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call: Original bcftools' -c calling now functional
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| Original file line number | Diff line number | Diff line change |
|---|---|---|
| @@ -0,0 +1,287 @@ | ||
| #include <math.h> | ||
| #include <htslib/kfunc.h> | ||
| #include "call.h" | ||
| #include "kmin.h" | ||
| #include "prob1.h" | ||
|
|
||
| // Most of the original -c calling was moved to bcftools as it was | ||
| // and its data structures were wrapped into the ccal_t to make it | ||
| // functional quickly. This is not the desired state. | ||
| struct _ccall_t | ||
| { | ||
| bcf_p1aux_t *p1; | ||
| }; | ||
|
|
||
| void ccall_init(call_t *call) | ||
| { | ||
| call->cdat = (ccall_t*) calloc(1,sizeof(ccall_t)); | ||
| call_init_pl2p(call); | ||
| call->cdat->p1 = bcf_p1_init(bcf_nsamples(call->hdr), call->ploidy); | ||
| call->gts = (int*) calloc(bcf_nsamples(call->hdr)*2,sizeof(int)); // assuming at most diploid everywhere | ||
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||
| bcf_hdr_append(call->hdr,"##FORMAT=<ID=GT,Number=1,Type=String,Description=\"Genotype\">"); | ||
| bcf_hdr_append(call->hdr,"##INFO=<ID=AF1,Number=1,Type=Float,Description=\"Max-likelihood estimate of the first ALT allele frequency (assuming HWE)\">"); | ||
| bcf_hdr_append(call->hdr,"##INFO=<ID=AC1,Number=1,Type=Float,Description=\"Max-likelihood estimate of the first ALT allele count (no HWE assumption)\">"); | ||
| bcf_hdr_append(call->hdr,"##INFO=<ID=MQ,Number=1,Type=Integer,Description=\"Root-mean-square mapping quality of covering reads\">\n"); | ||
| bcf_hdr_append(call->hdr,"##INFO=<ID=FQ,Number=1,Type=Float,Description=\"Phred probability of all samples being the same\">\n"); | ||
| bcf_hdr_append(call->hdr,"##INFO=<ID=PV4,Number=4,Type=Float,Description=\"P-values for strand bias, baseQ bias, mapQ bias and tail distance bias\">\n"); | ||
| bcf_hdr_append(call->hdr,"##INFO=<ID=G3,Number=3,Type=Float,Description=\"ML estimate of genotype frequencies\">\n"); | ||
| bcf_hdr_append(call->hdr,"##INFO=<ID=HWE,Number=1,Type=Float,Description=\"Chi^2 based HWE test P-value based on G3\">\n"); | ||
| // bcf_hdr_append(call->hdr,); | ||
| // bcf_hdr_append(call->hdr,); | ||
| bcf_hdr_append(call->hdr,"##INFO=<ID=DP4,Number=4,Type=Integer,Description=\"Number of high-quality ref-forward , ref-reverse, alt-forward and alt-reverse bases\">"); | ||
|
|
||
| return; | ||
| } | ||
| void ccall_destroy(call_t *call) | ||
| { | ||
| free(call->gts); | ||
| free(call->anno16); | ||
| free(call->PLs); | ||
| free(call->pdg); | ||
| bcf_p1_destroy(call->cdat->p1); | ||
| free(call->cdat); | ||
| return; | ||
| } | ||
|
|
||
| // Inits P(D|G): convert PLs from log space, only two alleles (three PLs) are used. | ||
| // NB: The original samtools calling code uses pdgs in reverse order (AA comes | ||
| // first, RR last), while the -m calling model uses the canonical order. | ||
