Logo Search packages:      
Sourcecode: samtools version File versions  Download package

call1.c

#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
#define VC_NO_INDEL 8192

typedef struct {
      int flag, prior_type, n1;
      char *fn_list, *prior_file;
      double theta, pref, indel_frac;
} 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=%.4lg;AFE=%.4lg;CI95=%.4lg,%.4lg", 1.-pr->f_em, 1.-pr->f_exp, pr->cil, pr->cih);
      ksprintf(&s, "AF1=%.4lg;CI95=%.4lg,%.4lg", 1.-pr->f_em, pr->cil, pr->cih);
      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);
      extern void bcf_p1_indel_prior(bcf_p1aux_t *ma, double x);
      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; vc.indel_frac = -1.;
      while ((c = getopt(argc, argv, "N1:l:cHAGvbSuP:t:p:QgLi:I")) >= 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 'I': vc.flag |= VC_NO_INDEL; break;
            case 't': vc.theta = atof(optarg); break;
            case 'p': vc.pref = atof(optarg); break;
            case 'i': vc.indel_frac = 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, "         -I        skip indels\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 substitution mutation rate [%.4lg]\n", vc.theta);
            fprintf(stderr, "         -i FLOAT  indel-to-substitution ratio [%.4lg]\n", vc.indel_frac);
            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.indel_frac > 0.) bcf_p1_indel_prior(p1, vc.indel_frac);
      }
      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) {
            int is_indel = bcf_is_indel(b);
            if ((vc.flag & VC_NO_INDEL) && is_indel) continue;
            if ((vc.flag & VC_ACGT_ONLY) && !is_indel) {
                  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;
}

Generated by  Doxygen 1.6.0   Back to index