#include <math.h>
+#include <assert.h>
#include "bam.h"
#include "bam_maqcns.h"
#include "ksort.h"
+#include "kaln.h"
KSORT_INIT_GENERIC(uint32_t)
-#define MAX_WINDOW 33
+#define INDEL_WINDOW_SIZE 50
+#define INDEL_EXT_DEP 0.9
typedef struct __bmc_aux_t {
int max;
/*
P(<b1,b2>) = \theta \sum_{i=1}^{N-1} 1/i
P(D|<b1,b2>) = \sum_{k=1}^{N-1} p_k 1/2 [(k/N)^n_2(1-k/N)^n_1 + (k/N)^n1(1-k/N)^n_2]
- p_k = i/k / \sum_{i=1}^{N-1} 1/i
+ p_k = 1/k / \sum_{i=1}^{N-1} 1/i
*/
static void cal_het(bam_maqcns_t *aa)
{
int k, n1, n2;
double sum_harmo; // harmonic sum
double poly_rate;
- double p1 = 0.0, p3 = 0.0; // just for testing
free(aa->lhet);
aa->lhet = (double*)calloc(256 * 256, sizeof(double));
for (n1 = 0; n1 < 256; ++n1) {
for (n2 = 0; n2 < 256; ++n2) {
long double sum = 0.0;
- double lC = lgamma(n1+n2+1) - lgamma(n1+1) - lgamma(n2+1); // \binom{n1+n2}{n1}
+ double lC = aa->is_soap? 0 : lgamma(n1+n2+1) - lgamma(n1+1) - lgamma(n2+1); // \binom{n1+n2}{n1}
for (k = 1; k <= aa->n_hap - 1; ++k) {
double pk = 1.0 / k / sum_harmo;
double log1 = log((double)k/aa->n_hap);
sum += pk * 0.5 * (expl(log1*n2) * expl(log2*n1) + expl(log1*n1) * expl(log2*n2));
}
aa->lhet[n1<<8|n2] = lC + logl(sum);
- if (n1 == 17 && n2 == 3) p3 = lC + logl(expl(logl(0.5) * 20));
- if (n1 == 19 && n2 == 1) p1 = lC + logl(expl(logl(0.5) * 20));
}
}
poly_rate = aa->het_rate * sum_harmo;
long double sum_a[257], b[256], q_c[256], tmp[256], fk2[256];
double *lC;
- lC = (double*)calloc(256 * 256, sizeof(double));
// aa->lhet will be allocated and initialized
free(aa->fk); free(aa->coef);
+ aa->coef = 0;
aa->fk = (double*)calloc(256, sizeof(double));
- aa->coef = (double*)calloc(256*256*64, sizeof(double));
aa->fk[0] = fk2[0] = 1.0;
for (n = 1; n != 256; ++n) {
aa->fk[n] = pow(aa->theta, n) * (1.0 - aa->eta) + aa->eta;
fk2[n] = aa->fk[n>>1]; // this is an approximation, assuming reads equally likely come from both strands
}
+ if (aa->is_soap) return;
+ aa->coef = (double*)calloc(256*256*64, sizeof(double));
+ lC = (double*)calloc(256 * 256, sizeof(double));
for (n = 1; n != 256; ++n)
for (k = 1; k <= n; ++k)
lC[n<<8|k] = lgamma(n+1) - lgamma(k+1) - lgamma(n-k+1);
if (w[k] < 0xff) ++w[k];
++b->c[k&3];
}
- tmp = (int)(info&0x7f) < bm->cap_mapQ? (int)(info&0x7f) : bm->cap_mapQ;
+ tmp = (int)(info&0xff) < bm->cap_mapQ? (int)(info&0xff) : bm->cap_mapQ;
rms += tmp * tmp;
}
b->rms_mapQ = (uint8_t)(sqrt((double)rms / n) + .499);
for (j = 0; j != 4; ++j) b->c[j] = (int)(254.0 * b->c[j] / c + 0.5);
