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SMR_data_p1.cpp
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//
// SMR_data_p1.cpp
// SMR_CPP
//
// Created by Futao Zhang on 10/03/2016.
// Copyright (c) 2016 Futao Zhang. All rights reserved.
//
#include "SMR_data_p1.h"
namespace SMRDATA
{
void get_top_sets(eqtlInfo* eqtlinfo, vector<string> &prbIds, vector<float> &beta, vector<float> &se, vector<string> &rs, float thres)
{
if(eqtlinfo->_rowid.empty())
{
for(int i=0;i<eqtlinfo->_include.size();i++)
{
string probeId=eqtlinfo->_epi_prbID[eqtlinfo->_include[i]];
int probechr=eqtlinfo->_epi_chr[eqtlinfo->_include[i]];
double top_zsqr=0, top_beta=0, top_se=0;
string snprs="";
for (int j = 0; j<eqtlinfo->_esi_include.size(); j++)
{
if (fabs(eqtlinfo->_sexz[eqtlinfo->_include[i]][eqtlinfo->_esi_include[j]] + 9) > 1e-6)
{
int snpchr=eqtlinfo->_esi_chr[eqtlinfo->_esi_include[j]];
string rstmp=eqtlinfo->_esi_rs[eqtlinfo->_esi_include[j]];
if(snpchr==probechr)
{
float bxz=eqtlinfo->_bxz[eqtlinfo->_include[i]][eqtlinfo->_esi_include[j]];
float sexz=eqtlinfo->_sexz[eqtlinfo->_include[i]][eqtlinfo->_esi_include[j]];
float zxz=bxz/sexz;
zxz*=zxz;
if(zxz-top_zsqr>1e-8) {
top_zsqr=zxz;
top_beta=bxz;
top_se=sexz;
snprs=rstmp;
}
}
}
}
double pval=pchisq(top_zsqr, 1);
if(pval<thres)
{
prbIds.push_back(probeId);
beta.push_back(top_beta);
se.push_back(top_se);
rs.push_back(snprs);
}
}
}
else
{
for(int i=0;i<eqtlinfo->_include.size();i++)
{
string probeId=eqtlinfo->_epi_prbID[eqtlinfo->_include[i]];
int probechr=eqtlinfo->_epi_chr[eqtlinfo->_include[i]];
double top_zsqr=0, top_beta=0, top_se=0;
string snprs="";
uint64_t beta_start=eqtlinfo->_cols[eqtlinfo->_include[i]<<1];
uint64_t se_start=eqtlinfo->_cols[1+(eqtlinfo->_include[i]<<1)];
uint64_t numsnps=se_start-beta_start;
for(int j=0;j<numsnps;j++)
{
int ge_rowid=eqtlinfo->_rowid[beta_start+j];
int snpchr=eqtlinfo->_esi_chr[ge_rowid];
string snptmp=eqtlinfo->_esi_rs[ge_rowid];
if(snpchr==probechr )
{
float bxz=eqtlinfo->_val[beta_start+j];
float sexz=eqtlinfo->_val[se_start+j];
float zxz=bxz/sexz;
zxz*=zxz;
if(zxz-top_zsqr>1e-8) {
top_zsqr=zxz;
top_beta=bxz;
top_se=sexz;
snprs=snptmp;
}
}
}
double pval=pchisq(top_zsqr, 1);
if(pval<thres)
{
prbIds.push_back(probeId);
beta.push_back(top_beta);
se.push_back(top_se);
rs.push_back(snprs);
}
}
}
}
void get_thres_sets(eqtlInfo* eqtlinfo, vector<string> &prbIds, vector<float> &beta, vector<float> &se, vector<string> &rs, float thres)
{
if(eqtlinfo->_rowid.empty())
{
for(int i=0;i<eqtlinfo->_include.size();i++)
{
string probeId=eqtlinfo->_epi_prbID[eqtlinfo->_include[i]];
int probechr=eqtlinfo->_epi_chr[eqtlinfo->_include[i]];
for (int j = 0; j<eqtlinfo->_esi_include.size(); j++)
{
if (fabs(eqtlinfo->_sexz[eqtlinfo->_include[i]][eqtlinfo->_esi_include[j]] + 9) > 1e-6)
{
int snpchr=eqtlinfo->_esi_chr[eqtlinfo->_esi_include[j]];
string rstmp=eqtlinfo->_esi_rs[eqtlinfo->_esi_include[j]];
if(snpchr==probechr)
{
float bxz=eqtlinfo->_bxz[eqtlinfo->_include[i]][eqtlinfo->_esi_include[j]];
