X-Git-Url: https://git.donarmstrong.com/?a=blobdiff_plain;f=bam_mcns.c;h=893d2efdcd7a26f6202e0d235f2c263df1cb1772;hb=6dc53c5ab2964e68e8936850d2339d047d2433ef;hp=845dfcda5a956305c66b3b5d51ceaff4204b803b;hpb=921db5eb2dfecd81e71c42934d0482efb869ab80;p=samtools.git diff --git a/bam_mcns.c b/bam_mcns.c index 845dfcd..893d2ef 100644 --- a/bam_mcns.c +++ b/bam_mcns.c @@ -1,30 +1,63 @@ #include #include +#include #include "bam_mcns.h" -#define MC_MIN_QUAL 20 +#define MC_MIN_QUAL 13 +#define MC_AVG_ERR 0.007 #define MC_MAX_SUMQ 3000 #define MC_MAX_SUMQP 1e-300 +#define MC_MAX_EM_ITER 16 +#define MC_EM_EPS 1e-4 struct __mc_aux_t { - int n, N; - int ref, alt; + int n, M; + int ref, alt, alt2; double *q2p, *pdg; // pdg -> P(D|g) + double *phi, *CMk; // CMk=\binom{M}{k} + double *z, *zswap; // aux for afs + double *afs, *afs1; // afs: accumulative AFS; afs1: site posterior distribution int *qsum, *bcnt; }; +void mc_init_prior(mc_aux_t *ma, int type, double theta) +{ + int i; + if (type == MC_PTYPE_COND2) { + for (i = 0; i <= 2 * ma->n; ++i) + ma->phi[i] = 2. * (i + 1) / (2 * ma->n + 1) / (2 * ma->n + 2); + } else if (type == MC_PTYPE_FLAT) { + for (i = 0; i <= ma->M; ++i) + ma->phi[i] = 1. / (ma->M + 1); + } else { + double sum; + for (i = 0, sum = 0.; i < 2 * ma->n; ++i) + sum += (ma->phi[i] = theta / (2 * ma->n - i)); + ma->phi[2 * ma->n] = 1. - sum; + } +} + mc_aux_t *mc_init(int n) // FIXME: assuming diploid { mc_aux_t *ma; int i; ma = calloc(1, sizeof(mc_aux_t)); - ma->n = n; ma->N = 2 * n; + ma->n = n; ma->M = 2 * n; ma->q2p = calloc(MC_MAX_SUMQ + 1, sizeof(double)); 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->phi = calloc(ma->M + 1, sizeof(double)); + ma->CMk = 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->afs = calloc(2 * ma->n + 1, sizeof(double)); + ma->afs1 = calloc(2 * ma->n + 1, sizeof(double)); for (i = 0; i <= MC_MAX_SUMQ; ++i) ma->q2p[i] = pow(10., -i / 10.); + for (i = 0; i <= ma->M; ++i) + ma->CMk[i] = exp(lgamma(ma->M + 1) - lgamma(i + 1) - lgamma(ma->M - i + 1)); + mc_init_prior(ma, MC_PTYPE_FULL, 1e-3); // the simplest prior return ma; } @@ -33,13 +66,16 @@ void mc_destroy(mc_aux_t *ma) if (ma) { free(ma->qsum); free(ma->bcnt); free(ma->q2p); free(ma->pdg); + free(ma->phi); free(ma->CMk); + free(ma->z); free(ma->zswap); + free(ma->afs); free(ma->afs1); free(ma); } } -static void sum_err(int *n, const bam_pileup1_t **plp, mc_aux_t *ma) +static int sum_err(int *n, const bam_pileup1_t **plp, mc_aux_t *ma) { - int i, j; + int i, j, tot = 0; memset(ma->qsum, 0, sizeof(int) * 4 * ma->n); memset(ma->bcnt, 0, sizeof(int) * 4 * ma->n); for (j = 0; j < ma->n; ++j) { @@ -56,8 +92,10 @@ static void sum_err(int *n, const bam_pileup1_t **plp, mc_aux_t *ma) if (b > 3) continue; // N qsum[b] += q; ++bcnt[b]; + ++tot; } } + return