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comparison PsiCLASS-1.0.2/samtools-0.1.19/bcftools/call1.c @ 0:903fc43d6227 draft default tip

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author lsong10
date Fri, 26 Mar 2021 16:52:45 +0000
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1 #include <unistd.h>
2 #include <stdlib.h>
3 #include <math.h>
4 #include <zlib.h>
5 #include <errno.h>
6 #include "bcf.h"
7 #include "prob1.h"
8 #include "kstring.h"
9 #include "time.h"
10
11 #ifdef _WIN32
12 #define srand48(x) srand(x)
13 #define lrand48() rand()
14 #endif
15
16 #include "kseq.h"
17 KSTREAM_INIT(gzFile, gzread, 16384)
18
19 #define VC_NO_GENO 2
20 #define VC_BCFOUT 4
21 #define VC_CALL 8
22 #define VC_VARONLY 16
23 #define VC_VCFIN 32
24 #define VC_UNCOMP 64
25 #define VC_KEEPALT 256
26 #define VC_ACGT_ONLY 512
27 #define VC_QCALL 1024
28 #define VC_CALL_GT 2048
29 #define VC_ADJLD 4096
30 #define VC_NO_INDEL 8192
31 #define VC_ANNO_MAX 16384
32 #define VC_FIX_PL 32768
33 #define VC_EM 0x10000
34 #define VC_PAIRCALL 0x20000
35 #define VC_QCNT 0x40000
36 #define VC_INDEL_ONLY 0x80000
37
38 typedef struct {
39 int flag, prior_type, n1, n_sub, *sublist, n_perm;
40 uint32_t *trio_aux;
41 char *prior_file, **subsam, *fn_dict;
42 uint8_t *ploidy;
43 double theta, pref, indel_frac, min_perm_p, min_smpl_frac, min_lrt, min_ma_lrt;
44 void *bed;
45 } viewconf_t;
46
47 void *bed_read(const char *fn);
48 void bed_destroy(void *_h);
49 int bed_overlap(const void *_h, const char *chr, int beg, int end);
50
51 static double ttest(int n1, int n2, int a[4])
52 {
53 extern double kf_betai(double a, double b, double x);
54 double t, v, u1, u2;
55 if (n1 == 0 || n2 == 0 || n1 + n2 < 3) return 1.0;
56 u1 = (double)a[0] / n1; u2 = (double)a[2] / n2;
57 if (u1 <= u2) return 1.;
58 t = (u1 - u2) / sqrt(((a[1] - n1 * u1 * u1) + (a[3] - n2 * u2 * u2)) / (n1 + n2 - 2) * (1./n1 + 1./n2));
59 v = n1 + n2 - 2;
60 // printf("%d,%d,%d,%d,%lf,%lf,%lf\n", a[0], a[1], a[2], a[3], t, u1, u2);
61 return t < 0.? 1. : .5 * kf_betai(.5*v, .5, v/(v+t*t));
62 }
63
64 static int test16_core(int anno[16], anno16_t *a)
65 {
66 extern double kt_fisher_exact(int n11, int n12, int n21, int n22, double *_left, double *_right, double *two);
67 double left, right;
68 int i;
69 a->p[0] = a->p[1] = a->p[2] = a->p[3] = 1.;
70 memcpy(a->d, anno, 4 * sizeof(int));
71 a->depth = anno[0] + anno[1] + anno[2] + anno[3];
72 a->is_tested = (anno[0] + anno[1] > 0 && anno[2] + anno[3] > 0);
73 if (a->depth == 0) return -1;
74 a->mq = (int)(sqrt((anno[9] + anno[11]) / a->depth) + .499);
75 kt_fisher_exact(anno[0], anno[1], anno[2], anno[3], &left, &right, &a->p[0]);
76 for (i = 1; i < 4; ++i)
77 a->p[i] = ttest(anno[0] + anno[1], anno[2] + anno[3], anno+4*i);
78 return 0;
79 }
80
81 int test16(bcf1_t *b, anno16_t *a)
82 {
83 char *p;
84 int i, anno[16];
85 a->p[0] = a->p[1] = a->p[2] = a->p[3] = 1.;
86 a->d[0] = a->d[1] = a->d[2] = a->d[3] = 0.;
87 a->mq = a->depth = a->is_tested = 0;
88 if ((p = strstr(b->info, "I16=")) == 0) return -1;
89 p += 4;
90 for (i = 0; i < 16; ++i) {
91 errno = 0; anno[i] = strtol(p, &p, 10);
92 if (anno[i] == 0 && (errno == EINVAL || errno == ERANGE)) return -2;
93 ++p;
94 }
95 return test16_core(anno, a);
96 }
97
98 static int update_bcf1(bcf1_t *b, const bcf_p1aux_t *pa, const bcf_p1rst_t *pr, double pref, int flag, double em[10], int cons_llr, int64_t cons_gt)
99 {
100 kstring_t s;
101 int has_I16, is_var;
102 double fq, r;
103 anno16_t a;
104
105 has_I16 = test16(b, &a) >= 0? 1 : 0;
106 //rm_info(b, "I16="); // FIXME: probably this function has a bug. If I move it below, I16 will not be removed!