float sexz=eqtlinfo->_sexz[eqtlinfo->_include[i]][eqtlinfo->_esi_include[j]];
float zxz=bxz/sexz;
zxz*=zxz;
double pval=pchisq(zxz, 1);
if(pval<thres) {
prbIds.push_back(probeId);
beta.push_back(bxz);
se.push_back(sexz);
rs.push_back(rstmp);
}
}
}
}
}
}
else
{
for(int i=0;i<eqtlinfo->_include.size();i++)
{
string probeId=eqtlinfo->_epi_prbID[eqtlinfo->_include[i]];
int probechr=eqtlinfo->_epi_chr[eqtlinfo->_include[i]];
uint64_t beta_start=eqtlinfo->_cols[eqtlinfo->_include[i]<<1];
uint64_t se_start=eqtlinfo->_cols[1+(eqtlinfo->_include[i]<<1)];
uint64_t numsnps=se_start-beta_start;
for(int j=0;j<numsnps;j++)
{
int ge_rowid=eqtlinfo->_rowid[beta_start+j];
int snpchr=eqtlinfo->_esi_chr[ge_rowid];
string snptmp=eqtlinfo->_esi_rs[ge_rowid];
if(snpchr==probechr )
{
float bxz=eqtlinfo->_val[beta_start+j];
float sexz=eqtlinfo->_val[se_start+j];
float zxz=bxz/sexz;
zxz*=zxz;
double pval=pchisq(zxz, 1);
if(pval<thres) {
prbIds.push_back(probeId);
beta.push_back(bxz);
se.push_back(sexz);
rs.push_back(snptmp);
}
}
}
}
}
}
long est_n(vector<float> &beta,vector<float> &se)
{
long n;
VectorXd Y(se.size());
MatrixXd X(beta.size(),2);
for(int i=0;i<se.size();i++)
{
Y(i)=se[i]*se[i];
X(i,0)=1.0;
X(i,1)=beta[i]*beta[i]-Y(i);
}
MatrixXd XtX_i=(X.transpose()*X).inverse();
VectorXd w_hat=XtX_i*X.transpose()*Y;
n=-1/w_hat[1];
return n;
}
void est_effect_splsize(char* eqtlsmaslstName, char* eqtlFileName, char* snplstName,char* problstName,char* snplst2exclde, char* problst2exclde,float thres)
{
vector<string> prbIds;
vector<float> beta;
vector<float> se;
vector<string> rs;
vector<string> smasNames;
if(eqtlsmaslstName!=NULL)
{
read_smaslist(smasNames, string(eqtlsmaslstName));
if(smasNames.size()==0) throw("No eqtl summary file list in [ "+ string(eqtlsmaslstName) +" ]");
for(int ii=0;ii<smasNames.size();ii++)
{
eqtlInfo eqtlinfo;
read_esifile(&eqtlinfo, smasNames[ii]+".esi");
if (snplstName != NULL) extract_eqtl_snp(&eqtlinfo, snplstName);
if(snplst2exclde != NULL) exclude_eqtl_snp(&eqtlinfo, snplst2exclde);
read_epifile(&eqtlinfo, smasNames[ii]+".epi");
if(problstName != NULL) extract_prob(&eqtlinfo, problstName);
if(problst2exclde != NULL) exclude_prob(&eqtlinfo, problst2exclde);
read_besdfile(&eqtlinfo, smasNames[ii]+".besd");
if(eqtlinfo._rowid.empty() && eqtlinfo._bxz.empty())
{
printf("No data included from %s in the analysis.\n",smasNames[ii].c_str());
exit(EXIT_FAILURE);
}
//get_top_sets(&eqtlinfo,prbIds,beta,se,rs,thres);
get_thres_sets(&eqtlinfo,prbIds,beta,se,rs,thres);
}
} else if(eqtlFileName!=NULL)
{
eqtlInfo eqtlinfo;
read_esifile(&eqtlinfo, string(eqtlFileName)+".esi");
if (snplstName != NULL) extract_eqtl_snp(&eqtlinfo, snplstName);
if(snplst2exclde != NULL) exclude_eqtl_snp(&eqtlinfo, snplst2exclde);
read_epifile(&eqtlinfo, string(eqtlFileName)+".epi");
if(problstName != NULL) extract_prob(&eqtlinfo, problstName);
if(problst2exclde != NULL) exclude_prob(&eqtlinfo, problst2exclde);
read_besdfile(&eqtlinfo, string(eqtlFileName)+".besd");
