#include "pysam.h" #include #include #include #include #include #include #include "prob1.h" #include "kseq.h" KSTREAM_INIT(gzFile, gzread, 16384) #define MC_MAX_EM_ITER 16 #define MC_EM_EPS 1e-5 #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, 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, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 4, 1, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 0, 4, 1, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 3, 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, 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, 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, 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, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 }; struct __bcf_p1aux_t { int n, M, n1, is_indel; uint8_t *ploidy; // haploid or diploid ONLY double *q2p, *pdg; // pdg -> P(D|g) double *phi, *phi_indel; double *z, *zswap; // aux for afs double *z1, *z2, *phi1, *phi2; // only calculated when n1 is set double **hg; // hypergeometric distribution double *lf; // log factorial double t, t1, t2; double *afs, *afs1; // afs: accumulative AFS; afs1: site posterior distribution const uint8_t *PL; // point to PL 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; if (type == MC_PTYPE_COND2) { 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 <= M; ++i) phi[i] = 1. / (M + 1); } else { double 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); bcf_p1_indel_prior(ma, MC_DEF_INDEL); } 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; kstring_t s; kstream_t *ks; long double sum; int dret, k; memset(&s, 0, sizeof(kstring_t)); fp = strcmp(fn, "-")? gzopen(fn, "r") : gzdopen(fileno(stdin), "r"); ks = ks_init(fp); memset(ma->phi, 0, sizeof(double) * (ma->M + 1)); while (ks_getuntil(ks, '\n', &s, &dret) >= 0) { if (strstr(s.s, "[afs] ") == s.s) { char *p = s.s + 6; for (k = 0; k <= ma->M; ++k) { int x; double y; x = strtol(p, &p, 10); if (x != k && (errno == EINVAL || errno == ERANGE)) return -1; ++p; y = strtod(p, &p); if (y == 0. && (errno == EINVAL || errno == ERANGE)) return -1; ma->phi[ma->M - k] += y; } } } ks_destroy(ks); gzclose(fp); free(s.s); for (sum = 0., k = 0; k <= ma->M; ++k) sum += ma->phi[k]; fprintf(pysamerr, "[prior]"); for (k = 0; k <= ma->M; ++k) ma->phi[k] /= sum; for (k = 0; k <= ma->M; ++k) fprintf(pysamerr, " %d:%.3lg", k, ma->phi[ma->M - k]); fputc('\n', pysamerr); for (sum = 0., k = 1; k < ma->M; ++k) sum += ma->phi[ma->M - k] * (2.* k * (ma->M - k) / ma->M / (ma->M - 1)); fprintf(pysamerr, "[%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(pysamerr, "theta=%lf\n", (double)sum); bcf_p1_indel_prior(ma, MC_DEF_INDEL); return 0; } bcf_p1aux_t *bcf_p1_init(int n, uint8_t *ploidy) { bcf_p1aux_t *ma; int i; ma = calloc(1, sizeof(bcf_p1aux_t)); ma->n1 = -1; ma->n = n; ma->M = 2 * n; if (ploidy) { ma->ploidy = malloc(n); memcpy(ma->ploidy, ploidy, n); for (i = 0, ma->M = 0; i < n; ++i) ma->M += ploidy[i]; if (ma->M == 2 * n) { free(ma->ploidy); ma->ploidy = 0; } } 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(ma->M + 1, sizeof(double)); ma->zswap = calloc(ma->M + 1, sizeof(double)); ma->z1 = calloc(ma->M + 1, sizeof(double)); // actually we do not need this large ma->z2 = calloc(ma->M + 1, sizeof(double)); ma->afs = calloc(ma->M + 1, sizeof(double)); ma->afs1 = calloc(ma->M + 1, sizeof(double)); ma->lf = calloc(ma->M + 1, sizeof(double)); for (i = 0; i < 256; ++i) ma->q2p[i] = pow(10., -i / 10.); for (i = 0; i <= ma->M; ++i) ma->lf[i] = lgamma(i + 1); bcf_p1_init_prior(ma, MC_PTYPE_FULL, 1e-3); // the simplest prior return ma; } int bcf_p1_set_n1(bcf_p1aux_t *b, int n1) { if (n1 == 0 || n1 >= b->n) return -1; if (b->M != b->n * 2) { fprintf(pysamerr, "[%s] unable to set `n1' when there are haploid samples.