467 lines
15 KiB
C
467 lines
15 KiB
C
#include <string.h>
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#include <stdlib.h>
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#include <math.h>
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#include "mmpriv.h"
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#include "kalloc.h"
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#include "khash.h"
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static inline void mm_cal_fuzzy_len(mm_reg1_t *r, const mm128_t *a)
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{
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int i;
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r->mlen = r->blen = 0;
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if (r->cnt <= 0) return;
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r->mlen = r->blen = a[r->as].y>>32&0xff;
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for (i = r->as + 1; i < r->as + r->cnt; ++i) {
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int span = a[i].y>>32&0xff;
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int tl = (int32_t)a[i].x - (int32_t)a[i-1].x;
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int ql = (int32_t)a[i].y - (int32_t)a[i-1].y;
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r->blen += tl > ql? tl : ql;
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r->mlen += tl > span && ql > span? span : tl < ql? tl : ql;
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}
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}
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static inline void mm_reg_set_coor(mm_reg1_t *r, int32_t qlen, const mm128_t *a, int is_qstrand)
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{ // NB: r->as and r->cnt MUST BE set correctly for this function to work
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int32_t k = r->as, q_span = (int32_t)(a[k].y>>32&0xff);
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r->rev = a[k].x>>63;
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r->rid = a[k].x<<1>>33;
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r->rs = (int32_t)a[k].x + 1 > q_span? (int32_t)a[k].x + 1 - q_span : 0; // NB: target span may be shorter, so this test is necessary
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r->re = (int32_t)a[k + r->cnt - 1].x + 1;
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if (!r->rev || is_qstrand) {
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r->qs = (int32_t)a[k].y + 1 - q_span;
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r->qe = (int32_t)a[k + r->cnt - 1].y + 1;
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} else {
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r->qs = qlen - ((int32_t)a[k + r->cnt - 1].y + 1);
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r->qe = qlen - ((int32_t)a[k].y + 1 - q_span);
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}
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mm_cal_fuzzy_len(r, a);
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}
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static inline uint64_t hash64(uint64_t key)
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{
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key = (~key + (key << 21));
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key = key ^ key >> 24;
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key = ((key + (key << 3)) + (key << 8));
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key = key ^ key >> 14;
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key = ((key + (key << 2)) + (key << 4));
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key = key ^ key >> 28;
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key = (key + (key << 31));
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return key;
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}
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mm_reg1_t *mm_gen_regs(void *km, uint32_t hash, int qlen, int n_u, uint64_t *u, mm128_t *a, int is_qstrand) // convert chains to hits
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{
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mm128_t *z, tmp;
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mm_reg1_t *r;
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int i, k;
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if (n_u == 0) return 0;
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// sort by score
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z = (mm128_t*)kmalloc(km, n_u * 16);
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for (i = k = 0; i < n_u; ++i) {
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uint32_t h;
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h = (uint32_t)hash64((hash64(a[k].x) + hash64(a[k].y)) ^ hash);
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z[i].x = u[i] ^ h; // u[i] -- higher 32 bits: chain score; lower 32 bits: number of seeds in the chain
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z[i].y = (uint64_t)k << 32 | (int32_t)u[i];
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k += (int32_t)u[i];
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}
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radix_sort_128x(z, z + n_u);
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for (i = 0; i < n_u>>1; ++i) // reverse, s.t. larger score first