tot; } static void set_allele(int ref, mc_aux_t *ma) @@ -71,9 +109,13 @@ static void set_allele(int ref, mc_aux_t *ma) for (i = 1; i < 4; ++i) // insertion sort for (j = i; j > 0 && sum[j] < sum[j-1]; --j) tmp = sum[j], sum[j] = sum[j-1], sum[j-1] = tmp; - ma->ref = sum[3]&3; ma->alt = sum[2]&3; - if (ref == ma->alt) tmp = ma->ref, ma->ref = ma->alt, ma->alt = tmp; - // note that ma->ref might not be ref in case of triallele + ma->ref = sum[3]&3; ma->alt = sum[2]&3; ma->alt2 = -1; + if (ma->ref != ref) { // the best base is not ref + if (ref >= 0 && ref <= 3) { // ref is not N + if (ma->alt == ref) tmp = ma->ref, ma->ref = ma->alt, ma->alt = tmp; // then switch alt and ref + else ma->alt2 = ma->alt, ma->alt = ma->ref, ma->ref = ref; // then set ref as ref + } else ma->alt2 = ma->alt, ma->alt = ma->ref, ma->ref = sum[0]&3; // then set the weakest as ref + } } static void cal_pdg(mc_aux_t *ma) @@ -85,43 +127,152 @@ static void cal_pdg(mc_aux_t *ma) qsum = ma->qsum + j * 4; bcnt = ma->bcnt + j * 4; pi[1] = 3 * (bcnt[ma->ref] + bcnt[ma->alt]); - pi[0] = qsum[ma->alt]; - pi[2] = qsum[ma->ref]; + pi[0] = qsum[ma->ref]; + pi[2] = qsum[ma->alt]; for (i = 0; i < 3; ++i) - pdg[i] = pi[i] < MC_MAX_SUMQ? MC_MAX_SUMQP : ma->q2p[pi[i]]; + pdg[i] = pi[i] > MC_MAX_SUMQ? MC_MAX_SUMQP : ma->q2p[pi[i]]; } } - -double mc_freq0(int ref, int *n, const bam_pileup1_t **plp, mc_aux_t *ma, int *_ref, int *alt) +// this calculates the naive allele frequency and Nielsen's frequency +static double mc_freq0(const mc_aux_t *ma, double *_f) { - int i, acnt[4], j; - double f0; - sum_err(n, plp, ma); - set_allele(ref, ma); - cal_pdg(ma); - acnt[0] = acnt[1] = acnt[2] = acnt[3] = 0; - for (i = 0; i < ma->n; ++i) - for (j = 0; j < 4; ++j) - acnt[j] += ma->bcnt[i * 4 + j]; - f0 = acnt[ma->ref] + acnt[ma->alt] == 0? -1. - : (double)acnt[ref] / (acnt[ma->ref] + acnt[ma->alt]); - *_ref = ma->ref; *alt = ma->alt; - return f0; + int i, cnt; + double f, f_nielsen, w_sum; + *_f = -1.; + for (i = cnt = 0, f = f_nielsen = w_sum = 0.; i < ma->n; ++i) { + int *bcnt = ma->bcnt + i * 4; + int x = bcnt[ma->ref] + bcnt[ma->alt]; + if (x) { + double w, p; + ++cnt; + f += (double)bcnt[ma->ref] / x; + p = (bcnt[ma->ref] - MC_AVG_ERR * x) / (1. - 2. * MC_AVG_ERR) / x; + w = 2. * x / (1. + x); + w_sum += w; + f_nielsen += p * w; + } + } + if (cnt) { + f_nielsen /= w_sum; + if (f_nielsen < 0.) f_nielsen = 0.; + if (f_nielsen > 1.) f_nielsen = 1.; + *_f = f_nielsen; + return f / cnt; + } else return -1.; } - -double mc_freq_iter(double f0, mc_aux_t *ma) +// f0 is the reference allele frequency +static double mc_freq_iter(double f0, const mc_aux_t *ma) { double f, f3[3]; - int i, j; - f3[0] = f0*f0; f3[1] = 2.*f0*(1.-f0); f3[2] = (1.-f0)*(1.-f0); + int i; + f3[0] = (1.