mirror of
https://github.com/chhylp123/hifiasm.git
synced 2026-09-15 12:47:57 +08:00
1391 lines
49 KiB
C++
1391 lines
49 KiB
C++
#include <stdio.h>
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#include <stdlib.h>
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#include <assert.h>
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#include <zlib.h>
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#include "kseq.h" // FASTA/Q parser
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#include "kavl.h"
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#include "khash.h"
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#include "kalloc.h"
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#include "kthread.h"
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#include "inter.h"
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#include "Overlaps.h"
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#include "CommandLines.h"
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#include "htab.h"
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#include "Hash_Table.h"
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KSEQ_INIT(gzFile, gzread)
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#define MG_SEED_IGNORE (1ULL<<41)
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#define MG_SEED_TANDEM (1ULL<<42)
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#define MG_SEED_KEPT (1ULL<<43)
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#define MG_MAX_SEG 255
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#define MG_SEED_SEG_SHIFT 48
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#define MG_SEED_SEG_MASK (0xffULL<<(MG_SEED_SEG_SHIFT))
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#define mg_seg_id(a) ((int32_t)(((a).y&MG_SEED_SEG_MASK) >> MG_SEED_SEG_SHIFT))
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#define MG_SEED_WT_SHIFT 56
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#define MG_MAX_SHORT_K 15
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#define MG_SHORT_K_EXT 10000 ///1000 in minigraph
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#define generic_key(x) (x)
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KRADIX_SORT_INIT(gfa64, uint64_t, generic_key, 8)
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struct mg_tbuf_s {
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void *km;
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int frag_gap;
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};
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typedef struct mg_tbuf_s mg_tbuf_t;
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mg_tbuf_t *mg_tbuf_init(void)
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{
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mg_tbuf_t *b;
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b = (mg_tbuf_t*)calloc(1, sizeof(mg_tbuf_t));
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b->km = km_init();
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return b;
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}
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void mg_tbuf_destroy(mg_tbuf_t *b)
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{
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if (b == 0) return;
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if (b->km) km_destroy(b->km);
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free(b);
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}
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void *mg_tbuf_get_km(mg_tbuf_t *b)
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{
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return b->km;
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}
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typedef struct {
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int w, k, bw, max_gap, is_HPC, hap_n, occ_weight, max_gap_pre;
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int max_lc_skip, max_lc_iter, min_lc_cnt, min_lc_score;
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float chn_pen_gap;
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} mg_idxopt_t;
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typedef struct {
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ha_abufl_t *abl;
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st_mt_t sp;
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Candidates_list clist;
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overlap_region_alloc olist;
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} ma_ov_buf_t;
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typedef struct { // global data structure for kt_pipeline()
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const void *ha_flt_tab;
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const ha_pt_t *ha_idx;
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const mg_idxopt_t *opt;
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const ma_ug_t *ug;
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kseq_t *ks;
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int64_t chunk_size;
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uint64_t n_thread;
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uint64_t total_base;
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uint64_t total_pair;
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} uldat_t;
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typedef struct { // data structure for each step in kt_pipeline()
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const mg_idxopt_t *opt;
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const void *ha_flt_tab;
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const ha_pt_t *ha_idx;
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const ma_ug_t *ug;
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int n, m, sum_len;
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uint64_t *len, id;
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char **seq;
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ha_mzl_v *mzs;
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st_mt_t *sps;
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mg_tbuf_t **buf;
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} utepdat_t;
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typedef struct {
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///off: start idx in mg128_t * a[];
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///cnt: how many eles in this chain
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///a[off, off+cnt) saves the eles in this chain
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int32_t off, cnt:31, inner_pre:1;
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///ref_id|rev
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uint32_t v;
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///chain in ref: [rs, re)
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///chain in query: [qs, qe)
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int32_t rs, re, qs, qe;
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///score: chain score
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int32_t score, dist_pre;
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uint32_t hash_pre;
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} mg_lchain_t;
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typedef struct {
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uint32_t v, d;
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int32_t pre;
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} mg_pathv_t;
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KHASH_MAP_INIT_INT(sp, sp_topk_t)
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KHASH_MAP_INIT_INT(sp2, uint64_t)
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///mg128_t->y: weight(8)seg_id(8)flag(8)span(8)pos(32)
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///mg128_t->x: rid(31)rev(1)pos(33); keep reference
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typedef struct { uint64_t x, y; } mg128_t;
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#define sort_key_128x(a) ((a).x)
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KRADIX_SORT_INIT(128x, mg128_t, sort_key_128x, 8)
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void radix_sort_128x(mg128_t *beg, mg128_t *end);
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typedef struct {
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uint32_t n; ///length of candidate list
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uint64_t q_span:31, rev:1, q_pos:32;
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uint32_t qid:16, weight:15, is_tandem:1;
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const ha_idxposl_t *cr; ///candidate list
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} mg_match_t;
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// shortest path
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typedef struct {
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// input
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///(lj_ref_id)|(lj_ref_rev^1)
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uint32_t v;
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///target_dist should like the overlap length in string graph
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///it should be used to evaluate if the identified path is close to real path/alignment
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int32_t target_dist;
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uint32_t target_hash;
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///inner: if li and lj are at the same ref id
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///meta: j
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uint32_t meta:30, check_hash:1, inner:1;
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/**
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* There are two cases:
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* (1) lj->qs************lj->qe
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* li->qs************li->qe
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* (2) lj->qs************lj->qe
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* li->qs************li->qe
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* qlen = li->qs - lj->qe;///might be negative
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* **/
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int32_t qlen;
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// output
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uint32_t n_path:31, is_0:1;///I guess n_path is how many path from src to dest
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int32_t path_end;///looks like an idx to alignment
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int32_t dist, mlen;
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uint32_t hash;
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// aux
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uint64_t srt_key;
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} mg_path_dst_t;
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typedef struct {
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uint32_t srt;
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int32_t i;
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} gc_frag_t;
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///I think this structure is just used for iteration
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///iterate each ref id, instead of alignment id
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typedef struct sp_node_s {
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uint64_t di; // dist<<32 | node_id in avl tree(doesn't matter too much)
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uint32_t v;///ref_id|rev
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int32_t pre;
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uint32_t hash;
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int32_t is_0;
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KAVL_HEAD(struct sp_node_s) head;
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} sp_node_t, *sp_node_p;
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typedef struct {
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int32_t k, mlen;//k: number of walks from src to this node
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int32_t qs, qe;
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sp_node_t *p[MG_MAX_SHORT_K]; // this forms a max-heap
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} sp_topk_t;
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#define gc_frag_key(p) ((p).srt)
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KRADIX_SORT_INIT(gc, gc_frag_t, gc_frag_key, 4)
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#define dst_key(p) ((p).srt_key)
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KRADIX_SORT_INIT(dst, mg_path_dst_t, dst_key, 8)
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#define sp_node_cmp(a, b) (((a)->di > (b)->di) - ((a)->di < (b)->di))
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KAVL_INIT(sp, sp_node_t, head, sp_node_cmp)
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#define sp_node_lt(a, b) ((a)->di < (b)->di)
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KSORT_INIT(sp, sp_node_p, sp_node_lt)
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void init_mg_opt(mg_idxopt_t *opt, int is_HPC, int k, int w, int hap_n)
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{
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opt->k = k;
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opt->w = w;
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opt->hap_n = hap_n;
