forked from ruanjue/wtdbg2
/
dbgcns.h
1380 lines (1331 loc) · 39.3 KB
/
dbgcns.h
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/*
*
* Copyright (c) 2011, Jue Ruan <ruanjue@gmail.com>
*
*
* This program is free software: you can redistribute it and/or modify
* it under the terms of the GNU General Public License as published by
* the Free Software Foundation, either version 3 of the License, or
* (at your option) any later version.
*
* This program is distributed in the hope that it will be useful,
* but WITHOUT ANY WARRANTY; without even the implied warranty of
* MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
* GNU General Public License for more details.
*
* You should have received a copy of the GNU General Public License
* along with this program. If not, see <http://www.gnu.org/licenses/>.
*/
#ifndef __DBGCNS_CNS_RJ_H
#define __DBGCNS_CNS_RJ_H
#include "dna.h"
#include "list.h"
#include "hashset.h"
#include "thread.h"
#include "ksw.h"
#include "string.h"
/*
#ifndef DBGCNS_DEBUG
#define DBGCNS_DEBUG 0
#endif
*/
static int DBGCNS_DEBUG = 0;
#define DBGCNS_KMER_MAX_SIZE 21
#define DBGCNS_KMER_MAX_NODE_COV 0x3FF
#define DBGCNS_KMER_MAX_EDGE_COV 0xFF
#define DBGCNS_MAX_UID 0xFFF
typedef struct {
uint64_t mer:42, cov:10, visit:12;
uint8_t edges[2][4];
} dbgcns_kmer_t;
define_list(dbgcnskmerv, dbgcns_kmer_t);
#define UD(E) ((dbgcnskmerv*)set->userdata)->buffer[E].mer
#define kmer_hashcode(E) u64hashcode(UD(E))
#define kmer_hashequals(E1, E2) UD(E1) == UD(E2)
define_hashset(dbgcnskmerhash, uint32_t, kmer_hashcode, kmer_hashequals);
#undef UD
typedef struct {
u4i ksize;
u8i kmask;
int hz;
dbgcnskmerv *kmers;
dbgcnskmerhash *khash;
u1v *zseq;
} DBG;
#define BT_SCORE_MIN -0x0FFFFFFF
typedef struct {
u8i mer:42, off:21, closed:1;
u2i n_in, n_visit;
u4i edges, bt_node, bt_edge;
int bt_score;
u8i ptr; // refer to dbg->kmers
} fbg_kmer_t;
#define fbgkmer_hashcode(E) u64hashcode((E).mer)
#define fbgkmer_equals(E1, E2) ((E1).mer == (E2).mer)
define_hashset(fbgkmerh, fbg_kmer_t, fbgkmer_hashcode, fbgkmer_equals);
typedef struct {
u4i node, cov:28, most:1, key:2, select:1;
u4i dist;
u4i link;
u4i next;
} fbg_edge_t;
define_list(fbgedgev, fbg_edge_t);
typedef struct {
u4i ridx, roff:15, rlen:15, key:1, select:1;
u4i next;
} fbg_link_t;
define_list(fbglinkv, fbg_link_t);
typedef struct {
u8i ridx:16, kidx:30, koff:17, closed:1;
} rd_kmer_t;
define_list(rdkmerv, rd_kmer_t);
typedef struct {
u4i lidx, len, gidx;
} link_grp_t;
define_list(linkgrpv, link_grp_t);
typedef struct {
fbgkmerh *kmers;
fbgedgev *edges;
fbglinkv *links;
linkgrpv *grps;
rdkmerv *mats;
u1v *starseq;
} FBG;
#define DBGCNS_DP_SCORE_MIN -0x7FFFFFFF
#define DBGCNS_PATH_M 0
#define DBGCNS_PATH_X 1
#define DBGCNS_PATH_I 2
#define DBGCNS_PATH_D 3
#define DBGCNS_CNS_NON 0
#define DBGCNS_CNS_TIP 1
#define DBGCNS_CNS_CUT 2
#define DBGCNS_CNS_EXT 3
#define DBGCNS_CNS_HIT 4
typedef struct {
union {
struct { uint32_t kidx:30, path:2; uint32_t qpos; };
uint64_t identifier;
};
int score;
uint32_t bt_idx;
} dbgcns_dp_t;
define_list(dbgcnsdpv, dbgcns_dp_t);
#define DD(E) ((dbgcnsdpv*)set->userdata)->buffer[E]
#define dp_hashcode(E) u64hashcode(DD(E).identifier)
#define dp_hashequals(E1, E2) DD(E1).identifier == DD(E2).identifier
define_hashset(dbgcnsdphash, uint32_t, dp_hashcode, dp_hashequals);
