#include #include #include #include #include #include #include #include #include #include #include "util.h" #include "bwt.h" #include "fmt_index.h" using namespace std; double t1 = 0, t2 = 0, t3 = 0, t4 = 0, t5 = 0, t6 = 0, t7 = 0, t8 = 0, t9 = 0, t10 = 0, t11 = 0, t12 = 0, t13 = 0, t14 = 0; long f1 = 0, f2 = 0, f3 = 0, f4 = 0, f5 = 0; const char BASE[4] = {'A', 'C', 'G', 'T'}; // 求反向互补序列 string calc_reverse_seq(string &seq) { string rseq(seq.size(), '0'); for (size_t i = 0; i < seq.size(); ++i) { if (seq[i] == 'A') rseq[i] = 'T'; else if (seq[i] == 'C') rseq[i] = 'G'; else if (seq[i] == 'G') rseq[i] = 'C'; else if (seq[i] == 'T') rseq[i] = 'A'; } std::reverse(rseq.begin(), rseq.end()); return rseq; } // 打印32位整型数据中包含的pre-bwt:bwt void print_base_uint32(uint32_t p) { for (int i = 30; i > 0; i -= 4) { int b1 = p >> i & 3; int b2 = p >> (i - 2) & 3; cout << BASE[b1] << BASE[b2] << endl; } } // 随机生成长度为len的序列 string generate_rand_seq(int len) { string seq(len, 'A'); for (int i = 0; i < len; ++i) { seq[i] = BASE[rand() % 4]; } return seq; } // 创建bwt矩阵 void create_bwt_mtx(string &seq) { bwtint_t seq_len = seq.size() + 1; string sarr[seq_len]; sarr[0] = seq + '$'; for (bwtint_t i = 1; i < seq_len; ++i) { sarr[i] = sarr[0].substr(i) + sarr[0].substr(0, i); } std::sort(sarr, sarr + seq_len); // print bwt matrix // for (int i = 0; i < seq_len; ++i) //{ // // cout << i << ' ' << sarr[i] << endl; // cout << sarr[i] << endl; //} // cout << "bwt string" << endl; // for (int i = 0; i < seq_len; ++i) // { // cout << sarr[i].back(); // } // cout << endl; // cout << "pre bwt string" << endl; // for (int i = 0; i < seq_len; ++i) // { // cout << sarr[i][seq_len - 2]; // } // cout << endl; } // 生成occ,每个字节对应一个pattern void fmt_gen_cnt_occ(FMTIndex *fmt) { // 0-8:大于a的occ,8-16:大于b的occ,16-24:b的occ int i, a, b, ti; uint32_t oa, ooa, ob, oob; for (i = 0; i != 256; ++i) // 遍历单个字节的各种情况 { for (a = 0; a < 4; ++a) // ba格式 { oa = 0; ooa = 0; oa += ((i >> 4 & 3) == a) + ((i & 3) == a); ooa += ((i >> 4 & 3) > a) + ((i & 3) > a); for (b = 0; b < 4; ++b) { oob = ob = 0; oob += ((i >> 6 & 3) > b && (i >> 4 & 3) == a) + ((i >> 2 & 3) > b && (i & 3) == a); ob += ((i >> 6 & 3) == b && (i >> 4 & 3) == a) + ((i >> 2 & 3) == b && (i & 3) == a); ti = a << 2 | b; fmt->cnt_occ[ti][i]= ob << 24 | oob << 16 | oa << 8 | ooa ; } } } } void dump_fmt(const char *fn, const FMTIndex *fmt) { FILE *fp; fp = xopen(fn, "wb"); err_fwrite(&fmt->primary, sizeof(bwtint_t), 1, fp); err_fwrite(&fmt->sec_primary, sizeof(bwtint_t), 1, fp); err_fwrite(&fmt->sec_bcp, sizeof(uint8_t), 