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opt->is_HPC = is_HPC;
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opt->bw = 2000;
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opt->max_gap = 5000;
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opt->occ_weight = 20;
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opt->max_gap_pre = 10000;///1000 in minigraph
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opt->max_lc_iter = 10000;
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opt->chn_pen_gap = 0.19;///using minimap2's value
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opt->max_lc_skip = 25;// mo->max_gc_skip = 25;
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opt->max_lc_iter = 10000;
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opt->min_lc_cnt = 2;
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opt->min_lc_score = 30;
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}
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void uidx_build(ma_ug_t *ug, mg_idxopt_t *opt)
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{
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int flag = asm_opt.flag;
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asm_opt.flag |= HA_F_NO_HPC;
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ha_flt_tab = ha_ft_ug_gen(&asm_opt, &(ug->u), opt->is_HPC, opt->k, opt->w, 1, opt->hap_n*10);
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ha_idx = ha_pt_ug_gen(&asm_opt, ha_flt_tab, &(ug->u), opt->is_HPC, opt->k, opt->w, 1);
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asm_opt.flag = flag;
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}
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void uidx_destory()
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{
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ha_ft_destroy(ha_flt_tab);
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ha_pt_destroy(ha_idx);
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}
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///only use non-repetitive minimizers
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static mg_match_t *collect_matches(void *km, int *_n_m, int max_occ, const void *ha_flt_tab, const ha_pt_t *ha_idx, int check_unique, const ha_mzl_v *mv, int64_t *n_a, int *rep_len, int *n_mini_pos, int32_t **mini_pos)
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{
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int rep_st = 0, rep_en = 0, n_m, tn, tw;
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size_t i;
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mg_match_t *m;
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*n_mini_pos = 0;
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KMALLOC(km, *mini_pos, mv->n);///mv->n how many minimizers in query
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m = (mg_match_t*)kmalloc(km, mv->n * sizeof(mg_match_t));
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for (i = 0, n_m = 0, *rep_len = 0, *n_a = 0; i < mv->n; ++i) {
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const ha_idxposl_t *cr;
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ha_mzl_t *z = &mv->a[i];
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cr = ha_ptl_get(ha_idx, z->x, &tn);
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tw = ha_ft_cnt(ha_flt_tab, z->x);
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if (tw > max_occ) { ///the frequency of repetitive regions; ignore those minimizers
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int en = z->pos + 1, st = en - z->span;//[st, en)
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if (st > rep_en) { ///just record the length of repetive regions
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*rep_len += rep_en - rep_st;
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rep_st = st, rep_en = en;
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} else rep_en = en;
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} else {
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mg_match_t *q = &m[n_m++];
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q->q_pos = z->pos, q->q_span = z->span, q->rev = z->rev, q->cr = cr, q->n = tn, q->qid = 0;
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q->is_tandem = 0, q->weight = 255;
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if(check_unique && tw != 1) q->is_tandem = 1, q->weight = 15;
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*n_a += q->n;///how many candidates
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(*mini_pos)[(*n_mini_pos)++] = z->pos;///minimizer offset in query
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}
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}
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*rep_len += rep_en - rep_st; ///the length of repetitive regions
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*_n_m = n_m;
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return m;
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}
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mg128_t *collect_seed_hits(void *km, const mg_idxopt_t *opt, int max_occ, const void *ha_flt_tab, const ha_pt_t *ha_idx,
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const ma_ug_t *ug, const ha_mzl_v *mv, int64_t *n_a, int *rep_len, int *n_mini_pos, int32_t **mini_pos)
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{
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int i, n_m;
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mg128_t *a = NULL;
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mg_match_t *m = collect_matches(km, &n_m, max_occ, ha_flt_tab, ha_idx, 1, mv, n_a, rep_len, n_mini_pos, mini_pos);
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a = (mg128_t*)kmalloc(km, *n_a * sizeof(mg128_t));///n_a: how many available candidates in total
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for (i = 0, *n_a = 0; i < n_m; ++i) {///n_m: how many available seeds, instead of candidates
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mg_match_t *q = &m[i];
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const ha_idxposl_t *r = q->cr;
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uint32_t k;
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for (k = 0; k < q->n; ++k) {///q->n: number of candidates belonging to seed m[i]
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mg128_t *p;
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p = &a[(*n_a)++];///pick up a slot for one candidate
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if (r[k].rev == q->rev) // forward strand
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p->x = (uint64_t)(r[k].rid)<<33|r[k].pos; ///reference: rid(31)|rev(1)|pos(32)
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else // reverse strand
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p->x = (uint64_t)(r[k].rid)<<33 | 1ULL<<32 | (ug->g->seq[r[k].rid].len - (r[k].pos + 1 - r[k].span) - 1);
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p->y = (uint64_t)q->q_span << 32 | q->q_pos;
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p->y |= (uint64_t)q->qid << MG_SEED_SEG_SHIFT;
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if (q->is_tandem) p->y |= MG_SEED_TANDEM;
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p->y |= (uint64_t)q->weight << MG_SEED_WT_SHIFT;
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///p->y: weight(8)seg_id(8)flag(8)span(8)pos(32)
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///p->x: rid(31)rev(1)pos(33); keep reference
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}
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}
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kfree(km, m);
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radix_sort_128x(a, a + (*n_a));
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return a;
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}
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///r is 1000 in default
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///remove isolated hits, whic are not close enough to others
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static int64_t flt_anchors(int64_t n_a, mg128_t *a, int32_t r)
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{
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int64_t i, j;
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for (i = 0; i < n_a; ++i) {
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for (j = i - 1; j >= 0; --j) {
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/**
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* a is sorted by x
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* a[].x: ref_id(31)rev(1)r_pos(32)
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* a[].y: weight(8)query_id(8)flag(8)span(8)q_pos(32)
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**/
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int32_t dq;
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int64_t dr = a[i].x - a[j].x;///a is sorted by x
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if (dr > r) break;///if two candidates coming from differnt unitigs, dr would be extremly large
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dq = (int32_t)a[i].y - (int32_t)a[j].y;
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if (dq > r || dq < 0) continue;
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a[j].y |= MG_SEED_KEPT;
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a[i].y |= MG_SEED_KEPT;
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break;
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}
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}
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for (i = n_a - 1; i >= 0; --i) {
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if (a[i].y & MG_SEED_KEPT) continue;
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for (j = i + 1; j < n_a; ++j) {
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int32_t dq;
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int64_t dr = a[j].x - a[i].x;
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if (dr > r) break;
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dq = (int32_t)a[j].y - (int32_t)a[i].y;
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if (dq > r || dq < 0) continue;
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a[j].y |= MG_SEED_KEPT;
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a[i].y |= MG_SEED_KEPT;
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break;
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}
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}
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for (i = j = 0; i < n_a; ++i)
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if (a[i].y & MG_SEED_KEPT)
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a[j++] = a[i];
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return j;
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}
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static inline float mg_log2(float x) // NB: this doesn't work when x<2
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{
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union { float f; uint32_t i; } z = { x };
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float log_2 = ((z.i >> 23) & 255) - 128;
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z.i &= ~(255 << 23);
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z.i += 127 << 23;
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log_2 += (-0.34484843f * z.f + 2.02466578f) * z.f - 0.67487759f;
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return log_2;
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}
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inline int32_t normal_sc(uint64_t w, int32_t sc)
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{
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if(w < 255){
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int32_t tmp = (int)(0.00392156862745098 * w * sc); // 0.00392... = 1/255
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sc = tmp > 1? tmp : 1;
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}
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return sc;
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}
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// ai[].x: ref_id(31)rev(1)r_pos(32)
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// ai[].y: weight(8)query_id(8)flag(8)span(8)q_pos(32)
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// comput_sc(&a[i], &a[j], max_dist_x, max_dist_y, bw, chn_pen_gap, chn_pen_skip, is_cdna, n_segs);
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static inline int32_t comput_sc(const mg128_t *ai, const mg128_t *aj, int32_t max_dist_x, int32_t max_dist_y, int32_t bw, float chn_pen_gap)
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{
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int32_t dq = (int32_t)ai->y - (int32_t)aj->y, dr = (int32_t)ai->x - (int32_t)aj->x, dd, dg, q_span, sc;
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///ai and aj has already been sorted by x
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///which means ai->x >= aj->x
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if (dq <= 0 || dq > max_dist_x) return INT32_MIN;
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if (dr <= 0 || dr > max_dist_y) return INT32_MIN;
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dd = dr > dq? dr - dq : dq - dr; ///indel, dd is always >= 0
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if (dd > bw) return INT32_MIN;
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dg = dr < dq? dr : dq;///MIN(dr, dq)
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q_span = aj->y>>32&0xff;///query span; should be ai->y>>32&0xff, is it a bug?
