(s->base_blk, 'N');
        }
        BLOCK_APPEND_CHAR(s->base_blk, '\0');
    }
    return cram_add_feature(c, s, r, &f);

 block_err:
    return -1;
}

/*
 * Encodes auxiliary data. Largely duplicated from above, but done so to
 * keep it simple and avoid a myriad of version ifs.
 *
 * Returns the RG header line pointed to by the BAM aux fields on success,
 *         NULL on failure or no rg present, also sets "*err" to non-zero
 */
static sam_hrec_rg_t *cram_encode_aux(cram_fd *fd, bam_seq_t *b,
                                      cram_container *c,
                                      cram_slice *s, cram_record *cr,
                                      int verbatim_NM, int verbatim_MD,
                                      int NM, kstring_t *MD, int cf_tag,
                                      int no_ref, int *err) {
    char *aux, *orig;
    sam_hrec_rg_t *brg = NULL;
    int aux_size = bam_get_l_aux(b);
    const char *aux_end = bam_data_end(b);
    cram_block *td_b = c->comp_hdr->TD_blk;
    int TD_blk_size = BLOCK_SIZE(td_b), new;
    char *key;
    khint_t k;

    if (err) *err = 1;

    orig = aux = (char *)bam_aux(b);


    // cF:i  => Extra CRAM bit flags.
    // 1:  Don't auto-decode MD (may be invalid)
    // 2:  Don't auto-decode NM (may be invalid)
    if (cf_tag && CRAM_MAJOR_VERS(fd->version) < 4) {
        // Temporary copy of aux so we can ammend it.
        aux = malloc(aux_size+4);
        if (!aux)
            return NULL;

        memcpy(aux, orig, aux_size);
        aux[aux_size++] = 'c';
        aux[aux_size++] = 'F';
        aux[aux_size++] = 'C';
        aux[aux_size++] = cf_tag;
        orig = aux;
        aux_end = aux + aux_size;
    }

    // Copy aux keys to td_b and aux values to slice aux blocks
    while (aux_end - aux >= 1 && aux[0] != 0) {
        int r;

        // Room for code + type + at least 1 byte of data
        if (aux - orig >= aux_size - 3)
            goto err;

        // RG:Z
        if (aux[0] == 'R' && aux[1] == 'G' && aux[2] == 'Z') {
            char *rg = &aux[3];
            aux = rg;
            while (aux < aux_end && *aux++);
            if (aux == aux_end && aux[-1] != '\0') {
                hts_log_error("Unterminated RG:Z tag for read \"%s\"",
                              bam_get_qname(b));
                goto err;
            }
            brg = sam_hrecs_find_rg(fd->header->hrecs, rg);
            if (brg) {
                if (CRAM_MAJOR_VERS(fd->version) >= 4)
                    BLOCK_APPEND(td_b, "RG*", 3);
                continue;
            } else {
                // RG:Z tag will be stored verbatim
                hts_log_warning("Missing @RG header for RG \"%s\"", rg);
                aux = rg - 3;
            }
        }

        // MD:Z
        if (aux[0] == 'M' && aux[1] == 'D' && aux[2] == 'Z') {
            if (cr->len && !no_ref && !(cr->flags & BAM_FUNMAP) && !verbatim_MD) {
                if (MD && MD->s && strncasecmp(MD->s, aux+3, orig + aux_size - (aux+3)) == 0) {
                    while (aux < aux_end && *aux++);
                    if (aux == aux_end && aux[-1] != '\0') {
                        hts_log_error("Unterminated MD:Z tag for read \"%s\"",
                                      bam_get_qname(b));
                        goto err;
                    }
                    if (CRAM_MAJOR_VERS(fd->version) >= 4)
                        BLOCK_APPEND(td_b, "MD*", 3);
                    continue;
                }
            }
        }

        // NM:i
        if (aux[0] == 'N' && aux[1] == 'M') {
            if (cr->len && !no_ref && !(cr->flags & BAM_FUNMAP) && !verbatim_NM) {
                int NM_ = bam_aux2i_end((uint8_t *)aux+2, (uint8_t *)aux_end);
                if (NM_ == NM) {
                    switch(aux[2]) {
                    case 'A': case 'C': case 'c': aux+=4; break;
                    case 'S': case 's':           aux+=5; break;
                    case 'I': case 'i': case 'f': aux+=7; break;
                    default:
                        hts_log_error("Unhandled type code for NM tag");
                        goto err;
                    }
                    if (CRAM_MAJOR_VERS(fd->version) >= 4)
                        BLOCK_APPEND(td_b, "NM*", 3);
                    continue;
                }
            }
        }

        BLOCK_APPEND(td_b, aux, 3);

        // Container level tags_used, for TD series
        // Maps integer key ('X0i') to cram_tag_map struct.
        int key = (((unsigned char *) aux)[0]<<16 |
                   ((unsigned char *) aux)[1]<<8  |
                   ((unsigned char *) aux)[2]);
        k = kh_put(m_tagmap, c->tags_used, key, &r);
        if (-1 == r)
            goto err;
        else if (r != 0)
            kh_val(c->tags_used, k) = NULL;

        if (r == 1) {
            khint_t k_global;

            // Global tags_used for cram_metrics support
            pthread_mutex_lock(&fd->metrics_lock);
            k_global = kh_put(m_metrics, fd->tags_used, key, &r);
            if (-1 == r) {
                pthread_mutex_unlock(&fd->metrics_lock);
                goto err;
            }
            if (r >= 1) {
                kh_val(fd->tags_used, k_global) = cram_new_metrics();
                if (!kh_val(fd->tags_used, k_global)) {
                    kh_del(m_metrics, fd->tags_used, k_global);
                    pthread_mutex_unlock(&fd->metrics_lock);
                    goto err;
                }
            }

            pthread_mutex_unlock(&fd->metrics_lock);

            int i2[2] = {'\t',key};
            size_t sk = key;
            cram_tag_map *m = calloc(1, sizeof(*m));
            if (!m)
                goto_err;
            kh_val(c->tags_used, k) = m;

            cram_codec *c;

