fast-bwa/bwt.c

/* The MIT License

   Copyright (c) 2008 Genome Research Ltd (GRL).

   Permission is hereby granted, free of charge, to any person obtaining
   a copy of this software and associated documentation files (the
   "Software"), to deal in the Software without restriction, including
   without limitation the rights to use, copy, modify, merge, publish,
   distribute, sublicense, and/or sell copies of the Software, and to
   permit persons to whom the Software is furnished to do so, subject to
   the following conditions:

   The above copyright notice and this permission notice shall be
   included in all copies or substantial portions of the Software.

   THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
   EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF
   MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND
   NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS
   BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN
   ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN
   CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE
   SOFTWARE.
*/

/* Contact: Heng Li <lh3@sanger.ac.uk> */

#include <stdlib.h>
#include <stdio.h>
#include <string.h>
#include <assert.h>
#include <stdint.h>
#include <limits.h>
#include "utils.h"
#include "bwt.h"
#include "kvec.h"

#ifdef USE_MALLOC_WRAPPERS
#  include "malloc_wrap.h"
#endif

// 计算一个字节构成的A,T,C,G序列，对应的每个碱基的个数，因为最多有4个相同的碱基，所以每次左移3位就行
void bwt_gen_cnt_table(bwt_t *bwt)
{
	int i, j;
	for (i = 0; i != 256; ++i) {
		uint32_t x = 0;
		for (j = 0; j != 4; ++j)
			x |= (((i&3) == j) + ((i>>2&3) == j) + ((i>>4&3) == j) + (i>>6 == j)) << (j<<3);
		bwt->cnt_table[i] = x;
	}
}

static inline bwtint_t bwt_invPsi(const bwt_t *bwt, bwtint_t k) // compute inverse CSA
{
	bwtint_t x = k - (k > bwt->primary);
	x = bwt_B0(bwt, x);
	x = bwt->L2[x] + bwt_occ(bwt, k, x);
	return k == bwt->primary ? 0 : x;
}

// 设置某一行的排序值，sa的索引有效值从1开始，（0设置为-1, 小端模式）
void inline bwt_set_sa(uint8_t *sa_arr, bwtint_t k, bwtint_t val)
{
	const bwtint_t block_idx = (k >> 3) * 33; // 8个数为一组，共享33个字节
	const int val_idx_in_block = k & 7;
	const bwtint_t start_byte_idx = block_idx + (val_idx_in_block << 2);
	bwtint_t *sa_addr = (bwtint_t *)(sa_arr + start_byte_idx);
	// *sa_addr &= (1 << val_idx_in_block) - 1; // 如果开辟内存的时候清零了，这一步可以省略，会清除后面的数据，只适合按递增顺序赋值
	*sa_addr |= (val & ((1L << 33) - 1)) << val_idx_in_block;
}

// 获取某一行的排序值（小端模式）
bwtint_t bwt_get_sa(uint8_t *sa_arr, bwtint_t k)
{
	const bwtint_t block_idx = (k >> 3) * 33; // 8个数为一组，共享33个字节
	const int val_idx_in_block = k & 7;
	const bwtint_t start_byte_idx = block_idx + (val_idx_in_block << 2);
	bwtint_t val = *(bwtint_t *)(sa_arr + start_byte_idx);
	val = (val >> val_idx_in_block) & 8589934591;
	return val;
}

// 获取kmer的fmt匹配信息
inline void kmer_getval_at(uint8_t *mem_addr, bwtintv_t *ok, int pos)
{
	bwtint_t x0, x1, x2;
	int byte_idx = pos * 14;
	uint8_t *arr = mem_addr + byte_idx;
	x0 = *arr;
	x0 = (x0 << 32) | *((uint32_t *)(arr + 1));
	arr += 5;
	x1 = *arr;
	x1 = (x1 << 32) | *((uint32_t *)(arr + 1));
	arr += 5;
	x2 = *((uint32_t *)arr);
	ok->x[0] = x0;
	ok->x[1] = x1;
	ok->x[2] = x2;
}

