#include <stdio.h>

#include <stdlib.h>

#include <assert.h>

#include <string.h>

#include "kvec.h"

#include "htab.h"

#include "ksort.h"

#include "Correct.h"

#include "kalloc.h"

#define MAX_HIGH_OCC 8 // TODO: don't hard code if we need to tune this parameter

#define MAX_MAX_HIGH_OCC 16

#define GMC(a, x,y,xn) ((a)[(x)*(xn)+(y)])

#define GL(x, i) ((int64_t)((uint32_t)((x).a[(i)])))

#define A_M(p, i) ((i) >= 0 && (p).a[(i)].rid > 0)

void debug_refine(ha_mz1_t *ma, uint64_t *mmt, int32_t sn, int32_t n, int32_t m, int32_t end)

}

void dbg_boundary(ha_mz1_v *p, st_mt_t *mt, int32_t w, int32_t k, int32_t tot_l)

}

void debug_pl(const char *str, int len, int w, int k, int is_hpc, ha_mz1_v *p, const void *hf, st_mt_t *mt)

}

static inline int mz1_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 mz1_mz_lt(a, b) (mz1_mzcmp(&(a), &(b)) < 0)

KSORT_INIT(mz1_mz, ha_mz1_t, mz1_mz_lt)

static inline int mz2_mzcmp(const ha_mzl_t *a, const ha_mzl_t *b){return a->rid < b->rid? -1 : a->rid > b->rid? 1 : ((a->x > b->x) - (a->x < b->x));}

#define mz2_mz_lt(a, b) (mz2_mzcmp(&(a), &(b)) < 0)

KSORT_INIT(mz2_mz, ha_mzl_t, mz2_mz_lt)

#define HA_SC_INIT(sf, HType, VType, RidBits, PosBits)\

inline void sf##_hf_select(VType *p, int32_t si, int32_t ei, int32_t n, int32_t len, int32_t sample_dist, HType *b, int32_t force)\

{\

if(ei - si <= 1) return;\

int32_t ps = si < 0? 0 : p->a[si].pos;\

int32_t pe = ei == n? len : p->a[ei].pos;\

int32_t j, k, st = si + 1, en = ei;\

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_##sf##_mz(k, b); /** initialize the binomial heap**/\

for (; j < en; ++j) { /** if there are more, choose top max_high_occ**/\

if (sf##_mz_lt(p->a[j], b[0])) { /** then update the heap**/\

b[0] = p->a[j], b[0].pos = j;\

ks_heapdown_##sf##_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 || force)\

p->a[b[j].pos].rid = 0;\

}\

static inline int sf##_mzcmp_l(const VType *p, int32_t ai, int32_t bi)\

{\

if(ai >= 0 && bi >= 0){\

HType *a = &(p->a[ai]), *b = &(p->a[bi]);\

if(a->rid > 0 && b->rid > 0) return sf##_mzcmp(a, b);\

return (a->rid == 0) - (b->rid == 0);\

}\

return (ai < 0) - (bi < 0);\

}\

int32_t sf##_qfw(VType *p, st_mt_t *mt, int32_t n, int32_t tot_l, int32_t ws, int32_t i, int32_t *mi)\

{\

int32_t m, si;\

for (si = i, (*mi) = -1; i < n; i++){\

if(GL(*mt, i) >= ws || (i+1 < n && GL(*mt, i) < ws && GL(*mt, i+1) > ws) || \

(i+1 == n && tot_l >= ws && GL(*mt, i) < ws)){\

for (m = si; m <= i; m++){\

if(!A_M(*p, m)) continue;\

if(sf##_mzcmp_l(p, *mi, m) >= 0) (*mi) = m;\

}\

if((*mi) >= 0 && A_M(*p, *mi)){\

for (m = si; m <= i; m++){\

if(!A_M(*p, m)) continue;\

if(sf##_mzcmp_l(p, *mi, m) == 0) mt->a[m] |= 0x100000000;\

}\

}\

break;\

}\

}\

return i;\

}\

static void sf##_select_mz_h(VType *p, st_mt_t *mt, int len, int sample_dist, int32_t w, int32_t k, int32_t tot_l)\