for (j = c = 0; j != 4; ++j) c += b->c[j];
}
- // generate likelihood
- for (j = 0; j != 4; ++j) {
- // homozygous
- float tmp1, tmp3;
- int tmp2, bar_e;
- for (k = 0, tmp1 = tmp3 = 0.0, tmp2 = 0; k != 4; ++k) {
- if (j == k) continue;
- tmp1 += b->esum[k]; tmp2 += b->c[k]; tmp3 += b->fsum[k];
- }
- if (tmp2) {
- bar_e = (int)(tmp1 / tmp3 + 0.5);
- if (bar_e < 4) bar_e = 4; // should not happen
- if (bar_e > 63) bar_e = 63;
- p[j<<2|j] = tmp1 + bm->coef[bar_e<<16|c<<8|tmp2];
- } else p[j<<2|j] = 0.0; // all the bases are j
- // heterozygous
- for (k = j + 1; k < 4; ++k) {
- for (i = 0, tmp2 = 0, tmp1 = tmp3 = 0.0; i != 4; ++i) {
- if (i == j || i == k) continue;
- tmp1 += b->esum[i]; tmp2 += b->c[i]; tmp3 += b->fsum[i];
+ if (!bm->is_soap) {
+ // generate likelihood
+ for (j = 0; j != 4; ++j) {
+ // homozygous
+ float tmp1, tmp3;
+ int tmp2, bar_e;
+ for (k = 0, tmp1 = tmp3 = 0.0, tmp2 = 0; k != 4; ++k) {
+ if (j == k) continue;
+ tmp1 += b->esum[k]; tmp2 += b->c[k]; tmp3 += b->fsum[k];
}
if (tmp2) {
bar_e = (int)(tmp1 / tmp3 + 0.5);
- if (bar_e < 4) bar_e = 4;
+ if (bar_e < 4) bar_e = 4; // should not happen
if (bar_e > 63) bar_e = 63;
- p[j<<2|k] = p[k<<2|j] = -4.343 * bm->lhet[b->c[j]<<8|b->c[k]] + tmp1 + bm->coef[bar_e<<16|c<<8|tmp2];
- } else p[j<<2|k] = p[k<<2|j] = -4.343 * bm->lhet[b->c[j]<<8|b->c[k]]; // all the bases are either j or k
+ p[j<<2|j] = tmp1 + bm->coef[bar_e<<16|c<<8|tmp2];
+ } else p[j<<2|j] = 0.0; // all the bases are j
+ // heterozygous
+ for (k = j + 1; k < 4; ++k) {
+ for (i = 0, tmp2 = 0, tmp1 = tmp3 = 0.0; i != 4; ++i) {
+ if (i == j || i == k) continue;
+ tmp1 += b->esum[i]; tmp2 += b->c[i]; tmp3 += b->fsum[i];
+ }
+ if (tmp2) {
+ bar_e = (int)(tmp1 / tmp3 + 0.5);
+ if (bar_e < 4) bar_e = 4;
+ if (bar_e > 63) bar_e = 63;
+ p[j<<2|k] = p[k<<2|j] = -4.343 * bm->lhet[b->c[j]<<8|b->c[k]] + tmp1 + bm->coef[bar_e<<16|c<<8|tmp2];
+ } else p[j<<2|k] = p[k<<2|j] = -4.343 * bm->lhet[b->c[j]<<8|b->c[k]]; // all the bases are either j or k
+ }
+ //
+ for (k = 0; k != 4; ++k)
+ if (p[j<<2|k] < 0.0) p[j<<2|k] = 0.0;
}
- //
- for (k = 0; k != 4; ++k)
- if (p[j<<2|k] < 0.0) p[j<<2|k] = 0.0;
- }
- { // fix p[k<<2|k]
- float max1, max2, min1, min2;
- int max_k, min_k;
- max_k = min_k = -1;
- max1 = max2 = -1.0; min1 = min2 = 1e30;
- for (k = 0; k < 4; ++k) {
- if (b->esum[k] > max1) {
- max2 = max1; max1 = b->esum[k]; max_k = k;
- } else if (b->esum[k] > max2) max2 = b->esum[k];
+ { // fix p[k<<2|k]
+ float max1, max2, min1, min2;
