#include <stdlib.h>

#include <string.h>

#include <stdio.h>

#include <math.h>

#include "kstring.h"

#include "bwamem.h"

#include "kvec.h"

#include "utils.h"

#include "ksort.h"

#include "ksw.h"

#ifdef USE_MALLOC_WRAPPERS

# include "malloc_wrap.h"

#endif

#define MIN_RATIO 0.8

#define MIN_DIR_CNT 10

#define MIN_DIR_RATIO 0.05

#define OUTLIER_BOUND 2.0

#define MAPPING_BOUND 3.0

#define MAX_STDDEV 4.0

static inline int mem_infer_dir(int64_t l_pac, int64_t b1, int64_t b2, int64_t *dist)

{

int64_t p2;

int r1 = (b1 >= l_pac), r2 = (b2 >= l_pac); p2 = r1 == r2? b2 : (l_pac<<1) - 1 - b2; // p2 is the coordinate of read 2 on the read 1 strand

*dist = p2 > b1? p2 - b1 : b1 - p2;

return (r1 == r2? 0 : 1) ^ (p2 > b1? 0 : 3);

}

static int cal_sub(const mem_opt_t *opt, mem_alnreg_v *r)

{

int j;

for (j = 1; j < r->n; ++j) { // choose unique alignment

int b_max = r->a[j].qb > r->a[0].qb? r->a[j].qb : r->a[0].qb;

int e_min = r->a[j].qe < r->a[0].qe? r->a[j].qe : r->a[0].qe;

if (e_min > b_max) { // have overlap

int min_l = r->a[j].qe - r->a[j].qb < r->a[0].qe - r->a[0].qb? r->a[j].qe - r->a[j].qb : r->a[0].qe - r->a[0].qb;

if (e_min - b_max >= min_l * opt->mask_level) break; // significant overlap

}

}

return j < r->n? r->a[j].score : opt->min_seed_len * opt->a;

}

typedef struct{

double FMEAS;

int x,y;

int score;

}FF_t;

#define flt_FF_t(a,b) ( (a).FMEAS > (b).FMEAS)

KSORT_INIT(ff_mem_flt,FF_t,flt_FF_t)

mem_alnreg_v mem_fmeas_fliter_se(mem_alnreg_v a , int n , int l_seq , int mode)

{

mem_alnreg_v aa ;

int i , j ;

kvec_t(FF_t) k_ff_t ;

kv_init(k_ff_t);

kv_init(aa);

// caculate FMEAS value

if(n == 0) return aa ;

for( i = 0 ; i < a.n ; i++){

mem_alnreg_t *p_ar = a.a + i ;

for( j = i + 1 ; j < a.n ; j++){

FF_t tmp ;

mem_alnreg_t *q_ar = a.a + j ;

double sens , spec ;

int FN = 0 , TP = 0 ,TN = 0 , FP = 0 ;

int A,B,C,D;

if( p_ar->qb < q_ar->qb || (p_ar->qb == q_ar->qb && p_ar->qe >= q_ar->qe)){ // p q

A = p_ar->qb ;

B = p_ar->qe - 1 ;

C = q_ar->qb ;

D = q_ar->qe - 1 ;

}else { // p q

A = q_ar->qb ;

B = q_ar->qe - 1;

C = p_ar->qb ;

D = p_ar->qe - 1;

}

if(B < C){

TP = B - A + D - C + 2 ;

FN = l_seq - D - 1 + A + C - B - 1 ;

TN = l_seq ;

FP = 0 ;

}else if( D <= B){ // contain

continue ;

}else{

TP = D - A + 1 ;

FN = l_seq - D - 1 + A ;

FP = B - C + 1 ;

TN = l_seq - FP;

}

sens = (double)TP/(double)(TP+FN);

spec = (double)TN/(double)(TN+FP);

tmp.FMEAS = (2*spec*sens)/(spec+sens);

tmp.score = p_ar->score + q_ar->score;

tmp.x = i , tmp.y = j ;

if(tmp.FMEAS > 0.95) kv_push(FF_t,k_ff_t,tmp);

}

}

ks_introsort(ff_mem_flt, k_ff_t.n, k_ff_t.a);

kv_push(mem_alnreg_t,aa,a.a[0]);

double max_feas ;

// int score ;

if( k_ff_t.n == 0 ) return aa;

max_feas = k_ff_t.a[0].FMEAS ;

