bwase.c

//#include <unistd.h>
#include <string.h>
#include <stdio.h>
#include <stdlib.h>
#include <math.h>
#include <time.h>
#include "stdaln.h"
#include "bwase.h"
#include "bwtaln.h"
#include "bntseq.h"
#include "utils.h"
#include "kstring.h"

#include "glibc_win64_flat/getopt.h"
#include "glibc_win64_flat/stdlib.h"

int g_log_n[256];
char *bwa_rg_line, *bwa_rg_id;

void bwa_print_sam_PG();

void bwa_aln2seq_core(int n_aln, const bwt_aln1_t *aln, bwa_seq_t *s, int set_main, int n_multi)
{
    int i, cnt, best;
    if (n_aln == 0) {
        s->type = BWA_TYPE_NO_MATCH;
        s->c1 = s->c2 = 0;
        return;
    }

    if (set_main) {
        best = aln[0].score;
        for (i = cnt = 0; i < n_aln; ++i) {
            const bwt_aln1_t *p = aln + i;
            if (p->score > best) break;
            if (drand48() * (p->l - p->k + 1 + cnt) > (double)cnt) {
                s->n_mm = p->n_mm; s->n_gapo = p->n_gapo; s->n_gape = p->n_gape;
                s->score = p->score;
                s->sa = p->k + (bwtint_t)((p->l - p->k + 1) * drand48());
            }
            cnt += p->l - p->k + 1;
        }
        s->c1 = cnt;
        for (; i < n_aln; ++i) cnt += aln[i].l - aln[i].k + 1;
        s->c2 = cnt - s->c1;
        s->type = s->c1 > 1? BWA_TYPE_REPEAT : BWA_TYPE_UNIQUE;
    }

    if (n_multi) {
        int k, rest, n_occ, z = 0;
        for (k = n_occ = 0; k < n_aln; ++k) {
            const bwt_aln1_t *q = aln + k;
            n_occ += q->l - q->k + 1;
        }
        if (s->multi) free(s->multi);
        if (n_occ > n_multi + 1) { // if there are too many hits, generate none of them
            s->multi = 0; s->n_multi = 0;
            return;
        }
        /* The following code is more flexible than what is required
         * here. In principle, due to the requirement above, we can
         * simply output all hits, but the following samples "rest"
         * number of random hits. */
        rest = n_occ > n_multi + 1? n_multi + 1 : n_occ; // find one additional for ->sa
        s->multi = calloc(rest, sizeof(bwt_multi1_t));
        for (k = 0; k < n_aln; ++k) {
            const bwt_aln1_t *q = aln + k;
            if (q->l - q->k + 1 <= rest) {
                bwtint_t l;
                for (l = q->k; l <= q->l; ++l) {
                    s->multi[z].pos = l;
                    s->multi[z].gap = q->n_gapo + q->n_gape;
                    s->multi[z++].mm = q->n_mm;
                }
                rest -= q->l - q->k + 1;
            } else { // Random sampling (http://code.activestate.com/recipes/272884/). In fact, we never come here. 
                int j, i, k;
                for (j = rest, i = q->l - q->k + 1, k = 0; j > 0; --j) {
                    double p = 1.0, x = drand48();
                    while (x < p) p -= p * j / (i--);
                    s->multi[z].pos = q->l - i;
                    s->multi[z].gap = q->n_gapo + q->n_gape;
                    s->multi[z++].mm = q->n_mm;
                }
                rest = 0;
                break;
            }
        }
        s->n_multi = z;
    }
}

void bwa_aln2seq(int n_aln, const bwt_aln1_t *aln, bwa_seq_t *s)
{
    bwa_aln2seq_core(n_aln, aln, s, 1, 0);
}

int bwa_approx_mapQ(const bwa_seq_t *p, int mm)
{
    int n;
    if (p->c1 == 0) return 23;
    if (p->c1 > 1) return 0;
    if (p->n_mm == mm) return 25;
    if (p->c2 == 0) return 37;
    n = (p->c2 >= 255)? 255 : p->c2;
    return (23 < g_log_n[n])? 0 : 23 - g_log_n[n];
}

