* preliminary multisample SNP caller.

 * something looks not so right, but it largely works

diff --git a/bam_mcns.c b/bam_mcns.c
index b69ec0f0abaceb6aa0408cb61a9adc51b0626765..cd64b0ac139814706632a05d2e7b75d619a36b8a 100644 (file)
--- a/bam_mcns.c
+++ b/bam_mcns.c
@@ -9,10 +9,22 @@
 struct __mc_aux_t {
        int n, N;
        int ref, alt;
+       double theta;
        double *q2p, *pdg; // pdg -> P(D|g)
+       double *alpha, *beta;
        int *qsum, *bcnt, rcnt[4];
 };
 
+void mc_init_prior(mc_aux_t *ma, double theta)
+{
+       double sum;
+       int i;
+       ma->theta = theta;
+       for (i = 0, sum = 0.; i < 2 * ma->n; ++i)
+               sum += (ma->alpha[i] = ma->theta / (2 * ma->n - i));
+       ma->alpha[2 * ma->n] = 1. - sum;
+}
+
 mc_aux_t *mc_init(int n) // FIXME: assuming diploid
 {
        mc_aux_t *ma;
@@ -23,8 +35,18 @@ mc_aux_t *mc_init(int n) // FIXME: assuming diploid
        ma->qsum = calloc(4 * ma->n, sizeof(int));
        ma->bcnt = calloc(4 * ma->n, sizeof(int));
        ma->pdg = calloc(3 * ma->n, sizeof(double));
+       ma->alpha = calloc(2 * ma->n + 1, sizeof(double));
+       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) {
+               double *bi = ma->beta + 3 * i;
+               double f = (double)i / (2 * ma->n);
+               bi[0] = (1. - f) * (1. - f);
+               bi[1] = 2 * f * (1. - f);
+               bi[2] = f * f;
+       }
+       mc_init_prior(ma, 1e-3); // the simplest prior
        return ma;
 }
 
@@ -33,6 +55,7 @@ void mc_destroy(mc_aux_t *ma)
        if (ma) {
                free(ma->qsum); free(ma->bcnt);
                free(ma->q2p); free(ma->pdg);
+               free(ma->alpha); free(ma->beta);
                free(ma);
        }
 }
@@ -101,7 +124,7 @@ static void cal_pdg(mc_aux_t *ma)
                        pdg[i] = pi[i] > MC_MAX_SUMQ? MC_MAX_SUMQP : ma->q2p[pi[i]];
        }
 }
-
+// return the reference allele frequency
 double mc_freq0(int ref, int *n, const bam_pileup1_t **plp, mc_aux_t *ma, int *_ref, int *alt)
 {
        int i, acnt[4], j;
@@ -120,7 +143,7 @@ double mc_freq0(int ref, int *n, const bam_pileup1_t **plp, mc_aux_t *ma, int *_
        *_ref = ma->ref; *alt = ma->alt;
        return ma->n == 1 || fr < 0.? f0 : fr;
 }
-
+// f0 is the reference allele frequency
 double mc_freq_iter(double f0, mc_aux_t *ma)
 {
        double f, f3[3];
@@ -138,3 +161,46 @@ double mc_freq_iter(double f0, mc_aux_t *ma)
        f /= ma->n * 2.;
        return f;
 }
+
+double mc_ref_prob(mc_aux_t *ma)
+{
+       int k, i, g;
+       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;
+               }
+               PD += x * ma->alpha[k];
+       }
+       for (k = 0; k <= ma->n * 2; ++k) {
+               long double x = 1.0;
+               for (i = 0; i < ma->n; ++i)
+                       x *= ma->pdg[i * 3 + 2] * ma->beta[k * 3 + 2];
+               Pref += x * ma->alpha[k];
+       }
+       return Pref / PD;
+}
+
+int mc_call_gt(const mc_aux_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;
+       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)(-3.434 * log(max) + .499);
+       if (q > 99) q = 99;
+       return q<<2|max_i;
+}

diff --git a/bam_mcns.h b/bam_mcns.h
index ac1e41c845a0f4f3073ae8017fb2f536e8476e6b..6d98de1320b57ebb695f33e73cd21aedfc4734d0 100644 (file)
--- a/bam_mcns.h
+++ b/bam_mcns.h
@@ -14,6 +14,8 @@ 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_ref_prob(mc_aux_t *ma);
+       int mc_call_gt(const mc_aux_t *ma, double f0, int k);
 
