]> git.donarmstrong.com Git - samtools.git/commitdiff
added revised MAQ error model
authorHeng Li <lh3@live.co.uk>
Fri, 20 Aug 2010 19:46:40 +0000 (19:46 +0000)
committerHeng Li <lh3@live.co.uk>
Fri, 20 Aug 2010 19:46:40 +0000 (19:46 +0000)
Makefile
bam_maqcns.c
bam_maqcns.h
bam_plcmd.c
errmod.c [new file with mode: 0644]
errmod.h [new file with mode: 0644]
ksort.h

index 6a04c1b51b195c16170c3dec210719f13b8a7889..c14d66357937889e64a76f384d90e8e30b9022ec 100644 (file)
--- a/Makefile
+++ b/Makefile
@@ -7,7 +7,7 @@ LOBJS=          bgzf.o kstring.o bam_aux.o bam.o bam_import.o sam.o bam_index.o \
                        $(KNETFILE_O) bam_sort.o sam_header.o bam_reheader.o
 AOBJS=         bam_tview.o bam_maqcns.o bam_plcmd.o sam_view.o \
                        bam_rmdup.o bam_rmdupse.o bam_mate.o bam_stat.o bam_color.o     \
-                       bamtk.o kaln.o bam_mcns.o bam2bcf.o
+                       bamtk.o kaln.o bam_mcns.o bam2bcf.o errmod.o
 PROG=          samtools
 INCLUDES=      -I.
 SUBDIRS=       . bcftools misc
index cad63d772268db289467c6a4fd625e50b7ac3889..9caa5d7b4dfac43d166d163339547a82def69ca3 100644 (file)
@@ -3,6 +3,7 @@
 #include "bam.h"
 #include "bam_maqcns.h"
 #include "ksort.h"
+#include "errmod.h"
 #include "kaln.h"
 KSORT_INIT_GENERIC(uint32_t)
 
@@ -12,12 +13,13 @@ KSORT_INIT_GENERIC(uint32_t)
 typedef struct __bmc_aux_t {
        int max;
        uint32_t *info;
+       uint16_t *info16;
+       errmod_t *em;
 } bmc_aux_t;
 
 typedef struct {
        float esum[4], fsum[4];
        uint32_t c[4];
-       uint32_t rms_mapQ;
 } glf_call_aux_t;
 
 char bam_nt16_nt4_table[] = { 4, 0, 1, 4, 2, 4, 4, 4, 3, 4, 4, 4, 4, 4, 4, 4 };
@@ -41,7 +43,7 @@ static void cal_het(bam_maqcns_t *aa)
        for (n1 = 0; n1 < 256; ++n1) {
                for (n2 = 0; n2 < 256; ++n2) {
                        long double sum = 0.0;
-                       double lC = aa->is_soap? 0 : lgamma(n1+n2+1) - lgamma(n1+1) - lgamma(n2+1); // \binom{n1+n2}{n1}
+                       double lC = aa->errmod == BAM_ERRMOD_SOAP? 0 : lgamma(n1+n2+1) - lgamma(n1+1) - lgamma(n2+1);
                        for (k = 1; k <= aa->n_hap - 1; ++k) {
                                double pk = 1.0 / k / sum_harmo;
                                double log1 = log((double)k/aa->n_hap);
@@ -62,6 +64,7 @@ static void cal_coef(bam_maqcns_t *aa)
        long double sum_a[257], b[256], q_c[256], tmp[256], fk2[256];
        double *lC;
 
