#include <stdlib.h>
#include <string.h>
#include <stdio.h>
+#include <errno.h>
#include "prob1.h"
-#define MC_AVG_ERR 0.007
+#include "kseq.h"
+KSTREAM_INIT(gzFile, gzread, 16384)
+
#define MC_MAX_EM_ITER 16
#define MC_EM_EPS 1e-4
+#define MC_DEF_INDEL 0.15
unsigned char seq_nt4_table[256] = {
4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
};
struct __bcf_p1aux_t {
- int n, M;
+ int n, M, n1, is_indel;
double *q2p, *pdg; // pdg -> P(D|g)
- double *phi;
+ double *phi, *phi_indel;
double *z, *zswap; // aux for afs
+ double *z1, *z2, *phi1, *phi2; // only calculated when n1 is set
+ double t, t1, t2;
double *afs, *afs1; // afs: accumulative AFS; afs1: site posterior distribution
const uint8_t *PL; // point to PL
int PL_len;
};
-void bcf_p1_init_prior(bcf_p1aux_t *ma, int type, double theta)
+void bcf_p1_indel_prior(bcf_p1aux_t *ma, double x)
+{
+ int i;
+ for (i = 0; i < ma->M; ++i)
+ ma->phi_indel[i] = ma->phi[i] * x;
+ ma->phi_indel[ma->M] = 1. - ma->phi[ma->M] * x;
+}
+
+static void init_prior(int type, double theta, int M, double *phi)
{
int i;
if (type == MC_PTYPE_COND2) {
- for (i = 0; i <= ma->M; ++i)
- ma->phi[i] = 2. * (i + 1) / (ma->M + 1) / (ma->M + 2);
+ for (i = 0; i <= M; ++i)
+ phi[i] = 2. * (i + 1) / (M + 1) / (M + 2);
} else if (type == MC_PTYPE_FLAT) {
- for (i = 0; i <= ma->M; ++i)
- ma->phi[i] = 1. / (ma->M + 1);
+ for (i = 0; i <= M; ++i)
+ phi[i] = 1. / (M + 1);
} else {
double sum;
- for (i = 0, sum = 0.; i < ma->M; ++i)
- sum += (ma->phi[i] = theta / (ma->M - i));
- ma->phi[ma->M] = 1. - sum;
+ for (i = 0, sum = 0.; i < M; ++i)
+ sum += (phi[i] = theta / (M - i));
+ phi[M] = 1. - sum;
+ }
+}
+
+void bcf_p1_init_prior(bcf_p1aux_t *ma, int type, double theta)
+{
+ init_prior(type, theta, ma->M, ma->phi);
+ bcf_p1_indel_prior(ma, MC_DEF_INDEL);
+}
+
+void bcf_p1_init_subprior(bcf_p1aux_t *ma, int type, double theta)
+{
+ if (ma->n1 <= 0 || ma->n1 >= ma->M) return;
+ init_prior(type, theta, 2*ma->n1, ma->phi1);
+ init_prior(type, theta, 2*(ma->n - ma->n1), ma->phi2);
+}
+
+int bcf_p1_read_prior(bcf_p1aux_t *ma, const char *fn)
+{
+ gzFile fp;
+ kstring_t s;
+ kstream_t *ks;
+ long double sum;
+ int dret, k;
+ memset(&s, 0, sizeof(kstring_t));
+ fp = strcmp(fn, "-")? gzopen(fn, "r") : gzdopen(fileno(stdin), "r");
+ ks = ks_init(fp);
+ memset(ma->phi, 0, sizeof(double) * (ma->M + 1));
+ while (ks_getuntil(ks, '\n', &s, &dret) >= 0) {
+ if (strstr(s.s, "[afs] ") == s.s) {
+ char *p = s.s + 6;
+ for (k = 0; k <= ma->M; ++k) {
+ int x;
+ double y;
+ x = strtol(p, &p, 10);
+ if (x != k && (errno == EINVAL || errno == ERANGE)) return -1;
+ ++p;
+ y = strtod(p, &p);
+ if (y == 0. && (errno == EINVAL || errno == ERANGE)) return -1;
+ ma->phi[ma->M - k] += y;
+ }
+ }
}