1, fp); err_fwrite(&fmt->first_base, sizeof(uint8_t), 1, fp); err_fwrite(&fmt->last_base, sizeof(uint8_t), 1, fp); err_fwrite(fmt->L2 + 1, sizeof(bwtint_t), 4, fp); err_fwrite(fmt->bwt, 4, fmt->bwt_size, fp); err_fflush(fp); err_fclose(fp); } FMTIndex *restore_fmt(const char *fn) { FMTIndex *fmt; fmt = (FMTIndex *)calloc(1, sizeof(FMTIndex)); FILE *fp = fopen(fn, "rb"); fseek(fp, 0, SEEK_END); fmt->bwt_size = (ftell(fp) - sizeof(bwtint_t) * 6 - 3) >> 2; // 以32位word为单位计算的size fmt->bwt = (uint32_t *)calloc(fmt->bwt_size, 4); fseek(fp, 0, SEEK_SET); fread(&fmt->primary, sizeof(bwtint_t), 1, fp); fread(&fmt->sec_primary, sizeof(bwtint_t), 1, fp); fread(&fmt->sec_bcp, sizeof(uint8_t), 1, fp); fread(&fmt->first_base, sizeof(uint8_t), 1, fp); fread(&fmt->last_base, sizeof(uint8_t), 1, fp); fread(fmt->L2 + 1, sizeof(bwtint_t), 4, fp); fread_fix(fp, fmt->bwt_size << 2, fmt->bwt); fmt->seq_len = fmt->L2[4]; fclose(fp); fmt_gen_cnt_occ(fmt); // 字节所能表示的各种碱基组合中,各个碱基的累积数量 return fmt; } // 根据interval-bwt创建fmt-index FMTIndex *create_fmt_from_bwt(bwt_t *bwt) { // FILE *fmt_out = fopen("fmt.txt", "w"); FMTIndex *fmt = (FMTIndex *)calloc(1, sizeof(FMTIndex)); fmt_gen_cnt_occ(fmt); bwtint_t i, j, k, m, n, n_occ, cnt[4], cnt2[4]; uint32_t c[4], c2[16]; /*c用来保存原来的bwt碱基串的累积值,c2用来保存pre-bwt和bwt碱基对的累计值,如AA..TT*/ uint32_t *buf; /* 计算之后变成fmt结构中bwt部分 */ fmt->seq_len = bwt->seq_len; // bwt碱基序列的长度,不包含$字符,也就是该长度比bwt matrix长度少1 for (i = 0; i < 5; ++i) fmt->L2[i] = bwt->L2[i]; // 每个碱基的总累积值 fmt->primary = bwt->primary; // $在末尾的行,在bwt matrix行中的排序位置 n_occ = (bwt->seq_len + FMT_OCC_INTERVAL - 1) / FMT_OCC_INTERVAL + 1; // check point 个数 fmt->bwt_size = (fmt->seq_len * 2 + 15) >> 4; // 要保存最后两列碱基 fmt->bwt_size += n_occ * 20; // A,C,G,T和AA,AC.....TG,TT共20个 buf = (uint32_t *)calloc(fmt->bwt_size, 4); // 开辟计算fmt用到的缓存 c[0] = c[1] = c[2] = c[3] = 0; // 首行的c2,应该是对应的ACGT对应的行,减去1的occ for (i = 0; i < 4; ++i) { bwtint_t before_first_line = fmt->L2[i]; bwt_occ4(bwt, before_first_line, cnt); for (j = i * 4, k = 0; k < 4; ++j, ++k) c2[j] = cnt[k]; } // k表示buf存储的偏移量 for (i = k = 0; i < bwt->seq_len; ++i) { // 记录occ if (i % FMT_OCC_INTERVAL == 0) { memcpy(buf + k, c, sizeof(uint32_t) * 4); // bwt str中各个碱基的occ k += 4; memcpy(buf + k, c2, sizeof(uint32_t) * 16); // pre-bwt:bwt碱基对的occ k += 16; } // 每个32位整数保存8个倒数第二列碱基(pre-bwt)和8个倒数第一列(bwt)碱基 if (i % 16 == 0) // 每个32位整数可以包含16个碱基,每次需要处理16个碱基,也就是间隔最小可以设置为16 { uint32_t pre_bwt_16_seq = 0; // 16个pre-bwt碱基串 uint32_t *bwt_addr = bwt_occ_intv(bwt, i) + 4; // 这里加4还是加8要看保存occ的是是uint32还是uint64,bwt字符串i对应的基准行,因为原始的bwt-cp(check point)包含由4个uint32_t(8个uint32_t)组成的occ信息 