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sc = normal_sc(aj->y>>MG_SEED_WT_SHIFT, (q_span<dg?q_span:dg)); ///positive part of sc
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///dd: there are indels
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///dg > q_span: there are some bases that are not covered between ai and aj
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///it is if (dd || dg > q_span) in minigraph
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if (dd) {
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float lin_pen, log_pen;
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lin_pen = chn_pen_gap * (float)dd;
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log_pen = dd >= 2? mg_log2(dd) : 0.0f; // mg_log2() only works for dd>=2
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sc -= (int)(lin_pen + log_pen);
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}
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return sc;
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}
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///p[]: id of last
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///f[]: the score ending at i, not always the peak
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///v[]: keeps the peak score up to i;
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///t[]: id of next
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///min_cnt = 2; min_sc = 30; extra_u = 0
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///u = mg_chain_backtrack(n, f, p, v, t, min_cnt, min_sc, 0, &n_u, &n_v);
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uint64_t *mg_chain_backtrack(void *km, int64_t n, const int32_t *f, const int64_t *p, int32_t *v, int32_t *t, int32_t min_cnt, int32_t min_sc, int32_t extra_u, int32_t *n_u_, int32_t *n_v_)
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{
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mg128_t *z;
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uint64_t *u;
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int64_t i, k, n_z, n_v;
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int32_t n_u;
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// v[] keeps the peak score up to i; f[] is the score ending at i, not always the peak
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*n_u_ = *n_v_ = 0;
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for (i = 0, n_z = 0; i < n; ++i) // precompute n_z
|
|
if (f[i] >= min_sc) ++n_z;
|
|
if (n_z == 0) return 0;
|
|
KMALLOC(km, z, n_z);
|
|
for (i = 0, k = 0; i < n; ++i) // populate z[]
|
|
if (f[i] >= min_sc) z[k].x = f[i], z[k++].y = i;
|
|
radix_sort_128x(z, z + n_z);///sort by score
|
|
|
|
memset(t, 0, n * 4);///t is a buffer
|
|
///from the largest to the smallest
|
|
for (k = n_z - 1, n_v = n_u = 0; k >= 0; --k) { // precompute n_u
|
|
int64_t n_v0 = n_v;
|
|
int32_t sc;
|
|
///note t[i] == 0 is not used to find local alignment
|
|
///say if we have already found a long chain, then the secondary might be able to merged to the long chain
|
|
///t[i] == 0 is used to find those chains
|
|
for (i = z[k].y; i >= 0 && t[i] == 0; i = p[i])
|
|
++n_v, t[i] = 1;
|
|
sc = i < 0? z[k].x : (int32_t)z[k].x - f[i];
|
|
if (sc >= min_sc && n_v > n_v0 && n_v - n_v0 >= min_cnt)
|
|
++n_u;///how many chains, including primary chains and non-primary chains
|
|
else n_v = n_v0;
|
|
}
|
|
KMALLOC(km, u, n_u + extra_u);
|
|
memset(t, 0, n * 4);
|
|
for (k = n_z - 1, n_v = n_u = 0; k >= 0; --k) { // populate u[]
|
|
int64_t n_v0 = n_v;
|
|
int32_t sc;
|
|
for (i = z[k].y; i >= 0 && t[i] == 0; i = p[i])
|
|
v[n_v++] = i, t[i] = 1;
|
|
sc = i < 0? z[k].x : (int32_t)z[k].x - f[i];
|
|
if (sc >= min_sc && n_v > n_v0 && n_v - n_v0 >= min_cnt)
|
|
u[n_u++] = (uint64_t)sc << 32 | (n_v - n_v0);
|
|
else n_v = n_v0;
|
|
}
|
|
kfree(km, z);
|
|
assert(n_v < INT32_MAX);
|
|
*n_u_ = n_u, *n_v_ = n_v;
|
|
return u;
|
|
}
|
|
|
|
//u[]: sc|occ of chains
|
|
//v[]: idx of each element
|
|
static mg128_t *compact_a(void *km, int32_t n_u, uint64_t *u, int32_t n_v, int32_t *v, mg128_t *a)
|
|
{
|
|
mg128_t *b, *w;
|
|
uint64_t *u2;
|
|
int64_t i, j, k;
|
|
|
|
// write the result to b[]
|
|
KMALLOC(km, b, n_v);
|
|
for (i = 0, k = 0; i < n_u; ++i) {
|
|
int32_t k0 = k, ni = (int32_t)u[i];
|
|
for (j = 0; j < ni; ++j)
|
|
b[k++] = a[v[k0 + (ni - j - 1)]];///write all elements of a chain together
|
|
}
|
|
kfree(km, v);
|
|
|
|
// sort u[] and a[] by the target position, such that adjacent chains may be joined
|
|
KMALLOC(km, w, n_u);
|
|
for (i = k = 0; i < n_u; ++i) {///n_u: how many chains
|
|
///x: ref_id(31)rev(1)r_pos(32)
|
|
w[i].x = b[k].x, w[i].y = (uint64_t)k<<32|i;
|
|
k += (int32_t)u[i];
|
|
}
|
|
radix_sort_128x(w, w + n_u);///sort by ref_id(31)rev(1)r_pos(32); r_pos is the start pos of chain
|
|
KMALLOC(km, u2, n_u);
|
|
for (i = k = 0; i < n_u; ++i) {///note merge chain; just place close chains together
|
|
///j is chain id; n is how many elements in j-th chain
|
|
int32_t j = (int32_t)w[i].y, n = (int32_t)u[j];
|
|
u2[i] = u[j];
|
|
memcpy(&a[k], &b[w[i].y>>32], n * sizeof(mg128_t));
|
|
k += n;
|
|
}
|
|
memcpy(u, u2, n_u * 8);
|
|
memcpy(b, a, k * sizeof(mg128_t)); // write _a_ to _b_ and deallocate _a_ because _a_ is oversized, sometimes a lot
|
|
kfree(km, a); kfree(km, w); kfree(km, u2);
|
|
return b;
|
|
}
|
|
|
|
/* Input:
|
|
* a[].x: ref_id(31)rev(1)r_pos(32)
|
|
* a[].y: weight(8)query_id(8)flag(8)span(8)q_pos(32)
|
|
* n: length of a[]
|
|
* Output:
|
|
* n_u: #chains
|
|
* u[]: score<<32 | #anchors (sum of lower 32 bits of u[] is the returned length of a[])
|
|
* input a[] is deallocated on return
|
|
*/
|
|
///is_cdna is is_splice
|
|
mg128_t *mg_lchain_dp(int max_dist_x, int max_dist_y, int bw, int max_skip, int max_iter, int min_cnt, int min_sc, float chn_pen_gap,
|
|
int64_t n, mg128_t *a, int *n_u_, uint64_t **_u, void *km)
|
|
{ // TODO: make sure this works when n has more than 32 bits
|
|
int32_t *f, *t, *v, n_u, n_v;
|
|
int64_t *p, i, j, max_ii, st = 0;
|
|
uint64_t *u;
|
|
|
|
if (_u) *_u = 0, *n_u_ = 0;
|
|
if (n == 0 || a == 0) return 0;
|
|
KMALLOC(km, p, n);///id of last cell
|
|
KMALLOC(km, f, n);///f[] is the score ending at i, not always the peak
|
|
KMALLOC(km, v, n);///v[] keeps the peak score up to i;
|
|
KCALLOC(km, t, n);///t doesn't matter too much; it is mainly used to accelrate the iteration
|
|
|
|
// a[].x: ref_id(31)rev(1)r_pos(32)
|
|
// a[].y: weight(8)query_id(8)flag(8)span(8)q_pos(32)
|
|
// fill the score and backtrack arrays
|
|
for (i = st = 0, max_ii = -1; i < n; ++i) {
|
|
int64_t max_j = -1, end_j;
|
|
///max_f -> minimizer span length in query, which is the initial score
|
|
int32_t max_f = normal_sc(a[i].y>>MG_SEED_WT_SHIFT, a[i].y>>32&0xff), n_skip = 0;
|
|
///until we are at the same rid, same direction, and the coordinates are close enough
|
|
while (st < i && (a[i].x>>32 != a[st].x>>32 || a[i].x > a[st].x + max_dist_x)) ++st;
|
|
///max_iter = 10000 in default, which means dp can go back to up to 10000 cells
|
|
if (i - st > max_iter) st = i - max_iter;
|
|
for (j = i - 1; j >= st; --j) {
|
|
int32_t sc;
|
|
sc = comput_sc(&a[i], &a[j], max_dist_x, max_dist_y, bw, chn_pen_gap);
|
|
if (sc == INT32_MIN) continue;
|
|
sc += f[j];
|
|
if (sc > max_f) {
|
|
max_f = sc, max_j = j;
|
|
if (n_skip > 0) --n_skip;
|
|
} else if (t[j] == (int32_t)i) {///note we scan j backwards; we don't need to update t[] for each i
|
|
if (++n_skip > max_skip)
|
|
break;
|
|
}
|
|
if (p[j] >= 0) t[p[j]] = i;
|
|
}
|
|
end_j = j;///end_j might be > 0
|
|
///if not close enough, select a new max
|
|
if (max_ii < 0 || (int64_t)(a[i].x - a[max_ii].x) > (int64_t)max_dist_x) {///select a new max
