#include "bam.h"
#include "kstring.h"
#include "bam2bcf.h"
+#include "errmod.h"
#include "bcftools/bcf.h"
#define END_DIST_THRES 11
#define CALL_ETA 0.03f
#define CALL_MAX 256
-#define CALL_DEFTHETA 0.85f
+#define CALL_DEFTHETA 0.83f
struct __bcf_callaux_t {
- int max_info, capQ, min_baseQ;
- double *fk;
- uint32_t *info;
+ int max_bases, capQ, min_baseQ;
+ uint16_t *bases;
+ errmod_t *e;
};
bcf_callaux_t *bcf_call_init(double theta, int min_baseQ)
{
bcf_callaux_t *bca;
- int n;
if (theta <= 0.) theta = CALL_DEFTHETA;
bca = calloc(1, sizeof(bcf_callaux_t));
bca->capQ = 60;
bca->min_baseQ = min_baseQ;
- bca->fk = calloc(CALL_MAX, sizeof(double));
- bca->fk[0] = 1.;
- for (n = 1; n < CALL_MAX; ++n)
- bca->fk[n] = theta >= 1.? 1. : pow(theta, n) * (1.0 - CALL_ETA) + CALL_ETA;
- bca->fk[CALL_MAX-1] = 0.;
+ bca->e = errmod_init(1. - theta);
return bca;
}
void bcf_call_destroy(bcf_callaux_t *bca)
{
- if (bca) {
- free(bca->info); free(bca->fk); free(bca);
- }
+ if (bca == 0) return;
+ errmod_destroy(bca->e);
+ free(bca->bases); free(bca);
}
-typedef struct {
- float esum[5], fsum[5];
- uint32_t c[5];
- int w[8];
-} auxaux_t;
-
-/*
- The following code is nearly identical to bam_maqcns_glfgen() under
- the simplified SOAPsnp model. It does the following:
-
- 1) Collect strand, base, quality and mapping quality information for
- each base and combine them in an integer:
-
- x = min{baseQ,mapQ}<<24 | 1<<21 | strand<<18 | base<<16 | baseQ<<8 | mapQ
-
- 2) Sort the list of integers for the next step.
-
- 3) For each base, calculate e_b, the sum of weighted qualities. For
- each type of base on each strand, the best quality has the highest
- weight. Only the top 255 bases on each strand are used (different
- from maqcns).
-
- 4) Rescale the total read depth to 255.
-
- 5) Calculate Q(D|g) = -10\log_{10}P(D|g) (d_a is the allele count):
-
- Q(D|<aa>)=\sum_{b\not=a}e_b
- Q(D|<aA>)=3*(d_a+d_A)+\sum_{b\not=a,b\not=A}e_b
- */
int bcf_call_glfgen(int _n, const bam_pileup1_t *pl, int ref_base /*4-bit*/, bcf_callaux_t *bca, bcf_callret1_t *r)
{
- int i, j, k, c, n, ref4;
- float *p = r->p;
- auxaux_t aux;
-
+ int i, k, n, ref4;
memset(r, 0, sizeof(bcf_callret1_t));
ref4 = bam_nt16_nt4_table[ref_base];
if (_n == 0) return -1;
- // enlarge the aux array if necessary
- if (bca->max_info < _n) {
- bca->max_info = _n;
- kroundup32(bca->max_info);
- bca->info = (uint32_t*)realloc(bca->info, 4 * bca->max_info);
+ // 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 aux array
- for (i = n = 0; i < _n; ++i) {
+ // fill the bases array
+ memset(r->qsum, 0, 4 * sizeof(float));
+ for (i = n = 0, r->sum_Q2 = 0; i < _n; ++i) {
const bam_pileup1_t *p = pl + i;
- uint32_t q, x = 0, qq;
+ int q, b, mapQ;
int min_dist;
+ // set base
if (p->is_del || (p->b->core.flag&BAM_FUNMAP)) continue; // skip unmapped reads and deleted bases
- q = (uint32_t)bam1_qual(p->b)[p->qpos]; // base quality
+ q = (int)bam1_qual(p->b)[p->qpos]; // base quality
if (q < bca->min_baseQ) continue;
- x |= (uint32_t)bam1_strand(p->b) << 18 | q << 8 | p->b->core.qual;
- if (p->b->core.qual < q) q = p->b->core.qual; // cap the overall quality at mapping quality
- x |= q << 24;
- qq = bam1_seqi(bam1_seq(p->b), p->qpos); // base
- q = bam_nt16_nt4_table[qq? qq : ref_base]; // q is the 2-bit base
- if (q < 4) x |= 1 << 21 | q << 16;
- k = (ref4 < 4 && q == ref4)? 0 : 1;
+ mapQ = p->b->core.qual < bca->capQ? p->b->core.qual : bca->capQ;
+ r->sum_Q2 += mapQ * mapQ;
