--- /dev/null
+#include "pysam.h"
+
+#include <math.h>
+#include <stdlib.h>
+#include <string.h>
+#include <stdio.h>
+#include <errno.h>
+#include <assert.h>
+#include "prob1.h"
+
+#include "kseq.h"
+KSTREAM_INIT(gzFile, gzread, 16384)
+
+#define MC_MAX_EM_ITER 16
+#define MC_EM_EPS 1e-5
+#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,
+ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 /*'-'*/, 4, 4,
+ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 0, 4, 1, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 4, 4, 4, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 0, 4, 1, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 4, 4, 4, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
+ 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4
+};
+
+struct __bcf_p1aux_t {
+ int n, M, n1, is_indel;
+ uint8_t *ploidy; // haploid or diploid ONLY
+ double *q2p, *pdg; // pdg -> P(D|g)
+ double *phi, *phi_indel;
+ double *z, *zswap; // aux for afs
+ double *z1, *z2, *phi1, *phi2; // only calculated when n1 is set
+ double **hg; // hypergeometric distribution
+ double *lf; // log factorial
+ 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_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 <= M; ++i)
+ phi[i] = 2. * (i + 1) / (M + 1) / (M + 2);
+ } else if (type == MC_PTYPE_FLAT) {
+ for (i = 0; i <= M; ++i)
+ phi[i] = 1. / (M + 1);
+ } else {
+ double 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(pysamerr, "[prior]");
+ for (k = 0; k <= ma->M; ++k) ma->phi[k] /= sum;
+ for (k = 0; k <= ma->M; ++k) fprintf(pysamerr, " %d:%.3lg", k, ma->phi[ma->M - k]);
+ fputc('\n', pysamerr);
+ 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(pysamerr, "[%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(pysamerr, "theta=%lf\n", (double)sum);
+ bcf_p1_indel_prior(ma, MC_DEF_INDEL);
+ return 0;
+}
+
+bcf_p1aux_t *bcf_p1_init(int n, uint8_t *ploidy)
+{
+ bcf_p1aux_t *ma;
+ int i;
+ ma = calloc(1, sizeof(bcf_p1aux_t));
+ ma->n1 = -1;
+ ma->n = n; ma->M = 2 * n;
+ if (ploidy) {
+ ma->ploidy = malloc(n);
+ memcpy(ma->ploidy, ploidy, n);
+ for (i = 0, ma->M = 0; i < n; ++i) ma->M += ploidy[i];
+ if (ma->M == 2 * n) {
+ free(ma->ploidy);
+ ma->ploidy = 0;
+ }
+ }
+ 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(ma->M + 1, sizeof(double));
+ ma->zswap = calloc(ma->M + 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(ma->M + 1, sizeof(double));
+ ma->afs1 = calloc(ma->M + 1, sizeof(double));
+ ma->lf = calloc(ma->M + 1, sizeof(double));
+ for (i = 0; i < 256; ++i)
+ ma->q2p[i] = pow(10., -i / 10.);
+ for (i = 0; i <= ma->M; ++i) ma->lf[i] = lgamma(i + 1);
+ bcf_p1_init_prior(ma, MC_PTYPE_FULL, 1e-3); // the simplest prior
+ return ma;
+}
+
+int bcf_p1_set_n1(bcf_p1aux_t *b, int n1)
+{
+ if (n1 == 0 || n1 >= b->n) return -1;
+ if (b->M != b->n * 2) {
+ fprintf(pysamerr, "[%s] unable to set `n1' when there are haploid samples.\n", __func__);
+ return -1;
+ }
+ b->n1 = n1;
+ return 0;
+}
+
+void bcf_p1_destroy(bcf_p1aux_t *ma)
+{
+ if (ma) {
+ int k;
+ free(ma->lf);
+ if (ma->hg && ma->n1 > 0) {
+ for (k = 0; k <= 2*ma->n1; ++k) free(ma->hg[k]);
+ free(ma->hg);
+ }
+ free(ma->ploidy); free(ma->q2p); free(ma->pdg);
+ 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);
+ }
+}
+
+static int cal_pdg(const bcf1_t *b, bcf_p1aux_t *ma)
+{
+ 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[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
+ for (j = i; j > 0 && p[j] < p[j-1]; --j)
+ tmp = p[j], p[j] = p[j-1], p[j-1] = tmp;
+ for (i = b->n_alleles - 1; i >= 0; --i)
+ if ((p[i]&0xf) == 0) break;
+ return i;
+}
+
+int bcf_p1_call_gt(const bcf_p1aux_t *ma, double f0, int k)
+{
+ double sum, g[3];
+ double max, f3[3], *pdg = ma->pdg + k * 3;
+ int q, i, max_i, ploidy;
