9 KSTREAM_INIT(gzFile, gzread, 16384)
11 #define MC_AVG_ERR 0.007
12 #define MC_MAX_EM_ITER 16
13 #define MC_EM_EPS 1e-4
15 unsigned char seq_nt4_table[256] = {
16 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
17 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
18 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4 /*'-'*/, 4, 4,
19 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
20 4, 0, 4, 1, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4,
21 4, 4, 4, 4, 3, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
22 4, 0, 4, 1, 4, 4, 4, 2, 4, 4, 4, 4, 4, 4, 4, 4,
23 4, 4, 4, 4, 3, 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,
28 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
29 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
30 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4,
31 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4, 4
34 struct __bcf_p1aux_t {
36 double *q2p, *pdg; // pdg -> P(D|g)
38 double *z, *zswap; // aux for afs
39 double *afs, *afs1; // afs: accumulative AFS; afs1: site posterior distribution
40 const uint8_t *PL; // point to PL
44 void bcf_p1_init_prior(bcf_p1aux_t *ma, int type, double theta)
47 if (type == MC_PTYPE_COND2) {
48 for (i = 0; i <= ma->M; ++i)
49 ma->phi[i] = 2. * (i + 1) / (ma->M + 1) / (ma->M + 2);
50 } else if (type == MC_PTYPE_FLAT) {
51 for (i = 0; i <= ma->M; ++i)
52 ma->phi[i] = 1. / (ma->M + 1);
55 for (i = 0, sum = 0.; i < ma->M; ++i)
56 sum += (ma->phi[i] = theta / (ma->M - i));
57 ma->phi[ma->M] = 1. - sum;
61 int bcf_p1_read_prior(bcf_p1aux_t *ma, const char *fn)
68 memset(&s, 0, sizeof(kstring_t));
69 fp = strcmp(fn, "-")? gzopen(fn, "r") : gzdopen(fileno(stdin), "r");
71 memset(ma->phi, 0, sizeof(double) * (ma->M + 1));
72 while (ks_getuntil(ks, '\n', &s, &dret) >= 0) {
73 if (strstr(s.s, "[afs] ") == s.s) {
75 for (k = 0; k <= ma->M; ++k) {
78 x = strtol(p, &p, 10);
79 if (x != k && (errno == EINVAL || errno == ERANGE)) return -1;
82 if (y == 0. && (errno == EINVAL || errno == ERANGE)) return -1;
83 ma->phi[ma->M - k] += y;
90 for (sum = 0., k = 0; k <= ma->M; ++k) sum += ma->phi[k];
91 fprintf(stderr, "[prior]");
92 for (k = 0; k <= ma->M; ++k) ma->phi[k] /= sum;
93 for (k = 0; k <= ma->M; ++k) fprintf(stderr, " %d:%.3lg", k, ma->phi[ma->M - k]);
98 bcf_p1aux_t *bcf_p1_init(int n) // FIXME: assuming diploid
102 ma = calloc(1, sizeof(bcf_p1aux_t));
103 ma->n = n; ma->M = 2 * n;
104 ma->q2p = calloc(256, sizeof(double));
105 ma->pdg = calloc(3 * ma->n, sizeof(double));
106 ma->phi = calloc(ma->M + 1, sizeof(double));
107 ma->z = calloc(2 * ma->n + 1, sizeof(double));
108 ma->zswap = calloc(2 * ma->n + 1, sizeof(double));
