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ibd.cpp
1077 lines (812 loc) · 23.8 KB
/
ibd.cpp
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#include "ibd.h"
#include "vcfReader.h"
#define BUF_NSITES 500000
const double NEG_INF = -std::numeric_limits<double>::infinity();
/*
* Binomial coefficient: n choose k
*
* @brief nCk - n choose k recursive function
* @param n
* @param k
* @return choose(n,k)
*/
int nCk(int n, int k) {
if (k == 0) {
return 1;
}
return (n * nCk(n - 1, k - 1)) / k;
}
/*
* [nCk_idx]
* Maps a given pair of objects to their index in
* the lexicographically ordered binomial coefficients
* a.k.a. array of pairs
*
* @param nInd: number of individuals
* @param i1: index of first individual
* @param i2: index of second individual
*
* @return: index of pair in lexicographically ordered array of pairs
*
* @example:
*
* 0 1 2 3
* 0 01 02 03
* 1 12 13
* 2 23
* 3
*
* 01 = 0, 02 = 1, 03 = 2, 12 = 3, 13 = 4, 23 = 5
*
* Formula:
* (nCk(nInd, 2) - nCk((nInd - i1), 2)) + (i2 - i1) - 1;
*
* e.g.:
* nInd=5, i1=1, i2=3
* nCk(5,2) - nCk(4,2) + (3-1) - 1 = 5 - 6 + 2 - 1 = 0
*
* Total number of pairs: nCk(nInd, 2)
* Starting index for each individual: nCk(nInd, 2) - nCk((nInd - i), 2)
* Difference between i2 and i1: (i2 - i1)
* Index of pair: (nCk(nInd, 2) - nCk((nInd - i1), 2)) + (i2 - i1) - 1;
*
*/
int nCk_idx(int nInd, int i1, int i2) {
ASSERT(i1 < nInd && i2 < nInd); // safeguard for wrong order of arguments
if (i2 > i1) {
return (nCk(nInd, 2) - nCk((nInd - i1), 2)) + (i2 - i1) - 1;
} else {
return (nCk(nInd, 2) - nCk((nInd - i2), 2)) + (i1 - i2) - 1;
}
}
///// if (args->minInd ) does not work with doibd
const int dosePairIndex[3][3] = { {0,1,5}, {1,2,3}, {5,3,4} };
void readSites_doIbd(vcfData* vcfd, paramStruct* pars) {
const int nInd = pars->names->len;
int skip_site = 0;
int contig_i = -1;
int site_i = 0;
char prev_contig[1024];
int nSites_contig_i = 0;
int* site2pos = (int*)malloc(BUF_NSITES * sizeof(int));
for (int i = 0;i < BUF_NSITES;++i) {
site2pos[i] = -1;
}
double* lngl = NULL;
if (args->doIbd == 1) {
lngl = (double*)malloc(nInd * 3 * sizeof(double));
for (int indi = 0; indi < nInd; indi++) {
const int lngls_ind_start = indi * 3;
for (int j = 0; j < 3; j++) {
lngl[lngls_ind_start + j] = NEG_INF;
}
}
}
double* ibdScores_lut = NULL;
double* hbdScores_lut = NULL;
if (args->doIbd == 2) {
ibdScores_lut = (double*)malloc(6 * sizeof(double));
hbdScores_lut = (double*)malloc(3 * sizeof(double));
}
int* a1 = new int;
int* a2 = new int;
while (1 == (vcfd->records_next())) {
ASSERT(site_i < BUF_NSITES - 1);//TODO
if (NULL != lngl) {
for (int indi = 0; indi < nInd; indi++) {
const int lngls_ind_start = indi * 3;
for (int j = 0; j < 3; j++) {
lngl[lngls_ind_start + j] = NEG_INF;
}
}
}
// if at the very beginning
if (-1 == contig_i) {
++contig_i;
strncpy(prev_contig, vcfd->get_contig_name(), sizeof(prev_contig));
if (prev_contig[sizeof(prev_contig) - 1] != '\0') {
ERROR("Contig name is too long");
}
site_i = 0;
}
// ** contig change **
if (0 != strcmp(vcfd->get_contig_name(), prev_contig)) {
if (contig_i >= vcfd->nContigs) {
