7 #define MC_AVG_ERR 0.007
8 #define MC_MAX_EM_ITER 16
11 unsigned char seq_nt4_table[256] = {
12 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
13 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
14 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 /*'-'*/, 4, 4,
15 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
16 4, 0, 4, 1, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4,
17 4, 4, 4, 4, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
18 4, 0, 4, 1, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4,
19 4, 4, 4, 4, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
20 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
21 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
22 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
23 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
24 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
25 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
26 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
27 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4
30 struct __bcf_p1aux_t {
32 double *q2p, *pdg; // pdg -> P(D|g)
34 double *z, *zswap; // aux for afs
35 double *afs, *afs1; // afs: accumulative AFS; afs1: site posterior distribution
36 const uint8_t *PL; // point to PL
40 void bcf_p1_init_prior(bcf_p1aux_t *ma, int type, double theta)
43 if (type == MC_PTYPE_COND2) {
44 for (i = 0; i <= ma->M; ++i)
45 ma->phi[i] = 2. * (i + 1) / (ma->M + 1) / (ma->M + 2);
46 } else if (type == MC_PTYPE_FLAT) {
47 for (i = 0; i <= ma->M; ++i)
48 ma->phi[i] = 1. / (ma->M + 1);
51 for (i = 0, sum = 0.; i < ma->M; ++i)
52 sum += (ma->phi[i] = theta / (ma->M - i));
53 ma->phi[ma->M] = 1. - sum;
57 bcf_p1aux_t *bcf_p1_init(int n) // FIXME: assuming diploid
61 ma = calloc(1, sizeof(bcf_p1aux_t));
62 ma->n = n; ma->M = 2 * n;
63 ma->q2p = calloc(256, sizeof(double));
64 ma->pdg = calloc(3 * ma->n, sizeof(double));
65 ma->phi = calloc(ma->M + 1, sizeof(double));
66 ma->z = calloc(2 * ma->n + 1, sizeof(double));
67 ma->zswap = calloc(2 * ma->n + 1, sizeof(double));
68 ma->afs = calloc(2 * ma->n + 1, sizeof(double));
69 ma->afs1 = calloc(2 * ma->n + 1, sizeof(double));
70 for (i = 0; i < 256; ++i)
71 ma->q2p[i] = pow(10., -i / 10.);
72 bcf_p1_init_prior(ma, MC_PTYPE_FULL, 1e-3); // the simplest prior
76 void bcf_p1_destroy(bcf_p1aux_t *ma)
79 free(ma->q2p); free(ma->pdg);
81 free(ma->z); free(ma->zswap);
82 free(ma->afs); free(ma->afs1);
87 #define char2int(s) (((int)s[0])<<8|s[1])
89 static int cal_pdg(const bcf1_t *b, bcf_p1aux_t *ma)
93 p = alloca(b->n_alleles * sizeof(long));
94 memset(p, 0, sizeof(long) * b->n_alleles);
95 for (j = 0; j < ma->n; ++j) {
96 const uint8_t *pi = ma->PL + j * ma->PL_len;
97 double *pdg = ma->pdg + j * 3;
98 pdg[0] = ma->q2p[pi[b->n_alleles]]; pdg[1] = ma->q2p[pi[1]]; pdg[2] = ma->q2p[pi[0]];
99 for (i = k = 0; i < b->n_alleles; ++i) {
101 k += b->n_alleles - i;
104 for (i = 0; i < b->n_alleles; ++i) p[i] = p[i]<<4 | i;
105 for (i = 1; i < b->n_alleles; ++i) // insertion sort
106 for (j = i; j > 0 && p[j] < p[j-1]; --j)
107 tmp = p[j], p[j] = p[j-1], p[j-1] = tmp;
108 for (i = b->n_alleles - 1; i >= 0; --i)
109 if ((p[i]&0xf) == 0) break;
112 // f0 is the reference allele frequency
113 static double mc_freq_iter(double f0, const bcf_p1aux_t *ma)
117 f3[0] = (1.-f0)*(1.-f0); f3[1] = 2.*f0*(1.-f0); f3[2] = f0*f0;
118 for (i = 0, f = 0.; i < ma->n; ++i) {
120 pdg = ma->pdg + i * 3;
121 f += (pdg[1] * f3[1] + 2. * pdg[2] * f3[2])
122 / (pdg[0] * f3[0] + pdg[1] * f3[1] + pdg[2] * f3[2]);
128 int bcf_p1_call_gt(const bcf_p1aux_t *ma, double f0, int k)
131 double max, f3[3], *pdg = ma->pdg + k * 3;
133 f3[0] = (1.-f0)*(1.-f0); f3[1] = 2.*f0*(1.-f0); f3[2] = f0*f0;