// 设置kmer第pos个碱基对应的fmt匹配信息
inline void kmer_setval_at(uint8_t *mem_addr, bwtintv_t ik, int pos)
{
	int byte_idx = pos * 14;
	uint8_t *arr = mem_addr + byte_idx;
	arr[0] = (uint8_t)(ik.x[0] >> 32);
	*((uint32_t *)(arr + 1)) = (uint32_t)ik.x[0];
	arr += 5;
	arr[0] = (uint8_t)(ik.x[1] >> 32);
	*((uint32_t *)(arr + 1)) = (uint32_t)ik.x[1];
	arr += 5;
	*((uint32_t *)arr) = (uint32_t)ik.x[2];
}

// 获取kmer对应的fmt匹配信息, pos should be [0, 13]
inline void bwt_kmer_get(const KmerHash *kmer_hash, bwtintv_t *ok, uint32_t qbit, int pos)
{
#if HASH_KMER_LEN == 14
	if (pos == 13)
		kmer_getval_at(kmer_hash->ke14[qbit].intv_arr, ok, 0);
	else if (pos == 12)
		kmer_getval_at(kmer_hash->ke13[qbit >> 2].intv_arr, ok, 0);
	else if (pos == 11)
		kmer_getval_at(kmer_hash->ke12[qbit >> 4].intv_arr, ok, 0);
	else if (pos == 10)
		kmer_getval_at(kmer_hash->ke11[qbit >> 6].intv_arr, ok, 0);
	else
		kmer_getval_at(kmer_hash->ke10[qbit >> 8].intv_arr, ok, pos);
#elif HASH_KMER_LEN == 13
	if (pos == 12)
		kmer_getval_at(kmer_hash->ke13[qbit].intv_arr, ok, 0);
	else if (pos == 11)
		kmer_getval_at(kmer_hash->ke12[qbit >> 2].intv_arr, ok, 0);
	else if (pos == 10)
		kmer_getval_at(kmer_hash->ke11[qbit >> 4].intv_arr, ok, 0);
	else
		kmer_getval_at(kmer_hash->ke10[qbit >> 6].intv_arr, ok, pos);
#else
	if (pos == 11)
		kmer_getval_at(kmer_hash->ke12[qbit].intv_arr, ok, 0);
	else if (pos == 10)
		kmer_getval_at(kmer_hash->ke11[qbit >> 2].intv_arr, ok, 0);
	else 
		kmer_getval_at(kmer_hash->ke10[qbit >> 4].intv_arr, ok, pos);
#endif
}

// bwt->bwt and bwt->occ must be precalculated
void bwt_cal_byte_sa(bwt_t *bwt, int intv)
{
	bwtint_t isa, sa, i, block_size; // S(isa) = sa isa是后缀数组的索引，sa表示位置
	double tmp_time, elapsed_time;
	int intv_round = intv; // 间隔多少来保存一个位置信息

	kv_roundup32(intv_round);
	xassert(intv_round == intv, "SA sample interval is not a power of 2.");
	xassert(bwt->bwt, "bwt_t::bwt is not initialized.");