            // Use a block content id based on the tag id.
            // Codec type depends on tag data type.
            switch(aux[2]) {
            case 'Z': case 'H':
                // string as byte_array_stop
                c = cram_encoder_init(E_BYTE_ARRAY_STOP, NULL,
                                      E_BYTE_ARRAY, (void *)i2,
                                      fd->version, &fd->vv);
                break;

            case 'A': case 'c': case 'C': {
                // byte array len, 1 byte
                cram_byte_array_len_encoder e;
                cram_stats st;

                if (CRAM_MAJOR_VERS(fd->version) <= 3) {
                    e.len_encoding = E_HUFFMAN;
                    e.len_dat = NULL; // will get codes from st
                } else {
                    e.len_encoding = E_CONST_INT;
                    e.len_dat = NULL; // will get codes from st
                }
                memset(&st, 0, sizeof(st));
                if (cram_stats_add(&st, 1) < 0) goto block_err;
                cram_stats_encoding(fd, &st);

                e.val_encoding = E_EXTERNAL;
                e.val_dat = (void *)sk;

                c = cram_encoder_init(E_BYTE_ARRAY_LEN, &st,
                                      E_BYTE_ARRAY, (void *)&e,
                                      fd->version, &fd->vv);
                break;
            }

            case 's': case 'S': {
                // byte array len, 2 byte
                cram_byte_array_len_encoder e;
                cram_stats st;

                if (CRAM_MAJOR_VERS(fd->version) <= 3) {
                    e.len_encoding = E_HUFFMAN;
                    e.len_dat = NULL; // will get codes from st
                } else {
                    e.len_encoding = E_CONST_INT;
                    e.len_dat = NULL; // will get codes from st
                }
                memset(&st, 0, sizeof(st));
                if (cram_stats_add(&st, 2) < 0) goto block_err;
                cram_stats_encoding(fd, &st);

                e.val_encoding = E_EXTERNAL;
                e.val_dat = (void *)sk;

                c = cram_encoder_init(E_BYTE_ARRAY_LEN, &st,
                                      E_BYTE_ARRAY, (void *)&e,
                                      fd->version, &fd->vv);
                break;
            }
            case 'i': case 'I': case 'f': {
                // byte array len, 4 byte
                cram_byte_array_len_encoder e;
                cram_stats st;

                if (CRAM_MAJOR_VERS(fd->version) <= 3) {
                    e.len_encoding = E_HUFFMAN;
                    e.len_dat = NULL; // will get codes from st
                } else {
                    e.len_encoding = E_CONST_INT;
                    e.len_dat = NULL; // will get codes from st
                }
                memset(&st, 0, sizeof(st));
                if (cram_stats_add(&st, 4) < 0) goto block_err;
                cram_stats_encoding(fd, &st);

                e.val_encoding = E_EXTERNAL;
                e.val_dat = (void *)sk;

                c = cram_encoder_init(E_BYTE_ARRAY_LEN, &st,
                                      E_BYTE_ARRAY, (void *)&e,
                                      fd->version, &fd->vv);
                break;
            }

            case 'B': {
                // Byte array of variable size, but we generate our tag
                // byte stream at the wrong stage (during reading and not
                // after slice header construction). So we use
                // BYTE_ARRAY_LEN with the length codec being external
                // too.
                cram_byte_array_len_encoder e;

                e.len_encoding = CRAM_MAJOR_VERS(fd->version) >= 4
                    ? E_VARINT_UNSIGNED
                    : E_EXTERNAL;
                e.len_dat = (void *)sk; // or key+128 for len?

                e.val_encoding = E_EXTERNAL;
                e.val_dat = (void *)sk;

                c = cram_encoder_init(E_BYTE_ARRAY_LEN, NULL,
                                      E_BYTE_ARRAY, (void *)&e,
                                      fd->version, &fd->vv);
                break;
            }

            default:
                hts_log_error("Unsupported SAM aux type '%c'", aux[2]);
                c = NULL;
            }

            if (!c)
                goto_err;

            m->codec = c;

            // Link to fd-global tag metrics
            pthread_mutex_lock(&fd->metrics_lock);
            m->m = k_global ? (cram_metrics *)kh_val(fd->tags_used, k_global) : NULL;
            pthread_mutex_unlock(&fd->metrics_lock);
        }

        cram_tag_map *tm = (cram_tag_map *)kh_val(c->tags_used, k);
        if (!tm) goto_err;
        cram_codec *codec = tm->codec;
        if (!tm->codec) goto_err;

        switch(aux[2]) {
        case 'A': case 'C': case 'c':
            if (aux_end - aux < 3+1)
                goto err;

            if (!tm->blk) {
                if (!(tm->blk = cram_new_block(EXTERNAL, key)))
                    goto err;
                codec->u.e_byte_array_len.val_codec->out = tm->blk;
            }

            aux+=3;
            //codec->encode(s, codec, aux, 1);
            // Functionally equivalent, but less code.
            BLOCK_APPEND_CHAR(tm->blk, *aux);
            aux++;
            break;

        case 'S': case 's':
            if (aux_end - aux < 3+2)
                goto err;

            if (!tm->blk) {
                if (!(tm->blk = cram_new_block(EXTERNAL, key)))
                    goto err;
                codec->u.e_byte_array_len.val_codec->out = tm->blk;
            }

            aux+=3;
            //codec->encode(s, codec, aux, 2);
            BLOCK_APPEND(tm->blk, aux, 2);
            aux+=2;
            break;

        case 'I': case 'i': case 'f':
            if (aux_end - aux < 3+4)
                goto err;

            if (!tm->blk) {
                if (!(tm->blk = cram_new_block(EXTERNAL, key)))
                    goto err;
                codec->u.e_byte_array_len.val_codec->out = tm->blk;
            }

            aux+=3;
            //codec->encode(s, codec, aux, 4);
            BLOCK_APPEND(tm->blk, aux, 4);
            aux+=4;
            break;

        case 'd':
            if (aux_end - aux < 3+8)
                goto err;

            if (!tm->blk) {
                if (!(tm->blk = cram_new_block(EXTERNAL, key)))
                    goto err;
                codec->u.e_byte_array_len.val_codec->out = tm->blk;
            }

            aux+=3; //*tmp++=*aux++; *tmp++=*aux++; *tmp++=*aux++;
            //codec->encode(s, codec, aux, 8);
            BLOCK_APPEND(tm->blk, aux, 8);
            aux+=8;
            break;

        case 'Z': case 'H': {
            if (aux_end - aux < 3)
                goto err;

            if (!tm->blk) {
                if (!(tm->blk = cram_new_block(EXTERNAL, key)))
                    goto err;
                codec->out = tm->blk;
            }

            char *aux_s;
            aux += 3;
            aux_s = aux;
            while (aux < aux_end && *aux++);
            if (aux == aux_end && aux[-1] != '\0') {
                hts_log_error("Unterminated %c%c:%c tag for read \"%s\"",
                              aux_s[-3], aux_s[-2], aux_s[-1],
                              bam_get_qname(b));
                goto err;
            }
            if (codec->encode(s, codec, aux_s, aux - aux_s) < 0)
                goto err;
            break;
        }

        case 'B': {
            if (aux_end - aux < 4+4)
                goto err;

            int type = aux[3];
            uint64_t count = (((uint64_t)((unsigned char *)aux)[4]) << 0 |
                              ((uint64_t)((unsigned char *)aux)[5]) << 8 |
                              ((uint64_t)((unsigned char *)aux)[6]) <<16 |
                              ((uint64_t)((unsigned char *)aux)[7]) <<24);
            uint64_t blen;
            if (!tm->blk) {
                if (!(tm->blk = cram_new_block(EXTERNAL, key)))
                    goto err;
                if (codec->u.e_byte_array_len.val_codec->codec == E_XDELTA) {
                    if (!(tm->blk2 = cram_new_block(EXTERNAL, key+128)))
                        goto err;
                    codec->u.e_byte_array_len.len_codec->out = tm->blk2;
                    codec->u.e_byte_array_len.val_codec->u.e_xdelta.sub_codec->out = tm->blk;
                } else {
                    codec->u.e_byte_array_len.len_codec->out = tm->blk;
                    codec->u.e_byte_array_len.val_codec->out = tm->blk;
                }
            }

