#include #include #include #include #include "kvec.h" #include "htab.h" #include "ksort.h" #define MAX_HIGH_OCC 8 // TODO: don't hard code if we need to tune this parameter #define MAX_MAX_HIGH_OCC 16 typedef struct { // a simplified version of kdq int front, count; int a[64]; } tiny_queue_t; static inline void tq_push(tiny_queue_t *q, int x) { q->a[((q->count++) + q->front) & 0x3f] = x; } static inline int tq_shift(tiny_queue_t *q) { int x; if (q->count == 0) return -1; x = q->a[q->front++]; q->front &= 0x3f; --q->count; return x; } static inline int mzcmp(const ha_mz1_t *a, const ha_mz1_t *b) { return a->rid < b->rid? -1 : a->rid > b->rid? 1 : ((a->x > b->x) - (a->x < b->x)); } #define mz_lt(a, b) (mzcmp(&(a), &(b)) < 0) KSORT_INIT(mz, ha_mz1_t, mz_lt) static void select_mz(ha_mz1_v *p, int len, int sample_dist) { // for high-occ minimizers, choose up to max_high_occ in each high-occ streak int32_t i, last0 = -1, n = (int32_t)p->n, m = 0; ha_mz1_t b[MAX_MAX_HIGH_OCC]; // this is to avoid a heap allocation if (n == 0 || n == 1) return; assert(n < 1<<27); // 27 is the number of bits for ha_mz1_t::pos; this should be safe as there are more bases than minimizers for (i = 0; i < n; ++i) if (p->a[i].rid != 0) ++m; if (m == 0) return; // no high-frequency k-mers; do nothing for (i = 0; i <= n; ++i) { if (i == n || p->a[i].rid == 0) { if (i - last0 > 1) { int32_t ps = last0 < 0? 0 : p->a[last0].pos; int32_t pe = i == n? len : p->a[i].pos; int32_t j, k, st = last0 + 1, en = i; int32_t max_high_occ = (int32_t)((double)(pe - ps) / sample_dist + .499); if (max_high_occ > MAX_MAX_HIGH_OCC) max_high_occ = MAX_MAX_HIGH_OCC; for (j = st, k = 0; j < en && k < max_high_occ; ++j, ++k) b[k] = p->a[j], b[k].pos = j; // b[].pos keeps the index in p->a[] ks_heapmake_mz(k, b); // initialize the binomial heap for (; j < en; ++j) { // if there are more, choose top max_high_occ if (mz_lt(p->a[j], b[0])) { // then update the heap b[0] = p->a[j], b[0].pos = j; ks_heapdown_mz(0, k, b); } } //ks_heapsort_mz(k, b); // sorting is not needed for now for (j = 0; j < k; ++j) if (b[j].rid < pe - ps) p->a[b[j].pos].rid = 0; } last0 = i; } } for (i = n = 0; i < (int32_t)p->n; ++i) // squeeze out filtered minimizers if (p->a[i].rid == 0) p->a[n++] = p->a[i]; p->n = n; } /** * Find symmetric (w,k)-minimizers on a DNA sequence * * @param str DNA sequence * @param len length of $str * @param w find a minimizer for every $w consecutive k-mers * @param k k-mer size * @param rid reference ID; will be copied to the output $p array * @param is_hpc homopolymer-compressed or not * @param p minimizers */ void ha_sketch(const char *str, int len, int w, int k, uint32_t rid, int is_hpc, ha_mz1_v *p, const void *hf, int sample_dist, kvec_t_u8_warp* k_flag, kvec_t_u64_warp* dbg_ct) { ///in default, w = 51, k = 51, is_hpc = 1 /** uint64_t x; uint64_t rid:28, pos:27, rev:1, span:8; **/ extern void *ha_ct_table; static const ha_mz1_t dummy = { UINT64_MAX, (1<<28) - 1, 0, 0 }; uint64_t shift1 = k - 1, mask = (1ULL< 0 && len < 1<<27 && rid < 1<<28 && (w > 0 && w < 256) && (k > 0 && k <= 63)); if (dbg_ct != NULL) dbg_ct->a.n = 0; if (k_flag != NULL) { kv_resize(uint8_t, k_flag->a, (uint64_t)len); k_flag->a.n = len; memset(k_flag->a.a, 0, k_flag->a.n); } memset(buf, 0xff, w * sizeof(ha_mz1_t)); memset(&tq, 0, sizeof(tiny_queue_t)); ///len/w is the evaluated minimizer numbers kv_resize(ha_mz1_t, *p, p->n + len/w); for (i = l = buf_pos = min_pos = 0; i < len; ++i) { int c = seq_nt4_table[(uint8_t)str[i]]; ha_mz1_t info = dummy; if (c < 4) { // not an ambiguous base int z; if (is_hpc) { int skip_len = 1; if (i + 1 < len && seq_nt4_table[(uint8_t)str[i + 1]] == c) { for (skip_len = 2; i + skip_len < len; ++skip_len) if (seq_nt4_table[(uint8_t)str[i + skip_len]] != c) break; i += skip_len - 1; // put $i at the end of the current homopolymer run } tq_push(&tq, skip_len); kmer_span += skip_len; ///how many bases that are covered by this HPC k-mer ///kmer_span includes at most k HPC elements if (tq.count > k) kmer_span -= tq_shift(&tq); } else kmer_span = l + 1 < k? l + 1 : k; ///kmer_span should be used for HPC k-mer ///non-HPC k-mer, kmer_span should be k ///kmer_span is used to calculate anchor pos on reverse complementary strand if (k_flag != NULL) k_flag->a.a[i] = 1;///lable all useful base, which are not ignored by HPC kmer[0] = (kmer[0] << 1 | (c&1)) & mask; // forward k-mer kmer[1] = (kmer[1] << 1 | (c>>1)) & mask; kmer[2] = kmer[2] >> 1 | (uint64_t)(1 - (c&1)) << shift1; // reverse k-mer kmer[3] = kmer[3] >> 1 | (uint64_t)(1 - (c>>1)) << shift1; if (kmer[1] == kmer[3]) continue; // skip "symmetric k-mers" as we don't know it strand z = kmer[1] < kmer[3]? 0 : 1; // strand ++l; if (l >= k && kmer_span < 256) { uint64_t y; int32_t cnt, filtered; y = yak_hash64_64(kmer[z<<1|0]) + yak_hash64_64(kmer[z<<1|1]); cnt = hf? ha_ft_cnt(hf, y) : 0; filtered = (cnt >= 1<<28); if (dbg_ct != NULL) kv_push(uint64_t, dbg_ct->a, ((((uint64_t)(query_ct_index(ha_ct_table, y))<<1)|filtered)<<32)|(uint64_t)(i)); if (!filtered) info.x = y, info.rid = cnt, info.pos = i, info.rev = z, info.span = kmer_span; // initially ha_mz1_t::rid keeps the k-mer count if (k_flag != NULL) k_flag->a.a[i]++; if (k_flag != NULL && filtered > 0) k_flag->a.a[i]++; } } else l = 0, tq.count = tq.front = 0, kmer_span = 0; //for non-HPC k-mer, l = i; but for HPC k-mer, l is always less than i //i is the real base iterator, while l is the HPC base iterator //only if l >= k, info is a useful minimizer (ha_mz1_t.x != UINT64_MAX) //but even if l < k, infor is still stored into buf buf[buf_pos] = info; // need to do this here as appropriate buf_pos and buf[buf_pos] are needed below if (l == w + k - 1 && min.x != UINT64_MAX) { // special case for the first window - because identical k-mers are not stored yet for (j = buf_pos + 1; j < w; ++j) if (mzcmp(&min, &buf[j]) == 0 && buf[j].pos != min.pos) kv_push(ha_mz1_t, *p, buf[j]); for (j = 0; j < buf_pos; ++j) if (mzcmp(&min, &buf[j]) == 0 && buf[j].pos != min.pos) kv_push(ha_mz1_t, *p, buf[j]); } /** * There are three cases: * 1. info.x <= min.x, means info is a new minimizer * 2. info.x > min.x, info is not a new minimizer * (1) buf_pos != min_pos, do nothing * (2) buf_pos == min_pos, means current minimizer has moved outside the window * **/ ///three cases: 1. if (info.x <= min.x) { // a new minimum; then write the old min if (l >= w + k && min.x != UINT64_MAX) kv_push(ha_mz1_t, *p, min); min = info, min_pos = buf_pos; } else if (buf_pos == min_pos) { // old min has moved outside the window if (l >= w + k - 1 && min.x != UINT64_MAX) kv_push(ha_mz1_t, *p, min); ///buf_pos == min_pos, means current minimizer has moved outside the window ///so for now we need to find a new minimizer at the current window (w k-mers) for (j = buf_pos + 1, min.x = UINT64_MAX; j < w; ++j) // the two loops are necessary when there are identical k-mers if (mzcmp(&min, &buf[j]) >= 0) min = buf[j], min_pos = j; // >= is important s.t. min is always the closest k-mer for (j = 0; j <= buf_pos; ++j) if (mzcmp(&min, &buf[j]) >= 0) min = buf[j], min_pos = j; if (l >= w + k - 1 && min.x != UINT64_MAX) { // write identical k-mers for (j = buf_pos + 1; j < w; ++j) // these two loops make sure the output is sorted if (mzcmp(&min, &buf[j]) == 0 && min.pos != buf[j].pos) kv_push(ha_mz1_t, *p, buf[j]); for (j = 0; j <= buf_pos; ++j) if (mzcmp(&min, &buf[j]) == 0 && min.pos != buf[j].pos) kv_push(ha_mz1_t, *p, buf[j]); } } if (++buf_pos == w) buf_pos = 0; } if (min.x != UINT64_MAX) kv_push(ha_mz1_t, *p, min); if (sample_dist > w) select_mz(p, len, MAX_HIGH_OCC); for (i = 0; i < (int)p->n; ++i) // populate .rid as this was keeping counts p->a[i].rid = rid; }