|
|
int32_t max = INT32_MIN;
|
|
max_ii = -1;
|
|
for (j = i - 1; j >= st; --j)
|
|
if (max < f[j]) max = f[j], max_ii = j;
|
|
}
|
|
///note: it will happen when `max_ii` < `end_j`;
|
|
///iteration is terminated at `end_j` mostly because of `max_skip` and `max_iter`
|
|
if (max_ii >= 0 && max_ii < end_j) {
|
|
int32_t tmp;
|
|
tmp = comput_sc(&a[i], &a[max_ii], max_dist_x, max_dist_y, bw, chn_pen_gap);
|
|
if (tmp != INT32_MIN && max_f < tmp + f[max_ii])
|
|
max_f = tmp + f[max_ii], max_j = max_ii;
|
|
}
|
|
// v[] keeps the peak score up to i; f[] is the score ending at i, not always the peak
|
|
f[i] = max_f, p[i] = max_j;
|
|
v[i] = max_j >= 0 && v[max_j] > max_f? v[max_j] : max_f;
|
|
if (max_ii < 0 || ((int64_t)(a[i].x - a[max_ii].x) <= (int64_t)max_dist_x && f[max_ii] < f[i]))
|
|
max_ii = i;
|
|
}
|
|
///after mg_chain_backtrack, the results are saved in u and v;
|
|
u = mg_chain_backtrack(km, n, f, p, v, t, min_cnt, min_sc, 0, &n_u, &n_v);
|
|
*n_u_ = n_u, *_u = u; // NB: note that u[] may not be sorted by score here
|
|
kfree(km, p); kfree(km, f); kfree(km, t);
|
|
if (n_u == 0) {
|
|
kfree(km, a); kfree(km, v);
|
|
return 0;
|
|
}
|
|
//u[]: sc|occ of chains
|
|
//v[]: idx of each element
|
|
return compact_a(km, n_u, u, n_v, v, a);
|
|
}
|
|
|
|
///qlen: query length
|
|
///u[]: sc|occ of chains
|
|
///a[]: candidate list
|
|
mg_lchain_t *mg_lchain_gen(void *km, int qlen, int n_u, uint64_t *u, mg128_t *a)
|
|
{
|
|
mg128_t *z;
|
|
mg_lchain_t *r;
|
|
int i, k;
|
|
|
|
if (n_u == 0) return 0;
|
|
KCALLOC(km, r, n_u); KMALLOC(km, z, n_u);
|
|
// u[] is sorted by query position
|
|
for (i = k = 0; i < n_u; ++i) {
|
|
/**
|
|
* a[].x: ref_id(31)rev(1)r_pos(32)
|
|
* a[].y: weight(8)query_id(8)flag(8)span(8)q_pos(32)
|
|
**/
|
|
///u[]: sc(32)occ(32)
|
|
int32_t qs = (int32_t)a[k].y + 1 - (a[k].y>>32 & 0xff);
|
|
z[i].x = (uint64_t)qs << 32 | u[i] >> 32;
|
|
z[i].y = (uint64_t)k << 32 | (int32_t)u[i];
|
|
k += (int32_t)u[i];
|
|
}
|
|
radix_sort_128x(z, z + n_u);//sort by qs|sc
|
|
|
|
// populate r[]
|
|
for (i = 0; i < n_u; ++i) {
|
|
mg_lchain_t *ri = &r[i];
|
|
/**
|
|
* z[].x: query start pos| chain score
|
|
* z[].y: idx in a[] | chain occ
|
|
* a[].x: ref_id(31)rev(1)r_pos(32)
|
|
* a[].y: weight(8)query_id(8)flag(8)span(8)q_pos(32)
|
|
* **/
|
|
int32_t k = z[i].y >> 32, q_span = a[k].y >> 32 & 0xff;
|
|
ri->off = k;
|
|
ri->cnt = (int32_t)z[i].y;
|
|
ri->score = (uint32_t)z[i].x;
|
|
ri->v = a[k].x >> 32;///ref_id|rev
|
|
ri->rs = (int32_t)a[k].x + 1 > q_span? (int32_t)a[k].x + 1 - q_span : 0; // for HPC k-mer
|
|
ri->qs = z[i].x >> 32;
|
|
ri->re = (int32_t)a[k + ri->cnt - 1].x + 1;
|
|
ri->qe = (int32_t)a[k + ri->cnt - 1].y + 1;
|
|
}
|
|
kfree(km, z);
|
|
return r;
|
|
}
|
|
|
|
static int32_t get_mini_idx(const mg128_t *a, int32_t n, const int32_t *mini_pos)
|
|
{
|
|
int32_t x, L = 0, R = n - 1;
|
|
x = (int32_t)a->y;
|
|
while (L <= R) { // binary search
|
|
int32_t m = ((uint64_t)L + R) >> 1;
|
|
int32_t y = mini_pos[m];
|
|
if (y < x) L = m + 1;
|
|
else if (y > x) R = m - 1;
|
|
else return m;
|
|
}
|
|
return -1;
|
|
}
|
|
|
|
/* Before:
|
|
* a[].x: ref_id(31)rev(1)r_pos(32)
|
|
* a[].y: weight(8)query_id(8)flag(8)span(8)q_pos(32)
|
|
* After:
|
|
* a[].x: idx_in_minimizer_arr(32)r_pos(32)
|
|
* a[].y: weight(8)query_id(8)flag(8)span(8)q_pos(32)
|
|
*/
|
|
void mg_update_anchors(int32_t n_a, mg128_t *a, int32_t n, const int32_t *mini_pos)
|
|
{
|
|
int32_t st, j, k;
|
|
if (n_a <= 0) return;
|
|
st = get_mini_idx(&a[0], n, mini_pos);
|
|
assert(st >= 0);
|
|
for (k = 0, j = st; j < n && k < n_a; ++j)
|
|
if ((int32_t)a[k].y == mini_pos[j])
|
|
a[k].x = (uint64_t)j << 32 | (a[k].x & 0xffffffffU), ++k;
|
|
assert(k == n_a);
|
|
}
|
|
|
|
static int32_t find_max(int32_t n, const gc_frag_t *gf, uint32_t x)
|
|
{
|
|
int32_t s = 0, e = n;
|
|
if (n == 0) return -1;
|
|
if (gf[n-1].srt < x) return n - 1;
|
|
if (gf[0].srt >= x) return -1;
|
|
while (e > s) { // TODO: finish this block
|
|
int32_t m = s + (e - s) / 2;
|
|
if (gf[m].srt >= x) e = m;
|
|
else s = m + 1;
|
|
}
|
|
assert(s == e);
|
|
return s;
|
|
}
|
|
///target_dist should like the overlap length in string graph
|
|
///it should be used to evaluate if the identified path is close to real path/alignment
|
|
static int32_t mg_target_dist(const asg_t *g, const mg_lchain_t *l0, const mg_lchain_t *l1)
|
|
{
|
|
/**
|
|
case 1: l0->qs************l0->qe
|
|
l1->qs************l1->qe
|
|
case 2: l0->qs************l0->qe
|
|
l1->qs************l1->qe
|
|
|
|
*****l0->rs************l0->re*****
|
|
****l1->rs************l1->re**
|
|
* **/
|
|
///min_dist = l1->rs + (g->seg[l0->v>>1].len - l0->re);
|
|
// below equals (l1->qs - l0->qe) - min_dist + g->seg[l1->v>>1].len; see mg_gchain1_dp() for the calculation of min_dist
|
|
//(l1->qs - l0->qe) is the gap in query, min_dist is the gap in reference
|
|
return (l1->qs - l0->qe) - (g->seq[l0->v>>1].len - l0->re) + (g->seq[l1->v>>1].len - l1->rs);
|
|
// when l0->v == l1->v, the above becomes (l1->qs - l0->qe) - (l1->rs - l0->re), which is what we want
|
|
}
|
|
|
|
static inline sp_node_t *gen_sp_node(void *km, uint32_t v, int32_t d, int32_t id)
|
|
{
|
|
sp_node_t *p;
|
|
KMALLOC(km, p, 1);
|
|
p->v = v, p->di = (uint64_t)d<<32 | id, p->pre = -1, p->is_0 = 1;
|
|
return p;
|
|
}
|
|
|
|
///max_dist is like the overlap length in string graph
|
|
///mg_shortest_k(km, g, li->v^1, n_dst, dst, max_dist_g + (g->seg[li->v>>1].len - li->rs), MG_MAX_SHORT_K, 0, 0, 1, 0);
|
|
///the end position of qs is li->qs; dst[]->->qlen indicate the region that need to be checked in bases
|
|
mg_pathv_t *mg_shortest_k(void *km0, const asg_t *g, uint32_t src, int32_t n_dst, mg_path_dst_t *dst, int32_t max_dist, int32_t max_k, int32_t ql, const char *qs, int is_rev, int32_t *n_pathv)
|
|
{
|
|
sp_node_t *p, *root = 0, **out;
|
|
sp_topk_t *q;
|
|
khash_t(sp) *h;
|
|
khash_t(sp2) *h2;
|
|
void *km;
|
|
khint_t k;
|
|
int absent;
|
|
int32_t i, j, n_done, n_found, n_seeds = 0;
|
|
uint32_t id, n_out, m_out;
|
|
int8_t *dst_done;
|
|
mg_pathv_t *ret = 0;
|
|
uint64_t *dst_group, *seeds = 0;
|
|
/** //path
|
|
void *h_seeds = 0;
|
|
mg128_v mini = {0,0,0};
|
|
**/
|
|
|
|
if (n_pathv) *n_pathv = 0;///for us, n_pathv = NULL
|
|
if (n_dst <= 0) return 0;///n_dst: how many candidate nodes
|
|
for (i = 0; i < n_dst; ++i) { // initialize
|
|
mg_path_dst_t *t = &dst[i];
|
|
///if src and dest are at the same ref id, there are already one path
|
|
if (t->inner)///if two chains are at the same ref id
|
|
t->dist = 0, t->n_path = 1, t->path_end = -1;
|
|
else
|
|
t->dist = -1, t->n_path = 0, t->path_end = -1;
|
|
}
|
|
if (max_k > MG_MAX_SHORT_K) max_k = MG_MAX_SHORT_K;
|
|
km = km_init2(km0, 0x4000);
|
|
|
|
/** //path
|
|
///for the first time, we just check th reachability without sequence (qs);
|
|
///but for the second round, we need to check sequence
|
|
///qs is the sequence between two minimizers
|
|
if (ql > 0 && qs) { // build the seed hash table for the query
|
|
mg_sketch(km, qs, ql, MG_SHORT_KW, MG_SHORT_KK, 0, &mini);
|
|
// mini->a[].x = hash_key<<8 | kmerSpan
|
|
// mini->a[].y = rid<<32 | lastPos<<1 | strand
|
|
if (is_rev)///is_rev = 1;
|
|
for (i = 0; i < mini.n; ++i)///reverse qs[0, ql) to qs(ql, 0]
|
|
mini.a[i].y = (ql - (((int32_t)mini.a[i].y>>1) + 1 - MG_SHORT_KK) - 1) << 1 | ((mini.a[i].y&1)^1);
|
|
///h_seeds is the ordinary hash index
|
|
h_seeds = mg_idx_a2h(km, mini.n, mini.a, 0, &seeds, &n_seeds);
|
|
///h_seeds+seeds+n_seeds ----> hash index of qs[0, ql)
|
|
}
|
|
**/
|
|
|
|
KCALLOC(km, dst_done, n_dst);
|
|
KMALLOC(km, dst_group, n_dst);
|
|
// multiple dst[] may have the same dst[].v. We need to group them first.
