quite a lot changes to the contrast caller, but I still feel something is missing...

diff --git a/bcftools/Makefile b/bcftools/Makefile
index e985bc9ec7fc410575e133da744d56f4fe814c57..5a3dc763f8105ba3dc8db43db390a4b13c0ba252 100644 (file)
--- a/bcftools/Makefile
+++ b/bcftools/Makefile
@@ -1,6 +1,6 @@
 CC=                    gcc
 CFLAGS=                -g -Wall -O2 #-m64 #-arch ppc
-DFLAGS=                -D_FILE_OFFSET_BITS=64 -D_USE_KNETFILE #-D_BCF_QUAD
+DFLAGS=                -D_FILE_OFFSET_BITS=64 -D_USE_KNETFILE
 LOBJS=         bcf.o vcf.o bcfutils.o prob1.o kfunc.o index.o fet.o
 OMISC=         ..
 AOBJS=         call1.o main.o $(OMISC)/kstring.o $(OMISC)/bgzf.o $(OMISC)/knetfile.o

diff --git a/bcftools/call1.c b/bcftools/call1.c
index c5d466e12b164d3df39b093b1cd07377207e2285..9589e891bfdc0ffb86a94c8ab0b7646da620c2d6 100644 (file)
--- a/bcftools/call1.c
+++ b/bcftools/call1.c
@@ -161,7 +161,7 @@ static int update_bcf1(int n_smpl, bcf1_t *b, const bcf_p1aux_t *pa, const bcf_p
        ksprintf(&s, "AF1=%.3lf;AFE=%.3lf", 1.-pr->f_em, 1.-pr->f_exp);
        ksprintf(&s, ";DP4=%d,%d,%d,%d;MQ=%d", a.d[0], a.d[1], a.d[2], a.d[3], a.mq);
        if (a.is_tested) {
-               if (pr->pc[0] >= 0.) ksprintf(&s, ";PC4=%.4lf,%.4lf,%.2lg,%.2lg", pr->pc[0], pr->pc[1], pr->pc[2], pr->pc[3]);
+               if (pr->pc[0] >= 0.) ksprintf(&s, ";PC4=%lg,%lg,%lg,%lg", pr->pc[0], pr->pc[1], pr->pc[2], pr->pc[3]);
                ksprintf(&s, ";PV4=%.2lg,%.2lg,%.2lg,%.2lg", a.p[0], a.p[1], a.p[2], a.p[3]);
        }
        if (pr->g[0] >= 0. && p_hwe <= .2)
@@ -257,7 +257,10 @@ int bcfview(int argc, char *argv[])
                                return 1;
                        }
                } else bcf_p1_init_prior(p1, vc.prior_type, vc.theta);
-               if (vc.n1 > 0) bcf_p1_set_n1(p1, vc.n1);
+               if (vc.n1 > 0) {
+                       bcf_p1_set_n1(p1, vc.n1);
+                       bcf_p1_init_subprior(p1, vc.prior_type, vc.theta);
+               }
        }
        if (vc.fn_list) hash = bcf_load_pos(vc.fn_list, h);
        if (optind + 1 < argc && !(vc.flag&VC_VCFIN)) {
@@ -277,7 +280,9 @@ int bcfview(int argc, char *argv[])
                if (hash) {
                        uint64_t x = (uint64_t)b->tid<<32 | b->pos;
                        khint_t k = kh_get(set64, hash, x);
+                       if (kh_size(hash) == 0) break;
                        if (k == kh_end(hash)) continue;
+                       kh_del(set64, hash, k);
                }
                if (tid >= 0) {
                        int l = strlen(b->ref);

diff --git a/bcftools/prob1.c b/bcftools/prob1.c
index 37dc8ed32f5af45edc9af6fb8a2d2e306a275e97..85c2945779f85c9cd050fd72f00cdc78f1deeacb 100644 (file)
--- a/bcftools/prob1.c
+++ b/bcftools/prob1.c
@@ -12,8 +12,6 @@ KSTREAM_INIT(gzFile, gzread, 16384)
 #define MC_MAX_EM_ITER 16
 #define MC_EM_EPS 1e-4
 