bwtint_t bwa_sa2pos(const bntseq_t *bns, const bwt_t *bwt, bwtint_t sapos, int len, int *strand)
{
    bwtint_t pos_f;
    int is_rev;
    pos_f = bns_depos(bns, bwt_sa(bwt, sapos), &is_rev); // pos_f
    *strand = !is_rev;
    /* NB: For gapped alignment, pacpos may not be correct, which will be fixed
     * in refine_gapped_core(). This line also determines the way "x" is
     * calculated in refine_gapped_core() when (ext < 0 && is_end == 0). */
    if (is_rev) pos_f = pos_f + 1 < len? 0 : pos_f - len + 1; // mapped to the forward strand
    return pos_f; // FIXME: it is possible that pos_f < bns->anns[ref_id].offset
}

/**
 * Derive the actual position in the read from the given suffix array
 * coordinates. Note that the position will be approximate based on
 * whether indels appear in the read and whether calculations are
 * performed from the start or end of the read.
 */
void bwa_cal_pac_pos_core(const bntseq_t *bns, const bwt_t *bwt, bwa_seq_t *seq, const int max_mm, const float fnr)
{
    int max_diff, strand;
    if (seq->type != BWA_TYPE_UNIQUE && seq->type != BWA_TYPE_REPEAT) return;
    max_diff = fnr > 0.0? bwa_cal_maxdiff(seq->len, BWA_AVG_ERR, fnr) : max_mm;
    seq->seQ = seq->mapQ = bwa_approx_mapQ(seq, max_diff);
    seq->pos = bwa_sa2pos(bns, bwt, seq->sa, seq->len, &strand);
    seq->strand = strand;
    seq->seQ = seq->mapQ = bwa_approx_mapQ(seq, max_diff);
}

void bwa_cal_pac_pos(const bntseq_t *bns, const char *prefix, int n_seqs, bwa_seq_t *seqs, int max_mm, float fnr)
{
    int i, j, strand, n_multi;
    char str[1024];
    bwt_t *bwt;
    // load forward SA
    strcpy(str, prefix); strcat(str, ".bwt");  bwt = bwt_restore_bwt(str);
    strcpy(str, prefix); strcat(str, ".sa"); bwt_restore_sa(str, bwt);
    for (i = 0; i != n_seqs; ++i) {
        bwa_seq_t *p = &seqs[i];
        bwa_cal_pac_pos_core(bns, bwt, p, max_mm, fnr);
        for (j = n_multi = 0; j < p->n_multi; ++j) {
            bwt_multi1_t *q = p->multi + j;
            q->pos = bwa_sa2pos(bns, bwt, q->pos, p->len, &strand);
            q->strand = strand;
            if (q->pos != p->pos)
                p->multi[n_multi++] = *q;
        }
        p->n_multi = n_multi;
    }
    bwt_destroy(bwt);
}

/* is_end_correct == 1 if (*pos+len) gives the correct coordinate on
 * forward strand. This happens when p->pos is calculated by
 * bwa_cal_pac_pos(). is_end_correct==0 if (*pos) gives the correct
 * coordinate. This happens only for color-converted alignment. */
static bwa_cigar_t *refine_gapped_core(bwtint_t l_pac, const ubyte_t *pacseq, int len, const ubyte_t *seq, bwtint_t *_pos,
                                    int ext, int *n_cigar, int is_end_correct)
{
    bwa_cigar_t *cigar = 0;
    ubyte_t *ref_seq;
    int l = 0, path_len, ref_len;
    AlnParam ap = aln_param_bwa;
    path_t *path;
    int64_t k, __pos = *_pos;

