double EAPEstimator::estimateSE(Prior prior, size_t question, int answer) {
const double theta_hat = estimateTheta(prior,question,answer);
integrableFunction denominator = [&](double theta) {
return likelihood(theta,question,answer) * prior.prior(theta);
};
integrableFunction numerator = [&](double theta) {
const double theta_difference = theta - theta_hat;
return theta_difference * theta_difference * denominator(theta);
};
return std::pow(integralQuotient(numerator, denominator, questionSet.lowerBound, questionSet.upperBound), 0.5);
}
///////////////////////////////////////////////////////////////////////////////
// main
int main(int argc, char** argv) {
int i, j, k, l, m, n;
char path[1000] = "", Ypath[1000]="", filename[1500], relationship[50];
double ***alleleFreqs, *tmparr1, *tmparr2;
int **samplesizes, *Ysamplesizes, *modYsamplesizes;
int **indiv1, **indiv2, *Yindiv1, *Yindiv2;
double *ks;
double *LRs;
int *nalleles;
int ***refHaps, totYindivs;
double **estYThetas, **YhapFreqs, **modYhapFreqs;
int *popmap;
double **FPRs;
int *nSameYchr;
//constants
int npops = 5;
int nSTRs = 13;
double ndatabase = 1824085.0;
int seed = time(NULL);
double simtheta = 0.010;
double calctheta = 0.010;
int niter = 10000;
char *STRs[] = {"CSF1PO", "FGA", "TH01", "TPOX", "vWA", "D3S1358", "D5S818",
"D7S820", "D8S1179", "D13S317", "D16S539", "D18S51", "D21S11"};
int nYpops = 13;
int nYSTRs = 16;
char *Ypopnames[] = {"African_American", "Asian", "Asian_Indian", "Caucasian", "Chinese",
"Filipino", "Hispanic", "Japanese", "Malay", "Native_American",
"Sub-sharan_African", "Thai", "Vietnamese"};
srandom(seed);
//parsing command line arguments
if(argc < 3) {
printf("Missing input file(s). \n\tUsage: ./autYsimUnrelPopPair -f PATH -g YPATH -n nLOCI -s simtheta -c calctheta -i nITER\n");
exit(0);
}
for(i=1; i<argc; i++) {
if(argv[i][0] == '-'){
switch(argv[i][1]) {
case 'f' :
(void) strcpy(path, &argv[i][3]); break;
case 'g' :
(void) strcpy(Ypath, &argv[i][3]); break;
case 'n' :
nSTRs = atoi(&argv[i][3]); break;
case 's' :
simtheta = atof(&argv[i][3]); break;
case 'c' :
calctheta = atof(&argv[i][3]); break;
case 'i' :
niter = atoi(&argv[i][3]); break;
default :
printf("Unknown option %s\n",argv[i]);
}
}
}
//malloc and fill-in nalleles
nalleles = (int*) malloc(13*sizeof(int));
//ALERT: use the first version for BudowleMoretti and the second for BudowleSheaNiezgodaChakraborty
nalleles[0]=11; nalleles[1]=23; nalleles[2]=9; nalleles[3]=7; nalleles[4]=10;
nalleles[5]=9; nalleles[6]=10; nalleles[7]=9; nalleles[8]=11; nalleles[9]=9;
nalleles[10]=9; nalleles[11]=16; nalleles[12]=23;
/*
nalleles[0]=14; nalleles[1]=31; nalleles[2]=10; nalleles[3]=10; nalleles[4]=12;
nalleles[5]=12; nalleles[6]=12; nalleles[7]=18; nalleles[8]=11; nalleles[9]=12;
nalleles[10]=11; nalleles[11]=20; nalleles[12]=34;
*/
//malloc samplesizes
samplesizes = (int**) malloc(13*sizeof(int*));
for(i=0; i<13; i++)
samplesizes[i] = (int*) malloc(npops*sizeof(int));
Ysamplesizes = (int*) malloc(nYpops*sizeof(int));
modYsamplesizes = (int*) malloc(nYpops*sizeof(int));