+ int max_k, min_k;
+ max_k = min_k = -1;
+ max1 = max2 = -1.0; min1 = min2 = 1e30;
+ for (k = 0; k < 4; ++k) {
+ if (b->esum[k] > max1) {
+ max2 = max1; max1 = b->esum[k]; max_k = k;
+ } else if (b->esum[k] > max2) max2 = b->esum[k];
+ }
+ for (k = 0; k < 4; ++k) {
+ if (p[k<<2|k] < min1) {
+ min2 = min1; min1 = p[k<<2|k]; min_k = k;
+ } else if (p[k<<2|k] < min2) min2 = p[k<<2|k];
+ }
+ if (max1 > max2 && (min_k != max_k || min1 + 1.0 > min2))
+ p[max_k<<2|max_k] = min1 > 1.0? min1 - 1.0 : 0.0;
}
- for (k = 0; k < 4; ++k) {
- if (p[k<<2|k] < min1) {
- min2 = min1; min1 = p[k<<2|k]; min_k = k;
- } else if (p[k<<2|k] < min2) min2 = p[k<<2|k];
+ } else { // apply the SOAP model
+ // generate likelihood
+ for (j = 0; j != 4; ++j) {
+ float tmp;
+ // homozygous
+ for (k = 0, tmp = 0.0; k != 4; ++k)
+ if (j != k) tmp += b->esum[k];
+ p[j<<2|j] = tmp;
+ // heterozygous
+ for (k = j + 1; k < 4; ++k) {
+ for (i = 0, tmp = 0.0; i != 4; ++i)
+ if (i != j && i != k) tmp += b->esum[i];
+ p[j<<2|k] = p[k<<2|j] = -4.343 * bm->lhet[b->c[j]<<8|b->c[k]] + tmp;
+ }
}
- if (max1 > max2 && (min_k != max_k || min1 + 1.0 > min2))
- p[max_k<<2|max_k] = min1 > 1.0? min1 - 1.0 : 0.0;
}
// convert necessary information to glf1_t
bam_maqindel_opt_t *mi = (bam_maqindel_opt_t*)calloc(1, sizeof(bam_maqindel_opt_t));
mi->q_indel = 40;
mi->r_indel = 0.00015;
+ mi->r_snp = 0.001;
//
mi->mm_penalty = 3;
mi->indel_err = 4;
free(mir->s[0]); free(mir->s[1]); free(mir);
}
+int bam_tpos2qpos(const bam1_core_t *c, const uint32_t *cigar, int32_t tpos, int is_left, int32_t *_tpos)
+{
+ int k, x = c->pos, y = 0, last_y = 0;
+ *_tpos = c->pos;
+ for (k = 0; k < c->n_cigar; ++k) {
+ int op = cigar[k] & BAM_CIGAR_MASK;
+ int l = cigar[k] >> BAM_CIGAR_SHIFT;
+ if (op == BAM_CMATCH) {
+ if (c->pos > tpos) return y;
+ if (x + l > tpos) {
+ *_tpos = tpos;
+ return y + (tpos - x);
+ }
+ x += l; y += l;
+ last_y = y;
+ } else if (op == BAM_CINS || op == BAM_CSOFT_CLIP) y += l;
+ else if (op == BAM_CDEL || op == BAM_CREF_SKIP) {
+ if (x + l > tpos) {
+ *_tpos = is_left? x : x + l;
+ return y;
+ }
+ x += l;
+ }
+ }
+ *_tpos = x;
+ return last_y;
+}
+
#define MINUS_CONST 0x10000000
bam_maqindel_ret_t *bam_maqindel(int n, int pos, const bam_maqindel_opt_t *mi, const bam_pileup1_t *pl, const char *ref,
int _n_types, int *_types)
{
- int i, j, n_types, *types, left, right;
+ int i, j, n_types, *types, left, right, max_rd_len = 0;
bam_maqindel_ret_t *ret = 0;