107
108 memset(&s, 0, sizeof(kstring_t));
109 kputc('\0', &s); kputs(b->ref, &s); kputc('\0', &s);
110 kputs(b->alt, &s); kputc('\0', &s); kputc('\0', &s);
111 kputs(b->info, &s);
112 if (b->info[0]) kputc(';', &s);
113 { // print EM
114 if (em[0] >= 0) ksprintf(&s, "AF1=%.4g", 1 - em[0]);
115 if (em[4] >= 0 && em[4] <= 0.05) ksprintf(&s, ";G3=%.4g,%.4g,%.4g;HWE=%.3g", em[3], em[2], em[1], em[4]);
116 if (em[5] >= 0 && em[6] >= 0) ksprintf(&s, ";AF2=%.4g,%.4g", 1 - em[5], 1 - em[6]);
117 if (em[7] >= 0) ksprintf(&s, ";LRT=%.3g", em[7]);
118 if (em[8] >= 0) ksprintf(&s, ";LRT2=%.3g", em[8]);
119 }
120 if (cons_llr > 0) {
121 ksprintf(&s, ";CLR=%d", cons_llr);
122 if (cons_gt > 0)
123 ksprintf(&s, ";UGT=%c%c%c;CGT=%c%c%c", cons_gt&0xff, cons_gt>>8&0xff, cons_gt>>16&0xff,
124 cons_gt>>32&0xff, cons_gt>>40&0xff, cons_gt>>48&0xff);
125 }
126 if (pr == 0) { // if pr is unset, return
127 kputc('\0', &s); kputs(b->fmt, &s); kputc('\0', &s);
128 free(b->str);
129 b->m_str = s.m; b->l_str = s.l; b->str = s.s;
130 bcf_sync(b);
131 return 1;
132 }
133
134 is_var = (pr->p_ref < pref);
135 r = is_var? pr->p_ref : pr->p_var;
136
137 // ksprintf(&s, ";CI95=%.4g,%.4g", pr->cil, pr->cih); // FIXME: when EM is not used, ";" should be omitted!
138 ksprintf(&s, ";AC1=%d", pr->ac);
139 if (has_I16) ksprintf(&s, ";DP4=%d,%d,%d,%d;MQ=%d", a.d[0], a.d[1], a.d[2], a.d[3], a.mq);
140 fq = pr->p_ref_folded < 0.5? -4.343 * log(pr->p_ref_folded) : 4.343 * log(pr->p_var_folded);
141 if (fq < -999) fq = -999;
142 if (fq > 999) fq = 999;
143 ksprintf(&s, ";FQ=%.3g", fq);
144 if (pr->cmp[0] >= 0.) { // two sample groups
145 int i, q[3];
146 for (i = 1; i < 3; ++i) {
147 double x = pr->cmp[i] + pr->cmp[0]/2.;
148 q[i] = x == 0? 255 : (int)(-4.343 * log(x) + .499);
149 if (q[i] > 255) q[i] = 255;
150 }
151 if (pr->perm_rank >= 0) ksprintf(&s, ";PR=%d", pr->perm_rank);
152 // ksprintf(&s, ";LRT3=%.3g", pr->lrt);
153 ksprintf(&s, ";PCHI2=%.3g;PC2=%d,%d", q[1], q[2], pr->p_chi2);
154 }
155 if (has_I16 && a.is_tested) ksprintf(&s, ";PV4=%.2g,%.2g,%.2g,%.2g", a.p[0], a.p[1], a.p[2], a.p[3]);
156 kputc('\0', &s);
157 rm_info(&s, "QS=");
158 rm_info(&s, "I16=");
159 kputs(b->fmt, &s); kputc('\0', &s);
160 free(b->str);
161 b->m_str = s.m; b->l_str = s.l; b->str = s.s;
162 b->qual = r < 1e-100? 999 : -4.343 * log(r);
163 if (b->qual > 999) b->qual = 999;
164 bcf_sync(b);
165 if (!is_var) bcf_shrink_alt(b, 1);
166 else if (!(flag&VC_KEEPALT))
167 bcf_shrink_alt(b, pr->rank0 < 2? 2 : pr->rank0+1);
168 if (is_var && (flag&VC_CALL_GT)) { // call individual genotype
169 int i, x, old_n_gi = b->n_gi;
170 s.m = b->m_str; s.l = b->l_str - 1; s.s = b->str;
171 kputs(":GT:GQ", &s); kputc('\0', &s);
172 b->m_str = s.m; b->l_str = s.l; b->str = s.s;
173 bcf_sync(b);
174 for (i = 0; i < b->n_smpl; ++i) {
175 x = bcf_p1_call_gt(pa, pr->f_exp, i);
176 ((uint8_t*)b->gi[old_n_gi].data)[i] = (x&3) == 0? 1<<3|1 : (x&3) == 1? 1 : 0;
177 ((uint8_t*)b->gi[old_n_gi+1].data)[i] = x>>2;
178 }
179 }
180 return is_var;
181 }
182
183 static char **read_samples(const char *fn, int *_n)
184 {
185 gzFile fp;
186 kstream_t *ks;
187 kstring_t s;
188 int dret, n = 0, max = 0;
189 char **sam = 0;
190 *_n = 0;
191 s.l = s.m = 0; s.s = 0;
192 fp = gzopen(fn, "r");
193 if (fp == 0)
194 {
195 // interpret as sample names, not as a file name
196 const char *t = fn, *p = t;
197 while (*t)
198 {
199 t++;
