--- /dev/null
+#include <unistd.h>
+#include <stdlib.h>
+#include <math.h>
+#include <zlib.h>
+#include <errno.h>
+#include "bcf.h"
+#include "prob1.h"
+#include "kstring.h"
+
+#include "khash.h"
+KHASH_SET_INIT_INT64(set64)
+
+#include "kseq.h"
+KSTREAM_INIT(gzFile, gzread, 16384)
+
+#define VC_NO_GENO 2
+#define VC_BCFOUT 4
+#define VC_CALL 8
+#define VC_VARONLY 16
+#define VC_VCFIN 32
+#define VC_UNCOMP 64
+#define VC_HWE 128
+#define VC_KEEPALT 256
+#define VC_ACGT_ONLY 512
+#define VC_QCALL 1024
+#define VC_CALL_GT 2048
+#define VC_ADJLD 4096
+
+typedef struct {
+ int flag, prior_type, n1;
+ char *fn_list, *prior_file;
+ double theta, pref;
+} viewconf_t;
+
+khash_t(set64) *bcf_load_pos(const char *fn, bcf_hdr_t *_h)
+{
+ void *str2id;
+ gzFile fp;
+ kstream_t *ks;
+ int ret, dret, lineno = 1;
+ kstring_t *str;
+ khash_t(set64) *hash = 0;
+
+ hash = kh_init(set64);
+ str2id = bcf_build_refhash(_h);
+ str = calloc(1, sizeof(kstring_t));
+ fp = strcmp(fn, "-")? gzopen(fn, "r") : gzdopen(fileno(stdin), "r");
+ ks = ks_init(fp);
+ while (ks_getuntil(ks, 0, str, &dret) >= 0) {
+ int tid = bcf_str2id(str2id, str->s);
+ if (tid >= 0 && dret != '\n') {
+ if (ks_getuntil(ks, 0, str, &dret) >= 0) {
+ uint64_t x = (uint64_t)tid<<32 | (atoi(str->s) - 1);
+ kh_put(set64, hash, x, &ret);
+ } else break;
+ } else fprintf(stderr, "[%s] %s is not a reference name (line %d).\n", __func__, str->s, lineno);
+ if (dret != '\n') while ((dret = ks_getc(ks)) > 0 && dret != '\n');
+ if (dret < 0) break;
+ ++lineno;
+ }
+ bcf_str2id_destroy(str2id);
+ ks_destroy(ks);
+ gzclose(fp);
+ free(str->s); free(str);
+ return hash;
+}
+
+static double test_hwe(const double g[3])
+{
+ extern double kf_gammaq(double p, double x);
+ double fexp, chi2, f[3], n;
+ int i;
+ n = g[0] + g[1] + g[2];
+ fexp = (2. * g[2] + g[1]) / (2. * n);
+ if (fexp > 1. - 1e-10) fexp = 1. - 1e-10;
+ if (fexp < 1e-10) fexp = 1e-10;
+ f[0] = n * (1. - fexp) * (1. - fexp);
+ f[1] = n * 2. * fexp * (1. - fexp);
+ f[2] = n * fexp * fexp;
+ for (i = 0, chi2 = 0.; i < 3; ++i)
+ chi2 += (g[i] - f[i]) * (g[i] - f[i]) / f[i];
+ return kf_gammaq(.5, chi2 / 2.);
+}
+
+typedef struct {
+ double p[4];
+ int mq, depth, is_tested, d[4];
+} anno16_t;
+
+static double ttest(int n1, int n2, int a[4])
+{
+ extern double kf_betai(double a, double b, double x);
+ double t, v, u1, u2;
+ if (n1 == 0 || n2 == 0 || n1 + n2 < 3) return 1.0;
+ u1 = (double)a[0] / n1; u2 = (double)a[2] / n2;
+ if (u1 <= u2) return 1.;
+ t = (u1 - u2) / sqrt(((a[1] - n1 * u1 * u1) + (a[3] - n2 * u2 * u2)) / (n1 + n2 - 2) * (1./n1 + 1./n2));
+ v = n1 + n2 - 2;
+// printf("%d,%d,%d,%d,%lf,%lf,%lf\n", a[0], a[1], a[2], a[3], t, u1, u2);
+ return t < 0.? 1. : .5 * kf_betai(.5*v, .5, v/(v+t*t));
+}
+
+static int test16_core(int anno[16], anno16_t *a)
+{
+ extern double kt_fisher_exact(int n11, int n12, int n21, int n22, double *_left, double *_right, double *two);
+ double left, right;
+ int i;
+ a->p[0] = a->p[1] = a->p[2] = a->p[3] = 1.;
+ memcpy(a->d, anno, 4 * sizeof(int));
