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bam2bcf.c

#include <math.h>
#include <stdint.h>
#include "bam.h"
#include "kstring.h"
#include "bam2bcf.h"
#include "errmod.h"
#include "bcftools/bcf.h"

extern      void ks_introsort_uint32_t(size_t n, uint32_t a[]);

#define CALL_ETA 0.03f
#define CALL_MAX 256
#define CALL_DEFTHETA 0.83f

#define CAP_DIST 25

bcf_callaux_t *bcf_call_init(double theta, int min_baseQ)
{
      bcf_callaux_t *bca;
      if (theta <= 0.) theta = CALL_DEFTHETA;
      bca = calloc(1, sizeof(bcf_callaux_t));
      bca->capQ = 60;
      bca->openQ = 40; bca->extQ = 20; bca->tandemQ = 100;
      bca->min_baseQ = min_baseQ;
      bca->e = errmod_init(1. - theta);
      return bca;
}

void bcf_call_destroy(bcf_callaux_t *bca)
{
      if (bca == 0) return;
      errmod_destroy(bca->e);
      free(bca->bases); free(bca->inscns); free(bca);
}
/* ref_base is the 4-bit representation of the reference base. It is
 * negative if we are looking at an indel. */
int bcf_call_glfgen(int _n, const bam_pileup1_t *pl, int ref_base, bcf_callaux_t *bca, bcf_callret1_t *r)
{
      int i, n, ref4, is_indel, ori_depth = 0;
      memset(r, 0, sizeof(bcf_callret1_t));
      if (ref_base >= 0) {
            ref4 = bam_nt16_nt4_table[ref_base];
            is_indel = 0;
      } else ref4 = 4, is_indel = 1;
      if (_n == 0) return -1;
      // enlarge the bases array if necessary
      if (bca->max_bases < _n) {
            bca->max_bases = _n;
            kroundup32(bca->max_bases);
            bca->bases = (uint16_t*)realloc(bca->bases, 2 * bca->max_bases);
      }
      // fill the bases array
      memset(r, 0, sizeof(bcf_callret1_t));
      for (i = n = 0; i < _n; ++i) {
            const bam_pileup1_t *p = pl + i;
            int q, b, mapQ, baseQ, is_diff, min_dist, seqQ;
            // set base
            if (p->is_del || p->is_refskip || (p->b->core.flag&BAM_FUNMAP)) continue;
            ++ori_depth;
            baseQ = q = is_indel? p->aux&0xff : (int)bam1_qual(p->b)[p->qpos]; // base/indel quality
            seqQ = is_indel? (p->aux>>8&0xff) : 99;
            if (q < bca->min_baseQ) continue;
            if (q > seqQ) q = seqQ;
            mapQ = p->b->core.qual < bca->capQ? p->b->core.qual : bca->capQ;
            if (q > mapQ) q = mapQ;
            if (q > 63) q = 63;
            if (q < 4) q = 4;
            if (!is_indel) {
                  b = bam1_seqi(bam1_seq(p->b), p->qpos); // base
                  b = bam_nt16_nt4_table[b? b : ref_base]; // b is the 2-bit base
                  is_diff = (ref4 < 4 && b == ref4)? 0 : 1;
            } else {
                  b = p->aux>>16&0x3f;
                  is_diff = (b != 0);
            }
            bca->bases[n++] = q<<5 | (int)bam1_strand(p->b)<<4 | b;
            // collect annotations
            r->qsum[b] += q;
            ++r->anno[0<<2|is_diff<<1|bam1_strand(p->b)];
            min_dist = p->b->core.l_qseq - 1 - p->qpos;
            if (min_dist > p->qpos) min_dist = p->qpos;
            if (min_dist > CAP_DIST) min_dist = CAP_DIST;
            r->anno[1<<2|is_diff<<1|0] += baseQ;
            r->anno[1<<2|is_diff<<1|1] += baseQ * baseQ;
            r->anno[2<<2|is_diff<<1|0] += mapQ;
            r->anno[2<<2|is_diff<<1|1] += mapQ * mapQ;
            r->anno[3<<2|is_diff<<1|0] += min_dist;
            r->anno[3<<2|is_diff<<1|1] += min_dist * min_dist;
      }
      r->depth = n; r->ori_depth = ori_depth;
      // glfgen
      errmod_cal(bca->e, n, 5, bca->bases, r->p);
      return r->depth;
}