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tmp = z[i], z[i] = z[n_u-1-i], z[n_u-1-i] = tmp;
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// populate r[]
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r = (mm_reg1_t*)calloc(n_u, sizeof(mm_reg1_t));
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for (i = 0; i < n_u; ++i) {
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mm_reg1_t *ri = &r[i];
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ri->id = i;
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ri->parent = MM_PARENT_UNSET;
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ri->score = ri->score0 = z[i].x >> 32;
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ri->hash = (uint32_t)z[i].x;
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ri->cnt = (int32_t)z[i].y;
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ri->as = z[i].y >> 32;
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ri->div = -1.0f;
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mm_reg_set_coor(ri, qlen, a, is_qstrand);
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}
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kfree(km, z);
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return r;
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}
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void mm_mark_alt(const mm_idx_t *mi, int n, mm_reg1_t *r)
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{
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int i;
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if (mi->n_alt == 0) return;
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for (i = 0; i < n; ++i)
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if (mi->seq[r[i].rid].is_alt)
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r[i].is_alt = 1;
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}
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static inline int mm_alt_score(int score, float alt_diff_frac)
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{
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if (score < 0) return score;
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score = (int)(score * (1.0 - alt_diff_frac) + .499);
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return score > 0? score : 1;
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}
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void mm_split_reg(mm_reg1_t *r, mm_reg1_t *r2, int n, int qlen, mm128_t *a, int is_qstrand)
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{
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if (n <= 0 || n >= r->cnt) return;
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*r2 = *r;
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r2->id = -1;
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r2->sam_pri = 0;
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r2->p = 0;
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r2->split_inv = 0;
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r2->cnt = r->cnt - n;
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r2->score = (int32_t)(r->score * ((float)r2->cnt / r->cnt) + .499);
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r2->as = r->as + n;
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if (r->parent == r->id) r2->parent = MM_PARENT_TMP_PRI;
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mm_reg_set_coor(r2, qlen, a, is_qstrand);
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r->cnt -= r2->cnt;
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r->score -= r2->score;
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mm_reg_set_coor(r, qlen, a, is_qstrand);
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r->split |= 1, r2->split |= 2;
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}
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void mm_set_parent(void *km, float mask_level, int mask_len, int n, mm_reg1_t *r, int sub_diff, int hard_mask_level, float alt_diff_frac) // and compute mm_reg1_t::subsc
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{
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int i, j, k, *w;
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uint64_t *cov;
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if (n <= 0) return;
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for (i = 0; i < n; ++i) r[i].id = i;
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cov = (uint64_t*)kmalloc(km, n * sizeof(uint64_t));
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w = (int*)kmalloc(km, n * sizeof(int));
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w[0] = 0, r[0].parent = 0;
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for (i = 1, k = 1; i < n; ++i) {
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mm_reg1_t *ri = &r[i];
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int si = ri->qs, ei = ri->qe, n_cov = 0, uncov_len = 0;
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if (hard_mask_level) goto skip_uncov;
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for (j = 0; j < k; ++j) { // traverse existing primary hits to find overlapping hits
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mm_reg1_t *rp = &r[w[j]];
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int sj = rp->qs, ej = rp->qe;
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if (ej <= si || sj >= ei) continue;
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if (sj < si) sj = si;
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if (ej > ei) ej = ei;
