calculate posterior allele frequency

diff --git a/bam_mcns.c b/bam_mcns.c
index dee2016507100888faf053163ec47a8b8b474828..c1cdb9077ff7b9278f631c5da3915348114ae5c9 100644 (file)
--- a/bam_mcns.c
+++ b/bam_mcns.c
@@ -39,7 +39,7 @@ mc_aux_t *mc_init(int n) // FIXME: assuming diploid
        ma->beta = calloc((2 * ma->n + 1) * 3, sizeof(double));
        for (i = 0; i <= MC_MAX_SUMQ; ++i)
                ma->q2p[i] = pow(10., -i / 10.);
-       for (i = 0; i <= 2 * ma->n; ++i) {
+       for (i = 0; i <= 2 * ma->n; ++i) { // beta[k][g]=P(g|k/M)
                double *bi = ma->beta + 3 * i;
                double f = (double)i / (2 * ma->n);
                bi[0] = (1. - f) * (1. - f);
@@ -153,18 +153,44 @@ double mc_freq_iter(double f0, mc_aux_t *ma)
        return f;
 }
 
+double mc_freq_post(mc_aux_t *ma)
+{
+       int i, k;
+       long double f = 0.;
+       for (i = 0; i < ma->n; ++i) {
+               double *pdg = ma->pdg + i * 3;
+               long double y = 0., z = 0.;
+               for (k = 0; k <= ma->n * 2; ++k) {
+                       double *bk = ma->beta + k * 3;
+/*
+                       int g;
+                       double yk = 0., zk = 0.;
+                       for (g = 0; g < 3; ++g) {
+                               yk += g * pdg[g] * bk[g];
+                               zk += pdg[g] * bk[g];
+                       }
+                       y += yk * ma->alpha[k];
+                       z += zk * ma->alpha[k];
+*/
+                       y += (pdg[1] * bk[1] + 2. * pdg[2] * bk[2]) * ma->alpha[k];
+                       z += (pdg[0] * bk[0] + pdg[1] * bk[1] + pdg[2] * bk[2]) * ma->alpha[k];
+               }
+               f += y / z;
+       }
+       return f / ma->n / 2;
+}
+
 double mc_ref_prob(mc_aux_t *ma)
 {
-       int k, i, g;
+       int k, i;
        long double PD = 0., Pref = 0.;
        for (k = 0; k <= ma->n * 2; ++k) {
                long double x = 1.;
                double *bk = ma->beta + k * 3;
                for (i = 0; i < ma->n; ++i) {
-                       double y = 0., *pdg = ma->pdg + i * 3;
-                       for (g = 0; g < 3; ++g)
-                               y += pdg[g] * bk[g];
-                       x *= y;
+                       double *pdg = ma->pdg + i * 3;
+//                     int g; double y=0.; for (g = 0; g < 3; ++g) y += pdg[g] * bk[g];
+                       x *= pdg[0] * bk[0] + pdg[1] * bk[1] + pdg[2] * bk[2];
                }
                PD += x * ma->alpha[k];
        }
@@ -189,6 +215,7 @@ int mc_call_gt(const mc_aux_t *ma, double f0, int k)
                g[i] /= sum;
                if (g[i] > max) max = g[i], max_i = i;
        }
+//     printf("***%lg,%lg,%lg,%lg,%lg,%lg\n", g[0], g[1], g[2], pdg[0], pdg[1], pdg[2]);
        max = 1. - max;
        if (max < 1e-308) max = 1e-308;
        q = (int)(-3.434 * log(max) + .499);

diff --git a/bam_mcns.h b/bam_mcns.h
index 6d98de1320b57ebb695f33e73cd21aedfc4734d0..89879fbc0f9cb76e924b8911fdc74442bc513c88 100644 (file)
--- a/bam_mcns.h
+++ b/bam_mcns.h
@@ -14,6 +14,7 @@ extern "C" {
        void mc_destroy(mc_aux_t *ma);
        double mc_freq0(int ref, int *n, const bam_pileup1_t **plp, mc_aux_t *ma, int *_ref, int *alt);
        double mc_freq_iter(double f0, mc_aux_t *ma);
+       double mc_freq_post(mc_aux_t *ma);
        double mc_ref_prob(mc_aux_t *ma);
        int mc_call_gt(const mc_aux_t *ma, double f0, int k);
 