ERROR("Number of contigs in the VCF file header is larger than the number of contigs in the VCF file");
}
// if we skipped all sites in the previous contig, reuse contig_i index for the new contig
if (0 == nSites_contig_i) {
} else {
++contig_i;
nSites_contig_i = 0;
}
strncpy(prev_contig, vcfd->get_contig_name(), sizeof(prev_contig));
if (prev_contig[sizeof(prev_contig) - 1] != '\0') {
ERROR("Contig name is too long");
}
site_i = 0;
}
ASSERT(1 == bcf_is_snp(vcfd->rec));
// if (1 != bcf_is_snp(vcfd->rec)) {
// skip_site=1;
// IO::vprint(2, "Skipping site at %s:%ld. Reason: VCF record is not a SNP.\n", vcfd->get_contig_name(), vcfd->rec->pos + 1);
// }
//TODO update
// ASSERT(0== read_site_with_alleles(contig_i, site_i, vcfd, pars, a1, a2));
// int ret = read_site_with_alleles(contig_i, site_i, vcfd, pars, a1, a2);
// if (0 == ret) {
// skip_site = 0;
// } else if (1 == ret) {
// // 1 if 'contig:site' in VCF cannot be found in alleles file
// skip_site = 1;
// break;
// } else if (2 == ret) {
// // 2 if an a1 is not a single character
// skip_site = 1;
// break;
// } else {
// NEVER;
// }
get_data<float> afData;
int n = bcf_get_info_float(vcfd->hdr, vcfd->rec, "AF", &afData.data, &afData.n);
if (n <= 0) {
ERROR("AF tag not found.");
}
double maf = afData.data[0];
if (maf > 0.5) {
NEVER;
}
// ------------------------------------------------
// FILTER: --min-af <DOUBLE>
if (args->min_af > 0) {
if (maf < args->min_af) {
skip_site = 1;
NEVER;
break;
}
}
// ------------------------------------------------
skip_site = 0;
double score = 0.0;
float* lgls = NULL;
/// -------------------
if (args->doIbd == 1) {
int size_e = 0;
int n_gls = 0;
// int n_missing_ind = 0;
int n_values = bcf_get_format_float(vcfd->hdr, vcfd->rec, "GL", &lgls, &size_e);
if (n_values <= 0) {
ERROR("Could not read GL tag from the VCF file.");
}
n_gls = n_values / pars->names->len;
// if (n_gls < ngt_to_use) {
// IO::vprint(2, "Skipping site at %s:%ld. Reason: Number of GLs is less than the number of GLs needed to perform the specified analysis (%d).\n", vcfd->get_contig_name(), vcfd->rec->pos + 1, ngt_to_use);
// return(1);
// }
bool ind_is_missing[nInd];
for (int i = 0; i < nInd; ++i) {
ind_is_missing[i] = false;
}
do {
//TODO assume only 3 gls for now
// int a1a1 = bcf_alleles_get_gtidx(*a1, *a1);D
// int a1a2 = bcf_alleles_get_gtidx(*a1, *a2);
// int a2a2 = bcf_alleles_get_gtidx(*a2, *a2);
int a1a1 = 0;
int a1a2 = 1;
int a2a2 = 2;
float* sample_lgls = NULL;
for (int indi = 0; indi < nInd; indi++) {
sample_lgls = lgls + indi * n_gls;
if (bcf_float_is_missing(sample_lgls[0])) {
// missing data check 1
ind_is_missing[indi] = true;
continue;
} else {
// missing data check 2
int z = 1;
for (int i = 1; i < n_gls; ++i) {
if (sample_lgls[0] == sample_lgls[i]) {
++z;
}
}
if (z == n_gls) {
// missing data (all gl values are the same)
ind_is_missing[indi] = true;
continue;
}
}
const int lngls_ind_start = indi * vcfd->nGT;
// TODO what if the 3 gls we are interested in are equal to each other for that sample? e.g. REF=A, ALT=C,G,T. We set major/ref/a1=A minor/alt/a2=C. But ind1 has only 1 G and 1 T observed, so A and C are both unobserved for ind1. What do we do in this case?