// score = k_ff_t.a[0].score ;

if(mode){

int cnt = 0 ;

for( i = 0 ; i < kv_size(k_ff_t) ; i++){

FF_t p = kv_A(k_ff_t,i);

if(p.x == 0 && cnt == 0){

kv_push(mem_alnreg_t,aa,a.a[p.y]);

cnt = 1 ;

}else if(p.x == 0){

kv_push(mem_alnreg_t,aa,a.a[0]);

kv_push(mem_alnreg_t,aa,a.a[p.y]);

}

}

for( i = 0 ; i < kv_size(k_ff_t); i++){

FF_t p = kv_A(k_ff_t,i);

if(max_feas != p.FMEAS ) break;

if(p.x == 0) continue ;

kv_push(mem_alnreg_t,aa,a.a[p.x]);

kv_push(mem_alnreg_t,aa,a.a[p.y]);

}

}else{

int cnt = 0 ;

for( i = 0 ; i < kv_size(k_ff_t); i++){

FF_t p = kv_A(k_ff_t,i);

if(max_feas != p.FMEAS ) break;

if(p.x == 0 && cnt == 0){

kv_push(mem_alnreg_t,aa,a.a[p.y]);

continue ;

}else if( p.x == 0 ){

kv_push(mem_alnreg_t,aa,a.a[0]);

kv_push(mem_alnreg_t,aa,a.a[p.y]);

continue ;

}

kv_push(mem_alnreg_t,aa,a.a[p.x]);

kv_push(mem_alnreg_t,aa,a.a[p.y]);

}

}

kv_destroy(k_ff_t);

#if 0

for( i = 0 ; i < kv_size(aa); i++){

mem_alnreg_t *q = aa.a + i;

printf("%db: %d %de:%d \t" , i, q->qb , i, q->qe);

if( i == kv_size(aa) -1 ) printf("\n");

}

#endif

return aa ;

}

void mem_pestat(const mem_opt_t *opt, int64_t l_pac, int n, const mem_alnreg_v *regs, mem_pestat_t pes[4])

{

int i, d, max;

uint64_v isize[4];

memset(pes, 0, 4 * sizeof(mem_pestat_t));

memset(isize, 0, sizeof(kvec_t(int)) * 4);

for (i = 0; i < n>>1; ++i) {

int dir;

int64_t is;

mem_alnreg_v *r[2];

r[0] = (mem_alnreg_v*)&regs[i<<1|0];

r[1] = (mem_alnreg_v*)&regs[i<<1|1];

if (r[0]->n == 0 || r[1]->n == 0) continue;

if (cal_sub(opt, r[0]) > MIN_RATIO * r[0]->a[0].score) continue;

if (cal_sub(opt, r[1]) > MIN_RATIO * r[1]->a[0].score) continue;

dir = mem_infer_dir(l_pac, r[0]->a[0].rb, r[1]->a[0].rb, &is);

if (is && is <= opt->max_ins) kv_push(uint64_t, isize[dir], is);

}

if (bwa_verbose >= 3) fprintf(stderr, "[M::%s] # candidate unique pairs for (FF, FR, RF, RR): (%ld, %ld, %ld, %ld)\n", __func__, isize[0].n, isize[1].n, isize[2].n, isize[3].n);

for (d = 0; d < 4; ++d) { // TODO: this block is nearly identical to the one in bwtsw2_pair.c. It would be better to merge these two.

mem_pestat_t *r = &pes[d];

uint64_v *q = &isize[d];

int p25, p50, p75, x;

if (q->n < MIN_DIR_CNT) {

fprintf(stderr, "[M::%s] skip orientation %c%c as there are not enough pairs\n", __func__, "FR"[d>>1&1], "FR"[d&1]);

r->failed = 1;

continue;

} else fprintf(stderr, "[M::%s] analyzing insert size distribution for orientation %c%c...\n", __func__, "FR"[d>>1&1], "FR"[d&1]);

ks_introsort_64(q->n, q->a);

p25 = q->a[(int)(.25 * q->n + .499)];

p50 = q->a[(int)(.50 * q->n + .499)];

p75 = q->a[(int)(.75 * q->n + .499)];

r->low = (int)(p25 - OUTLIER_BOUND * (p75 - p25) + .499);

if (r->low < 1) r->low = 1;

r->high = (int)(p75 + OUTLIER_BOUND * (p75 - p25) + .499);

fprintf(stderr, "[M::%s] (25, 50, 75) percentile: (%d, %d, %d)\n", __func__, p25, p50, p75);

