text: #include <assert.h>
  #include <string.h>
  #include <stdlib.h>
  #include <math.h>
  #include "minimap.h"
  #include "mmpriv.h"
  #include "ksw2.h"
  
  static void ksw_gen_simple_mat(int m, int8_t *mat, int8_t a, int8_t b)
  {
  	int i, j;
  	a = a < 0? -a : a;
  	b = b > 0? -b : b;
  	for (i = 0; i < m - 1; ++i) {
  		for (j = 0; j < m - 1; ++j)
  			mat[i * m + j] = i == j? a : b;
  		mat[i * m + m - 1] = 0;
  	}
  	for (j = 0; j < m; ++j)
  		mat[(m - 1) * m + j] = 0;
  }
  
  static inline void mm_seq_rev(uint32_t len, uint8_t *seq)
  {
  	uint32_t i;
  	uint8_t t;
  	for (i = 0; i < len>>1; ++i)
  		t = seq[i], seq[i] = seq[len - 1 - i], seq[len - 1 - i] = t;
  }
  
  static inline int test_zdrop_aux(int32_t score, int i, int j, int32_t *max, int *max_i, int *max_j, int e, int zdrop)
  {
  	if (score < *max) {
  		int li = i - *max_i;
  		int lj = j - *max_j;
  		int diff = li > lj? li - lj : lj - li;
  		if (*max - score > zdrop + diff * e)
  			return 1;
  	} else *max = score, *max_i = i, *max_j = j;
  	return 0;
  }
  
  static int mm_check_zdrop(const uint8_t *qseq, const uint8_t *tseq, uint32_t n_cigar, uint32_t *cigar, const int8_t *mat, int8_t q, int8_t e, int zdrop)
  {
  	uint32_t k;
  	int32_t score = 0, max = 0, max_i = -1, max_j = -1, i = 0, j = 0;
  	for (k = 0; k < n_cigar; ++k) {
  		uint32_t l, op = cigar[k]&0xf, len = cigar[k]>>4;
  		if (op == 0) {
  			for (l = 0; l < len; ++l) {
  				score += mat[tseq[i + l] * 5 + qseq[j + l]];
  				if (test_zdrop_aux(score, i+l, j+l, &max, &max_i, &max_j, e, zdrop)) return 1;
  			}
  			i += len, j += len;
  		} else if (op == 1) {
  			score -= q + e * len, j += len;
  			if (test_zdrop_aux(score, i, j, &max, &max_i, &max_j, e, zdrop)) return 1;
  		} else if (op == 2 || op == 3) {
  			score -= q + e * len, i += len;
  			if (test_zdrop_aux(score, i, j, &max, &max_i, &max_j, e, zdrop)) return 1;
  		}
  	}
  	return 0;
  }
  
  static void mm_fix_cigar(mm_reg1_t *r, const uint8_t *qseq, const uint8_t *tseq, int *qshift, int *tshift)
  {
  	mm_extra_t *p = r->p;
  	int32_t k, toff = 0, qoff = 0, to_shrink = 0;
  	*qshift = *tshift = 0;
  	if (p->n_cigar <= 1) return;
  	for (k = 0; k < p->n_cigar; ++k) { // indel left alignment
  		uint32_t op = p->cigar[k]&0xf, len = p->cigar[k]>>4;
  		if (len == 0) to_shrink = 1;
  		if (op == 0) {
  			toff += len, qoff += len;
  		} else if (op == 1 || op == 2) { // insertion or deletion
  			if (k > 0 && k < p->n_cigar - 1 && (p->cigar[k-1]&0xf) == 0 && (p->cigar[k+1]&0xf) == 0) {
  				int l, prev_len = p->cigar[k-1] >> 4;
  				if (op == 1) {
  					for (l = 0; l < prev_len; ++l)
  						if (qseq[qoff - 1 - l] != qseq[qoff + len - 1 - l])
  							break;
  				} else {
  					for (l = 0; l < prev_len; ++l)
  						if (tseq[toff - 1 - l] != tseq[toff + len - 1 - l])
  							break;
  				}
  				if (l > 0)
  					p->cigar[k-1] -= l<<4, p->cigar[k+1] += l<<4, qoff -= l, toff -= l;
  				if (l == prev_len) to_shrink = 1;
  			}
  			if (op == 1) qoff += len;
  			else toff += len;
  		} else if (op == 3) {
  			toff += len;
  		}
  	}
  	assert(qoff == r->qe - r->qs && toff == r->re - r->rs);
  	if (to_shrink) { // squeeze out zero-length operations
  		int32_t l = 0;
  		for (k = 0; k < p->n_cigar; ++k) // squeeze out zero-length operations
  			if (p->cigar[k]>>4 != 0)
  				p->cigar[l++] = p->cigar[k];
  		p->n_cigar = l;
  		for (k = l = 0; k < p->n_cigar; ++k) // merge two adjacent operations if they are the same
  			if (k == p->n_cigar - 1 || (p->cigar[k]&0xf) != (p->cigar[k+1]&0xf))
  				p->cigar[l++] = p->cigar[k];
  			else p->cigar[k+1] += p->cigar[k]>>4<<4; // add length to the next CIGAR operator
  		p->n_cigar = l;
  	}
  	if ((p->cigar[0]&0xf) == 1 || (p->cigar[0]&0xf) == 2) { // get rid of leading I or D
  		int32_t l = p->cigar[0] >> 4;
  		if ((p->cigar[0]&0xf) == 1) {
  			if (r->rev) r->qe -= l;
  			else r->qs += l;
  			*qshift = l;
  		} else r->rs += l, *tshift = l;
  		--p->n_cigar;
  		memmove(p->cigar, p->cigar + 1, p->n_cigar * 4);
  	}
  }
  