// if ((lgls.ind_ptr(indi)[a1a1] == lgls.ind_ptr(indi)[a1a2]) && (lgls.ind_ptr(indi)[a1a1] == lgls.ind_ptr(indi)[a2a2])) {
// ind_is_missing[indi] = true;
float* indgls = lgls + indi * n_gls;
lngl[lngls_ind_start + 0] = (double)LOG2LN(indgls[a1a1]);
lngl[lngls_ind_start + 1] = (double)LOG2LN(indgls[a1a2]);
lngl[lngls_ind_start + 2] = (double)LOG2LN(indgls[a2a2]);
double mmax = lngl[lngls_ind_start + 0];
for (int ii = 1;ii < 3;ii++) {
if (lngl[lngls_ind_start + ii] > mmax) {
mmax = lngl[lngls_ind_start + ii];
}
}
for (int ii = 0;(!std::isinf(mmax)) && ii < 3;ii++) {
lngl[lngls_ind_start + ii] -= mmax;
if (std::isnan(lngl[lngls_ind_start + ii])) {
fprintf(stderr, "mmax: %f\n", mmax);
exit(0);
}
}
}
bool isCor = false;//TODO
score = 0.0;
for (int i1 = 0; i1 < nInd; ++i1) {
for (int i2 = i1 + 1; i2 < nInd; ++i2) {
if (ind_is_missing[i1] == true || ind_is_missing[i2] == true) {
///if any ind in the pair is missing define LOD score of the pair at the locus as 0
score = 0.0;
} else {
if (isCor == false) {
score = pars->ibd->ibdScore_GL(i1, i2, vcfd, pars, maf, site_i, lngl);
} else {
NEVER;
// score=0.0;
}
}
int pair_idx = nCk_idx(nInd, i1, i2);
pars->ibd->pairScores[pair_idx][site_i] = score;
// VALIDATION GL1
// fprintf(stdout, "VGL1,%d,%d,%d,%f\n",i1,i2,site_i,score);
// fprintf(stdout, "VGL1,%d,%d,%d,%f\n",i1,i2,vcfd->rec->pos+1,score);
}
}
} while (0);
} else if (args->doIbd == 2) {
// precalculate the dose pair ibd scores
//
// getIbdScores
// int nIndices = 6;
int N_DOSES = 3;
// int index = -1;
for (int dose1 = 0; dose1 < N_DOSES; ++dose1) {
for (int dose2 = dose1; dose2 < N_DOSES; ++dose2) {
ibdScores_lut[dosePairIndex[dose1][dose2]] = pars->ibd->ibdScore(dose1, dose2, maf);
ibdScores_lut[dosePairIndex[dose2][dose1]] = pars->ibd->ibdScore(dose1, dose2, maf);
}
}
// getHbdScores
for (int dose = 0; dose < N_DOSES; ++dose) {
hbdScores_lut[dose] = pars->ibd->hbdScore(dose, maf);
}
do {
// vcfd->site_gts_get(*a1, *a2);
//TODO get a1 a2
//TODO check minind thres
// if (!vcfd->gts->pass_minInd_threshold(nInd)) {
// skip_site = 1;
// break;
// }
for (int ind = 0; ind < nInd; ++ind) {
// int ind_nder = vcfd->gts->get_n_derived_alleles_ind(ind);
int ind_nder = 0; //TODO
if (-2 == ind_nder) {
// individual's allelic state cannot be found in d.allele
NEVER;
}
if (-1 == ind_nder) {
continue;
}
}
// ------------------------------------------------
// FILTER: --ibdseq-minalleles <INT>
//
bool has_ac_tag = false;
// First, if exists try using AC tag for this filter
// AC : allele count in genotypes, for each ALT allele, in the same order as listed
get_data<int32_t> acData;
int nac = bcf_get_info_int32(vcfd->hdr, vcfd->rec, "AC", &acData.data, &acData.n);
if (nac <= 0) {
has_ac_tag = false;
// ERROR("AC tag not found.");
} else {
has_ac_tag = true;
if (acData.data[0] < args->ibdseq_minalleles) {