            // skip TN field
            aux+=3;

            // We use BYTE_ARRAY_LEN with external length, so store that first
            switch (type) {
            case 'c': case 'C':
                blen = count;
                break;
            case 's': case 'S':
                blen = 2*count;
                break;
            case 'i': case 'I': case 'f':
                blen = 4*count;
                break;
            default:
                hts_log_error("Unknown sub-type '%c' for aux type 'B'", type);
                goto err;
            }

            blen += 5; // sub-type & length
            if (aux_end - aux < blen || blen > INT_MAX)
                goto err;

            if (codec->encode(s, codec, aux, (int) blen) < 0)
                goto err;
            aux += blen;
            break;
        }
        default:
            hts_log_error("Unknown aux type '%c'", aux_end - aux < 2 ? '?' : aux[2]);
            goto err;
        }
        tm->blk->m = tm->m;
    }

    // FIXME: sort BLOCK_DATA(td_b) by char[3] triples

    // And and increment TD hash entry
    BLOCK_APPEND_CHAR(td_b, 0);

    // Duplicate key as BLOCK_DATA() can be realloced to a new pointer.
    key = string_ndup(c->comp_hdr->TD_keys,
                      (char *)BLOCK_DATA(td_b) + TD_blk_size,
                      BLOCK_SIZE(td_b) - TD_blk_size);
    if (!key)
        goto block_err;
    k = kh_put(m_s2i, c->comp_hdr->TD_hash, key, &new);
    if (new < 0) {
        goto err;
    } else if (new == 0) {
        BLOCK_SIZE(td_b) = TD_blk_size;
    } else {
        kh_val(c->comp_hdr->TD_hash, k) = c->comp_hdr->nTL;
        c->comp_hdr->nTL++;
    }

    cr->TL = kh_val(c->comp_hdr->TD_hash, k);
    if (cram_stats_add(c->stats[DS_TL], cr->TL) < 0)
        goto block_err;

    if (orig != (char *)bam_aux(b))
        free(orig);

    if (err) *err = 0;

    return brg;

 err:
 block_err:
    if (orig != (char *)bam_aux(b))
        free(orig);
    return NULL;
}

/*
 * During cram_next_container or before the final flush at end of
 * file, we update the current slice headers and increment the slice
 * number to the next slice.
 *
 * See cram_next_container() and cram_close().
 */
void cram_update_curr_slice(cram_container *c, int version) {
    cram_slice *s = c->slice;
    if (c->multi_seq) {
        s->hdr->ref_seq_id    = -2;
        s->hdr->ref_seq_start = 0;
        s->hdr->ref_seq_span  = 0;
    } else if (c->curr_ref == -1 && CRAM_ge31(version)) {
        // Spec states span=0, but it broke our range queries.
        // See commit message for this and prior.
        s->hdr->ref_seq_id    = -1;
        s->hdr->ref_seq_start = 0;
        s->hdr->ref_seq_span  = 0;
    } else {
        s->hdr->ref_seq_id    = c->curr_ref;
        s->hdr->ref_seq_start = c->first_base;
        s->hdr->ref_seq_span  = MAX(0, c->last_base - c->first_base + 1);
    }
    s->hdr->num_records   = c->curr_rec;

    if (c->curr_slice == 0) {
        if (c->ref_seq_id != s->hdr->ref_seq_id)
            c->ref_seq_id  = s->hdr->ref_seq_id;
        c->ref_seq_start = c->first_base;
    }

    c->curr_slice++;
}

/*
 * Handles creation of a new container or new slice, flushing any
 * existing containers when appropriate.
 *
 * Really this is next slice, which may or may not lead to a new container.
 *
 * Returns cram_container pointer on success
 *         NULL on failure.
 */
static cram_container *cram_next_container(cram_fd *fd, bam_seq_t *b) {
    cram_container *c = fd->ctr;
    int i;

    /* First occurrence */
    if (c->curr_ref == -2)
        c->curr_ref = bam_ref(b);

    if (c->slice)
        cram_update_curr_slice(c, fd->version);

    /* Flush container */
    if (c->curr_slice == c->max_slice ||
        (bam_ref(b) != c->curr_ref && !c->multi_seq)) {
        c->ref_seq_span = fd->last_base - c->ref_seq_start + 1;
        hts_log_info("Flush container %d/%"PRId64"..%"PRId64,
                     c->ref_seq_id, c->ref_seq_start,
                     c->ref_seq_start + c->ref_seq_span -1);

        /* Encode slices */
        if (-1 == cram_flush_container_mt(fd, c))
            return NULL;
        if (!fd->pool) {
            // Move to sep func, as we need cram_flush_container for
            // the closing phase to flush the partial 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;

            /* Easy approach for purposes of freeing stats */
            cram_free_container(c);
        }

        c = fd->ctr = cram_new_container(fd->seqs_per_slice,
                                         fd->slices_per_container);
        if (!c)
            return NULL;

        pthread_mutex_lock(&fd->ref_lock);
        c->no_ref = fd->no_ref;
        c->embed_ref = fd->embed_ref;
        c->record_counter = fd->record_counter;
        pthread_mutex_unlock(&fd->ref_lock);
        c->curr_ref = bam_ref(b);
    }

    c->last_pos = c->first_base = c->last_base = bam_pos(b)+1;

    /* New slice */
    c->slice = c->slices[c->curr_slice] =
        cram_new_slice(MAPPED_SLICE, c->max_rec);
    if (!c->slice)
        return NULL;

    if (c->multi_seq) {
        c->slice->hdr->ref_seq_id = -2;
        c->slice->hdr->ref_seq_start = 0;
        c->slice->last_apos = 1;
    } else {
        c->slice->hdr->ref_seq_id = bam_ref(b);
        // wrong for unsorted data, will fix during encoding.
        c->slice->hdr->ref_seq_start = bam_pos(b)+1;
        c->slice->last_apos = bam_pos(b)+1;
    }

    c->curr_rec = 0;
    c->s_num_bases = 0;
    c->n_mapped = 0;