// if there is no proposed indel, check if there is an indel from the alignment
if (_n_types == 0) {
const bam_pileup1_t *p = pl + i;
if (!(p->b->core.flag&BAM_FUNMAP) && p->indel != 0)
aux[m++] = MINUS_CONST + p->indel;
+ j = bam_cigar2qlen(&p->b->core, bam1_cigar(p->b));
+ if (j > max_rd_len) max_rd_len = j;
}
if (_n_types) // then also add this to aux[]
for (i = 0; i < _n_types; ++i)
free(aux);
}
{ // calculate left and right boundary
- bam_segreg_t seg;
- left = 0x7fffffff; right = 0;
- for (i = 0; i < n; ++i) {
- const bam_pileup1_t *p = pl + i;
- if (!(p->b->core.flag&BAM_FUNMAP)) {
- bam_segreg(pos, &p->b->core, bam1_cigar(p->b), &seg);
- if (seg.tbeg < left) left = seg.tbeg;
- if (seg.tend > right) right = seg.tend;
- }
- }
- if (pos - left > MAX_WINDOW) left = pos - MAX_WINDOW;
- if (right - pos> MAX_WINDOW) right = pos + MAX_WINDOW;
+ left = pos > INDEL_WINDOW_SIZE? pos - INDEL_WINDOW_SIZE : 0;
+ right = pos + INDEL_WINDOW_SIZE;
+ if (types[0] < 0) right -= types[0];
+ // in case the alignments stand out the reference
+ for (i = pos; i < right; ++i)
+ if (ref[i] == 0) break;
+ right = i;
}
{ // the core part
- char *ref2, *inscns = 0;
- int k, l, *score, *pscore, max_ins = types[n_types-1];
- ref2 = (char*)calloc(right - left + types[n_types-1] + 2, 1);
+ char *ref2, *rs, *inscns = 0;
+ int qr_snp, k, l, *score, *pscore, max_ins = types[n_types-1];
+ qr_snp = (int)(-4.343 * log(mi->r_snp) + .499);
if (max_ins > 0) { // get the consensus of inserted sequences
int *inscns_aux = (int*)calloc(4 * n_types * max_ins, sizeof(int));
// count occurrences
free(inscns_aux);
}
// calculate score
+ ref2 = (char*)calloc(right - left + types[n_types-1] + 2, 1);
+ rs = (char*)calloc(right - left + max_rd_len + types[n_types-1] + 2, 1);
score = (int*)calloc(n_types * n, sizeof(int));
pscore = (int*)calloc(n_types * n, sizeof(int));
for (i = 0; i < n_types; ++i) {
+ ka_param_t ap = ka_param_blast;
+ ap.band_width = 2 * types[n_types - 1] + 2;
+ ap.gap_end = 0;
// write ref2
for (k = 0, j = left; j <= pos; ++j)
- ref2[k++] = bam_nt16_table[(int)ref[j]];
+ ref2[k++] = bam_nt16_nt4_table[bam_nt16_table[(int)ref[j]]];
if (types[i] <= 0) j += -types[i];
else for (l = 0; l < types[i]; ++l)
- ref2[k++] = inscns[i*max_ins + l];
+ ref2[k++] = bam_nt16_nt4_table[(int)inscns[i*max_ins + l]];
+ if (types[0] < 0) { // mask deleted sequences
+ int jj, tmp = types[i] >= 0? -types[0] : -types[0] + types[i];
+ for (jj = 0; jj < tmp && j < right && ref[j]; ++jj, ++j)
+ ref2[k++] = 4;
+ }