IO::vprint(2, "Skipping site at %s:%ld. Reason: --ibdseq-minalleles filter is not met.");
skip_site = 1;
break;
}
}
if (false == has_ac_tag) {
int sum_nder = 0;
for (int ind = 0; ind < nInd; ++ind) {
// int ind_nder = vcfd->gts->get_n_derived_alleles_ind(ind);
int ind_nder = 0; // TODO
if (ind_nder != -1) {
sum_nder += ind_nder;
}
}
if (sum_nder < args->ibdseq_minalleles) {
IO::vprint(2, "Skipping site at %s:%ld. Reason: --ibdseq-minalleles filter is not met.");
skip_site = 1;
break;
}
}
// ------------------------------------------------
score = 0.0;
bool isCor = false;//TODO
for (int i1 = 0; i1 < nInd; ++i1) {
for (int i2 = i1 + 1; i2 < nInd; ++i2) {
if (i1 == i2) {
NEVER;
//
// int dose=vcfd->gts->get_n_derived_alleles_ind(i1);
//
// ASSERT(dose>=0);
//
// if (dose>=0 && (isCor==false || dose==1) ) {
// score=hbdScores_lut[dose];
// }else {
// score=0.0;
// }
//
// pars->ibd->selfScores[i1][site_i]=score;
// VALIDATION1
// fprintf(stdout, "V1,%d,%d,%d,%d,%d,%f\n",dose,dose,i1,i2,site_i,score);
} else {
// int dose1 = vcfd->gts->get_n_derived_alleles_ind(i1);
int dose1 = 0; //TODO
// int dose2 = vcfd->gts->get_n_derived_alleles_ind(i2);
int dose2 = 0; //TODO
if (dose1 == -1 || dose2 == -1) {
score = 0.0;
} else {
// TODO HERE we dont have this in gl method
bool notIbs = (dose1 == 0 && dose2 == 2) || (dose1 == 2 && dose2 == 0);
if ((notIbs || isCor == false) && dose1 >= 0 && dose2 >= 0) {
score = ibdScores_lut[dosePairIndex[dose1][dose2]];
} else {
score = 0.0;
}
int pair_idx = nCk_idx(nInd, i1, i2);
pars->ibd->pairScores[pair_idx][site_i] = score;
// VALIDATION1
// VALIDATION GT1
// fprintf(stdout, "VGT1,%d,%d,%d,%f\n",i1,i2,site_i,score);
// fprintf(stdout, "VGT1,%d,%d,%d,%f\n",i1,i2,vcfd->rec->pos+1,score);
}
}
}
}
} while (0);
} else {
NEVER;
}
if (lgls != NULL) {
FREE(lgls);
}
/// -------------------
site2pos[site_i] = vcfd->rec->pos + 1;
if (skip_site == 1) {
IO::vprint(1, "Skipping site at %s:%ld", vcfd->get_contig_name(), vcfd->rec->pos + 1);
pars->totSites++;
site_i++;
continue;
}
++site_i;
pars->nSites++;
pars->totSites++;
nSites_contig_i++;
}
delete a1;
delete a2;
get_ibd_segments(vcfd->get_contig_name(), pars, site2pos);
BEGIN_LOGSECTION;
LOG("Finished reading sites.");
LOG("Read %d (out of %d) contigs from the VCF file.", contig_i + 1, vcfd->nContigs);
LOG("Number of contigs retained: %d", contig_i + 1);
LOG("Number of contigs skipped: %d", vcfd->nContigs - contig_i - 1);
LOG("Total number of sites processed: %lu", pars->totSites);
LOG("Total number of sites skipped for all individual pairs: %lu", pars->totSites - pars->nSites);
LOG("Total number of sites retained: %lu", pars->nSites);
END_LOGSECTION;
FREE(site2pos);
if (NULL != ibdScores_lut) {
FREE(ibdScores_lut);
}
if (NULL != hbdScores_lut) {
FREE(hbdScores_lut);
}
if (NULL != lngl) {
FREE(lngl);
}
}