|
|
// in other words, one ref id may have multiple dst alignment chains
|
|
for (i = 0; i < n_dst; ++i)
|
|
dst_group[i] = (uint64_t)dst[i].v<<32 | i;
|
|
radix_sort_gfa64(dst_group, dst_group + n_dst);
|
|
|
|
h2 = kh_init2(sp2, km); // this hash table keeps all destinations from the same ref id
|
|
kh_resize(sp2, h2, n_dst * 2);
|
|
///please note that one contig in ref may have multiple alignment chains
|
|
///so h2 is a index that helps us to query it
|
|
///key(h2) = ref id; value(h2) = start_idx | occ
|
|
for (i = 1, j = 0; i <= n_dst; ++i) {
|
|
if (i == n_dst || dst_group[i]>>32 != dst_group[j]>>32) {
|
|
k = kh_put(sp2, h2, dst_group[j]>>32, &absent);
|
|
kh_val(h2, k) = (uint64_t)j << 32 | (i - j);
|
|
assert(absent);
|
|
j = i;
|
|
}
|
|
}
|
|
|
|
|
|
|
|
h = kh_init2(sp, km); // this hash table keeps visited vertices; path to each visited vertice
|
|
kh_resize(sp, h, 16);
|
|
|
|
m_out = 16, n_out = 0;///16 is just the initial size
|
|
KMALLOC(km, out, m_out);
|
|
|
|
/**
|
|
typedef struct {
|
|
int32_t k, mlen;//k: number of walks from src to this node
|
|
int32_t qs, qe;
|
|
sp_node_t *p[MG_MAX_SHORT_K]; // this forms a max-heap; all path
|
|
} sp_topk_t;
|
|
**/
|
|
id = 0;
|
|
p = gen_sp_node(km, src, 0, id++);///just malloc a node for src; the distance is 0
|
|
p->hash = __ac_Wang_hash(src);
|
|
kavl_insert(sp, &root, p, 0);///should be avl tree
|
|
|
|
k = kh_put(sp, h, src, &absent);///here is a hash table
|
|
q = &kh_val(h, k);
|
|
q->k = 1, q->p[0] = p, q->mlen = 0, q->qs = q->qe = -1;
|
|
|
|
n_done = 0;
|
|
///the key of avl tree: #define sp_node_cmp(a, b) (((a)->di > (b)->di) - ((a)->di < (b)->di))
|
|
///the higher bits of (*)->di is distance to src node
|
|
///so the key of avl tree is distance
|
|
while (kavl_size(head, root) > 0) {///thr first root is src
|
|
int32_t i, nv;
|
|
asg_arc_t *av;
|
|
sp_node_t *r;
|
|
///note that one node might be visited multiple times if there are circles
|
|
///delete the first node
|
|
r = kavl_erase_first(sp, &root); // take out the closest vertex in the heap (as a binary tree)
|
|
//fprintf(stderr, "XX\t%d\t%d\t%d\t%c%s[%d]\t%d\n", n_out, kavl_size(head, root), n_finished, "><"[(r->v&1)^1], g->seg[r->v>>1].name, r->v, (int32_t)(r->di>>32));
|
|
if (n_out == m_out) KEXPAND(km, out, m_out);
|
|
///higher 32 bits might be the distance to root node
|
|
// lower 32 bits now for position in the out[] array
|
|
r->di = r->di>>32<<32 | n_out; ///n_out is just the id in out
|
|
///so one node id in graph might be saved multiple times in avl tree and out[]
|
|
out[n_out++] = r;///out[0] = src
|
|
|
|
///r->v is the dst vertex id
|
|
///sometimes k==kh_end(h2). Some nodes are found by graph travesal but not in linear chain alignment
|
|
k = kh_get(sp2, h2, r->v);
|
|
// we have reached one dst vertex
|
|
// note that one dst vertex may have multipe alignment chains
|
|
// we can visit some nodes in graph which are not reachable during chaining
|
|
// h2 is used to determine if one node is reachable or not
|
|
if (k != kh_end(h2)) {
|
|
///node r->v might be visited multiple times
|
|
int32_t j, dist = r->di>>32, off = kh_val(h2, k) >> 32, cnt = (int32_t)kh_val(h2, k);
|
|
//src can reach ref id r->v; there might be not only one alignment chain in r->v
|
|
//so we need to scan all of them
|
|
for (j = 0; j < cnt; ++j) {
|
|
mg_path_dst_t *t = &dst[(int32_t)dst_group[off + j]];
|
|
int32_t done = 0;
|
|
///the src and dest are at the same ref id, say we directly find the shortest path
|
|
if (t->inner) {
|
|
done = 1;
|
|
} else {
|
|
int32_t mlen = 0, copy = 0;
|
|
///in the first round, we just check reachability without sequence
|
|
///so h_seeds = NULL; we can assume mlen = 0
|
|
/** //path
|
|
mlen = h_seeds? path_mlen(out, n_out - 1, h, t->qlen) : 0;
|
|
**/
|
|
//if (mg_dbg_flag & MG_DBG_GC1) fprintf(stderr, " src=%c%s[%d],qlen=%d\tdst=%c%s[%d]\ttarget_distx=%d,target_hash=%x\tdistx=%d,mlen=%d,hash=%x\n", "><"[src&1], g->seg[src>>1].name, src, ql, "><"[t->v&1], g->seg[t->v>>1].name, t->v, t->target_dist - g->seg[src>>1].len, t->target_hash, dist - g->seg[src>>1].len, mlen, r->hash);
|
|
// note: t indicates a linear alignmnet, instead of a node in graph
|
|
///target_dist should be the distance on query
|
|
if (t->n_path == 0) { // keep the shortest path
|
|
copy = 1;
|
|
} else if (t->target_dist >= 0) { // we have a target distance; choose the closest
|
|
if (dist == t->target_dist && t->check_hash && r->hash == t->target_hash) { // we found the target path
|
|
copy = 1, done = 1;
|
|
} else {
|
|
int32_t d0 = t->dist, d1 = dist;
|
|
d0 = d0 > t->target_dist? d0 - t->target_dist : t->target_dist - d0;
|
|
d1 = d1 > t->target_dist? d1 - t->target_dist : t->target_dist - d1;
|
|
///if the new distance (d1) is smaller than the old distance (d0), update the results
|
|
///in other words, the length of new path should be closer to t->target_dist
|
|
if (d1 - mlen/2 < d0 - t->mlen/2) copy = 1;
|
|
}
|
|
}
|
|
if (copy) {
|
|
t->path_end = n_out - 1, t->dist = dist, t->hash = r->hash, t->mlen = mlen, t->is_0 = r->is_0;
|
|
if (t->target_dist >= 0) {
|
|
///src is from li from li to lj, so the dis is generally increased
|
|
///target_dist should be the distance on query
|
|
if (dist == t->target_dist && t->check_hash && r->hash == t->target_hash) done = 1;
|
|
else if (dist > t->target_dist + MG_SHORT_K_EXT) done = 1;
|
|
}
|
|
}
|
|
++t->n_path;///we found a path to the alignment t
|
|
if (t->n_path >= max_k) done = 1;
|
|
}
|
|
if (dst_done[off + j] == 0 && done)
|
|
dst_done[off + j] = 1, ++n_done;
|
|
}
|
|
///if all alignments have been settle down
|
|
///pre-end; accelerate the loop
|
|
if (n_done == n_dst) break;
|
|
}
|
|
|
|
///below is used to push new nodes to avl tree for iteration
|
|
nv = asg_arc_n(g, r->v);
|
|
av = asg_arc_a(g, r->v);
|
|
for (i = 0; i < nv; ++i) { // visit all neighbors
|
|
asg_arc_t *ai = &av[i];
|
|
///v_lv is the (dest_length - overlap_length); it is a normal path length in string graph
|
|
///ai->v_lv is the path length from r->v to ai->w
|
|
///(r->di>>32)
|
|
int32_t d = (r->di>>32) + (uint32_t)ai->ul;
|
|
if (d > max_dist) continue; // don't probe vertices too far away
|
|
///ai->w is the dest ref id; we insert a new ref id, instead of an alignment chain
|
|
k = kh_put(sp, h, ai->v, &absent);///one node might be visited multiple times
|
|
q = &kh_val(h, k);
|
|
if (absent) { // a new vertex visited
|
|
///q->k: number of walks from src to ai->w
|
|
q->k = 0, q->qs = q->qe = -1; q->mlen = 0;
|
|
///h_seeds = NULL; so q->mlen = 0
|
|
/** //path
|
|
q->mlen = h_seeds && d + gfa_arc_lw(g, *ai) <= max_dist? node_mlen(km, g, ai->w, &mini, h_seeds, n_seeds, seeds, &q->qs, &q->qe) : 0;
|
|
**/
|
|
//if (ql && qs) fprintf(stderr, "ql=%d,src=%d\tv=%c%s[%d],n_seeds=%d,mlen=%d\n", ql, src, "><"[ai->w&1], g->seg[ai->w>>1].name, ai->w, n_seeds, q->mlen);
|
|
}
|
|
///if there are less than <max_k> walks from src to ai->w, directly add
|
|
///if there are more, keep the smallest <max_k> walks
|
|
if (q->k < max_k) { // enough room: add to the heap
|
|
p = gen_sp_node(km, ai->v, d, id++);
|
|
p->pre = n_out - 1;///the parent node of this one
|
|
p->hash = r->hash + __ac_Wang_hash(ai->v);
|
|
p->is_0 = r->is_0;
|
|
/** //path
|
|
if (ai->rank > 0) p->is_0 = 0;
|
|
**/
|
|
kavl_insert(sp, &root, p, 0);
|
|
q->p[q->k++] = p;
|
|
ks_heapup_sp(q->k, q->p);///adjust heap by distance
|
|
} else if (q->p[0]->di>>32 > d) { // shorter than the longest path so far: replace the longest
|
|
p = kavl_erase(sp, &root, q->p[0], 0);
|
|
if (p) {
|
|
p->di = (uint64_t)d<<32 | (id++);
|
|
p->pre = n_out - 1;
|
|
p->hash = r->hash + __ac_Wang_hash(ai->v);
|
|
p->is_0 = r->is_0;
|
|
/** //path
|
|
if (ai->rank > 0) p->is_0 = 0;
|
|
**/
|
|
kavl_insert(sp, &root, p, 0);
|
|
ks_heapdown_sp(0, q->k, q->p);
|
|
} else {
|
|
fprintf(stderr, "Warning: logical bug in gfa_shortest_k(): q->k=%d,q->p[0]->{d,i}={%d,%d},d=%d,src=%u,max_dist=%d,n_dst=%d\n", q->k, (int32_t)(q->p[0]->di>>32), (int32_t)q->p[0]->di, d, src, max_dist, n_dst);
|
|
km_destroy(km);
|
|
return 0;
|
|
}
|
|
} // else: the path is longer than all the existing paths ended at ai->w
|
|
}
|
|
}
|
|
|
|
kfree(km, dst_group);
|
|
kfree(km, dst_done);
|
|
kh_destroy(sp, h);
|
|
mg_idx_hfree(h_seeds);
|
|
kfree(km, seeds);
|
|
kfree(km, mini.a);
|
|
// NB: AVL nodes are not deallocated. When km==0, they are memory leaks.