+ ks_destroy(ks);
+ gzclose(fp);
+ free(s.s);
+ for (sum = 0., k = 0; k <= ma->M; ++k) sum += ma->phi[k];
+ fprintf(stderr, "[prior]");
+ for (k = 0; k <= ma->M; ++k) ma->phi[k] /= sum;
+ for (k = 0; k <= ma->M; ++k) fprintf(stderr, " %d:%.3lg", k, ma->phi[ma->M - k]);
+ fputc('\n', stderr);
+ for (sum = 0., k = 1; k < ma->M; ++k) sum += ma->phi[ma->M - k] * (2.* k * (ma->M - k) / ma->M / (ma->M - 1));
+ fprintf(stderr, "[%s] heterozygosity=%lf, ", __func__, (double)sum);
+ for (sum = 0., k = 1; k <= ma->M; ++k) sum += k * ma->phi[ma->M - k] / ma->M;
+ fprintf(stderr, "theta=%lf\n", (double)sum);
+ bcf_p1_indel_prior(ma, MC_DEF_INDEL);
+ return 0;
}
-bcf_p1aux_t *bcf_p1_init(int n) // FIXME: assuming diploid
+bcf_p1aux_t *bcf_p1_init(int n)
{
bcf_p1aux_t *ma;
int i;
ma = calloc(1, sizeof(bcf_p1aux_t));
+ ma->n1 = -1;
ma->n = n; ma->M = 2 * n;
ma->q2p = calloc(256, sizeof(double));
ma->pdg = calloc(3 * ma->n, sizeof(double));
ma->phi = calloc(ma->M + 1, sizeof(double));
+ ma->phi_indel = calloc(ma->M + 1, sizeof(double));
+ ma->phi1 = calloc(ma->M + 1, sizeof(double));
+ ma->phi2 = calloc(ma->M + 1, sizeof(double));
ma->z = calloc(2 * ma->n + 1, sizeof(double));
ma->zswap = calloc(2 * ma->n + 1, sizeof(double));
+ ma->z1 = calloc(ma->M + 1, sizeof(double)); // actually we do not need this large
+ ma->z2 = calloc(ma->M + 1, sizeof(double));
ma->afs = calloc(2 * ma->n + 1, sizeof(double));
ma->afs1 = calloc(2 * ma->n + 1, sizeof(double));
for (i = 0; i < 256; ++i)
return ma;
}
+int bcf_p1_set_n1(bcf_p1aux_t *b, int n1)
+{
+ if (n1 == 0 || n1 >= b->n) return -1;
+ b->n1 = n1;
+ return 0;
+}
+
void bcf_p1_destroy(bcf_p1aux_t *ma)
{
if (ma) {
free(ma->q2p); free(ma->pdg);
- free(ma->phi);
- free(ma->z); free(ma->zswap);
+ free(ma->phi); free(ma->phi_indel); free(ma->phi1); free(ma->phi2);
+ free(ma->z); free(ma->zswap); free(ma->z1); free(ma->z2);
free(ma->afs); free(ma->afs1);
free(ma);
}
}
-#define char2int(s) (((int)s[0])<<8|s[1])
-
static int cal_pdg(const bcf1_t *b, bcf_p1aux_t *ma)
{
- int i, j, k;
+ int i, j;
long *p, tmp;
p = alloca(b->n_alleles * sizeof(long));
memset(p, 0, sizeof(long) * b->n_alleles);
for (j = 0; j < ma->n; ++j) {
const uint8_t *pi = ma->PL + j * ma->PL_len;
double *pdg = ma->pdg + j * 3;
- pdg[0] = ma->q2p[pi[b->n_alleles]]; pdg[1] = ma->q2p[pi[1]]; pdg[2] = ma->q2p[pi[0]];
- for (i = k = 0; i < b->n_alleles; ++i) {
- p[i] += (int)pi[k];
- k += b->n_alleles - i;
- }
+ pdg[0] = ma->q2p[pi[2]]; pdg[1] = ma->q2p[pi[1]]; pdg[2] = ma->q2p[pi[0]];
+ for (i = 0; i < b->n_alleles; ++i)
+ p[i] += (int)pi[(i+1)*(i+2)/2-1];
}
for (i = 0; i < b->n_alleles; ++i) p[i] = p[i]<<4 | i;
for (i = 1; i < b->n_alleles; ++i) // insertion sort
}
max = 1. - max;
if (max < 1e-308) max = 1e-308;