	if (bwt->byte_sa) free(bwt->byte_sa);
	bwt->sa_intv = intv;
	bwt->n_sa = (bwt->seq_len + intv) / intv;
	bwt->byte_sa = (uint8_t *)calloc(SA_BYTES(bwt->n_sa), 1); // 用33位表示位置
	fprintf(stderr, "bytes: %ld, sa size: %ld\n", SA_BYTES(bwt->n_sa), bwt->n_sa);
	// calculate SA value
	isa = 0; sa = bwt->seq_len;
	block_size = bwt->seq_len / 100;
	tmp_time = realtime();
	for (i = 0; i < bwt->seq_len; ++i)
	{
		if (i % block_size == 0) {
			elapsed_time = realtime() - tmp_time;
			fprintf(stderr, "%ld%% percent complished. %f s elapsed.\n", i / block_size, elapsed_time);
		}
		if (isa % intv == 0) {
			bwt_set_sa(bwt->byte_sa, isa / intv, sa); // 第一个位置是$，所以位置就是序列长度
			if (i % (block_size / 2) == 0)
			{
				fprintf(stderr, "%ld    %ld\n", sa, bwt_get_sa(bwt->byte_sa, isa / intv));
			}
		}
		--sa; // 从后往前，一个位置一个位置的找对应的后缀数组，isa就是与sa对应的后缀数组排序后在sa数组中的相对位置
		isa = bwt_invPsi(bwt, isa); // 下一个后缀数组的相对位置
	}
	if (isa % intv == 0) bwt_set_sa(bwt->byte_sa, isa / intv, sa);
	// bwt_set_sa(bwt->byte_sa, 0, (bwtint_t)-1); // 赋值成-1也没问题，set_sa那里已经修正了
	bwt_set_sa(bwt->byte_sa, 0, 8589934591); // before this line, bwt->sa[0] = bwt->seq_len
}

// bwt->bwt and bwt->occ must be precalculated
void bwt_cal_sa(bwt_t *bwt, int intv)
{
	bwtint_t isa, sa, i; // S(isa) = sa
	int intv_round = intv;

	kv_roundup32(intv_round);
	xassert(intv_round == intv, "SA sample interval is not a power of 2.");
	xassert(bwt->bwt, "bwt_t::bwt is not initialized.");

	if (bwt->sa) free(bwt->sa);
	bwt->sa_intv = intv;
	bwt->n_sa = (bwt->seq_len + intv) / intv;
	bwt->sa = (bwtint_t*)calloc(bwt->n_sa, sizeof(bwtint_t));
	// calculate SA value
	isa = 0; sa = bwt->seq_len;
	for (i = 0; i < bwt->seq_len; ++i) {
		if (isa % intv == 0) bwt->sa[isa/intv] = sa;
		--sa;
		isa = bwt_invPsi(bwt, isa);
	}
	if (isa % intv == 0) bwt->sa[isa/intv] = sa;
	bwt->sa[0] = (bwtint_t)-1; // before this line, bwt->sa[0] = bwt->seq_len
}

bwtint_t bwt_sa(const bwt_t *bwt, bwtint_t k)
{
	bwtint_t sa = 0, mask = bwt->sa_intv - 1;
	while (k & mask) {
		++sa;
		k = bwt_invPsi(bwt, k);
	}
	return sa + bwt->sa[k / bwt->sa_intv];
}

static inline int __occ_aux(uint64_t y, int c)
{
	// reduce nucleotide counting to bits counting
	y = ((c&2)? y : ~y) >> 1 & ((c&1)? y : ~y) & 0x5555555555555555ull;
	// count the number of 1s in y
	y = (y & 0x3333333333333333ull) + (y >> 2 & 0x3333333333333333ull);
	return ((y + (y >> 4)) & 0xf0f0f0f0f0f0f0full) * 0x101010101010101ull >> 56;
}

bwtint_t bwt_occ(const bwt_t *bwt, bwtint_t k, ubyte_t c)
{
	bwtint_t n;
	uint32_t *p, *end;

	if (k == bwt->seq_len) return bwt->L2[c+1] - bwt->L2[c];
	if (k == (bwtint_t)(-1)) return 0;
	k -= (k >= bwt->primary); // because $ is not in bwt

	// retrieve Occ at k/OCC_INTERVAL
	n = ((bwtint_t*)(p = bwt_occ_intv(bwt, k)))[c];
	p += sizeof(bwtint_t); // jump to the start of the first BWT cell