  static void mm_update_extra(mm_reg1_t *r, const uint8_t *qseq, const uint8_t *tseq, const int8_t *mat, int8_t q, int8_t e)
  {
  	uint32_t k, l, toff = 0, qoff = 0;
  	int32_t s = 0, max = 0, qshift, tshift;
  	mm_extra_t *p = r->p;
  	if (p == 0) return;
  	mm_fix_cigar(r, qseq, tseq, &qshift, &tshift);
  	qseq += qshift, tseq += tshift; // qseq and tseq may be shifted due to the removal of leading I/D
  	r->blen = r->mlen = 0;
  	for (k = 0; k < p->n_cigar; ++k) {
  		uint32_t op = p->cigar[k]&0xf, len = p->cigar[k]>>4;
  		if (op == 0) { // match/mismatch
  			int n_ambi = 0, n_diff = 0;
  			for (l = 0; l < len; ++l) {
  				int cq = qseq[qoff + l], ct = tseq[toff + l];
  				if (ct > 3 || cq > 3) ++n_ambi;
  				else if (ct != cq) ++n_diff;
  				s += mat[ct * 5 + cq];
  				if (s < 0) s = 0;
  				else max = max > s? max : s;
  			}
  			r->blen += len - n_ambi, r->mlen += len - (n_ambi + n_diff), p->n_ambi += n_ambi;
  			toff += len, qoff += len;
  		} else if (op == 1) { // insertion
  			int n_ambi = 0;
  			for (l = 0; l < len; ++l)
  				if (qseq[qoff + l] > 3) ++n_ambi;
  			r->blen += len - n_ambi, p->n_ambi += n_ambi;
  			s -= q + e * len;
  			if (s < 0) s = 0;
  			qoff += len;
  		} else if (op == 2) { // deletion
  			int n_ambi = 0;
  			for (l = 0; l < len; ++l)
  				if (tseq[toff + l] > 3) ++n_ambi;
  			r->blen += len - n_ambi, p->n_ambi += n_ambi;
  			s -= q + e * len;
  			if (s < 0) s = 0;
  			toff += len;
  		} else if (op == 3) { // intron
  			toff += len;
  		}
  	}
  	p->dp_max = max;
  	assert(qoff == r->qe - r->qs && toff == r->re - r->rs);
  }
  
  static void mm_append_cigar(mm_reg1_t *r, uint32_t n_cigar, uint32_t *cigar) // TODO: this calls the libc realloc()
  {
  	mm_extra_t *p;
  	if (n_cigar == 0) return;
  	if (r->p == 0) {
  		uint32_t capacity = n_cigar + sizeof(mm_extra_t);
  		kroundup32(capacity);
  		r->p = (mm_extra_t*)calloc(capacity, 4);
  		r->p->capacity = capacity;
  	} else if (r->p->n_cigar + n_cigar + sizeof(mm_extra_t) > r->p->capacity) {
  		r->p->capacity = r->p->n_cigar + n_cigar + sizeof(mm_extra_t);
  		kroundup32(r->p->capacity);
  		r->p = (mm_extra_t*)realloc(r->p, r->p->capacity * 4);
  	}
  	p = r->p;
  	if (p->n_cigar > 0 && (p->cigar[p->n_cigar-1]&0xf) == (cigar[0]&0xf)) { // same CIGAR op at the boundary
  		p->cigar[p->n_cigar-1] += cigar[0]>>4<<4;
  		if (n_cigar > 1) memcpy(p->cigar + p->n_cigar, cigar + 1, (n_cigar - 1) * 4);
  		p->n_cigar += n_cigar - 1;
  	} else {
  		memcpy(p->cigar + p->n_cigar, cigar, n_cigar * 4);
  		p->n_cigar += n_cigar;
  	}
  }
  