#undef DD
typedef struct {uint64_t off:40, len:23, solid:1;} blk_t;
define_list(blkv, blk_t);
typedef struct {
DBG *g;
FBG *fbg;
int C, M, X, I, D, E, H, L;
int Z, W;
u1v *qseqs;
blkv *qblks;
uint8_t *qry;
uint32_t qlen;
u4i qidx;
int avg_cov;
dbgcnsdpv *dps;
u4v *heap;
dbgcnsdphash *hash;
b4v *qmaxs;
uint32_t qtop;
int max_score;
uint32_t best_idx;
String *seq;
u1v *cns;
u1v *cigars;
int alns[4];
} CNS;
static inline DBG* init_dbg(uint32_t ksize){
DBG *g;
if(ksize > DBGCNS_KMER_MAX_SIZE){
fprintf(stderr, " -- ksize MUST be no greater than %d, but is %d in %s -- %s:%d --\n", DBGCNS_KMER_MAX_SIZE, ksize, __FUNCTION__, __FILE__, __LINE__); fflush(stderr);
exit(1);
}
g = malloc(sizeof(DBG));
g->hz = 0;
g->ksize = ksize;
g->kmask = 0xFFFFFFFFFFFFFFFFLLU >> ((32 - ksize) << 1);
g->kmers = init_dbgcnskmerv(32);
next_ref_dbgcnskmerv(g->kmers);
memset(g->kmers->buffer, 0, sizeof(dbgcns_kmer_t));
g->khash = init_dbgcnskmerhash(1023);
set_userdata_dbgcnskmerhash(g->khash, g->kmers);
g->zseq = init_u1v(64);
return g;
}
static inline void free_dbg(DBG *g){
free_dbgcnskmerv(g->kmers);
free_dbgcnskmerhash(g->khash);
free_u1v(g->zseq);
free(g);
}
static inline void clear_dbg(DBG *g){
clear_dbgcnskmerv(g->kmers);
next_ref_dbgcnskmerv(g->kmers);
memset(g->kmers->buffer, 0, sizeof(dbgcns_kmer_t));
clear_dbgcnskmerhash(g->khash);
}
static inline int add_kmer_dbg(DBG *g, u8i kmer, u4i ridx, uint8_t fbase, uint8_t rbase, int inc){
dbgcns_kmer_t *k;
u8i krev;
uint32_t *u;
int dir, exists;
if(0){
krev = dna_rev_seq(kmer, g->ksize);
if(kmer < krev){ dir = 0; }
else { kmer = krev; dir = 1; }
} else {
dir = 0;
}
g->kmers->buffer[0].mer = kmer;
u = prepare_dbgcnskmerhash(g->khash, 0, &exists);
if(exists){
k = ref_dbgcnskmerv(g->kmers, *u);
} else {
*u = g->kmers->size;
k = next_ref_dbgcnskmerv(g->kmers);
memset(k, 0, sizeof(dbgcns_kmer_t));
k->mer = kmer;
k->cov = 0;
k->visit = 0;
}
if(k->visit != ridx + 1 && k->cov < DBGCNS_KMER_MAX_NODE_COV && (inc || k->cov == 0)){
k->cov ++;
}
k->visit = ridx + 1;
if(dir){
if(fbase < 4){
fbase = (~fbase) & 0x03;
if(k->edges[1][fbase] < DBGCNS_KMER_MAX_EDGE_COV && (inc || k->edges[1][fbase] == 0)) k->edges[1][fbase] ++;
}
if(rbase < 4){
if(k->edges[0][rbase] < DBGCNS_KMER_MAX_EDGE_COV && (inc || k->edges[0][rbase] == 0)) k->edges[0][rbase] ++;
}
} else {
if(fbase < 4){
if(k->edges[0][fbase] < DBGCNS_KMER_MAX_EDGE_COV && (inc || k->edges[0][fbase] == 0)) k->edges[0][fbase] ++;
}
if(rbase < 4){
rbase = (~rbase) & 0x03;
if(k->edges[1][rbase] < DBGCNS_KMER_MAX_EDGE_COV && (inc || k->edges[1][rbase] == 0)) k->edges[1][rbase] ++;
}
}
return exists;
}
static inline void homopolymer_compress_dbg(DBG *g, u1i *seq, u4i len){
u4i i;
u1i b;
clear_u1v(g->zseq);
b = 4;
for(i=0;i<len;i++){
if(seq[i] == b) continue;
b = seq[i];
push_u1v(g->zseq, b);
}
}
static inline void add_seq_dbg(DBG *g, u4i ridx, uint8_t *seq, uint32_t len, int cov_inc){
u8i kmer;
uint32_t i;
uint8_t b, f, r;
if(g->hz){
homopolymer_compress_dbg(g, seq, len);
seq = g->zseq->buffer;
len = g->zseq->size;
}
kmer = 0;
for(i=0;i<len;){
b = seq[i];
kmer = ((kmer << 2) | b) & g->kmask;
i ++;
if(i < g->ksize) continue;
f = (i < len)? seq[i] : 4;
r = (i > g->ksize)? seq[i - g->ksize] : 4;
add_kmer_dbg(g, kmer, ridx, f, r, cov_inc);
}
}
static inline int kmer_cov_seq_dbg(DBG *g, u1i *seq, u4i len, u4i uid){