	// calculate Occ up to the last k/32
	end = p + (((k>>5) - ((k&~OCC_INTV_MASK)>>5))<<1);
	for (; p < end; p += 2) n += __occ_aux((uint64_t)p[0]<<32 | p[1], c);

	// calculate Occ
	n += __occ_aux(((uint64_t)p[0]<<32 | p[1]) & ~((1ull<<((~k&31)<<1)) - 1), c);
	if (c == 0) n -= ~k&31; // corrected for the masked bits

	return n;
}

// an analogy to bwt_occ() but more efficient, requiring k <= l
void bwt_2occ(const bwt_t *bwt, bwtint_t k, bwtint_t l, ubyte_t c, bwtint_t *ok, bwtint_t *ol)
{
	bwtint_t _k, _l;
	_k = (k >= bwt->primary)? k-1 : k;
	_l = (l >= bwt->primary)? l-1 : l;
	if (_l/OCC_INTERVAL != _k/OCC_INTERVAL || k == (bwtint_t)(-1) || l == (bwtint_t)(-1)) {
		*ok = bwt_occ(bwt, k, c);
		*ol = bwt_occ(bwt, l, c);
	} else {
		bwtint_t m, n, i, j;
		uint32_t *p;
		if (k >= bwt->primary) --k;
		if (l >= bwt->primary) --l;
		n = ((bwtint_t*)(p = bwt_occ_intv(bwt, k)))[c];
		p += sizeof(bwtint_t);
		// calculate *ok
		j = k >> 5 << 5;
		for (i = k/OCC_INTERVAL*OCC_INTERVAL; i < j; i += 32, p += 2)
			n += __occ_aux((uint64_t)p[0]<<32 | p[1], c);
		m = n;
		n += __occ_aux(((uint64_t)p[0]<<32 | p[1]) & ~((1ull<<((~k&31)<<1)) - 1), c);
		if (c == 0) n -= ~k&31; // corrected for the masked bits
		*ok = n;
		// calculate *ol
		j = l >> 5 << 5;
		for (; i < j; i += 32, p += 2)
			m += __occ_aux((uint64_t)p[0]<<32 | p[1], c);
		m += __occ_aux(((uint64_t)p[0]<<32 | p[1]) & ~((1ull<<((~l&31)<<1)) - 1), c);
		if (c == 0) m -= ~l&31; // corrected for the masked bits
		*ol = m;
	}
}

#define __occ_aux4(bwt, b)											\
	((bwt)->cnt_table[(b)&0xff] + (bwt)->cnt_table[(b)>>8&0xff]		\
	 + (bwt)->cnt_table[(b)>>16&0xff] + (bwt)->cnt_table[(b)>>24])

void bwt_occ4(const bwt_t *bwt, bwtint_t k, bwtint_t cnt[4])
{
	bwtint_t x;
	uint32_t *p, tmp, *end;
	if (k == (bwtint_t)(-1)) {
		memset(cnt, 0, 4 * sizeof(bwtint_t));
		return;
	}
	k -= (k >= bwt->primary); // because $ is not in bwt
	p = bwt_occ_intv(bwt, k);
	memcpy(cnt, p, 4 * sizeof(bwtint_t));
	p += sizeof(bwtint_t); // sizeof(bwtint_t) = 4*(sizeof(bwtint_t)/sizeof(uint32_t))
	end = p + ((k>>4) - ((k&~OCC_INTV_MASK)>>4)); // this is the end point of the following loop
	for (x = 0; p < end; ++p) x += __occ_aux4(bwt, *p);
	tmp = *p & ~((1U<<((~k&15)<<1)) - 1);
	x += __occ_aux4(bwt, tmp) - (~k&15);
	cnt[0] += x&0xff; cnt[1] += x>>8&0xff; cnt[2] += x>>16&0xff; cnt[3] += x>>24;
}