{ /**for high-occ minimizers, choose up to max_high_occ in each high-occ streak**/\

int32_t i, mi = -1, si, last0 = -1, n = (int32_t)p->n, m = 0, ws = w + k - 1;\

if (n == 0) return;\

assert((int64_t)(n) < (int64_t)((((uint64_t)1)<<PosBits)));\

for (i = m = 0, last0 = -1; 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;\

if(((int32_t)((double)(pe - ps) / sample_dist + .499)) > 0){\

last0 = -2;\

m++;\

break;\

}\

}\

last0 = i;\

}\

}\

if (m == 0) return; /**no high-frequency k-mers; do nothing**/\

if(last0 >= -1) goto sf##_ff;\

i = 0;\

i = sf##_qfw(p, mt, n, tot_l, ws, i, &mi);\

if(i == n) goto sf##_ff;\

for (si = 0, i++; i < n; i++){\

for (; si < i; si++){\

if(GL(*mt, si) + w > GL(*mt, i)) break;\

}\

/**a new minimum; then write the old min**/\

if(sf##_mzcmp_l(p, i, mi) <= 0) {\

if(A_M(*p, mi)) mt->a[mi] |= 0x100000000;\

mi = i;\

}/**old min has moved outside the window**/\

else if(si > mi){\

if(A_M(*p, mi)) mt->a[mi] |= 0x100000000;\

for (m = si, mi = -1; m <= i; m++){\

if(sf##_mzcmp_l(p, mi, m) >= 0) mi = m;\

}\

if(A_M(*p, mi)){\

for (m = si; m <= i; m++){\

if(!A_M(*p, m)) continue;\

if(sf##_mzcmp_l(p, mi, m) == 0) mt->a[m] |= 0x100000000;\

}\

}\

}\

}\

if(A_M(*p, mi)) mt->a[mi] |= 0x100000000;\

for (i = n - 1; si < n && GL(*mt, si) + w <= tot_l + 1; si++){\

if(si > mi){\

if(A_M(*p, mi)) mt->a[mi] |= 0x100000000;\

for (m = si, mi = -1; m <= i; m++){\

if(sf##_mzcmp_l(p, mi, m) >= 0) mi = m;\

}\

if(A_M(*p, mi)){\

for (m = si; m <= i; m++){\

if(!A_M(*p, m)) continue;\

if(sf##_mzcmp_l(p, mi, m) == 0) mt->a[m] |= 0x100000000;\

}\

}\

}\

}\

/**dbg_boundary(p, mt, w, k, tot_l);**/\

HType b[MAX_MAX_HIGH_OCC];\

for (i = 0, last0 = -1; 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;\

if(((int32_t)((double)(pe - ps) / sample_dist + .499)) > 0){\

for (m = last0 + 1, mi = 0; m < i; ++m){\

if(mt->a[m]&0x100000000) p->a[m].rid = 0, mi++;\

}\

if(mi == 0) sf##_hf_select(p, last0, i, n, len, sample_dist, b, 0);\

}\

}\

last0 = i;\

}\

}\

sf##_ff:\

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;\

}\

void sf##_refine_select(VType *mz, int32_t sidx, int32_t eidx, int32_t sn, int32_t min_freq, st_mt_t *mm, int32_t *rsi, int32_t *rei, void *km)\