 #ifdef __cplusplus
 }

diff --git a/bam_plcmd.c b/bam_plcmd.c
index 708e63e7e8b600baf166e23979990711d9bf5829..285477050d19f489d7be34722846eca8e6407e14 100644 (file)
--- a/bam_plcmd.c
+++ b/bam_plcmd.c
@@ -450,7 +450,7 @@ int bam_pileup(int argc, char *argv[])
  ***********/
 
 typedef struct {
-       int vcf, max_mq, min_mq;
+       int vcf, max_mq, min_mq, var_only;
        char *reg, *fn_pos;
        faidx_t *fai;
        kh_64_t *hash;
@@ -520,6 +520,7 @@ static int mpileup(mplp_conf_t *conf, int n, char **fn)
        if (conf->vcf) {
                kstring_t s;
                s.l = s.m = 0; s.s = 0;
+               puts("##fileformat=VCFv4.0");
                kputs("#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT", &s);
                for (i = 0; i < n; ++i) {
                        const char *p;
@@ -548,24 +549,33 @@ static int mpileup(mplp_conf_t *conf, int n, char **fn)
                        ref_tid = tid;
                }
                if (conf->vcf) {
-                       double f0, f; // the reference allele frequency
-                       int j, _ref, _alt, _ref0, depth, rms_q, _ref0b;
+                       double f0, f, 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);
                        if (f >= 0.0) {
-                               double flast = f;
-                               for (j = 0; j < 10; ++j) {
+                               double q, flast = f;
+                               for (j = 0; j < 10; ++j){
                                        f = mc_freq_iter(flast, ma);
                                        if (fabs(f - flast) < 1e-3) break;
                                        flast = f;
                                }
+                               pref = mc_ref_prob(ma);
+                               is_var = (pref < .5);
+                               q = is_var? pref : 1. - pref;
+                               if (q < 1e-308) q = 1e-308;
+                               qref = (int)(-3.434 * log(q) + .499);
+                               if (qref > 99) qref = 99;
                        }
+                       if (conf->var_only && !is_var) continue;
                        printf("%s\t%d\t.\t%c\t", h->target_name[tid], pos + 1, _ref0b);
-                       if (_ref0 == _ref) putchar("ACGTN"[_alt]);
-                       else printf("%c,%c", "ACGTN"[_ref], "ACGTN"[_alt]);
-                       printf("\t0\t"); // FIXME: currently these not available
+                       if (is_var) {
+                               if (_ref0 == _ref) putchar("ACGTN"[_alt]);
+                               else printf("%c,%c", "ACGTN"[_ref], "ACGTN"[_alt]);
+                       } else putchar('.');
+                       printf("\t%d\t", qref);
                        if (f0 < 0.) printf("Q13\t");
                        else printf(".\t");
                        for (i = depth = 0, sqr_sum = 0; i < n; ++i) {
@@ -578,10 +588,12 @@ 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("\tDP");
+                       printf("\tGT:GQ:DP");
                        // output genotype information; FIXME: to be implmented...
-                       for (i = 0; i < n; ++i)
-                               printf("\t%d", n_plp[i]);
+                       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]);
+                       }
                        putchar('\n');
                } else {
                        printf("%s\t%d\t%c", h->target_name[tid], pos + 1, (ref && pos < ref_len)? ref[pos] : 'N');
@@ -628,7 +640,7 @@ int bam_mpileup(int argc, char *argv[])
        mplp_conf_t mplp;
        memset(&mplp, 0, sizeof(mplp_conf_t));
        mplp.max_mq = 60;
-       while ((c = getopt(argc, argv, "f:r:l:VM:q:")) >= 0) {
+       while ((c = getopt(argc, argv, "f:r:l:VvM:q:")) >= 0) {
                switch (c) {
                case 'f':
                        mplp.fai = fai_load(optarg);
@@ -636,6 +648,7 @@ int bam_mpileup(int argc, char *argv[])
                        break;
                case 'r': mplp.reg = strdup(optarg); break;
                case 'l': mplp.fn_pos = strdup(optarg); break;
+               case 'v': mplp.var_only = 1; break;
                case 'V': mplp.vcf = 1; break;
                case 'M': mplp.max_mq = atoi(optarg); break;
                case 'q': mplp.min_mq = atoi(optarg); break;

diff --git a/bam_tview.c b/bam_tview.c
index 7b326fc40e7bf276b7adc3848c0667d5628a68ad..24cd12a5bf743dba2948ee92bd9c5c490c30e4ce 100644 (file)
--- a/bam_tview.c
+++ b/bam_tview.c
@@ -292,7 +292,7 @@ static void tv_win_goto(tview_t *tv, int *tid, int *pos)
                } else if (c == KEY_ENTER || c == '\012' || c == '\015') {
                        int _tid = -1, _beg, _end;
                        if (str[0] == '=') {
-                               _beg = strtol(str+1, &p, 10);
+                               _beg = strtol(str+1, &p, 10) - 1;
                                if (_beg > 0) {
                                        *pos = _beg;
                                        return;