200 if ( *t==',' || !*t )
201 {
202 sam = realloc(sam, sizeof(void*)*(n+1));
203 sam[n] = (char*) malloc(sizeof(char)*(t-p+2));
204 memcpy(sam[n], p, t-p);
205 sam[n][t-p] = 0;
206 sam[n][t-p+1] = 2; // assume diploid
207 p = t+1;
208 n++;
209 }
210 }
211 *_n = n;
212 return sam; // fail to open file
213 }
214 ks = ks_init(fp);
215 while (ks_getuntil(ks, 0, &s, &dret) >= 0) {
216 int l;
217 if (max == n) {
218 max = max? max<<1 : 4;
219 sam = realloc(sam, sizeof(void*)*max);
220 }
221 l = s.l;
222 sam[n] = malloc(s.l + 2);
223 strcpy(sam[n], s.s);
224 sam[n][l+1] = 2; // by default, diploid
225 if (dret != '\n') {
226 if (ks_getuntil(ks, 0, &s, &dret) >= 0) { // read ploidy, 1 or 2
227 int x = (int)s.s[0] - '0';
228 if (x == 1 || x == 2) sam[n][l+1] = x;
229 else fprintf(stderr, "(%s) ploidy can only be 1 or 2; assume diploid\n", __func__);
230 }
231 if (dret != '\n') ks_getuntil(ks, '\n', &s, &dret);
232 }
233 ++n;
234 }
235 ks_destroy(ks);
236 gzclose(fp);
237 free(s.s);
238 *_n = n;
239 return sam;
240 }
241
242 static void write_header(bcf_hdr_t *h)
243 {
244 kstring_t str;
245 str.l = h->l_txt? h->l_txt - 1 : 0;
246 str.m = str.l + 1; str.s = h->txt;
247 if (!strstr(str.s, "##INFO=<ID=DP,"))
248 kputs("##INFO=<ID=DP,Number=1,Type=Integer,Description=\"Raw read depth\">\n", &str);
249 if (!strstr(str.s, "##INFO=<ID=DP4,"))
250 kputs("##INFO=<ID=DP4,Number=4,Type=Integer,Description=\"# high-quality ref-forward bases, ref-reverse, alt-forward and alt-reverse bases\">\n", &str);
251 if (!strstr(str.s, "##INFO=<ID=MQ,"))
252 kputs("##INFO=<ID=MQ,Number=1,Type=Integer,Description=\"Root-mean-square mapping quality of covering reads\">\n", &str);
253 if (!strstr(str.s, "##INFO=<ID=FQ,"))
254 kputs("##INFO=<ID=FQ,Number=1,Type=Float,Description=\"Phred probability of all samples being the same\">\n", &str);
255 if (!strstr(str.s, "##INFO=<ID=AF1,"))
256 kputs("##INFO=<ID=AF1,Number=1,Type=Float,Description=\"Max-likelihood estimate of the first ALT allele frequency (assuming HWE)\">\n", &str);
257 if (!strstr(str.s, "##INFO=<ID=AC1,"))
258 kputs("##INFO=<ID=AC1,Number=1,Type=Float,Description=\"Max-likelihood estimate of the first ALT allele count (no HWE assumption)\">\n", &str);
259 if (!strstr(str.s, "##INFO=<ID=AN,"))
260 kputs("##INFO=<ID=AN,Number=1,Type=Integer,Description=\"Total number of alleles in called genotypes\">\n", &str);
261 if (!strstr(str.s, "##INFO=<ID=IS,"))
262 kputs("##INFO=<ID=IS,Number=2,Type=Float,Description=\"Maximum number of reads supporting an indel and fraction of indel reads\">\n", &str);
263 if (!strstr(str.s, "##INFO=<ID=AC,"))
264 kputs("##INFO=<ID=AC,Number=A,Type=Integer,Description=\"Allele count in genotypes for each ALT allele, in the same order as listed\">\n", &str);
265 if (!strstr(str.s, "##INFO=<ID=G3,"))
266 kputs("##INFO=<ID=G3,Number=3,Type=Float,Description=\"ML estimate of genotype frequencies\">\n", &str);
267 if (!strstr(str.s, "##INFO=<ID=HWE,"))
268 kputs("##INFO=<ID=HWE,Number=1,Type=Float,Description=\"Chi^2 based HWE test P-value based on G3\">\n", &str);
269 if (!strstr(str.s, "##INFO=<ID=CLR,"))
270 kputs("##INFO=<ID=CLR,Number=1,Type=Integer,Description=\"Log ratio of genotype likelihoods with and without the constraint\">\n", &str);
271 if (!strstr(str.s, "##INFO=<ID=UGT,"))
272 kputs("##INFO=<ID=UGT,Number=1,Type=String,Description=\"The most probable unconstrained genotype configuration in the trio\">\n", &str);