{\

int32_t n = sn, m = eidx + 1 - sidx, i, k, t, mk=-1;\

uint64_t ix, kx, ks;\

kv_resize_km(km, uint64_t, *mm, mm->n+n*m);\

HType *ma = mz->a + sidx;\

uint64_t *mmt = mm->a + mm->n;\

/**fprintf(stderr, "[M::%s::] ==> +n: %d, m: %d, sn: %d, sidx: %d, eidx: %d\n", __func__, n, m, sn, sidx, eidx);**/\

for (i = 0; i < n; i++) /**how many selected minimizers**/\

{\

for (k = 0, mk = -1; k < m; k++) /**how many minimizers in total**/\

{\

if((int32_t)(ma[k].rid)<min_freq) continue;\

ks = ma[k].pos + 1 - ma[k].span; t = -1;\

if(i > 0){\

for (t = k-1; t >= 0 && (ma[t].pos >= ks||(int32_t)(ma[t].rid)<min_freq); t--);\

}\

ix = (i <= 0?0:(t<0?0xffffffff:(GMC(mmt, i-1,t,m)&0xffffffff)));\

if(ix < 0xffffffff) ix += (ma[k].rid);\

kx = (mk < 0?0xffffffff:(GMC(mmt, i, mk,m)&0xffffffff));\

ks = MIN(ix, kx);\

/**fprintf(stderr, "ks: %lu, i: %d (n-%d), k: %d (m-%d), ix: %lu, kx: %lu, t: %d, mk: %d\n", ks, i, n, k, m, ix, kx, t, mk);**/\

if((ks&0xffffffff) == 0xffffffff) ks |= ((uint64_t)0xffffffff)<<32;\

else if(ks == ix) ks |= (uint64_t)(i>0?(i-1)*m+t:0xffffffff)<<32;\

else if(ks == kx) ks |= (uint64_t)(mk>=0?i*m+mk:0xffffffff)<<32;\

GMC(mmt, i,k,m) = ks;\

mk = k;\

}\

}\

/**fprintf(stderr, "[M::%s::] ==> ++n: %d, m: %d, sn: %d, sidx: %d, eidx: %d\n", __func__, n, m, sn, sidx, eidx);**/\

ks = (n-1)*m + mk; ix = (uint64_t)-1; kx = 0;\

while (ks != 0xffffffff)\

{\

i = ks/m; k = ks%m;\

ks = mmt[ks]>>32;\

/**fprintf(stderr, "i: %d, k: %d, ks: %lu\n", i, k, ks);**/\

if(ks == 0xffffffff || (int32_t)(ks/m) == (i-1)){\

mm->a[sidx+k] = 1;\

ix = MIN((uint64_t)k, ix); kx = MAX((uint64_t)k, kx);\

}\

}\

/**debug_refine(ma, mmt, sn, n, m, (n-1)*m + mk);**/\

if(rsi) (*rsi) = ix + sidx;\

if(rei) (*rei) = kx + sidx;\

}\

void sf##_refine_sketch(VType *p, ha_pt_t *pt, int32_t rlen, int32_t dp_min_len, float er, int32_t min_freq, st_mt_t *mt, void *km)\

{\

/**fprintf(stderr, "[M::%s::] ==> #########10#########, rlen: %d\n", __func__, rlen);**/\

int32_t i, n = p->n, bd, len = MIN(rlen, dp_min_len), sublen, cnt, ei, li, ri;\

int32_t sn = len*er + 1;\

kv_resize_km(km, uint64_t, *mt, (int64_t)p->n);\

mt->n = p->n; memset(mt->a, 0, sizeof(uint64_t)*p->n);\

for (i = 0; i < n; i++) p->a[i].rid = ha_pt_cnt(pt, p->a[i].x);\

for (i = cnt = 0, bd = -1, ei = -1; i < n; i++){\

if((int32_t)(p->a[i].rid)<min_freq) continue;\

sublen = p->a[i].pos + 1;\

if(sublen > len) break;\

else ei = i;\

if((int32_t)(p->a[i].pos + 1 - p->a[i].span) > bd){\

bd = p->a[i].pos;\

cnt++;\

}\

}\

/**fprintf(stderr, "[M::%s::] ==> +cnt: %d, sn: %d, ei: %d, n: %d\n", __func__, cnt, sn, ei, n);**/\