+       if (aa->errmod == BAM_ERRMOD_MAQ2) return; // no need to do the following
        // aa->lhet will be allocated and initialized 
        free(aa->fk); free(aa->coef);
        aa->coef = 0;
@@ -71,7 +74,7 @@ static void cal_coef(bam_maqcns_t *aa)
                aa->fk[n] = pow(aa->theta, n) * (1.0 - aa->eta) + aa->eta;
                fk2[n] = aa->fk[n>>1]; // this is an approximation, assuming reads equally likely come from both strands
        }
-       if (aa->is_soap) return;
+       if (aa->errmod == BAM_ERRMOD_SOAP) return;
        aa->coef = (double*)calloc(256*256*64, sizeof(double));
        lC = (double*)calloc(256 * 256, sizeof(double));
        for (n = 1; n != 256; ++n)
@@ -116,19 +119,21 @@ bam_maqcns_t *bam_maqcns_init()
 
 void bam_maqcns_prepare(bam_maqcns_t *bm)
 {
+       if (bm->errmod == BAM_ERRMOD_MAQ2) bm->aux->em = errmod_init(1. - bm->theta);
        cal_coef(bm); cal_het(bm);
 }
 
 void bam_maqcns_destroy(bam_maqcns_t *bm)
 {
        if (bm == 0) return;
-       free(bm->lhet); free(bm->fk); free(bm->coef); free(bm->aux->info);
+       free(bm->lhet); free(bm->fk); free(bm->coef); free(bm->aux->info); free(bm->aux->info16);
+       if (bm->aux->em) errmod_destroy(bm->aux->em);
        free(bm->aux); free(bm);
 }
 
 glf1_t *bam_maqcns_glfgen(int _n, const bam_pileup1_t *pl, uint8_t ref_base, bam_maqcns_t *bm)
 {
-       glf_call_aux_t *b;
+       glf_call_aux_t *b = 0;
        int i, j, k, w[8], c, n;
        glf1_t *g = (glf1_t*)calloc(1, sizeof(glf1_t));
        float p[16], min_p = 1e30;
@@ -142,28 +147,38 @@ glf1_t *bam_maqcns_glfgen(int _n, const bam_pileup1_t *pl, uint8_t ref_base, bam
                bm->aux->max = _n;
                kroundup32(bm->aux->max);
                bm->aux->info = (uint32_t*)realloc(bm->aux->info, 4 * bm->aux->max);
+               bm->aux->info16 = (uint16_t*)realloc(bm->aux->info16, 2 * bm->aux->max);
        }
-       for (i = n = 0; i < _n; ++i) {
+       for (i = n = 0, rms = 0; i < _n; ++i) {
                const bam_pileup1_t *p = pl + i;
                uint32_t q, x = 0, qq;
+               uint16_t y = 0;
                if (p->is_del || (p->b->core.flag&BAM_FUNMAP)) continue;
                q = (uint32_t)bam1_qual(p->b)[p->qpos];
                x |= (uint32_t)bam1_strand(p->b) << 18 | q << 8 | p->b->core.qual;
+               y |= bam1_strand(p->b)<<4;
                if (p->b->core.qual < q) q = p->b->core.qual;
+               c = p->b->core.qual < bm->cap_mapQ? p->b->core.qual : bm->cap_mapQ;
+               rms += c * c;
                x |= q << 24;
+               y |= q << 5;
                qq = bam1_seqi(bam1_seq(p->b), p->qpos);
                q = bam_nt16_nt4_table[qq? qq : ref_base];
-               if (!p->is_del && q < 4) x |= 1 << 21 | q << 16;
+               if (!p->is_del && q < 4) x |= 1 << 21 | q << 16, y |= q;
+               bm->aux->info16[n] = y;
                bm->aux->info[n++] = x;
        }
+       rms = (uint8_t)(sqrt((double)rms / n) + .499);
+       if (bm->errmod == BAM_ERRMOD_MAQ2) {
+               errmod_cal(bm->aux->em, n, 4, bm->aux->info16, p);
+               goto goto_glf;
+       }
        ks_introsort(uint32_t, n, bm->aux->info);
        // generate esum and fsum
        b = (glf_call_aux_t*)calloc(1, sizeof(glf_call_aux_t));
        for (k = 0; k != 8; ++k) w[k] = 0;
-       rms = 0;
        for (j = n - 1; j >= 0; --j) { // calculate esum and fsum
                uint32_t info = bm->aux->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) {
@@ -172,17 +187,14 @@ glf1_t *bam_maqcns_glfgen(int _n, const bam_pileup1_t *pl, uint8_t ref_base, bam
                        if (w[k] < 0xff) ++w[k];
                        ++b->c[k&3];
                }
-               tmp = (int)(info&0xff) < bm->cap_mapQ? (int)(info&0xff) : bm->cap_mapQ;
-               rms += tmp * tmp;
        }
-       b->rms_mapQ = (uint8_t)(sqrt((double)rms / n) + .499);
        // rescale ->c[]
        for (j = c = 0; j != 4; ++j) c += b->c[j];
        if (c > 255) {
                for (j = 0; j != 4; ++j) b->c[j] = (int)(254.0 * b->c[j] / c + 0.5);
                for (j = c = 0; j != 4; ++j) c += b->c[j];
        }
-       if (!bm->is_soap) {
+       if (bm->errmod == BAM_ERRMOD_MAQ) {
                // generate likelihood
                for (j = 0; j != 4; ++j) {
                        // homozygous
@@ -234,7 +246,7 @@ glf1_t *bam_maqcns_glfgen(int _n, const bam_pileup1_t *pl, uint8_t ref_base, bam
                        if (max1 > max2 && (min_k != max_k || min1 + 1.0 > min2))
                                p[max_k<<2|max_k] = min1 > 1.0? min1 - 1.0 : 0.0;
                }
-       } else { // apply the SOAP model
+       } else if (bm->errmod == BAM_ERRMOD_SOAP) { // apply the SOAP model
                // generate likelihood
                for (j = 0; j != 4; ++j) {
                        float tmp;
@@ -251,8 +263,9 @@ glf1_t *bam_maqcns_glfgen(int _n, const bam_pileup1_t *pl, uint8_t ref_base, bam
                }
        }
 