for (; j < right && ref[j]; ++j)
- ref2[k++] = bam_nt16_table[(int)ref[j]];
+ ref2[k++] = bam_nt16_nt4_table[bam_nt16_table[(int)ref[j]]];
+ if (j < right) right = j;
// calculate score for each read
for (j = 0; j < n; ++j) {
const bam_pileup1_t *p = pl + j;
- uint32_t *cigar;
- bam1_core_t *c = &p->b->core;
- int s, ps;
- bam_segreg_t seg;
- if (c->flag&BAM_FUNMAP) continue;
- cigar = bam1_cigar(p->b);
- bam_segreg(pos, c, cigar, &seg);
- for (ps = s = 0, l = seg.qbeg; c->pos + l < right && l < seg.qend; ++l) {
- int cq = bam1_seqi(bam1_seq(p->b), l), ct;
- // in the following line, "<" will happen if reads are too long
- ct = c->pos + l - seg.qbeg >= left? ref2[c->pos + l - seg.qbeg - left] : 15;
- if (cq < 15 && ct < 15) {
- s += cq == ct? 1 : -mi->mm_penalty;
- if (cq != ct) ps += bam1_qual(p->b)[l];
+ int qbeg, qend, tbeg, tend;
+ if (p->b->core.flag & BAM_FUNMAP) continue;
+ qbeg = bam_tpos2qpos(&p->b->core, bam1_cigar(p->b), left, 0, &tbeg);
+ qend = bam_tpos2qpos(&p->b->core, bam1_cigar(p->b), right, 1, &tend);
+ assert(tbeg >= left);
+ for (l = qbeg; l < qend; ++l)
+ rs[l - qbeg] = bam_nt16_nt4_table[bam1_seqi(bam1_seq(p->b), l)];
+ {
+ int x, y, n_acigar, ps;
+ uint32_t *acigar;
+ ps = 0;
+ if (tend - tbeg + types[i] <= 0) {
+ score[i*n+j] = -(1<<20);
+ pscore[i*n+j] = 1<<20;
+ continue;
}
- }
- score[i*n + j] = s; pscore[i*n + j] = ps;
- if (types[i] != 0) { // then try the other way to calculate the score
- for (ps = s = 0, l = seg.qbeg; c->pos + l + types[i] < right && l < seg.qend; ++l) {
- int cq = bam1_seqi(bam1_seq(p->b), l), ct;
- ct = c->pos + l - seg.qbeg + types[i] >= left? ref2[c->pos + l - seg.qbeg + types[i] - left] : 15;
- if (cq < 15 && ct < 15) {
- s += cq == ct? 1 : -mi->mm_penalty;
- if (cq != ct) ps += bam1_qual(p->b)[l];
+ acigar = ka_global_core((uint8_t*)ref2 + tbeg - left, tend - tbeg + types[i], (uint8_t*)rs, qend - qbeg, &ap, &score[i*n+j], &n_acigar);
+ x = tbeg - left; y = 0;
+ for (l = 0; l < n_acigar; ++l) {
+ int op = acigar[l]&0xf;
+ int len = acigar[l]>>4;
+ if (op == BAM_CMATCH) {
+ int k;
+ for (k = 0; k < len; ++k)
+ if (ref2[x+k] != rs[y+k] && ref2[x+k] < 4)
+ ps += bam1_qual(p->b)[y+k] < qr_snp? bam1_qual(p->b)[y+k] : qr_snp;
+ x += len; y += len;
+ } else if (op == BAM_CINS || op == BAM_CSOFT_CLIP) {
+ if (op == BAM_CINS && l > 0 && l < n_acigar - 1) ps += mi->q_indel * len;
+ y += len;
+ } else if (op == BAM_CDEL) {
+ if (l > 0 && l < n_acigar - 1) ps += mi->q_indel * len;
+ x += len;
}
}