// an analogy to bwt_occ4() but more efficient, requiring k <= l
void bwt_2occ4(const bwt_t *bwt, bwtint_t k, bwtint_t l, bwtint_t cntk[4], bwtint_t cntl[4])
{
	bwtint_t _k, _l;
	_k = k - (k >= bwt->primary);
	_l = l - (l >= bwt->primary);
	if (_l>>OCC_INTV_SHIFT != _k>>OCC_INTV_SHIFT || k == (bwtint_t)(-1) || l == (bwtint_t)(-1)) {
		bwt_occ4(bwt, k, cntk);
		bwt_occ4(bwt, l, cntl);
	} else {
		bwtint_t x, y;
		uint32_t *p, tmp, *endk, *endl;
		k -= (k >= bwt->primary); // because $ is not in bwt
		l -= (l >= bwt->primary);
		p = bwt_occ_intv(bwt, k);
		memcpy(cntk, p, 4 * sizeof(bwtint_t));
		p += sizeof(bwtint_t); // sizeof(bwtint_t) = 4*(sizeof(bwtint_t)/sizeof(uint32_t))
		// prepare cntk[]
		endk = p + ((k>>4) - ((k&~OCC_INTV_MASK)>>4));
		endl = p + ((l>>4) - ((l&~OCC_INTV_MASK)>>4));
		for (x = 0; p < endk; ++p) x += __occ_aux4(bwt, *p);
		y = x;
		tmp = *p & ~((1U<<((~k&15)<<1)) - 1);
		x += __occ_aux4(bwt, tmp) - (~k&15);
		// calculate cntl[] and finalize cntk[]
		for (; p < endl; ++p) y += __occ_aux4(bwt, *p);
		tmp = *p & ~((1U<<((~l&15)<<1)) - 1);
		y += __occ_aux4(bwt, tmp) - (~l&15);
		memcpy(cntl, cntk, 4 * sizeof(bwtint_t));
		cntk[0] += x&0xff; cntk[1] += x>>8&0xff; cntk[2] += x>>16&0xff; cntk[3] += x>>24;
		cntl[0] += y&0xff; cntl[1] += y>>8&0xff; cntl[2] += y>>16&0xff; cntl[3] += y>>24;
	}
}

int bwt_match_exact(const bwt_t *bwt, int len, const ubyte_t *str, bwtint_t *sa_begin, bwtint_t *sa_end)
{
	bwtint_t k, l, ok, ol;
	int i;
	k = 0; l = bwt->seq_len;
	for (i = len - 1; i >= 0; --i) {
		ubyte_t c = str[i];
		if (c > 3) return 0; // no match
		bwt_2occ(bwt, k - 1, l, c, &ok, &ol);
		k = bwt->L2[c] + ok + 1;
		l = bwt->L2[c] + ol;
		if (k > l) break; // no match
	}
	if (k > l) return 0; // no match
	if (sa_begin) *sa_begin = k;
	if (sa_end)   *sa_end = l;
	return l - k + 1;
}

int bwt_match_exact_alt(const bwt_t *bwt, int len, const ubyte_t *str, bwtint_t *k0, bwtint_t *l0)
{
	int i;
	bwtint_t k, l, ok, ol;
	k = *k0; l = *l0;
	for (i = len - 1; i >= 0; --i) {
		ubyte_t c = str[i];
		if (c > 3) return 0; // there is an N here. no match
		bwt_2occ(bwt, k - 1, l, c, &ok, &ol);
		k = bwt->L2[c] + ok + 1;
		l = bwt->L2[c] + ol;
		if (k > l) return 0; // no match
	}
	*k0 = k; *l0 = l;
	return l - k + 1;
}