    // QO field: 0 implies original orientation, 1 implies sequence orientation
    // 1 is often preferable for NovaSeq, but impact is slight. ~0.5% diff.
    // Conversely other data sets it's often better than 1% saving for 0.
    // Short of trying both and learning, for now we use use 0 for V4, 1 for V3.
    c->qs_seq_orient = CRAM_MAJOR_VERS(fd->version) >= 4 ? 0 : 1;

    return c;
}


/*
 * Converts a single bam record into a cram record.
 * Possibly used within a thread.
 *
 * Returns 0 on success;
 *        -1 on failure
 */
static int process_one_read(cram_fd *fd, cram_container *c,
                            cram_slice *s, cram_record *cr,
                            bam_seq_t *b, int rnum, kstring_t *MD,
                            int embed_ref, int no_ref) {
    int i, fake_qual = -1, NM = 0;
    char *cp;
    char *ref, *seq, *qual;

    // Any places with N in seq and/or reference can lead to ambiguous
    // interpretation of the SAM NM:i tag.  So we store these verbatim
    // to ensure valid data round-trips the same regardless of who
    // defines it as valid.
    // Similarly when alignments go beyond end of the reference.
    int verbatim_NM = fd->store_nm;
    int verbatim_MD = fd->store_md;

    // FIXME: multi-ref containers

    cr->flags       = bam_flag(b);
    cr->len         = bam_seq_len(b);
    uint8_t *md;
    if (!(md = bam_aux_get(b, "MD")))
        MD = NULL;
    else
        MD->l = 0;

    int cf_tag = 0;

    if (embed_ref == 2) {
        cf_tag  = MD ? 0 : 1;                   // No MD
        cf_tag |= bam_aux_get(b, "NM") ? 0 : 2; // No NM
    }

    //fprintf(stderr, "%s => %d\n", rg ? rg : "\"\"", cr->rg);

    ref = c->ref ? c->ref - (c->ref_start-1) : NULL;
    cr->ref_id      = bam_ref(b);
    if (cram_stats_add(c->stats[DS_RI], cr->ref_id) < 0)
        goto block_err;
    if (cram_stats_add(c->stats[DS_BF], fd->cram_flag_swap[cr->flags & 0xfff]) < 0)
        goto block_err;

    // Non reference based encoding means storing the bases verbatim as features, which in
    // turn means every base also has a quality already stored.
    if (!no_ref || CRAM_MAJOR_VERS(fd->version) >= 3)
        cr->cram_flags |= CRAM_FLAG_PRESERVE_QUAL_SCORES;

    if (cr->len <= 0 && CRAM_MAJOR_VERS(fd->version) >= 3)
        cr->cram_flags |= CRAM_FLAG_NO_SEQ;
    //cram_stats_add(c->stats[DS_CF], cr->cram_flags & CRAM_FLAG_MASK);

    c->num_bases   += cr->len;
    cr->apos        = bam_pos(b)+1;
    if (cr->apos < 0 || cr->apos > INT64_MAX/2)
        goto err;
    if (c->pos_sorted) {
        if (cr->apos < s->last_apos && !fd->ap_delta) {
            c->pos_sorted = 0;
        } else {
            if (cram_stats_add(c->stats[DS_AP], cr->apos - s->last_apos) < 0)
                goto block_err;
            s->last_apos = cr->apos;
        }
    } else {
        //cram_stats_add(c->stats[DS_AP], cr->apos);
    }
    c->max_apos += (cr->apos > c->max_apos) * (cr->apos - c->max_apos);

    /*
     * This seqs_ds is largely pointless and it could reuse the same memory
     * over and over.
     * s->base_blk is what we need for encoding.
     */
    cr->seq         = BLOCK_SIZE(s->seqs_blk);
    cr->qual        = BLOCK_SIZE(s->qual_blk);
    BLOCK_GROW(s->seqs_blk, cr->len+1);
    BLOCK_GROW(s->qual_blk, cr->len);

    // Convert BAM nibble encoded sequence to string of base pairs
    seq = cp = (char *)BLOCK_END(s->seqs_blk);
    *seq = 0;
    nibble2base(bam_seq(b), cp, cr->len);
    BLOCK_SIZE(s->seqs_blk) += cr->len;

    qual = cp = (char *)bam_qual(b);


    /* Copy and parse */
    if (!(cr->flags & BAM_FUNMAP)) {
        uint32_t *cig_to, *cig_from;
        int64_t apos = cr->apos-1, spos = 0;
        int64_t MD_last = apos; // last position of edit in MD tag

        if (apos < 0) {
            hts_log_error("Mapped read with position <= 0 is disallowed");
            return -1;
        }

        cr->cigar       = s->ncigar;
        cr->ncigar      = bam_cigar_len(b);
        while (cr->cigar + cr->ncigar >= s->cigar_alloc) {
            s->cigar_alloc = s->cigar_alloc ? s->cigar_alloc*2 : 1024;
            s->cigar = realloc(s->cigar, s->cigar_alloc * sizeof(*s->cigar));
            if (!s->cigar)
                return -1;
        }

        cig_to = (uint32_t *)s->cigar;
        cig_from = (uint32_t *)bam_cigar(b);

        cr->feature = 0;
        cr->nfeature = 0;
        for (i = 0; i < cr->ncigar; i++) {
            enum cigar_op cig_op = cig_from[i] & BAM_CIGAR_MASK;
            uint32_t cig_len = cig_from[i] >> BAM_CIGAR_SHIFT;
            cig_to[i] = cig_from[i];

            /* Can also generate events from here for CRAM diffs */

            switch (cig_op) {
                int l;