    ref_len = len + abs(ext);
    if (ext > 0) {
        ref_seq = (ubyte_t*)calloc(ref_len, 1);
        for (k = __pos; k < __pos + ref_len && k < l_pac; ++k)
            ref_seq[l++] = pacseq[k>>2] >> ((~k&3)<<1) & 3;
    } else {
        int64_t x = __pos + (is_end_correct? len : ref_len);
        ref_seq = (ubyte_t*)calloc(ref_len, 1);
        for (l = 0, k = x - ref_len > 0? x - ref_len : 0; k < x && k < l_pac; ++k)
            ref_seq[l++] = pacseq[k>>2] >> ((~k&3)<<1) & 3;
    }
    path = (path_t*)calloc(l+len, sizeof(path_t));

    aln_global_core(ref_seq, l, (ubyte_t*)seq, len, &ap, path, &path_len);
    cigar = bwa_aln_path2cigar(path, path_len, n_cigar);
    
    if (ext < 0 && is_end_correct) { // fix coordinate for reads mapped to the forward strand
        for (l = k = 0; k < *n_cigar; ++k) {
            if (__cigar_op(cigar[k]) == FROM_D) l -= __cigar_len(cigar[k]);
            else if (__cigar_op(cigar[k]) == FROM_I) l += __cigar_len(cigar[k]);
        }
        __pos += l;
    }

    if (__cigar_op(cigar[0]) == FROM_D) { // deletion at the 5'-end
        __pos += __cigar_len(cigar[0]);
        for (k = 0; k < *n_cigar - 1; ++k) cigar[k] = cigar[k+1];
        --(*n_cigar);
    }
    if (__cigar_op(cigar[*n_cigar-1]) == FROM_D) --(*n_cigar); // deletion at the 3'-end

    // change "I" at either end of the read to S. just in case. This should rarely happen...
    if (__cigar_op(cigar[*n_cigar-1]) == FROM_I) cigar[*n_cigar-1] = __cigar_create(3, (__cigar_len(cigar[*n_cigar-1])));
    if (__cigar_op(cigar[0]) == FROM_I) cigar[0] = __cigar_create(3, (__cigar_len(cigar[0])));

    *_pos = (bwtint_t)__pos;
    free(ref_seq); free(path);
    return cigar;
}

char *bwa_cal_md1(int n_cigar, bwa_cigar_t *cigar, int len, bwtint_t pos, ubyte_t *seq,
                  bwtint_t l_pac, ubyte_t *pacseq, kstring_t *str, int *_nm)
{
    bwtint_t x, y;
    int z, u, c, nm = 0;
    str->l = 0; // reset
    x = pos; y = 0;
    if (cigar) {
        int k, l;
        for (k = u = 0; k < n_cigar; ++k) {
            l = __cigar_len(cigar[k]);
            if (__cigar_op(cigar[k]) == FROM_M) {
                for (z = 0; z < l && x+z < l_pac; ++z) {
                    c = pacseq[(x+z)>>2] >> ((~(x+z)&3)<<1) & 3;
                    if (c > 3 || seq[y+z] > 3 || c != seq[y+z]) {
                        ksprintf(str, "%d", u);
                        kputc("ACGTN"[c], str);
                        ++nm;
                        u = 0;
                    } else ++u;
                }
                x += l; y += l;
            } else if (__cigar_op(cigar[k]) == FROM_I || __cigar_op(cigar[k]) == FROM_S) {
                y += l;
                if (__cigar_op(cigar[k]) == FROM_I) nm += l;
            } else if (__cigar_op(cigar[k]) == FROM_D) {
                ksprintf(str, "%d", u);
                kputc('^', str);
                for (z = 0; z < l && x+z < l_pac; ++z)
                    kputc("ACGT"[pacseq[(x+z)>>2] >> ((~(x+z)&3)<<1) & 3], str);
                u = 0;
                x += l; nm += l;
            }
        }
    } else { // no gaps
        for (z = u = 0; z < (bwtint_t)len; ++z) {
            c = pacseq[(x+z)>>2] >> ((~(x+z)&3)<<1) & 3;
            if (c > 3 || seq[y+z] > 3 || c != seq[y+z]) {
                ksprintf(str, "%d", u);
                kputc("ACGTN"[c], str);
                ++nm;
                u = 0;
            } else ++u;
        }
    }
    ksprintf(str, "%d", u);
    *_nm = nm;
    return strdup(str->s);
}