109 ma->afs = calloc(2 * ma->n + 1, sizeof(double));
110 ma->afs1 = calloc(2 * ma->n + 1, sizeof(double));
111 for (i = 0; i < 256; ++i)
112 ma->q2p[i] = pow(10., -i / 10.);
113 bcf_p1_init_prior(ma, MC_PTYPE_FULL, 1e-3); // the simplest prior
117 void bcf_p1_destroy(bcf_p1aux_t *ma)
120 free(ma->q2p); free(ma->pdg);
122 free(ma->z); free(ma->zswap);
123 free(ma->afs); free(ma->afs1);
128 #define char2int(s) (((int)s[0])<<8|s[1])
130 static int cal_pdg(const bcf1_t *b, bcf_p1aux_t *ma)
134 p = alloca(b->n_alleles * sizeof(long));
135 memset(p, 0, sizeof(long) * b->n_alleles);
136 for (j = 0; j < ma->n; ++j) {
137 const uint8_t *pi = ma->PL + j * ma->PL_len;
138 double *pdg = ma->pdg + j * 3;
139 pdg[0] = ma->q2p[pi[b->n_alleles]]; pdg[1] = ma->q2p[pi[1]]; pdg[2] = ma->q2p[pi[0]];
140 for (i = k = 0; i < b->n_alleles; ++i) {
142 k += b->n_alleles - i;
145 for (i = 0; i < b->n_alleles; ++i) p[i] = p[i]<<4 | i;
146 for (i = 1; i < b->n_alleles; ++i) // insertion sort
147 for (j = i; j > 0 && p[j] < p[j-1]; --j)
148 tmp = p[j], p[j] = p[j-1], p[j-1] = tmp;
149 for (i = b->n_alleles - 1; i >= 0; --i)
150 if ((p[i]&0xf) == 0) break;
153 // f0 is the reference allele frequency
154 static double mc_freq_iter(double f0, const bcf_p1aux_t *ma)
158 f3[0] = (1.-f0)*(1.-f0); f3[1] = 2.*f0*(1.-f0); f3[2] = f0*f0;
159 for (i = 0, f = 0.; i < ma->n; ++i) {
161 pdg = ma->pdg + i * 3;
162 f += (pdg[1] * f3[1] + 2. * pdg[2] * f3[2])
163 / (pdg[0] * f3[0] + pdg[1] * f3[1] + pdg[2] * f3[2]);
169 int bcf_p1_call_gt(const bcf_p1aux_t *ma, double f0, int k)
172 double max, f3[3], *pdg = ma->pdg + k * 3;
174 f3[0] = (1.-f0)*(1.-f0); f3[1] = 2.*f0*(1.-f0); f3[2] = f0*f0;
175 for (i = 0, sum = 0.; i < 3; ++i)
176 sum += (g[i] = pdg[i] * f3[i]);
177 for (i = 0, max = -1., max_i = 0; i < 3; ++i) {
179 if (g[i] > max) max = g[i], max_i = i;
182 if (max < 1e-308) max = 1e-308;
183 q = (int)(-3.434 * log(max) + .499);
190 static void mc_cal_y(bcf_p1aux_t *ma)
192 double *z[2], *tmp, *pdg;
193 int k, j, last_min, last_max;
197 memset(z[0], 0, sizeof(double) * (ma->M + 1));
198 memset(z[1], 0, sizeof(double) * (ma->M + 1));
200 last_min = last_max = 0;
201 for (j = 0; j < ma->n; ++j) {
202 int _min = last_min, _max = last_max;
204 pdg = ma->pdg + j * 3;
205 p[0] = pdg[0]; p[1] = 2. * pdg[1]; p[2] = pdg[2];
206 for (; _min < _max && z[0][_min] < TINY; ++_min) z[0][_min] = z[1][_min] = 0.;
207 for (; _max > _min && z[0][_max] < TINY; --_max) z[0][_max] = z[1][_max] = 0.;
210 k = 0, z[1][k] = (2*j+2-k)*(2*j-k+1) * p[0] * z[0][k];
212 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];
213 for (k = _min < 2? 2 : _min; k <= _max; ++k)
214 z[1][k] = (2*j+2-k)*(2*j-k+1) * p[0] * z[0][k]