diff --git a/bam_plcmd.c b/bam_plcmd.c
index 2afebeadf85bc2ee020e3c8aecd0209dccebc51d..258b83fd72b6ac21db863ea837d46c92d0ff0aef 100644 (file)
--- a/bam_plcmd.c
+++ b/bam_plcmd.c
@@ -521,6 +521,10 @@ static int mpileup(mplp_conf_t *conf, int n, char **fn)
                kstring_t s;
                s.l = s.m = 0; s.s = 0;
                puts("##fileformat=VCFv4.0");
+               puts("##INFO=<ID=DP,Number=1,Type=Integer,Description=\"Total read depth\">");
+               puts("##INFO=<ID=AF,Number=1,Type=Float,Description=\"Posterior non-reference allele frequency\">");
+               puts("##INFO=<ID=AFEM,Number=1,Type=Float,Description=\"Prior-free non-reference allele frequency by EM\">");
+               puts("##FILTER=<ID=Q13,Description=\"All min{baseQ,mapQ} below 13\">");
                kputs("#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT", &s);
                for (i = 0; i < n; ++i) {
                        const char *p;
@@ -549,12 +553,12 @@ static int mpileup(mplp_conf_t *conf, int n, char **fn)
                        ref_tid = tid;
                }
                if (conf->vcf) {
-                       double f0, f, pref = -1.0; // the reference allele frequency
+                       double f0, f, fpost, pref = -1.0; // the reference allele frequency
                        int j, _ref, _alt, _ref0, depth, rms_q, _ref0b, is_var = 0, qref = 0;
                        uint64_t sqr_sum;
                        _ref0 = _ref0b = (ref && pos < ref_len)? ref[pos] : 'N';
                        _ref0 = bam_nt16_nt4_table[bam_nt16_table[_ref0]];
-                       f = f0 = mc_freq0(_ref0, n_plp, plp, ma, &_ref, &_alt);
+                       f = f0 = fpost = mc_freq0(_ref0, n_plp, plp, ma, &_ref, &_alt);
                        if (f >= 0.0) {
                                double q, flast = f;
                                for (j = 0; j < 10; ++j) {
@@ -563,8 +567,10 @@ static int mpileup(mplp_conf_t *conf, int n, char **fn)
                                        if (fabs(f - flast) < 1e-3) break;
                                        flast = f;
                                }
-                               if (1. - f < 1e-4) f = 1.;
                                pref = mc_ref_prob(ma);
+                               fpost = mc_freq_post(ma);
+                               if (1. - f < 1e-4) f = 1.;
+                               if (1. - fpost < 1e-4) fpost = 1.;
                                is_var = (pref < .5);
                                q = is_var? pref : 1. - pref;
                                if (q < 1e-308) q = 1e-308;
@@ -589,13 +595,15 @@ static int mpileup(mplp_conf_t *conf, int n, char **fn)
                                }
                        }
                        rms_q = (int)(sqrt((double)sqr_sum / depth) + .499);
-                       printf("DP=%d;MQ=%d;AF=%.3lg", depth, rms_q, f0<0.?0.:1.-f);
-                       printf("\tGT:GQ:DP");
-                       // output genotype information; FIXME: to be implmented...
-                       for (i = 0; i < n; ++i) {
-                               int x = mc_call_gt(ma, f, i);
-                               printf("\t%c/%c:%d:%d", "10"[((x&3)==2)], "10"[((x&3)>0)], x>>2, n_plp[i]);
-                       }
+                       printf("DP=%d;MQ=%d", depth, rms_q);
+                       if (fpost >= 0. && fpost <= 1.) printf(";AF=%.3lg", 1. - fpost);
+                       if (f >= 0. && f <= 1.) printf(";AFEM=%.3lg", 1. - f);
+                       if (fpost >= 0. && fpost <= 1.) {
+                               for (i = 0; i < n; ++i) {
+                                       int x = mc_call_gt(ma, fpost, i);
+                                       printf("\t%c/%c:%d:%d", "10"[((x&3)==2)], "10"[((x&3)>0)], x>>2, n_plp[i]);
+                               }
+                       } else for (i = 0; i < n; ++i) printf("\t./.:0:0");
                        putchar('\n');
                } else {
                        printf("%s\t%d\t%c", h->target_name[tid], pos + 1, (ref && pos < ref_len)? ref[pos] : 'N');