int mc_cal(int ref, int *n, const bam_pileup1_t **plp, mc_aux_t *ma, mc_rst_t *rst, int level)
{
int i, tot;
memset(rst, 0, sizeof(mc_rst_t));
rst->f_em = rst->f_exp = -1.; rst->ref = rst->alt = -1;
// precalculation
tot = sum_err(n, plp, ma);
if (tot == 0) return 0; // no good bases
set_allele(ref, ma);
cal_pdg(ma);
// set ref/major allele
rst->ref = ma->ref; rst->alt = ma->alt; rst->alt2 = ma->alt2;
// calculate naive and Nielsen's freq
rst->f_naive = mc_freq0(ma, &rst->f_nielsen);
{ // calculate f_em
double flast = rst->f_naive;
for (i = 0; i < MC_MAX_EM_ITER; ++i) {
rst->f_em = mc_freq_iter(flast, ma);
if (fabs(rst->f_em - flast) < MC_EM_EPS) break;
flast = rst->f_em;
}
}
if (level >= 2) {
rst->f_exp = mc_add_afs(ma);
rst->p_ref = ma->afs1[ma->M];
}
return tot;
}
int bcf_p1_cal(bcf1_t *b, bcf_p1aux_t *ma, bcf_p1rst_t *rst)
{
int i, k;
long double sum = 0.;
// set PL and PL_len
for (i = 0; i < b->n_gi; ++i) {
if (b->gi[i].fmt == bcf_str2int("PL", 2)) {
ma->PL = (uint8_t*)b->gi[i].data;
ma->PL_len = b->gi[i].len;
break;
}
}
if (b->n_alleles < 2) return -1; // FIXME: find a better solution
//
rst->rank0 = cal_pdg(b, ma);
rst->f_exp = mc_cal_afs(ma);
rst->p_ref = ma->afs1[ma->M];
// calculate f_flat and f_em
for (k = 0, sum = 0.; k <= ma->M; ++k)
sum += (long double)ma->z[k];
rst->f_flat = 0.;
for (k = 0; k <= ma->M; ++k) {
double p = ma->z[k] / sum;
rst->f_flat += k * p;
}
rst->f_flat /= ma->M;
{ // calculate f_em
double flast = rst->f_flat;
for (i = 0; i < MC_MAX_EM_ITER; ++i) {
rst->f_em = mc_freq_iter(flast, ma);
if (fabs(rst->f_em - flast) < MC_EM_EPS) break;
flast = rst->f_em;
}
}
rst->g[0] = rst->g[1] = rst->g[2] = -1.;
contrast(ma, rst->pc);
return 0;
}
int bcf_p1_cal(const bcf1_t *b, int do_contrast, bcf_p1aux_t *ma, bcf_p1rst_t *rst)
{
int i, k;
long double sum = 0.;
ma->is_indel = bcf_is_indel(b);
rst->perm_rank = -1;
// set PL and PL_len
for (i = 0; i < b->n_gi; ++i) {
if (b->gi[i].fmt == bcf_str2int("PL", 2)) {
ma->PL = (uint8_t*)b->gi[i].data;
ma->PL_len = b->gi[i].len;
break;
}
}
if (i == b->n_gi) return -1; // no PL
if (b->n_alleles < 2) return -1; // FIXME: find a better solution
//
rst->rank0 = cal_pdg(b, ma);
rst->f_exp = mc_cal_afs(ma, &rst->p_ref_folded, &rst->p_var_folded);
rst->p_ref = ma->afs1[ma->M];
for (k = 0, sum = 0.; k < ma->M; ++k)
sum += ma->afs1[k];
rst->p_var = (double)sum;
{ // compute the allele count
double max = -1;
rst->ac = -1;
for (k = 0; k <= ma->M; ++k)
if (max < ma->z[k]) max = ma->z[k], rst->ac = k;
rst->ac = ma->M - rst->ac;
}
// calculate f_flat and f_em
for (k = 0, sum = 0.; k <= ma->M; ++k)
sum += (long double)ma->z[k];
rst->f_flat = 0.;
for (k = 0; k <= ma->M; ++k) {
double p = ma->z[k] / sum;
rst->f_flat += k * p;
}
rst->f_flat /= ma->M;
{ // estimate equal-tail credible interval (95% level)
int l, h;
double p;
for (i = 0, p = 0.; i <= ma->M; ++i)
if (p + ma->afs1[i] > 0.025) break;
else p += ma->afs1[i];
l = i;
for (i = ma->M, p = 0.; i >= 0; --i)
if (p + ma->afs1[i] > 0.025) break;
else p += ma->afs1[i];
h = i;
rst->cil = (double)(ma->M - h) / ma->M; rst->cih = (double)(ma->M - l) / ma->M;
}
if (ma->n1 > 0) { // compute LRT
double max0, max1, max2;
for (k = 0, max0 = -1; k <= ma->M; ++k)
if (max0 < ma->z[k]) max0 = ma->z[k];
for (k = 0, max1 = -1; k <= ma->n1 * 2; ++k)
if (max1 < ma->z1[k]) max1 = ma->z1[k];
for (k = 0, max2 = -1; k <= ma->M - ma->n1 * 2; ++k)
if (max2 < ma->z2[k]) max2 = ma->z2[k];
rst->lrt = log(max1 * max2 / max0);
rst->lrt = rst->lrt < 0? 1 : kf_gammaq(.5, rst->lrt);
} else rst->lrt = -1.0;
rst->cmp[0] = rst->cmp[1] = rst->cmp[2] = rst->p_chi2 = -1.0;
if (do_contrast && rst->p_var > 0.5) // skip contrast2() if the locus is a strong non-variant
rst->p_chi2 = contrast2(ma, rst->cmp);
return 0;
}