dbgcns_kmer_t *k;
u8i kmer;
uint32_t i, *u;
uint8_t b;
int cov;
uid = uid % DBGCNS_MAX_UID;
if(g->hz){
homopolymer_compress_dbg(g, seq, len);
seq = g->zseq->buffer;
len = g->zseq->size;
}
cov = 0;
kmer = 0;
for(i=0;i<len;){
b = seq[i];
kmer = ((kmer << 2) | b) & g->kmask;
i ++;
if(i < g->ksize) continue;
g->kmers->buffer[0].mer = kmer;
u = get_dbgcnskmerhash(g->khash, 0);
if(u){
k = ref_dbgcnskmerv(g->kmers, *u);
if(k->visit == uid){ cov --; continue; }
k->visit = uid;
cov += k->cov > 1? k->cov + 1 : - 1;
}
}
return cov;
}
static inline void print_kmers_dbg(DBG *g, FILE *out){
dbgcns_kmer_t *k;
uint64_t i;
char seq[DBGCNS_KMER_MAX_SIZE + 1];
for(i=1;i<g->kmers->size;i++){
k = ref_dbgcnskmerv(g->kmers, i);
kmer2seq(seq, k->mer, g->ksize);
fprintf(out, "%s\t%d\t%d,%d,%d,%d\t%d,%d,%d,%d\n", seq, k->cov,
k->edges[0][0], k->edges[0][1], k->edges[0][2], k->edges[0][3],
k->edges[1][0], k->edges[1][1], k->edges[1][2], k->edges[1][3]);
}
}
static inline CNS* init_cns(uint32_t ksize, int Z, int W, int M, int X, int I, int D, int E, int H, int L){
CNS *cns;
cns = malloc(sizeof(CNS));
cns->g = init_dbg(ksize);
cns->fbg = malloc(sizeof(FBG));
cns->fbg->kmers = init_fbgkmerh(1023);
cns->fbg->edges = init_fbgedgev(32);
memset(next_ref_fbgedgev(cns->fbg->edges), 0, sizeof(fbg_edge_t));
cns->fbg->links = init_fbglinkv(32);
memset(next_ref_fbglinkv(cns->fbg->links), 0, sizeof(fbg_link_t));
cns->fbg->grps = init_linkgrpv(32);
cns->fbg->mats = init_rdkmerv(32);
cns->fbg->starseq = init_u1v(32);
cns->qseqs = init_u1v(32);
cns->qblks = init_blkv(32);
cns->Z = Z;
cns->W = W;
cns->C = 1;
cns->M = M;
cns->X = X;
cns->I = I;
cns->D = D;
cns->E = E;
cns->H = H;
cns->L = L;
cns->qlen = 0;
cns->qidx = 0;
cns->avg_cov = 0;
cns->dps = init_dbgcnsdpv(32);
next_ref_dbgcnsdpv(cns->dps);
memset(cns->dps->buffer, 0, sizeof(dbgcns_dp_t)); // no need, it is always zero-filled
cns->heap = init_u4v(32);
cns->hash = init_dbgcnsdphash(1023);
set_userdata_dbgcnsdphash(cns->hash, cns->dps);
cns->qmaxs = init_b4v(32);
cns->qtop = 0;
cns->max_score = DBGCNS_DP_SCORE_MIN;
cns->best_idx = 0;
cns->seq = init_string(32);
cns->cns = init_u1v(32);
cns->cigars = init_u1v(32);
return cns;
}
static inline void free_cns(CNS *cns){
free_dbg(cns->g);
free_fbgkmerh(cns->fbg->kmers);
free_fbgedgev(cns->fbg->edges);
free_fbglinkv(cns->fbg->links);
free_linkgrpv(cns->fbg->grps);
free_rdkmerv(cns->fbg->mats);
free_u1v(cns->fbg->starseq);
free(cns->fbg);
free_u1v(cns->qseqs);
free_blkv(cns->qblks);
free_dbgcnsdpv(cns->dps);
free_u4v(cns->heap);
free_dbgcnsdphash(cns->hash);
free_b4v(cns->qmaxs);
free_string(cns->seq);
free_u1v(cns->cns);
free_u1v(cns->cigars);
free(cns);
}
static inline void reset_cns(CNS *cns){
clear_dbg(cns->g);
clear_u1v(cns->qseqs);
clear_blkv(cns->qblks);
clear_fbgkmerh(cns->fbg->kmers);
clear_fbgedgev(cns->fbg->edges);
memset(next_ref_fbgedgev(cns->fbg->edges), 0, sizeof(fbg_edge_t));
clear_fbglinkv(cns->fbg->links);
memset(next_ref_fbglinkv(cns->fbg->links), 0, sizeof(fbg_link_t));
cns->qry = NULL;
cns->qlen = 0;
}
static inline void add_seq_cns(CNS *cns, char *seq, int len, int solid){
blk_t *b;
int i;
b = next_ref_blkv(cns->qblks);
b->off = cns->qseqs->size;
b->len = len;
b->solid = solid;
for(i=0;i<len;i++) push_u1v(cns->qseqs, base_bit_table[(int)seq[i]]);
}
static inline void ready_cns(CNS *cns){