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cov[n_cov++] = (uint64_t)sj<<32 | ej;
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}
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if (n_cov == 0) {
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goto set_parent_test; // no overlapping primary hits; then i is a new primary hit
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} else if (n_cov > 0) { // there are overlapping primary hits; find the length not covered by existing primary hits
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int j, x = si;
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radix_sort_64(cov, cov + n_cov);
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for (j = 0; j < n_cov; ++j) {
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if ((int)(cov[j]>>32) > x) uncov_len += (cov[j]>>32) - x;
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x = (int32_t)cov[j] > x? (int32_t)cov[j] : x;
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}
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if (ei > x) uncov_len += ei - x;
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}
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skip_uncov:
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for (j = 0; j < k; ++j) { // traverse existing primary hits again
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mm_reg1_t *rp = &r[w[j]];
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int sj = rp->qs, ej = rp->qe, min, max, ol;
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if (ej <= si || sj >= ei) continue; // no overlap
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min = ej - sj < ei - si? ej - sj : ei - si;
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max = ej - sj > ei - si? ej - sj : ei - si;
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ol = si < sj? (ei < sj? 0 : ei < ej? ei - sj : ej - sj) : (ej < si? 0 : ej < ei? ej - si : ei - si); // overlap length; TODO: this can be simplified
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if ((float)ol / min - (float)uncov_len / max > mask_level && uncov_len <= mask_len) { // then this is a secondary hit
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int cnt_sub = 0, sci = ri->score;
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ri->parent = rp->parent;
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if (!rp->is_alt && ri->is_alt) sci = mm_alt_score(sci, alt_diff_frac);
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rp->subsc = rp->subsc > sci? rp->subsc : sci;
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if (ri->cnt >= rp->cnt) cnt_sub = 1;
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if (rp->p && ri->p && (rp->rid != ri->rid || rp->rs != ri->rs || rp->re != ri->re || ol != min)) { // the last condition excludes identical hits after DP
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sci = ri->p->dp_max;
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if (!rp->is_alt && ri->is_alt) sci = mm_alt_score(sci, alt_diff_frac);
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rp->p->dp_max2 = rp->p->dp_max2 > sci? rp->p->dp_max2 : sci;
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if (rp->p->dp_max - ri->p->dp_max <= sub_diff) cnt_sub = 1;
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}
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if (cnt_sub) ++rp->n_sub;
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break;
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}
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}
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set_parent_test:
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if (j == k) w[k++] = i, ri->parent = i, ri->n_sub = 0;
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}
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kfree(km, cov);
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kfree(km, w);
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}
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void mm_hit_sort(void *km, int *n_regs, mm_reg1_t *r, float alt_diff_frac)
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{
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int32_t i, n_aux, n = *n_regs, has_cigar = 0, no_cigar = 0;
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mm128_t *aux;
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mm_reg1_t *t;
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if (n <= 1) return;
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aux = (mm128_t*)kmalloc(km, n * 16);
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t = (mm_reg1_t*)kmalloc(km, n * sizeof(mm_reg1_t));
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for (i = n_aux = 0; i < n; ++i) {
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if (r[i].inv || r[i].cnt > 0) { // squeeze out elements with cnt==0 (soft deleted)
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int score;
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if (r[i].p) score = r[i].p->dp_max, has_cigar = 1;
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else score = r[i].score, no_cigar = 1;
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if (r[i].is_alt) score = mm_alt_score(score, alt_diff_frac);
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aux[n_aux].x = (uint64_t)score << 32 | r[i].hash;
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aux[n_aux++].y = i;