/*********************
 * Bidirectional BWT *
 *********************/

void bwt_extend(const bwt_t *bwt, const bwtintv_t *ik, bwtintv_t ok[4], int is_back)
{
	bwtint_t tk[4], tl[4];
	int i;
	bwt_2occ4(bwt, ik->x[!is_back] - 1, ik->x[!is_back] - 1 + ik->x[2], tk, tl);
	for (i = 0; i != 4; ++i) {
		ok[i].x[!is_back] = bwt->L2[i] + 1 + tk[i];
		ok[i].x[2] = tl[i] - tk[i];
	}
	ok[3].x[is_back] = ik->x[is_back] + (ik->x[!is_back] <= bwt->primary && ik->x[!is_back] + ik->x[2] - 1 >= bwt->primary);
	ok[2].x[is_back] = ok[3].x[is_back] + ok[3].x[2];
	ok[1].x[is_back] = ok[2].x[is_back] + ok[2].x[2];
	ok[0].x[is_back] = ok[1].x[is_back] + ok[1].x[2];
}

// 创建正向的kmer
inline uint64_t build_forward_kmer(const uint8_t *q, int qlen, int kmer_len, int *base_consumed)
{
	uint64_t qbit = 0, i;
    qlen = qlen < kmer_len ? qlen : kmer_len;
    for (i = 0; i < qlen; ++i) {
        if (q[i] > 3) break; // 要考虑碱基是N 
        qbit |= (uint64_t)q[i] << ((kmer_len - 1 - i) << 1);
    }
    *base_consumed = i;
    return qbit;
}

// 创建f反向的kmer
inline uint64_t build_backward_kmer(const uint8_t *q, int start_pos, int kmer_len, int *base_consumed)
{
	uint64_t qbit = 0;
	int i, j, end_pos;
	end_pos = start_pos - kmer_len;
	end_pos = end_pos < 0 ? -1 : end_pos;
	for (i = start_pos, j = 0; i > end_pos; --i, ++j) {
		if (q[i] > 3) break; // 要考虑碱基是N
		qbit |= (uint64_t)q[i] << ((kmer_len - 1 - j) << 1);
	}
	*base_consumed = start_pos - i;
	return (~qbit) & ((1L << (kmer_len << 1)) - 1);
}

static void bwt_reverse_intvs(bwtintv_v *p)
{
	if (p->n > 1) {
		int j;
		for (j = 0; j < p->n>>1; ++j) {
			bwtintv_t tmp = p->a[p->n - 1 - j];
			p->a[p->n - 1 - j] = p->a[j];
			p->a[j] = tmp;
		}
	}
}
// NOTE: $max_intv is not currently used in BWA-MEM
// 找smem（seed）
int bwt_smem1a(const bwt_t *bwt, int len, const uint8_t *q, int x, int min_intv, uint64_t max_intv, bwtintv_v *mem, bwtintv_v *tmpvec[2])
{
	int i, j, c, ret;
	bwtintv_t ik = {0}, ok[4] = {0};
	bwtintv_v a[2], *prev, *curr, *swap;

	mem->n = 0;
	if (q[x] > 3) return x + 1;
	if (min_intv < 1) min_intv = 1; // the interval size should be at least 1
	kv_init(a[0]); kv_init(a[1]);
	prev = tmpvec && tmpvec[0]? tmpvec[0] : &a[0]; // use the temporary vector if provided
	curr = tmpvec && tmpvec[1]? tmpvec[1] : &a[1];
	bwt_set_intv(bwt, q[x], ik); // the initial interval of a single base
	ik.info = x + 1;

	for (i = x + 1, curr->n = 0; i < len; ++i)
	{ // forward search
		if (ik.x[2] < max_intv) { // an interval small enough
			kv_push(bwtintv_t, *curr, ik);
			break;
		} else if (q[i] < 4) { // an A/C/G/T base
			c = 3 - q[i]; // complement of q[i]

			bwt_extend(bwt, &ik, ok, 0);
			if (ok[c].x[2] != ik.x[2]) { // change of the interval size
				kv_push(bwtintv_t, *curr, ik);
				if (ok[c].x[2] < min_intv) break; // the interval size is too small to be extended further
			}
			ik = ok[c]; ik.info = i + 1;
		} else { // an ambiguous base
			kv_push(bwtintv_t, *curr, ik);
			break; // always terminate extension at an ambiguous base; in this case, i<len always stands
		}
	}