\n", __func__); return -1; } b->n1 = n1; return 0; } void bcf_p1_destroy(bcf_p1aux_t *ma) { if (ma) { int k; free(ma->lf); if (ma->hg && ma->n1 > 0) { for (k = 0; k <= 2*ma->n1; ++k) free(ma->hg[k]); free(ma->hg); } free(ma->ploidy); free(ma->q2p); free(ma->pdg); 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); } } static int cal_pdg(const bcf1_t *b, bcf_p1aux_t *ma) { 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[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 for (j = i; j > 0 && p[j] < p[j-1]; --j) tmp = p[j], p[j] = p[j-1], p[j-1] = tmp; for (i = b->n_alleles - 1; i >= 0; --i) if ((p[i]&0xf) == 0) break; return i; } int bcf_p1_call_gt(const bcf_p1aux_t *ma, double f0, int k) { double sum, g[3]; double max, f3[3], *pdg = ma->pdg + k * 3; int q, i, max_i, ploidy; ploidy = ma->ploidy? ma->ploidy[k] : 2; if (ploidy == 2) { f3[0] = (1.-f0)*(1.-f0); f3[1] = 2.*f0*(1.-f0); f3[2] = f0*f0; } else { f3[0] = 1. - f0; f3[1] = 0; f3[2] = 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)(-4.343 * log(max) + .499); if (q > 99) q = 99; return q<<2|max_i; } #define TINY 1e-20 static void mc_cal_y_core(bcf_p1aux_t *ma, int beg) { double *z[2], *tmp, *pdg; int _j, last_min, last_max; assert(beg == 0 || ma->M == ma->n*2); z[0] = ma->z; z[1] = ma->zswap; pdg = ma->pdg; memset(z[0], 0, sizeof(double) * (ma->M + 1)); memset(z[1], 0, sizeof(double) * (ma->M + 1)); z[0][0] = 1.; last_min = last_max = 0; ma->t = 0.; if (ma->M == ma->n * 2) { int M = 0; for (_j = beg; _j < ma->n; ++_j) { int k, j = _j - beg, _min = last_min, _max = last_max, M0; double p[3], sum; M0 = M; M += 2; pdg = ma->pdg + _j * 3; p[0] = pdg[0]; p[1] = 2. * pdg[1]; p[2] = pdg[2]; for (; _min < _max && z[0][_min] < TINY; ++_min) z[0][_min] = z[1][_min] = 0.; for (; _max > _min && z[0][_max] < TINY; --_max) z[0][_max] = z[1][_max] = 0.; _max += 2; if (_min == 0) k = 0, z[1][k] = (M0-k+1) * (M0-k+2) * p[0] * z[0][k]; if (_min <= 1) k = 1, z[1][k] = (M0-k+1) * (M0-k+2) * p[0] * z[0][k] + k*(M0-k+2) * p[1] * z[0][k-1]; for (k = _min < 2? 2 : _min; k <= _max; ++k) z[1][k] = (M0-k+1)*(M0-k+2) * p[0] * z[0][k] + k*(M0-k+2) * p[1] * z[0][k-1] + k*(k-1)* p[2] * z[0][k-2]; for (k = _min, sum = 0.; k <= _max; ++k) sum += z[1][k]; ma->t += log(sum / (M * (M - 1.))); for (k = _min; k <= _max; ++k) z[1][k] /= sum; if (_min >= 1) z[1][_min-1] = 0.; if (_min >= 2) z[1][_min-2] = 0.; if (j < ma->n - 1) z[1][_max+1] = z[1][_max+2] = 0.; if (_j == ma->n1 - 1) { // set pop1; ma->n1==-1 when unset ma->t1 = ma->t; memcpy(ma->z1, z[1], sizeof(double) * (ma->n1 * 2 + 1)); } tmp = z[0]; z[0] = z[1]; z[1] = tmp; last_min = _min; last_max = _max; } //for (_j = 0; _j < last_min; ++_j) z[0][_j] = 0.; // TODO: are these necessary? //for (_j = last_max + 1; _j < ma->M; ++_j) z[0][_j] = 0.; } else { // this block is very similar to the block above; these two might be merged in future int j, M = 0; for (j = 0; j < ma->n; ++j) { int k, M0, _min = last_min, _max = last_max; double p[3], sum; pdg = ma->pdg + j * 3; for (; _min < _max && z[0][_min] < TINY; ++_min) z[0][_min] = z[1][_min] = 0.; for (; _max > _min && z[0][_max] < TINY; --_max) z[0][_max] = z[1][_max] = 0.; M0 = M; M += ma->ploidy[j]; if (ma->ploidy[j] == 1) { p[0] = pdg[0]; p[1] = pdg[2]; _max++; if (_min == 0) k = 0, z[1][k] = (M0+1-k) * p[0] * z[0][k]; for (k = _min < 1? 