  static void mm_align_pair(void *km, const mm_mapopt_t *opt, int qlen, const uint8_t *qseq, int tlen, const uint8_t *tseq, const int8_t *mat, int w, int end_bonus, int flag, ksw_extz_t *ez)
  {
  	int zdrop = opt->zdrop;
  	if (mm_dbg_flag & MM_DBG_PRINT_ALN_SEQ) {
  		int i;
  		fprintf(stderr, "===> q=(%d,%d), e=(%d,%d), bw=%d, flag=%d, zdrop=%d <===\n", opt->q, opt->q2, opt->e, opt->e2, w, flag, opt->zdrop);
  		for (i = 0; i < tlen; ++i) fputc("ACGTN"[tseq[i]], stderr);
  		fputc('\n', stderr);
  		for (i = 0; i < qlen; ++i) fputc("ACGTN"[qseq[i]], stderr);
  		fputc('\n', stderr);
  	}
  	if (opt->flag & MM_F_SPLICE)
  		ksw_exts2_sse(km, qlen, qseq, tlen, tseq, 5, mat, opt->q, opt->e, opt->q2, opt->noncan, zdrop, flag, ez);
  	else if (opt->q == opt->q2 && opt->e == opt->e2)
  		ksw_extz2_sse(km, qlen, qseq, tlen, tseq, 5, mat, opt->q, opt->e, w, zdrop, end_bonus, flag, ez);
  	else
  		ksw_extd2_sse(km, qlen, qseq, tlen, tseq, 5, mat, opt->q, opt->e, opt->q2, opt->e2, w, zdrop, end_bonus, flag, ez);
  }
  
  static inline int mm_get_hplen_back(const mm_idx_t *mi, uint32_t rid, uint32_t x)
  {
  	int64_t i, off0 = mi->seq[rid].offset, off = off0 + x;
  	int c = mm_seq4_get(mi->S, off);
  	for (i = off - 1; i >= off0; --i)
  		if (mm_seq4_get(mi->S, i) != c) break;
  	return (int)(off - i);
  }
  
  static inline void mm_adjust_minier(const mm_idx_t *mi, uint8_t *const qseq0[2], mm128_t *a, int32_t *r, int32_t *q)
  {
  	if (mi->flag & MM_I_HPC) {
  		const uint8_t *qseq = qseq0[a->x>>63];
  		int i, c;
  		*q = (int32_t)a->y;
  		for (i = *q - 1, c = qseq[*q]; i > 0; --i)
  			if (qseq[i] != c) break;
  		*q = i + 1;
  		c = mm_get_hplen_back(mi, a->x<<1>>33, (int32_t)a->x);
  		*r = (int32_t)a->x + 1 - c;
  	} else {
  		*r = (int32_t)a->x - (mi->k>>1);
  		*q = (int32_t)a->y - (mi->k>>1);
  	}
  }
  
  static void mm_filter_bad_seeds(void *km, int as1, int cnt1, mm128_t *a, int min_gap, int diff_thres, int max_ext_len, int max_ext_cnt)
  {
  	int max_st, max_en, n, i, k, max, *K;
  	for (i = 1, n = 0; i < cnt1; ++i) { // count the number of gaps longer than min_gap
  		int gap = ((int32_t)a[as1 + i].y - a[as1 + i - 1].y) - ((int32_t)a[as1 + i].x - a[as1 + i - 1].x);
  		if (gap < -min_gap || gap > min_gap) ++n;
  	}
  	if (n <= 1) return;
  	K = (int*)kmalloc(km, n * sizeof(int));
  	for (i = 1, n = 0; i < cnt1; ++i) { // store the positions of long gaps
  		int gap = ((int32_t)a[as1 + i].y - a[as1 + i - 1].y) - ((int32_t)a[as1 + i].x - a[as1 + i - 1].x);
  		if (gap < -min_gap || gap > min_gap)
  			K[n++] = i;
  	}
  	max = 0, max_st = max_en = -1;
  	for (k = 0;; ++k) { // traverse long gaps
  		int gap, l, n_ins = 0, n_del = 0, qs, rs, max_diff = 0, max_diff_l = -1;
  		if (k == n || k >= max_en) {
  			if (max_en > 0)
  				for (i = K[max_st]; i < K[max_en]; ++i)
  					a[as1 + i].y |= MM_SEED_IGNORE;
  			max = 0, max_st = max_en = -1;
  			if (k == n) break;
  		}
  		i = K[k];
  		gap = ((int32_t)a[as1 + i].y - a[as1 + i - 1].y) - ((int32_t)a[as1 + i].x - a[as1 + i - 1].x);
  		if (gap > 0) n_ins += gap;
  		else n_del += -gap;
  		qs = (int32_t)a[as1 + i - 1].y;
  		rs = (int32_t)a[as1 + i - 1].x;
  		for (l = k + 1; l < n && l <= k + max_ext_cnt; ++l) {
  			int j = K[l], diff;
  			if ((int32_t)a[as1 + j].y - qs > max_ext_len || (int32_t)a[as1 + j].x - rs > max_ext_len) break;
  			gap = ((int32_t)a[as1 + j].y - (int32_t)a[as1 + j - 1].y) - (a[as1 + j].x - a[as1 + j - 1].x);
  			if (gap > 0) n_ins += gap;
  			else n_del += -gap;
  			diff = n_ins + n_del - abs(n_ins - n_del);
  			if (max_diff < diff)
  				max_diff = diff, max_diff_l = l;
  		}
  		if (max_diff > diff_thres && max_diff > max)
  			max = max_diff, max_st = k, max_en = max_diff_l;
  	}
  	kfree(km, K);
  }
  