	if (i == len) kv_push(bwtintv_t, *curr, ik); // push the last interval if we reach the end
	bwt_reverse_intvs(curr); // s.t. smaller intervals (i.e. longer matches) visited first
	ret = curr->a[0].info; // this will be the returned value
	swap = curr; curr = prev; prev = swap;

	for (i = x - 1; i >= -1; --i) { // backward search for MEMs
		c = i < 0? -1 : q[i] < 4? q[i] : -1; // c==-1 if i<0 or q[i] is an ambiguous base
		for (j = 0, curr->n = 0; j < prev->n; ++j) {
			bwtintv_t *p = &prev->a[j];
			if (c >= 0 && ik.x[2] >= max_intv) bwt_extend(bwt, p, ok, 1);
			if (c < 0 || ik.x[2] < max_intv || ok[c].x[2] < min_intv) { // keep the hit if reaching the beginning or an ambiguous base or the intv is small enough
				if (curr->n == 0) { // test curr->n>0 to make sure there are no longer matches
					if (mem->n == 0 || i + 1 < mem->a[mem->n-1].info>>32) { // skip contained matches
						ik = *p; ik.info |= (uint64_t)(i + 1)<<32;
						kv_push(bwtintv_t, *mem, ik);
					}
				} // otherwise the match is contained in another longer match
			} else if (curr->n == 0 || ok[c].x[2] != curr->a[curr->n-1].x[2]) {
				ok[c].info = p->info;
				kv_push(bwtintv_t, *curr, ok[c]);
			}
		}
		if (curr->n == 0) break;
		swap = curr; curr = prev; prev = swap;
	}
	bwt_reverse_intvs(mem); // s.t. sorted by the start coordinate

	if (tmpvec == 0 || tmpvec[0] == 0) free(a[0].a);
	if (tmpvec == 0 || tmpvec[1] == 0) free(a[1].a);
	return ret;
}

int bwt_smem1(const bwt_t *bwt, int len, const uint8_t *q, int x, int min_intv, bwtintv_v *mem, bwtintv_v *tmpvec[2])
{
	return bwt_smem1a(bwt, len, q, x, min_intv, 0, mem, tmpvec);
}

int bwt_seed_strategy1(const bwt_t *bwt, int len, const uint8_t *q, int x, int min_len, int max_intv, bwtintv_t *mem)
{
	int i = x + 1, c, kmer_len;
	bwtintv_t ik = {0}, ok[4] = {0};

	memset(mem, 0, sizeof(bwtintv_t));
	if (q[x] > 3) return x + 1;

	uint32_t qbit = build_forward_kmer(&q[x], len - x, HASH_KMER_LEN, &kmer_len);
	bwt_kmer_get(&bwt->kmer_hash, &ik, qbit, kmer_len - 1);
	ik.info = x + kmer_len;
	i = (int)ik.info;

	//bwt_set_intv(bwt, q[x], ik); // the initial interval of a single base
	//i = x + 1;

	for (; i < len; ++i) { // forward search
		if (q[i] < 4) { // an A/C/G/T base
			c = 3 - q[i]; // complement of q[i]
			bwt_extend(bwt, &ik, ok, 0);
			if (ok[c].x[2] < max_intv && i - x >= min_len) {
				*mem = ok[c];
				mem->info = (uint64_t)x<<32 | (i + 1);
				return i + 1;
			}
			ik = ok[c];
		} else return i + 1;
	}
	return len;
}