                // Don't trust = and X ops to be correct.
            case BAM_CMATCH:
            case BAM_CBASE_MATCH:
            case BAM_CBASE_MISMATCH:
                //fprintf(stderr, "\nBAM_CMATCH\nR: %.*s\nS: %.*s\n",
                //      cig_len, &ref[apos], cig_len, &seq[spos]);
                l = 0;
                if (!no_ref && cr->len) {
                    int end = cig_len+apos < c->ref_end
                        ? cig_len : c->ref_end - apos;
                    char *sp = &seq[spos];
                    char *rp = &ref[apos];
                    char *qp = &qual[spos];
                    if (end > cr->len) {
                        hts_log_error("CIGAR and query sequence are of different length");
                        return -1;
                    }
                    for (l = 0; l < end; l++) {
                        // This case is just too disputed and different tools
                        // interpret these in different ways.  We give up and
                        // store verbatim.
                        if (rp[l] == 'N' && sp[l] == 'N')
                            verbatim_NM = verbatim_MD = 1;
                        if (rp[l] != sp[l]) {
                            // Build our own MD tag if one is on the sequence, so
                            // we can ensure it matches and thus can be discarded.
                            if (MD && ref) {
                                if (kputuw(apos+l - MD_last, MD) < 0) goto err;
                                if (kputc(rp[l], MD) < 0) goto err;
                                MD_last = apos+l+1;
                            }
                            NM++;
                            if (!sp[l])
                                break;
                            if (0 && CRAM_MAJOR_VERS(fd->version) >= 3) {
#if 0
                                // Disabled for the time being as it doesn't
                                // seem to gain us much.
                                int ol=l;
                                while (l<end && rp[l] != sp[l])
                                    l++;
                                if (l-ol > 1) {
                                    if (cram_add_bases(fd, c, s, cr, spos+ol,
                                                       l-ol, &seq[spos+ol]))
                                        return -1;
                                    l--;
                                } else {
                                    l = ol;
                                    if (cram_add_substitution(fd, c, s, cr,
                                                              spos+l, sp[l],
                                                              qp[l], rp[l]))
                                        return -1;
                                }
#else
                                // With urmap pushed to the limit and lots
                                // of unaligned data (should be soft-clipped)
                                // this saves ~2-7%. Worth it?
                                int nl = l;
                                int max_end = nl, max_score = 0, score = 0;
                                while (nl < end) {
                                    if (rp[nl] != sp[nl]) {
                                        score += 3;
                                        if (max_score < score) {
                                            max_score = score;
                                            max_end = nl;
                                        }
                                    } else {
                                        score--;
                                        if (score < -2 ||
                                            max_score - score > 7)
                                            break;
                                    }
                                    nl++;
                                }
                                if (max_score > 20) {
                                    cram_add_bases(fd, c, s, cr, spos+l,
                                                   max_end-l, &seq[spos+l]);
                                    l = max_end-1;
                                } else {
                                    while (l < nl) {
                                        if (rp[l] != sp[l])
                                            cram_add_substitution(fd, c, s,
                                                                  cr, spos+l,
                                                                  sp[l], qp[l],
                                                                  rp[l]);
                                        l++;
                                    }
                                    l--;
                                }
#endif
                            } else {
                                if (cram_add_substitution(fd, c, s, cr, spos+l,
                                                          sp[l], qp[l], rp[l]))
                                    return -1;
                            }
                        }
                    }
                    spos += l;
                    apos += l;
                }

                if (l < cig_len && cr->len) {
                    if (no_ref) {
                        if (CRAM_MAJOR_VERS(fd->version) == 3) {
                            if (cram_add_bases(fd, c, s, cr, spos,
                                               cig_len-l, &seq[spos]))
                                return -1;
                            spos += cig_len-l;
                        } else {
                            for (; l < cig_len && seq[spos]; l++, spos++) {
                                if (cram_add_base(fd, c, s, cr, spos,
                                                  seq[spos], qual[spos]))
                                    return -1;
                            }
                        }
                    } else {
                        /* off end of sequence or non-ref based output */
                        verbatim_NM = verbatim_MD = 1;
                        for (; l < cig_len && seq[spos]; l++, spos++) {
                            if (cram_add_base(fd, c, s, cr, spos,
                                              seq[spos], qual[spos]))
                                return -1;
                        }
                    }
                    apos += cig_len;
                } else if (!cr->len) {
                    /* Seq "*" */
                    verbatim_NM = verbatim_MD = 1;
                    apos += cig_len;
                    spos += cig_len;
                }
                break;

            case BAM_CDEL:
                if (MD && ref) {
                    if (kputuw(apos - MD_last, MD) < 0) goto err;
                    if (apos < c->ref_end) {
                        if (kputc_('^', MD) < 0) goto err;
                        if (kputsn(&ref[apos], MIN(c->ref_end - apos, cig_len), MD) < 0)
                            goto err;
                    }
                }
                NM += cig_len;

                if (cram_add_deletion(c, s, cr, spos, cig_len, &seq[spos]))
                    return -1;
                apos += cig_len;
                MD_last = apos;
                break;

            case BAM_CREF_SKIP:
                if (cram_add_skip(c, s, cr, spos, cig_len, &seq[spos]))
                    return -1;
                apos += cig_len;
                MD_last += cig_len;
                break;

            case BAM_CINS:
                if (cram_add_insertion(c, s, cr, spos, cig_len,
                                       cr->len ? &seq[spos] : NULL))
                    return -1;
                if (no_ref && cr->len) {
                    for (l = 0; l < cig_len; l++, spos++) {
                        cram_add_quality(fd, c, s, cr, spos, qual[spos]);
                    }
                } else {
                    spos += cig_len;
                }
                NM += cig_len;
                break;

            case BAM_CSOFT_CLIP:
                if (cram_add_softclip(c, s, cr, spos, cig_len,
                                      cr->len ? &seq[spos] : NULL,
                                      fd->version))
                    return -1;

                if (no_ref &&
                    !(cr->cram_flags & CRAM_FLAG_PRESERVE_QUAL_SCORES)) {
                    if (cr->len) {
                        for (l = 0; l < cig_len; l++, spos++) {
                            cram_add_quality(fd, c, s, cr, spos, qual[spos]);
                        }
                    } else {
                        for (l = 0; l < cig_len; l++, spos++) {
                            cram_add_quality(fd, c, s, cr, spos, -1);
                        }
                    }
                } else {
                    spos += cig_len;
                }
                break;

            case BAM_CHARD_CLIP:
                if (cram_add_hardclip(c, s, cr, spos, cig_len, &seq[spos]))
                    return -1;
                break;

            case BAM_CPAD:
                if (cram_add_pad(c, s, cr, spos, cig_len, &seq[spos]))
                    return -1;
                break;

            default:
                hts_log_error("Unknown CIGAR op code %d", cig_op);
                return -1;
            }
        }
        if (cr->len && spos != cr->len) {
            hts_log_error("CIGAR and query sequence are of different length");
            return -1;
        }
        fake_qual = spos;
        // Protect against negative length refs (fuzz 382922241)
        cr->aend = no_ref ? apos : MIN(apos, MAX(0, c->ref_end));
        if (cram_stats_add(c->stats[DS_FN], cr->nfeature) < 0)
            goto block_err;

        if (MD && ref)
            if (kputuw(apos - MD_last, MD) < 0) goto err;
    } else {
        // Unmapped
        cr->cram_flags |= CRAM_FLAG_PRESERVE_QUAL_SCORES;
        cr->cigar  = 0;
        cr->ncigar = 0;
        cr->nfeature = 0;
        cr->aend = MIN(cr->apos, c->ref_end);
        for (i = 0; i < cr->len; i++)
            if (cram_stats_add(c->stats[DS_BA], seq[i]) < 0)
                goto block_err;
        fake_qual = 0;
    }

    cr->ntags      = 0; //cram_stats_add(c->stats[DS_TC], cr->ntags);
    int err = 0;
    sam_hrec_rg_t *brg =
        cram_encode_aux(fd, b, c, s, cr, verbatim_NM, verbatim_MD, NM, MD,
                        cf_tag, no_ref, &err);
    if (err)
        goto block_err;

