#ifndef KSW2_H_

#define KSW2_H_

#define __STDC_LIMIT_MACROS

#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

#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, int flag, 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, 0, 1), --i, --j; // match

else if (state == 1 || (state == 3 && min_intron_len <= 0)) cigar = ksw_push_cigar(km, &n_cigar, &m_cigar, cigar, 2, 1), --i; // deletion

else if (state == 3 && min_intron_len > 0) cigar = ksw_push_cigar(km, &n_cigar, &m_cigar, cigar, 3, 1), --i; // intron

else cigar = ksw_push_cigar(km, &n_cigar, &m_cigar, cigar, 1, 1), --j; // insertion

}

if (i >= 0) cigar = ksw_push_cigar(km, &n_cigar, &m_cigar, cigar, min_intron_len > 0 && i >= min_intron_len? 3 : 2, i + 1); // first deletion

if (j >= 0) cigar = ksw_push_cigar(km, &n_cigar, &m_cigar, cigar, 1, 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