if(eqtlinfo._rowid.empty() && eqtlinfo._bxz.empty())
{
printf("No data included from %s in the analysis.\n",eqtlFileName);
exit(EXIT_FAILURE);
}
//get_top_sets(&eqtlinfo,prbIds,beta,se,rs,thres);
get_thres_sets(&eqtlinfo,prbIds,beta,se,rs,thres);
}else {
throw("Error: please input eQTL summary data files list or eQTL summary data by the flag --beqtl-summaries or --beqtl-summary.");
}
cout<<prbIds.size()<<" eQTLs are inluded to estimate the effective population size."<<endl;
///////
string tstfile = "tst.top.bse.txt";
ofstream tst(tstfile.c_str());
if (!tst) throw ("Error: can not open the fam file " + tstfile + " to save!");
tst << "Probe" <<'\t'<<"SNP"<<'\t'<< "b" <<'\t' << "se"<<'\n';
for (int i = 0;i <beta.size(); i++) {
tst<<prbIds[i]<<'\t'<<rs[i]<<'\t'<<beta[i]<<'\t'<<se[i]<< '\n';
}
tst.close();
//////
long n=est_n(beta,se);
cout<<"The estimated effective population size is: "<<n<<endl;
}
void read_esmr(eSMRrlt* erlt, string smrFileName)
{
cout << "Reading SMR result information from [" + smrFileName + "]." << endl;
ifstream flptr;
flptr.open(smrFileName.c_str());
if (!flptr) throw ("Error: can not open the file [" + smrFileName + "] to read.");
char tbuf[MAX_LINE_SIZE];
int lineNum(0);
flptr.getline(tbuf,MAX_LINE_SIZE);// the header
while(!flptr.eof())
{
string tmpStr;
flptr.getline(tbuf,MAX_LINE_SIZE);
if(tbuf[0]!='\0'){
istringstream iss(tbuf);
iss>>tmpStr;
erlt->_Expo_id.push_back(tmpStr);
iss>>tmpStr;
erlt->_Expo_chr.push_back(atoi(tmpStr.c_str()));
iss>>tmpStr;
erlt->_Expo_gene.push_back(tmpStr);
iss>>tmpStr;
erlt->_Expo_bp.push_back(atoi(tmpStr.c_str()));
iss>>tmpStr;
erlt->_Outco_id.push_back(tmpStr);
iss>>tmpStr;
erlt->_Outco_chr.push_back(atoi(tmpStr.c_str()));
iss>>tmpStr;
erlt->_Outco_gene.push_back(tmpStr);
iss>>tmpStr;
erlt->_Outco_bp.push_back(atoi(tmpStr.c_str()));
iss>>tmpStr;
erlt->_snp_rs.push_back(tmpStr);
iss>>tmpStr;
erlt->_snp_chr.push_back(atoi(tmpStr.c_str()));
iss>>tmpStr;
erlt->_snp_bp.push_back(atoi(tmpStr.c_str()));
iss>>tmpStr;
to_upper(tmpStr);
erlt->_snp_a1.push_back(tmpStr.c_str());
iss>>tmpStr;
to_upper(tmpStr);
erlt->_snp_a2.push_back(tmpStr.c_str());
iss>>tmpStr;
erlt->_snp_frq.push_back(atof(tmpStr.c_str()));
iss>>tmpStr; // b_outcome
iss>>tmpStr; // se_outcome
iss>>tmpStr; // p_outcome
iss>>tmpStr; // b_exposure
iss>>tmpStr; // se_exposure
iss>>tmpStr; // p_exposure
iss>>tmpStr;
erlt->_b.push_back(atof(tmpStr.c_str()));
iss>>tmpStr;
erlt->_se.push_back(atof(tmpStr.c_str()));
iss>>tmpStr;
erlt->_p_smr.push_back(atof(tmpStr.c_str()));
iss>>tmpStr;
if(!tmpStr.compare("NA")) erlt->_p_heidi.push_back(-9);
else erlt->_p_heidi.push_back(atof(tmpStr.c_str()));
iss>>tmpStr;
if(!tmpStr.compare("NA")) erlt->_nsnp.push_back(-9);
else erlt->_nsnp.push_back(atoi(tmpStr.c_str()));
erlt->_include.push_back(lineNum);
lineNum++;
}
}
erlt->lineNum=lineNum;
flptr.close();
cout << lineNum << " SNPs summary info to be included from [" + smrFileName + "]." << endl;
}