int offset = (i % FMT_OCC_INTERVAL) / 16; // 每OCC_INTERVAL个碱基共享同一个基准地址,每16个碱基共用一个uint32整型,因此需要偏移量来获取当前碱基串的首地址 uint32_t bwt_16_seq = *(bwt_addr + offset); // 待处理的当前16个碱基串的首地址 for (j = 0; j < 16; ++j) // 对于bwt碱基串,一个一个碱基分别处理 { bwtint_t cur_str_line = i + j; // 当前碱基在bwt str中的行排序 if (cur_str_line < bwt->seq_len) // 当前碱基行不应超出bwt str总碱基长度(bwt str长度比bwt matrix长度少1,因为bwt str不包含$) { uint8_t bwt_base = bwt_B0(bwt, cur_str_line); // 对应行的bwt的碱基 // 先求出该碱基对应在第一列的行(对应的bwt matrix行) bwtint_t cur_mtx_line = cur_str_line; if (cur_str_line >= bwt->primary) // 因为bwt序列里除去了$符号,所以,超过$所在行之后,对应的seq位置应该加一,才是真正对应bwt matrix的行 cur_mtx_line += 1; bwt_occ4(bwt, cur_mtx_line, cnt); // 获取原来bwt-checkpoint中的occ值 for (m=0; m<4; ++m) c[m] = (uint32_t)cnt[m]; // 碱基m在cur_bwt_mtx_line(包含)之前的累积值,直接拷贝原bwt中的occ即可 cnt[bwt_base] -= 1; // 得到cur_bwt_mtx_line(不包含)之前的累积量,即bwt_occ4(bwt, cur_bwt_mtx_line-1, cnt) bwtint_t bwt_base_mtx_line = bwt->L2[bwt_base] + 1 + cnt[bwt_base]; // bwt_base对应的bwt matrix行(LF变换) bwt_occ4(bwt, bwt_base_mtx_line, cnt2); // 计算bwt_base_mtx_line之前的occ for (n = 0; n < 4; ++n) { int c2_idx = bwt_base << 2 | n; // bwt base放在前边 c2[c2_idx] = (uint32_t)cnt2[n]; // pre-bwt:bwt 碱基对的累计值 } bwtint_t bwt_base_str_line = bwt_base_mtx_line; // bwt-str中对应的行排序 if (bwt_base_str_line >= bwt->primary) // base_line表示在bwt str中的位置,所以超出$为最尾所在行之后,要减掉1 bwt_base_str_line -= 1; // bwt碱基序列行(不包含$) uint32_t pre_bwt_base = bwt_B0(bwt, bwt_base_str_line); // bwt列碱基对应的前一个碱基pre-bwt // 此时,bwt_base对应的bwt matrix首行,是$排在最尾的行,说明bwt_base就是序列的第一个碱基, // 此时计算出来的pre_bwt_base就是primary前一行的bwt base,以此来代替$字符,在后续的计算过程中需要考虑 if (bwt_base_mtx_line == bwt->primary) { // 计算sec_bcp fmt->sec_bcp = pre_bwt_base << 2 | bwt_base; // 因为把$当成A处理了 fmt->sec_primary = cur_mtx_line; // pre-bwt base为$的行排序(bwt-matrix行) fmt->first_base = bwt_base; // 原始序列第一个碱基 fmt->last_base = pre_bwt_base; // 计算后替代$字符的碱基(应该是primary行上边一行对应的bwt base) } // 暂存 pre-bwt碱基序列 pre_bwt_16_seq = pre_bwt_16_seq | (pre_bwt_base << (15-j)*2); // 序列靠前的碱基排在uint32_t数据中的高位 // 输出调试信息 // cout << "mtx line: " << cur_mtx_line << ' ' << c[0] << ' ' << c[1] << ' ' << c[2] << ' ' << c[3] << ' '; // for (m = 0; m < 16; ++m) // cout << c2[m] << ' '; // cout << endl; } else break; } // 保存bwt和pre_bwt uint32_t pre_and_bwt_seq = 0; for (m = 0; m < 8; ++m) { int lshift_bit = 30 - 2 * m; pre_and_bwt_seq |= (((pre_bwt_16_seq & (3 << lshift_bit)) >> (m * 2)) | ((bwt_16_seq & (3 << lshift_bit)) >> ((m * 2) + 2))); } buf[k++] = pre_and_bwt_seq; if (j > 8) { pre_and_bwt_seq = 0; for (m = 8; m > 0; --m) { int lshift_bit = 2 * m - 2; pre_and_bwt_seq |= (((pre_bwt_16_seq & (3 << lshift_bit)) << (m * 2)) | ((bwt_16_seq & (3 << lshift_bit)) << (m * 2 - 2))); } buf[k++] = pre_and_bwt_seq; } } } // the last element memcpy(buf + k, c, sizeof(uint32_t) * 4); k += 4; memcpy(buf + k, c2, sizeof(uint32_t) * 16); k += 16; // cout << "n occ: " << n_occ << endl; // cout << "size: " << k << '\t' << fmt->bwt_size << endl; xassert(k == fmt->bwt_size, "inconsistent bwt_size"); // update fmt fmt->bwt = buf; return fmt; } // 扩展两个个碱基,计算bwt base为b的pre-bwt str中各个碱基的occ void fmt_e2_occ(const FMTIndex *fmt, bwtint_t k, int b1, int b2, bwtint_t cnt[4]) { uint32_t x; uint32_t *p, *q, tmp, *end; bwtint_t bwt_k_line = k, bwt_k_base_line = k >> FMT_OCC_INTV_SHIFT << FMT_OCC_INTV_SHIFT; int i, ti; cnt[0] = 0; cnt[1] = 0; cnt[2] = 0; if (k == (bwtint_t)(-1)) { p = fmt->bwt + 4 + b1 * 4; for (i = 3; i > b2; --i) cnt[2] += p[i]; cnt[3] = p[b2]; return; } ti = b1 << 2 | b2; // _mm_prefetch((const char *)(&fmt->cnt_occ[ti]), _MM_HINT_T0); k -= (k >= fmt->primary); // k由bwt矩阵对应的行转换成bwt字符串对应的行(去掉了$,所以大于$的行,都减掉1) p = fmt_occ_intv(fmt, k); // cout << "k-base: " << k << "; occ: " << p[0] << ' ' << p[1] << ' ' << p[2] << ' ' << p[3] << endl; for (i = 3; i > b1; --i) cnt[0] += p[i]; cnt[1] = p[b1]; q = p + 4 + b1 * 4; for (i = 3; i > b2; --i) cnt[2] += q[i]; cnt[3] = q[b2]; p += 20; // 该地址是bwt和pre_bwt字符串数据的首地址 end = p + ((k >> 3) - ((k & ~FMT_OCC_INTV_MASK) >> 3)); // this is the end point of the following loop // p = end - (end - p) / 4; // cout << "k - kbase: " << k - bwt_k_base_line << endl; for (x = 0; p < end; ++p) { x += __fmt_occ_e2_aux2(fmt, ti, *p); // print_base_uint32(*p); } tmp = *p & ~((1U << ((~k & 7) << 2)) - 1); // print_base_uint32(tmp); x += __fmt_occ_e2_aux2(fmt, ti, tmp); // end = p + (end - p) / 4; // end = p + 2; // p = end - (end - p) / 32; // if (k % 2 == 0) // x += __fmt_occ_e2_aux2(fmt, ti, *p); // p += 1; // tmp = *p & ~((1U << ((~k & 7) << 2)) - 1); // x += __fmt_occ_e2_aux2(fmt, ti, tmp); if (b1 == 0) { x -= (~k & 7) << 8; if (b2 == 0) x -= (~k & 7) << 24; } // 如果跨过了second_primary,那么可能需要减掉一次累积值 if (b1 == fmt->first_base && bwt_k_base_line < fmt->sec_primary && bwt_k_line >= fmt->sec_primary) { if (b2 == fmt->last_base) x -= 1 << 24; else if (b2 < fmt->last_base) x -= 1 << 16; } cnt[0] += x & 0xff; cnt[1] += x >> 8 & 0xff; cnt[2] += x >> 16 & 0xff; cnt[3] += x >> 24 & 0xff; } // 扩展两个碱基 void fmt_extend2(const FMTIndex *fmt, bwtintv_t *ik, bwtintv_t *ok, int is_back, int b1, int b2) { bwtint_t tk[4], tl[4], first_pos; // tk表示在k行之前所有各个碱基累积出现次数,tl表示在l行之前的累积 fmt_e2_occ(fmt, ik->x[!is_back] - 