UNUSED(cns);
//blk_t *b;
//u4i i;
//for(i=0;i<cns->qblks->size;i++){
//b = ref_blkv(cns->qblks, i);
//add_seq_dbg(cns->g, cns->qseqs->buffer + b->off, b->len);
//}
}
static inline int dbg_cns_core(CNS *cns){
dbgcns_dp_t *dp, *dp2;
dbgcns_kmer_t *k;
u8i kmer, knew;
uint32_t i, dp_idx, kidx, *u;
int sum, cov, cut;
uint8_t b, q;
int exists, score, nadd, mat_only;
if(cns->heap->size == 0) return DBGCNS_CNS_NON;
dp_idx = cns->heap->buffer[0]; //array_heap_pop(cns->heap->buffer, cns->heap->size, cns->heap->cap, uint32_t, num_cmp(cns->dps->buffer[b].score, cns->dps->buffer[a].score));
encap_dbgcnsdpv(cns->dps, 9);
dp = ref_dbgcnsdpv(cns->dps, dp_idx);
mat_only = 0;
if(dp->qpos >= cns->qlen) return DBGCNS_CNS_HIT;
if(dp->qpos + cns->W < cns->qtop){
mat_only = 1;
//array_heap_remove(cns->heap->buffer, cns->heap->size, cns->heap->cap, uint32_t, 0, num_cmp(cns->dps->buffer[b].score, cns->dps->buffer[a].score));
//return DBGCNS_CNS_CUT;
} else if(dp->qpos > cns->qtop){
cns->qtop = dp->qpos;
for(i=cns->heap->size;i>0;i--){
if(cns->dps->buffer[cns->heap->buffer[i-1]].qpos + cns->W < cns->qtop){
array_heap_remove(cns->heap->buffer, cns->heap->size, cns->heap->cap, uint32_t, i - 1, num_cmp(cns->dps->buffer[b].score, cns->dps->buffer[a].score));
}
}
}
if(dp->score < cns->qmaxs->buffer[dp->qpos]){
mat_only = 1;
//array_heap_remove(cns->heap->buffer, cns->heap->size, cns->heap->cap, uint32_t, 0, num_cmp(cns->dps->buffer[b].score, cns->dps->buffer[a].score));
//return DBGCNS_CNS_CUT;
} else if(dp->score + cns->Z * cns->X > cns->qmaxs->buffer[dp->qpos]){
cns->qmaxs->buffer[dp->qpos] = dp->score + cns->Z * cns->X;
}
u = prepare_dbgcnsdphash(cns->hash, dp_idx, &exists);
if(exists){
dp2 = ref_dbgcnsdpv(cns->dps, *u);
if(dp->score > dp2->score){
*u = dp_idx;
} else {
array_heap_remove(cns->heap->buffer, cns->heap->size, cns->heap->cap, uint32_t, 0, num_cmp(cns->dps->buffer[b].score, cns->dps->buffer[a].score));
return DBGCNS_CNS_CUT;
}
} else {
*u = dp_idx;
}
array_heap_remove(cns->heap->buffer, cns->heap->size, cns->heap->cap, uint32_t, 0, num_cmp(cns->dps->buffer[b].score, cns->dps->buffer[a].score));
k = ref_dbgcnskmerv(cns->g->kmers, dp->kidx);
kmer = k->mer;
q = cns->qry[dp->qpos];
sum = k->edges[0][0] + k->edges[0][1] + k->edges[0][2] + k->edges[0][3];
if(sum == 0) return DBGCNS_CNS_TIP;
cut = num_max((cns->avg_cov + cns->L - 1) / cns->L, 1);
//cut = num_max((cns->avg_cov + 2) / 3, 1);
nadd = 0;
for(b=0;b<4;b++){
if((cov = k->edges[0][b]) == 0) continue;
if(b == q){
score = dp->score + cns->M;
} else if(mat_only){
continue;
} else {
score = dp->score + cns->X;
}
//score += (cov > 1)? (cov >= cut? 1 : 0) : -1;
score += (cov > cut)? (cns->H + (b == q? 1 : 0)) : cov - cut;
//score += (cov > cut)? cns->H : cov - cut;
knew = ((kmer << 2) | b) & cns->g->kmask;
cns->g->kmers->buffer[0].mer = knew;
u = get_dbgcnskmerhash(cns->g->khash, 0);
kidx = *u;
dp2 = next_ref_dbgcnsdpv(cns->dps);
dp2->kidx = kidx;
dp2->path = (b == q)? DBGCNS_PATH_M : DBGCNS_PATH_X;
dp2->qpos = dp->qpos + 1;
dp2->score = score;
dp2->bt_idx = dp_idx;
array_heap_push(cns->heap->buffer, cns->heap->size, cns->heap->cap, uint32_t, cns->dps->size - 1, num_cmp(cns->dps->buffer[b].score, cns->dps->buffer[a].score));
nadd ++;
// deletion
if(dp->path != DBGCNS_PATH_I){
dp2 = next_ref_dbgcnsdpv(cns->dps);