+ pscore[i*n+j] = ps;
+ /*if (1) { // for debugging only
+ fprintf(stderr, "id=%d, pos=%d, type=%d, j=%d, score=%d, psore=%d, %d, %d, %d, %d, %d, ",
+ j, pos+1, types[i], j, score[i*n+j], pscore[i*n+j], tbeg, tend, qbeg, qend, mi->q_indel);
+ for (l = 0; l < n_acigar; ++l) fprintf(stderr, "%d%c", acigar[l]>>4, "MIDS"[acigar[l]&0xf]);
+ fprintf(stderr, "\n");
+ for (l = 0; l < tend - tbeg + types[i]; ++l) fputc("ACGTN"[ref2[l+tbeg-left]], stderr);
+ fputc('\n', stderr);
+ for (l = 0; l < qend - qbeg; ++l) fputc("ACGTN"[rs[l]], stderr);
+ fputc('\n', stderr);
+ }*/
+ free(acigar);
}
- if (score[i*n+j] < s) score[i*n+j] = s; // choose the higher of the two scores
- if (pscore[i*n+j] > ps) pscore[i*n+j] = ps;
- if (types[i] != 0) score[i*n+j] -= mi->indel_err;
- //printf("%d, %d, %d, %d, %d, %d, %d\n", p->b->core.pos + 1, seg.qbeg, i, types[i], j,
- // score[i*n+j], pscore[i*n+j]);
}
}
{ // get final result
else if (p->indel == ret->indel2) ++ret->cnt2;
else ++ret->cnt_anti;
}
- // write gl[]
- ret->gl[0] = ret->gl[1] = 0;
- for (j = 0; j < n; ++j) {
- int s1 = pscore[max1_i*n + j], s2 = pscore[max2_i*n + j];
- //printf("%d, %d, %d, %d, %d\n", pl[j].b->core.pos+1, max1_i, max2_i, s1, s2);
- if (s1 > s2) ret->gl[0] += s1 - s2 < mi->q_indel? s1 - s2 : mi->q_indel;
- else ret->gl[1] += s2 - s1 < mi->q_indel? s2 - s1 : mi->q_indel;
+ { // write gl[]
+ int tmp, seq_err = 0;
+ double x = 1.0;
+ tmp = max1_i - max2_i;
+ if (tmp < 0) tmp = -tmp;
+ for (j = 0; j < tmp + 1; ++j) x *= INDEL_EXT_DEP;
+ seq_err = mi->q_indel * (1.0 - x) / (1.0 - INDEL_EXT_DEP);
+ ret->gl[0] = ret->gl[1] = 0;
+ for (j = 0; j < n; ++j) {
+ int s1 = pscore[max1_i*n + j], s2 = pscore[max2_i*n + j];
+ //fprintf(stderr, "id=%d, %d, %d, %d, %d, %d\n", j, pl[j].b->core.pos+1, types[max1_i], types[max2_i], s1, s2);
+ if (s1 > s2) ret->gl[0] += s1 - s2 < seq_err? s1 - s2 : seq_err;
+ else ret->gl[1] += s2 - s1 < seq_err? s2 - s1 : seq_err;
+ }
+ }
+ // write cnt_ref and cnt_ambi
+ if (max1_i != 0 && max2_i != 0) {
+ for (j = 0; j < n; ++j) {
+ int diff1 = score[j] - score[max1_i * n + j];
+ int diff2 = score[j] - score[max2_i * n + j];
+ if (diff1 > 0 && diff2 > 0) ++ret->cnt_ref;
+ else if (diff1 == 0 || diff2 == 0) ++ret->cnt_ambi;
+ }
}
}
- free(score); free(pscore); free(ref2); free(inscns);
+ free(score); free(pscore); free(ref2); free(rs); free(inscns);
}
{ // call genotype
int q[3], qr_indel = (int)(-4.343 * log(mi->r_indel) + 0.5);
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