int bcf_call_combine(int n, const bcf_callret1_t *calls, int ref_base /*4-bit*/, bcf_call_t *call)
{
      int ref4, i, j, qsum[4];
      int64_t tmp;
      if (ref_base >= 0) {
            call->ori_ref = ref4 = bam_nt16_nt4_table[ref_base];
            if (ref4 > 4) ref4 = 4;
      } else call->ori_ref = -1, ref4 = 0;
      // calculate qsum
      memset(qsum, 0, 4 * sizeof(int));
      for (i = 0; i < n; ++i)
            for (j = 0; j < 4; ++j)
                  qsum[j] += calls[i].qsum[j];
      for (j = 0; j < 4; ++j) qsum[j] = qsum[j] << 2 | j;
      // find the top 2 alleles
      for (i = 1; i < 4; ++i) // insertion sort
            for (j = i; j > 0 && qsum[j] < qsum[j-1]; --j)
                  tmp = qsum[j], qsum[j] = qsum[j-1], qsum[j-1] = tmp;
      // set the reference allele and alternative allele(s)
      for (i = 0; i < 5; ++i) call->a[i] = -1;
      call->unseen = -1;
      call->a[0] = ref4;
      for (i = 3, j = 1; i >= 0; --i) {
            if ((qsum[i]&3) != ref4) {
                  if (qsum[i]>>2 != 0) call->a[j++] = qsum[i]&3;
                  else break;
            }
      }
      if (ref_base >= 0) { // for SNPs, find the "unseen" base
            if (((ref4 < 4 && j < 4) || (ref4 == 4 && j < 5)) && i >= 0)
                  call->unseen = j, call->a[j++] = qsum[i]&3;
            call->n_alleles = j;
      } else {
            call->n_alleles = j;
            if (call->n_alleles == 1) return -1; // no reliable supporting read. stop doing anything
      }
      // set the PL array
      if (call->n < n) {
            call->n = n;
            call->PL = realloc(call->PL, 15 * n);
      }
      {
            int x, g[15], z;
            double sum_min = 0.;
            x = call->n_alleles * (call->n_alleles + 1) / 2;
            // get the possible genotypes
            for (i = z = 0; i < call->n_alleles; ++i)
                  for (j = i; j < call->n_alleles; ++j)
                        g[z++] = call->a[i] * 5 + call->a[j];
            for (i = 0; i < n; ++i) {
                  uint8_t *PL = call->PL + x * i;
                  const bcf_callret1_t *r = calls + i;
                  float min = 1e37;
                  for (j = 0; j < x; ++j)
                        if (min > r->p[g[j]]) min = r->p[g[j]];
                  sum_min += min;
                  for (j = 0; j < x; ++j) {
                        int y;
                        y = (int)(r->p[g[j]] - min + .499);
                        if (y > 255) y = 255;
                        PL[j] = y;
                  }
            }
//          if (ref_base < 0) fprintf(stderr, "%d,%d,%f,%d\n", call->n_alleles, x, sum_min, call->unseen);
            call->shift = (int)(sum_min + .499);
      }
      // combine annotations
      memset(call->anno, 0, 16 * sizeof(int));
      for (i = call->depth = call->ori_depth = 0, tmp = 0; i < n; ++i) {
            call->depth += calls[i].depth;
            call->ori_depth += calls[i].ori_depth;
            for (j = 0; j < 16; ++j) call->anno[j] += calls[i].anno[j];
      }
      return 0;
}