void bwa_correct_trimmed(bwa_seq_t *s)
{
    if (s->len == s->full_len) return;
    if (s->strand == 0) { // forward
        if (s->cigar && __cigar_op(s->cigar[s->n_cigar-1]) == FROM_S) { // the last is S
            s->cigar[s->n_cigar-1] += s->full_len - s->len;
        } else {
            if (s->cigar == 0) {
                s->n_cigar = 2;
                s->cigar = calloc(s->n_cigar, sizeof(bwa_cigar_t));
                s->cigar[0] = __cigar_create(0, s->len);
            } else {
                ++s->n_cigar;
                s->cigar = realloc(s->cigar, s->n_cigar * sizeof(bwa_cigar_t));
            }
            s->cigar[s->n_cigar-1] = __cigar_create(3, (s->full_len - s->len));
        }
    } else { // reverse
        if (s->cigar && __cigar_op(s->cigar[0]) == FROM_S) { // the first is S
            s->cigar[0] += s->full_len - s->len;
        } else {
            if (s->cigar == 0) {
                s->n_cigar = 2;
                s->cigar = calloc(s->n_cigar, sizeof(bwa_cigar_t));
                s->cigar[1] = __cigar_create(0, s->len);
            } else {
                ++s->n_cigar;
                s->cigar = realloc(s->cigar, s->n_cigar * sizeof(bwa_cigar_t));
                memmove(s->cigar + 1, s->cigar, (s->n_cigar-1) * sizeof(bwa_cigar_t));
            }
            s->cigar[0] = __cigar_create(3, (s->full_len - s->len));
        }
    }
    s->len = s->full_len;
}

void bwa_refine_gapped(const bntseq_t *bns, int n_seqs, bwa_seq_t *seqs, ubyte_t *_pacseq, bntseq_t *ntbns)
{
    ubyte_t *pacseq, *ntpac = 0;
    int i, j;
    kstring_t *str;

    if (ntbns) { // in color space
        ntpac = (ubyte_t*)calloc(ntbns->l_pac/4+1, 1);
        rewind(ntbns->fp_pac);
        fread(ntpac, 1, ntbns->l_pac/4 + 1, ntbns->fp_pac);
    }

    if (!_pacseq) {
        pacseq = (ubyte_t*)calloc(bns->l_pac/4+1, 1);
        rewind(bns->fp_pac);
        fread(pacseq, 1, bns->l_pac/4+1, bns->fp_pac);
    } else pacseq = _pacseq;
    for (i = 0; i != n_seqs; ++i) {
        bwa_seq_t *s = seqs + i;
        seq_reverse(s->len, s->seq, 0); // IMPORTANT: s->seq is reversed here!!!
        for (j = 0; j < s->n_multi; ++j) {
            bwt_multi1_t *q = s->multi + j;
            int n_cigar;
            if (q->gap == 0) continue;
            q->cigar = refine_gapped_core(bns->l_pac, pacseq, s->len, q->strand? s->rseq : s->seq, &q->pos,
                                          (q->strand? 1 : -1) * q->gap, &n_cigar, 1);
            q->n_cigar = n_cigar;
        }
        if (s->type == BWA_TYPE_NO_MATCH || s->type == BWA_TYPE_MATESW || s->n_gapo == 0) continue;
        s->cigar = refine_gapped_core(bns->l_pac, pacseq, s->len, s->strand? s->rseq : s->seq, &s->pos,
                                      (s->strand? 1 : -1) * (s->n_gapo + s->n_gape), &s->n_cigar, 1);
    }

