1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
|
#ifndef KSW2_H_
#define KSW2_H_
#include <stdint.h>
#define KSW_NEG_INF -0x40000000
#define KSW_EZ_SCORE_ONLY 0x01 // don't record alignment path/cigar
#define KSW_EZ_RIGHT 0x02 // right-align gaps
#define KSW_EZ_GENERIC_SC 0x04 // without this flag: match/mismatch only; last symbol is a wildcard
#define KSW_EZ_APPROX_MAX 0x08 // approximate max; this is faster with sse
#define KSW_EZ_APPROX_DROP 0x10 // approximate Z-drop; faster with sse
#define KSW_EZ_EXTZ_ONLY 0x40 // only perform extension
#define KSW_EZ_REV_CIGAR 0x80 // reverse CIGAR in the output
#define KSW_EZ_SPLICE_FOR 0x100
#define KSW_EZ_SPLICE_REV 0x200
#define KSW_EZ_SPLICE_FLANK 0x400
#define KSW_EZ_SPLICE_CMPLX 0x800
// The subset of CIGAR operators used by ksw code.
// Use MM_CIGAR_* from minimap.h if you need the full list.
#define KSW_CIGAR_MATCH 0
#define KSW_CIGAR_INS 1
#define KSW_CIGAR_DEL 2
#define KSW_CIGAR_N_SKIP 3
#ifdef __cplusplus
extern "C" {
#endif
typedef struct {
uint32_t max:31, zdropped:1;
int max_q, max_t; // max extension coordinate
int mqe, mqe_t; // max score when reaching the end of query
int mte, mte_q; // max score when reaching the end of target
int score; // max score reaching both ends; may be KSW_NEG_INF
int m_cigar, n_cigar;
int reach_end;
uint32_t *cigar;
} ksw_extz_t;
/**
* NW-like extension
*
* @param km memory pool, when used with kalloc
* @param qlen query length
* @param query query sequence with 0 <= query[i] < m
* @param tlen target length
* @param target target sequence with 0 <= target[i] < m
* @param m number of residue types
* @param mat m*m scoring mattrix in one-dimension array
* @param gapo gap open penalty; a gap of length l cost "-(gapo+l*gape)"
* @param gape gap extension penalty
* @param w band width (<0 to disable)
* @param zdrop off-diagonal drop-off to stop extension (positive; <0 to disable)
* @param flag flag (see KSW_EZ_* macros)
* @param ez (out) scores and cigar
*/
void ksw_extz(void *km, int qlen, const uint8_t *query, int tlen, const uint8_t *target, int8_t m, const int8_t *mat,
int8_t q, int8_t e, int w, int zdrop, int flag, ksw_extz_t *ez);
void ksw_extz2_sse(void *km, int qlen, const uint8_t *query, int tlen, const uint8_t *target, int8_t m, const int8_t *mat,
int8_t q, int8_t e, int w, int zdrop, int end_bonus, int flag, ksw_extz_t *ez);
void ksw_extd(void *km, int qlen, const uint8_t *query, int tlen, const uint8_t *target, int8_t m, const int8_t *mat,
int8_t gapo, int8_t gape, int8_t gapo2, int8_t gape2, int w, int zdrop, int flag, ksw_extz_t *ez);
void ksw_extd2_sse(void *km, int qlen, const uint8_t *query, int tlen, const uint8_t *target, int8_t m, const int8_t *mat,
int8_t gapo, int8_t gape, int8_t gapo2, int8_t gape2, int w, int zdrop, int end_bonus, int flag, ksw_extz_t *ez);
void ksw_exts2_sse(void *km, int qlen, const uint8_t *query, int tlen, const uint8_t *target, int8_t m, const int8_t *mat,
int8_t gapo, int8_t gape, int8_t gapo2, int8_t noncan, int zdrop, int8_t junc_bonus, int flag, const uint8_t *junc, ksw_extz_t *ez);
void ksw_extf2_sse(void *km, int qlen, const uint8_t *query, int tlen, const uint8_t *target, int8_t mch, int8_t mis, int8_t e, int w, int xdrop, ksw_extz_t *ez);
/**
* Global alignment
*
* (first 10 parameters identical to ksw_extz_sse())
* @param m_cigar (modified) max CIGAR length; feed 0 if cigar==0
* @param n_cigar (out) number of CIGAR elements
* @param cigar (out) BAM-encoded CIGAR; caller need to deallocate with kfree(km, )
*
* @return score of the alignment
*/
int ksw_gg(void *km, int qlen, const uint8_t *query, int tlen, const uint8_t *target, int8_t m, const int8_t *mat, int8_t gapo, int8_t gape, int w, int *m_cigar_, int *n_cigar_, uint32_t **cigar_);
int ksw_gg2(void *km, int qlen, const uint8_t *query, int tlen, const uint8_t *target, int8_t m, const int8_t *mat, int8_t gapo, int8_t gape, int w, int *m_cigar_, int *n_cigar_, uint32_t **cigar_);
int ksw_gg2_sse(void *km, int qlen, const uint8_t *query, int tlen, const uint8_t *target, int8_t m, const int8_t *mat, int8_t gapo, int8_t gape, int w, int *m_cigar_, int *n_cigar_, uint32_t **cigar_);