if(cnt >= sn) sf##_refine_select(p, 0, ei, sn, min_freq, mt, NULL, &li, km);\

else{\

li = i-1;\

for (i = 0; i <= li; i++) mt->a[i] = 1;\

}\

if(len < rlen){\

for (i = n-1, cnt = 0, bd = rlen+1, ei = -1; i >= 0; i--){\

if((int32_t)(p->a[i].rid)<min_freq) continue;\

sublen = rlen - (p->a[i].pos + 1 - p->a[i].span);\

if(sublen > len) break;\

else ei = i;\

if((int32_t)(p->a[i].pos) < bd){\

bd = p->a[i].pos + 1 - p->a[i].span;\

cnt++;\

}\

}\

/**fprintf(stderr, "[M::%s::] ==> -cnt: %d, sn: %d, ei: %d, n: %d\n", __func__, cnt, sn, ei, n);**/\

if(cnt >= sn) sf##_refine_select(p, ei, n-1, sn, min_freq, mt, &ri, NULL, km);\

else {\

ri = i+1;\

for (i = ri; i <= n-1; i++) mt->a[i] = 1;\

}\

/**fprintf(stderr, "[M::%s::] ==> --cnt: %d, sn: %d, ei: %d, n: %d\n", __func__, cnt, sn, ei, n);**/\

if(ri - li >= 2){\

li++; ri--;\

sn = (p->a[ri].pos - p->a[li].pos + p->a[li].span)*er + 1;\

for (i = li, cnt = 0, bd = -1; i <= ri; i++){\

if((int32_t)(p->a[i].rid)<min_freq) continue;\

if((int32_t)(p->a[i].pos + 1 - p->a[i].span) > bd){\

bd = p->a[i].pos;\

cnt++;\

if(cnt >= sn) break;\

}\

}\

if(cnt >= sn) sf##_refine_select(p, li, ri, sn, min_freq, mt, NULL, NULL, km);\

else for (i = li; i <= ri; i++) mt->a[i] = 1;\

}\

}\

/**fprintf(stderr, "[M::%s::] ==> #########20#########, p->n: %u, n: %d\n", __func__, p->n, n);**/\

for (i = sn = 0; i < n; i++){\

if(mt->a[i]){\

p->a[sn] = p->a[i];\

sn++;\

}\

}\

/**if(p->n != sn) fprintf(stderr, "[M::%s::] ==> #########21#########, p->n: %u, sn: %d\n", __func__, p->n, sn);**/\

p->n = sn;\

}\

/**\

* 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 sf##_ha_sketch(const char *str, int len, int w, int k, uint32_t rid, int is_hpc, VType *p, const void *hf, int sample_dist, kvec_t_u8_warp* k_flag, kvec_t_u64_warp* dbg_ct, ha_pt_t *pt, int min_freq, int32_t dp_min_len, float dp_e, st_mt_t *mt, int32_t ws, int32_t is_unique, void *km)\

{ /**in default, w = 51, k = 51, is_hpc = 1**/\

extern void *ha_ct_table;\

static const HType dummy = { UINT64_MAX, (((uint64_t)1)<<RidBits) - 1, 0, 0, 0};\

uint64_t shift1 = k - 1, mask = (1ULL<<k) - 1, kmer[4] = {0,0,0,0};\

int i, j, l, tl = 0, buf_pos, min_pos, kmer_span = 0;\

HType buf[256], min = dummy;\

uint32_t buf_p[256], min_s = (uint32_t)-1;\

tiny_queue_t tq;\

assert(len > 0 && (int64_t)(len) < (int64_t)((((uint64_t)1)<<PosBits)) && (int64_t)(rid) < (int64_t)((((uint64_t)1)<<RidBits)) && (w > 0 && w < 256) && (k > 0 && k <= 63));\