-f0)*(1.-f0); f3[1] = 2.*f0*(1.-f0); f3[2] = f0*f0; for (i = 0, f = 0.; i < ma->n; ++i) { - double up, dn, *pdg; + double *pdg; pdg = ma->pdg + i * 3; - for (j = 1, up = 0.; j < 3; ++j) - up += j * pdg[j] * f3[j]; - for (j = 0, dn = 0.; j < 3; ++j) - dn += pdg[j] * f3[j]; - f += up / dn; + f += (pdg[1] * f3[1] + 2. * pdg[2] * f3[2]) + / (pdg[0] * f3[0] + pdg[1] * f3[1] + pdg[2] * f3[2]); } + f /= ma->n * 2.; return f; } + +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; +} + +static void mc_cal_z(mc_aux_t *ma) +{ + double *z[2], *tmp, *pdg; + int i, j; + z[0] = ma->z; + z[1] = ma->zswap; + pdg = ma->pdg; + z[0][0] = 1.; z[0][1] = z[0][2] = 0.; + for (j = 0; j < ma->n; ++j) { + int max = (j + 1) * 2; + double p[3]; + pdg = ma->pdg + j * 3; + p[0] = pdg[0]; p[1] = 2. * pdg[1]; p[2] = pdg[2]; + z[1][0] = p[0] * z[0][0]; + z[1][1] = p[0] * z[0][1] + p[1] * z[0][0]; + for (i = 2; i <= max; ++i) + z[1][i] = p[0] * z[0][i] + p[1] * z[0][i-1] + p[2] * z[0][i-2]; + if (j < ma->n - 1) z[1][max+1] = z[1][max+2] = 0.; +// int k; for (k = 0; k <= max; ++k) printf("%d:%.3lg ", k, z[1][k]); putchar('\n'); + tmp = z[0]; z[0] = z[1]; z[1] = tmp; + } + if (z[0] != ma->z) memcpy(ma->z, z[0], sizeof(double) * (2 * ma->n + 1)); +} + +static double mc_add_afs(mc_aux_t *ma) +{ + int k; + long double sum = 0.; + memset(ma->afs1, 0, sizeof(double) * (ma->M + 1)); + mc_cal_z(ma); + for (k = 0, sum = 0.; k <= ma->M; ++k) + sum += (long double)ma->phi[k] * ma->z[k] / ma->CMk[k]; + for (k = 0; k <= ma->M; ++k) { + ma->afs1[k] = ma->phi[k] * ma->z[k] / ma->CMk[k] / sum; + if (isnan(ma->afs1[k]) || isinf(ma->afs1[k])) return -1.; + } + 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 mc_cal(int ref, int *n, const bam_pileup1_t **plp, mc_aux_t *ma, mc_rst_t *rst, int level) +{ + int i, tot; + memset(rst, 0, sizeof(mc_rst_t)); + rst->f_em = rst->f_exp = -1.; rst->ref = rst->alt = -1; + // precalculation + tot = sum_err(n, plp, ma); + if (tot == 0) return 0; // no good bases + set_allele(ref, ma); + cal_pdg(ma); + // set ref/major allele + rst->ref = ma->ref; rst->alt = ma->alt; rst->alt2 = ma->alt2; + // calculate naive and Nielsen's freq + rst->f_naive = mc_freq0(ma, &rst->f_nielsen); + { // calculate f_em + double flast = rst->f_naive; + for (i = 0; i < MC_MAX_EM_ITER; ++i) { + rst->f_em = mc_freq_iter(flast, ma); + if (fabs(rst->f_em - flast) < MC_EM_EPS) break; + flast = rst->f_em; + } + } + if (level >= 2) { + rst->f_exp = mc_add_afs(ma); + rst->p_ref = ma->afs1[ma->M]; + } + return tot; +} + +void mc_dump_afs(mc_aux_t *ma) +{ + int k; + fprintf(stderr, "[afs]"); + for (k = 0; k <= ma->M; ++k) + fprintf(stderr, " %d:%.3lf", k, ma->afs[ma->M - k]); + fprintf(stderr, "\n"); + memset(ma->afs, 0, sizeof(double) * (ma->M + 1)); +}