  static void mm_fix_bad_ends(const mm_reg1_t *r, const mm128_t *a, int bw, int32_t *as, int32_t *cnt)
  {
  	int32_t i, l;
  	*as = r->as, *cnt = r->cnt;
  	if (r->cnt < 3) return;
  	l = a[r->as].y >> 32 & 0xff;
  	for (i = r->as + 1; i < r->as + r->cnt - 1; ++i) {
  		int32_t lq, lr, min, max;
  		lr = (int32_t)a[i].x - (int32_t)a[i-1].x;
  		lq = (int32_t)a[i].y - (int32_t)a[i-1].y;
  		min = lr < lq? lr : lq;
  		max = lr > lq? lr : lq;
  		if (max - min > l >> 1) *as = i;
  		l += min;
  		if (l >= bw << 1) break;
  	}
  	*cnt = r->as + r->cnt - *as;
  	l = a[r->as + r->cnt - 1].y >> 32 & 0xff;
  	for (i = r->as + r->cnt - 2; i > *as; --i) {
  		int32_t lq, lr, min, max;
  		lr = (int32_t)a[i+1].x - (int32_t)a[i].x;
  		lq = (int32_t)a[i+1].y - (int32_t)a[i].y;
  		min = lr < lq? lr : lq;
  		max = lr > lq? lr : lq;
  		if (max - min > l >> 1) *cnt = i + 1 - *as;
  		l += min;
  		if (l >= bw) break;
  	}
  }
  
  static void mm_max_stretch(const mm_mapopt_t *opt, const mm_reg1_t *r, const mm128_t *a, int32_t *as, int32_t *cnt)
  {
  	int32_t i, score, max_score, len, max_i, max_len;
  
  	*as = r->as, *cnt = r->cnt;
  	if (r->cnt < 2) return;
  
  	max_score = -1, max_i = -1, max_len = 0;
  	score = a[r->as].y >> 32 & 0xff, len = 1;
  	for (i = r->as + 1; i < r->as + r->cnt; ++i) {
  		int32_t lq, lr, q_span;
  		q_span = a[i].y >> 32 & 0xff;
  		lr = (int32_t)a[i].x - (int32_t)a[i-1].x;
  		lq = (int32_t)a[i].y - (int32_t)a[i-1].y;
  		if (lq == lr) {
  			score += lq < q_span? lq : q_span;
  			++len;
  		} else {
  			if (score > max_score)
  				max_score = score, max_len = len, max_i = i - len;
  			score = q_span, len = 1;
  		}
  	}
  	if (score > max_score)
  		max_score = score, max_len = len, max_i = i - len;
  	*as = max_i, *cnt = max_len;
  }
  
  static int mm_seed_ext_score(void *km, const mm_mapopt_t *opt, const mm_idx_t *mi, const int8_t mat[25], int qlen, uint8_t *qseq0[2], const mm128_t *a)
  {
  	uint8_t *qseq, *tseq;
  	int q_span = a->y>>32&0xff, qs, qe, rs, re, rid, score, q_off, t_off, ext_len = opt->anchor_ext_len;
  	void *qp;
  	rid = a->x<<1>>33;
  	re = (uint32_t)a->x + 1, rs = re - q_span;
  	qe = (uint32_t)a->y + 1, qs = qe - q_span;
  	rs = rs - ext_len > 0? rs - ext_len : 0;
  	qs = qs - ext_len > 0? qs - ext_len : 0;
  	re = re + ext_len < mi->seq[rid].len? re + ext_len : mi->seq[rid].len;
  	qe = qe + ext_len < qlen? qe + ext_len : qlen;
  	tseq = (uint8_t*)kmalloc(km, re - rs);
  	mm_idx_getseq(mi, rid, rs, re, tseq);
  	qseq = qseq0[a->x>>63] + qs;
  	qp = ksw_ll_qinit(km, 2, qe - qs, qseq, 5, mat);
  	score = ksw_ll_i16(qp, re - rs, tseq, opt->q, opt->e, &q_off, &t_off);
  	kfree(km, tseq);
  	kfree(km, qp);
  	return score;
  }
  
  static void mm_fix_bad_ends_splice(void *km, const mm_mapopt_t *opt, const mm_idx_t *mi, const mm_reg1_t *r, const int8_t mat[25], int qlen, uint8_t *qseq0[2], const mm128_t *a, int *as1, int *cnt1)
  { // this assumes a very crude k-mer based mode; it is not necessary to use a good model just for filtering bounary exons
  	int score;
  	double log_gap;
  	*as1 = r->as, *cnt1 = r->cnt;
  	if (r->cnt < 3) return;
  	log_gap = log((int32_t)a[r->as + 1].x - (int32_t)a[r->as].x);
  	if ((a[r->as].y>>32&0xff) < log_gap + opt->anchor_ext_shift) {
  		score = mm_seed_ext_score(km, opt, mi, mat, qlen, qseq0, &a[r->as]);
  		if ((double)score / mat[0] < log_gap + opt->anchor_ext_shift) // a more exact format is "score < log_4(gap) + shift"
  			++(*as1), --(*cnt1);
  	}
  	log_gap = log((int32_t)a[r->as + r->cnt - 1].x - (int32_t)a[r->as + r->cnt - 2].x);
  	if ((a[r->as + r->cnt - 1].y>>32&0xff) < log_gap + opt->anchor_ext_shift) {
  		score = mm_seed_ext_score(km, opt, mi, mat, qlen, qseq0, &a[r->as + r->cnt - 1]);
  		if ((double)score / mat[0] < log_gap + opt->anchor_ext_shift)
  			--(*cnt1);
  	}
  }
  