273 if (!strstr(str.s, "##INFO=<ID=CGT,"))
274 kputs("##INFO=<ID=CGT,Number=1,Type=String,Description=\"The most probable constrained genotype configuration in the trio\">\n", &str);
275 // if (!strstr(str.s, "##INFO=<ID=CI95,"))
276 // kputs("##INFO=<ID=CI95,Number=2,Type=Float,Description=\"Equal-tail Bayesian credible interval of the site allele frequency at the 95% level\">\n", &str);
277 if (!strstr(str.s, "##INFO=<ID=PV4,"))
278 kputs("##INFO=<ID=PV4,Number=4,Type=Float,Description=\"P-values for strand bias, baseQ bias, mapQ bias and tail distance bias\">\n", &str);
279 if (!strstr(str.s, "##INFO=<ID=INDEL,"))
280 kputs("##INFO=<ID=INDEL,Number=0,Type=Flag,Description=\"Indicates that the variant is an INDEL.\">\n", &str);
281 if (!strstr(str.s, "##INFO=<ID=PC2,"))
282 kputs("##INFO=<ID=PC2,Number=2,Type=Integer,Description=\"Phred probability of the nonRef allele frequency in group1 samples being larger (,smaller) than in group2.\">\n", &str);
283 if (!strstr(str.s, "##INFO=<ID=PCHI2,"))
284 kputs("##INFO=<ID=PCHI2,Number=1,Type=Float,Description=\"Posterior weighted chi^2 P-value for testing the association between group1 and group2 samples.\">\n", &str);
285 if (!strstr(str.s, "##INFO=<ID=QCHI2,"))
286 kputs("##INFO=<ID=QCHI2,Number=1,Type=Integer,Description=\"Phred scaled PCHI2.\">\n", &str);
287 if (!strstr(str.s, "##INFO=<ID=RP,"))
288 kputs("##INFO=<ID=PR,Number=1,Type=Integer,Description=\"# permutations yielding a smaller PCHI2.\">\n", &str);
289 if (!strstr(str.s, "##INFO=<ID=QBD,"))
290 kputs("##INFO=<ID=QBD,Number=1,Type=Float,Description=\"Quality by Depth: QUAL/#reads\">\n", &str);
291 //if (!strstr(str.s, "##INFO=<ID=RPS,"))
292 // kputs("##INFO=<ID=RPS,Number=3,Type=Float,Description=\"Read Position Stats: depth, average, stddev\">\n", &str);
293 if (!strstr(str.s, "##INFO=<ID=RPB,"))
294 kputs("##INFO=<ID=RPB,Number=1,Type=Float,Description=\"Read Position Bias\">\n", &str);
295 if (!strstr(str.s, "##INFO=<ID=MDV,"))
296 kputs("##INFO=<ID=MDV,Number=1,Type=Integer,Description=\"Maximum number of high-quality nonRef reads in samples\">\n", &str);
297 if (!strstr(str.s, "##INFO=<ID=VDB,"))
298 kputs("##INFO=<ID=VDB,Number=1,Type=Float,Description=\"Variant Distance Bias (v2) for filtering splice-site artefacts in RNA-seq data. Note: this version may be broken.\">\n", &str);
299 if (!strstr(str.s, "##FORMAT=<ID=GT,"))
300 kputs("##FORMAT=<ID=GT,Number=1,Type=String,Description=\"Genotype\">\n", &str);
301 if (!strstr(str.s, "##FORMAT=<ID=GQ,"))
302 kputs("##FORMAT=<ID=GQ,Number=1,Type=Integer,Description=\"Genotype Quality\">\n", &str);
303 if (!strstr(str.s, "##FORMAT=<ID=GL,"))
304 kputs("##FORMAT=<ID=GL,Number=3,Type=Float,Description=\"Likelihoods for RR,RA,AA genotypes (R=ref,A=alt)\">\n", &str);
305 if (!strstr(str.s, "##FORMAT=<ID=DP,"))
306 kputs("##FORMAT=<ID=DP,Number=1,Type=Integer,Description=\"# high-quality bases\">\n", &str);
307 if (!strstr(str.s, "##FORMAT=<ID=DV,"))
308 kputs("##FORMAT=<ID=DV,Number=1,Type=Integer,Description=\"# high-quality non-reference bases\">\n", &str);
309 if (!strstr(str.s, "##FORMAT=<ID=SP,"))
310 kputs("##FORMAT=<ID=SP,Number=1,Type=Integer,Description=\"Phred-scaled strand bias P-value\">\n", &str);
311 if (!strstr(str.s, "##FORMAT=<ID=PL,"))