+goto_glf:
        // convert necessary information to glf1_t
-       g->ref_base = ref_base; g->max_mapQ = b->rms_mapQ;
+       g->ref_base = ref_base; g->max_mapQ = rms;
        g->depth = n > 16777215? 16777215 : n;
        for (j = 0; j != 4; ++j)
                for (k = j; k < 4; ++k)
index 6cc5355fc2db2b1b19e6a3d2d330306a240fa15a..28733a5dbd8f467105d736bc4ffa1919be4d9e56 100644 (file)
@@ -3,11 +3,15 @@
 
 #include "glf.h"
 
+#define BAM_ERRMOD_MAQ2 0
+#define BAM_ERRMOD_MAQ  1
+#define BAM_ERRMOD_SOAP 2
+
 struct __bmc_aux_t;
 
 typedef struct {
        float het_rate, theta;
-       int n_hap, cap_mapQ, is_soap;
+       int n_hap, cap_mapQ, errmod;
 
        float eta, q_r;
        double *fk, *coef;
index 0cf081d046a0614303957723a94061069545cc86..aef10d38e37797bd24e728e3dd13955e92dc7b64 100644 (file)
@@ -343,12 +343,12 @@ int bam_pileup(int argc, char *argv[])
     d->max_depth = 0;
        d->tid = -1; d->mask = BAM_DEF_MASK;
        d->c = bam_maqcns_init();
-       d->c->is_soap = 1; // change the default model
+       d->c->errmod = BAM_ERRMOD_MAQ2; // change the default model
        d->ido = bam_maqindel_opt_init();
        while ((c = getopt(argc, argv, "st:f:cT:N:r:l:d:im:gI:G:vM:S2aR:PA")) >= 0) {
                switch (c) {
-               case 'a': d->c->is_soap = 1; break;
-               case 'A': d->c->is_soap = 0; break;
+               case 'a': d->c->errmod = BAM_ERRMOD_SOAP; break;
+               case 'A': d->c->errmod = BAM_ERRMOD_MAQ; break;
                case 's': d->format |= BAM_PLF_SIMPLE; break;
                case 't': fn_list = strdup(optarg); break;
                case 'l': fn_pos = strdup(optarg); break;
diff --git a/errmod.c b/errmod.c
new file mode 100644 (file)
index 0000000..fba9a8d
--- /dev/null
+++ b/errmod.c
@@ -0,0 +1,130 @@
+#include <math.h>
+#include "errmod.h"
+#include "ksort.h"
+KSORT_INIT_GENERIC(uint16_t)
+
+typedef struct __errmod_coef_t {
+       double *fk, *beta, *lhet;
+} errmod_coef_t;
+
+typedef struct {
+       double fsum[16], bsum[16];
+       uint32_t c[16];
+} call_aux_t;
+
+static errmod_coef_t *cal_coef(double depcorr, double eta)
+{
+       int k, n, q;
+       long double sum, sum1;
+       double *lC;
+       errmod_coef_t *ec;
+
+       ec = calloc(1, sizeof(errmod_coef_t));
+       // initialize ->fk
+       ec->fk = (double*)calloc(256, sizeof(double));
+       ec->fk[0] = 1.0;
+       for (n = 1; n != 256; ++n)
+               ec->fk[n] = pow(1. - depcorr, n) * (1.0 - eta) + eta;
+       // initialize ->coef
+       ec->beta = (double*)calloc(256 * 256 * 64, sizeof(double));
+       lC = (double*)calloc(256 * 256, sizeof(double));
+       for (n = 1; n != 256; ++n) {
+               double lgn = lgamma(n+1);
+               for (k = 1; k <= n; ++k)
+                       lC[n<<8|k] = lgn - lgamma(k+1) - lgamma(n-k+1);
+       }
+       for (q = 1; q != 64; ++q) {
+               double e = pow(10.0, -q/10.0);
+               double le = log(e);
+               double le1 = log(1.0 - e);
+               for (n = 1; n <= 255; ++n) {