    if (ntbns) { // in color space
        for (i = 0; i < n_seqs; ++i) {
            bwa_seq_t *s = seqs + i;
            bwa_cs2nt_core(s, bns->l_pac, ntpac);
            for (j = 0; j < s->n_multi; ++j) {
                bwt_multi1_t *q = s->multi + j;
                int n_cigar;
                if (q->gap == 0) continue;
                free(q->cigar);
                q->cigar = refine_gapped_core(bns->l_pac, ntpac, s->len, q->strand? s->rseq : s->seq, &q->pos,
                                              (q->strand? 1 : -1) * q->gap, &n_cigar, 0);
                q->n_cigar = n_cigar;
            }
            if (s->type != BWA_TYPE_NO_MATCH && s->cigar) { // update cigar again
                free(s->cigar);
                s->cigar = refine_gapped_core(bns->l_pac, ntpac, s->len, s->strand? s->rseq : s->seq, &s->pos,
                                              (s->strand? 1 : -1) * (s->n_gapo + s->n_gape), &s->n_cigar, 0);
            }
        }
    }

    // generate MD tag
    str = (kstring_t*)calloc(1, sizeof(kstring_t));
    for (i = 0; i != n_seqs; ++i) {
        bwa_seq_t *s = seqs + i;
        if (s->type != BWA_TYPE_NO_MATCH) {
            int nm;
            s->md = bwa_cal_md1(s->n_cigar, s->cigar, s->len, s->pos, s->strand? s->rseq : s->seq,
                                bns->l_pac, ntbns? ntpac : pacseq, str, &nm);
            s->nm = nm;
        }
    }
    free(str->s); free(str);

    // correct for trimmed reads
    if (!ntbns) // trimming is only enabled for Illumina reads
        for (i = 0; i < n_seqs; ++i) bwa_correct_trimmed(seqs + i);

    if (!_pacseq) free(pacseq);
    free(ntpac);
}

int64_t pos_end(const bwa_seq_t *p)
{
    if (p->cigar) {
        int j;
        int64_t x = p->pos;
        for (j = 0; j != p->n_cigar; ++j) {
            int op = __cigar_op(p->cigar[j]);
            if (op == 0 || op == 2) x += __cigar_len(p->cigar[j]);
        }
        return x;
    } else return p->pos + p->len;
}

int64_t pos_end_multi(const bwt_multi1_t *p, int len) // analogy to pos_end()
{
    if (p->cigar) {
        int j;
        int64_t x = p->pos;
        for (j = 0; j != p->n_cigar; ++j) {
            int op = __cigar_op(p->cigar[j]);
            if (op == 0 || op == 2) x += __cigar_len(p->cigar[j]);
        }
        return x;
    } else return p->pos + len;
}

static int64_t pos_5(const bwa_seq_t *p)
{
    if (p->type != BWA_TYPE_NO_MATCH)
        return p->strand? pos_end(p) : p->pos;
    return -1;
}

void bwa_print_sam1(const bntseq_t *bns, bwa_seq_t *p, const bwa_seq_t *mate, int mode, int max_top2)
{
    int j;
    if (p->type != BWA_TYPE_NO_MATCH || (mate && mate->type != BWA_TYPE_NO_MATCH)) {
        int seqid, nn, am = 0, flag = p->extra_flag;
        char XT;

        if (p->type == BWA_TYPE_NO_MATCH) {
            p->pos = mate->pos;
            p->strand = mate->strand;
            flag |= SAM_FSU;
            j = 1;
        } else j = pos_end(p) - p->pos; // j is the length of the reference in the alignment

        // get seqid
        nn = bns_cnt_ambi(bns, p->pos, j, &seqid);
        if (p->type != BWA_TYPE_NO_MATCH && p->pos + j - bns->anns[seqid].offset > bns->anns[seqid].len)
            flag |= SAM_FSU; // flag UNMAP as this alignment bridges two adjacent reference sequences