score = dp->score + (cns->E + (dp->path == DBGCNS_PATH_D? 0 : cns->D));
if(dp->path != DBGCNS_PATH_D) score += (cov > cut)? 0 : cov - cut;
else score += (cov > cut)? cns->H : cov - cut;
dp2->kidx = kidx;
dp2->path = DBGCNS_PATH_D;
dp2->qpos = dp->qpos;
dp2->score = score;
dp2->bt_idx = dp_idx;
array_heap_push(cns->heap->buffer, cns->heap->size, cns->heap->cap, uint32_t, cns->dps->size - 1, num_cmp(cns->dps->buffer[b].score, cns->dps->buffer[a].score));
nadd ++;
}
}
// insertion
if(mat_only == 0 && dp->path != DBGCNS_PATH_D){
dp2 = next_ref_dbgcnsdpv(cns->dps);
score = dp->score + (cns->E + (dp->path == DBGCNS_PATH_I? 0 : cns->I));
//if(dp->qpos && cns->qry[dp->qpos] == cns->qry[dp->qpos - 1]) score += 1; // homopolymer merge
score += 1 - cut;
dp2->kidx = dp->kidx;
dp2->path = DBGCNS_PATH_I;
dp2->qpos = dp->qpos + 1;
dp2->score = score;
dp2->bt_idx = dp_idx;
array_heap_push(cns->heap->buffer, cns->heap->size, cns->heap->cap, uint32_t, cns->dps->size - 1, num_cmp(cns->dps->buffer[b].score, cns->dps->buffer[a].score));
nadd ++;
}
return nadd? DBGCNS_CNS_EXT : DBGCNS_CNS_CUT;
}
static inline void ready_core_cns(CNS *cns, int candidate_mode, int reflen){
blk_t *b;
u4i i;
int tot;
if(candidate_mode == 3) i = 1;
else i = 0;
tot = 0;
for(;i<cns->qblks->size;i++){
b = ref_blkv(cns->qblks, i);
add_seq_dbg(cns->g, i, cns->qseqs->buffer + b->off, b->len, 1);
tot += b->len;
}
if(candidate_mode == 3){
b = ref_blkv(cns->qblks, 0);
add_seq_dbg(cns->g, i, cns->qseqs->buffer + b->off, b->len, 0);
tot += b->len;
}
cns->avg_cov = (tot + reflen - 1) / reflen;
}
static inline int run_core_cns(CNS *cns, uint8_t *qry, uint32_t qlen){
dbgcns_dp_t *dp;
dbgcns_kmer_t *k;
uint32_t i, kmer, kidx, dp_idx, *u;
int status;
{
cns->qry = qry;
cns->qlen = qlen;
// reset auxiliaries
clear_dbgcnsdpv(cns->dps);
next_ref_dbgcnsdpv(cns->dps);
memset(cns->dps->buffer, 0, sizeof(dbgcns_dp_t));
clear_u4v(cns->heap);
clear_dbgcnsdphash(cns->hash);
clear_b4v(cns->qmaxs);
for(i=0;i<qlen;i++) push_b4v(cns->qmaxs, DBGCNS_DP_SCORE_MIN);
cns->qtop = 0;
cns->max_score= DBGCNS_DP_SCORE_MIN;
cns->best_idx = 0;
clear_u1v(cns->cns);
clear_string(cns->seq);
clear_u1v(cns->cigars);
cns->alns[0] = cns->alns[1] = cns->alns[2] = cns->alns[3] = 0;
}
// set first kmer
kmer = 0;
for(cns->qtop=0;cns->qtop<cns->g->ksize;cns->qtop++){
kmer = (kmer << 2) | qry[cns->qtop];
}
cns->g->kmers->buffer[0].mer = kmer;
u = get_dbgcnskmerhash(cns->g->khash, 0);
if(u == NULL) return 0;
kidx = *u;
dp = next_ref_dbgcnsdpv(cns->dps);
dp->kidx = kidx;
dp->path = DBGCNS_PATH_M;
dp->qpos = cns->qtop;
dp->score = 0;
dp->bt_idx = 0;
array_heap_push(cns->heap->buffer, cns->heap->size, cns->heap->cap, uint32_t, cns->dps->size - 1, num_cmp(cns->dps->buffer[b].score, cns->dps->buffer[a].score));
// dbg traversing
while(cns->heap->size){
status = dbg_cns_core(cns);
if(status == DBGCNS_CNS_HIT){
dp_idx = cns->heap->buffer[0];
array_heap_remove(cns->heap->buffer, cns->heap->size, cns->heap->cap, uint32_t, 0, num_cmp(cns->dps->buffer[b].score, cns->dps->buffer[a].score));
dp = ref_dbgcnsdpv(cns->dps, dp_idx);
if(dp->score > cns->max_score){
cns->max_score = dp->score;
cns->best_idx = dp_idx;
}
}
}
if(cns->best_idx == 0) return 0;
// traceback to get cns seq
dp_idx = cns->best_idx;
while(dp_idx){
dp = ref_dbgcnsdpv(cns->dps, dp_idx);