  static void mm_align1(void *km, const mm_mapopt_t *opt, const mm_idx_t *mi, int qlen, uint8_t *qseq0[2], mm_reg1_t *r, mm_reg1_t *r2, int n_a, mm128_t *a, ksw_extz_t *ez, int splice_flag)
  {
  	int is_sr = !!(opt->flag & MM_F_SR), is_splice = !!(opt->flag & MM_F_SPLICE);
  	int32_t rid = a[r->as].x<<1>>33, rev = a[r->as].x>>63, as1, cnt1;
  	uint8_t *tseq, *qseq;
  	int32_t i, l, bw, dropped = 0, extra_flag = 0, rs0, re0, qs0, qe0;
  	int32_t rs, re, qs, qe;
  	int32_t rs1, qs1, re1, qe1;
  	int8_t mat[25];
  
  	if (is_sr) assert(!(mi->flag & MM_I_HPC)); // HPC won't work with SR because with HPC we can't easily tell if there is a gap
  
  	r2->cnt = 0;
  	if (r->cnt == 0) return;
  	ksw_gen_simple_mat(5, mat, opt->a, opt->b);
  	bw = (int)(opt->bw * 1.5 + 1.);
  
  	if (is_sr && !(mi->flag & MM_I_HPC)) {
  		mm_max_stretch(opt, r, a, &as1, &cnt1);
  		rs = (int32_t)a[as1].x + 1 - (int32_t)(a[as1].y>>32&0xff);
  		qs = (int32_t)a[as1].y + 1 - (int32_t)(a[as1].y>>32&0xff);
  		re = (int32_t)a[as1+cnt1-1].x + 1;
  		qe = (int32_t)a[as1+cnt1-1].y + 1;
  	} else {
  		if (is_splice) {
  			mm_fix_bad_ends_splice(km, opt, mi, r, mat, qlen, qseq0, a, &as1, &cnt1);
  		} else {
  			mm_fix_bad_ends(r, a, opt->bw, &as1, &cnt1);
  		}
  		mm_filter_bad_seeds(km, as1, cnt1, a, 10, 40, opt->max_gap>>1, 10);
  		mm_adjust_minier(mi, qseq0, &a[as1], &rs, &qs);
  		mm_adjust_minier(mi, qseq0, &a[as1 + cnt1 - 1], &re, &qe);
  	}
  	assert(cnt1 > 0);
  
  	if (is_splice) {
  		if (splice_flag & MM_F_SPLICE_FOR) extra_flag |= rev? KSW_EZ_SPLICE_REV : KSW_EZ_SPLICE_FOR;
  		if (splice_flag & MM_F_SPLICE_REV) extra_flag |= rev? KSW_EZ_SPLICE_FOR : KSW_EZ_SPLICE_REV;
  		if (opt->flag & MM_F_SPLICE_FLANK) extra_flag |= KSW_EZ_SPLICE_FLANK;
  	}
  