fprintf(stderr, "[M::%s] low and high boundaries for computing mean and std.dev: (%d, %d)\n", __func__, r->low, r->high);

for (i = x = 0, r->avg = 0; i < q->n; ++i)

if (q->a[i] >= r->low && q->a[i] <= r->high)

r->avg += q->a[i], ++x;

r->avg /= x;

for (i = 0, r->std = 0; i < q->n; ++i)

if (q->a[i] >= r->low && q->a[i] <= r->high)

r->std += (q->a[i] - r->avg) * (q->a[i] - r->avg);

r->std = sqrt(r->std / x);

fprintf(stderr, "[M::%s] mean and std.dev: (%.2f, %.2f)\n", __func__, r->avg, r->std);

r->low = (int)(p25 - MAPPING_BOUND * (p75 - p25) + .499);

r->high = (int)(p75 + MAPPING_BOUND * (p75 - p25) + .499);

if (r->low > r->avg - MAX_STDDEV * r->std) r->low = (int)(r->avg - MAX_STDDEV * r->std + .499);

if (r->high < r->avg - MAX_STDDEV * r->std) r->high = (int)(r->avg + MAX_STDDEV * r->std + .499);

if (r->low < 1) r->low = 1;

fprintf(stderr, "[M::%s] low and high boundaries for proper pairs: (%d, %d)\n", __func__, r->low, r->high);

free(q->a);

}

for (d = 0, max = 0; d < 4; ++d)

max = max > isize[d].n? max : isize[d].n;

for (d = 0; d < 4; ++d)

if (pes[d].failed == 0 && isize[d].n < max * MIN_DIR_RATIO) {

pes[d].failed = 1;

fprintf(stderr, "[M::%s] skip orientation %c%c\n", __func__, "FR"[d>>1&1], "FR"[d&1]);

}

}

int mem_matesw(const mem_opt_t *opt, int64_t l_pac, const uint8_t *pac, const mem_pestat_t pes[4], const mem_alnreg_t *a, int l_ms, const uint8_t *ms, mem_alnreg_v *ma)

{

extern int mem_sort_and_dedup(int n, mem_alnreg_t *a, float mask_level_redun);

int i, r, skip[4], n = 0;

for (r = 0; r < 4; ++r)

skip[r] = pes[r].failed? 1 : 0;

for (i = 0; i < ma->n; ++i) { // check which orinentation has been found

int64_t dist;

r = mem_infer_dir(l_pac, a->rb, ma->a[i].rb, &dist);

if (dist >= pes[r].low && dist <= pes[r].high)

skip[r] = 1;

}

if (skip[0] + skip[1] + skip[2] + skip[3] == 4) return 0; // consistent pair exist; no need to perform SW

for (r = 0; r < 4; ++r) {

int is_rev, is_larger;

uint8_t *seq, *rev = 0, *ref;

int64_t rb, re, len;

if (skip[r]) continue;

is_rev = (r>>1 != (r&1)); // whether to reverse complement the mate

is_larger = !(r>>1); // whether the mate has larger coordinate

if (is_rev) {

rev = malloc(l_ms); // this is the reverse complement of $ms

for (i = 0; i < l_ms; ++i) rev[l_ms - 1 - i] = ms[i] < 4? 3 - ms[i] : 4;

seq = rev;

} else seq = (uint8_t*)ms;

if (!is_rev) {

rb = is_larger? a->rb + pes[r].low : a->rb - pes[r].high;

re = (is_larger? a->rb + pes[r].high: a->rb - pes[r].low) + l_ms; // if on the same strand, end position should be larger to make room for the seq length

} else {

rb = (is_larger? a->rb + pes[r].low : a->rb - pes[r].high) - l_ms; // similarly on opposite strands

re = is_larger? a->rb + pes[r].high: a->rb - pes[r].low;