+ a->depth = anno[0] + anno[1] + anno[2] + anno[3];
+ a->is_tested = (anno[0] + anno[1] > 0 && anno[2] + anno[3] > 0);
+ if (a->depth == 0) return -1;
+ a->mq = (int)(sqrt((anno[9] + anno[11]) / a->depth) + .499);
+ kt_fisher_exact(anno[0], anno[1], anno[2], anno[3], &left, &right, &a->p[0]);
+ for (i = 1; i < 4; ++i)
+ a->p[i] = ttest(anno[0] + anno[1], anno[2] + anno[3], anno+4*i);
+ return 0;
+}
+
+static int test16(bcf1_t *b, anno16_t *a)
+{
+ char *p;
+ int i, anno[16];
+ a->p[0] = a->p[1] = a->p[2] = a->p[3] = 1.;
+ a->d[0] = a->d[1] = a->d[2] = a->d[3] = 0.;
+ a->mq = a->depth = a->is_tested = 0;
+ if ((p = strstr(b->info, "I16=")) == 0) return -1;
+ p += 4;
+ for (i = 0; i < 16; ++i) {
+ anno[i] = strtol(p, &p, 10);
+ if (anno[i] == 0 && (errno == EINVAL || errno == ERANGE)) return -2;
+ ++p;
+ }
+ return test16_core(anno, a);
+}
+
+static void rm_info(bcf1_t *b, const char *key)
+{
+ char *p, *q;
+ if ((p = strstr(b->info, key)) == 0) return;
+ for (q = p; *q && *q != ';'; ++q);
+ if (p > b->info && *(p-1) == ';') --p;
+ memmove(p, q, b->l_str - (q - b->str));
+ b->l_str -= q - p;
+ bcf_sync(b);
+}
+
+static int update_bcf1(int n_smpl, bcf1_t *b, const bcf_p1aux_t *pa, const bcf_p1rst_t *pr, double pref, int flag)
+{
+ kstring_t s;
+ int is_var = (pr->p_ref < pref);
+ double p_hwe, r = is_var? pr->p_ref : 1. - pr->p_ref;
+ anno16_t a;
+
+ p_hwe = pr->g[0] >= 0.? test_hwe(pr->g) : 1.0; // only do HWE g[] is calculated
+ test16(b, &a);
+ rm_info(b, "I16=");
+
+ memset(&s, 0, sizeof(kstring_t));
+ kputc('\0', &s); kputs(b->ref, &s); kputc('\0', &s);
+ kputs(b->alt, &s); kputc('\0', &s); kputc('\0', &s);
+ kputs(b->info, &s);
+ if (b->info[0]) kputc(';', &s);
+ ksprintf(&s, "AF1=%.3lf;AFE=%.3lf", 1.-pr->f_em, 1.-pr->f_exp);
+ ksprintf(&s, ";DP4=%d,%d,%d,%d;MQ=%d", a.d[0], a.d[1], a.d[2], a.d[3], a.mq);
+ if (a.is_tested) {
+ if (pr->pc[0] >= 0.) ksprintf(&s, ";PC4=%lg,%lg,%lg,%lg", pr->pc[0], pr->pc[1], pr->pc[2], pr->pc[3]);
+ ksprintf(&s, ";PV4=%.2lg,%.2lg,%.2lg,%.2lg", a.p[0], a.p[1], a.p[2], a.p[3]);
+ }
+ if (pr->g[0] >= 0. && p_hwe <= .2)
+ ksprintf(&s, ";GC=%.2lf,%.2lf,%.2lf;HWE=%.3lf", pr->g[2], pr->g[1], pr->g[0], p_hwe);
+ kputc('\0', &s);
+ kputs(b->fmt, &s); kputc('\0', &s);
+ free(b->str);
+ b->m_str = s.m; b->l_str = s.l; b->str = s.s;
+ b->qual = r < 1e-100? 99 : -4.343 * log(r);
+ if (b->qual > 99) b->qual = 99;
+ bcf_sync(b);
+ if (!is_var) bcf_shrink_alt(b, 1);
+ else if (!(flag&VC_KEEPALT))
+ bcf_shrink_alt(b, pr->rank0 < 2? 2 : pr->rank0+1);
+ if (is_var && (flag&VC_CALL_GT)) { // call individual genotype
+ int i, x, old_n_gi = b->n_gi;
+ s.m = b->m_str; s.l = b->l_str - 1; s.s = b->str;
+ kputs(":GT:GQ", &s); kputc('\0', &s);
+ b->m_str = s.m; b->l_str = s.l; b->str = s.s;
+ bcf_sync(b);
+ for (i = 0; i < b->n_smpl; ++i) {
+ x = bcf_p1_call_gt(pa, pr->f_em, i);
+ ((uint8_t*)b->gi[old_n_gi].data)[i] = (x&3) == 0? 1<<3|1 : (x&3) == 1? 1 : 0;
+ ((uint8_t*)b->gi[old_n_gi+1].data)[i] = x>>2;
+ }
+ }
+ return is_var;
+}
+
+double bcf_ld_freq(const bcf1_t *b0, const bcf1_t *b1, double f[4]);