  	/* Look for the start and end of regions to perform DP. This sounds easy
  	 * but is in fact tricky. Excessively small regions lead to unnecessary
  	 * clippings and lose alignable sequences. Excessively large regions
  	 * occasionally lead to large overlaps between two chains and may cause
  	 * loss of alignments in corner cases. */
  	if (is_sr) {
  		qs0 = 0, qe0 = qlen;
  		l = qs;
  		l += l * opt->a + opt->end_bonus > opt->q? (l * opt->a + opt->end_bonus - opt->q) / opt->e : 0;
  		rs0 = rs - l > 0? rs - l : 0;
  		l = qlen - qe;
  		l += l * opt->a + opt->end_bonus > opt->q? (l * opt->a + opt->end_bonus - opt->q) / opt->e : 0;
  		re0 = re + l < mi->seq[rid].len? re + l : mi->seq[rid].len;
  	} else {
  		// compute rs0 and qs0
  		rs0 = (int32_t)a[r->as].x + 1 - (int32_t)(a[r->as].y>>32&0xff);
  		qs0 = (int32_t)a[r->as].y + 1 - (int32_t)(a[r->as].y>>32&0xff);
  		if (rs0 < 0) rs0 = 0; // this may happen when HPC is in use
  		assert(qs0 >= 0); // this should never happen, or it is logic error
  		rs1 = qs1 = 0;
  		for (i = r->as - 1, l = 0; i >= 0 && a[i].x>>32 == a[r->as].x>>32; --i) { // inspect nearby seeds
  			int32_t x = (int32_t)a[i].x + 1 - (int32_t)(a[i].y>>32&0xff);
  			int32_t y = (int32_t)a[i].y + 1 - (int32_t)(a[i].y>>32&0xff);
  			if (x < rs0 && y < qs0) {
  				if (++l > opt->min_cnt) {
  					l = rs0 - x > qs0 - y? rs0 - x : qs0 - y;
  					rs1 = rs0 - l, qs1 = qs0 - l;
  					break;
  				}
  			}
  		}
  		if (qs > 0 && rs > 0) {
  			l = qs < opt->max_gap? qs : opt->max_gap;
  			qs1 = qs1 > qs - l? qs1 : qs - l;
  			qs0 = qs0 < qs1? qs0 : qs1; // at least include qs0
  			l += l * opt->a > opt->q? (l * opt->a - opt->q) / opt->e : 0;
  			l = l < opt->max_gap? l : opt->max_gap;
  			l = l < rs? l : rs;
  			rs1 = rs1 > rs - l? rs1 : rs - l;
  			rs0 = rs0 < rs1? rs0 : rs1;
  		} else rs0 = rs, qs0 = qs;
  		// compute re0 and qe0
  		re0 = (int32_t)a[r->as + r->cnt - 1].x + 1;
  		qe0 = (int32_t)a[r->as + r->cnt - 1].y + 1;
  		re1 = mi->seq[rid].len, qe1 = qlen;
  		for (i = r->as + r->cnt, l = 0; i < n_a && a[i].x>>32 == a[r->as].x>>32; ++i) { // inspect nearby seeds
  			int32_t x = (int32_t)a[i].x + 1;
  			int32_t y = (int32_t)a[i].y + 1;
  			if (x > re0 && y > qe0) {
  				if (++l > opt->min_cnt) {
  					l = x - re0 > y - qe0? x - re0 : y - qe0;
  					re1 = re0 + l, qe1 = qe0 + l;
  					break;
  				}
  			}
  		}
  		if (qe < qlen && re < mi->seq[rid].len) {
  			l = qlen - qe < opt->max_gap? qlen - qe : opt->max_gap;
  			qe1 = qe1 < qe + l? qe1 : qe + l;
  			qe0 = qe0 > qe1? qe0 : qe1; // at least include qe0
  			l += l * opt->a > opt->q? (l * opt->a - opt->q) / opt->e : 0;
  			l = l < opt->max_gap? l : opt->max_gap;
  			l = l < mi->seq[rid].len - re? l : mi->seq[rid].len - re;
  			re1 = re1 < re + l? re1 : re + l;
  			re0 = re0 > re1? re0 : re1;
  		} else re0 = re, qe0 = qe;
  	}
  
  	assert(re0 > rs0);
  	tseq = (uint8_t*)kmalloc(km, re0 - rs0);
  
  	if (qs > 0 && rs > 0) { // left extension
  		qseq = &qseq0[rev][qs0];
  		mm_idx_getseq(mi, rid, rs0, rs, tseq);
  		mm_seq_rev(qs - qs0, qseq);
  		mm_seq_rev(rs - rs0, tseq);
  		mm_align_pair(km, opt, qs - qs0, qseq, rs - rs0, tseq, mat, bw, opt->end_bonus, extra_flag|KSW_EZ_EXTZ_ONLY|KSW_EZ_RIGHT|KSW_EZ_REV_CIGAR, ez);
  		if (ez->n_cigar > 0) {
  			mm_append_cigar(r, ez->n_cigar, ez->cigar);
  			r->p->dp_score += ez->max;
  		}
  		rs1 = rs - (ez->reach_end? ez->mqe_t + 1 : ez->max_t + 1);
  		qs1 = qs - (ez->reach_end? qs - qs0 : ez->max_q + 1);
  		mm_seq_rev(qs - qs0, qseq);
  	} else rs1 = rs, qs1 = qs;
  	re1 = rs, qe1 = qs;
  	assert(qs1 >= 0 && rs1 >= 0);
  
  	for (i = is_sr? cnt1 - 1 : 1; i < cnt1; ++i) { // gap filling
  		if ((a[as1+i].y & (MM_SEED_IGNORE|MM_SEED_TANDEM)) && i != cnt1 - 1) continue;
  		if (is_sr && !(mi->flag & MM_I_HPC)) {
  			re = (int32_t)a[as1 + i].x + 1;
  			qe = (int32_t)a[as1 + i].y + 1;
  		} else mm_adjust_minier(mi, qseq0, &a[as1 + i], &re, &qe);
  		re1 = re, qe1 = qe;
  		if (i == cnt1 - 1 || (a[as1+i].y&MM_SEED_LONG_JOIN) || (qe - qs >= opt->min_ksw_len && re - rs >= opt->min_ksw_len)) {
  			int j, bw1 = bw;
  			if (a[as1+i].y & MM_SEED_LONG_JOIN)
  				bw1 = qe - qs > re - rs? qe - qs : re - rs;
  			qseq = &qseq0[rev][qs];
  			mm_idx_getseq(mi, rid, rs, re, tseq);
  			if (is_sr) { // perform ungapped alignment
  				assert(qe - qs == re - rs);
  				ksw_reset_extz(ez);
  				for (j = 0, ez->score = 0; j < qe - qs; ++j) {
  					if (qseq[j] >= 4 || tseq[j] >= 4) ez->score += opt->e2;
  					else ez->score += qseq[j] == tseq[j]? opt->a : -opt->b;
  				}
  				ez->cigar = ksw_push_cigar(km, &ez->n_cigar, &ez->m_cigar, ez->cigar, 0, qe - qs);
  			} else { // perform normal gapped alignment
  				mm_align_pair(km, opt, qe - qs, qseq, re - rs, tseq, mat, bw1, -1, extra_flag|KSW_EZ_APPROX_MAX, ez); // first pass: with approximate Z-drop
  			}
  			if (mm_check_zdrop(qseq, tseq, ez->n_cigar, ez->cigar, mat, opt->q, opt->e, opt->zdrop))
  				mm_align_pair(km, opt, qe - qs, qseq, re - rs, tseq, mat, bw1, -1, extra_flag, ez); // second pass: lift approximate
  			if (ez->n_cigar > 0)
  				mm_append_cigar(r, ez->n_cigar, ez->cigar);
  			if (ez->zdropped) { // truncated by Z-drop; TODO: sometimes Z-drop kicks in because the next seed placement is wrong. This can be fixed in principle.
  				for (j = i - 1; j >= 0; --j)
  					if ((int32_t)a[as1 + j].x <= rs + ez->max_t)
  						break;
  				dropped = 1;
  				if (j < 0) j = 0;
  				r->p->dp_score += ez->max;
  				re1 = rs + (ez->max_t + 1);
  				qe1 = qs + (ez->max_q + 1);
  				if (cnt1 - (j + 1) >= opt->min_cnt)
  					mm_split_reg(r, r2, as1 + j + 1 - r->as, qlen, a);
  				break;
  			} else r->p->dp_score += ez->score;
  			rs = re, qs = qe;
  		}
  	}
  