- q = (int)(-3.434 * log(max) + .499);
+ q = (int)(-4.343 * log(max) + .499);
if (q > 99) q = 99;
return q<<2|max_i;
}
#define TINY 1e-20
-static void mc_cal_y(bcf_p1aux_t *ma)
+static void mc_cal_y_core(bcf_p1aux_t *ma, int beg)
{
- double *z[2], *tmp, *pdg, last_min, last_max;
- int k, j;
+ double *z[2], *tmp, *pdg;
+ int _j, last_min, last_max;
z[0] = ma->z;
z[1] = ma->zswap;
pdg = ma->pdg;
- z[0][0] = 1.; z[0][1] = z[0][2] = 0.;
+ memset(z[0], 0, sizeof(double) * (ma->M + 1));
+ memset(z[1], 0, sizeof(double) * (ma->M + 1));
+ z[0][0] = 1.;
last_min = last_max = 0;
- for (j = 0; j < ma->n; ++j) {
- int _min = last_min, _max = last_max;
+ ma->t = 0.;
+ for (_j = beg; _j < ma->n; ++_j) {
+ int k, j = _j - beg, _min = last_min, _max = last_max;
double p[3], sum;
- pdg = ma->pdg + j * 3;
+ pdg = ma->pdg + _j * 3;
p[0] = pdg[0]; p[1] = 2. * pdg[1]; p[2] = pdg[2];
-// for (; _min < _max && z[0][_min] < TINY; ++_min) z[1][_min] = 0.;
-// for (; _max > _min && z[0][_max] < TINY; --_max) z[1][_max] = 0.;
+ for (; _min < _max && z[0][_min] < TINY; ++_min) z[0][_min] = z[1][_min] = 0.;
+ for (; _max > _min && z[0][_max] < TINY; --_max) z[0][_max] = z[1][_max] = 0.;
_max += 2;
if (_min == 0)
k = 0, z[1][k] = (2*j+2-k)*(2*j-k+1) * p[0] * z[0][k];
+ k*(2*j+2-k) * p[1] * z[0][k-1]
+ k*(k-1)* p[2] * z[0][k-2];
for (k = _min, sum = 0.; k <= _max; ++k) sum += z[1][k];
+ ma->t += log(sum / ((2. * j + 2) * (2. * j + 1)));
for (k = _min; k <= _max; ++k) z[1][k] /= sum;
+ if (_min >= 1) z[1][_min-1] = 0.;
+ if (_min >= 2) z[1][_min-2] = 0.;
if (j < ma->n - 1) z[1][_max+1] = z[1][_max+2] = 0.;
+ if (_j == ma->n1 - 1) { // set pop1
+ ma->t1 = ma->t;
+ memcpy(ma->z1, z[1], sizeof(double) * (ma->n1 * 2 + 1));
+ }
tmp = z[0]; z[0] = z[1]; z[1] = tmp;
last_min = _min; last_max = _max;
}
if (z[0] != ma->z) memcpy(ma->z, z[0], sizeof(double) * (ma->M + 1));
}
-static double mc_cal_afs(bcf_p1aux_t *ma)
+static void mc_cal_y(bcf_p1aux_t *ma)
+{
+ if (ma->n1 > 0 && ma->n1 < ma->n) {
+ int k;
+ long double x;
+ memset(ma->z1, 0, sizeof(double) * (2 * ma->n1 + 1));
+ memset(ma->z2, 0, sizeof(double) * (2 * (ma->n - ma->n1) + 1));
+ ma->t1 = ma->t2 = 0.;
+ mc_cal_y_core(ma, ma->n1);
+ ma->t2 = ma->t;
+ memcpy(ma->z2, ma->z, sizeof(double) * (2 * (ma->n - ma->n1) + 1));
+ mc_cal_y_core(ma, 0);
+ // rescale z
+ x = expl(ma->t - (ma->t1 + ma->t2));
+ for (k = 0; k <= ma->M; ++k) ma->z[k] *= x;
+ } else mc_cal_y_core(ma, 0);
+}
+
+static void contrast(bcf_p1aux_t *ma, double pc[4]) // mc_cal_y() must be called before hand
+{
+ int k, n1 = ma->n1, n2 = ma->n - ma->n1;
+ long double sum1, sum2;
+ pc[0] = pc[1] = pc[2] = pc[3] = -1.;
+ if (n1 <= 0 || n2 <= 0) return;
+ for (k = 0, sum1 = 0.; k <= 2*n1; ++k) sum1 += ma->phi1[k] * ma->z1[k];