int get_ibd_segments(const char* contigName, paramStruct* pars, int* site2pos) {
double maxSum = 0.0;
int start = 0;
int end = 0;
double thisSum = 0.0;
double thisScore = 0.0;
int pair_idx = -1;
const int nInd = pars->names->len;
for (int i1 = 0; i1 < nInd; ++i1) {
for (int i2 = i1 + 1; i2 < nInd; ++i2) {
if (i1 == i2) {
NEVER;
pair_idx = -1;
} else {
pair_idx = nCk_idx(nInd, i1, i2);
}
thisSum = 0.0;
maxSum = 0.0;
start = 0;
end = 0;
//TODO work with multiple contigs
for (int site = 0;site < (int)pars->nSites;site++) {
thisScore = 0.0;
if (pair_idx == -1) {
NEVER;
// thisScore=pars->ibd->selfScores[i1][site];
} else {
thisScore = pars->ibd->pairScores[pair_idx][site];
}
thisSum += thisScore;
// VALIDATION
// if(i1==0&&i2==1){
// fprintf(stdout,"V4,%d,%d,%ld\n",i1,i2,site,thisScore,thisSum,maxSum);
// fprintf(stdout,"%d,%d,%ld,%f\n",i1,i2,site,thisScore);
// fprintf(stdout,"V3,%d,%d,%ld,%f,%f\n",i1,i2,site,maxSum,thisSum);
// fprintf(stdout,"V4,%d,%d,%ld,%f,%f,%f\n",i1,i2,site,thisScore,thisSum,maxSum);
// }
if (thisSum > maxSum) {
maxSum = thisSum;
end = site;
} else if (thisSum <= 0.0) {
if (maxSum >= args->ibdseq_ibdlod) {
start = trimmedStart(pars, i1, i2, start, end);
end = trimmedEnd(pars, i1, i2, start, end);
if (end > start) {
if (-1 == pair_idx) { //hbd
NEVER;
// fprintf(hbdOut,"%d\t%d\t%s\t%d\t%d\t%f\n",i1,i2,contigName,site2pos[start],site2pos[end], maxSum);
} else { //ibd
#if 1
fprintf(stdout, "%d\t%d\t%s\t%d\t%d\t%f\n", i1, i2, contigName, site2pos[start], site2pos[end], maxSum);
#endif
}
}
}
start = site + 1;
end = start;
thisSum = 0.0;
maxSum = 0.0;
}
}// sites loop
if (maxSum >= args->ibdseq_ibdlod) {
start = trimmedStart(pars, i1, i2, start, end);
end = trimmedEnd(pars, i1, i2, start, end);
if (end > start) {
if (-1 == pair_idx) { //hbd
// fprintf(hbdOut,"%d\t%d\t%s\t%d\t%d\t%f\n",i1,i2,contigName,site2pos[start],site2pos[end], maxSum);
NEVER;
} else { //ibd
#if 1
fprintf(stdout, "%d\t%d\t%s\t%d\t%d\t%f\n", i1, i2, contigName, site2pos[start], site2pos[end], maxSum);
#endif
}
}
}
}// i2 loop
}// i1 loop
return 0;
}
int trimmedStart(paramStruct* pars, const int i1, const int i2, const int start, const int end) {
if (args->ibdseq_ibdtrim <= 0.0) {
return(start);
}
double sum = 0.0;
int index = start;
int pair_idx = -1;
if (i1 == i2) {
NEVER;
pair_idx = -1;
} else {
pair_idx = nCk_idx(pars->names->len, i1, i2);
}
while (index <= end && sum < args->ibdseq_ibdtrim) {
// sum += score(s1, s2, index, vcfData.isCorrelated(index));
if (pair_idx == -1) {
NEVER;
// sum+=pars->ibd->selfScores[i1][index];
} else {
sum += pars->ibd->pairScores[pair_idx][index];
}
++index;
}
return(index - 1);
}
int trimmedEnd(paramStruct* pars, const int i1, const int i2, const int start, const int end) {
if (args->ibdseq_ibdtrim <= 0.0) {
return(end);
}
double sum = 0.0;
int index = end;
int pair_idx = -1;
if (i1 == i2) {
NEVER;
pair_idx = -1;
