// get the 3 genotype likelihoods
static double *get_pdg3(const bcf1_t *b)
{
double *pdg;
const uint8_t *PL = 0;
int i, PL_len = 0;
// initialize g_q2p if necessary
if (g_q2p[0] == 0.)
for (i = 0; i < 256; ++i)
g_q2p[i] = pow(10., -i / 10.);
// set PL and PL_len
for (i = 0; i < b->n_gi; ++i) {
if (b->gi[i].fmt == bcf_str2int("PL", 2)) {
PL = (const uint8_t*)b->gi[i].data;
PL_len = b->gi[i].len;
break;
}
}
if (i == b->n_gi) return 0; // no PL
// fill pdg
pdg = malloc(3 * b->n_smpl * sizeof(double));
for (i = 0; i < b->n_smpl; ++i) {
const uint8_t *pi = PL + i * PL_len;
double *p = pdg + i * 3;
p[0] = g_q2p[pi[2]]; p[1] = g_q2p[pi[1]]; p[2] = g_q2p[pi[0]];
}
return pdg;
}
int bcf_2qcall(bcf_hdr_t *h, bcf1_t *b)
{
int a[4], k, g[10], l, map[4], k1, j, i, i0, anno[16], dp, mq, d_rest;
char *s;
if (b->ref[1] != 0 || b->n_alleles > 4) return -1; // ref is not a single base
for (i = 0; i < b->n_gi; ++i)
if (b->gi[i].fmt == bcf_str2int("PL", 2)) break;
if (i == b->n_gi) return -1; // no PL
if (read_I16(b, anno) != 0) return -1; // no I16; FIXME: can be improved
d_rest = dp = anno[0] + anno[1] + anno[2] + anno[3];
if (dp == 0) return -1; // depth is zero
mq = (int)(sqrt((double)(anno[9] + anno[11]) / dp) + .499);
i0 = i;
a[0] = nt4_table[(int)b->ref[0]];
if (a[0] > 3) return -1; // ref is not A/C/G/T
a[1] = a[2] = a[3] = -2; // -1 has a special meaning
if (b->alt[0] == 0) return -1; // no alternate allele
map[0] = map[1] = map[2] = map[3] = -2;
map[a[0]] = 0;
for (k = 0, s = b->alt, k1 = -1; k < 3 && *s; ++k, s += 2) {
if (s[1] != ',' && s[1] != 0) return -1; // ALT is not single base
a[k+1] = nt4_table[(int)*s];
if (a[k+1] >= 0) map[a[k+1]] = k+1;
else k1 = k+1;
if (s[1] == 0) break;
}
for (k = 0; k < 4; ++k)
if (map[k] < 0) map[k] = k1;
for (i = 0; i < h->n_smpl; ++i) {
int d;
uint8_t *p = (uint8_t*)b->gi[i0].data + i * b->gi[i0].len; //dong code, verify
for (j = 0; j < b->gi[i0].len; ++j)
if (p[j]) break;
d = (int)((double)d_rest / (h->n_smpl - i) + .499);
if (d == 0) d = 1;
if (j == b->gi[i0].len) d = 0;
d_rest -= d;
for (k = j = 0; k < 4; ++k) {
for (l = k; l < 4; ++l) {
int t, x = map[k], y = map[l];
if (x > y) t = x, x = y, y = t; // swap
g[j++] = p[y * (y+1) / 2 + x];
}
}
printf("%s\t%d\t%c", h->ns[b->tid], b->pos+1, *b->ref);
printf("\t%d\t%d\t0", d, mq);
for (j = 0; j < 10; ++j)
printf("\t%d", g[j]);
printf("\t%s\n", h->sns[i]);
}
return 0;
}
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;
}
int vcf_read(bcf_t *bp, bcf_hdr_t *h, bcf1_t *b)
{
int dret, k, i, sync = 0;
vcf_t *v = (vcf_t*)bp->v;
char *p, *q;
kstring_t str, rn;
ks_tokaux_t aux, a2;
if (!bp->is_vcf) return bcf_read(bp, h, b);
v->line.l = 0;
str.l = 0; str.m = b->m_str; str.s = b->str;