}

if (rb < 0) rb = 0;

if (re > l_pac<<1) re = l_pac<<1;

ref = bns_get_seq(l_pac, pac, rb, re, &len);

if (len == re - rb) { // no funny things happening

kswr_t aln;

mem_alnreg_t b;

int tmp, xtra = KSW_XSUBO | KSW_XSTART | (l_ms * opt->a < 250? KSW_XBYTE : 0) | opt->min_seed_len;

aln = ksw_align(l_ms, seq, len, ref, 5, opt->mat, opt->q, opt->r, xtra, 0);

memset(&b, 0, sizeof(mem_alnreg_t));

if (aln.score >= opt->min_seed_len && aln.qb >= 0) { // something goes wrong if aln.qb < 0

b.qb = is_rev? l_ms - (aln.qe + 1) : aln.qb;

b.qe = is_rev? l_ms - aln.qb : aln.qe + 1;

b.rb = is_rev? (l_pac<<1) - (rb + aln.te + 1) : rb + aln.tb;

b.re = is_rev? (l_pac<<1) - (rb + aln.tb) : rb + aln.te + 1;

b.score = aln.score;

b.csub = aln.score2;

b.secondary = -1;

b.seedcov = (b.re - b.rb < b.qe - b.qb? b.re - b.rb : b.qe - b.qb) >> 1;

// printf("*** %d, [%lld,%lld], %d:%d, (%lld,%lld), (%lld,%lld) == (%lld,%lld)\n", aln.score, rb, re, is_rev, is_larger, a->rb, a->re, ma->a[0].rb, ma->a[0].re, b.rb, b.re);

kv_push(mem_alnreg_t, *ma, b); // make room for a new element

// move b s.t. ma is sorted

for (i = 0; i < ma->n - 1; ++i) // find the insertion point

if (ma->a[i].score < b.score) break;

tmp = i;

for (i = ma->n - 1; i > tmp; --i) ma->a[i] = ma->a[i-1];

ma->a[i] = b;

}

++n;

}

if (n) ma->n = mem_sort_and_dedup(ma->n, ma->a, opt->mask_level_redun);

if (rev) free(rev);

free(ref);

}

return n;

}

int mem_pair(const mem_opt_t *opt, int64_t l_pac, const uint8_t *pac, const mem_pestat_t pes[4], bseq1_t s[2], mem_alnreg_v a[2], int id, int *sub, int *n_sub, int z[2])

{

pair64_v v, u;

int r, i, k, y[4], ret; // y[] keeps the last hit

kv_init(v); kv_init(u);

for (r = 0; r < 2; ++r) { // loop through read number

for (i = 0; i < a[r].n; ++i) {

pair64_t key;

mem_alnreg_t *e = &a[r].a[i];

key.x = e->rb < l_pac? e->rb : (l_pac<<1) - 1 - e->rb; // forward position

key.y = (uint64_t)e->score << 32 | i << 2 | (e->rb >= l_pac)<<1 | r;

kv_push(pair64_t, v, key);

}

}

ks_introsort_128(v.n, v.a);

y[0] = y[1] = y[2] = y[3] = -1;

//for (i = 0; i < v.n; ++i) printf("[%d]\t%d\t%c%ld\n", i, (int)(v.a[i].y&1)+1, "+-"[v.a[i].y>>1&1], (long)v.a[i].x);

for (i = 0; i < v.n; ++i) {

for (r = 0; r < 2; ++r) { // loop through direction

int dir = r<<1 | (v.a[i].y>>1&1), which;

if (pes[dir].failed) continue; // invalid orientation

which = r<<1 | ((v.a[i].y&1)^1);

if (y[which] < 0) continue; // no previous hits

for (k = y[which]; k >= 0; --k) { // TODO: this is a O(n^2) solution in the worst case; remember to check if this loop takes a lot of time (I doubt)

int64_t dist;

int q;

double ns;

pair64_t *p;

if ((v.a[k].y&3) != which) continue;

dist = (int64_t)v.a[i].x - v.a[k].x;

//printf("%d: %lld\n", k, dist);

if (dist > pes[dir].high) break;

if (dist < pes[dir].low) continue;

ns = (dist - pes[dir].avg) / pes[dir].std;

q = (int)((v.a[i].y>>32) + (v.a[k].y>>32) + .721 * log(2. * erfc(fabs(ns) * M_SQRT1_2)) * opt->a + .499); // .721 = 1/log(4)

if (q < 0) q = 0;

p = kv_pushp(pair64_t, u);

p->y = (uint64_t)k<<32 | i;

p->x = (uint64_t)q<<32 | (hash_64(p->y ^ id<<8) & 0xffffffffU);

//printf("[%lld,%lld]\t%d\tdist=%ld\n", v.a[k].x, v.a[i].x, q, (long)dist);

}

}

y[v.a[i].y&3] = i;