312 kputs("##FORMAT=<ID=PL,Number=G,Type=Integer,Description=\"List of Phred-scaled genotype likelihoods\">\n", &str);
313 h->l_txt = str.l + 1; h->txt = str.s;
314 }
315
316 double bcf_pair_freq(const bcf1_t *b0, const bcf1_t *b1, double f[4]);
317
318 int bcfview(int argc, char *argv[])
319 {
320 extern int bcf_2qcall(bcf_hdr_t *h, bcf1_t *b);
321 extern void bcf_p1_indel_prior(bcf_p1aux_t *ma, double x);
322 extern int bcf_fix_gt(bcf1_t *b);
323 extern int bcf_anno_max(bcf1_t *b);
324 extern int bcf_shuffle(bcf1_t *b, int seed);
325 extern uint32_t *bcf_trio_prep(int is_x, int is_son);
326 extern int bcf_trio_call(uint32_t *prep, const bcf1_t *b, int *llr, int64_t *gt);
327 extern int bcf_pair_call(const bcf1_t *b);
328 extern int bcf_min_diff(const bcf1_t *b);
329 extern int bcf_p1_get_M(bcf_p1aux_t *b);
330
331 extern gzFile bcf_p1_fp_lk;
332
333 bcf_t *bp, *bout = 0;
334 bcf1_t *b, *blast;
335 int c, *seeds = 0;
336 uint64_t n_processed = 0, qcnt[256];
337 viewconf_t vc;
338 bcf_p1aux_t *p1 = 0;
339 bcf_hdr_t *hin, *hout;
340 int tid, begin, end;
341 char moder[4], modew[4];
342
343 tid = begin = end = -1;
344 memset(&vc, 0, sizeof(viewconf_t));
345 vc.prior_type = vc.n1 = -1; vc.theta = 1e-3; vc.pref = 0.5; vc.indel_frac = -1.; vc.n_perm = 0; vc.min_perm_p = 0.01; vc.min_smpl_frac = 0; vc.min_lrt = 1; vc.min_ma_lrt = -1;
346 memset(qcnt, 0, 8 * 256);
347 while ((c = getopt(argc, argv, "FN1:l:cC:eHAGvbSuP:t:p:QgLi:IMs:D:U:X:d:T:Ywm:K:")) >= 0) {
348 switch (c) {
349 case '1': vc.n1 = atoi(optarg); break;
350 case 'l': vc.bed = bed_read(optarg); if (!vc.bed) { fprintf(stderr,"Could not read \"%s\"\n", optarg); return 1; } break;
351 case 'D': vc.fn_dict = strdup(optarg); break;
352 case 'F': vc.flag |= VC_FIX_PL; break;
353 case 'N': vc.flag |= VC_ACGT_ONLY; break;
354 case 'G': vc.flag |= VC_NO_GENO; break;
355 case 'A': vc.flag |= VC_KEEPALT; break;
356 case 'b': vc.flag |= VC_BCFOUT; break;
357 case 'S': vc.flag |= VC_VCFIN; break;
358 case 'c': vc.flag |= VC_CALL; break;
359 case 'e': vc.flag |= VC_EM; break;
360 case 'v': vc.flag |= VC_VARONLY | VC_CALL; break;
361 case 'u': vc.flag |= VC_UNCOMP | VC_BCFOUT; break;
362 case 'g': vc.flag |= VC_CALL_GT | VC_CALL; break;
363 case 'I': vc.flag |= VC_NO_INDEL; break;
364 case 'w': vc.flag |= VC_INDEL_ONLY; break;
365 case 'M': vc.flag |= VC_ANNO_MAX; break;
366 case 'Y': vc.flag |= VC_QCNT; break;
367 case 'm': vc.min_ma_lrt = atof(optarg); break;
368 case 't': vc.theta = atof(optarg); break;
369 case 'p': vc.pref = atof(optarg); break;
370 case 'i': vc.indel_frac = atof(optarg); break;
371 case 'Q': vc.flag |= VC_QCALL; break;
372 case 'L': vc.flag |= VC_ADJLD; break;
373 case 'U': vc.n_perm = atoi(optarg); break;
374 case 'C': vc.min_lrt = atof(optarg); break;
375 case 'X': vc.min_perm_p = atof(optarg); break;
376 case 'd': vc.min_smpl_frac = atof(optarg); break;
377 case 'K': bcf_p1_fp_lk = gzopen(optarg, "w"); break;
378 case 's': vc.subsam = read_samples(optarg, &vc.n_sub);
379 vc.ploidy = calloc(vc.n_sub + 1, 1);
380 for (tid = 0; tid < vc.n_sub; ++tid) vc.ploidy[tid] = vc.subsam[tid][strlen(vc.subsam[tid]) + 1];
381 tid = -1;
382 break;
383 case 'T':
384 if (strcmp(optarg, "trioauto") == 0) vc.trio_aux = bcf_trio_prep(0, 0);
385 else if (strcmp(optarg, "trioxd") == 0) vc.trio_aux = bcf_trio_prep(1, 0);
386 else if (strcmp(optarg, "trioxs") == 0) vc.trio_aux = bcf_trio_prep(1, 1);
