X-Git-Url: http://woldlab.caltech.edu/gitweb/?p=samtools.git;a=blobdiff_plain;f=bcftools%2Fcall1.c;fp=bcftools%2Fcall1.c;h=2b284527185c0e12747ca1dfb5387aa0bd615c36;hp=0000000000000000000000000000000000000000;hb=8d2494d1fb7cd0fa7c63be5ffba8dd1a11457522;hpb=cb12a866906ec4ac644de0e658679261c82ab098 diff --git a/bcftools/call1.c b/bcftools/call1.c new file mode 100644 index 0000000..2b28452 --- /dev/null +++ b/bcftools/call1.c @@ -0,0 +1,372 @@ +#include +#include +#include +#include +#include +#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] [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)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; +}