//malloc indiv1 and indiv2 [STR][allele]
indiv1 = (int**) malloc(nSTRs*sizeof(int*));
indiv2 = (int**) malloc(nSTRs*sizeof(int*));
for(j=0; j<nSTRs; j++) {
indiv1[j] = (int*) malloc(2*sizeof(int));
indiv2[j] = (int*) malloc(2*sizeof(int));
}
//malloc ks
ks = (double*) malloc(3*sizeof(double*));
//malloc tmparrs
tmparr1 = (double*) malloc(nYpops*sizeof(double));
tmparr2 = (double*) malloc(nYpops*sizeof(double));
//malloc LRs[assumed pop number]
LRs = (double*) malloc(npops*sizeof(double));
//malloc FPRs[sim pop1][sim pop 2
FPRs = (double**) malloc(npops*sizeof(double*));
for(i=0; i<npops; i++)
FPRs[i] = (double*) malloc(npops*sizeof(double));
//malloc alleleFreqs[STR number][allele][population]
alleleFreqs = (double***) malloc(13*sizeof(double**));
for(i=0; i<13; i++) {
alleleFreqs[i] = (double**) malloc(nalleles[i]*sizeof(double*));
for(j=0; j<nalleles[i]; j++) {
alleleFreqs[i][j] = (double*) malloc(npops*sizeof(double));
}
}
//read in sample sizes for Y haps
readYSampleSizes(Ypath, nYpops, Ysamplesizes);
//printf("ysamplesizes are: \n");
//printIntArr(Ysamplesizes, nYpops);
//init totYindivs
totYindivs = 0;
for(i=0; i<nYpops; i++)
totYindivs += Ysamplesizes[i];
//malloc refHaps[population][indiv][STR]
refHaps = (int***) malloc(nYpops*sizeof(int**));
for(i=0; i<nYpops; i++) {
refHaps[i] = (int**) malloc(Ysamplesizes[i]*sizeof(int*));
for(j=0; j<Ysamplesizes[i]; j++) {
refHaps[i][j] = (int*) malloc(nYSTRs*sizeof(int));
}
}
//malloc estYThetas[pop1][pop2]
estYThetas = (double**) malloc(nYpops*sizeof(double*));
for(i=0; i<nYpops; i++)
estYThetas[i] = (double*) malloc(nYpops*sizeof(double));
//malloc YhapFreqs[population][haplotype]
YhapFreqs = (double**) malloc(nYpops*sizeof(double*));
for(i=0; i<nYpops; i++)
YhapFreqs[i] = (double*) malloc(totYindivs*sizeof(double));
//malloc modYhapFreqs[population][haplotype]
modYhapFreqs = (double**) malloc(nYpops*sizeof(double*));
for(i=0; i<nYpops; i++)
modYhapFreqs[i] = (double*) malloc(totYindivs*sizeof(double));
//malloc and set popmap to be popmap[auto pop i] = Y pop i
popmap = (int*) malloc(npops*sizeof(int));
popmap[0] = 12;
popmap[1] = 0;
popmap[2] = 3;
popmap[3] = 6;
popmap[4] = 9;
//malloc Yindivs
Yindiv1 = (int*) malloc(1*sizeof(int));
Yindiv2 = (int*) malloc(1*sizeof(int));
//read in allele frequencies
readAlleleFreqs(path, STRs, nalleles, npops, alleleFreqs, samplesizes);
//read in reference haplotypes
readRefHaps(Ypath, nYpops, refHaps, Ysamplesizes, nYSTRs, Ypopnames);
//estimate theta for Y chr simulations
estimateTheta(refHaps, nYpops, Ysamplesizes, nYSTRs, estYThetas);
//print2dDouArr(estYThetas, nYpops, nYpops);
//get Y hap frequencies
calcHapFreqs(refHaps, nYpops, Ysamplesizes, nYSTRs, YhapFreqs);
sprintf(filename, "results/autYsimUnrelPopPair/%s/YhapFreqs1.res", path);
write2dDouArr(YhapFreqs, nYpops, totYindivs, filename);
//loop through relationships
for(n=0; n<2; n++) {
//set relationship as p-o and sib
switch(n) {
case 0: //set parent-offspring
ks[0] = 0.0; ks[1] = 1.0; ks[2] = 0.0;
sprintf(relationship, "p-o");
break;
case 1: //set sib