387 else if (strcmp(optarg, "pair") == 0) vc.flag |= VC_PAIRCALL;
388 else {
389 fprintf(stderr, "[%s] Option '-T' can only take value trioauto, trioxd or trioxs.\n", __func__);
390 return 1;
391 }
392 break;
393 case 'P':
394 if (strcmp(optarg, "full") == 0) vc.prior_type = MC_PTYPE_FULL;
395 else if (strcmp(optarg, "cond2") == 0) vc.prior_type = MC_PTYPE_COND2;
396 else if (strcmp(optarg, "flat") == 0) vc.prior_type = MC_PTYPE_FLAT;
397 else vc.prior_file = strdup(optarg);
398 break;
399 }
400 }
401 if (argc == optind) {
402 fprintf(stderr, "\n");
403 fprintf(stderr, "Usage: bcftools view [options] <in.bcf> [reg]\n\n");
404 fprintf(stderr, "Input/output options:\n\n");
405 fprintf(stderr, " -A keep all possible alternate alleles at variant sites\n");
406 fprintf(stderr, " -b output BCF instead of VCF\n");
407 fprintf(stderr, " -D FILE sequence dictionary for VCF->BCF conversion [null]\n");
408 fprintf(stderr, " -F PL generated by r921 or before (which generate old ordering)\n");
409 fprintf(stderr, " -G suppress all individual genotype information\n");
410 fprintf(stderr, " -l FILE list of sites (chr pos) or regions (BED) to output [all sites]\n");
411 fprintf(stderr, " -L calculate LD for adjacent sites\n");
412 fprintf(stderr, " -N skip sites where REF is not A/C/G/T\n");
413 fprintf(stderr, " -Q output the QCALL likelihood format\n");
414 fprintf(stderr, " -s FILE list of samples to use [all samples]\n");
415 fprintf(stderr, " -S input is VCF\n");
416 fprintf(stderr, " -u uncompressed BCF output (force -b)\n");
417 fprintf(stderr, "\nConsensus/variant calling options:\n\n");
418 fprintf(stderr, " -c SNP calling (force -e)\n");
419 fprintf(stderr, " -d FLOAT skip loci where less than FLOAT fraction of samples covered [0]\n");
420 fprintf(stderr, " -e likelihood based analyses\n");
421 fprintf(stderr, " -g call genotypes at variant sites (force -c)\n");
422 fprintf(stderr, " -i FLOAT indel-to-substitution ratio [%.4g]\n", vc.indel_frac);
423 fprintf(stderr, " -I skip indels\n");
424 fprintf(stderr, " -m FLOAT alternative model for multiallelic and rare-variant calling, include if P(chi^2)>=FLOAT\n");
425 fprintf(stderr, " -p FLOAT variant if P(ref|D)<FLOAT [%.3g]\n", vc.pref);
426 fprintf(stderr, " -P STR type of prior: full, cond2, flat [full]\n");
427 fprintf(stderr, " -t FLOAT scaled substitution mutation rate [%.4g]\n", vc.theta);
428 fprintf(stderr, " -T STR constrained calling; STR can be: pair, trioauto, trioxd and trioxs (see manual) [null]\n");
429 fprintf(stderr, " -v output potential variant sites only (force -c)\n");
430 fprintf(stderr, "\nContrast calling and association test options:\n\n");
431 fprintf(stderr, " -1 INT number of group-1 samples [0]\n");
432 fprintf(stderr, " -C FLOAT posterior constrast for LRT<FLOAT and P(ref|D)<0.5 [%g]\n", vc.min_lrt);
433 fprintf(stderr, " -U INT number of permutations for association testing (effective with -1) [0]\n");
434 fprintf(stderr, " -X FLOAT only perform permutations for P(chi^2)<FLOAT [%g]\n", vc.min_perm_p);
435 fprintf(stderr, "\n");
436 return 1;
437 }
438
439 if (vc.flag & VC_CALL) vc.flag |= VC_EM;
440 if ((vc.flag & VC_VCFIN) && (vc.flag & VC_BCFOUT) && vc.fn_dict == 0) {
441 fprintf(stderr, "[%s] For VCF->BCF conversion please specify the sequence dictionary with -D\n", __func__);
442 return 1;
443 }
444 if (vc.n1 <= 0) vc.n_perm = 0; // TODO: give a warning here!