+                       double *beta = ec->beta + (q<<16|n<<8);
+                       sum1 = sum = 0.0;
+                       for (k = n; k >= 0; --k, sum1 = sum) {
+                               sum = sum1 + expl(lC[n<<8|k] + k*le + (n-k)*le1);
+                               beta[k] = -10. / M_LN10 * logl(sum1 / sum);
+                       }
+               }
+       }
+       // initialize ->lhet
+       ec->lhet = (double*)calloc(256 * 256, sizeof(double));
+       for (n = 0; n < 256; ++n)
+               for (k = 0; k < 256; ++k)
+                       ec->lhet[n<<8|k] = lC[n<<8|k] - M_LN2 * n;
+       free(lC);
+       return ec;
+}
+
+errmod_t *errmod_init(float depcorr)
+{
+       errmod_t *em;
+       em = (errmod_t*)calloc(1, sizeof(errmod_t));
+       em->depcorr = depcorr;
+       em->coef = cal_coef(depcorr, 0.03);
+       return em;
+}
+
+void errmod_destroy(errmod_t *em)
+{
+       if (em == 0) return;
+       free(em->coef->lhet); free(em->coef->fk); free(em->coef->beta);
+       free(em->coef); free(em);
+}
+// qual:6, strand:1, base:4
+int errmod_cal(const errmod_t *em, int n, int m, uint16_t *bases, float *q)
+{
+       call_aux_t aux;
+       int i, j, k, w[32];
+
+       if (m > m) return -1;
+       memset(q, 0, m * m * sizeof(float));
+       if (n == 0) return 0;
+       // calculate aux.esum and aux.fsum
+       if (n > 255) { // then sample 255 bases
+               ks_shuffle(uint16_t, n, bases);
+               n = 255;
+       }
+       ks_introsort(uint16_t, n, bases);
+       memset(w, 0, 32 * sizeof(int));
+       memset(&aux, 0, sizeof(call_aux_t));
+       for (j = n - 1; j >= 0; --j) { // calculate esum and fsum
+               uint16_t b = bases[j];
+               int q = b>>5 < 4? 4 : b>>5;
+               if (q > 63) q = 63;
+               k = b&0x1f;
+               aux.fsum[k&0xf] += em->coef->fk[w[k]];
+               aux.bsum[k&0xf] += em->coef->fk[w[k]] * em->coef->beta[q<<16|n<<8|aux.c[k&0xf]];
+               ++aux.c[k&0xf];
+               ++w[k];
+       }
+       // generate likelihood
+       for (j = 0; j != m; ++j) {
+               float tmp1, tmp3;
+               int tmp2, bar_e;
+               // homozygous
+               for (k = 0, tmp1 = tmp3 = 0.0, tmp2 = 0; k != m; ++k) {
+                       if (k == j) continue;
+                       tmp1 += aux.bsum[k]; tmp2 += aux.c[k]; tmp3 += aux.fsum[k];
+               }
+               if (tmp2) {
+                       bar_e = (int)(tmp1 / tmp3 + 0.499);
+                       if (bar_e > 63) bar_e = 63;
+                       q[j*m+j] = tmp1;
+               }
+               // heterozygous
+               for (k = j + 1; k < m; ++k) {
+                       int cjk = aux.c[j] + aux.c[k];
+                       for (i = 0, tmp2 = 0, tmp1 = tmp3 = 0.0; i < m; ++i) {
+                               if (i == j || i == k) continue;
+                               tmp1 += aux.bsum[i]; tmp2 += aux.c[i]; tmp3 += aux.fsum[i];
+                       }
+                       if (tmp2) {
+                               bar_e = (int)(tmp1 / tmp3 + 0.499);