1 : _min; k <= _max; ++k) z[1][k] = (M0+1-k) * p[0] * z[0][k] + k * p[1] * z[0][k-1]; for (k = _min, sum = 0.; k <= _max; ++k) sum += z[1][k]; ma->t += log(sum / M); for (k = _min; k <= _max; ++k) z[1][k] /= sum; if (_min >= 1) z[1][_min-1] = 0.; if (j < ma->n - 1) z[1][_max+1] = 0.; } else if (ma->ploidy[j] == 2) { p[0] = pdg[0]; p[1] = 2 * pdg[1]; p[2] = pdg[2]; _max += 2; if (_min == 0) k = 0, z[1][k] = (M0-k+1) * (M0-k+2) * p[0] * z[0][k]; if (_min <= 1) k = 1, z[1][k] = (M0-k+1) * (M0-k+2) * p[0] * z[0][k] + k*(M0-k+2) * p[1] * z[0][k-1]; for (k = _min < 2? 2 : _min; k <= _max; ++k) z[1][k] = (M0-k+1)*(M0-k+2) * p[0] * z[0][k] + k*(M0-k+2) * p[1] * z[0][k-1] + k*(k-1)* p[2] * z[0][k-2]; for (k = _min, sum = 0.; k <= _max; ++k) sum += z[1][k]; ma->t += log(sum / (M * (M - 1.))); for (k = _min; k <= _max; ++k) z[1][k] /= sum; if (_min >= 1) z[1][_min-1] = 0.; if (_min >= 2) z[1][_min-2] = 0.; if (j < ma->n - 1) z[1][_max+1] = z[1][_max+2] = 0.; } tmp = z[0]; z[0] = z[1]; z[1] = tmp; last_min = _min; last_max = _max; } } if (z[0] != ma->z) memcpy(ma->z, z[0], sizeof(double) * (ma->M + 1)); } static void mc_cal_y(bcf_p1aux_t *ma) { if (ma->n1 > 0 && ma->n1 < ma->n && ma->M == ma->n * 2) { // NB: ma->n1 is ineffective when there are haploid samples int k; 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.; mc_cal_y_core(ma, ma->n1); ma->t2 = ma->t; memcpy(ma->z2, ma->z, sizeof(double) * (2 * (ma->n - ma->n1) + 1)); mc_cal_y_core(ma, 0); // rescale z 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); } #define CONTRAST_TINY 1e-30 extern double kf_gammaq(double s, double z); // incomplete gamma function for chi^2 test static inline double chi2_test(int a, int b, int c, int d) { double x, z; x = (double)(a+b) * (c+d) * (b+d) * (a+c); if (x == 0.) return 1; z = a * d - b * c; return kf_gammaq(.5, .5 * z * z * (a+b+c+d) / x); } // chi2=(a+b+c+d)(ad-bc)^2/[(a+b)(c+d)(a+c)(b+d)] static inline double contrast2_aux(const bcf_p1aux_t *p1, double sum, int k1, int k2, double x[3]) { double p = p1->phi[k1+k2] * p1->z1[k1] * p1->z2[k2] / sum * p1->hg[k1][k2]; int n1 = p1->n1, n2 = p1->n - p1->n1; if (p < CONTRAST_TINY) return -1; if (.5*k1/n1 < .5*k2/n2) x[1] += p; else if (.5*k1/n1 > .5*k2/n2) x[2] += p; else x[0] += p; return p * chi2_test(k1, k2, (n1<<1) - k1, (n2<<1) - k2); } static double contrast2(bcf_p1aux_t *p1, double ret[3]) { int k, k1, k2, k10, k20, n1, n2; double sum; // get n1 and n2 n1 = p1->n1; n2 = p1->n - p1->n1; if (n1 <= 0 || n2 <= 0) return 0.; if (p1->hg == 0) { // initialize the hypergeometric distribution /* NB: the hg matrix may take a lot of memory when there are many samples. There is a way to avoid precomputing this matrix, but it is slower and quite intricate. The following computation in this block can be accelerated with a similar strategy, but perhaps this is not a serious concern for now. */ double tmp = lgamma(2*(n1+n2)+1) - (lgamma(2*n1+1) + lgamma(2*n2+1)); p1->hg = calloc(2*n1+1, sizeof(void*)); for (k1 = 0; k1 <= 2*n1; ++k1) { p1->hg[k1] = calloc(2*n2+1, sizeof(double)); for (k2 = 0; k2 <= 2*n2; ++k2) p1->hg[k1][k2] = exp(lgamma(k1+k2+1) + lgamma(p1->M-k1-k2+1) - (lgamma(k1+1) + lgamma(k2+1) + lgamma(2*n1-k1+1) + lgamma(2*n2-k2+1) + tmp)); } } { // compute long double suml = 0; for (k = 0; k <= p1->M; ++k) suml += p1->phi[k] * p1->z[k]; sum = suml; } { // get the max k1 and k2 double max; int max_k; for (k = 0, max = 0, max_k = -1; k <= 2*n1; ++k) { double x = p1->phi1[k] * p1->z1[k]; if (x > max) max = x, max_k = k; } k10 = max_k; for (k = 0, max = 0, max_k = -1; k <= 2*n2; ++k) { double x = p1->phi2[k] * p1->z2[k]; if (x > max) max = x, max_k = k; } k20 = max_k; } { // We can do the following with one nested loop, but that is an O(N^2) thing. The following code block is much faster for large N. double x[3], y; long double z = 0., L[2]; x[0] = x[1] = x[2] = 0; L[0] = L[1] = 0; for (k1 = k10; k1 >= 0; --k1) { for (k2 = k20; k2 >= 0; --k2) { if ((y = contrast2_aux(p1, sum, k1, k2, x)) < 0) break; else z += y; } for (k2 = k20 + 1; k2 <= 2*n2; ++k2) { if ((y = contrast2_aux(p1, sum, k1, k2, x)) < 0) break; else z += y; } } ret[0] = x[0]; ret[1] = x[1]; ret[2] = x[2]; x[0] = x[1] = x[2] = 0; for (k1 = k10 + 1; k1 <= 2*n1; ++k1) { for (k2 = k20; k2 >= 0; --k2) { if ((y = contrast2_aux(p1, sum, k1, k2, x)) < 0) break; else z += y; } for (k2 = k20 + 1; k2 <= 2*n2; ++k2) { if ((y = contrast2_aux(p1, sum, k1, k2, x)) < 0) break; else z += y; } } ret[0] += x[0]; ret[1] += x[1]; ret[2] += x[2]; if (ret[0] + ret[1] + ret[2] < 0.95) { // in case of bad things happened ret[0] = ret[1] = ret[2] = 0; L[0] = L[1] = 0; for (k1 = 0, z = 0.; k1 <= 2*n1; ++k1) for (k2 = 0; k2 <= 2*n2; ++k2) if ((y = contrast2_aux(p1, sum, k1, k2, ret)) >= 0) z += y; if (ret[0] + ret[1] + ret[2] < 0.95) // It seems that this may be caused by floating point errors. I do not really understand why... z = 1.0, ret[0] = ret[1] = ret[2] = 1./3; } return (double)z; } } static double mc_cal_afs(bcf_p1aux_t *ma, double *p_ref_folded, double *p_var_folded) { int k; 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)phi[k] * ma->z[k]; for (k = 0; k <= ma->M; ++k) { 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]; } return sum / ma->M; } int bcf_p1_cal(const bcf1_t *b, int do_contrast, bcf_p1aux_t *ma, bcf_p1rst_t *rst) { int i, k; long double sum = 0.; ma->is_indel = bcf_is_indel(b); rst->perm_rank = -1; // set PL and PL_len for (i = 0; i < b->n_gi; ++i) { if (b->gi[i].fmt == bcf_str2int("PL", 2)) { ma->PL = (uint8_t*)b->gi[i].data; ma->PL_len = b->gi[i].len; break; } } if (i == b->n_gi) return -1; // no PL 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->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; { // compute the allele count double max = -1; rst->ac = -1; for (k = 0; k <= ma->M; ++k) if (max < ma->z[k]) max = ma->z[k], rst->ac = k; rst->ac = ma->M - rst->ac; } // calculate f_flat and f_em for (k = 0, sum = 0.; k <= ma->M; ++k) sum += (long double)ma->z[k]; rst->f_flat = 0.; for (k = 0; k <= ma->M; ++k) { double p = ma->z[k] / sum; rst->f_flat += k * p; } rst->f_flat /= ma->M; { // 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, 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; } if (ma->n1 > 0) { // compute LRT double max0, max1, max2; for (k = 0, max0 = -1; k <= ma->M; ++k) if (max0 < ma->z[k]) max0 = ma->z[k]; for (k = 0, max1 = -1; k <= ma->n1 * 2; ++k) if (max1 < ma->z1[k]) max1 = ma->z1[k]; for (k = 0, max2 = -1; k <= ma->M - ma->n1 * 2; ++k) if (max2 < ma->z2[k]) max2 = ma->z2[k]; rst->lrt = log(max1 * max2 / max0); rst->lrt = rst->lrt < 0? 1 : kf_gammaq(.5, rst->lrt); } else rst->lrt = -1.0; rst->cmp[0] = rst->cmp[1] = rst->cmp[2] = rst->p_chi2 = -1.0; if (do_contrast && rst->p_var > 0.5) // skip contrast2() if the locus is a strong non-variant rst->p_chi2 = contrast2(ma, rst->cmp); return 0; } void bcf_p1_dump_afs(bcf_p1aux_t *ma) { int k; fprintf(pysamerr, "[afs]"); for (k = 0; k <= ma->M; ++k) fprintf(pysamerr, " %d:%.3lf", k, ma->afs[ma->M - k]); fprintf(pysamerr, "\n"); memset(ma->afs, 0, sizeof(double) * (ma->M + 1)); }