134 for (i = 0, sum = 0.; i < 3; ++i)
135 sum += (g[i] = pdg[i] * f3[i]);
136 for (i = 0, max = -1., max_i = 0; i < 3; ++i) {
138 if (g[i] > max) max = g[i], max_i = i;
141 if (max < 1e-308) max = 1e-308;
142 q = (int)(-3.434 * log(max) + .499);
149 static void mc_cal_y(bcf_p1aux_t *ma)
151 double *z[2], *tmp, *pdg;
152 int k, j, last_min, last_max;
156 memset(z[0], 0, sizeof(double) * (ma->M + 1));
157 memset(z[1], 0, sizeof(double) * (ma->M + 1));
159 last_min = last_max = 0;
160 for (j = 0; j < ma->n; ++j) {
161 int _min = last_min, _max = last_max;
163 pdg = ma->pdg + j * 3;
164 p[0] = pdg[0]; p[1] = 2. * pdg[1]; p[2] = pdg[2];
165 for (; _min < _max && z[0][_min] < TINY; ++_min) z[0][_min] = z[1][_min] = 0.;
166 for (; _max > _min && z[0][_max] < TINY; --_max) z[0][_max] = z[1][_max] = 0.;
169 k = 0, z[1][k] = (2*j+2-k)*(2*j-k+1) * p[0] * z[0][k];
171 k = 1, z[1][k] = (2*j+2-k)*(2*j-k+1) * p[0] * z[0][k] + k*(2*j+2-k) * p[1] * z[0][k-1];
172 for (k = _min < 2? 2 : _min; k <= _max; ++k)
173 z[1][k] = (2*j+2-k)*(2*j-k+1) * p[0] * z[0][k]
174 + k*(2*j+2-k) * p[1] * z[0][k-1]
175 + k*(k-1)* p[2] * z[0][k-2];
176 for (k = _min, sum = 0.; k <= _max; ++k) sum += z[1][k];
177 for (k = _min; k <= _max; ++k) z[1][k] /= sum;
178 if (_min >= 1) z[1][_min-1] = 0.;
179 if (_min >= 2) z[1][_min-2] = 0.;
180 if (j < ma->n - 1) z[1][_max+1] = z[1][_max+2] = 0.;
181 tmp = z[0]; z[0] = z[1]; z[1] = tmp;
182 last_min = _min; last_max = _max;
184 if (z[0] != ma->z) memcpy(ma->z, z[0], sizeof(double) * (ma->M + 1));
187 static double mc_cal_afs(bcf_p1aux_t *ma)
190 long double sum = 0.;
191 memset(ma->afs1, 0, sizeof(double) * (ma->M + 1));
193 for (k = 0, sum = 0.; k <= ma->M; ++k)
194 sum += (long double)ma->phi[k] * ma->z[k];
195 for (k = 0; k <= ma->M; ++k) {
196 ma->afs1[k] = ma->phi[k] * ma->z[k] / sum;
197 if (isnan(ma->afs1[k]) || isinf(ma->afs1[k])) return -1.;
199 for (k = 0, sum = 0.; k <= ma->M; ++k) {
200 ma->afs[k] += ma->afs1[k];
201 sum += k * ma->afs1[k];
206 static long double p1_cal_g3(bcf_p1aux_t *p1a, double g[3])
208 long double pd = 0., g2[3];
210 memset(g2, 0, sizeof(long double) * 3);
211 for (k = 0; k < p1a->M; ++k) {
212 double f = (double)k / p1a->M, f3[3], g1[3];
214 g1[0] = g1[1] = g1[2] = 0.;
215 f3[0] = (1. - f) * (1. - f); f3[1] = 2. * f * (1. - f); f3[2] = f * f;
216 for (i = 0; i < p1a->n; ++i) {
217 double *pdg = p1a->pdg + i * 3;
218 double x = pdg[0] * f3[0] + pdg[1] * f3[1] + pdg[2] * f3[2];
220 g1[0] += pdg[0] * f3[0] / x;
221 g1[1] += pdg[1] * f3[1] / x;
222 g1[2] += pdg[2] * f3[2] / x;
224 pd += p1a->phi[k] * z;
225 for (i = 0; i < 3; ++i)
226 g2[i] += p1a->phi[k] * z * g1[i];
228 for (i = 0; i < 3; ++i) g[i] = g2[i] / pd;
232 int bcf_p1_cal(bcf1_t *b, bcf_p1aux_t *ma, bcf_p1rst_t *rst)
235 long double sum = 0.;
237 for (i = 0; i < b->n_gi; ++i) {
238 if (b->gi[i].fmt == char2int("PL")) {
239 ma->PL = (uint8_t*)b->gi[i].data;
240 ma->PL_len = b->gi[i].len;
244 if (b->n_alleles < 2) return -1; // FIXME: find a better solution
246 rst->rank0 = cal_pdg(b, ma);
247 rst->f_exp = mc_cal_afs(ma);
248 rst->p_ref = ma->afs1[ma->M];
249 // calculate f_flat and f_em
250 for (k = 0, sum = 0.; k <= ma->M; ++k)
251 sum += (long double)ma->z[k];
253 for (k = 0; k <= ma->M; ++k) {
254 double p = ma->z[k] / sum;
255 rst->f_flat += k * p;
257 rst->f_flat /= ma->M;
259 double flast = rst->f_flat;
260 for (i = 0; i < MC_MAX_EM_ITER; ++i) {
261 rst->f_em = mc_freq_iter(flast, ma);
262 if (fabs(rst->f_em - flast) < MC_EM_EPS) break;
266 p1_cal_g3(ma, rst->g);
270 void bcf_p1_dump_afs(bcf_p1aux_t *ma)
273 fprintf(stderr, "[afs]");
274 for (k = 0; k <= ma->M; ++k)
275 fprintf(stderr, " %d:%.3lf", k, ma->afs[ma->M - k]);
276 fprintf(stderr, "\n");
277 memset(ma->afs, 0, sizeof(double) * (ma->M + 1));