  	if (!dropped && qe < qe0 && re < re0) { // right extension
  		qseq = &qseq0[rev][qe];
  		mm_idx_getseq(mi, rid, re, re0, tseq);
  		mm_align_pair(km, opt, qe0 - qe, qseq, re0 - re, tseq, mat, bw, opt->end_bonus, extra_flag|KSW_EZ_EXTZ_ONLY, ez);
  		if (ez->n_cigar > 0) {
  			mm_append_cigar(r, ez->n_cigar, ez->cigar);
  			r->p->dp_score += ez->max;
  		}
  		re1 = re + (ez->reach_end? ez->mqe_t + 1 : ez->max_t + 1);
  		qe1 = qe + (ez->reach_end? qe0 - qe : ez->max_q + 1);
  	}
  	assert(qe1 <= qlen);
  
  	r->rs = rs1, r->re = re1;
  	if (rev) r->qs = qlen - qe1, r->qe = qlen - qs1;
  	else r->qs = qs1, r->qe = qe1;
  
  	assert(re1 - rs1 <= re0 - rs0);
  	if (r->p) {
  		mm_idx_getseq(mi, rid, rs1, re1, tseq);
  		mm_update_extra(r, &qseq0[r->rev][qs1], tseq, mat, opt->q, opt->e);
  		if (rev && r->p->trans_strand)
  			r->p->trans_strand ^= 3; // flip to the read strand
  	}
  
  	kfree(km, tseq);
  }
  
  static int mm_align1_inv(void *km, const mm_mapopt_t *opt, const mm_idx_t *mi, int qlen, uint8_t *qseq0[2], const mm_reg1_t *r1, const mm_reg1_t *r2, mm_reg1_t *r_inv, ksw_extz_t *ez)
  {
  	int tl, ql, score, ret = 0, q_off, t_off;
  	uint8_t *tseq, *qseq;
  	int8_t mat[25];
  	void *qp;
  
  	memset(r_inv, 0, sizeof(mm_reg1_t));
  	if (!(r1->split&1) || !(r2->split&2)) return 0;
  	if (r1->id != r1->parent && r1->parent != MM_PARENT_TMP_PRI) return 0;
  	if (r2->id != r2->parent && r2->parent != MM_PARENT_TMP_PRI) return 0;
  	if (r1->rid != r2->rid || r1->rev != r2->rev) return 0;
  	ql = r2->qs - r1->qe;
  	tl = r2->rs - r1->re;
  	if (ql < opt->min_chain_score || ql > opt->max_gap) return 0;
  	if (tl < opt->min_chain_score || tl > opt->max_gap) return 0;
  
  	ksw_gen_simple_mat(5, mat, opt->a, opt->b);
  	tseq = (uint8_t*)kmalloc(km, tl);
  	mm_idx_getseq(mi, r1->rid, r1->re, r2->rs, tseq);
  	qseq = &qseq0[!r1->rev][qlen - r2->qs];
  