| static void set_pdg3(double *pl2p, int *PLs, double *pdg, int n_smpl, int n_gt) | ||
| { | ||
| int i; | ||
| for (i=0; i<n_smpl; i++) | ||
| { | ||
| pdg[2] = pl2p[ PLs[0] ]; | ||
| pdg[1] = pl2p[ PLs[1] ]; | ||
| pdg[0] = pl2p[ PLs[2] ]; | ||
| PLs += n_gt; | ||
| pdg += 3; | ||
| } | ||
| } | ||
|
|
||
| static double ttest(int n1, int n2, float a[4]) | ||
| { | ||
| extern double kf_betai(double a, double b, double x); | ||
| double t, v, u1, u2; | ||
| if (n1 == 0 || n2 == 0 || n1 + n2 < 3) return 1.0; | ||
| u1 = (double)a[0] / n1; u2 = (double)a[2] / n2; | ||
| if (u1 <= u2) return 1.; | ||
| t = (u1 - u2) / sqrt(((a[1] - n1 * u1 * u1) + (a[3] - n2 * u2 * u2)) / (n1 + n2 - 2) * (1./n1 + 1./n2)); | ||
| v = n1 + n2 - 2; | ||
| return t < 0.? 1. : .5 * kf_betai(.5*v, .5, v/(v+t*t)); | ||
| } | ||
|
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||
| static int test16_core(float anno[16], anno16_t *a) | ||
| { | ||
| extern double kt_fisher_exact(int n11, int n12, int n21, int n22, double *_left, double *_right, double *two); | ||
| double left, right; | ||
| int i; | ||
| a->p[0] = a->p[1] = a->p[2] = a->p[3] = 1.; | ||
| for (i=0; i<4; i++) a->d[i] = anno[i]; | ||
| a->depth = anno[0] + anno[1] + anno[2] + anno[3]; | ||
| a->is_tested = (anno[0] + anno[1] > 0 && anno[2] + anno[3] > 0); | ||
| if (a->depth == 0) return -1; | ||
| a->mq = (int)(sqrt((anno[9] + anno[11]) / a->depth) + .499); | ||
| kt_fisher_exact(anno[0], anno[1], anno[2], anno[3], &left, &right, &a->p[0]); | ||
| for (i = 1; i < 4; ++i) | ||
| a->p[i] = ttest(anno[0] + anno[1], anno[2] + anno[3], anno+4*i); | ||
| return 0; | ||
| } | ||
|
|
||
| int test16(float *anno16, anno16_t *a) | ||
| { | ||
| a->p[0] = a->p[1] = a->p[2] = a->p[3] = 1.; | ||
| a->d[0] = a->d[1] = a->d[2] = a->d[3] = 0.; | ||
| a->mq = a->depth = a->is_tested = 0; | ||
| return test16_core(anno16, a); | ||
| } | ||
| static int update_bcf1(call_t *call, bcf1_t *rec, const bcf_p1rst_t *pr, double em[10]) | ||
| { | ||
| int has_I16, is_var; | ||
| float fq, r; | ||
| anno16_t a; | ||
| float tmpf[4], tmpi; | ||
|
|
||
| bcf_get_info_float(call->hdr, rec, "I16", &call->anno16, &call->n16); | ||
|
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| has_I16 = test16(call->anno16, &a) >= 0? 1 : 0; | ||
|
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||
| // print EM | ||
| if (em[0] >= 0) | ||
| { | ||
| tmpf[0] = 1 - em[0]; | ||
| bcf1_update_info_float(call->hdr, rec, "AF1", tmpf, 1); | ||
| } | ||
| if (em[4] >= 0 && em[4] <= 0.05) | ||
| { | ||
| tmpf[0] = em[3]; tmpf[1] = em[2]; tmpf[2] = em[1]; tmpf[3] = em[4]; | ||
| bcf1_update_info_float(call->hdr, rec, "G3", tmpf, 3); | ||
| bcf1_update_info_float(call->hdr, rec, "HWE", &tmpf[3], 1); | ||
| } | ||
| if (em[5] >= 0 && em[6] >= 0) | ||
| { | ||
| tmpf[0] = 1 - em[5]; tmpf[1] = 1 - em[6]; | ||
| bcf1_update_info_float(call->hdr, rec, "AF2", tmpf, 2); | ||
| } | ||
| if (em[7] >= 0) | ||
| { | ||
| tmpf[0] = em[7]; | ||