-//#define _BCF_QUAD
-
 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, 
@@ -38,31 +36,42 @@ struct __bcf_p1aux_t {
        double *q2p, *pdg; // pdg -> P(D|g)
        double *phi;
        double *z, *zswap; // aux for afs
-       double *z1, *z2; // only calculated when n1 is set
+       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
-       double *k1k2;
        const uint8_t *PL; // point to PL
        int PL_len;
 };
 
-void bcf_p1_init_prior(bcf_p1aux_t *ma, int type, double theta)
+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);
+}
+
+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;
@@ -112,6 +121,8 @@ 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->phi1 = calloc(ma->M + 1, sizeof(double));
+       ma->phi2 = 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->z1 = calloc(ma->M + 1, sizeof(double)); // actually we do not need this large
@@ -124,26 +135,10 @@ bcf_p1aux_t *bcf_p1_init(int n)
        return ma;
 }
 
-#ifdef _BCF_QUAD
-static double lbinom(int n, int k)
-{
-       return lgamma(n+1) - lgamma(k+1) - lgamma(n-k+1);
-}
-#endif
-
 int bcf_p1_set_n1(bcf_p1aux_t *b, int n1)
 {
        if (n1 == 0 || n1 >= b->n) return -1;
        b->n1 = n1;
-#ifdef _BCF_QUAD
-       {
-               int k1, k2, n2 = b->n - b->n1;
-               b->k1k2 = calloc((2*n1+1) * (2*n2+1), sizeof(double));
-               for (k1 = 0; k1 <= 2*n1; ++k1)
-                       for (k2 = 0; k2 <= 2*n2; ++k2)
-                               b->k1k2[k1*(2*n2+1)+k2] = exp(lbinom(2*n1,k1) + lbinom(2*n2,k2) - lbinom(b->M,k1+k2));
-       }
-#endif
        return 0;
 }
 
@@ -151,10 +146,9 @@ void bcf_p1_destroy(bcf_p1aux_t *ma)
 {
        if (ma) {
                free(ma->q2p); free(ma->pdg);
-               free(ma->phi);
+               free(ma->phi); 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->k1k2);
                free(ma);
        }
 }
@@ -281,77 +275,28 @@ static void mc_cal_y(bcf_p1aux_t *ma)
                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);
-#ifdef _BCF_QUAD
-/*
-       if (ma->n1 > 0 && ma->n1 < ma->n) { // DEBUG: consistency check; z[i] should equal y[i]
-               int i, k1, k2, n1 = ma->n1, n2 = ma->n - n1;
-               double *y;
-               printf("*** ");
-               y = calloc(ma->M + 1, sizeof(double));
-               for (k1 = 0; k1 <= 2*n1; ++k1)
-                       for (k2 = 0; k2 <= 2*n2; ++k2)
-                               y[k1+k2] += ma->k1k2[k1*(2*n2+1)+k2] * ma->z1[k1] * ma->z2[k2];
-               for (i = 0; i <= ma->M; ++i) printf("(%lf,%lf) ", ma->z[i], y[i]);
-               printf("\n");
-               free(y);
-       }
-*/
-#endif
 }
 