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} else if (r[i].p) {
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free(r[i].p);
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r[i].p = 0;
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}
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}
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assert(has_cigar + no_cigar == 1);
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radix_sort_128x(aux, aux + n_aux);
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for (i = n_aux - 1; i >= 0; --i)
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t[n_aux - 1 - i] = r[aux[i].y];
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memcpy(r, t, sizeof(mm_reg1_t) * n_aux);
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*n_regs = n_aux;
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kfree(km, aux);
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kfree(km, t);
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}
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int mm_set_sam_pri(int n, mm_reg1_t *r)
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{
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int i, n_pri = 0;
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for (i = 0; i < n; ++i)
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if (r[i].id == r[i].parent) {
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++n_pri;
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r[i].sam_pri = (n_pri == 1);
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} else r[i].sam_pri = 0;
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return n_pri;
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}
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void mm_sync_regs(void *km, int n_regs, mm_reg1_t *regs) // keep mm_reg1_t::{id,parent} in sync; also reset id
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{
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int *tmp, i, max_id = -1, n_tmp;
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if (n_regs <= 0) return;
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for (i = 0; i < n_regs; ++i) // NB: doesn't work if mm_reg1_t::id is negative
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max_id = max_id > regs[i].id? max_id : regs[i].id;
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n_tmp = max_id + 1;
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tmp = (int*)kmalloc(km, n_tmp * sizeof(int));
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for (i = 0; i < n_tmp; ++i) tmp[i] = -1;
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for (i = 0; i < n_regs; ++i)
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if (regs[i].id >= 0) tmp[regs[i].id] = i;
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for (i = 0; i < n_regs; ++i) {
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mm_reg1_t *r = ®s[i];
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r->id = i;
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if (r->parent == MM_PARENT_TMP_PRI)
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r->parent = i;
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else if (r->parent >= 0 && tmp[r->parent] >= 0)
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r->parent = tmp[r->parent];
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else r->parent = MM_PARENT_UNSET;
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}
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kfree(km, tmp);
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mm_set_sam_pri(n_regs, regs);
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}
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void mm_select_sub(void *km, float pri_ratio, int min_diff, int best_n, int check_strand, int min_strand_sc, int *n_, mm_reg1_t *r)
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{
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if (pri_ratio > 0.0f && *n_ > 0) {
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int i, k, n = *n_, n_2nd = 0;
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for (i = k = 0; i < n; ++i) {
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int p = r[i].parent;
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if (p == i || r[i].inv) { // primary or inversion
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r[k++] = r[i];
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} else if ((r[i].score >= r[p].score * pri_ratio || r[i].score + min_diff >= r[p].score) && n_2nd < best_n) {
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if (!(r[i].qs == r[p].qs && r[i].qe == r[p].qe && r[i].rid == r[p].rid && r[i].rs == r[p].rs && r[i].re == r[p].re)) // not identical hits
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r[k++] = r[i], ++n_2nd;
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else if (r[i].p) free(r[i].p);
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} else if (check_strand && n_2nd < best_n && r[i].score > min_strand_sc && r[i].rev != r[p].rev) {
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r[i].strand_retained = 1;
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r[k++] = r[i], ++n_2nd;
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} else if (r[i].p) free(r[i].p);
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}
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if (k != n) mm_sync_regs(km, k, r); // removing hits requires sync()
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*n_ = k;