if (dbg_ct != NULL) dbg_ct->a.n = 0;\

if (k_flag != NULL) {\

kv_resize_km(km, 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(HType));\

memset(&tq, 0, sizeof(tiny_queue_t));\

/**len/w is the evaluated minimizer numbers**/\

kv_resize_km(km, HType, *p, p->n + len/w);\

kv_resize_km(km, uint64_t, *mt, (int64_t)p->m); mt->n = p->n;\

for (i = l = tl = buf_pos = min_pos = 0; i < len; ++i) {\

int c = seq_nt4_table[(uint8_t)str[i]];\

HType 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; tl++;\

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(is_unique && (!filtered)) {\

filtered = (cnt == 0);\

cnt = (cnt == 1? 0:cnt);\

}\

if (dbg_ct != NULL) kv_push_km(km, 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;\

buf[buf_pos] = info; /**need to do this here as appropriate buf_pos and buf[buf_pos] are needed below**/\

buf_p[buf_pos] = l;\

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 (sf##_mzcmp(&min, &buf[j]) == 0 && buf[j].pos != min.pos){\

kv_push_km(km, HType, *p, buf[j]); kv_push_km(km, uint64_t, *mt, buf_p[j]);\

}\

}\

for (j = 0; j < buf_pos; ++j){\

if (sf##_mzcmp(&min, &buf[j]) == 0 && buf[j].pos != min.pos){\

kv_push_km(km, HType, *p, buf[j]); kv_push_km(km, uint64_t, *mt, buf_p[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 (sf##_mzcmp(&min, &info) >= 0) { /**a new minimum; then write the old min**/\

if (l >= w + k && min.x != UINT64_MAX){\

kv_push_km(km, HType, *p, min); kv_push_km(km, uint64_t, *mt, min_s);\

}\

min = info, min_pos = buf_pos, min_s = buf_p[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_km(km, HType, *p, min); kv_push_km(km, uint64_t, *mt, min_s);\

}\

/**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 = dummy; j < w; ++j) /**the two loops are necessary when there are identical k-mers**/\

if (sf##_mzcmp(&min, &buf[j]) >= 0) min = buf[j], min_pos = j, min_s = buf_p[j]; /** >= is important s.t. min is always the closest k-mer**/\

for (j = 0; j <= buf_pos; ++j)\

if (sf##_mzcmp(&min, &buf[j]) >= 0) min = buf[j], min_pos = j, min_s = buf_p[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 (sf##_mzcmp(&min, &buf[j]) == 0 && min.pos != buf[j].pos){\

kv_push_km(km, HType, *p, buf[j]); kv_push_km(km, uint64_t, *mt, buf_p[j]);\

}\

for (j = 0; j <= buf_pos; ++j)\

if (sf##_mzcmp(&min, &buf[j]) == 0 && min.pos != buf[j].pos){\

kv_push_km(km, HType, *p, buf[j]); kv_push_km(km, uint64_t, *mt, buf_p[j]);\

}\

}\

}\

if (++buf_pos == w) buf_pos = 0;\

}\

if (min.x != UINT64_MAX){\

kv_push_km(km, HType, *p, min); kv_push_km(km, uint64_t, *mt, min_s);\

}\

/**debug_pl(str, len, w, k, is_hpc, p, hf, mt);**/\

if (sample_dist > w) sf##_select_mz_h(p, mt, len, sample_dist, ws, k, tl);\

if (dp_min_len > 0 && pt && mt) sf##_refine_sketch(p, pt, len, dp_min_len, dp_e, min_freq, mt, km);\

for (i = 0; i < (int)p->n; ++i) /**populate .rid as this was keeping counts**/\

p->a[i].rid = rid;\

}

HA_SC_INIT(mz1, ha_mz1_t, ha_mz1_v, 28, 27)

HA_SC_INIT(mz2, ha_mzl_t, ha_mzl_v, 31, 32)