445 if (vc.n_perm > 0) {
446 seeds = malloc(vc.n_perm * sizeof(int));
447 srand48(time(0));
448 for (c = 0; c < vc.n_perm; ++c) seeds[c] = lrand48();
449 }
450 b = calloc(1, sizeof(bcf1_t));
451 blast = calloc(1, sizeof(bcf1_t));
452 strcpy(moder, "r");
453 if (!(vc.flag & VC_VCFIN)) strcat(moder, "b");
454 strcpy(modew, "w");
455 if (vc.flag & VC_BCFOUT) strcat(modew, "b");
456 if (vc.flag & VC_UNCOMP) strcat(modew, "u");
457 bp = vcf_open(argv[optind], moder);
458 hin = hout = vcf_hdr_read(bp);
459 if (vc.fn_dict && (vc.flag & VC_VCFIN))
460 vcf_dictread(bp, hin, vc.fn_dict);
461 bout = vcf_open("-", modew);
462 if (!(vc.flag & VC_QCALL)) {
463 if (vc.n_sub) {
464 vc.sublist = calloc(vc.n_sub, sizeof(int));
465 hout = bcf_hdr_subsam(hin, vc.n_sub, vc.subsam, vc.sublist);
466 }
467 write_header(hout); // always print the header
468 vcf_hdr_write(bout, hout);
469 }
470 if (vc.flag & VC_CALL) {
471 p1 = bcf_p1_init(hout->n_smpl, vc.ploidy);
472 if (vc.prior_file) {
473 if (bcf_p1_read_prior(p1, vc.prior_file) < 0) {
474 fprintf(stderr, "[%s] fail to read the prior AFS.\n", __func__);
475 return 1;
476 }
477 } else bcf_p1_init_prior(p1, vc.prior_type, vc.theta);
478 if (vc.n1 > 0 && vc.min_lrt > 0.) { // set n1
479 bcf_p1_set_n1(p1, vc.n1);
480 bcf_p1_init_subprior(p1, vc.prior_type, vc.theta);
481 }
482 if (vc.indel_frac > 0.) bcf_p1_indel_prior(p1, vc.indel_frac); // otherwise use the default indel_frac
483 }
484 if (optind + 1 < argc && !(vc.flag&VC_VCFIN)) {
485 void *str2id = bcf_build_refhash(hout);
486 if (bcf_parse_region(str2id, argv[optind+1], &tid, &begin, &end) >= 0) {
487 bcf_idx_t *idx;
488 idx = bcf_idx_load(argv[optind]);
489 if (idx) {
490 uint64_t off;
491 off = bcf_idx_query(idx, tid, begin);
492 if (off == 0) {
493 fprintf(stderr, "[%s] no records in the query region.\n", __func__);
494 return 1; // FIXME: a lot of memory leaks...
495 }
496 bgzf_seek(bp->fp, off, SEEK_SET);
497 bcf_idx_destroy(idx);
498 }
499 }
500 }
501 if (bcf_p1_fp_lk && p1) {
502 int32_t M = bcf_p1_get_M(p1);
503 gzwrite(bcf_p1_fp_lk, &M, 4);
504 }
505 while (vcf_read(bp, hin, b) > 0) {
506 int is_indel, cons_llr = -1;
507 int64_t cons_gt = -1;
508 double em[10];
509 if ((vc.flag & VC_VARONLY) && strcmp(b->alt, "X") == 0) continue;
510 if ((vc.flag & VC_VARONLY) && vc.min_smpl_frac > 0.) {
511 extern int bcf_smpl_covered(const bcf1_t *b);
512 int n = bcf_smpl_covered(b);
513 if ((double)n / b->n_smpl < vc.min_smpl_frac) continue;
514 }
515 if (vc.n_sub) bcf_subsam(vc.n_sub, vc.sublist, b);
516 if (vc.flag & VC_FIX_PL) bcf_fix_pl(b);
517 is_indel = bcf_is_indel(b);
518 if ((vc.flag & VC_NO_INDEL) && is_indel) continue;
519 if ((vc.flag & VC_INDEL_ONLY) && !is_indel) continue;
520 if ((vc.flag & VC_ACGT_ONLY) && !is_indel) {
521 int x;
522 if (b->ref[0] == 0 || b->ref[1] != 0) continue;
523 x = toupper(b->ref[0]);
524 if (x != 'A' && x != 'C' && x != 'G' && x != 'T') continue;
525 }
526 if (vc.bed && !bed_overlap(vc.bed, hin->ns[b->tid], b->pos, b->pos + strlen(b->ref))) continue;
527 if (tid >= 0) {
528 int l = strlen(b->ref);
529 l = b->pos + (l > 0? l : 1);
530 if (b->tid != tid || b->pos >= end) break;
531 if (!(l > begin && end > b->pos)) continue;
532 }
533 ++n_processed;
534 if ((vc.flag & VC_QCNT) && !is_indel) { // summarize the difference
535 int x = bcf_min_diff(b);
536 if (x > 255) x = 255;
