* use the revised MAQ error model for mpileup

 * prepare to remove the independent model from mpileup

diff --git a/bam2bcf.c b/bam2bcf.c
index 1f7a0c042b2dad49abe5bb9d1668d90ddc96edf5..7fe178a4dd66a780c2f5385620c669b49bcb177d 100644 (file)
--- a/bam2bcf.c
+++ b/bam2bcf.c
@@ -3,6 +3,7 @@
 #include "bam.h"
 #include "kstring.h"
 #include "bam2bcf.h"
+#include "errmod.h"
 #include "bcftools/bcf.h"
 
 #define END_DIST_THRES 11
@@ -11,180 +12,108 @@ extern    void ks_introsort_uint32_t(size_t n, uint32_t a[]);
 
 #define CALL_ETA 0.03f
 #define CALL_MAX 256
-#define CALL_DEFTHETA 0.85f
+#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) {
@@ -215,6 +144,7 @@ int bcf_call_combine(int n, const bcf_callret1_t *calls, int ref_base /*4-bit*/,
                }
                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) {
@@ -237,13 +167,12 @@ int bcf_call2bcf(int tid, int pos, bcf_call_t *bc, bcf1_t *b)
        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);

diff --git a/bam2bcf.h b/bam2bcf.h
index 4038f39ba687b900f777b31835aca5204de20b97..ddc6b6146fb4e9daab037bd61197b2a1ab21de2d 100644 (file)
--- a/bam2bcf.h
+++ b/bam2bcf.h
@@ -8,9 +8,9 @@ struct __bcf_callaux_t;
 typedef struct __bcf_callaux_t bcf_callaux_t;
 
 typedef struct {
-       int depth, d[4], ed[4];
+       int depth, d[4], ed[4], qsum[4];
        uint64_t sum_Q2;
-       float p[25], esum[5];
+       float p[25];
 } bcf_callret1_t;
 
 typedef struct {