preliminary contrast variant caller

diff --git a/bcftools/Makefile b/bcftools/Makefile
index 5a3dc763f8105ba3dc8db43db390a4b13c0ba252..e3b92e9d29f96734495a4acb0c536642a1918d42 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
+DFLAGS=                -D_FILE_OFFSET_BITS=64 -D_USE_KNETFILE -D_BCF_QUAD
 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 c722b355afd8752031044ef63f98e9eef7c2876e..e8ecb51a3e0b73d0c4020133f8caedba43938298 100644 (file)
--- a/bcftools/call1.c
+++ b/bcftools/call1.c
@@ -162,7 +162,10 @@ static int update_bcf1(int n_smpl, bcf1_t *b, const bcf_p1aux_t *pa, const bcf_p
        if (b->info[0]) kputc(';', &s);
        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) ksprintf(&s, ";PV4=%.2lg,%.2lg,%.2lg,%.2lg", a.p[0], a.p[1], a.p[2], a.p[3]);
+       if (a.is_tested) {
+               if (pr->pc[0] >= 0.) ksprintf(&s, ";PC4=%.2lg,%.2lg,%.2lg,%.2lg", 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)
                ksprintf(&s, ";GC=%.2lf,%.2lf,%.2lf;HWE=%.3lf", pr->g[2], pr->g[1], pr->g[0], p_hwe);
        kputc('\0', &s);
@@ -224,6 +227,7 @@ int bcfview(int argc, char *argv[])
                fprintf(stderr, "         -L        discard the PL genotype field\n");
                fprintf(stderr, "         -H        perform Hardy-Weinberg test (slower)\n");
                fprintf(stderr, "         -v        output potential variant sites only\n");
+               fprintf(stderr, "         -1 INT    number of group-1 samples [0]\n");
                fprintf(stderr, "         -l FILE   list of sites to output [all sites]\n");
                fprintf(stderr, "         -t FLOAT  scaled mutation rate [%.4lg]\n", vc.theta);
                fprintf(stderr, "         -p FLOAT  variant if P(ref|D)<FLOAT [%.3lg]\n", vc.pref);

diff --git a/bcftools/prob1.c b/bcftools/prob1.c
index afbbd419cd0242aeefd1e31776e45fecdf36a981..e2c090ac0dca832292b84a6533446469d63e6ed3 100644 (file)
--- a/bcftools/prob1.c
+++ b/bcftools/prob1.c
@@ -12,6 +12,8 @@ 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, 
@@ -39,6 +41,7 @@ struct __bcf_p1aux_t {
        double *z1, *z2; // 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;
 };
@@ -97,7 +100,7 @@ int bcf_p1_read_prior(bcf_p1aux_t *ma, const char *fn)
        return 0;
 }
 
-bcf_p1aux_t *bcf_p1_init(int n) // FIXME: assuming diploid
+bcf_p1aux_t *bcf_p1_init(int n)
 {
        bcf_p1aux_t *ma;
        int i;
@@ -119,10 +122,26 @@ bcf_p1aux_t *bcf_p1_init(int n) // FIXME: assuming diploid
        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;
 }
 
@@ -133,6 +152,7 @@ void bcf_p1_destroy(bcf_p1aux_t *ma)
                free(ma->phi);
                free(ma->z); free(ma->zswap); free(ma->z1); free(ma->z2);
                free(ma->afs); free(ma->afs1);
+               free(ma->k1k2);
                free(ma);
        }
 }
@@ -247,7 +267,7 @@ static void mc_cal_y(bcf_p1aux_t *ma)
 {
        if (ma->n1 > 0 && ma->n1 < ma->n) {
                int k;
-               double x;
+               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.;
@@ -256,26 +276,68 @@ static void mc_cal_y(bcf_p1aux_t *ma)
                memcpy(ma->z2, ma->z, sizeof(double) * (2 * (ma->n - ma->n1) + 1));
                mc_cal_y_core(ma, 0);
                // rescale z
-               x = exp(ma->t - (ma->t1 + ma->t2));
+               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) {
-               int i;
-               double y[5];
-               printf("*****\n");
-               for (i = 0; i <= 2; ++i)
-                       printf("(%lf,%lf) ", ma->z1[i], ma->z2[i]);
-               printf("\n");
-               y[0] = ma->z1[0] * ma->z2[0];
-               y[1] = 1./2. * (ma->z1[0] * ma->z2[1] + ma->z1[1] * ma->z2[0]);
-               y[2] = 1./6. * (ma->z1[0] * ma->z2[2] + ma->z1[2] * ma->z2[0]) + 4./6. * ma->z1[1] * ma->z2[1];
-               y[3] = 1./2. * (ma->z1[1] * ma->z2[2] + ma->z1[2] * ma->z2[1]);
-               y[4] = ma->z1[2] * ma->z2[2];
-               for (i = 0; i <= 4; ++i) printf("(%lf,%lf) ", ma->z[i], y[i]);
+       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.;
+       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;
+       }
+#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;
+       y = lgamma(2*n1 + 1) - lgamma(ma->M + 1);
+       for (k = 1, x = 0.; k <= 2 * n2; ++k)
+               x += ma->phi[k] * ma->z2[k] * exp(lgamma(ma->M - k + 1) - lgamma(2*n2 - k + 1) + y);
+       pc[0] = ma->z1[0] * x / sum;
+       y = lgamma(2*n2 + 1) - lgamma(ma->M + 1);
+       for (k = 1, x = 0.; k <= 2 * n1; ++k)
+               x += ma->phi[k] * ma->z1[k] * exp(lgamma(ma->M - k + 1) - lgamma(2*n1 - k + 1) + y);
+       pc[1] = ma->z2[0] * x / sum;
+       for (k = 0; k < 4; ++k) {
+               y = 1. - pc[k];
+               if (y <= 0.) y = 1e-100;
+               pc[k] = (int)(-3.434 * log(y) + .499);
+               if (pc[k] > 99.) pc[k] = 99.;
+       }
 }
 
 static double mc_cal_afs(bcf_p1aux_t *ma)
@@ -358,6 +420,7 @@ 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 6bb7440efde77043476de22ca922d590ebf2cf66..35c794fa1f78d8cea6781cb158dafbfff3553b93 100644 (file)
--- a/bcftools/prob1.h
+++ b/bcftools/prob1.h
@@ -8,7 +8,9 @@ typedef struct __bcf_p1aux_t bcf_p1aux_t;
 
 typedef struct {
        int rank0;
-       double f_em, f_exp, f_flat, p_ref, g[3];
+       double f_em, f_exp, f_flat, p_ref;
+       double pc[4];
+       double g[3];
 } bcf_p1rst_t;
 
 #define MC_PTYPE_FULL  1