void read_probevarfile(eqtlInfo* eqtlinfo, string vpFileName)
{
cout << "Reading variance information from [" + vpFileName + "]." << endl;
ifstream flptr;
flptr.open(vpFileName.c_str());
if (!flptr) throw ("Error: can not open the file [" + vpFileName + "] to read.");
char tbuf[MAX_LINE_SIZE];
int lineNum(0);
vector<string> tmp_prbid;
vector<double> tmp_var;
while(!flptr.eof())
{
string tmpStr;
flptr.getline(tbuf,MAX_LINE_SIZE);
if(tbuf[0]!='\0'){
istringstream iss(tbuf);
iss>>tmpStr;
tmp_prbid.push_back(tmpStr.c_str());
iss>>tmpStr;
tmp_var.push_back(atof(tmpStr.c_str()));
lineNum++;
}
}
flptr.close();
eqtlinfo->_epi_var.resize(eqtlinfo->_epi_prbID.size());
vector<int> idx;
match_only(eqtlinfo->_epi_prbID, tmp_prbid, idx);
if(idx.size()!=eqtlinfo->_epi_prbID.size())
{
cout<<"Some Probes in summary data are not in variance data!"<<endl;
exit(1);
}
for(int i=0;i<idx.size();i++)
{
eqtlinfo->_epi_var[i]=tmp_var[idx[i]];
}
cout << idx.size() << " probes variance info to be included from [" + vpFileName + "]." << endl;
}
void make_cojo(char* outFileName,char* eqtlFileName, char* snplstName,char* snplst2exclde, char* problstName, char* problst2exclde, char* genelistName, bool bFlag)
{
eqtlInfo eqtlinfo;
cout<<endl<<"Reading eQTL summary data..."<<endl;
if(eqtlFileName != NULL)
{
read_esifile(&eqtlinfo, string(eqtlFileName)+".esi");
if (snplstName != NULL) extract_eqtl_snp(&eqtlinfo, snplstName);
if(snplst2exclde != NULL) exclude_eqtl_snp(&eqtlinfo, snplst2exclde);
read_epifile(&eqtlinfo, string(eqtlFileName)+".epi");
if(problstName != NULL) extract_prob(&eqtlinfo, problstName);
if(genelistName != NULL) extract_prob_by_gene(&eqtlinfo, genelistName);
if(problst2exclde != NULL) exclude_prob(&eqtlinfo, problst2exclde);
read_besdfile(&eqtlinfo, string(eqtlFileName)+".besd");
if(eqtlinfo._rowid.empty() && eqtlinfo._bxz.empty())
{
printf("No data included from %s in the analysis.\n",eqtlFileName);
exit(EXIT_FAILURE);
}
}
else throw ("Error: please input the eQTL summary information for the eQTL data files by the option --beqtl-summary.");
vector<int> out_esi_id;
vector<int> out_epi_id;
vector<float> out_beta;
vector<float> out_se;
vector<double> out_pval;
if(eqtlinfo._valNum==0)
{
for(uint32_t i=0;i<eqtlinfo._probNum;i++)
{
for(uint32_t j=0;j<eqtlinfo._snpNum;j++)
{
double beta=eqtlinfo._bxz[i][j];
double se=eqtlinfo._sexz[i][j];
if(fabs(se+9)<1e-6) continue;
double zsxz=beta/se;
double pxz=pchisq(zsxz*zsxz, 1);
out_esi_id.push_back(j);
out_epi_id.push_back(i);
out_beta.push_back(beta);
out_se.push_back(se);
out_pval.push_back(pxz);
}
}
}
else
{
if(eqtlinfo._val.size()==0)
{
throw ("Error: No data extracted from the input, please check.");
}
for(uint32_t i=0;i<eqtlinfo._probNum;i++)
{
uint64_t proid=eqtlinfo._include[i];
uint64_t pos=eqtlinfo._cols[proid<<1];
uint64_t pos1=eqtlinfo._cols[(proid<<1)+1];
uint64_t num=pos1-pos;
for(int j=0;j<num;j++)
{
double beta=eqtlinfo._val[pos+j];
double se=eqtlinfo._val[pos+j+num];
double zsxz=beta/se;
double pxz=pchisq(zsxz*zsxz, 1);