| bcf1_update_info_float(call->hdr, rec, "LRT", tmpf, 1); | ||
| } | ||
| if (em[8] >= 0) | ||
| { | ||
| tmpf[0] = em[8]; | ||
| bcf1_update_info_float(call->hdr, rec, "LRT2", tmpf, 1); | ||
| } | ||
|
|
||
| bcf_p1aux_t *p1 = call->cdat->p1; | ||
| if (p1->cons_llr > 0) | ||
| { | ||
| tmpi = p1->cons_llr; | ||
| bcf1_update_info_int32(call->hdr, rec, "CLR", &tmpi, 1); | ||
| if (p1->cons_gt > 0) | ||
| { | ||
| char tmp[4]; | ||
| tmp[0] = p1->cons_gt&0xff; tmp[1] = p1->cons_gt>>8&0xff; tmp[2] = p1->cons_gt>>16&0xff; tmp[3] = 0; | ||
| bcf1_update_info_string(call->hdr, rec, "UGT", tmp); | ||
| tmp[0] = p1->cons_gt>>32&0xff; tmp[1] = p1->cons_gt>>40&0xff; tmp[2] = p1->cons_gt>>48&0xff; | ||
| bcf1_update_info_string(call->hdr, rec, "CGT", tmp); | ||
| } | ||
| } | ||
| if (pr == 0) return 1; | ||
|
|
||
| is_var = (pr->p_ref < call->pref); | ||
| r = is_var? pr->p_ref : pr->p_var; | ||
|
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||
| bcf1_update_info_int32(call->hdr, rec, "AC1", &pr->ac, 1); | ||
| int32_t dp[4]; dp[0] = call->anno16[0]; dp[1] = call->anno16[1]; dp[2] = call->anno16[2]; dp[3] = call->anno16[3]; | ||
| bcf1_update_info_int32(call->hdr, rec, "DP4", dp, 4); | ||
| bcf1_update_info_int32(call->hdr, rec, "MQ", &a.mq, 1); | ||
|
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||
| fq = pr->p_ref_folded < 0.5? -4.343 * log(pr->p_ref_folded) : 4.343 * log(pr->p_var_folded); | ||
| if (fq < -999) fq = -999; | ||
| if (fq > 999) fq = 999; | ||
| bcf1_update_info_float(call->hdr, rec, "FQ", &fq, 1); | ||
|
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||
| assert( pr->cmp[0]<0 ); | ||
| // todo | ||
| // if (pr->cmp[0] >= 0.) { // two sample groups | ||
| // int i, q[3]; | ||
| // for (i = 1; i < 3; ++i) { | ||
| // double x = pr->cmp[i] + pr->cmp[0]/2.; | ||
| // q[i] = x == 0? 255 : (int)(-4.343 * log(x) + .499); | ||
| // if (q[i] > 255) q[i] = 255; | ||
| // } | ||
| // if (pr->perm_rank >= 0) ksprintf(&s, "PR=%d;", pr->perm_rank); | ||
| // | ||
| // ksprintf(&s, "PCHI2=%.3g;PC2=%d,%d;", q[1], q[2], pr->p_chi2); | ||
| // } | ||
|
|
||
| if (has_I16 && a.is_tested) | ||
| { | ||
| int i; | ||
| for (i=0; i<4; i++) tmpf[i] = a.p[i]; | ||
| bcf1_update_info_float(call->hdr, rec, "PV4", tmpf, 4); | ||
| } | ||
| bcf1_update_info_int32(call->hdr, rec, "I16", NULL, 0); // remove I16 tag | ||
| bcf1_update_info_int32(call->hdr, rec, "QS", NULL, 0); // remove QS tag | ||
|
|
||
| rec->qual = r < 1e-100? 999 : -4.343 * log(r); | ||
| if (rec->qual > 999) rec->qual = 999; | ||
|
|
||
| // Remove unused alleles | ||
| int nals = !is_var ? 1 : pr->rank0 < 2? 2 : pr->rank0+1; | ||
| if ( nals<rec->n_allele ) | ||
| { | ||
| bcf1_update_alleles(call->hdr, rec, (const char**)rec->d.allele, nals); | ||
|
|
||
| // Update PLs | ||
| int npls_src = call->nPLs / rec->n_sample, npls_dst = nals*(nals+1)/2; | ||
| int *pls_src = call->PLs - npls_src, *pls_dst = call->PLs - npls_dst; | ||
| int isample, i; | ||