        // update flag and print it
        if (p->strand) flag |= SAM_FSR;
        if (mate) {
            if (mate->type != BWA_TYPE_NO_MATCH) {
                if (mate->strand) flag |= SAM_FMR;
            } else flag |= SAM_FMU;
        }
        err_printf("%s\t%d\t%s\t", p->name, flag, bns->anns[seqid].name);
        err_printf("%d\t%d\t", (int)(p->pos - bns->anns[seqid].offset + 1), p->mapQ);

        // print CIGAR
        if (p->cigar) {
            for (j = 0; j != p->n_cigar; ++j)
                err_printf("%d%c", __cigar_len(p->cigar[j]), "MIDS"[__cigar_op(p->cigar[j])]);
        } else if (p->type == BWA_TYPE_NO_MATCH) err_printf("*");
        else err_printf("%dM", p->len);

        // print mate coordinate
        if (mate && mate->type != BWA_TYPE_NO_MATCH) {
            int m_seqid, m_is_N;
            long long isize;
            am = mate->seQ < p->seQ? mate->seQ : p->seQ; // smaller single-end mapping quality
            // redundant calculation here, but should not matter too much
            m_is_N = bns_cnt_ambi(bns, mate->pos, mate->len, &m_seqid);
            err_printf("\t%s\t", (seqid == m_seqid)? "=" : bns->anns[m_seqid].name);
            isize = (seqid == m_seqid)? pos_5(mate) - pos_5(p) : 0;
            if (p->type == BWA_TYPE_NO_MATCH) isize = 0;
            err_printf("%d\t%lld\t", (int)(mate->pos - bns->anns[m_seqid].offset + 1), isize);
        } else if (mate) err_printf("\t=\t%d\t0\t", (int)(p->pos - bns->anns[seqid].offset + 1));
        else err_printf("\t*\t0\t0\t");

        // print sequence and quality
        if (p->strand == 0)
            for (j = 0; j != p->full_len; ++j) putchar("ACGTN"[(int)p->seq[j]]);
        else for (j = 0; j != p->full_len; ++j) putchar("TGCAN"[p->seq[p->full_len - 1 - j]]);
        putchar('\t');
        if (p->qual) {
            if (p->strand) seq_reverse(p->len, p->qual, 0); // reverse quality
            err_printf("%s", p->qual);
        } else err_printf("*");

        if (bwa_rg_id) err_printf("\tRG:Z:%s", bwa_rg_id);
        if (p->bc[0]) err_printf("\tBC:Z:%s", p->bc);
        if (p->clip_len < p->full_len) err_printf("\tXC:i:%d", p->clip_len);
        if (p->type != BWA_TYPE_NO_MATCH) {
            int i;
            // calculate XT tag
            XT = "NURM"[p->type];
            if (nn > 10) XT = 'N';
            // print tags
            err_printf("\tXT:A:%c\t%s:i:%d", XT, (mode & BWA_MODE_COMPREAD)? "NM" : "CM", p->nm);
            if (nn) err_printf("\tXN:i:%d", nn);
            if (mate) err_printf("\tSM:i:%d\tAM:i:%d", p->seQ, am);
            if (p->type != BWA_TYPE_MATESW) { // X0 and X1 are not available for this type of alignment
                err_printf("\tX0:i:%d", p->c1);
                if (p->c1 <= max_top2) err_printf("\tX1:i:%d", p->c2);
            }
            err_printf("\tXM:i:%d\tXO:i:%d\tXG:i:%d", p->n_mm, p->n_gapo, p->n_gapo+p->n_gape);
            if (p->md) err_printf("\tMD:Z:%s", p->md);
            // print multiple hits
            if (p->n_multi) {
                err_printf("\tXA:Z:");
                for (i = 0; i < p->n_multi; ++i) {
                    bwt_multi1_t *q = p->multi + i;
                    int k;
                    j = pos_end_multi(q, p->len) - q->pos;
                    nn = bns_cnt_ambi(bns, q->pos, j, &seqid);
                    err_printf("%s,%c%d,", bns->anns[seqid].name, q->strand? '-' : '+',
                           (int)(q->pos - bns->anns[seqid].offset + 1));
                    if (q->cigar) {
                        for (k = 0; k < q->n_cigar; ++k)
                            err_printf("%d%c", __cigar_len(q->cigar[k]), "MIDS"[__cigar_op(q->cigar[k])]);
                    } else err_printf("%dM", p->len);
                    err_printf(",%d;", q->gap + q->mm);
                }
            }
        }
        putchar('\n');
    } else { // this read has no match
        ubyte_t *s = p->strand? p->rseq : p->seq;
        int flag = p->extra_flag | SAM_FSU;
        if (mate && mate->type == BWA_TYPE_NO_MATCH) flag |= SAM_FMU;
        err_printf("%s\t%d\t*\t0\t0\t*\t*\t0\t0\t", p->name, flag);
        for (j = 0; j != p->len; ++j) putchar("ACGTN"[(int)s[j]]);
        putchar('\t');
        if (p->qual) {
            if (p->strand) seq_reverse(p->len, p->qual, 0); // reverse quality
            err_printf("%s", p->qual);
        } else err_printf("*");
        if (bwa_rg_id) err_printf("\tRG:Z:%s", bwa_rg_id);
        if (p->bc[0]) err_printf("\tBC:Z:%s", p->bc);
        if (p->clip_len < p->full_len) err_printf("\tXC:i:%d", p->clip_len);
        putchar('\n');
    }
}