+                               if (bar_e > 63) bar_e = 63;
+                               q[j*m+k] = q[k*m+j] = -4.343 * em->coef->lhet[cjk<<8|aux.c[k]] + tmp1;
+                       } else q[j*m+k] = q[k*m+j] = -4.343 * em->coef->lhet[cjk<<8|aux.c[k]]; // all the bases are either j or k
+               }
+               for (k = 0; k != m; ++k) if (q[j*m+k] < 0.0) q[j*m+k] = 0.0;
+       }
+       return 0;
+}
diff --git a/errmod.h b/errmod.h
new file mode 100644 (file)
index 0000000..e3e9a90
--- /dev/null
+++ b/errmod.h
@@ -0,0 +1,17 @@
+#ifndef ERRMOD_H
+#define ERRMOD_H
+
+#include <stdint.h>
+
+struct __errmod_coef_t;
+
+typedef struct {
+       double depcorr;
+       struct __errmod_coef_t *coef;
+} errmod_t;
+
+errmod_t *errmod_init(float depcorr);
+void errmod_destroy(errmod_t *em);
+int errmod_cal(const errmod_t *em, int n, int m, uint16_t *bases, float *q);
+
+#endif
diff --git a/ksort.h b/ksort.h
index 16a03fd1aad8be1d3b4a090b52c4daf37ae7b217..fa850ab0762a9225bae5b3bcad6739a3bb6a3c27 100644 (file)
--- a/ksort.h
+++ b/ksort.h
@@ -250,6 +250,15 @@ typedef struct {
                        if (hh <= k) low = ll;                                                                          \
                        if (hh >= k) high = hh - 1;                                                                     \
                }                                                                                                                               \
+       }                                                                                                                                       \
+       void ks_shuffle_##name(size_t n, type_t a[])                                            \
+       {                                                                                                                                       \
+               int i, j;                                                                                                               \
+               for (i = n; i > 1; --i) {                                                                               \
+                       type_t tmp;                                                                                                     \
+                       j = (int)(drand48() * i);                                                                       \
+                       tmp = a[j]; a[j] = a[i-1]; a[i-1] = tmp;                                        \
+               }                                                                                                                               \
        }
 
 #define ks_mergesort(name, n, a, t) ks_mergesort_##name(n, a, t)
@@ -259,6 +268,7 @@ typedef struct {
 #define ks_heapmake(name, n, a) ks_heapmake_##name(n, a)
 #define ks_heapadjust(name, i, n, a) ks_heapadjust_##name(i, n, a)
 #define ks_ksmall(name, n, a, k) ks_ksmall_##name(n, a, k)
+#define ks_shuffle(name, n, a) ks_shuffle_##name(n, a)
 
 #define ks_lt_generic(a, b) ((a) < (b))
 #define ks_lt_str(a, b) (strcmp((a), (b)) < 0)