} else {
pair_idx = nCk_idx(pars->names->len, i1, i2);
}
while (index >= start && sum < args->ibdseq_ibdtrim) {
// sum += score(s1, s2, index, vcfData.isCorrelated(index));
if (pair_idx == -1) {
NEVER;
// sum+=pars->ibd->selfScores[i1][index];
} else {
sum += pars->ibd->pairScores[pair_idx][index];
}
--index;
}
return(index + 1);
}
double* ibdStruct::errorArray(double e) {
double* errArray = (double*)malloc(5 * sizeof(double));
double x = 1.0 - e;
// errArray[j] = (errArray[j-1] * e) / x;// unroll
errArray[0] = x * x * x * x;
errArray[1] = (e) * (x * x * x);
errArray[2] = (e * e) * (x * x);
errArray[3] = (e * e * e) * (x);
errArray[4] = (e * e * e * e);
return (errArray);
}
double ibdStruct::errorRate(double fB) {
double e = args->ibdseq_errorprop * fB;
return(MIN(e, args->ibdseq_errormax));
// return(e); //TEST
}
double ibdStruct::ibdLike(int dose1, int dose2, double err, double pB) {
double ret = 0.0;
double pA = 1.0 - pB;
double* e = NULL;
if (err == args->ibdseq_errormax) {
e = (double*)malloc(5 * sizeof(double));
for (int i = 0;i < 5;++i) {
e[i] = this->maxErrorArray[i];
}
} else {
e = this->errorArray(err);
}
switch (dose1 + dose2) {
case 0:
ret = (e[0] * (pA * pA * pA) + 2 * e[1] * pA * pA * pB + e[2] * pA * pB);
break;
case 1:
ret = (2 * (e[0] * pA * pA * pB + e[1] * (pA * pB + 2 * (pA * pA * pA)) + 3 * e[2] * pA * pB));
break;
case 2:
if (dose1 == dose2) {
ret = ((e[0] + 4 * e[1] + 2 * e[2]) * pA * pB + 4 * e[2] * ((pA * pA * pA) + (pB * pB * pB)));
} else {
ret = (2 * ((e[1] + e[2] + e[3]) * pA * pB + e[2] * ((pA * pA * pA) + (pB * pB * pB))));
}
break;
case 3:
ret = (2 * (e[0] * pA * pB * pB + 2 * e[1] * (pB * pB * pB) + (e[1] + 3 * e[2] + e[3]) * pA * pB + 2 * e[3] * (pA * pA * pA)));
break;
case 4:
ret = ((e[0] * (pB * pB * pB) + 2 * e[1] * pA * pB * pB + e[2] * pA * pB + 2 * e[3] * pA * pA * pB + e[4] * (pA * pA * pA)));
break;
default: NEVER;
}
FREE(e);
return(ret);
}
// IBD = 1
double ibdStruct::ibdLike_GL(const int idx, vcfData* vcfd, paramStruct* pars, double fm) {
double fM = 1.0 - fm;
//
// double M[9] = {0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0};
// M[0]=fM*fM*fM; // A
// M[1]=fM*fM * fm; // B
// // M[2]=0.0 // C
// M[3]= M[1]; // D
// M[4]=fM*fm; // E
// M[5]=fM*fm*fm; // F
// // M[6]=0.0; // G
// M[7]=M[5]; // H
// M[8]=fm*fm*fm; // I
switch (idx) {
case 0:
return(fM * fM * fM);
case 1:
return(fM * fM * fm);
case 2:
return (0.0);
case 3:
return(fM * fM * fm);
case 4:
return (fM * fm);
case 5:
return (fM * fm * fm);
case 6:
return (0.0);
case 7:
return (fM * fm * fm);
case 8:
return (fm * fm * fm);
default: NEVER;
}
}
double ibdStruct::nullLike_GL(const int idx, vcfData* vcfd, paramStruct* pars, double fm) {
double fM = 1.0 - fm;
// double M[9] = {0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0};
// M[0]=fM*fM*fM; // A
// M[1]=fM*fM * fm; // B