bntseq_t *bwa_open_nt(const char *prefix)
{
    bntseq_t *ntbns;
    char *str;
    str = (char*)calloc(strlen(prefix) + 10, 1);
    strcat(strcpy(str, prefix), ".nt");
    ntbns = bns_restore(str);
    free(str);
    return ntbns;
}

void bwa_print_sam_SQ(const bntseq_t *bns)
{
    int i;
    for (i = 0; i < bns->n_seqs; ++i)
        err_printf("@SQ\tSN:%s\tLN:%d\n", bns->anns[i].name, bns->anns[i].len);
    if (bwa_rg_line) err_printf("%s\n", bwa_rg_line);
}

void bwase_initialize() 
{
    int i;
    for (i = 1; i != 256; ++i) g_log_n[i] = (int)(4.343 * log(i) + 0.5);
}

char *bwa_escape(char *s)
{
    char *p, *q;
    for (p = q = s; *p; ++p) {
        if (*p == '\\') {
            ++p;
            if (*p == 't') *q++ = '\t';
            else if (*p == 'n') *q++ = '\n';
            else if (*p == 'r') *q++ = '\r';
            else if (*p == '\\') *q++ = '\\';
        } else *q++ = *p;
    }
    *q = '\0';
    return s;
}

int bwa_set_rg(const char *s)
{
    char *p, *q, *r;
    if (strstr(s, "@RG") != s) return -1;
    if (bwa_rg_line) free(bwa_rg_line);
    if (bwa_rg_id) free(bwa_rg_id);
    bwa_rg_line = strdup(s);
    bwa_rg_id = 0;
    bwa_escape(bwa_rg_line);
    p = strstr(bwa_rg_line, "\tID:");
    if (p == 0) return -1;
    p += 4;
    for (q = p; *q && *q != '\t' && *q != '\n'; ++q);
    bwa_rg_id = calloc(q - p + 1, 1);
    for (q = p, r = bwa_rg_id; *q && *q != '\t' && *q != '\n'; ++q)
        *r++ = *q;
    return 0;
}

void bwa_sai2sam_se_core(const char *prefix, const char *fn_sa, const char *fn_fa, int n_occ)
{
    extern bwa_seqio_t *bwa_open_reads(int mode, const char *fn_fa);
    int i, n_seqs, tot_seqs = 0, m_aln;
    bwt_aln1_t *aln = 0;
    bwa_seq_t *seqs;
    bwa_seqio_t *ks;
    clock_t t;
    bntseq_t *bns, *ntbns = 0;
    FILE *fp_sa;
    gap_opt_t opt;

