11 KHASH_SET_INIT_INT64(set64)
14 KSTREAM_INIT(gzFile, gzread, 16384)
24 #define VC_KEEPALT 256
27 int flag, prior_type, n1;
28 char *fn_list, *prior_file;
32 khash_t(set64) *bcf_load_pos(const char *fn, bcf_hdr_t *_h)
37 int ret, dret, lineno = 1;
39 khash_t(set64) *hash = 0;
41 hash = kh_init(set64);
42 str2id = bcf_build_refhash(_h);
43 str = calloc(1, sizeof(kstring_t));
44 fp = strcmp(fn, "-")? gzopen(fn, "r") : gzdopen(fileno(stdin), "r");
46 while (ks_getuntil(ks, 0, str, &dret) >= 0) {
47 int tid = bcf_str2id(str2id, str->s);
48 if (tid >= 0 && dret != '\n') {
49 if (ks_getuntil(ks, 0, str, &dret) >= 0) {
50 uint64_t x = (uint64_t)tid<<32 | (atoi(str->s) - 1);
51 kh_put(set64, hash, x, &ret);
53 } else fprintf(stderr, "[%s] %s is not a reference name (line %d).\n", __func__, str->s, lineno);
54 if (dret != '\n') while ((dret = ks_getc(ks)) > 0 && dret != '\n');
58 bcf_str2id_destroy(str2id);
61 free(str->s); free(str);
65 static double test_hwe(const double g[3])
67 extern double kf_gammaq(double p, double x);
68 double fexp, chi2, f[3], n;
70 n = g[0] + g[1] + g[2];
71 fexp = (2. * g[2] + g[1]) / (2. * n);
72 if (fexp > 1. - 1e-10) fexp = 1. - 1e-10;
73 if (fexp < 1e-10) fexp = 1e-10;
74 f[0] = n * (1. - fexp) * (1. - fexp);
75 f[1] = n * 2. * fexp * (1. - fexp);
76 f[2] = n * fexp * fexp;
77 for (i = 0, chi2 = 0.; i < 3; ++i)
78 chi2 += (g[i] - f[i]) * (g[i] - f[i]) / f[i];
79 return kf_gammaq(.5, chi2 / 2.);
84 int mq, depth, is_tested, d[4];
87 static double ttest(int n1, int n2, int a[4])
89 extern double kf_betai(double a, double b, double x);
91 if (n1 == 0 || n2 == 0 || n1 + n2 < 3) return 1.0;
92 u1 = (double)a[0] / n1; u2 = (double)a[2] / n2;
93 if (u1 <= u2) return 1.;
94 t = (u1 - u2) / sqrt(((a[1] - n1 * u1 * u1) + (a[3] - n2 * u2 * u2)) / (n1 + n2 - 2) * (1./n1 + 1./n2));
96 // printf("%d,%d,%d,%d,%lf,%lf,%lf\n", a[0], a[1], a[2], a[3], t, u1, u2);
97 return t < 0.? 1. : .5 * kf_betai(.5*v, .5, v/(v+t*t));
100 static int test16_core(int anno[16], anno16_t *a)
102 extern double kt_fisher_exact(int n11, int n12, int n21, int n22, double *_left, double *_right, double *two);
105 a->p[0] = a->p[1] = a->p[2] = a->p[3] = 1.;
106 memcpy(a->d, anno, 4 * sizeof(int));
107 a->depth = anno[0] + anno[1] + anno[2] + anno[3];
108 a->is_tested = (anno[0] + anno[1] > 0 && anno[2] + anno[3] > 0);
109 if (a->depth == 0) return -1;
110 a->mq = (int)(sqrt((anno[9] + anno[11]) / a->depth) + .499);
111 kt_fisher_exact(anno[0], anno[1], anno[2], anno[3], &left, &right, &a->p[0]);
112 for (i = 1; i < 4; ++i)
113 a->p[i] = ttest(anno[0] + anno[1], anno[2] + anno[3], anno+4*i);
117 static int test16(bcf1_t *b, anno16_t *a)
121 a->p[0] = a->p[1] = a->p[2] = a->p[3] = 1.;
122 a->d[0] = a->d[1] = a->d[2] = a->d[3] = 0.;
123 a->mq = a->depth = a->is_tested = 0;
124 if ((p = strstr(b->info, "I16=")) == 0) return -1;
126 for (i = 0; i < 16; ++i) {
127 anno[i] = strtol(p, &p, 10);
128 if (anno[i] == 0 && (errno == EINVAL || errno == ERANGE)) return -2;