215 + k*(2*j+2-k) * p[1] * z[0][k-1]
216 + k*(k-1)* p[2] * z[0][k-2];
217 for (k = _min, sum = 0.; k <= _max; ++k) sum += z[1][k];
218 for (k = _min; k <= _max; ++k) z[1][k] /= sum;
219 if (_min >= 1) z[1][_min-1] = 0.;
220 if (_min >= 2) z[1][_min-2] = 0.;
221 if (j < ma->n - 1) z[1][_max+1] = z[1][_max+2] = 0.;
222 tmp = z[0]; z[0] = z[1]; z[1] = tmp;
223 last_min = _min; last_max = _max;
225 if (z[0] != ma->z) memcpy(ma->z, z[0], sizeof(double) * (ma->M + 1));
228 static double mc_cal_afs(bcf_p1aux_t *ma)
231 long double sum = 0.;
232 memset(ma->afs1, 0, sizeof(double) * (ma->M + 1));
234 for (k = 0, sum = 0.; k <= ma->M; ++k)
235 sum += (long double)ma->phi[k] * ma->z[k];
236 for (k = 0; k <= ma->M; ++k) {
237 ma->afs1[k] = ma->phi[k] * ma->z[k] / sum;
238 if (isnan(ma->afs1[k]) || isinf(ma->afs1[k])) return -1.;
240 for (k = 0, sum = 0.; k <= ma->M; ++k) {
241 ma->afs[k] += ma->afs1[k];
242 sum += k * ma->afs1[k];
247 static long double p1_cal_g3(bcf_p1aux_t *p1a, double g[3])
249 long double pd = 0., g2[3];
251 memset(g2, 0, sizeof(long double) * 3);
252 for (k = 0; k < p1a->M; ++k) {
253 double f = (double)k / p1a->M, f3[3], g1[3];
255 g1[0] = g1[1] = g1[2] = 0.;
256 f3[0] = (1. - f) * (1. - f); f3[1] = 2. * f * (1. - f); f3[2] = f * f;
257 for (i = 0; i < p1a->n; ++i) {
258 double *pdg = p1a->pdg + i * 3;
259 double x = pdg[0] * f3[0] + pdg[1] * f3[1] + pdg[2] * f3[2];
261 g1[0] += pdg[0] * f3[0] / x;
262 g1[1] += pdg[1] * f3[1] / x;
263 g1[2] += pdg[2] * f3[2] / x;
265 pd += p1a->phi[k] * z;
266 for (i = 0; i < 3; ++i)
267 g2[i] += p1a->phi[k] * z * g1[i];
269 for (i = 0; i < 3; ++i) g[i] = g2[i] / pd;
273 int bcf_p1_cal(bcf1_t *b, bcf_p1aux_t *ma, bcf_p1rst_t *rst)
276 long double sum = 0.;
278 for (i = 0; i < b->n_gi; ++i) {
279 if (b->gi[i].fmt == char2int("PL")) {
280 ma->PL = (uint8_t*)b->gi[i].data;
281 ma->PL_len = b->gi[i].len;
285 if (b->n_alleles < 2) return -1; // FIXME: find a better solution
287 rst->rank0 = cal_pdg(b, ma);
288 rst->f_exp = mc_cal_afs(ma);
289 rst->p_ref = ma->afs1[ma->M];
290 // calculate f_flat and f_em
291 for (k = 0, sum = 0.; k <= ma->M; ++k)
292 sum += (long double)ma->z[k];
294 for (k = 0; k <= ma->M; ++k) {
295 double p = ma->z[k] / sum;
296 rst->f_flat += k * p;
298 rst->f_flat /= ma->M;
300 double flast = rst->f_flat;
301 for (i = 0; i < MC_MAX_EM_ITER; ++i) {
302 rst->f_em = mc_freq_iter(flast, ma);
303 if (fabs(rst->f_em - flast) < MC_EM_EPS) break;
307 p1_cal_g3(ma, rst->g);
311 void bcf_p1_dump_afs(bcf_p1aux_t *ma)
314 fprintf(stderr, "[afs]");
315 for (k = 0; k <= ma->M; ++k)
316 fprintf(stderr, " %d:%.3lf", k, ma->afs[ma->M - k]);
317 fprintf(stderr, "\n");
318 memset(ma->afs, 0, sizeof(double) * (ma->M + 1));