// // M[2]=0.0 // C
// M[3]= M[1]; // D
// M[4]=fM*fm; // E
// M[5]=fM*fm*fm; // F
// // M[6]=0.0; // G
// M[7]=M[5]; // H
// M[8]=fm*fm*fm; // I
switch (idx) {
case 0:
return(fM * fM * fM * fM);
case 1:
return(2 * fM * fM * fM * fm);
case 2:
return (fM * fM * fm * fm);
case 3:
return (2 * fM * fM * fM * fm);
case 4:
return (4 * fM * fM * fm * fm);
case 5:
return (2 * fM * fm * fm * fm);
case 6:
return (fM * fM * fm * fm);
case 7:
return (2 * fM * fm * fm * fm);
case 8:
return (fm * fm * fm * fm);
default: NEVER;
}
}
double ibdStruct::ibdScore_GL(const int i1, const int i2, vcfData* vcfd, paramStruct* pars, const double fa, const size_t site_i, double* lngl) {
//TODO missing gls check
double r = 0.0;
double i1gl1 = lngl[(i1 * vcfd->nGT) + 0];
double i1gl2 = lngl[(i1 * vcfd->nGT) + 1];
double i1gl3 = lngl[(i1 * vcfd->nGT) + 2];
if ((i1gl1 == i1gl2) && (i1gl1 == i1gl3)) {//TODO delme
NEVER;
}
double i2gl1 = lngl[(i2 * vcfd->nGT) + 0];
double i2gl2 = lngl[(i2 * vcfd->nGT) + 1];
double i2gl3 = lngl[(i2 * vcfd->nGT) + 2];
if ((i2gl1 == i2gl2) && (i2gl1 == i2gl3)) {//TODO delme
NEVER;
}
double GLS[9] = { 0.0 };
GLS[0] = exp(i1gl1 + i2gl1);
GLS[1] = exp(i1gl2 + i2gl1);
GLS[2] = exp(i1gl3 + i2gl1);
GLS[3] = exp(i1gl1 + i2gl2);
GLS[4] = exp(i1gl2 + i2gl2);
GLS[5] = exp(i1gl3 + i2gl2);
GLS[6] = exp(i1gl1 + i2gl3);
GLS[7] = exp(i1gl2 + i2gl3);
GLS[8] = exp(i1gl3 + i2gl3);
double m = 0.0;
double n = 0.0;
for (int i = 0;i < 9;++i) {
if (GLS[i] != 0.0) {
// fprintf(stderr,"%ld i1:%d i2:%d i1gl1:%f i1gl2:%f i1gl3:%f i2gl1:%f i2gl2:%f i2gl3:%f\n",site_i,i1,i2,i1gl1,i1gl2,i1gl3,i2gl1,i2gl1,i1gl3);
m += GLS[i] * ibdLike_GL(i, vcfd, pars, fa);
n += GLS[i] * nullLike_GL(i, vcfd, pars, fa);
}
}
ASSERT(0.0 != n);
ASSERT(0.0 != m);
r = (double)(m / n);
ASSERT(r > 0.0);
r = (double)log10(r);
return r;
}
double ibdStruct::nullLike(int dose1, int dose2, double fB) {
double fA = 1.0 - fB;
switch (dose1 + dose2) {
case 0:
return (fA * fA * fA * fA);
case 1:
return (4 * (fA * fA * fA) * fB);
case 2:
if (dose1 == dose2) {
return ((2 * fA * fB) * (2 * fA * fB));
} else {
return ((fA * fB) * (fA * fB)) + ((fA * fB) * (fA * fB));
}
case 3:
return (4 * fA * (fB * fB * fB));
case 4:
return (fB * fB * fB * fB);
default:
NEVER;
}
}
double estimate_true_maf(double fB, double errorRate) {
// return (fB);//TEST
return ((fB - errorRate) / (1.0 - 2 * errorRate));
}
double ibdStruct::ibdScore(const int dose1, const int dose2, const double fB) {
if (dose1 < 0 || dose2 < 0) {
NEVER;
// unknown dose
return(0.0);
}
ASSERT(fB <= 0.5);
double e = this->errorRate(fB);
double pB = estimate_true_maf(fB, e);
double r = ibdLike(dose1, dose2, e, pB) / nullLike(dose1, dose2, fB);
return log10(r);
}
double ibdStruct::hbdScore(int dose, double fB) {
ASSERT(fB > 0.0 && fB < 1.0);
ASSERT(dose<3 && dose>-1);
if (dose < 0) {
NEVER;
// return 0.0;
}