push_u1v(cns->cigars, dp->path);
cns->alns[dp->path] ++;
if(dp->path != DBGCNS_PATH_I){
k = ref_dbgcnskmerv(cns->g->kmers, dp->kidx);
push_u1v(cns->cns, k->mer & 0x03);
if(k->cov == 1){
add_char_string(cns->seq, "acgt"[k->mer & 0x03]);
} else {
add_char_string(cns->seq, "ACGT"[k->mer & 0x03]);
}
}
dp_idx = dp->bt_idx;
}
// first ksize - 1 bases may be not corrected, truncated
reverse_string(cns->seq);
reverse_u1v(cns->cns);
reverse_u1v(cns->cigars);
return cns->seq->size;
}
static inline int hierarchical_clustering_edge_links(FBG *fbg, fbg_edge_t *e, linkgrpv *grps, double max_var){
fbg_link_t *lnk;
u4i lidx, gidx;
u4i i, b;
double sum, avg;
clear_linkgrpv(grps);
lidx = e->link;
while(lidx){
lnk = ref_fbglinkv(fbg->links, lidx);
push_linkgrpv(grps, (link_grp_t){lidx, lnk->rlen, 0});
lidx = lnk->next;
}
if(grps->size == 0) return 0;
sort_array(grps->buffer, grps->size, link_grp_t, num_cmpgt(a.len, b.len));
gidx = 0;
b = 0;
sum = avg = grps->buffer[0].len;
for(i=1;i<grps->size;i++){
if(grps->buffer[i].len - avg > avg * max_var){
gidx ++;
sum = avg = grps->buffer[i].len;
b = i;
} else {
sum += grps->buffer[i].len;
avg = sum / (i - b + 1);
if(avg - grps->buffer[b].len > avg * max_var || grps->buffer[i].len - avg > avg * max_var){
gidx ++;
sum = avg = grps->buffer[i].len;
b = i;
}
}
grps->buffer[i].gidx = gidx;
}
return gidx + 1;
}
static inline int revise_edge_fbg(FBG *fbg, u4i kidx, u4i eidx, linkgrpv *grps, double max_var){
fbg_kmer_t *k;
fbg_edge_t *e, *p;
fbg_link_t *lnk;
u4i eidx2, eidx3;
u4i i, b, j, ng, avg, gidx;
u4i max_cov, max_eidx, key;
double sum;
e = ref_fbgedgev(fbg->edges, eidx);
ng = hierarchical_clustering_edge_links(fbg, e, grps, max_var);
encap_fbgedgev(fbg->edges, ng - 1);
k = ref_fbgkmerh(fbg->kmers, kidx);
e = ref_fbgedgev(fbg->edges, eidx);
e->key = key = e->key? 2 : 0;
e->most = 0;
if(DBGCNS_DEBUG){
if(ng > 1){
fprintf(stderr, "REVISE K%d -> K%d cov = %d into %d edges --\n", k->off, ref_fbgkmerh(fbg->kmers, e->node)->off, e->cov, ng); fflush(stderr);
}
}
ref_fbgkmerh(fbg->kmers, e->node)->n_in += ng - 1;
p = e;
p->link = 0;
eidx3 = e->next;
gidx = 0;
sum = 0;
max_cov = 0;
max_eidx = 0;
for(i=b=0;i<=grps->size;i++){
if(i == grps->size || grps->buffer[i].gidx != gidx){
avg = sum / (i - b) + 0.5;
if(p == NULL){
eidx2 = fbg->edges->size;
p = next_ref_fbgedgev(fbg->edges);
p->node = e->node;
e->next = eidx2;
p->next = eidx3;
}
p->link = 0;
p->cov = i - b;
p->dist = avg;
p->key = key;
p->select = 0;
p->most = 0;
if(p->cov > max_cov){
max_cov = p->cov;
max_eidx = offset_fbgedgev(fbg->edges, p);
} else if(p->cov == max_cov){
max_eidx = 0;
}
if(DBGCNS_DEBUG){
if(ng > 1){
fprintf(stderr, "+ %d %d --\n", p->cov, p->dist); fflush(stderr);
}
}
for(j=b;j<i;j++){
lnk = ref_fbglinkv(fbg->links, grps->buffer[j].lidx);
lnk->next = p->link;
p->link = grps->buffer[j].lidx;
if(lnk->key) p->key = 1;
}
e = p;
p = NULL;
b = i;
gidx ++;
sum = 0;
}
if(i < grps->size) sum += grps->buffer[i].len;
}
if(max_eidx){
ref_fbgedgev(fbg->edges, max_eidx)->most = 1;
}
return gidx;
}
static inline void revise_edge_cov_fbg(FBG *fbg, fbg_edge_t *e){
fbg_link_t *lnk;
u4i lidx, cnt;
double sum, var, max, avg, std;
sum = 0;
var = 0;
max = 0;
cnt = 0;
lidx = e->link;
while(lidx){
lnk = ref_fbglinkv(fbg->links, lidx);
if((double)lnk->rlen > max) max = lnk->rlen;
sum += lnk->rlen;