+ ploidy = ma->ploidy? ma->ploidy[k] : 2;
+ if (ploidy == 2) {
+ f3[0] = (1.-f0)*(1.-f0); f3[1] = 2.*f0*(1.-f0); f3[2] = f0*f0;
+ } else {
+ f3[0] = 1. - f0; f3[1] = 0; f3[2] = f0;
+ }
+ for (i = 0, sum = 0.; i < 3; ++i)
+ sum += (g[i] = pdg[i] * f3[i]);
+ for (i = 0, max = -1., max_i = 0; i < 3; ++i) {
+ g[i] /= sum;
+ if (g[i] > max) max = g[i], max_i = i;
+ }
+ max = 1. - max;
+ if (max < 1e-308) max = 1e-308;
+ 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_core(bcf_p1aux_t *ma, int beg)
+{
+ double *z[2], *tmp, *pdg;
+ int _j, last_min, last_max;
+ assert(beg == 0 || ma->M == ma->n*2);
+ z[0] = ma->z;
+ z[1] = ma->zswap;
+ pdg = ma->pdg;
+ 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;
+ ma->t = 0.;
+ if (ma->M == ma->n * 2) {
+ int M = 0;
+ for (_j = beg; _j < ma->n; ++_j) {
+ int k, j = _j - beg, _min = last_min, _max = last_max, M0;
+ double p[3], sum;
+ M0 = M; M += 2;
+ 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[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] = (M0-k+1) * (M0-k+2) * p[0] * z[0][k];
+ if (_min <= 1) k = 1, z[1][k] = (M0-k+1) * (M0-k+2) * p[0] * z[0][k] + k*(M0-k+2) * p[1] * z[0][k-1];
+ for (k = _min < 2? 2 : _min; k <= _max; ++k)
+ z[1][k] = (M0-k+1)*(M0-k+2) * p[0] * z[0][k] + k*(M0-k+2) * 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 / (M * (M - 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->n1==-1 when unset
+ 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;
+ }
+ //for (_j = 0; _j < last_min; ++_j) z[0][_j] = 0.; // TODO: are these necessary?
+ //for (_j = last_max + 1; _j < ma->M; ++_j) z[0][_j] = 0.;
+ } else { // this block is very similar to the block above; these two might be merged in future
+ int j, M = 0;
+ for (j = 0; j < ma->n; ++j) {
+ int k, M0, _min = last_min, _max = last_max;
+ double p[3], sum;
+ pdg = ma->pdg + j * 3;
+ 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.;
+ M0 = M;
+ M += ma->ploidy[j];
+ if (ma->ploidy[j] == 1) {
+ p[0] = pdg[0]; p[1] = pdg[2];
+ _max++;
+ if (_min == 0) k = 0, z[1][k] = (M0+1-k) * p[0] * z[0][k];
+ for (k = _min < 1? 1 : _min; k <= _max; ++k)
+ z[1][k] = (M0+1-k) * p[0] * z[0][k] + k * p[1] * z[0][k-1];
+ for (k = _min, sum = 0.; k <= _max; ++k) sum += z[1][k];
+ ma->t += log(sum / M);
+ for (k = _min; k <= _max; ++k) z[1][k] /= sum;
+ if (_min >= 1) z[1][_min-1] = 0.;
+ if (j < ma->n - 1) z[1][_max+1] = 0.;
+ } else if (ma->ploidy[j] == 2) {
+ p[0] = pdg[0]; p[1] = 2 * pdg[1]; p[2] = pdg[2];
+ _max += 2;
+ if (_min == 0) k = 0, z[1][k] = (M0-k+1) * (M0-k+2) * p[0] * z[0][k];
+ if (_min <= 1) k = 1, z[1][k] = (M0-k+1) * (M0-k+2) * p[0] * z[0][k] + k*(M0-k+2) * p[1] * z[0][k-1];
+ for (k = _min < 2? 2 : _min; k <= _max; ++k)
+ z[1][k] = (M0-k+1)*(M0-k+2) * p[0] * z[0][k] + k*(M0-k+2) * 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 / (M * (M - 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.;
+ }
+ 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 void mc_cal_y(bcf_p1aux_t *ma)
+{
+ if (ma->n1 > 0 && ma->n1 < ma->n && ma->M == ma->n * 2) { // NB: ma->n1 is ineffective when there are haploid samples
+ 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);
+}
+
+#define CONTRAST_TINY 1e-30
+
+extern double kf_gammaq(double s, double z); // incomplete gamma function for chi^2 test
+
+static inline double chi2_test(int a, int b, int c, int d)
+{
+ double x, z;
+ x = (double)(a+b) * (c+d) * (b+d) * (a+c);
+ if (x == 0.) return 1;
+ z = a * d - b * c;
+ return kf_gammaq(.5, .5 * z * z * (a+b+c+d) / x);
+}
+
+// chi2=(a+b+c+d)(ad-bc)^2/[(a+b)(c+d)(a+c)(b+d)]
+static inline double contrast2_aux(const bcf_p1aux_t *p1, double sum, int k1, int k2, double x[3])
+{
+ double p = p1->phi[k1+k2] * p1->z1[k1] * p1->z2[k2] / sum * p1->hg[k1][k2];