  	mm_seq_rev(ql, qseq);
  	mm_seq_rev(tl, tseq);
  	qp = ksw_ll_qinit(km, 2, ql, qseq, 5, mat);
  	score = ksw_ll_i16(qp, tl, tseq, opt->q, opt->e, &q_off, &t_off);
  	kfree(km, qp);
  	mm_seq_rev(ql, qseq);
  	mm_seq_rev(tl, tseq);
  	if (score < opt->min_dp_max) goto end_align1_inv;
  	q_off = ql - (q_off + 1), t_off = tl - (t_off + 1);
  	mm_align_pair(km, opt, ql - q_off, qseq + q_off, tl - t_off, tseq + t_off, mat, (int)(opt->bw * 1.5), -1, KSW_EZ_EXTZ_ONLY, ez);
  	if (ez->n_cigar == 0) goto end_align1_inv; // should never be here
  	mm_append_cigar(r_inv, ez->n_cigar, ez->cigar);
  	r_inv->p->dp_score = ez->max;
  	r_inv->id = -1;
  	r_inv->parent = MM_PARENT_UNSET;
  	r_inv->inv = 1;
  	r_inv->rev = !r1->rev;
  	r_inv->rid = r1->rid;
  	r_inv->div = -1.0f;
  	r_inv->qs = r1->qe + q_off, r_inv->qe = r_inv->qs + ez->max_q + 1;
  	r_inv->rs = r1->re + t_off, r_inv->re = r_inv->rs + ez->max_t + 1;
  	mm_update_extra(r_inv, &qseq[q_off], &tseq[t_off], mat, opt->q, opt->e);
  	ret = 1;
  end_align1_inv:
  	kfree(km, tseq);
  	return ret;
  }
  
  static inline mm_reg1_t *mm_insert_reg(const mm_reg1_t *r, int i, int *n_regs, mm_reg1_t *regs)
  {
  	regs = (mm_reg1_t*)realloc(regs, (*n_regs + 1) * sizeof(mm_reg1_t));
  	if (i + 1 != *n_regs)
  		memmove(&regs[i + 2], &regs[i + 1], sizeof(mm_reg1_t) * (*n_regs - i - 1));
  	regs[i + 1] = *r;
  	++*n_regs;
  	return regs;
  }
  
  mm_reg1_t *mm_align_skeleton(void *km, const mm_mapopt_t *opt, const mm_idx_t *mi, int qlen, const char *qstr, int *n_regs_, mm_reg1_t *regs, mm128_t *a)
  {
  	extern unsigned char seq_nt4_table[256];
  	int32_t i, n_regs = *n_regs_, n_a;
  	uint8_t *qseq0[2];
  	ksw_extz_t ez;
  
  	// encode the query sequence
  	qseq0[0] = (uint8_t*)kmalloc(km, qlen * 2);
  	qseq0[1] = qseq0[0] + qlen;
  	for (i = 0; i < qlen; ++i) {
  		qseq0[0][i] = seq_nt4_table[(uint8_t)qstr[i]];
  		qseq0[1][qlen - 1 - i] = qseq0[0][i] < 4? 3 - qseq0[0][i] : 4;
  	}
  
  	// align through seed hits
  	n_a = mm_squeeze_a(km, n_regs, regs, a);
  	memset(&ez, 0, sizeof(ksw_extz_t));
  	for (i = 0; i < n_regs; ++i) {
  		mm_reg1_t r2;
  		if ((opt->flag&MM_F_SPLICE) && (opt->flag&MM_F_SPLICE_FOR) && (opt->flag&MM_F_SPLICE_REV)) { // then do two rounds of alignments for both strands
  			mm_reg1_t s[2], s2[2];
  			int which, trans_strand;
  			s[0] = s[1] = regs[i];
  			mm_align1(km, opt, mi, qlen, qseq0, &s[0], &s2[0], n_a, a, &ez, MM_F_SPLICE_FOR);
  			mm_align1(km, opt, mi, qlen, qseq0, &s[1], &s2[1], n_a, a, &ez, MM_F_SPLICE_REV);
  			if (s[0].p->dp_score > s[1].p->dp_score) which = 0, trans_strand = 1;
  			else if (s[0].p->dp_score < s[1].p->dp_score) which = 1, trans_strand = 2;
  			else trans_strand = 3, which = (qlen + s[0].p->dp_score) & 1; // randomly choose a strand, effectively
  			if (which == 0) {
  				regs[i] = s[0], r2 = s2[0];
  				free(s[1].p);
  			} else {
  				regs[i] = s[1], r2 = s2[1];
  				free(s[0].p);
  			}
  			regs[i].p->trans_strand = trans_strand;
  		} else { // one round of alignment
  			mm_align1(km, opt, mi, qlen, qseq0, &regs[i], &r2, n_a, a, &ez, opt->flag);
  			if (opt->flag&MM_F_SPLICE)
  				regs[i].p->trans_strand = opt->flag&MM_F_SPLICE_FOR? 1 : 2;
  		}
  		if (r2.cnt > 0) regs = mm_insert_reg(&r2, i, &n_regs, regs);
  		if (!(opt->flag&MM_F_SPLICE) && !(opt->flag&MM_F_SR) && i > 0) { // don't try inversion alignment for -xsplice or -xsr
  			if (mm_align1_inv(km, opt, mi, qlen, qseq0, &regs[i-1], &regs[i], &r2, &ez)) {
  				regs = mm_insert_reg(&r2, i, &n_regs, regs);
  				++i; // skip the inserted INV alignment
  			}
  		}
  	}
  	*n_regs_ = n_regs;
  	kfree(km, qseq0[0]);
  	kfree(km, ez.cigar);
  	mm_filter_regs(km, opt, n_regs_, regs);
  	mm_hit_sort_by_dp(km, n_regs_, regs);
  	return regs;
  }
  