+ if (q > mapQ) q = mapQ;
+ if (q > 63) q = 63;
+ if (q < 4) q = 4;
+ 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
+ bca->bases[n++] = q<<5 | (int)bam1_strand(p->b)<<4 | b;
+ // collect other information
+ r->qsum[b] += q;
+ k = (ref4 < 4 && b == ref4)? 0 : 1;
k = k<<1 | bam1_strand(p->b);
++r->d[k];
- bca->info[n++] = x;
// calculate min_dist
min_dist = p->b->core.l_qseq - 1 - p->qpos;
if (min_dist > p->qpos) min_dist = p->qpos;
k = (k&2) | (min_dist <= END_DIST_THRES);
++r->ed[k];
}
- ks_introsort_uint32_t(n, bca->info);
r->depth = n;
- // generate esum and fsum
- memset(&aux, 0, sizeof(auxaux_t));
- for (j = n - 1, r->sum_Q2 = 0; j >= 0; --j) { // calculate esum and fsum
- uint32_t info = bca->info[j];
- int tmp;
- if (info>>24 < 4 && (info>>8&0x3f) != 0) info = 4<<24 | (info&0xffffff);
- k = info>>16&7;
- if (info>>24 > 0) {
- aux.esum[k&3] += bca->fk[aux.w[k]] * (info>>24);
- aux.fsum[k&3] += bca->fk[aux.w[k]];
- if (aux.w[k] + 1 < CALL_MAX) ++aux.w[k];
- ++aux.c[k&3];
- }
- tmp = (int)(info&0xff) < bca->capQ? (int)(info&0xff) : bca->capQ;
- r->sum_Q2 += tmp * tmp;
- }
- memcpy(r->esum, aux.esum, 5 * sizeof(float));
- // rescale ->c[]
- for (j = c = 0; j != 4; ++j) c += aux.c[j];
- if (c > 255) {
- for (j = 0; j != 4; ++j) aux.c[j] = (int)(254.0 * aux.c[j] / c + 0.499);
- for (j = c = 0; j != 4; ++j) c += aux.c[j];
- }
- // generate likelihood
- for (j = 0; j != 5; ++j) {
- float tmp;
- // homozygous
- for (k = 0, tmp = 0.0; k != 5; ++k)
- if (j != k) tmp += aux.esum[k];
- p[j*5+j] = tmp; // anything that is not j
- // heterozygous
- for (k = j + 1; k < 5; ++k) {
- for (i = 0, tmp = 0.0; i != 5; ++i)
- if (i != j && i != k) tmp += aux.esum[i];
- p[j*5+k] = p[k*5+j] = 3.01 * (aux.c[j] + aux.c[k]) + tmp;
- }
- }
+ // 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;
- int64_t sum[5], tmp;
+ int ref4, i, j, qsum[4];
+ int64_t tmp;
call->ori_ref = ref4 = bam_nt16_nt4_table[ref_base];
if (ref4 > 4) ref4 = 4;
- { // calculate esum
- double esum[5];
- memset(esum, 0, sizeof(double) * 4);
- for (i = 0; i < n; ++i) {
- for (j = 0; j < 4; ++j)
- esum[j] += calls[i].esum[j];
- }
+ // calculate esum
+ memset(qsum, 0, 4 * sizeof(int));
+ for (i = 0; i < n; ++i)
for (j = 0; j < 4; ++j)
- sum[j] = (int)(esum[j] * 100. + .499) << 2 | 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 && sum[j] < sum[j-1]; --j)
- tmp = sum[j], sum[j] = sum[j-1], sum[j-1] = tmp;
+ 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 ((sum[i]&3) != ref4) {
- if (sum[i]>>2 != 0) call->a[j++] = sum[i]&3;
+ if ((qsum[i]&3) != ref4) {
+ if (qsum[i]>>2 != 0) call->a[j++] = qsum[i]&3;
else break;
}
}
if (((ref4 < 4 && j < 4) || (ref4 == 4 && j < 5)) && i >= 0)
- call->unseen = j, call->a[j++] = sum[i]&3;
+ call->unseen = j, call->a[j++] = qsum[i]&3;
call->n_alleles = j;
// set the PL array
if (call->n < n) {
}
call->shift = (int)(sum_min + .499);
}
+ // combine annotations
memset(call->d, 0, 4 * sizeof(int));
memset(call->ed, 0, 4 * sizeof(int));
for (i = call->depth = 0, tmp = 0; i < n; ++i) {
for (i = 1; i < 5; ++i) {
if (bc->a[i] < 0) break;
if (i > 1) kputc(',', &s);
-// kputc(bc->unseen == i && i != 3? 'X' : "ACGT"[bc->a[i]], &s);
kputc(bc->unseen == i? 'X' : "ACGT"[bc->a[i]], &s);
}
kputc('\0', &s);
kputc('\0', &s);
// INFO
- kputs("MQ=", &s); kputw(bc->rmsQ, &s); // kputs(";DP=", &s); kputw(bc->depth, &s);
+ kputs("MQ=", &s); kputw(bc->rmsQ, &s);
kputs(";DP4=", &s);
for (i = 0; i < 4; ++i) {
if (i) kputc(',', &s);