}

if (u.n) { // found at least one proper pair

int tmp = opt->a + opt->b > opt->q + opt->r? opt->a + opt->b : opt->q + opt->r;

ks_introsort_128(u.n, u.a);

i = u.a[u.n-1].y >> 32; k = u.a[u.n-1].y << 32 >> 32;

z[v.a[i].y&1] = v.a[i].y<<32>>34; // index of the best pair

z[v.a[k].y&1] = v.a[k].y<<32>>34;

ret = u.a[u.n-1].x >> 32;

*sub = u.n > 1? u.a[u.n-2].x>>32 : 0;

for (i = (long)u.n - 2, *n_sub = 0; i >= 0; --i)

if (*sub - (int)(u.a[i].x>>32) <= tmp) ++*n_sub;

} else ret = 0, *sub = 0, *n_sub = 0;

free(u.a); free(v.a);

return ret;

}

int mem_sam_pe(const mem_opt_t *opt, const bntseq_t *bns, const uint8_t *pac, const mem_pestat_t pes[4], uint64_t id, bseq1_t s[2], mem_alnreg_v a[2])

{

extern void mem_mark_primary_se(const mem_opt_t *opt, int n, mem_alnreg_t *a, int64_t id );

extern int mem_approx_mapq_se(const mem_opt_t *opt, const mem_alnreg_t *a);

extern void mem_reg2sam_se(const mem_opt_t *opt, const bntseq_t *bns, const uint8_t *pac, bseq1_t *s, mem_alnreg_v *a, int extra_flag, const mem_aln_t *m);

extern void mem_aln2sam(const bntseq_t *bns, kstring_t *str, bseq1_t *s, int n, const mem_aln_t *list, int which, const mem_aln_t *m);

int n = 0, i, j, z[2], o, subo, n_sub, extra_flag = 1;

kstring_t str;

mem_aln_t h[2];

mem_alnreg_v aa[2];

str.l = str.m = 0; str.s = 0;

if (!(opt->flag & MEM_F_NO_RESCUE)) { // then perform SW for the best alignment

mem_alnreg_v b[2];

kv_init(b[0]); kv_init(b[1]);

for (i = 0; i < 2; ++i)

for (j = 0; j < a[i].n; ++j)

if (a[i].a[j].score >= a[i].a[0].score - opt->pen_unpaired)

kv_push(mem_alnreg_t, b[i], a[i].a[j]);

for (i = 0; i < 2; ++i)

for (j = 0; j < b[i].n && j < opt->max_matesw; ++j)

n += mem_matesw(opt, bns->l_pac, pac, pes, &b[i].a[j], s[!i].l_seq, (uint8_t*)s[!i].seq, &a[!i]);

free(b[0].a); free(b[1].a);

}

mem_mark_primary_se(opt, a[0].n, a[0].a, id<<1|0);

mem_mark_primary_se(opt, a[1].n, a[1].a, id<<1|1);

if (opt->flag&MEM_F_NOPAIRING) goto no_pairing;

// pairing single-end hits

if (a[0].n && a[1].n && (o = mem_pair(opt, bns->l_pac, pac, pes, s, a, id, &subo, &n_sub, z)) > 0) {

int is_multi[2], q_pe, score_un, q_se[2];

// check if an end has multiple hits even after mate-SW

for (i = 0; i < 2; ++i) {

for (j = 1; j < a[i].n; ++j)

if (a[i].a[j].secondary < 0 && a[i].a[j].score >= opt->T) break;

is_multi[i] = j < a[i].n? 1 : 0;

}

//if (is_multi[0] || is_multi[1]) goto no_pairing; // TODO: in rare cases, the true hit may be long but with low score

// compute mapQ for the best SE hit

score_un = a[0].a[0].score + a[1].a[0].score - opt->pen_unpaired;

//q_pe = o && subo < o? (int)(MEM_MAPQ_COEF * (1. - (double)subo / o) * log(a[0].a[z[0]].seedcov + a[1].a[z[1]].seedcov) + .499) : 0;

subo = subo > score_un? subo : score_un;

q_pe = (o - subo) * 6;

if (n_sub > 0) q_pe -= (int)(4.343 * log(n_sub+1) + .499);

if (q_pe < 0) q_pe = 0;

if (q_pe > 60) q_pe = 60;

// the following assumes no split hits

if (o > score_un) { // paired alignment is preferred

mem_alnreg_t *c[2], tmp;

c[0] = &a[0].a[z[0]]; c[1] = &a[1].a[z[1]];

for (i = 0; i < 2; ++i) {

if (c[i]->secondary >= 0)

c[i]->sub = a[i].a[c[i]->secondary].score, c[i]->secondary = -2;

q_se[i] = mem_approx_mapq_se(opt, c[i]);

