Merge commit 'upstream/0.1.13'

[samtools.git] / bcftools / prob1.c

diff --git a/bcftools/prob1.c b/bcftools/prob1.c
index e3b0f7344d096f22c37048b2131219378bcb7ba5..193c4a0c535126496b254869a6aee193ac4ebbf6 100644 (file)
--- a/bcftools/prob1.c
+++ b/bcftools/prob1.c
@@ -8,9 +8,9 @@
 #include "kseq.h"
 KSTREAM_INIT(gzFile, gzread, 16384)
 
-#define MC_AVG_ERR 0.007
 #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, 
@@ -32,9 +32,9 @@ unsigned char seq_nt4_table[256] = {
 };
 
 struct __bcf_p1aux_t {
-       int n, M, n1;
+       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;
@@ -43,6 +43,14 @@ struct __bcf_p1aux_t {
        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;
@@ -63,6 +71,7 @@ static void init_prior(int type, double theta, int M, double *phi)
 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)
@@ -110,6 +119,7 @@ int bcf_p1_read_prior(bcf_p1aux_t *ma, const char *fn)
        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;
 }
 
@@ -123,6 +133,7 @@ bcf_p1aux_t *bcf_p1_init(int 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));
@@ -148,7 +159,7 @@ void bcf_p1_destroy(bcf_p1aux_t *ma)
 {
        if (ma) {
                free(ma->q2p); free(ma->pdg);
-               free(ma->phi); free(ma->phi1); free(ma->phi2);
+               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);
@@ -157,18 +168,16 @@ void bcf_p1_destroy(bcf_p1aux_t *ma)
 
 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
@@ -299,18 +308,28 @@ static void contrast(bcf_p1aux_t *ma, double pc[4]) // mc_cal_y() must be called
        pc[1] = pc[1] == 1.? 99 : (int)(-4.343 * log(1. - pc[1]) + .499);
 }
 
-static double mc_cal_afs(bcf_p1aux_t *ma)
+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];
@@ -344,10 +363,11 @@ long double bcf_p1_cal_g3(bcf_p1aux_t *p1a, double g[3])
        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 == bcf_str2int("PL", 2)) {
@@ -359,8 +379,11 @@ 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];
@@ -378,6 +401,19 @@ int bcf_p1_cal(bcf1_t *b, bcf_p1aux_t *ma, bcf_p1rst_t *rst)
                        flast = rst->f_em;
                }
        }
+       { // 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;