 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 sum = -1., x, sum_alt;
-       double y;
-       pc[0] = pc[1] = pc[2] = pc[3] = -1.;
+       long double sum1, sum2;
+       pc[0] = pc[1] = pc[2] = pc[3] = 0.;
        if (n1 <= 0 || n2 <= 0) return;
-#ifdef _BCF_QUAD
-       { // FIXME: can be improved by skipping zero cells
-               int k1, k2;
-               long double z[3];
-               z[0] = z[1] = z[2] = 0.;
-               for (k1 = 0; k1 <= 2*n1; ++k1)
-                       for (k2 = 0; k2 <= 2*n2; ++k2) {
-                               double zz = ma->phi[k1+k2] * ma->z1[k1] * ma->z2[k2] * ma->k1k2[k1*(2*n2+1)+k2];
-                               if ((double)k1/n1 < (double)k2/n2) z[0] += zz;
-                               else if ((double)k1/n1 > (double)k2/n2) z[1] += zz;
-                               else z[2] += zz;
-                       }
-               sum = z[0] + z[1] + z[2];
-               pc[2] = z[0] / sum; pc[3] = z[1] / sum;
-       }
-#else
-       pc[2] = pc[3] = 0.;
-#endif
-       for (k = 0, sum_alt = 0.; k <= ma->M; ++k)
-               sum_alt += (long double)ma->phi[k] * ma->z[k];
-//     printf("* %lg, %lg *\n", (double)sum, (double)sum_alt); // DEBUG: sum should equal sum_alt
-       sum = sum_alt;
-       // the variant is specific to group2
-//     printf("%lg %lg %lg %lg\n", ma->z[2*(n1+n2)]/exp(ma->t - (ma->t1 + ma->t2)), ma->z1[2*n1], ma->z2[2*n2], (double)sum);
-       y = lgamma(2*n2 + 1) - lgamma(ma->M + 1);
-       for (k = 0, x = 0.; k < 2 * n2; ++k)
-               x += ma->phi[2*n1+k] * ma->z2[k] * expl(lgamma(2*n1 + k + 1) - lgamma(k + 1) + y);
-       pc[1] = ma->z1[2*n1] * x / sum;
-       for (k = 1, x = 0.; k <= 2 * n2; ++k)
-               x += ma->phi[k] * ma->z2[k] * expl(lgamma(ma->M - k + 1) - lgamma(2*n2 - k + 1) + y);
-       pc[1] += ma->z1[0] * x / sum;
-       // the variant is specific to group1
-       y = lgamma(2*n1 + 1) - lgamma(ma->M + 1);
-       for (k = 0, x = 0.; k < 2 * n1; ++k)
-               x += ma->phi[2*n2+k] * ma->z1[k] * expl(lgamma(2*n2 + k + 1) - lgamma(k + 1) + y);
-       pc[0] = ma->z2[2*n2] * x / sum;
-       for (k = 1, x = 0.; k <= 2 * n1; ++k)
-               x += ma->phi[k] * ma->z1[k] * expl(lgamma(ma->M - k + 1) - lgamma(2*n1 - k + 1) + y);
-       pc[0] += ma->z2[0] * x / sum;
-       // rescale
+       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) {
-               y = 1. - pc[k];
-               if (y <= 0.) y = 1e-100;
-               pc[k] = (int)(-4.343 * log(y) + .499);
-               if (pc[k] > 99.) pc[k] = 99.;
+               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)
@@ -435,7 +380,6 @@ int bcf_p1_cal(bcf1_t *b, bcf_p1aux_t *ma, bcf_p1rst_t *rst)
        }
        rst->g[0] = rst->g[1] = rst->g[2] = -1.;
        contrast(ma, rst->pc);
-//     bcf_p1_cal_g3(ma, rst->g);
        return 0;
 }
 

diff --git a/bcftools/prob1.h b/bcftools/prob1.h
index 35c794fa1f78d8cea6781cb158dafbfff3553b93..7158fe29f89bee73dda2f2bdc9426af038a363c6 100644 (file)
--- a/bcftools/prob1.h
+++ b/bcftools/prob1.h
@@ -23,6 +23,7 @@ extern "C" {
 
        bcf_p1aux_t *bcf_p1_init(int n);
        void bcf_p1_init_prior(bcf_p1aux_t *ma, int type, double theta);
+       void bcf_p1_init_subprior(bcf_p1aux_t *ma, int type, double theta);
        void bcf_p1_destroy(bcf_p1aux_t *ma);
        int bcf_p1_cal(bcf1_t *b, bcf_p1aux_t *ma, bcf_p1rst_t *rst);
        int bcf_p1_call_gt(const bcf_p1aux_t *ma, double f0, int k);