1, b1, b2, tk); fmt_e2_occ(fmt, ik->x[!is_back] - 1 + ik->x[2], b1, b2, tl); //fmt_e2_occ_2way(fmt, ik->x[!is_back] - 1, b1, b2, tk); //fmt_e2_occ_2way(fmt, ik->x[!is_back] - 1 + ik->x[2], b1, b2, tl); // 这里是反向扩展 //cout << BASE[b1] << BASE[b2] << endl; //cout << "fmt: interval-1: " << tl[0] - tk[0] << ' ' << tl[0] << ' ' << tk[0] << endl; //cout << "fmt: interval-2: " << tl[2] - tk[2] << ' ' << tl[2] << ' ' << tk[2] << endl; ok->x[!is_back] = fmt->L2[b2] + 1 + tk[3]; ok->x[2] = tl[3] - tk[3]; // 第一次正向扩展 ok->x[is_back] = ik->x[is_back] + (ik->x[!is_back] <= fmt->primary && ik->x[!is_back] + ik->x[2] - 1 >= fmt->primary) + tl[0] - tk[0]; // 第二次正向扩展 first_pos = fmt->L2[b1] + 1 + tk[1]; ok->x[is_back] = ok->x[is_back] + (first_pos <= fmt->primary && first_pos + tl[1] - tk[1] - 1 >= fmt->primary) + tl[2] - tk[2]; } // 扩展一个碱基 void fmt_extend1(const FMTIndex *fmt, bwtintv_t *ik, bwtintv_t *ok, int is_back, int b1) { bwtint_t tk[4], tl[4]; int b2 = 3; // tk表示在k行之前所有各个碱基累积出现次数,tl表示在l行之前的累积 fmt_e2_occ(fmt, ik->x[!is_back] - 1, b1, b2, tk); fmt_e2_occ(fmt, ik->x[!is_back] - 1 + ik->x[2], b1, b2, tl); //fmt_e2_occ_2way(fmt, ik->x[!is_back] - 1, b1, b2, tk); //fmt_e2_occ_2way(fmt, ik->x[!is_back] - 1 + ik->x[2], b1, b2, tl); // 这里是反向扩展 ok->x[!is_back] = fmt->L2[b1] + 1 + tk[1]; ok->x[2] = tl[1] - tk[1]; // 第一次正向扩展 ok->x[is_back] = ik->x[is_back] + (ik->x[!is_back] <= fmt->primary && ik->x[!is_back] + ik->x[2] - 1 >= fmt->primary) + tl[0] - tk[0]; } // 利用fmt搜索seed,完整搜索,只需要单向搜索 bwtintv_t fmt_search(FMTIndex *fmt, const string &q) { bwtintv_t ik; bwtintv_t ok; int i, c1, c2, x = 0; int qlen = (int)q.size(); fmt_set_intv(fmt, bval(q[x]), ik); ik.info = x + 1; // cout << "fmt : " << ik.x[0] << '\t' << ik.x[1] << '\t' << ik.x[2] << endl; for (i = x + 1; i + 1 < qlen; i += 2) { if (bval(q[i]) < 4 && bval(q[i + 1]) < 4) { c1 = cbval(q[i]); c2 = cbval(q[i + 1]); //double tm_t = realtime(); fmt_extend2(fmt, &ik, &ok, 0, c1, c2); ik = ok; // t8 += realtime() - tm_t; ik.info = i + 1; // cout << "fmt : " << ik.x[0] << '\t' << ik.x[1] << '\t' << ik.x[2] << endl; } else { break; } } if (i < qlen && bval(q[i]) < 4) { // 最后一次扩展 c1 = cbval(q[i]); // double tm_t = realtime(); fmt_extend1(fmt, &ik, &ok, 0, c1); ik = ok; // t9 += realtime() - tm_t; ik.info = i + 1; //cout << "fmt : " << ik.x[0] << '\t' << ik.x[1] << '\t' << ik.x[2] << endl; } // cout << ik.x[0] << '\t' << ik.x[1] << '\t' << ik.x[2] << endl; return ik; } int main_fmtidx(int argc, char **argv) { // string seq("ACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTA"); string seq("ACCCT"); string rseq = calc_reverse_seq(seq); seq = seq + rseq; //create_bwt_mtx(seq); //cout << seq << endl; //string bwt_str = string(argv[1]) + ".bwt.str"; // string bwt_idx = string(argv[1]) + ".128.bwt"; string bwt_idx = string(argv[1]) + ".64.bwt"; // string bwt_idx = string(argv[1]) + ".16.bwt"; // string bwt_idx = string(argv[1]) + ".bwt"; //bwt_t *bwt = restore_bwt(bwt_str.c_str()); //create_interval_occ_bwt(bwt); //dump_bwt(bwt_idx.c_str(), bwt); //string fmt_idx = string(argv[1]) + ".fmt"; // string fmt_idx = string(argv[1]) + ".256.fmt"; string fmt_idx = string(argv[1]) + ".64.fmt"; // string fmt_idx = string(argv[1]) + ".32.fmt"; bwt_t *bwt = restore_bwt(bwt_idx.c_str()); FMTIndex *fmt = restore_fmt(fmt_idx.c_str()); // FMTIndex *fmt = create_fmt_from_bwt(bwt); // dump_fmt(fmt_idx.c_str(), fmt); vector seed_arr(10000000); seed_arr[0] = "GCGATACTAAGA"; srand(time(NULL)); t1 = realtime(); for (int i = 0; i < (int)seed_arr.size(); ++i) seed_arr[i] = generate_rand_seq(13); t1 = realtime() - t1; cout << "[time gen seed:] " << t1 << "s" << endl; t2 = realtime(); for (int i = 0; i < (int)seed_arr.size(); ++i) bwt_search(bwt, seed_arr[i]); t2 = realtime() - t2; cout << "[time bwt search:] " << t2 << "s" << endl; t3 = realtime(); for (int i = 0; i < (int)seed_arr.size(); ++i) fmt_search(fmt, seed_arr[i]); t3 = realtime() - t3; cout << "[time fmt search:] " << t3 << "s" << endl; t4 = realtime(); for (int i = 0; i < (int)seed_arr.size(); ++i) { bwtintv_t p1 = bwt_search2(bwt, seed_arr[i]); bwtintv_t p2 = fmt_search(fmt, seed_arr[i]); if (p1.x[0] != p2.x[0] || p1.x[1] != p2.x[1] || p1.x[2] != p2.x[2]) cout << seed_arr[i] << endl << p1.x[0] << ' ' << p1.x[1] << ' ' << p1.x[2] << endl << p2.x[0] << ' ' << p2.x[1] << ' ' << p2.x[2] << endl; } t4 = realtime() - t4; cout << "[time bwt search 2:] " << t4 << "s" << endl; //cout << "bwt occ: " << t5 << "s; " << t7 << '\t' << t10 << endl; //cout << "fmt occ: " << t6 << "s; " << t11 << '\t' << t8 << '\t' << t9 << endl; // bwt_search(bwt, s); // bwt_search2(bwt, s); // for (int i = 0; i < 120; ++i) // { // cout << i << '\t' << bwt_B0(bwt, i) << endl; // } // TGGGAT // FMTIndex *fmt = create_fmt_from_bwt(bwt); // dump_fmt("ref.fmt", fmt); // FMTIndex *fmt = restore_fmt("tiny.fmt"); //fmt_search(fmt, s); // cout << bwt->bwt_size << endl; // cout << bwt->seq_len << endl; //cout << "sec_: " << fmt->sec_bcp << '\t' << fmt->sec_primary << endl; //uint8_t b8 = 2 << 4 | 2; //cout << "AGAG: " << fmt->cnt_table[2][b8] << endl; //cout << (((b8 >> 6) == 0 && (b8 >> 4 & 3) == 2) + ((b8 >> 2 & 3) == 0 && (b8 & 3) == 2)) << endl; return 0; }