X-Git-Url: https://git.donarmstrong.com/?a=blobdiff_plain;f=bcftools%2Fprob1.c;h=4804e6e24c3c6787f2ca3a18fb6e83687f379ed4;hb=f528e7da717a1a2a6ab2672c7c55f37d315452f3;hp=1acd49b48295d4d315f52c2f3969bd6c3b66e36f;hpb=b65b44f2a48848bfcc1c1f2e738251819bcbb518;p=samtools.git

diff --git a/bcftools/prob1.c b/bcftools/prob1.c
index 1acd49b..4804e6e 100644
--- a/bcftools/prob1.c
+++ b/bcftools/prob1.c
@@ -2,11 +2,16 @@
 #include <stdlib.h>
 #include <string.h>
 #include <stdio.h>
+#include <errno.h>
+#include <assert.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, 
@@ -28,78 +33,166 @@ unsigned char seq_nt4_table[256] = {
 };
 
 struct __bcf_p1aux_t {
-	int n, M;
+	int n, M, n1, is_indel;
+	uint8_t *ploidy; // haploid or diploid ONLY
 	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, 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->z = calloc(2 * ma->n + 1, sizeof(double));
-	ma->zswap = calloc(2 * ma->n + 1, sizeof(double));
-	ma->afs = calloc(2 * ma->n + 1, sizeof(double));
-	ma->afs1 = calloc(2 * ma->n + 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));
 	for (i = 0; i < 256; ++i)
 		ma->q2p[i] = pow(10., -i / 10.);
 	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(stderr, "[%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) {
-		free(ma->q2p); free(ma->pdg);
-		free(ma->phi);
-		free(ma->z); free(ma->zswap);
+		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);
 	}
 }
 
-#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
@@ -129,69 +222,175 @@ 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;
-	f3[0] = (1.-f0)*(1.-f0); f3[1] = 2.*f0*(1.-f0); f3[2] = f0*f0;
+	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) {
+	for (i = 0, max = -1., max_i = 0; i <= ploidy; ++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)(-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;
+	assert(beg == 0 || ma->M == ma->n*2);
 	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;
-		double p[3], sum;
-		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.;
-		_max += 2;
-		if (_min == 0) 
-			k = 0, z[1][k] = (2*j+2-k)*(2*j-k+1) * p[0] * z[0][k];
-		if (_min <= 1)
-			k = 1, 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];
-		for (k = _min < 2? 2 : _min; k <= _max; ++k)
-			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];
-		for (k = _min; k <= _max; ++k) z[1][k] /= sum;
-		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;
+	ma->t = 0.;
+	if (ma->M == ma->n * 2) {
+		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;
+			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] = (2*j+2-k)*(2*j-k+1) * p[0] * z[0][k];
+			if (_min <= 1)
+				k = 1, 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];
+			for (k = _min < 2? 2 : _min; k <= _max; ++k)
+				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->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;
+		}
+	} 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 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 && 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);
+}
+
+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];
@@ -199,39 +398,14 @@ static double mc_cal_afs(bcf_p1aux_t *ma)
 	return sum / ma->M;
 }
 
-static long double p1_cal_g3(bcf_p1aux_t *p1a, double g[3])
-{
-	long double pd = 0., g2[3];
-	int i, k;
-	memset(g2, 0, sizeof(long double) * 3);
-	for (k = 0; k < p1a->M; ++k) {
-		double f = (double)k / p1a->M, f3[3], g1[3];
-		long double z = 1.;
-		g1[0] = g1[1] = g1[2] = 0.;
-		f3[0] = (1. - f) * (1. - f); f3[1] = 2. * f * (1. - f); f3[2] = f * f;
-		for (i = 0; i < p1a->n; ++i) {
-			double *pdg = p1a->pdg + i * 3;
-			double x = pdg[0] * f3[0] + pdg[1] * f3[1] + pdg[2] * f3[2];
-			z *= x;
-			g1[0] += pdg[0] * f3[0] / x;
-			g1[1] += pdg[1] * f3[1] / x;
-			g1[2] += pdg[2] * f3[2] / x;
-		}
-		pd += p1a->phi[k] * z;
-		for (i = 0; i < 3; ++i)
-			g2[i] += p1a->phi[k] * z * g1[i];
-	}
-	for (i = 0; i < 3; ++i) g[i] = g2[i] / pd;
-	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;
@@ -240,8 +414,11 @@ int bcf_p1_cal(bcf1_t *b, bcf_p1aux_t *ma, bcf_p1rst_t *rst)
 	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];
@@ -259,7 +436,21 @@ int bcf_p1_cal(bcf1_t *b, bcf_p1aux_t *ma, bcf_p1rst_t *rst)
 			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;
 }