ks[0] = .25; ks[1] = .5; ks[2] = .25;
sprintf(relationship, "sib");
break;
}
//init FPRs
for(i=0; i<npops; i++)
for(j=0; j<npops; j++)
FPRs[i][j] = 0.0;
/*
nSameYchr = (int*) malloc(npops*sizeof(int));
for(i=0; i<npops; i++)
nSameYchr[i] = 0;
*/
for(k=0; k<niter; k++) {
//run through each population pair, making rand indivs and calcing LR for a match
for(i=0; i<npops; i++) {
for(j=i; j<npops; j++) {
//make two unrel individuals assuming memberships in each population
if(i!=j) {
thetaRandIndiv(alleleFreqs, 13, nalleles, i, simtheta, indiv1);
thetaRandIndiv(alleleFreqs, 13, nalleles, j, simtheta, indiv2);
thetaRandIndivYchr(YhapFreqs[popmap[i]], modYhapFreqs[popmap[i]], totYindivs, Yindiv1, Ysamplesizes, modYsamplesizes, popmap[i], nYpops);
thetaRandIndivYchr(YhapFreqs[popmap[j]], modYhapFreqs[popmap[j]], totYindivs, Yindiv2, Ysamplesizes, modYsamplesizes, popmap[j], nYpops);
} else {
thetaRandUnrelIndivPair(alleleFreqs, 13, nalleles, i, simtheta, indiv1, indiv2);
//thetaRandUnrelIndivPairYchr(YhapFreqs[popmap[i]], modYhapFreqs[popmap[i]], totYindivs, estYThetas[popmap[i]][popmap[i]], Yindiv1, Yindiv2, Ysamplesizes, modYsamplesizes, popmap[i], nYpops);
randUnrelIndivPairYchr(YhapFreqs[popmap[i]], modYhapFreqs[popmap[i]], totYindivs, Yindiv1, Yindiv2, Ysamplesizes, modYsamplesizes, popmap[i], nYpops);
/*if(Yindiv1[0] == Yindiv2[0]) {
nSameYchr[i]++;
//printf("got same Ychr in pop %d\n", i);
}*/
}
LR(indiv1, indiv2, alleleFreqs, npops, nalleles, samplesizes, tmparr1, calctheta, ks);
for(l=0; l<npops; l++)
LRs[l] = tmparr1[l];
YLR(Yindiv1[0], Yindiv2[0], modYhapFreqs, nYpops, modYsamplesizes, tmparr1);
for(l=0; l<npops; l++)
LRs[l] *= tmparr1[popmap[l]];
//check if would be a positive
if(isfinite(LRs[1]) && isfinite(LRs[2]) && isfinite(LRs[3])
&& !isnan(LRs[1]) && !isnan(LRs[2]) && !isnan(LRs[3])
&& LRs[1]/ndatabase>.1 && LRs[2]/ndatabase>.1 && LRs[3]/ndatabase>.1
&& (LRs[1]/ndatabase>1 || LRs[2]/ndatabase>1 || LRs[3]/ndatabase>.1)) {
//printf("!!!got positive with pop %d and %d, with Yhaps %d and %d, aut genos:\n", i, j, Yindiv1[0], Yindiv2[0]);
//print2dIntArr(indiv1, 13, 2);
//print2dIntArr(indiv2, 13, 2);
//printf("LRs:\n");
//printDouArr(LRs, npops);
FPRs[i][j]++;
}
} //end pop j loop
} //end pop i loop
}//end niter loop
//print nSameYchrs
//printIntArr(nSameYchr, npops);
//normalize FPRs
for(i=0; i<npops; i++)
for(j=i; j<npops; j++)
FPRs[i][j] /= niter;
//write results to files
sprintf(filename, "results/autYsimUnrelPopPair/%s/fpr/%s_%diter_simtheta%1.3f_calctheta%1.3f_FPRtab_rep2.res", path, relationship, niter, simtheta, calctheta);
write2dDouArr(FPRs, npops, npops, filename);
}//end relationship loop
//free memory
for(i=0; i<nSTRs; i++) {
for(j=0; j<nalleles[i]; j++)
free(alleleFreqs[i][j]);
free(alleleFreqs[i]);
}
free(alleleFreqs);
free(nalleles);
for(i=0; i<nSTRs; i++)
free(samplesizes[i]);
free(samplesizes);
for(j=0; j<nSTRs; j++) {
free(indiv1[j]);
free(indiv2[j]);
}
free(indiv1);
free(indiv2);
free(ks);
free(tmparr1);
free(tmparr2);
free(LRs);
free(Yindiv1);
free(Yindiv2);
return 0;
}