131 return test16_core(anno, a);
134 static void rm_info(int n_smpl, bcf1_t *b, const char *key)
137 if ((p = strstr(b->info, key)) == 0) return;
138 for (q = p; *q && *q != ';'; ++q);
139 if (p > b->info && *(p-1) == ';') --p;
140 memmove(p, q, b->l_str - (q - b->str));
145 static int update_bcf1(int n_smpl, bcf1_t *b, const bcf_p1aux_t *pa, const bcf_p1rst_t *pr, double pref, int flag)
148 int is_var = (pr->p_ref < pref);
149 double p_hwe, r = is_var? pr->p_ref : 1. - pr->p_ref;
152 p_hwe = pr->g[0] >= 0.? test_hwe(pr->g) : 1.0; // only do HWE g[] is calculated
154 rm_info(n_smpl, b, "I16=");
156 memset(&s, 0, sizeof(kstring_t));
157 kputc('\0', &s); kputs(b->ref, &s); kputc('\0', &s);
158 kputs(b->alt, &s); kputc('\0', &s); kputc('\0', &s);
160 if (b->info[0]) kputc(';', &s);
161 ksprintf(&s, "AF1=%.3lf;AFE=%.3lf", 1.-pr->f_em, 1.-pr->f_exp);
162 ksprintf(&s, ";DP4=%d,%d,%d,%d;MQ=%d", a.d[0], a.d[1], a.d[2], a.d[3], a.mq);
164 if (pr->pc[0] >= 0.) ksprintf(&s, ";PC4=%lg,%lg,%lg,%lg", pr->pc[0], pr->pc[1], pr->pc[2], pr->pc[3]);
165 ksprintf(&s, ";PV4=%.2lg,%.2lg,%.2lg,%.2lg", a.p[0], a.p[1], a.p[2], a.p[3]);
167 if (pr->g[0] >= 0. && p_hwe <= .2)
168 ksprintf(&s, ";GC=%.2lf,%.2lf,%.2lf;HWE=%.3lf", pr->g[2], pr->g[1], pr->g[0], p_hwe);
170 kputs(b->fmt, &s); kputc('\0', &s);
172 b->m_str = s.m; b->l_str = s.l; b->str = s.s;
173 b->qual = r < 1e-100? 99 : -4.343 * log(r);
174 if (b->qual > 99) b->qual = 99;
176 if (!is_var) bcf_shrink_alt(n_smpl, b, 1);
177 else if (!(flag&VC_KEEPALT))
178 bcf_shrink_alt(n_smpl, b, pr->rank0 < 2? 2 : pr->rank0+1);
182 int bcfview(int argc, char *argv[])
184 bcf_t *bp, *bout = 0;
187 uint64_t n_processed = 0;
192 char moder[4], modew[4];
193 khash_t(set64) *hash = 0;
195 tid = begin = end = -1;
196 memset(&vc, 0, sizeof(viewconf_t));
197 vc.prior_type = vc.n1 = -1; vc.theta = 1e-3; vc.pref = 0.5;
198 while ((c = getopt(argc, argv, "1:l:cHAGvLbSuP:t:p:")) >= 0) {
200 case '1': vc.n1 = atoi(optarg); break;
201 case 'l': vc.fn_list = strdup(optarg); break;
202 case 'G': vc.flag |= VC_NO_GENO; break;
203 case 'L': vc.flag |= VC_NO_PL; break;
204 case 'A': vc.flag |= VC_KEEPALT; break;
205 case 'b': vc.flag |= VC_BCFOUT; break;
206 case 'S': vc.flag |= VC_VCFIN; break;
207 case 'c': vc.flag |= VC_CALL; break;
208 case 'v': vc.flag |= VC_VARONLY; break;
209 case 'u': vc.flag |= VC_UNCOMP | VC_BCFOUT; break;
210 case 'H': vc.flag |= VC_HWE; break;
211 case 't': vc.theta = atof(optarg); break;
212 case 'p': vc.pref = atof(optarg); break;
214 if (strcmp(optarg, "full") == 0) vc.prior_type = MC_PTYPE_FULL;
215 else if (strcmp(optarg, "cond2") == 0) vc.prior_type = MC_PTYPE_COND2;
216 else if (strcmp(optarg, "flat") == 0) vc.prior_type = MC_PTYPE_FLAT;
217 else vc.prior_file = strdup(optarg);
221 if (argc == optind) {
222 fprintf(stderr, "\n");
223 fprintf(stderr, "Usage: bcftools view [options] <in.bcf> [reg]\n\n");
224 fprintf(stderr, "Options: -c SNP calling\n");