var += lnk->rlen * lnk->rlen;
cnt ++;
lidx = lnk->next;
}
if(cnt == 0) return;
avg = sum / cnt;
std = sqrt(var / cnt - avg * avg);
if(std > 10 && std > 0.2 * avg) std = 0.2 * max;
if(std < 1) std = 1;
cnt = 0;
sum = 0;
lidx = e->link;
while(lidx){
lnk = ref_fbglinkv(fbg->links, lidx);
if(num_diff((double)lnk->rlen, avg) <= std){
sum += lnk->rlen;
cnt ++;
}
lidx = lnk->next;
}
if(cnt == 0) cnt = 1;
avg = sum / cnt;
e->cov = cnt;
e->dist = avg + 0.5;
}
static inline void build_DirectFuzzyBruijnGraph(CNS *cns, u4i ridx, u4i cov_cutoff, double max_dist_var){
DBG *g;
dbgcns_kmer_t *k;
fbg_kmer_t A, *a;
fbg_edge_t *e;
fbg_link_t *l;
rd_kmer_t *rk;
u8i kmer;
u4i r, rr, i, j, beg, end, c, len, idx1, off1, idx2, off2, *u;
u4i eidx;
u1i b, *seq;
int exists;
g = cns->g;
// select high cov kmers
if(cov_cutoff){
seq = cns->qseqs->buffer + cns->qblks->buffer[ridx].off;
len = cns->qblks->buffer[ridx].len;
memset(&A, 0, sizeof(fbg_kmer_t));
kmer = 0;
j = 0x0000FFFFU;
for(i=0;i<len;){
b = seq[i];
kmer = ((kmer << 2) | b) & g->kmask;
i ++;
if(i < g->ksize) continue;
g->kmers->buffer[0].mer = kmer;
u = get_dbgcnskmerhash(g->khash, 0);
if(u == NULL) continue;
k = ref_dbgcnskmerv(g->kmers, *u);
if(k->cov < cov_cutoff) continue;
//if(j + 1 == i){ j = i; continue; }
A.mer = kmer;
a = prepare_fbgkmerh(cns->fbg->kmers, A, &exists);
if(exists){
a->closed = 1;
} else {
a->mer = kmer;
a->off = i - g->ksize;
a->closed = 0;
a->n_in = 0;
a->n_visit = 0;
a->edges = 0;
a->ptr = *u;
j = i;
}
}
} else {
// select best cov per 10 bp, but cov >= 4
clear_rdkmerv(cns->fbg->mats);
seq = cns->qseqs->buffer + cns->qblks->buffer[ridx].off;
len = cns->qblks->buffer[ridx].len;
memset(&A, 0, sizeof(fbg_kmer_t));
kmer = 0;
for(i=0;i<len;){
b = seq[i];
kmer = ((kmer << 2) | b) & g->kmask;
i ++;
if(i < g->ksize) continue;
g->kmers->buffer[0].mer = kmer;
u = get_dbgcnskmerhash(g->khash, 0);
if(u == NULL) continue;
if(g->kmers->buffer[*u].cov < 4) continue;
push_rdkmerv(cns->fbg->mats, (rd_kmer_t){ridx, *u, i - g->ksize, 0});
}
sort_array(cns->fbg->mats->buffer, cns->fbg->mats->size, rd_kmer_t, num_cmpgtx(g->kmers->buffer[b.kidx].cov, g->kmers->buffer[a.kidx].cov, a.kidx, b.kidx));
for(i=1;i<cns->fbg->mats->size;i++){
rk = ref_rdkmerv(cns->fbg->mats, i);
if(rk->kidx == ref_rdkmerv(cns->fbg->mats, i - 1)->kidx){
rk->closed = 1;
ref_rdkmerv(cns->fbg->mats, i - 1)->closed = 1;
}
}
sort_array(cns->fbg->mats->buffer, cns->fbg->mats->size, rd_kmer_t, num_cmpgt(a.koff, b.koff));
beg = 0;
j = 0xFFFFFFFFU;
for(i=0;i<cns->fbg->mats->size;i++){
rk = ref_rdkmerv(cns->fbg->mats, i);
if(rk->closed) continue;
if(j == 0xFFFFFFFFU) j = i;
if(rk->koff - beg < 10){
if(g->kmers->buffer[rk->kidx].cov > g->kmers->buffer[cns->fbg->mats->buffer[j].kidx].cov){
j = i;
}
continue;
}
rk = ref_rdkmerv(cns->fbg->mats, j);
beg = rk->koff;
j = i;
i --;
k = ref_dbgcnskmerv(g->kmers, rk->kidx);
kmer = k->mer;
A.mer = kmer;
a = prepare_fbgkmerh(cns->fbg->kmers, A, &exists);
if(exists){
a->closed = 1;
} else {
a->mer = kmer;
a->off = rk->koff;
a->closed = 0;
a->n_in = 0;
a->n_visit = 0;
a->edges = 0;
a->ptr = rk->kidx;
}
}
}
clear_rdkmerv(cns->fbg->mats);
for(r=0;r<cns->qblks->size;r++){
seq = cns->qseqs->buffer + cns->qblks->buffer[r].off;
len = cns->qblks->buffer[r].len;
memset(&A, 0, sizeof(fbg_kmer_t));
kmer = 0;
for(i=0;i<len;){