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}
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}
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int mm_filter_strand_retained(int n_regs, mm_reg1_t *r)
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{
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int i, k;
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for (i = k = 0; i < n_regs; ++i) {
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int p = r[i].parent;
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if (!r[i].strand_retained || r[i].div < r[p].div * 5.0f || r[i].div < 0.01f) {
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if (k < i) r[k++] = r[i];
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else ++k;
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}
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}
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return k;
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}
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void mm_filter_regs(const mm_mapopt_t *opt, int qlen, int *n_regs, mm_reg1_t *regs)
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{ // NB: after this call, mm_reg1_t::parent can be -1 if its parent filtered out
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int i, k;
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for (i = k = 0; i < *n_regs; ++i) {
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mm_reg1_t *r = ®s[i];
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int flt = 0;
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if (!r->inv && !r->seg_split && r->cnt < opt->min_cnt) flt = 1;
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if (r->p) { // these filters are only applied when base-alignment is available
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if (r->mlen < opt->min_chain_score) flt = 1;
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else if (r->p->dp_max < opt->min_dp_max) flt = 1;
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else if (r->qs > qlen * opt->max_clip_ratio && qlen - r->qe > qlen * opt->max_clip_ratio) flt = 1;
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if (flt) free(r->p);
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}
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if (!flt) {
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if (k < i) regs[k++] = regs[i];
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else ++k;
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}
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}
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*n_regs = k;
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}
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int mm_squeeze_a(void *km, int n_regs, mm_reg1_t *regs, mm128_t *a)
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{ // squeeze out regions in a[] that are not referenced by regs[]
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int i, as = 0;
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uint64_t *aux;
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aux = (uint64_t*)kmalloc(km, n_regs * 8);
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for (i = 0; i < n_regs; ++i)
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aux[i] = (uint64_t)regs[i].as << 32 | i;
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radix_sort_64(aux, aux + n_regs);
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for (i = 0; i < n_regs; ++i) {
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mm_reg1_t *r = ®s[(int32_t)aux[i]];
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if (r->as != as) {
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memmove(&a[as], &a[r->as], r->cnt * 16);
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r->as = as;
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}
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as += r->cnt;
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}
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kfree(km, aux);
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return as;
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}
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mm_seg_t *mm_seg_gen(void *km, uint32_t hash, int n_segs, const int *qlens, int n_regs0, const mm_reg1_t *regs0, int *n_regs, mm_reg1_t **regs, const mm128_t *a)
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{
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int s, i, j, acc_qlen[MM_MAX_SEG+1], qlen_sum = 0;
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mm_seg_t *seg;
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assert(n_segs <= MM_MAX_SEG);
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for (s = 1, acc_qlen[0] = 0; s < n_segs; ++s)
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acc_qlen[s] = acc_qlen[s-1] + qlens[s-1];
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qlen_sum = acc_qlen[n_segs - 1] + qlens[n_segs - 1];
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seg = (mm_seg_t*)kcalloc(km, n_segs, sizeof(mm_seg_t));
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for (s = 0; s < n_segs; ++s) {
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seg[s].u = (uint64_t*)kmalloc(km, n_regs0 * 8);
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for (i = 0; i < n_regs0; ++i)
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seg[s].u[i] = (uint64_t)regs0[i].score << 32;