int bcf_call2bcf(int tid, int pos, bcf_call_t *bc, bcf1_t *b, bcf_callret1_t *bcr, int is_SP,
                         const bcf_callaux_t *bca, const char *ref)
{
      extern double kt_fisher_exact(int n11, int n12, int n21, int n22, double *_left, double *_right, double *two);
      kstring_t s;
      int i, j;
      b->n_smpl = bc->n;
      b->tid = tid; b->pos = pos; b->qual = 0;
      s.s = b->str; s.m = b->m_str; s.l = 0;
      kputc('\0', &s);
      if (bc->ori_ref < 0) { // an indel
            // write REF
            kputc(ref[pos], &s);
            for (j = 0; j < bca->indelreg; ++j) kputc(ref[pos+1+j], &s);
            kputc('\0', &s);
            // write ALT
            kputc(ref[pos], &s);
            for (i = 1; i < 4; ++i) {
                  if (bc->a[i] < 0) break;
                  if (i > 1) {
                        kputc(',', &s); kputc(ref[pos], &s);
                  }
                  if (bca->indel_types[bc->a[i]] < 0) { // deletion
                        for (j = -bca->indel_types[bc->a[i]]; j < bca->indelreg; ++j)
                              kputc(ref[pos+1+j], &s);
                  } else { // insertion; cannot be a reference unless a bug
                        char *inscns = &bca->inscns[bc->a[i] * bca->maxins];
                        for (j = 0; j < bca->indel_types[bc->a[i]]; ++j)
                              kputc("ACGTN"[(int)inscns[j]], &s);
                        for (j = 0; j < bca->indelreg; ++j) kputc(ref[pos+1+j], &s);
                  }
            }
            kputc('\0', &s);
      } else { // a SNP
            kputc("ACGTN"[bc->ori_ref], &s); kputc('\0', &s);
            for (i = 1; i < 5; ++i) {
                  if (bc->a[i] < 0) break;
                  if (i > 1) kputc(',', &s);
                  kputc(bc->unseen == i? 'X' : "ACGT"[bc->a[i]], &s);
            }
            kputc('\0', &s);
      }
      kputc('\0', &s);
      // INFO
      if (bc->ori_ref < 0) kputs("INDEL;", &s);
      kputs("DP=", &s); kputw(bc->ori_depth, &s); kputs(";I16=", &s);
      for (i = 0; i < 16; ++i) {
            if (i) kputc(',', &s);
            kputw(bc->anno[i], &s);
      }
      kputc('\0', &s);
      // FMT
      kputs("PL", &s);
      if (bcr) {
            kputs(":DP", &s);
            if (is_SP) kputs(":SP", &s);
      }
      kputc('\0', &s);
      b->m_str = s.m; b->str = s.s; b->l_str = s.l;
      bcf_sync(b);
      memcpy(b->gi[0].data, bc->PL, b->gi[0].len * bc->n);
      if (bcr) {
            uint16_t *dp = (uint16_t*)b->gi[1].data;
            uint8_t *sp = is_SP? b->gi[2].data : 0;
            for (i = 0; i < bc->n; ++i) {
                  bcf_callret1_t *p = bcr + i;
                  dp[i] = p->depth < 0xffff? p->depth : 0xffff;
                  if (is_SP) {
                        if (p->anno[0] + p->anno[1] < 2 || p->anno[2] + p->anno[3] < 2
                              || p->anno[0] + p->anno[2] < 2 || p->anno[1] + p->anno[3] < 2)
                        {
                              sp[i] = 0;
                        } else {
                              double left, right, two;
                              int x;
                              kt_fisher_exact(p->anno[0], p->anno[1], p->anno[2], p->anno[3], &left, &right, &two);
                              x = (int)(-4.343 * log(two) + .499);
                              if (x > 255) x = 255;
                              sp[i] = x;
                        }
                  }
            }
      }
      return 0;
}

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