void *ksw_ll_qinit(void *km, int size, int qlen, const uint8_t *query, int m, const int8_t *mat);
int ksw_ll_i16(void *q, int tlen, const uint8_t *target, int gapo, int gape, int *qe, int *te);
#ifdef __cplusplus
}
#endif
/************************************
*** Private macros and functions ***
************************************/
#ifdef HAVE_KALLOC
#include "kalloc.h"
#else
#include <stdlib.h>
#define kmalloc(km, size) malloc((size))
#define kcalloc(km, count, size) calloc((count), (size))
#define krealloc(km, ptr, size) realloc((ptr), (size))
#define kfree(km, ptr) free((ptr))
#endif
static inline uint32_t *ksw_push_cigar(void *km, int *n_cigar, int *m_cigar, uint32_t *cigar, uint32_t op, int len)
{
if (*n_cigar == 0 || op != (cigar[(*n_cigar) - 1]&0xf)) {
if (*n_cigar == *m_cigar) {
*m_cigar = *m_cigar? (*m_cigar)<<1 : 4;
cigar = (uint32_t*)krealloc(km, cigar, (*m_cigar) << 2);
}
cigar[(*n_cigar)++] = len<<4 | op;
} else cigar[(*n_cigar)-1] += len<<4;
return cigar;
}
// In the backtrack matrix, value p[] has the following structure:
// bit 0-2: which type gets the max - 0 for H, 1 for E, 2 for F, 3 for \tilde{E} and 4 for \tilde{F}
// bit 3/0x08: 1 if a continuation on the E state (bit 5/0x20 for a continuation on \tilde{E})
// bit 4/0x10: 1 if a continuation on the F state (bit 6/0x40 for a continuation on \tilde{F})
static inline void ksw_backtrack(void *km, int is_rot, int is_rev, int min_intron_len, const uint8_t *p, const int *off, const int *off_end, int n_col, int i0, int j0,
int *m_cigar_, int *n_cigar_, uint32_t **cigar_)
{ // p[] - lower 3 bits: which type gets the max; bit
int n_cigar = 0, m_cigar = *m_cigar_, i = i0, j = j0, r, state = 0;
uint32_t *cigar = *cigar_, tmp;
while (i >= 0 && j >= 0) { // at the beginning of the loop, _state_ tells us which state to check
int force_state = -1;
if (is_rot) {
r = i + j;
if (i < off[r]) force_state = 2;
if (off_end && i > off_end[r]) force_state = 1;
tmp = force_state < 0? p[(size_t)r * n_col + i - off[r]] : 0;
} else {
if (j < off[i]) force_state = 2;
if (off_end && j > off_end[i]) force_state = 1;
tmp = force_state < 0? p[(size_t)i * n_col + j - off[i]] : 0;
}
if (state == 0) state = tmp & 7; // if requesting the H state, find state one maximizes it.
else if (!(tmp >> (state + 2) & 1)) state = 0; // if requesting other states, _state_ stays the same if it is a continuation; otherwise, set to H
if (state == 0) state = tmp & 7; // TODO: probably this line can be merged into the "else if" line right above; not 100% sure
if (force_state >= 0) state = force_state;
if (state == 0) cigar = ksw_push_cigar(km, &n_cigar, &m_cigar, cigar, KSW_CIGAR_MATCH, 1), --i, --j;
else if (state == 1 || (state == 3 && min_intron_len <= 0)) cigar = ksw_push_cigar(km, &n_cigar, &m_cigar, cigar, KSW_CIGAR_DEL, 1), --i;
else if (state == 3 && min_intron_len > 0) cigar = ksw_push_cigar(km, &n_cigar, &m_cigar, cigar, KSW_CIGAR_N_SKIP, 1), --i;
else cigar = ksw_push_cigar(km, &n_cigar, &m_cigar, cigar, KSW_CIGAR_INS, 1), --j;
}
if (i >= 0) cigar = ksw_push_cigar(km, &n_cigar, &m_cigar, cigar, min_intron_len > 0 && i >= min_intron_len? KSW_CIGAR_N_SKIP : KSW_CIGAR_DEL, i + 1); // first deletion
if (j >= 0) cigar = ksw_push_cigar(km, &n_cigar, &m_cigar, cigar, KSW_CIGAR_INS, j + 1); // first insertion
if (!is_rev)
for (i = 0; i < n_cigar>>1; ++i) // reverse CIGAR
tmp = cigar[i], cigar[i] = cigar[n_cigar-1-i], cigar[n_cigar-1-i] = tmp;
*m_cigar_ = m_cigar, *n_cigar_ = n_cigar, *cigar_ = cigar;
}
static inline void ksw_reset_extz(ksw_extz_t *ez)
{
ez->max_q = ez->max_t = ez->mqe_t = ez->mte_q = -1;
ez->max = 0, ez->score = ez->mqe = ez->mte = KSW_NEG_INF;
ez->n_cigar = 0, ez->zdropped = 0, ez->reach_end = 0;
}
static inline int ksw_apply_zdrop(ksw_extz_t *ez, int is_rot, int32_t H, int a, int b, int zdrop, int8_t e)
{
int r, t;
if (is_rot) r = a, t = b;
else r = a + b, t = a;
if (H > (int32_t)ez->max) {
ez->max = H, ez->max_t = t, ez->max_q = r - t;
} else if (t >= ez->max_t && r - t >= ez->max_q) {
int tl = t - ez->max_t, ql = (r - t) - ez->max_q, l;
l = tl > ql? tl - ql : ql - tl;
if (zdrop >= 0 && ez->max - H > zdrop + l * e) {
ez->zdropped = 1;
return 1;
}
}
return 0;
}
#endif
|