|
|
|
|
for (i = 0, n_found = 0; i < n_dst; ++i)
|
|
if (dst[i].n_path > 0) ++n_found;///n_path might be larger than 16
|
|
///we can assume n_pathv = NULL for now
|
|
if (n_found > 0 && n_pathv) { // then generate the backtrack array
|
|
int32_t n, *trans;
|
|
KCALLOC(km, trans, n_out); // used to squeeze unused elements in out[]
|
|
for (i = 0; i < n_dst; ++i) { // mark dst vertices with a target distance
|
|
mg_path_dst_t *t = &dst[i];
|
|
if (t->n_path > 0 && t->target_dist >= 0 && t->path_end >= 0)
|
|
trans[(int32_t)out[t->path_end]->di] = 1;
|
|
}
|
|
for (i = 0; i < n_out; ++i) { // mark dst vertices without a target distance
|
|
k = kh_get(sp2, h2, out[i]->v);
|
|
if (k != kh_end(h2)) { // TODO: check if this is correct!
|
|
int32_t off = kh_val(h2, k)>>32, cnt = (int32_t)kh_val(h2, k);
|
|
for (j = off; j < off + cnt; ++j)
|
|
if (dst[j].target_dist < 0)
|
|
trans[i] = 1;
|
|
}
|
|
}
|
|
for (i = n_out - 1; i >= 0; --i) // mark all predecessors
|
|
if (trans[i] && out[i]->pre >= 0)
|
|
trans[out[i]->pre] = 1;
|
|
for (i = n = 0; i < n_out; ++i) // generate coordinate translations
|
|
if (trans[i]) trans[i] = n++;
|
|
else trans[i] = -1;
|
|
|
|
*n_pathv = n;
|
|
KMALLOC(km0, ret, n);
|
|
for (i = 0; i < n_out; ++i) { // generate the backtrack array
|
|
mg_pathv_t *p;
|
|
if (trans[i] < 0) continue;
|
|
p = &ret[trans[i]];
|
|
p->v = out[i]->v, p->d = out[i]->di >> 32;
|
|
p->pre = out[i]->pre < 0? out[i]->pre : trans[out[i]->pre];
|
|
}
|
|
for (i = 0; i < n_dst; ++i) // translate "path_end"
|
|
if (dst[i].path_end >= 0)
|
|
dst[i].path_end = trans[dst[i].path_end];
|
|
}
|
|
|
|
km_destroy(km);
|
|
return ret;
|
|
}
|
|
|
|
|
|
int32_t mg_gchain1_dp(void *km, const ma_ug_t *ug, int32_t *n_lc_, mg_lchain_t *lc, int32_t qlen, int32_t max_dist_g, int32_t max_dist_q, int32_t bw, int32_t max_skip,
|
|
int32_t ref_bonus, float chn_pen_gap, float chn_pen_skip, float mask_level, int32_t max_gc_seq_ext, const char *qseq, const mg128_t *an, uint64_t **u_)
|
|
{
|
|
int32_t i, j, k, m_dst, n_dst, n_ext, n_u, n_v, n_lc = *n_lc_;
|
|
int32_t *f, *v, *t;
|
|
int64_t *p;
|
|
uint64_t *u;
|
|
mg_path_dst_t *dst;
|
|
gc_frag_t *a;
|
|
mg_lchain_t *swap;
|
|
char *qs;
|
|
asg_t *g = ug->g;
|
|
|
|
*u_ = 0;
|
|
if (n_lc == 0) return 0;
|
|
|
|
KMALLOC(km, a, n_lc);
|
|
///n_lc how many linear chains
|
|
for (i = n_ext = 0; i < n_lc; ++i) { // a[] is a view of frag[]; for sorting
|
|
mg_lchain_t *r = &lc[i];
|
|
gc_frag_t *ai = &a[i];
|
|
int32_t is_isolated = 0, min_end_dist_g;
|
|
r->dist_pre = -1;///indicate parent in graph chain
|
|
min_end_dist_g = g->seq[r->v>>1].len - r->re;///r->v: ref_id|rev
|
|
if (r->rs < min_end_dist_g) min_end_dist_g = r->rs;
|
|
if (min_end_dist_g > max_dist_g) is_isolated = 1; // if too far from segment ends
|
|
else if (min_end_dist_g>>3 > r->score) is_isolated = 1; // if the lchain too small relative to distance to the segment ends
|
|
ai->srt = (uint32_t)is_isolated<<31 | r->qe;
|
|
ai->i = i;
|
|
if (!is_isolated) ++n_ext;
|
|
}
|
|
///if the alignment is too far from segment ends, which means it cannot contribute to graph alignment
|
|
if (n_ext < 2) { // no graph chaining needed; early return
|
|
kfree(km, a);
|
|
KMALLOC(km, u, n_lc);
|
|
for (i = 0; i < n_lc; ++i)
|
|
u[i] = (uint64_t)lc[i].score<<32 | 1;
|
|
*u_ = u;
|
|
return n_lc;
|
|
}
|
|
radix_sort_gc(a, a + n_lc);///sort by: is_isolated(1):qe
|
|
|
|
KMALLOC(km, v, n_lc);
|
|
KMALLOC(km, f, n_ext);
|
|
KMALLOC(km, p, n_ext);
|
|
KCALLOC(km, t, n_ext);
|
|
// KMALLOC(km, qs, max_dist_q + 1);//for
|
|
|
|
m_dst = n_dst = 0, dst = 0;
|
|
///n_ext is number of linear chains that might be included in graph chains
|
|
///sorted by the positions in query; sorted by qe of each chain
|
|
for (i = 0; i < n_ext; ++i) { // core loop
|
|
gc_frag_t *ai = &a[i];
|
|
mg_lchain_t *li = &lc[ai->i];///linear chain; sorted by qe, i.e. end position in query
|
|
///note segi is query id, instead of ref id; it is not such useful
|
|
/**
|
|
* a[].x: idx_in_minimizer_arr(32)r_pos(32)
|
|
* a[].y: weight(8)query_id(8)flag(8)span(8)q_pos(32)
|
|
**/
|
|
{ // collect end points potentially reachable from _i_
|
|
int32_t x = li->qs + bw, n_skip = 0;
|
|
if (x > qlen) x = qlen;
|
|
///collect alignments that can be reachable from the left side
|
|
///that is, a[x].qe <= x
|
|
x = find_max(i, a, x);
|
|
n_dst = 0;
|
|
for (j = x; j >= 0; --j) { // collect potential destination vertices
|
|
gc_frag_t *aj = &a[j];
|
|
//potential chains that might be overlapped with the left side of li
|
|
mg_lchain_t *lj = &lc[aj->i];
|
|
mg_path_dst_t *q;
|
|
int32_t target_dist, dq;
|
|
///lj->qs >= li->qs && lj->qe <= li->qs, so lj is contained
|
|
if (lj->qs >= li->qs) continue; // lj is contained in li on the query coordinate
|
|
///lj->qs************lj->qe
|
|
/// li->qs************li->qe
|
|
if (lj->qe > li->qs) { // test overlap on the query
|
|
int o = lj->qe - li->qs;
|
|
///mask_level = 0.5, if overlap is too long
|
|
///note here is the overlap in query, so too long overlaps might be wrong
|
|
if (o > (lj->qe - lj->qs) * mask_level || o > (li->qe - li->qs) * mask_level)
|
|
continue;
|
|
}
|
|
dq = li->qs - lj->qe;///dq might be smaller than 0
|
|
if (dq > max_dist_q) break; // if query gap too large, stop
|
|
///The above filter chains like:
|
|
///1. lj is contained in li
|
|
///2. the overlap between li and lj is too large
|
|
///3. li and lj are too far
|
|
/**
|
|
lj->qs************lj->qe
|
|
li->qs************li->qe
|
|
|
|
*****lj->rs************lj->re*****
|
|
****li->rs************li->re**
|
|
**/
|
|
///above we have checked gap/overlap in query
|
|
///then we need to check gap/overlap in reference
|
|
if (li->v != lj->v) { // the two linear chains are on two different refs
|
|
// minimal graph gap; the real graph gap might be larger
|
|
int32_t min_dist = li->rs + (g->seq[lj->v>>1].len - lj->re);
|
|
if (min_dist > max_dist_g) continue; // graph gap too large
|
|
//note here min_dist - (lj->qs - li->qe) > bw is important
|
|
//min_dist is always larger than 0, (lj->qs - li->qe) might be negative
|
|
if (min_dist - bw > li->qs - lj->qe) continue; ///note seg* is the query id, instead of ref id
|
|
target_dist = mg_target_dist(g, lj, li);
|
|
if (target_dist < 0) continue; // this may happen if the query overlap is far too large
|
|
} else if (lj->rs >= li->rs || lj->re >= li->re) { // not colinear
|
|
continue;
|
|
} else {///li->v == lj->v and colinear; at the same ref id
|
|
/**
|
|
case 1: lj->qs************lj->qe
|
|
li->qs************li->qe
|
|
case 2: lj->qs************lj->qe
|
|
li->qs************li->qe
|
|
|
|
*****lj->rs************lj->re*****
|
|
****li->rs************li->re**
|
|
* **/
|
|
///w is indel, w is always positive
|
|
int32_t dr = li->rs - lj->re, w = dr > dq? dr - dq : dq - dr;
|
|
///note that l*->v is the ref id, while seg* is the query id
|
|
if (w > bw) continue; // test bandwidth
|
|
if (dr > max_dist_g || dr < -max_dist_g) continue;
|
|
if (lj->re > li->rs) { // test overlap on the graph segment
|
|
int o = lj->re - li->rs;
|
|
if (o > (lj->re - lj->rs) * mask_level || o > (li->re - li->rs) * mask_level)
|
|
continue;
|
|
}
|
|
target_dist = mg_target_dist(g, lj, li);
|
|
}
|
|
if (n_dst == m_dst) KEXPAND(km, dst, m_dst); // TODO: watch out the quadratic behavior!