/*************************
 * Read/write BWT and SA *
 *************************/

void bwt_dump_bwt(const char *fn, const bwt_t *bwt)
{
	FILE *fp;
	fp = xopen(fn, "wb");
	err_fwrite(&bwt->primary, sizeof(bwtint_t), 1, fp);
	err_fwrite(bwt->L2+1, sizeof(bwtint_t), 4, fp);
	err_fwrite(bwt->bwt, 4, bwt->bwt_size, fp);
	err_fflush(fp);
	err_fclose(fp);
}

void bwt_dump_sa(const char *fn, const bwt_t *bwt)
{
	FILE *fp;
	fp = xopen(fn, "wb");
	err_fwrite(&bwt->primary, sizeof(bwtint_t), 1, fp);
	err_fwrite(bwt->L2+1, sizeof(bwtint_t), 4, fp);
	err_fwrite(&bwt->sa_intv, sizeof(bwtint_t), 1, fp);
	err_fwrite(&bwt->seq_len, sizeof(bwtint_t), 1, fp);
	err_fwrite(bwt->sa + 1, sizeof(bwtint_t), bwt->n_sa - 1, fp);
	err_fflush(fp);
	err_fclose(fp);
}

void bwt_dump_byte_sa(const char *fn, const bwt_t *bwt)
{
	FILE *fp;
	fp = xopen(fn, "wb");
	err_fwrite(&bwt->primary, sizeof(bwtint_t), 1, fp);
	err_fwrite(bwt->L2 + 1, sizeof(bwtint_t), 4, fp);
	err_fwrite(&bwt->sa_intv, sizeof(bwtint_t), 1, fp);
	err_fwrite(&bwt->seq_len, sizeof(bwtint_t), 1, fp);
	err_fwrite(bwt->byte_sa, sizeof(bwtint_t), SA_BYTES(bwt->n_sa) >> 3, fp);
	err_fflush(fp);
	err_fclose(fp);
}

void bwt_restore_sa(const char *fn, bwt_t *bwt)
{
	char skipped[256];
	FILE *fp;
	bwtint_t primary;

	fp = xopen(fn, "rb");
	err_fread_noeof(&primary, sizeof(bwtint_t), 1, fp);
	xassert(primary == bwt->primary, "SA-BWT inconsistency: primary is not the same.");
	err_fread_noeof(skipped, sizeof(bwtint_t), 4, fp); // skip
	err_fread_noeof(&bwt->sa_intv, sizeof(bwtint_t), 1, fp);
	err_fread_noeof(&primary, sizeof(bwtint_t), 1, fp);
	xassert(primary == bwt->seq_len, "SA-BWT inconsistency: seq_len is not the same.");

	bwt->n_sa = (bwt->seq_len + bwt->sa_intv) / bwt->sa_intv;

	bwt->sa = (bwtint_t *)calloc(bwt->n_sa, sizeof(bwtint_t));
	bwt->sa[0] = -1;
	fread_fix(fp, sizeof(bwtint_t) * (bwt->n_sa - 1), bwt->sa + 1);

	err_fclose(fp);
}

bwt_t *bwt_restore_bwt(const char *fn)
{
	bwt_t *bwt;
	FILE *fp;

	bwt = (bwt_t*)calloc(1, sizeof(bwt_t));
	fp = xopen(fn, "rb");
	err_fseek(fp, 0, SEEK_END);
	bwt->bwt_size = (err_ftell(fp) - sizeof(bwtint_t) * 5) >> 2;
	bwt->bwt = (uint32_t*)calloc(bwt->bwt_size, 4);
	err_fseek(fp, 0, SEEK_SET);
	err_fread_noeof(&bwt->primary, sizeof(bwtint_t), 1, fp);
	err_fread_noeof(bwt->L2+1, sizeof(bwtint_t), 4, fp);
	fread_fix(fp, bwt->bwt_size<<2, bwt->bwt);
	bwt->seq_len = bwt->L2[4];
	err_fclose(fp);
	bwt_gen_cnt_table(bwt);

	return bwt;
}

void bwt_destroy(bwt_t *bwt)
{
	if (bwt == 0) return;
	free(bwt->sa); free(bwt->bwt);
	free(bwt);
}