+
+int bcfview(int argc, char *argv[])
+{
+ extern int bcf_2qcall(bcf_hdr_t *h, bcf1_t *b);
+ bcf_t *bp, *bout = 0;
+ bcf1_t *b, *blast;
+ int c;
+ uint64_t n_processed = 0;
+ viewconf_t vc;
+ bcf_p1aux_t *p1 = 0;
+ bcf_hdr_t *h;
+ int tid, begin, end;
+ char moder[4], modew[4];
+ khash_t(set64) *hash = 0;
+
+ tid = begin = end = -1;
+ memset(&vc, 0, sizeof(viewconf_t));
+ vc.prior_type = vc.n1 = -1; vc.theta = 1e-3; vc.pref = 0.5;
+ while ((c = getopt(argc, argv, "N1:l:cHAGvbSuP:t:p:QgL")) >= 0) {
+ switch (c) {
+ case '1': vc.n1 = atoi(optarg); break;
+ case 'l': vc.fn_list = strdup(optarg); break;
+ case 'N': vc.flag |= VC_ACGT_ONLY; break;
+ case 'G': vc.flag |= VC_NO_GENO; break;
+ case 'A': vc.flag |= VC_KEEPALT; break;
+ case 'b': vc.flag |= VC_BCFOUT; break;
+ case 'S': vc.flag |= VC_VCFIN; break;
+ case 'c': vc.flag |= VC_CALL; break;
+ case 'v': vc.flag |= VC_VARONLY | VC_CALL; break;
+ case 'u': vc.flag |= VC_UNCOMP | VC_BCFOUT; break;
+ case 'H': vc.flag |= VC_HWE; break;
+ case 'g': vc.flag |= VC_CALL_GT | VC_CALL; break;
+ case 't': vc.theta = atof(optarg); break;
+ case 'p': vc.pref = atof(optarg); break;
+ case 'Q': vc.flag |= VC_QCALL; break;
+ case 'L': vc.flag |= VC_ADJLD; break;
+ case 'P':
+ if (strcmp(optarg, "full") == 0) vc.prior_type = MC_PTYPE_FULL;
+ else if (strcmp(optarg, "cond2") == 0) vc.prior_type = MC_PTYPE_COND2;
+ else if (strcmp(optarg, "flat") == 0) vc.prior_type = MC_PTYPE_FLAT;
+ else vc.prior_file = strdup(optarg);
+ break;
+ }
+ }
+ if (argc == optind) {
+ fprintf(stderr, "\n");
+ fprintf(stderr, "Usage: bcftools view [options] <in.bcf> [reg]\n\n");
+ fprintf(stderr, "Options: -c SNP calling\n");
+ fprintf(stderr, " -v output potential variant sites only (force -c)\n");
+ fprintf(stderr, " -g call genotypes at variant sites (force -c)\n");
+ fprintf(stderr, " -b output BCF instead of VCF\n");
+ fprintf(stderr, " -u uncompressed BCF output (force -b)\n");
+ fprintf(stderr, " -S input is VCF\n");
+ fprintf(stderr, " -A keep all possible alternate alleles at variant sites\n");
+ fprintf(stderr, " -G suppress all individual genotype information\n");
+ fprintf(stderr, " -H perform Hardy-Weinberg test (slower)\n");
+ fprintf(stderr, " -N skip sites where REF is not A/C/G/T\n");
+ fprintf(stderr, " -Q output the QCALL likelihood format\n");
+ fprintf(stderr, " -L calculate LD for adjacent sites\n");
+ fprintf(stderr, " -1 INT number of group-1 samples [0]\n");
+ fprintf(stderr, " -l FILE list of sites to output [all sites]\n");
+ fprintf(stderr, " -t FLOAT scaled mutation rate [%.4lg]\n", vc.theta);
+ fprintf(stderr, " -p FLOAT variant if P(ref|D)<FLOAT [%.3lg]\n", vc.pref);
+ fprintf(stderr, " -P STR type of prior: full, cond2, flat [full]\n");
+ fprintf(stderr, "\n");
+ return 1;
+ }
+
+ b = calloc(1, sizeof(bcf1_t));
+ blast = calloc(1, sizeof(bcf1_t));
+ strcpy(moder, "r");
+ if (!(vc.flag & VC_VCFIN)) strcat(moder, "b");
+ strcpy(modew, "w");
+ if (vc.flag & VC_BCFOUT) strcat(modew, "b");
+ if (vc.flag & VC_UNCOMP) strcat(modew, "u");