out_esi_id.push_back(eqtlinfo._rowid[pos+j]);
out_epi_id.push_back(i);
out_beta.push_back(beta);
out_se.push_back(se);
out_pval.push_back(pxz);
}
}
}
string smrfile = string(outFileName)+".raw";
ofstream smr(smrfile.c_str());
if (!smr) throw ("Error: can not open the fam file " + smrfile + " to save!");
smr << "ProbeID"<<'\t' << "SNP" <<'\t'<< "Chr" <<'\t' << "A1" << '\t'<< "A2"<< '\t' << "b"<<'\t'<< "SE" << '\t'<<"p"<<'\n';
for (int i = 0;i <out_esi_id.size(); i++) {
smr<<eqtlinfo._epi_prbID[out_epi_id[i]]<<'\t'<<eqtlinfo._esi_rs[out_esi_id[i]]<<'\t'<<eqtlinfo._esi_chr[out_esi_id[i]]<<'\t'<<eqtlinfo._esi_allele1[out_esi_id[i]]<<'\t'<<eqtlinfo._esi_allele2[out_esi_id[i]]<<'\t'<<out_beta[i]<<'\t'<<out_se[i]<<'\t'<<out_pval[i]<< '\n';
}
smr.close();
cout<<"Extracted results of "<<out_esi_id.size()<<" items have been saved in the plaint text file [" + smrfile + "]."<<endl;
}
/*
void standardization(char* outFileName, char* eqtlFileName,bool bFlag,char* freqName, char* vpFileName)
{
eqtlInfo esdata;
if(eqtlFileName==NULL) throw("Error: please input eQTL summary data for SMR analysis by the flag --eqtl-summary.");
if(freqName==NULL && vpFileName==NULL) throw("Error: please input feq data or variance data for standardisation by the flag --freq or --probe-var.");
read_esifile(&esdata, string(eqtlFileName)+".esi");
read_epifile(&esdata, string(eqtlFileName)+".epi");
read_besdfile(&esdata, string(eqtlFileName)+".besd");
if(esdata._rowid.empty() && esdata._bxz.empty())
{
printf("No data included from %s in the analysis.\n",eqtlFileName);
exit(EXIT_FAILURE);
}
if(vpFileName!=NULL)
{
read_probevarfile(&esdata, string(vpFileName));
for(int i=0;i<esdata._probNum;i++)
{
double prbvar_sqrt=sqrt(esdata._epi_var[i]);
if(esdata._rowid.empty())
{
for (int j = 0; j<esdata._esi_include.size(); j++)
{
if (fabs(esdata._sexz[i][j] + 9) > 1e-6)
{
float bxz=esdata._bxz[i][j];
float sexz=esdata._sexz[i][j];
esdata._bxz[i][j]=bxz/prbvar_sqrt;
esdata._sexz[i][j]=sexz/prbvar_sqrt;
}
}
}
else{
uint64_t beta_start=esdata._cols[i<<1];
uint64_t se_start=esdata._cols[1+(i<<1)];
uint64_t numsnps=se_start-beta_start;
for(uint64_t j=0;j<numsnps;j++)
{
float bxz=esdata._val[beta_start+j];
float sexz=esdata._val[se_start+j];
esdata._val[beta_start+j]=bxz/prbvar_sqrt;
esdata._val[se_start+j]=sexz/prbvar_sqrt;
}
}
}
}
else if(freqName!=NULL)
{
update_freq(&esdata, string(freqName));
for(int i=0;i<esdata._probNum;i++)
{
if(esdata._rowid.empty())
{
for (int j = 0; j<esdata._esi_include.size(); j++)
{
if (fabs(esdata._sexz[i][j] + 9) > 1e-6)
{
float bxz=esdata._bxz[i][j];
float sexz=esdata._sexz[i][j];
float p=esdata._esi_freq[j];
float z=bxz/sexz;
float b=z/sqrt(2*p*(1-p)*(n+z*z));
float se=1/sqrt(2*p*(1-p)*(n+z*z));
esdata._bxz[i][j]=b;
esdata._sexz[i][j]=se;
}
}
}
else{
uint64_t beta_start=esdata._cols[i<<1];
uint64_t se_start=esdata._cols[1+(i<<1)];
uint64_t numsnps=se_start-beta_start;
for(uint64_t j=0;j<numsnps;j++)
{
uint64_t ge_rowid=esdata._rowid[beta_start+j];
float bxz=esdata._val[beta_start+j];