    /* Read group, identified earlier */
    if (brg) {
        cr->rg = brg->id;
    } else if (CRAM_MAJOR_VERS(fd->version) == 1) {
        sam_hrec_rg_t *brg = sam_hrecs_find_rg(fd->header->hrecs, "UNKNOWN");
        if (!brg) goto block_err;
        cr->rg = brg->id;
    } else {
        cr->rg = -1;
    }
    if (cram_stats_add(c->stats[DS_RG], cr->rg) < 0)
        goto block_err;

    /*
     * Append to the qual block now. We do this here as
     * cram_add_substitution() can generate BA/QS events which need to
     * be in the qual block before we append the rest of the data.
     */
    if (cr->cram_flags & CRAM_FLAG_PRESERVE_QUAL_SCORES) {
        /* Special case of seq "*" */
        if (cr->len == 0) {
            cr->len = fake_qual;
            BLOCK_GROW(s->qual_blk, cr->len);
            cp = (char *)BLOCK_END(s->qual_blk);
            memset(cp, 255, cr->len);
        } else {
            BLOCK_GROW(s->qual_blk, cr->len);
            cp = (char *)BLOCK_END(s->qual_blk);
            char *from = (char *)&bam_qual(b)[0];
            char *to = &cp[0];
            memcpy(to, from, cr->len);

            // Store quality in original orientation for better compression.
            if (!c->qs_seq_orient) {
                if (cr->flags & BAM_FREVERSE) {
                    int i, j;
                    for (i = 0, j = cr->len-1; i < j; i++, j--) {
                        unsigned char c;
                        c = to[i];
                        to[i] = to[j];
                        to[j] = c;
                    }
                }
            }
        }
        BLOCK_SIZE(s->qual_blk) += cr->len;
    } else {
        if (cr->len == 0)
            cr->len = fake_qual >= 0 ? fake_qual : cr->aend - cr->apos + 1;
    }

    if (cram_stats_add(c->stats[DS_RL], cr->len) < 0)
        goto block_err;

    /* Now we know apos and aend both, update mate-pair information */
    {
        int new;
        khint_t k;
        int sec = (cr->flags & BAM_FSECONDARY) ? 1 : 0;

        //fprintf(stderr, "Checking %"PRId64"/%.*s\t", rnum,
        //      cr->name_len, DSTRING_STR(s->name_ds)+cr->name);
        if (cr->flags & BAM_FPAIRED) {
            char *key = string_ndup(s->pair_keys, bam_name(b), bam_name_len(b));
            if (!key)
                return -1;

            k = kh_put(m_s2i, s->pair[sec], key, &new);
            if (-1 == new)
                return -1;
            else if (new > 0)
                kh_val(s->pair[sec], k) = rnum
                    | ((unsigned)((cr->flags & BAM_FREAD1)!=0)<<30)
                    | ((unsigned)((cr->flags & BAM_FREAD2)!=0)<<31);
        } else {
            new = 1;
            k = 0; // Prevents false-positive warning from gcc -Og
        }

        if (new == 0) {
            cram_record *p = &s->crecs[kh_val(s->pair[sec], k) & ((1<<30)-1)];
            int64_t aleft, aright;
            int sign;

            aleft = MIN(cr->apos, p->apos);
            aright = MAX(cr->aend, p->aend);
            if (cr->apos < p->apos) {
                sign = 1;
            } else if (cr->apos > p->apos) {
                sign = -1;
            } else if (cr->flags & BAM_FREAD1) {
                sign = 1;
            } else {
                sign = -1;
            }

            // Multiple sets of secondary reads means we cannot tell which is
            // which, so we store TLEN etc verbatim.
            int has_r1 = kh_val(s->pair[sec], k) & (1<<30);
            unsigned int has_r2 = kh_val(s->pair[sec], k) & (1u<<31);
            if ((has_r1 && (cr->flags & BAM_FREAD1)) ||
                (has_r2 && (cr->flags & BAM_FREAD2)))
                goto detached;

            // This vs p: tlen, matepos, flags. Permit TLEN 0 and/or TLEN +/-
            // a small amount, if appropriate options set.
            if ((!fd->tlen_zero && MAX(bam_mate_pos(b)+1, 0) != p->apos) &&
                !(fd->tlen_zero && bam_mate_pos(b) == 0))
                goto detached;

            if (((bam_flag(b) & BAM_FMUNMAP) != 0) !=
                ((p->flags & BAM_FUNMAP) != 0))
                goto detached;

            if (((bam_flag(b) & BAM_FMREVERSE) != 0) !=
                ((p->flags & BAM_FREVERSE) != 0))
                goto detached;


            // p vs this: tlen, matepos, flags
            if (p->ref_id != cr->ref_id &&
                !(fd->tlen_zero && p->ref_id == -1))
                goto detached;

            if (p->mate_pos != cr->apos &&
                !(fd->tlen_zero && p->mate_pos == 0))
                goto detached;

            if (((p->flags & BAM_FMUNMAP) != 0) !=
                ((p->mate_flags & CRAM_M_UNMAP) != 0))
                goto detached;

            if (((p->flags & BAM_FMREVERSE) != 0) !=
                ((p->mate_flags & CRAM_M_REVERSE) != 0))
                goto detached;

            // Supplementary reads are just too ill defined
            if ((cr->flags & BAM_FSUPPLEMENTARY) ||
                (p->flags & BAM_FSUPPLEMENTARY))
                goto detached;

            // When in lossy name mode, if a read isn't detached we
            // cannot store the name.  The corollary is that when we
            // must store the name, it must be detached (inefficient).
            if (fd->lossy_read_names &&
                (!(cr->cram_flags & CRAM_FLAG_DISCARD_NAME) ||
                 !((p->cram_flags & CRAM_FLAG_DISCARD_NAME))))
                goto detached;