|
|
q = &dst[n_dst++];///q saves information for i->j
|
|
memset(q, 0, sizeof(mg_path_dst_t));
|
|
///note v is (rid:rev), so two alignment chains might be at the same ref id with different directions
|
|
q->inner = (li->v == lj->v);
|
|
q->v = lj->v^1;///must be v^1 instead of v
|
|
q->meta = j;
|
|
///lj->qs************lj->qe
|
|
/// li->qs************li->qe
|
|
q->qlen = li->qs - lj->qe;///might be negative
|
|
q->target_dist = target_dist;///cannot understand the target_dist
|
|
q->target_hash = 0;
|
|
q->check_hash = 0;
|
|
if (t[j] == i) {///this pre-cut is weird; attention
|
|
if (++n_skip > max_skip)
|
|
break;
|
|
}
|
|
if (p[j] >= 0) t[p[j]] = i;
|
|
}
|
|
}
|
|
///the above saves all linear chains that might be reached to the left side of chain i
|
|
///all those chains are saved to dst<n_dst>
|
|
{ // confirm reach-ability
|
|
int32_t k;
|
|
// test reach-ability without sequences
|
|
/**
|
|
*****lj->rs************lj->re*****
|
|
****li->rs************li->re***
|
|
(g->seg[li->v>>1].len - li->rs) ----> is like the node length in string graph
|
|
**/
|
|
mg_shortest_k(km, g, li->v^1, n_dst, dst, max_dist_g + (g->seq[li->v>>1].len - li->rs), MG_MAX_SHORT_K, 0, 0, 1, 0);
|
|
// remove unreachable destinations
|
|
for (j = k = 0; j < n_dst; ++j) {
|
|
mg_path_dst_t *dj = &dst[j];
|
|
int32_t sc;
|
|
if (dj->n_path == 0) continue; // unreachable
|
|
sc = cal_sc(dj, li, lc, an, a, f, bw, ref_bonus, chn_pen_gap);
|
|
if (sc == INT32_MIN) continue; // out of band
|
|
if (sc + li->score < 0) continue; // negative score and too low
|
|
dst[k] = dst[j];
|
|
dst[k++].srt_key = INT64_MAX/2 - (int64_t)sc; // sort in the descending order
|
|
}
|
|
n_dst = k;
|
|
if (n_dst > 0) {
|
|
radix_sort_dst(dst, dst + n_dst);
|
|
// discard weaker chains if the best score is much larger (assuming base-level heuristic won't lift it to the top chain)
|
|
// dst[0].srt_key has the largest score
|
|
for (j = 1; j < n_dst; ++j)
|
|
if (dst[j].srt_key - dst[0].srt_key > li->score)//discard chains with too small weight
|
|
break;
|
|
n_dst = j;
|
|
if (n_dst > max_gc_seq_ext) n_dst = max_gc_seq_ext; // discard weaker chains
|
|
}
|
|
}
|
|
if (n_dst > 0) { // find paths with sequences
|
|
int32_t min_qs = li->qs;
|
|
for (j = 0; j < n_dst; ++j) {
|
|
const mg_lchain_t *lj;
|
|
assert(dst[j].n_path > 0);
|
|
///a[]->srt = (uint32_t)is_isolated<<31 | r->qe;
|
|
///a[]->i = i;
|
|
lj = &lc[a[dst[j].meta].i];
|
|
if (lj->qe < min_qs) min_qs = lj->qe;
|
|
}
|
|
///qs keeps the sequence at the gap between the li and lj in query
|
|
memcpy(qs, &qseq[min_qs], li->qs - min_qs);
|
|
mg_shortest_k(km, g, li->v^1, n_dst, dst, max_dist_g + (g->seg[li->v>>1].len - li->rs), MG_MAX_SHORT_K, li->qs - min_qs, qs, 1, 0);
|
|
if (mg_dbg_flag & MG_DBG_GC1) fprintf(stderr, "[src:%d] q_intv=[%d,%d), src=%c%s[%d], n_dst=%d, max_dist=%d, min_qs=%d, lc_score=%d\n", ai->i, li->qs, li->qe, "><"[(li->v&1)^1], g->seg[li->v>>1].name, li->v^1, n_dst, max_dist_g + (g->seg[li->v>>1].len - li->rs), min_qs, li->score);
|
|
}
|
|
{ // DP
|
|
int32_t max_f = li->score, max_j = -1, max_d = -1, max_inner = 0;
|
|
uint32_t max_hash = 0;
|
|
for (j = 0; j < n_dst; ++j) {
|
|
mg_path_dst_t *dj = &dst[j];
|
|
int32_t sc;
|
|
sc = cal_sc(dj, li, lc, an, a, f, bw, ref_bonus, chn_pen_gap);
|
|
if (sc == INT32_MIN) continue;
|
|
if (mg_dbg_flag & MG_DBG_GC1) {
|
|
mg_lchain_t *lj = &lc[a[dj->meta].i];
|
|
fprintf(stderr, " [dst:%d] dst=%c%s[%d], n_path=%d, target=%d, opt_dist=%d, score=%d, q_intv=[%d,%d), g_intv=[%d,%d)\n", dj->meta, "><"[dj->v&1], g->seg[dj->v>>1].name, dj->v, dj->n_path, dj->target_dist - g->seg[li->v>>1].len, dj->dist - g->seg[li->v>>1].len, sc, lj->qs, lj->qe, lj->rs, lj->re);
|
|
}
|
|
if (sc > max_f) max_f = sc, max_j = dj->meta, max_d = dj->dist, max_hash = dj->hash, max_inner = dj->inner;
|
|
}
|
|
f[i] = max_f, p[i] = max_j;
|
|
li->dist_pre = max_d;
|
|
li->hash_pre = max_hash;
|
|
li->inner_pre = max_inner;
|
|
v[i] = max_j >= 0 && v[max_j] > max_f? v[max_j] : max_f;
|
|
if (mg_dbg_flag & MG_DBG_GC1) fprintf(stderr, " [opt:%d] opt=%d, max_f=%d\n", ai->i, max_j, max_f);
|
|
}
|
|
}
|
|
kfree(km, dst);
|
|
kfree(km, qs);
|
|
if (mg_dbg_flag & MG_DBG_GC1) {
|
|
int32_t mmax_f = 0, mmax_i = -1;
|
|
for (i = 0; i < n_ext; ++i) if (f[i] > mmax_f) mmax_f = f[i], mmax_i = i;
|
|
i = mmax_i; while (i >= 0) { fprintf(stderr, "[best] i=%d, seg=%s, max_f=%d, chn_pen_gap=%f\n", a[i].i, g->seg[lc[a[i].i].v>>1].name, f[i], chn_pen_gap); i = p[i]; }
|
|
}
|
|
///n_ext: number of useful chains
|
|
///n_lc - n_ext: number of isoated chains
|
|
u = mg_chain_backtrack(km, n_ext, f, p, v, t, 0, 0, n_lc - n_ext, &n_u, &n_v);
|
|
kfree(km, f); kfree(km, p); kfree(km, t);
|
|
///store the extra isoated chains
|
|
for (i = 0; i < n_lc - n_ext; ++i) {
|
|
u[n_u++] = (uint64_t)lc[a[n_ext + i].i].score << 32 | 1;
|
|
v[n_v++] = n_ext + i;
|
|
}
|
|
|
|
///reorganize lc;
|
|
KMALLOC(km, swap, n_v);
|
|
for (i = 0, k = 0; i < n_u; ++i) {
|
|
int32_t k0 = k, ni = (int32_t)u[i];
|
|
for (j = 0; j < ni; ++j)
|
|
swap[k++] = lc[a[v[k0 + (ni - j - 1)]].i];
|
|
}
|
|
assert(k == n_v);
|
|
memcpy(lc, swap, n_v * sizeof(mg_lchain_t));
|
|
*n_lc_ = n_v;
|
|
*u_ = u;
|
|
|
|
kfree(km, a);
|
|
kfree(km, swap);
|
|
kfree(km, v);
|
|