+ int n1 = p1->n1, n2 = p1->n - p1->n1;
+ if (p < CONTRAST_TINY) return -1;
+ if (.5*k1/n1 < .5*k2/n2) x[1] += p;
+ else if (.5*k1/n1 > .5*k2/n2) x[2] += p;
+ else x[0] += p;
+ return p * chi2_test(k1, k2, (n1<<1) - k1, (n2<<1) - k2);
+}
+
+static double contrast2(bcf_p1aux_t *p1, double ret[3])
+{
+ int k, k1, k2, k10, k20, n1, n2;
+ double sum;
+ // get n1 and n2
+ n1 = p1->n1; n2 = p1->n - p1->n1;
+ if (n1 <= 0 || n2 <= 0) return 0.;
+ if (p1->hg == 0) { // initialize the hypergeometric distribution
+ /* NB: the hg matrix may take a lot of memory when there are many samples. There is a way
+ to avoid precomputing this matrix, but it is slower and quite intricate. The following
+ computation in this block can be accelerated with a similar strategy, but perhaps this
+ is not a serious concern for now. */
+ double tmp = lgamma(2*(n1+n2)+1) - (lgamma(2*n1+1) + lgamma(2*n2+1));
+ p1->hg = calloc(2*n1+1, sizeof(void*));
+ for (k1 = 0; k1 <= 2*n1; ++k1) {
+ p1->hg[k1] = calloc(2*n2+1, sizeof(double));
+ for (k2 = 0; k2 <= 2*n2; ++k2)
+ p1->hg[k1][k2] = exp(lgamma(k1+k2+1) + lgamma(p1->M-k1-k2+1) - (lgamma(k1+1) + lgamma(k2+1) + lgamma(2*n1-k1+1) + lgamma(2*n2-k2+1) + tmp));
+ }
+ }
+ { // compute
+ long double suml = 0;
+ for (k = 0; k <= p1->M; ++k) suml += p1->phi[k] * p1->z[k];
+ sum = suml;
+ }
+ { // get the max k1 and k2
+ double max;
+ int max_k;
+ for (k = 0, max = 0, max_k = -1; k <= 2*n1; ++k) {
+ double x = p1->phi1[k] * p1->z1[k];
+ if (x > max) max = x, max_k = k;
+ }
+ k10 = max_k;
+ for (k = 0, max = 0, max_k = -1; k <= 2*n2; ++k) {
+ double x = p1->phi2[k] * p1->z2[k];
+ if (x > max) max = x, max_k = k;
+ }
+ k20 = max_k;
+ }
+ { // We can do the following with one nested loop, but that is an O(N^2) thing. The following code block is much faster for large N.
+ double x[3], y;
+ long double z = 0., L[2];
+ x[0] = x[1] = x[2] = 0; L[0] = L[1] = 0;
+ for (k1 = k10; k1 >= 0; --k1) {
+ for (k2 = k20; k2 >= 0; --k2) {
+ if ((y = contrast2_aux(p1, sum, k1, k2, x)) < 0) break;
+ else z += y;
+ }
+ for (k2 = k20 + 1; k2 <= 2*n2; ++k2) {
+ if ((y = contrast2_aux(p1, sum, k1, k2, x)) < 0) break;
+ else z += y;
+ }
+ }
+ ret[0] = x[0]; ret[1] = x[1]; ret[2] = x[2];
+ x[0] = x[1] = x[2] = 0;
+ for (k1 = k10 + 1; k1 <= 2*n1; ++k1) {
+ for (k2 = k20; k2 >= 0; --k2) {
+ if ((y = contrast2_aux(p1, sum, k1, k2, x)) < 0) break;
+ else z += y;
+ }
+ for (k2 = k20 + 1; k2 <= 2*n2; ++k2) {
+ if ((y = contrast2_aux(p1, sum, k1, k2, x)) < 0) break;
+ else z += y;
+ }
+ }
+ ret[0] += x[0]; ret[1] += x[1]; ret[2] += x[2];
+ if (ret[0] + ret[1] + ret[2] < 0.95) { // in case of bad things happened
+ ret[0] = ret[1] = ret[2] = 0; L[0] = L[1] = 0;
+ for (k1 = 0, z = 0.; k1 <= 2*n1; ++k1)
+ for (k2 = 0; k2 <= 2*n2; ++k2)
+ if ((y = contrast2_aux(p1, sum, k1, k2, ret)) >= 0) z += y;
+ if (ret[0] + ret[1] + ret[2] < 0.95) // It seems that this may be caused by floating point errors. I do not really understand why...
+ z = 1.0, ret[0] = ret[1] = ret[2] = 1./3;
+ }
+ return (double)z;
+ }
+}
+
+static double mc_cal_afs(bcf_p1aux_t *ma, double *p_ref_folded, double *p_var_folded)
+{
+ int k;
+ 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)phi[k] * ma->z[k];
+ for (k = 0; k <= ma->M; ++k) {
+ 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;
+}
+
+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;
+ // 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-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->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;
+}
+
+void bcf_p1_dump_afs(bcf_p1aux_t *ma)
+{
+ int k;
+ fprintf(pysamerr, "[afs]");
+ for (k = 0; k <= ma->M; ++k)
+ fprintf(pysamerr, " %d:%.3lf", k, ma->afs[ma->M - k]);
+ fprintf(pysamerr, "\n");
+ memset(ma->afs, 0, sizeof(double) * (ma->M + 1));
+}