+ for (k = 0, sum2 = 0.; k <= 2*n2; ++k) sum2 += ma->phi2[k] * ma->z2[k];
+ pc[2] = ma->phi1[2*n1] * ma->z1[2*n1] / sum1;
+ pc[3] = ma->phi2[2*n2] * ma->z2[2*n2] / sum2;
+ for (k = 2; k < 4; ++k) {
+ pc[k] = pc[k] > .5? -(-4.343 * log(1. - pc[k] + TINY) + .499) : -4.343 * log(pc[k] + TINY) + .499;
+ pc[k] = (int)pc[k];
+ if (pc[k] > 99) pc[k] = 99;
+ if (pc[k] < -99) pc[k] = -99;
+ }
+ pc[0] = ma->phi2[2*n2] * ma->z2[2*n2] / sum2 * (1. - ma->phi1[2*n1] * ma->z1[2*n1] / sum1);
+ pc[1] = ma->phi1[2*n1] * ma->z1[2*n1] / sum1 * (1. - ma->phi2[2*n2] * ma->z2[2*n2] / sum2);
+ pc[0] = pc[0] == 1.? 99 : (int)(-4.343 * log(1. - pc[0]) + .499);
+ pc[1] = pc[1] == 1.? 99 : (int)(-4.343 * log(1. - pc[1]) + .499);
+}
+
+static double mc_cal_afs(bcf_p1aux_t *ma, double *p_ref_folded, double *p_var_folded)
{
int k;
- long double sum = 0.;
+ long double sum = 0., sum2;
+ double *phi = ma->is_indel? ma->phi_indel : ma->phi;
memset(ma->afs1, 0, sizeof(double) * (ma->M + 1));
mc_cal_y(ma);
+ // compute AFS
for (k = 0, sum = 0.; k <= ma->M; ++k)
- sum += (long double)ma->phi[k] * ma->z[k];
+ sum += (long double)phi[k] * ma->z[k];
for (k = 0; k <= ma->M; ++k) {
- ma->afs1[k] = ma->phi[k] * ma->z[k] / sum;
+ ma->afs1[k] = phi[k] * ma->z[k] / sum;
if (isnan(ma->afs1[k]) || isinf(ma->afs1[k])) return -1.;
}
+ // compute folded variant probability
+ for (k = 0, sum = 0.; k <= ma->M; ++k)
+ sum += (long double)(phi[k] + phi[ma->M - k]) / 2. * ma->z[k];
+ for (k = 1, sum2 = 0.; k < ma->M; ++k)
+ sum2 += (long double)(phi[k] + phi[ma->M - k]) / 2. * ma->z[k];
+ *p_var_folded = sum2 / sum;
+ *p_ref_folded = (phi[k] + phi[ma->M - k]) / 2. * (ma->z[ma->M] + ma->z[0]) / sum;
+ // the expected frequency
for (k = 0, sum = 0.; k <= ma->M; ++k) {
ma->afs[k] += ma->afs1[k];
sum += k * ma->afs1[k];
return sum / ma->M;
}
-static long double p1_cal_g3(bcf_p1aux_t *p1a, double g[3])
+long double bcf_p1_cal_g3(bcf_p1aux_t *p1a, double g[3])
{
long double pd = 0., g2[3];
int i, k;
return pd;
}
-int bcf_p1_cal(bcf1_t *b, bcf_p1aux_t *ma, bcf_p1rst_t *rst)
+int bcf_p1_cal(const bcf1_t *b, bcf_p1aux_t *ma, bcf_p1rst_t *rst)
{
int i, k;
long double sum = 0.;
+ ma->is_indel = bcf_is_indel(b);
// set PL and PL_len
for (i = 0; i < b->n_gi; ++i) {
- if (b->gi[i].fmt == char2int("PL")) {
+ 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->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;
// calculate f_flat and f_em
for (k = 0, sum = 0.; k <= ma->M; ++k)
sum += (long double)ma->z[k];
flast = rst->f_em;
}
}
- p1_cal_g3(ma, rst->g);
+ { // 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-1, 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;
+ }
+ rst->g[0] = rst->g[1] = rst->g[2] = -1.;
+ contrast(ma, rst->pc);
return 0;
}