| for (isample = 0; isample < rec->n_sample; isample++) | ||
| { | ||
| pls_src += npls_src; | ||
| pls_dst += npls_dst; | ||
| if ( !call->ploidy || call->ploidy[isample]==2 ) | ||
| { | ||
| for (i=0; i<npls_dst; i++) | ||
| pls_dst[i] = pls_src[i]; | ||
| } | ||
| else | ||
| { | ||
| for (i=0; i<nals; i++) | ||
| { | ||
| int isrc = (i+1)*(i+2)/2-1; | ||
| pls_dst[i] = pls_src[isrc]; | ||
| } | ||
| if (i<npls_dst) pls_dst[i] = bcf_int32_vector_end; | ||
| } | ||
| } | ||
| bcf1_update_format_int32(call->hdr, rec, "PL", call->PLs, npls_dst*rec->n_sample); | ||
| } | ||
|
|
||
| // Call genotypes | ||
| int i; | ||
| for (i=0; i<rec->n_sample; i++) | ||
| { | ||
| int x = bcf_p1_call_gt(p1, pr->f_exp, i); | ||
| int gt = x&3; | ||
| if ( !call->ploidy || call->ploidy[i]==2 ) | ||
| { | ||
| if ( gt==1 ) | ||
| { | ||
| call->gts[2*i] = bcf_gt_unphased(0); | ||
| call->gts[2*i+1] = bcf_gt_unphased(1); | ||
| } | ||
| else if ( gt==0 ) | ||
| { | ||
| call->gts[2*i] = bcf_gt_unphased(1); | ||
| call->gts[2*i+1] = bcf_gt_unphased(1); | ||
| } | ||
| else | ||
| { | ||
| call->gts[2*i] = bcf_gt_unphased(0); | ||
| call->gts[2*i+1] = bcf_gt_unphased(0); | ||
| } | ||
| } | ||
| else | ||
| { | ||
| if ( gt==0 ) call->gts[2*i] = bcf_gt_unphased(1); | ||
| else call->gts[2*i] = bcf_gt_unphased(0); | ||
| call->gts[2*i+1] = bcf_int32_vector_end; | ||
| } | ||
| // GQ: todo | ||
| } | ||
| bcf1_update_genotypes(call->hdr, rec, call->gts, rec->n_sample*2); | ||
| return is_var; | ||
| } | ||
|
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||
|
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||
| int ccall(call_t *call, bcf1_t *rec) | ||
| { | ||
| int nsmpl = bcf_nsamples(call->hdr); | ||
|
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||
| // Get the genotype likelihoods | ||
| int nals = rec->n_allele; | ||
| call->nPLs = bcf_get_format_int(call->hdr, rec, "PL", &call->PLs, &call->mPLs); | ||
| if ( call->nPLs!=nsmpl*nals*(nals+1)/2 && call->nPLs!=nsmpl*nals ) // diploid+haploid or haploid only | ||
| error("Wrong number of PL fields? nals=%d npl=%d\n", nals,call->nPLs); | ||
|
|
||
| // Convert PLs to probabilities, only first two alleles are considered | ||
| int ngts = nals*(nals+1)/2; | ||
| hts_expand(double, 3*nsmpl, call->npdg, call->pdg); | ||
| set_pdg3(call->pl2p, call->PLs, call->pdg, nsmpl, ngts); | ||
|
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||
| double em[10]; | ||
| int ret = bcf_em1(call, rec, call->ngrp1_samples, 0x1ff, em); | ||
|
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||
| bcf_p1rst_t pr; | ||
| int do_contrast = (em[7] >= 0 && em[7] < call->min_lrt) ? 1 : 0; | ||
| ret = bcf_p1_cal(call, rec, do_contrast, call->cdat->p1, &pr); | ||
| if (pr.p_ref >= call->pref && (call->flag & CALL_VARONLY)) return 0; | ||
| if (ret >= 0) ret = update_bcf1(call, rec, &pr, em); | ||
| return ret; | ||
| } | ||
|
|
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