            // Now check TLEN.  We do this last as sometimes it's the
            // only thing that differs.  In CRAM4 we have a better way
            // of handling this that doesn't break detached status
            int explicit_tlen = 0;
            int tflag1 = ((bam_ins_size(b) &&
                           llabs(bam_ins_size(b) - sign*(aright-aleft+1))
                           > fd->tlen_approx)
                          || (!bam_ins_size(b) && !fd->tlen_zero));

            int tflag2 = ((p->tlen && llabs(p->tlen - -sign*(aright-aleft+1))
                           > fd->tlen_approx)
                          || (!p->tlen && !fd->tlen_zero));

            if (tflag1 || tflag2) {
                if (CRAM_MAJOR_VERS(fd->version) >= 4) {
                    explicit_tlen = CRAM_FLAG_EXPLICIT_TLEN;
                } else {
                    // Stil do detached for unmapped data in CRAM4 as this
                    // also impacts RNEXT calculation.
                    goto detached;
                }
            }

            /*
             * The fields below are unused when encoding this read as it is
             * no longer detached.  In theory they may get referred to when
             * processing a 3rd or 4th read in this template?, so we set them
             * here just to be sure.
             *
             * They do not need cram_stats_add() calls those as they are
             * not emitted.
             */
            cr->mate_pos = p->apos;
            cram_stats_add(c->stats[DS_NP], cr->mate_pos);
            cr->tlen = explicit_tlen ? bam_ins_size(b) : sign*(aright-aleft+1);
            cram_stats_add(c->stats[DS_TS], cr->tlen);
            cr->mate_flags =
                ((p->flags & BAM_FMUNMAP)   == BAM_FMUNMAP)   * CRAM_M_UNMAP +
                ((p->flags & BAM_FMREVERSE) == BAM_FMREVERSE) * CRAM_M_REVERSE;

            // Decrement statistics aggregated earlier
            if (p->cram_flags & CRAM_FLAG_STATS_ADDED) {
                cram_stats_del(c->stats[DS_NP], p->mate_pos);
                cram_stats_del(c->stats[DS_MF], p->mate_flags);
                if (!(p->cram_flags & CRAM_FLAG_EXPLICIT_TLEN))
                    cram_stats_del(c->stats[DS_TS], p->tlen);
                cram_stats_del(c->stats[DS_NS], p->mate_ref_id);
            }

            /* Similarly we could correct the p-> values too, but these will no
             * longer have any code that refers back to them as the new 'p'
             * for this template is our current 'cr'.
             */
            //p->mate_pos = cr->apos;
            //p->mate_flags =
            //  ((cr->flags & BAM_FMUNMAP)   == BAM_FMUNMAP)  * CRAM_M_UNMAP +
            //  ((cr->flags & BAM_FMREVERSE) == BAM_FMREVERSE)* CRAM_M_REVERSE;
            //p->tlen = p->apos - cr->aend;

            // Clear detached from cr flags
            cr->cram_flags &= ~CRAM_FLAG_DETACHED;
            cr->cram_flags |= explicit_tlen;
            if (cram_stats_add(c->stats[DS_CF], cr->cram_flags & CRAM_FLAG_MASK) < 0)
                goto block_err;

            // Clear detached from p flags and set downstream
            if (p->cram_flags & CRAM_FLAG_STATS_ADDED) {
                cram_stats_del(c->stats[DS_CF], p->cram_flags & CRAM_FLAG_MASK);
                p->cram_flags &= ~CRAM_FLAG_STATS_ADDED;
            }

            p->cram_flags  &= ~CRAM_FLAG_DETACHED;
            p->cram_flags  |=  CRAM_FLAG_MATE_DOWNSTREAM | explicit_tlen;;
            if (cram_stats_add(c->stats[DS_CF], p->cram_flags & CRAM_FLAG_MASK) < 0)
                goto block_err;

            p->mate_line = rnum - ((kh_val(s->pair[sec], k) & ((1<<30)-1)) + 1);
            if (cram_stats_add(c->stats[DS_NF], p->mate_line) < 0)
                goto block_err;

            int r12_flags = kh_val(s->pair[sec], k) & (3u<<30);
            kh_val(s->pair[sec], k) = (unsigned int)rnum | r12_flags
                | (((cr->flags & BAM_FREAD1)!=0)<<30)
                | ((unsigned)((cr->flags & BAM_FREAD2)!=0)<<31);
        } else {
        detached:
            //fprintf(stderr, "unpaired\n");

            /* Derive mate flags from this flag */
            cr->mate_flags = 0;
            if (bam_flag(b) & BAM_FMUNMAP)
                cr->mate_flags |= CRAM_M_UNMAP;
            if (bam_flag(b) & BAM_FMREVERSE)
                cr->mate_flags |= CRAM_M_REVERSE;

            if (cram_stats_add(c->stats[DS_MF], cr->mate_flags) < 0)
                goto block_err;

            cr->mate_pos    = MAX(bam_mate_pos(b)+1, 0);
            if (cram_stats_add(c->stats[DS_NP], cr->mate_pos) < 0)
                goto block_err;

            cr->tlen        = bam_ins_size(b);
            if (cram_stats_add(c->stats[DS_TS], cr->tlen) < 0)
                goto block_err;

            cr->cram_flags |= CRAM_FLAG_DETACHED;
            if (cram_stats_add(c->stats[DS_CF], cr->cram_flags & CRAM_FLAG_MASK) < 0)
                goto block_err;
            if (cram_stats_add(c->stats[DS_NS], bam_mate_ref(b)) < 0)
                goto block_err;

            cr->cram_flags |= CRAM_FLAG_STATS_ADDED;
        }
    }

    cr->mqual       = bam_map_qual(b);
    if (cram_stats_add(c->stats[DS_MQ], cr->mqual) < 0)
        goto block_err;

    cr->mate_ref_id = bam_mate_ref(b);

    if (!(bam_flag(b) & BAM_FUNMAP)) {
        if (c->first_base > cr->apos)
            c->first_base = cr->apos;

        if (c->last_base < cr->aend)
            c->last_base = cr->aend;
    }

    return 0;

 block_err:
 err:
    return -1;
}

/*
 * Write iterator: put BAM format sequences into a CRAM file.
 * We buffer up a containers worth of data at a time.
 *
 * Returns 0 on success
 *        -1 on failure
 */
int cram_put_bam_seq(cram_fd *fd, bam_seq_t *b) {
    cram_container *c;

    if (!fd->ctr) {
        fd->ctr = cram_new_container(fd->seqs_per_slice,
                                     fd->slices_per_container);
        if (!fd->ctr)
            return -1;
        fd->ctr->record_counter = fd->record_counter;

        pthread_mutex_lock(&fd->ref_lock);
        fd->ctr->no_ref = fd->no_ref;
        fd->ctr->embed_ref = fd->embed_ref;
        pthread_mutex_unlock(&fd->ref_lock);
    }
    c = fd->ctr;

    int embed_ref = c->embed_ref;

    if (!c->slice || c->curr_rec == c->max_rec ||
        (bam_ref(b) != c->curr_ref && c->curr_ref >= -1) ||
        (c->s_num_bases + c->s_aux_bytes >= fd->bases_per_slice)) {
        int slice_rec, curr_rec, multi_seq = fd->multi_seq == 1;
        int curr_ref = c->slice ? c->curr_ref : bam_ref(b);

