fast-bwa/bwt.c

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/* 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); // bwt中不包含$所以位置超过序列长度后要减掉1因为后边加上了互补链
// x = bwt_B0(bwt, x); // 获取x位置对应的字符
uint32_t t1 = (bwt->bwt[((x) >> 7 << 4) + sizeof(bwtint_t) + (((x) & 0x7f) >> 4)]);
uint32_t t2 = t1 >> ((~(x) & 0xf) << 1) & 3;
x = t2;
x = bwt->L2[x] + bwt_occ(bwt, k, x); // 获取x字符在k位置后缀索引
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 << 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;
}
// bwt->bwt and bwt->occ must be precalculated
void bwt_cal_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->sa) free(bwt->sa);
bwt->sa_intv = intv;
bwt->n_sa = (bwt->seq_len + intv) / intv;
bwt->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->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->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->sa, isa / intv, sa);
bwt_set_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);
}
/* without setting bwt->sa[0] = -1, the following line should be
changed to (sa + bwt->sa[k/bwt->sa_intv]) % (bwt->seq_len + 1) */
#ifdef SHOW_PERF
int64_t tmp_time = realtime_msec();
#endif
sa += bwt_get_sa(bwt->sa, k / bwt->sa_intv);
#ifdef SHOW_PERF
tmp_time = realtime_msec() - tmp_time;
__sync_fetch_and_add(&time_bwt_sa_read, tmp_time);
#endif
return sa;
}
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];
}
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smemseed
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, ok[4];
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, c;
bwtintv_t ik, ok[4];
memset(mem, 0, sizeof(bwtintv_t));
if (q[x] > 3) return x + 1;
bwt_set_intv(bwt, q[x], ik); // the initial interval of a single base
for (i = x + 1; 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, sizeof(bwtint_t), SA_BYTES(bwt->n_sa) >> 3, fp);
err_fflush(fp);
err_fclose(fp);
}
static bwtint_t fread_fix(FILE *fp, bwtint_t size, void *a)
{ // Mac/Darwin has a bug when reading data longer than 2GB. This function fixes this issue by reading data in small chunks
const int bufsize = 0x1000000; // 16M block
bwtint_t offset = 0;
while (size) {
int x = bufsize < size? bufsize : size;
if ((x = err_fread_noeof(a + offset, 1, x, fp)) == 0) break;
size -= x; offset += x;
}
return offset;
}
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 = (uint8_t*)malloc(SA_BYTES(bwt->n_sa));
fread_fix(fp, SA_BYTES(bwt->n_sa), bwt->sa);
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);
}