225 fprintf(stderr, " -b output BCF instead of VCF\n");
226 fprintf(stderr, " -u uncompressed BCF output\n");
227 fprintf(stderr, " -S input is VCF\n");
228 fprintf(stderr, " -A keep all possible alternate alleles at variant sites\n");
229 fprintf(stderr, " -G suppress all individual genotype information\n");
230 fprintf(stderr, " -L discard the PL genotype field\n");
231 fprintf(stderr, " -H perform Hardy-Weinberg test (slower)\n");
232 fprintf(stderr, " -v output potential variant sites only\n");
233 fprintf(stderr, " -1 INT number of group-1 samples [0]\n");
234 fprintf(stderr, " -l FILE list of sites to output [all sites]\n");
235 fprintf(stderr, " -t FLOAT scaled mutation rate [%.4lg]\n", vc.theta);
236 fprintf(stderr, " -p FLOAT variant if P(ref|D)<FLOAT [%.3lg]\n", vc.pref);
237 fprintf(stderr, " -P STR type of prior: full, cond2, flat [full]\n");
238 fprintf(stderr, "\n");
242 b = calloc(1, sizeof(bcf1_t));
244 if (!(vc.flag & VC_VCFIN)) strcat(moder, "b");
246 if (vc.flag & VC_BCFOUT) strcat(modew, "b");
247 if (vc.flag & VC_UNCOMP) strcat(modew, "u");
248 bp = vcf_open(argv[optind], moder);
249 h = vcf_hdr_read(bp);
250 bout = vcf_open("-", modew);
251 vcf_hdr_write(bout, h);
252 if (vc.flag & VC_CALL) {
253 p1 = bcf_p1_init(h->n_smpl);
255 if (bcf_p1_read_prior(p1, vc.prior_file) < 0) {
256 fprintf(stderr, "[%s] fail to read the prior AFS.\n", __func__);
259 } else bcf_p1_init_prior(p1, vc.prior_type, vc.theta);
261 bcf_p1_set_n1(p1, vc.n1);
262 bcf_p1_init_subprior(p1, vc.prior_type, vc.theta);
265 if (vc.fn_list) hash = bcf_load_pos(vc.fn_list, h);
266 if (optind + 1 < argc && !(vc.flag&VC_VCFIN)) {
267 void *str2id = bcf_build_refhash(h);
268 if (bcf_parse_region(str2id, argv[optind+1], &tid, &begin, &end) >= 0) {
270 idx = bcf_idx_load(argv[optind]);
273 off = bcf_idx_query(idx, tid, begin, end);
274 bgzf_seek(bp->fp, off, SEEK_SET);
275 bcf_idx_destroy(idx);
279 while (vcf_read(bp, h, b) > 0) {
281 uint64_t x = (uint64_t)b->tid<<32 | b->pos;
282 khint_t k = kh_get(set64, hash, x);
283 if (kh_size(hash) == 0) break;
284 if (k == kh_end(hash)) continue;
285 kh_del(set64, hash, k);
288 int l = strlen(b->ref);
289 l = b->pos + (l > 0? l : 1);
290 if (b->tid != tid || b->pos >= end) break;
291 if (!(l > begin && end > b->pos)) continue;
294 if (vc.flag & VC_CALL) {
296 bcf_gl2pl(h->n_smpl, b);
297 bcf_p1_cal(b, p1, &pr); // pr.g[3] is not calculated here
298 if (vc.flag&VC_HWE) bcf_p1_cal_g3(p1, pr.g);
299 if (n_processed % 100000 == 0) {
300 fprintf(stderr, "[%s] %ld sites processed.\n", __func__, (long)n_processed);
303 if (pr.p_ref >= vc.pref && (vc.flag & VC_VARONLY)) continue;
304 update_bcf1(h->n_smpl, b, p1, &pr, vc.pref, vc.flag);
306 if (vc.flag & VC_NO_GENO) {
310 vcf_write(bout, h, b);
312 if (vc.prior_file) free(vc.prior_file);
313 if (vc.flag & VC_CALL) bcf_p1_dump_afs(p1);
316 vcf_close(bp); vcf_close(bout);
317 if (hash) kh_destroy(set64, hash);
318 if (vc.fn_list) free(vc.fn_list);
319 if (p1) bcf_p1_destroy(p1);