        /*
         * Start packing slices when we routinely have under 1/4tr full.
         *
         * This option isn't available if we choose to embed references
         * since we can only have one per slice.
         *
         * The multi_seq var here refers to our intention for the next slice.
         * This slice has already been encoded so we output as-is.
         */
        if (fd->multi_seq == -1 && c->curr_rec < c->max_rec/4+10 &&
            fd->last_slice && fd->last_slice < c->max_rec/4+10 &&
            embed_ref<=0) {
            if (!c->multi_seq)
                hts_log_info("Multi-ref enabled for next container");
            multi_seq = 1;
        } else if (fd->multi_seq == 1) {
            pthread_mutex_lock(&fd->metrics_lock);
            if (fd->last_RI_count <= c->max_slice && fd->multi_seq_user != 1) {
                multi_seq = 0;
                hts_log_info("Multi-ref disabled for next container");
            }
            pthread_mutex_unlock(&fd->metrics_lock);
        }

        slice_rec = c->slice_rec;
        curr_rec  = c->curr_rec;

        if (CRAM_MAJOR_VERS(fd->version) == 1 ||
            c->curr_rec == c->max_rec || fd->multi_seq != 1 || !c->slice ||
            c->s_num_bases + c->s_aux_bytes >= fd->bases_per_slice) {
            if (NULL == (c = cram_next_container(fd, b))) {
                if (fd->ctr) {
                    // prevent cram_close attempting to flush
                    fd->ctr_mt = fd->ctr; // delay free when threading
                    fd->ctr = NULL;
                }
                return -1;
            }
        }

        /*
         * Due to our processing order, some things we've already done we
         * cannot easily undo. So when we first notice we should be packing
         * multiple sequences per container we emit the small partial
         * container as-is and then start a fresh one in a different mode.
         */
        if (multi_seq == 0 && fd->multi_seq == 1 && fd->multi_seq_user == -1) {
            // User selected auto-mode, we're currently using multi-seq, but
            // have detected we don't need to.  Switch back to auto.
            fd->multi_seq = -1;
        } else if (multi_seq) {
            // We detected we need multi-seq
            fd->multi_seq = 1;
            c->multi_seq = 1;
            c->pos_sorted = 0;

            // Cram_next_container may end up flushing an existing one and
            // triggering fd->embed_ref=2 if no reference is found.
            // Embedded refs are incompatible with multi-seq, so we bail
            // out and switch to no_ref in this scenario.  We do this
            // within the container only, as multi_seq may be temporary
            // and we switch back away from it again.
            pthread_mutex_lock(&fd->ref_lock);
            if (fd->embed_ref > 0 && c->curr_rec == 0 && c->curr_slice == 0) {
                hts_log_warning("Changing from embed_ref to no_ref mode");
                // Should we update fd->embed_ref and no_ref here too?
                // Doing so means if we go into multi-seq and back out
                // again, eg due a cluster of tiny refs in the middle of
                // much larger ones, then we bake in no-ref mode.
                //
                // However for unsorted data we're realistically not
                // going to switch back.
                c->embed_ref = fd->embed_ref = 0; // or -1 for auto?
                c->no_ref = fd->no_ref = 1;
            }
            pthread_mutex_unlock(&fd->ref_lock);

            if (!c->refs_used) {
                pthread_mutex_lock(&fd->ref_lock);
                c->refs_used = calloc(fd->refs->nref, sizeof(int));
                pthread_mutex_unlock(&fd->ref_lock);
                if (!c->refs_used)
                    return -1;
            }
        }

        fd->last_slice = curr_rec - slice_rec;
        c->slice_rec = c->curr_rec;

        // Have we seen this reference before?
        if (bam_ref(b) >= 0 && curr_ref >= 0 && bam_ref(b) != curr_ref &&
            embed_ref<=0 && !fd->unsorted && multi_seq) {

            if (!c->refs_used) {
                pthread_mutex_lock(&fd->ref_lock);
                c->refs_used = calloc(fd->refs->nref, sizeof(int));
                pthread_mutex_unlock(&fd->ref_lock);
                if (!c->refs_used)
                    return -1;
            } else if (c->refs_used && c->refs_used[bam_ref(b)]) {
                pthread_mutex_lock(&fd->ref_lock);
                fd->unsorted = 1;
                fd->multi_seq = 1;
                pthread_mutex_unlock(&fd->ref_lock);
            }
        }

        c->curr_ref = bam_ref(b);
        if (c->refs_used && c->curr_ref >= 0) c->refs_used[c->curr_ref]++;
    }

    if (!c->bams) {
        /* First time through, allocate a set of bam pointers */
        pthread_mutex_lock(&fd->bam_list_lock);
        if (fd->bl) {
            spare_bams *spare = fd->bl;
            c->bams = spare->bams;
            fd->bl = spare->next;
            free(spare);
        } else {
            c->bams = calloc(c->max_c_rec, sizeof(bam_seq_t *));
            if (!c->bams) {
                pthread_mutex_unlock(&fd->bam_list_lock);
                return -1;
            }
        }
        pthread_mutex_unlock(&fd->bam_list_lock);
    }

    /* Copy or alloc+copy the bam record, for later encoding */
    if (c->bams[c->curr_c_rec]) {
        if (bam_copy1(c->bams[c->curr_c_rec], b) == NULL)
            return -1;
    } else {
        c->bams[c->curr_c_rec] = bam_dup1(b);
        if (c->bams[c->curr_c_rec] == NULL)
            return -1;
    }
    if (bam_seq_len(b)) {
        c->s_num_bases += bam_seq_len(b);
    } else {
        // No sequence in BAM record.  CRAM doesn't directly support this
        // case, it ends up being stored as a string of N's for each query
        // consuming CIGAR operation.  As this can become very inefficient
        // in time and memory, data where the query length is excessively
        // long are rejected.
        hts_pos_t qlen = bam_cigar2qlen(b->core.n_cigar, bam_get_cigar(b));
        if (qlen > 100000000) {
            hts_log_error("CIGAR query length %"PRIhts_pos
                          " for read \"%s\" is too long",
                          qlen, bam_get_qname(b));
            return -1;
        }
        c->s_num_bases += qlen;
    }
    c->curr_rec++;
    c->curr_c_rec++;
    c->s_aux_bytes += bam_get_l_aux(b);
    c->n_mapped += (bam_flag(b) & BAM_FUNMAP) ? 0 : 1;
    fd->record_counter++;

    return 0;
}

Coverage Report

Created: 2025-12-14 06:43