}

q_se[0] = q_se[0] > q_pe? q_se[0] : q_pe < q_se[0] + 40? q_pe : q_se[0] + 40;

q_se[1] = q_se[1] > q_pe? q_se[1] : q_pe < q_se[1] + 40? q_pe : q_se[1] + 40;

extra_flag |= 2;

// cap at the tandem repeat score

q_se[0] = q_se[0] < (c[0]->score - c[0]->csub) * 6? q_se[0] : (c[0]->score - c[0]->csub) * 6;

q_se[1] = q_se[1] < (c[1]->score - c[1]->csub) * 6? q_se[1] : (c[1]->score - c[1]->csub) * 6;

for( i = 0 ; i < 2 ; i++){

tmp = *c[i];

a[i].a[z[i]] = a[i].a[0];

a[i].a[0] = tmp ;

}

} else { // the unpaired alignment is preferred

q_se[0] = mem_approx_mapq_se(opt, &a[0].a[0]);

q_se[1] = mem_approx_mapq_se(opt, &a[1].a[0]);

}

z[0] = z[1] = 0;

// write SAM

// find the breakpoint

int bp_i = 0 ;

// for( k = 1 ; k < a[0].n ; k++) a[0].a[k].secondary = 1 ;

// for( k = 1 ; k < a[1].n ; k++) a[1].a[k].secondary = 1 ;

bp_i = (a[0].a[0].score > a[1].a[0].score) ? 1 : 0 ;

aa[bp_i] = mem_fmeas_fliter_se(a[bp_i],a[bp_i].n,s[bp_i].l_seq,1);

kv_init(aa[1-bp_i]);

kv_push(mem_alnreg_t,aa[1-bp_i],a[1-bp_i].a[0]);

#if 1

h[0] = mem_reg2aln(opt, bns, pac, s[0].l_seq, s[0].seq, &aa[0].a[z[0]]); h[0].mapq = q_se[0]; h[0].flag |= 0x40 | extra_flag;

h[1] = mem_reg2aln(opt, bns, pac, s[1].l_seq, s[1].seq, &aa[1].a[z[1]]); h[1].mapq = q_se[1]; h[1].flag |= 0x80 | extra_flag;

mem_reg2sam_se(opt, bns, pac, &s[0], &aa[0], 0x41|extra_flag, &h[1]);

mem_reg2sam_se(opt, bns, pac, &s[1], &aa[1], 0x81|extra_flag, &h[0]);

#endif

if (strcmp(s[0].name, s[1].name) != 0) err_fatal(__func__, "paired reads have different names: \"%s\", \"%s\"\n", s[0].name, s[1].name);

free(h[0].cigar); free(h[1].cigar);free(aa[0].a); free(aa[1].a);

} else goto no_pairing;

return n;

no_pairing:

#if 1

for (i = 0; i < 2; ++i) {

if (a[i].n && a[i].a[0].score >= opt->T)

h[i] = mem_reg2aln(opt, bns, pac, s[i].l_seq, s[i].seq, &a[i].a[0]);

else h[i] = mem_reg2aln(opt, bns, pac, s[i].l_seq, s[i].seq, 0);

}

aa[0] = mem_fmeas_fliter_se(a[0],a[0].n,s[0].l_seq,0);

aa[1] = mem_fmeas_fliter_se(a[1],a[1].n,s[1].l_seq,0);

if (!(opt->flag & MEM_F_NOPAIRING) && h[0].rid == h[1].rid && h[0].rid >= 0) { // if the top hits from the two ends constitute a proper pair, flag it.

int64_t dist;

int d;

d = mem_infer_dir(bns->l_pac, a[0].a[0].rb, a[1].a[0].rb, &dist);

if (!pes[d].failed && dist >= pes[d].low && dist <= pes[d].high) extra_flag |= 2;

}

mem_reg2sam_se(opt, bns, pac, &s[0], &aa[0], 0x41|extra_flag, &h[1]);

mem_reg2sam_se(opt, bns, pac, &s[1], &aa[1], 0x81|extra_flag, &h[0]);

if (strcmp(s[0].name, s[1].name) != 0) err_fatal(__func__, "paired reads have different names: \"%s\", \"%s\"\n", s[0].name, s[1].name);

free(h[0].cigar); free(h[1].cigar);free(aa[0].a);free(aa[1].a);

#endif

return n;

}