--- /dev/null
+#include "pysam.h"
+
+#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 DEF_MAPQ 20
+
+#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);
+ bca->min_frac = 0.002;
+ bca->min_support = 1;
+ 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 < 255? p->b->core.qual : DEF_MAPQ; // special case for mapQ==255
+ mapQ = mapQ < bca->capQ? mapQ : 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
+ if (b < 4) 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 = 0; j <= i; ++j)
+ g[z++] = call->a[j] * 5 + call->a[i];
+ 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(pysamerr, "%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;
+}
projects / pysam.git / blobdiff