rn.l = rn.m = h->l_nm; rn.s = h->name;
if (ks_getuntil(v->ks, '\n', &v->line, &dret) < 0) return -1;
b->n_smpl = h->n_smpl;
for (p = kstrtok(v->line.s, "\t", &aux), k = 0; p; p = kstrtok(0, 0, &aux), ++k) {
*(char*)aux.p = 0;
if (k == 0) { // ref
int tid = bcf_str2id(v->refhash, p);
if (tid < 0) {
tid = bcf_str2id_add(v->refhash, strdup(p));
kputs(p, &rn); kputc('\0', &rn);
sync = 1;
}
b->tid = tid;
} else if (k == 1) { // pos
b->pos = atoi(p) - 1;
} else if (k == 5) { // qual
b->qual = (p[0] >= '0' && p[0] <= '9')? atof(p) : 0;
} else if (k <= 8) { // variable length strings
kputs(p, &str); kputc('\0', &str);
b->l_str = str.l; b->m_str = str.m; b->str = str.s;
if (k == 8) bcf_sync(b);
} else { // k > 9
if (strncmp(p, "./.", 3) == 0) {
for (i = 0; i < b->n_gi; ++i) {
if (b->gi[i].fmt == bcf_str2int("GT", 2)) {
((uint8_t*)b->gi[i].data)[k-9] = 1<<7;
} else if (b->gi[i].fmt == bcf_str2int("GQ", 2)) {
((uint8_t*)b->gi[i].data)[k-9] = 0;
} else if (b->gi[i].fmt == bcf_str2int("SP", 2)) {
((int32_t*)b->gi[i].data)[k-9] = 0;
} else if (b->gi[i].fmt == bcf_str2int("DP", 2)) {
((uint16_t*)b->gi[i].data)[k-9] = 0;
} else if (b->gi[i].fmt == bcf_str2int("PL", 2)) {
int y = b->n_alleles * (b->n_alleles + 1) / 2;
memset((uint8_t*)b->gi[i].data + (k - 9) * y, 0, y);
} else if (b->gi[i].fmt == bcf_str2int("GL", 2)) {
int y = b->n_alleles * (b->n_alleles + 1) / 2;
memset((float*)b->gi[i].data + (k - 9) * y, 0, y * 4);
}
}
goto endblock;
}
for (q = kstrtok(p, ":", &a2), i = 0; q && i < b->n_gi; q = kstrtok(0, 0, &a2), ++i) {
if (b->gi[i].fmt == bcf_str2int("GT", 2)) {
((uint8_t*)b->gi[i].data)[k-9] = (q[0] - '0')<<3 | (q[2] - '0') | (q[1] == '/'? 0 : 1) << 6;
} else if (b->gi[i].fmt == bcf_str2int("GQ", 2)) {
double _x = strtod(q, &q);
int x = (int)(_x + .499);
if (x > 255) x = 255;
((uint8_t*)b->gi[i].data)[k-9] = x;
} else if (b->gi[i].fmt == bcf_str2int("SP", 2)) {
int x = strtol(q, &q, 10);
if (x > 0xffff) x = 0xffff;
((uint32_t*)b->gi[i].data)[k-9] = x;
} else if (b->gi[i].fmt == bcf_str2int("DP", 2)) {
int x = strtol(q, &q, 10);
if (x > 0xffff) x = 0xffff;
((uint16_t*)b->gi[i].data)[k-9] = x;
} else if (b->gi[i].fmt == bcf_str2int("PL", 2)) {
int x, y, j;
uint8_t *data = (uint8_t*)b->gi[i].data;
y = b->n_alleles * (b->n_alleles + 1) / 2;
for (j = 0; j < y; ++j) {
x = strtol(q, &q, 10);
if (x > 255) x = 255;
data[(k-9) * y + j] = x;
++q;
}
} else if (b->gi[i].fmt == bcf_str2int("GL", 2)) {
int j, y;
float x, *data = (float*)b->gi[i].data;
y = b->n_alleles * (b->n_alleles + 1) / 2;
for (j = 0; j < y; ++j) {
x = strtod(q, &q);
data[(k-9) * y + j] = x > 0? -x/10. : x;
++q;
}
}
}
endblock: i = i;
}
}
h->l_nm = rn.l; h->name = rn.s;
if (sync) bcf_hdr_sync(h);
return v->line.l + 1;
}