b = seq[i];
kmer = ((kmer << 2) | b) & g->kmask;
i ++;
if(i < g->ksize) continue;
A.mer = kmer;
a = get_fbgkmerh(cns->fbg->kmers, A);
if(a == NULL) continue;
if(a->closed) continue;
push_rdkmerv(cns->fbg->mats, (rd_kmer_t){r, offset_fbgkmerh(cns->fbg->kmers, a), i - g->ksize, 0});
}
}
sort_array(cns->fbg->mats->buffer, cns->fbg->mats->size, rd_kmer_t, num_cmpgtx(a.ridx, b.ridx, a.kidx, b.kidx));
for(i=1;i<cns->fbg->mats->size;i++){
if(cns->fbg->mats->buffer[i-1].ridx == cns->fbg->mats->buffer[i].ridx && cns->fbg->mats->buffer[i-1].kidx == cns->fbg->mats->buffer[i].kidx){
ref_fbgkmerh(cns->fbg->kmers, cns->fbg->mats->buffer[i].kidx)->closed = 1;
}
}
for(i=0;i<cns->fbg->mats->size;i++){
if(ref_fbgkmerh(cns->fbg->kmers, cns->fbg->mats->buffer[i].kidx)->closed){
cns->fbg->mats->buffer[i].closed = 1;
}
}
sort_array(cns->fbg->mats->buffer, cns->fbg->mats->size, rd_kmer_t, num_cmpgtx(a.ridx, b.ridx, a.koff, b.koff));
// add edges
for(i=0;i+1<cns->fbg->mats->size;i++){
if(cns->fbg->mats->buffer[i].closed) continue;
idx1 = cns->fbg->mats->buffer[i].kidx;
off1 = cns->fbg->mats->buffer[i].koff;
a = ref_fbgkmerh(cns->fbg->kmers, idx1);
for(j=i+1,c=0;j<cns->fbg->mats->size&&c<1;j++){
if(cns->fbg->mats->buffer[j].ridx != cns->fbg->mats->buffer[i].ridx) break;
if(cns->fbg->mats->buffer[j].closed) continue;
idx2 = cns->fbg->mats->buffer[j].kidx;
off2 = cns->fbg->mats->buffer[j].koff;
if(a->off >= ref_fbgkmerh(cns->fbg->kmers, idx2)->off) continue;
c ++;
eidx = a->edges;
while(eidx){
e = ref_fbgedgev(cns->fbg->edges, eidx);
if(e->node == idx2) break;
eidx = e->next;
}
if(eidx == 0){
eidx = cns->fbg->edges->size;
e = next_ref_fbgedgev(cns->fbg->edges);
e->node = idx2;
e->link = 0;
e->next = a->edges;
e->cov = 0;
e->dist = 0;
e->key = 0;
e->select = 0;
a->edges = eidx;
ref_fbgkmerh(cns->fbg->kmers, idx2)->n_in ++;
}
e = ref_fbgedgev(cns->fbg->edges, eidx);
if(cns->fbg->mats->buffer[i].ridx == ridx) e->key = 1;
e->cov ++;
l = next_ref_fbglinkv(cns->fbg->links);
l->ridx = cns->fbg->mats->buffer[i].ridx;
l->roff = off1;
l->rlen = off2 - off1;
l->key = (cns->fbg->mats->buffer[i].ridx == ridx);
l->select = 0;
l->next = e->link;
e->link = cns->fbg->links->size - 1;
}
}
rr = 0xFFFFFFFFU;
for(beg=end=0;beg<cns->fbg->mats->size;beg=end){
r = rr;
for(;end<cns->fbg->mats->size;end++){
if(cns->fbg->mats->buffer[end].closed) continue;
if(r == 0xFFFFFFFFU){
r = cns->fbg->mats->buffer[end].ridx;
} else if(cns->fbg->mats->buffer[end].ridx == r) continue;
else { rr = cns->fbg->mats->buffer[end].ridx; break; }
}
if(r == ridx) continue; // reference seq
for(i=beg;i+2<end;i++){
if(cns->fbg->mats->buffer[i].closed) continue;
idx1 = cns->fbg->mats->buffer[i].kidx;
off1 = cns->fbg->mats->buffer[i].koff;
a = ref_fbgkmerh(cns->fbg->kmers, idx1);
c = 0;
for(j=i+1;j<end;j++){
if(cns->fbg->mats->buffer[j].closed) continue;
idx2 = cns->fbg->mats->buffer[j].kidx;
off2 = cns->fbg->mats->buffer[j].koff;
if(a->off >= ref_fbgkmerh(cns->fbg->kmers, idx2)->off) continue;
c ++;
if(c < 2) continue;
if(c > 5) break;
eidx = a->edges;
while(eidx){
e = ref_fbgedgev(cns->fbg->edges, eidx);
if(e->node == idx2) break;
eidx = e->next;
}
if(eidx == 0) continue;
e = ref_fbgedgev(cns->fbg->edges, eidx);
e->cov ++;
l = next_ref_fbglinkv(cns->fbg->links);
l->ridx = r;
l->roff = off1;
l->rlen = off2 - off1;
l->key = 0;