    // initialization
    bwase_initialize();
    bns = bns_restore(prefix);
    srand48(bns->seed);
    fp_sa = xopen(fn_sa, "rb");

    m_aln = 0;
    fread(&opt, sizeof(gap_opt_t), 1, fp_sa);
    if (!(opt.mode & BWA_MODE_COMPREAD)) // in color space; initialize ntpac
        ntbns = bwa_open_nt(prefix);
    bwa_print_sam_SQ(bns);
    bwa_print_sam_PG();
    // set ks
    ks = bwa_open_reads(opt.mode, fn_fa);
    // core loop
    while ((seqs = bwa_read_seq(ks, 0x40000, &n_seqs, opt.mode, opt.trim_qual)) != 0) {
        tot_seqs += n_seqs;
        t = clock();

        // read alignment
        for (i = 0; i < n_seqs; ++i) {
            bwa_seq_t *p = seqs + i;
            int n_aln;
            fread(&n_aln, 4, 1, fp_sa);
            if (n_aln > m_aln) {
                m_aln = n_aln;
                aln = (bwt_aln1_t*)realloc(aln, sizeof(bwt_aln1_t) * m_aln);
            }
            fread(aln, sizeof(bwt_aln1_t), n_aln, fp_sa);
            bwa_aln2seq_core(n_aln, aln, p, 1, n_occ);
        }

        fprintf(stderr, "[bwa_aln_core] convert to sequence coordinate... ");
        bwa_cal_pac_pos(bns, prefix, n_seqs, seqs, opt.max_diff, opt.fnr); // forward bwt will be destroyed here
        fprintf(stderr, "%.2f sec\n", (float)(clock() - t) / CLOCKS_PER_SEC); t = clock();

        fprintf(stderr, "[bwa_aln_core] refine gapped alignments... ");
        bwa_refine_gapped(bns, n_seqs, seqs, 0, ntbns);
        fprintf(stderr, "%.2f sec\n", (float)(clock() - t) / CLOCKS_PER_SEC); t = clock();

        fprintf(stderr, "[bwa_aln_core] print alignments... ");
        for (i = 0; i < n_seqs; ++i)
            bwa_print_sam1(bns, seqs + i, 0, opt.mode, opt.max_top2);
        fprintf(stderr, "%.2f sec\n", (float)(clock() - t) / CLOCKS_PER_SEC); t = clock();

        bwa_free_read_seq(n_seqs, seqs);
        fprintf(stderr, "[bwa_aln_core] %d sequences have been processed.\n", tot_seqs);
    }

    // destroy
    bwa_seq_close(ks);
    if (ntbns) bns_destroy(ntbns);
    bns_destroy(bns);
    fclose(fp_sa);
    free(aln);
}

int bwa_sai2sam_se(int argc, char *argv[])
{
    int c, n_occ = 3;
    while ((c = getopt(argc, argv, "hn:f:r:")) >= 0) {
        switch (c) {
        case 'h': break;
        case 'r':
            if (bwa_set_rg(optarg) < 0) {
                fprintf(stderr, "[%s] malformated @RG line\n", __FUNCTION__);
                return 1;
            }
            break;
        case 'n': n_occ = atoi(optarg); break;
        case 'f': xreopen(optarg, "w", stdout); break;
        default: return 1;
        }
    }

    if (optind + 3 > argc) {
        fprintf(stderr, "Usage: bwa samse [-n max_occ] [-f out.sam] [-r RG_line] <prefix> <in.sai> <in.fq>\n");
        return 1;
    }
    bwa_sai2sam_se_core(argv[optind], argv[optind+1], argv[optind+2], n_occ);
    free(bwa_rg_line); free(bwa_rg_id);
    return 0;
}