return n_u;
|
|
}
|
|
|
|
|
|
void mg_map_frag(const void *ha_flt_tab, const ha_pt_t *ha_idx, const ma_ug_t *ug, const uint32_t qid, const int qlen, const char *qseq, ha_mzl_v *mz,
|
|
st_mt_t *sp, mg_tbuf_t *b, int32_t w, int32_t k, int32_t hpc, int32_t mz_sd, int32_t mz_rewin, const mg_idxopt_t *opt)
|
|
{
|
|
mg128_t *a = NULL;
|
|
int64_t n_a;
|
|
int32_t *mini_pos;
|
|
int i, rep_len, n_mini_pos, n_lc, max_chain_gap_qry, max_chain_gap_ref;
|
|
uint64_t *u;
|
|
mg_lchain_t *lc;
|
|
mz->n = 0;
|
|
mz2_ha_sketch(qseq, qlen, w, k, 0, hpc, mz, ha_flt_tab, mz_sd, NULL, NULL, NULL, -1, -1, -1, sp, mz_rewin, 1);
|
|
///a[]->y: weight(8)seg_id(8)flag(8)span(8)pos(32);--->query
|
|
///a[]->x: rid(31)rev(1)rpos(33);--->reference
|
|
a = collect_seed_hits(b->km, opt, opt->hap_n, ha_flt_tab, ha_idx, ug, mz, &n_a, &rep_len, &n_mini_pos, &mini_pos);
|
|
if (opt->max_gap_pre > 0 && opt->max_gap_pre * 2 < opt->max_gap) n_a = flt_anchors(n_a, a, opt->max_gap_pre);
|
|
max_chain_gap_qry = max_chain_gap_ref = opt->max_gap;
|
|
if (n_a == 0) {
|
|
if(a) kfree(b->km, a);
|
|
a = 0, n_lc = 0, u = 0;
|
|
} else {
|
|
a = mg_lchain_dp(max_chain_gap_ref, max_chain_gap_qry, opt->bw, opt->max_lc_skip, opt->max_lc_iter,
|
|
opt->min_lc_cnt, opt->min_lc_score, opt->chn_pen_gap, n_a, a, &n_lc, &u, b->km);
|
|
}
|
|
|
|
if (n_lc) {///n_lc is how many chain we found
|
|
lc = mg_lchain_gen(b->km, qlen, n_lc, u, a);
|
|
for (i = 0; i < n_lc; ++i)///update a[] since ref_id|rev has already been saved to lc[].v
|
|
mg_update_anchors(lc[i].cnt, &a[lc[i].off], n_mini_pos, mini_pos);///update a[].x
|
|
} else lc = 0;
|
|
kfree(b->km, mini_pos); kfree(b->km, u);
|
|
|
|
/**
|
|
* up to here, a[] has been changed
|
|
* a[].x: idx_in_minimizer_arr(32)r_pos(32)
|
|
* a[].y: weight(8)query_id(8)flag(8)span(8)q_pos(32)
|
|
**/
|
|
|
|
}
|
|
|
|
static void worker_for_ul_alignment(void *data, long i, int tid) // callback for kt_for()
|
|
{
|
|
utepdat_t *s = (utepdat_t*)data;
|
|
// ma_ov_buf_t *b = s->mo[tid];
|
|
mg_map_frag(s->ha_flt_tab, s->ha_idx, s->ug, s->id+i, s->len[i], s->seq[i], &(s->mzs[tid]), &(s->sps[tid]), s->buf[tid], s->opt->w, s->opt->k,
|
|
s->opt->is_HPC, asm_opt.mz_sample_dist, asm_opt.mz_rewin, s->opt);
|
|
|
|
}
|
|
|
|
static void *worker_ul_pipeline(void *data, int step, void *in) // callback for kt_pipeline()
|
|
{
|
|
uldat_t *p = (uldat_t*)data;
|
|
///uint64_t total_base = 0, total_pair = 0;
|
|
if (step == 0) { // step 1: read a block of sequences
|
|
int ret;
|
|
uint64_t l;
|
|
utepdat_t *s;
|
|
CALLOC(s, 1);
|
|
s->ha_flt_tab = p->ha_flt_tab; s->ha_idx = p->ha_idx; s->id = p->total_pair; s->opt = p->opt; s->ug = p->ug;
|
|
while ((ret = kseq_read(p->ks)) >= 0)
|
|
{
|
|
if (p->ks->seq.l < (uint64_t)p->opt->k) continue;
|
|
if (s->n == s->m) {
|
|
s->m = s->m < 16? 16 : s->m + (s->n>>1);
|
|
REALLOC(s->len, s->m);
|
|
REALLOC(s->seq, s->m);
|
|
}
|
|
l = p->ks->seq.l;
|
|
MALLOC(s->seq[s->n], l);
|
|
s->sum_len += l;
|
|
memcpy(s->seq[s->n], p->ks->seq.s, l);
|
|
s->len[s->n++] = l;
|
|
if (s->sum_len >= p->chunk_size) break;
|
|
}
|
|
p->total_pair += s->n;
|
|
if (s->sum_len == 0) free(s);
|
|
else return s;
|
|
}
|
|
else if (step == 1) { // step 2: alignment
|
|
uint64_t i;
|
|
utepdat_t *s = (utepdat_t*)in;
|
|
CALLOC(s->mzs, p->n_thread);
|
|
CALLOC(s->sps, p->n_thread);
|
|
|
|
s->buf = (mg_tbuf_t**)calloc(p->n_thread, sizeof(mg_tbuf_t*));
|
|
for (i = 0; i < p->n_thread; ++i) s->buf[i] = mg_tbuf_init();
|
|
/**
|
|
CALLOC(s->pos, s->n);
|
|
**/
|
|
kt_for(p->n_thread, worker_for_ul_alignment, s, s->n);
|
|
for (i = 0; i < (uint64_t)s->n; ++i) {
|
|
free(s->seq[i]);
|
|
p->total_base += s->len[i];
|
|
}
|
|
free(s->seq); free(s->len);
|
|
|
|
for (i = 0; i < p->n_thread; ++i) mg_tbuf_destroy(s->buf[i]);
|
|
free(s->buf);
|
|
return s;
|
|
}
|
|
else if (step == 2) { // step 3: dump
|
|
utepdat_t *s = (utepdat_t*)in;
|
|
/**
|
|
int i;
|
|
for (i = 0; i < s->n; ++i) {
|
|
// if(s->pos[i].a == NULL) continue;
|
|
// kv_push(pe_hit_hap, p->hits, s->pos[i]);
|
|
if(s->pos[i].s == (uint64_t)-1) continue;
|
|
kv_push(pe_hit, p->hits.a, s->pos[i]);
|
|
}
|
|
free(s->pos);
|
|
**/
|
|
free(s);
|
|
}
|
|
return 0;
|
|
}
|
|
|
|
int alignment_ul_pipeline(uldat_t* sl, const enzyme *fn)
|
|
{
|
|
double index_time = yak_realtime();
|
|
int i;
|
|
for (i = 0; i < fn->n; i++){
|
|
gzFile fp;
|
|
if ((fp = gzopen(fn->a[i], "r")) == 0) return 0;
|
|
sl->ks = kseq_init(fp);
|
|
kt_pipeline(3, worker_ul_pipeline, sl, 3);
|
|
kseq_destroy(sl->ks);
|
|
gzclose(fp);
|
|
}
|
|
fprintf(stderr, "[M::%s::%.3f] ==> Qualification\n", __func__, yak_realtime()-index_time);
|
|
return 1;
|
|
}
|
|
|
|
int ul_align(mg_idxopt_t *opt, const enzyme *fn, void *ha_flt_tab, ha_pt_t *ha_idx, ma_ug_t *ug)
|
|
{
|
|
uldat_t sl; memset(&sl, 0, sizeof(sl));
|
|
sl.ha_flt_tab = ha_flt_tab;
|
|
sl.ha_idx = ha_idx;
|
|
sl.opt = opt;
|
|
sl.chunk_size = 20000000;
|
|
sl.n_thread = asm_opt.thread_num;
|
|
sl.ug = ug;
|
|
alignment_ul_pipeline(&sl, fn);
|
|
return 1;
|
|
}
|
|
|
|
void ul_resolve(ma_ug_t *ug, int hap_n)
|
|
{
|
|
mg_idxopt_t opt;
|
|
init_mg_opt(&opt, 0, 19, 10, hap_n);
|
|
uidx_build(ug, &opt);
|
|
ul_align(&opt, asm_opt.ar, ha_flt_tab, ha_idx, ug);
|
|
|
|
|
|
|
|
|
|
uidx_destory();
|
|
} |