537 if (x >= 0) ++qcnt[x];
538 }
539 if (vc.flag & VC_QCALL) { // output QCALL format; STOP here
540 bcf_2qcall(hout, b);
541 continue;
542 }
543 if (vc.trio_aux) // do trio calling
544 bcf_trio_call(vc.trio_aux, b, &cons_llr, &cons_gt);
545 else if (vc.flag & VC_PAIRCALL)
546 cons_llr = bcf_pair_call(b);
547 if (vc.flag & (VC_CALL|VC_ADJLD|VC_EM)) bcf_gl2pl(b);
548 if (vc.flag & VC_EM) bcf_em1(b, vc.n1, 0x1ff, em);
549 else {
550 int i;
551 for (i = 0; i < 9; ++i) em[i] = -1.;
552 }
553 if ( !(vc.flag&VC_KEEPALT) && (vc.flag&VC_CALL) && vc.min_ma_lrt>=0 )
554 {
555 bcf_p1_set_ploidy(b, p1); // could be improved: do this per site to allow pseudo-autosomal regions
556 int gts = call_multiallelic_gt(b, p1, vc.min_ma_lrt, vc.flag&VC_VARONLY);
557 if ( gts<=1 && vc.flag & VC_VARONLY ) continue;
558 }
559 else if (vc.flag & VC_CALL) { // call variants
560 bcf_p1rst_t pr;
561 int calret;
562 gzwrite(bcf_p1_fp_lk, &b->tid, 4);
563 gzwrite(bcf_p1_fp_lk, &b->pos, 4);
564 gzwrite(bcf_p1_fp_lk, &em[0], sizeof(double));
565 calret = bcf_p1_cal(b, (em[7] >= 0 && em[7] < vc.min_lrt), p1, &pr);
566 if (n_processed % 100000 == 0) {
567 fprintf(stderr, "[%s] %ld sites processed.\n", __func__, (long)n_processed);
568 bcf_p1_dump_afs(p1);
569 }
570 if (pr.p_ref >= vc.pref && (vc.flag & VC_VARONLY)) continue;
571 if (vc.n_perm && vc.n1 > 0 && pr.p_chi2 < vc.min_perm_p) { // permutation test
572 bcf_p1rst_t r;
573 int i, n = 0;
574 for (i = 0; i < vc.n_perm; ++i) {
575 #ifdef BCF_PERM_LRT // LRT based permutation is much faster but less robust to artifacts
576 double x[10];
577 bcf_shuffle(b, seeds[i]);
578 bcf_em1(b, vc.n1, 1<<7, x);
579 if (x[7] < em[7]) ++n;
580 #else
581 bcf_shuffle(b, seeds[i]);
582 bcf_p1_cal(b, 1, p1, &r);
583 if (pr.p_chi2 >= r.p_chi2) ++n;
584 #endif
585 }
586 pr.perm_rank = n;
587 }
588 if (calret >= 0) update_bcf1(b, p1, &pr, vc.pref, vc.flag, em, cons_llr, cons_gt);
589 } else if (vc.flag & VC_EM) update_bcf1(b, 0, 0, 0, vc.flag, em, cons_llr, cons_gt);
590 if (vc.flag & VC_ADJLD) { // compute LD
591 double f[4], r2;
592 if ((r2 = bcf_pair_freq(blast, b, f)) >= 0) {
593 kstring_t s;
594 s.m = s.l = 0; s.s = 0;
595 if (*b->info) kputc(';', &s);
596 ksprintf(&s, "NEIR=%.3f;NEIF4=%.3f,%.3f,%.3f,%.3f", r2, f[0], f[1], f[2], f[3]);
597 bcf_append_info(b, s.s, s.l);
598 free(s.s);
599 }
600 bcf_cpy(blast, b);
601 }
602 if (vc.flag & VC_ANNO_MAX) bcf_anno_max(b);
603 if (vc.flag & VC_NO_GENO) { // do not output GENO fields
604 b->n_gi = 0;
605 b->fmt[0] = '\0';
606 b->l_str = b->fmt - b->str + 1;
607 } else bcf_fix_gt(b);
608 vcf_write(bout, hout, b);
609 }
610
611 if (bcf_p1_fp_lk) gzclose(bcf_p1_fp_lk);
612 if (vc.prior_file) free(vc.prior_file);
613 if (vc.flag & VC_CALL) bcf_p1_dump_afs(p1);
614 if (hin != hout) bcf_hdr_destroy(hout);
615 bcf_hdr_destroy(hin);
616 bcf_destroy(b); bcf_destroy(blast);
617 vcf_close(bp); vcf_close(bout);
618 if (vc.fn_dict) free(vc.fn_dict);
619 if (vc.ploidy) free(vc.ploidy);
620 if (vc.trio_aux) free(vc.trio_aux);
621 if (vc.n_sub) {
622 int i;
623 for (i = 0; i < vc.n_sub; ++i) free(vc.subsam[i]);
624 free(vc.subsam); free(vc.sublist);
625 }
626 if (vc.bed) bed_destroy(vc.bed);
627 if (vc.flag & VC_QCNT)
628 for (c = 0; c < 256; ++c)
629 fprintf(stderr, "QT\t%d\t%lld\n", c, (long long)qcnt[c]);
630 if (seeds) free(seeds);
631 if (p1) bcf_p1_destroy(p1);
632 return 0;
633 }