+ bp = vcf_open(argv[optind], moder);
+ h = vcf_hdr_read(bp);
+ bout = vcf_open("-", modew);
+ if (!(vc.flag & VC_QCALL)) vcf_hdr_write(bout, h);
+ if (vc.flag & VC_CALL) {
+ p1 = bcf_p1_init(h->n_smpl);
+ if (vc.prior_file) {
+ if (bcf_p1_read_prior(p1, vc.prior_file) < 0) {
+ fprintf(stderr, "[%s] fail to read the prior AFS.\n", __func__);
+ return 1;
+ }
+ } else bcf_p1_init_prior(p1, vc.prior_type, vc.theta);
+ if (vc.n1 > 0) {
+ bcf_p1_set_n1(p1, vc.n1);
+ bcf_p1_init_subprior(p1, vc.prior_type, vc.theta);
+ }
+ }
+ if (vc.fn_list) hash = bcf_load_pos(vc.fn_list, h);
+ if (optind + 1 < argc && !(vc.flag&VC_VCFIN)) {
+ void *str2id = bcf_build_refhash(h);
+ if (bcf_parse_region(str2id, argv[optind+1], &tid, &begin, &end) >= 0) {
+ bcf_idx_t *idx;
+ idx = bcf_idx_load(argv[optind]);
+ if (idx) {
+ uint64_t off;
+ off = bcf_idx_query(idx, tid, begin);
+ if (off == 0) {
+ fprintf(stderr, "[%s] no records in the query region.\n", __func__);
+ return 1; // FIXME: a lot of memory leaks...
+ }
+ bgzf_seek(bp->fp, off, SEEK_SET);
+ bcf_idx_destroy(idx);
+ }
+ }
+ }
+ while (vcf_read(bp, h, b) > 0) {
+ if (vc.flag & VC_ACGT_ONLY) {
+ int x;
+ if (b->ref[0] == 0 || b->ref[1] != 0) continue;
+ x = toupper(b->ref[0]);
+ if (x != 'A' && x != 'C' && x != 'G' && x != 'T') continue;
+ }
+ if (hash) {
+ uint64_t x = (uint64_t)b->tid<<32 | b->pos;
+ khint_t k = kh_get(set64, hash, x);
+ if (kh_size(hash) == 0) break;
+ if (k == kh_end(hash)) continue;
+ kh_del(set64, hash, k);
+ }
+ if (tid >= 0) {
+ int l = strlen(b->ref);
+ l = b->pos + (l > 0? l : 1);
+ if (b->tid != tid || b->pos >= end) break;
+ if (!(l > begin && end > b->pos)) continue;
+ }
+ ++n_processed;
+ if (vc.flag & VC_QCALL) { // output QCALL format; STOP here
+ bcf_2qcall(h, b);
+ continue;
+ }
+ if (vc.flag & (VC_CALL|VC_ADJLD)) bcf_gl2pl(b);
+ if (vc.flag & VC_CALL) { // call variants
+ bcf_p1rst_t pr;
+ bcf_p1_cal(b, p1, &pr); // pr.g[3] is not calculated here
+ if (vc.flag&VC_HWE) bcf_p1_cal_g3(p1, pr.g);
+ if (n_processed % 100000 == 0) {
+ fprintf(stderr, "[%s] %ld sites processed.\n", __func__, (long)n_processed);
+ bcf_p1_dump_afs(p1);
+ }
+ if (pr.p_ref >= vc.pref && (vc.flag & VC_VARONLY)) continue;
+ update_bcf1(h->n_smpl, b, p1, &pr, vc.pref, vc.flag);
+ }
+ if (vc.flag & VC_ADJLD) { // compute LD
+ double f[4], r2;
+ if ((r2 = bcf_ld_freq(blast, b, f)) >= 0) {
+ kstring_t s;
+ s.m = s.l = 0; s.s = 0;
+ if (*b->info) kputc(';', &s);
+ ksprintf(&s, "NEIR=%.3lf;NEIF=%.3lf,%.3lf", r2, f[0]+f[2], f[0]+f[1]);
+ bcf_append_info(b, s.s, s.l);
+ free(s.s);
+ }
+ bcf_cpy(blast, b);
+ }
+ if (vc.flag & VC_NO_GENO) { // do not output GENO fields
+ b->n_gi = 0;
+ b->fmt[0] = '\0';
+ }
+ vcf_write(bout, h, b);
+ }
+ if (vc.prior_file) free(vc.prior_file);
+ if (vc.flag & VC_CALL) bcf_p1_dump_afs(p1);
+ bcf_hdr_destroy(h);
+ bcf_destroy(b); bcf_destroy(blast);
+ vcf_close(bp); vcf_close(bout);
+ if (hash) kh_destroy(set64, hash);
+ if (vc.fn_list) free(vc.fn_list);
+ if (p1) bcf_p1_destroy(p1);
+ return 0;
+}
projects / samtools.git / blobdiff