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}
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for (i = 0; i < n_regs0; ++i) {
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const mm_reg1_t *r = ®s0[i];
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for (j = 0; j < r->cnt; ++j) {
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int sid = (a[r->as + j].y&MM_SEED_SEG_MASK)>>MM_SEED_SEG_SHIFT;
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++seg[sid].u[i];
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++seg[sid].n_a;
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}
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}
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for (s = 0; s < n_segs; ++s) {
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mm_seg_t *sr = &seg[s];
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for (i = 0, sr->n_u = 0; i < n_regs0; ++i) // squeeze out zero-length per-segment chains
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if ((int32_t)sr->u[i] != 0)
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sr->u[sr->n_u++] = sr->u[i];
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sr->a = (mm128_t*)kmalloc(km, sr->n_a * sizeof(mm128_t));
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sr->n_a = 0;
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}
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for (i = 0; i < n_regs0; ++i) {
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const mm_reg1_t *r = ®s0[i];
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for (j = 0; j < r->cnt; ++j) {
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int sid = (a[r->as + j].y&MM_SEED_SEG_MASK)>>MM_SEED_SEG_SHIFT;
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mm128_t a1 = a[r->as + j];
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// on reverse strand, the segment position is:
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// x_for_cat = qlen_sum - 1 - (int32_t)a1.y - 1 + q_span
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// (int32_t)new_a1.y = qlens[sid] - (x_for_cat - acc_qlen[sid] + 1 - q_span) - 1 = (int32_t)a1.y - (qlen_sum - (qlens[sid] + acc_qlen[sid]))
|
|
a1.y -= a1.x>>63? qlen_sum - (qlens[sid] + acc_qlen[sid]) : acc_qlen[sid];
|
|
seg[sid].a[seg[sid].n_a++] = a1;
|
|
}
|
|
}
|
|
for (s = 0; s < n_segs; ++s) {
|
|
regs[s] = mm_gen_regs(km, hash, qlens[s], seg[s].n_u, seg[s].u, seg[s].a, 0);
|
|
n_regs[s] = seg[s].n_u;
|
|
for (i = 0; i < n_regs[s]; ++i) {
|
|
regs[s][i].seg_split = 1;
|
|
regs[s][i].seg_id = s;
|
|
}
|
|
}
|
|
return seg;
|
|
}
|
|
|
|
void mm_seg_free(void *km, int n_segs, mm_seg_t *segs)
|
|
{
|
|
int i;
|
|
for (i = 0; i < n_segs; ++i) kfree(km, segs[i].u);
|
|
for (i = 0; i < n_segs; ++i) kfree(km, segs[i].a);
|
|
kfree(km, segs);
|
|
}
|
|
|
|
static void mm_set_inv_mapq(void *km, int n_regs, mm_reg1_t *regs)
|
|
{
|
|
int i, n_aux;
|
|
mm128_t *aux;
|
|
if (n_regs < 3) return;
|
|
for (i = 0; i < n_regs; ++i)
|
|
if (regs[i].inv) break;
|
|
if (i == n_regs) return; // no inversion hits
|
|
|
|
aux = (mm128_t*)kmalloc(km, n_regs * 16);
|
|
for (i = n_aux = 0; i < n_regs; ++i)
|
|
if (regs[i].parent == i || regs[i].parent < 0)
|
|
aux[n_aux].y = i, aux[n_aux++].x = (uint64_t)regs[i].rid << 32 | regs[i].rs;
|
|
radix_sort_128x(aux, aux + n_aux);
|
|
|
|
for (i = 1; i < n_aux - 1; ++i) {
|
|
mm_reg1_t *inv = ®s[aux[i].y];
|
|
if (inv->inv) {
|
|
mm_reg1_t *l = ®s[aux[i-1].y];
|
|
mm_reg1_t *r = ®s[aux[i+1].y];
|
|
inv->mapq = l->mapq < r->mapq? l->mapq : r->mapq;
|
|
}
|
|
}
|
|
kfree(km, aux);
|
|
}
|
|
|
|
void mm_set_mapq(void *km, int n_regs, mm_reg1_t *regs, int min_chain_sc, int match_sc, int rep_len, int is_sr)
|
|
{
|
|
static const float q_coef = 40.0f;
|
|
int64_t sum_sc = 0;
|
|
float uniq_ratio;
|
|
int i;
|
|
if (n_regs == 0) return;
|
|
for (i = 0; i < n_regs; ++i)
|
|
if (regs[i].parent == regs[i].id)
|
|
sum_sc += regs[i].score;
|
|
uniq_ratio = (float)sum_sc / (sum_sc + rep_len);
|
|
for (i = 0; i < n_regs; ++i) {
|
|
mm_reg1_t *r = ®s[i];
|
|
if (r->inv) {
|
|
r->mapq = 0;
|
|
} else if (r->parent == r->id) {
|
|
int mapq, subsc;
|
|
float pen_s1 = (r->score > 100? 1.0f : 0.01f * r->score) * uniq_ratio;
|
|
float pen_cm = r->cnt > 10? 1.0f : 0.1f * r->cnt;
|
|
pen_cm = pen_s1 < pen_cm? pen_s1 : pen_cm;
|
|
subsc = r->subsc > min_chain_sc? r->subsc : min_chain_sc;
|
|
if (r->p && r->p->dp_max2 > 0 && r->p->dp_max > 0) {
|
|
float identity = (float)r->mlen / r->blen;
|
|
float x = (float)r->p->dp_max2 * subsc / r->p->dp_max / r->score0;
|
|
mapq = (int)(identity * pen_cm * q_coef * (1.0f - x * x) * logf((float)r->p->dp_max / match_sc));
|
|
if (!is_sr) {
|
|
int mapq_alt = (int)(6.02f * identity * identity * (r->p->dp_max - r->p->dp_max2) / match_sc + .499f); // BWA-MEM like mapQ, mostly for short reads
|
|
mapq = mapq < mapq_alt? mapq : mapq_alt; // in case the long-read heuristic fails
|
|
}
|
|
} else {
|
|
float x = (float)subsc / r->score0;
|
|
if (r->p) {
|
|
float identity = (float)r->mlen / r->blen;
|
|
mapq = (int)(identity * pen_cm * q_coef * (1.0f - x) * logf((float)r->p->dp_max / match_sc));
|
|
} else {
|
|
mapq = (int)(pen_cm * q_coef * (1.0f - x) * logf(r->score));
|
|
}
|
|
}
|
|
mapq -= (int)(4.343f * logf(r->n_sub + 1) + .499f);
|
|
mapq = mapq > 0? mapq : 0;
|
|
r->mapq = mapq < 60? mapq : 60;
|
|
if (r->p && r->p->dp_max > r->p->dp_max2 && r->mapq == 0) r->mapq = 1;
|
|
} else r->mapq = 0;
|
|
}
|
|
mm_set_inv_mapq(km, n_regs, regs);
|
|
}
|