float sexz=esdata._val[se_start+j];
float p=esdata._esi_freq[ge_rowid];
float z=bxz/sexz;
float b=z/sqrt(2*p*(1-p)*(n+z*z));
float se=1/sqrt(2*p*(1-p)*(n+z*z));
esdata._val[beta_start+j]=b;
esdata._val[se_start+j]=se;
}
}
}
}
write_besd(outFileName, &esdata);
}
*/
void lookup(char* outFileName,char* eqtlFileName, char* snplstName, char* problstName,char* genelistName, double plookup,bool bFlag, int chr, int prbchr,int snpchr, char* snprs, char* fromsnprs, char* tosnprs, char* prbname, char* fromprbname, char* toprbname,int snpWind, int prbWind,char* genename,int fromsnpkb, int tosnpkb, int fromprbkb, int toprbkb, bool snpwindFlag, bool prbwindFlag,bool cis_flag, int cis_itvl,char* snpproblstName)
{
string logstr;
int flag4chr=0;
if(chr!=0) flag4chr++;
if(prbchr!=0 || snpchr!=0) flag4chr++;
if(flag4chr==2)
{
logstr="WARNING: --chr is not surpposed to use together with --probe-chr or --snp-chr. --chr will be disabled.\n";
chr=0;
fputs(logstr.c_str(), stdout);
}
map<string, string> prb_snp;
map<string, string>::iterator iter;
eqtlInfo eqtlinfo;
cout<<endl<<"Reading eQTL summary data..."<<endl;
if(eqtlFileName != NULL)
{
read_epifile(&eqtlinfo, string(eqtlFileName)+".epi");
epi_man(&eqtlinfo, problstName, genelistName, chr, prbchr, prbname, fromprbname, toprbname, prbWind, fromprbkb, toprbkb, prbwindFlag, genename);
read_esifile(&eqtlinfo, string(eqtlFileName)+".esi");
esi_man(&eqtlinfo, snplstName, chr, snpchr, snprs, fromsnprs, tosnprs, snpWind, fromsnpkb, tosnpkb, snpwindFlag, cis_flag, cis_itvl, prbname);
if(snpproblstName) extract_targets(&eqtlinfo, snpproblstName, prb_snp);
read_besdfile(&eqtlinfo, string(eqtlFileName)+".besd");
if(eqtlinfo._rowid.empty() && eqtlinfo._bxz.empty())
{
printf("No data included from %s in the analysis.\n",eqtlFileName);
exit(EXIT_FAILURE);
}
}
else throw ("Error: please input the eQTL summary information for the eQTL data files by the option --beqtl-summary.\n");
vector<int> out_esi_id;
vector<int> out_epi_id;
vector<float> out_beta;
vector<float> out_se;
vector<double> out_pval;
if(eqtlinfo._valNum==0)
{
for(uint32_t i=0;i<eqtlinfo._probNum;i++)
{
string rstarget="";
if(snpproblstName)
{
iter=prb_snp.find(eqtlinfo._epi_prbID[i]);
if(iter==prb_snp.end())
{
printf("ERROR: Bugs found.\n ");
exit(EXIT_FAILURE);
}
rstarget=iter->second;
}
for(uint32_t j=0;j<eqtlinfo._snpNum;j++)
{
if(!snpproblstName || (snpproblstName && (rstarget==eqtlinfo._esi_rs[j])))
{
double beta=eqtlinfo._bxz[i][j];
double se=eqtlinfo._sexz[i][j];
if(fabs(se+9)<1e-6) continue;
double zsxz=beta/se;
double pxz=pchisq(zsxz*zsxz, 1);
if(pxz<=plookup)
{
out_esi_id.push_back(j);
out_epi_id.push_back(i);
out_beta.push_back(beta);
out_se.push_back(se);
out_pval.push_back(pxz);
}
}
}
}
}
else
{
if(eqtlinfo._val.size()==0)
{
throw ("Error: No data extracted from the input, please check.\n");
}
for(uint32_t i=0;i<eqtlinfo._probNum;i++)
{
uint64_t proid=eqtlinfo._include[i];
uint64_t pos=eqtlinfo._cols[proid<<1];
uint64_t pos1=eqtlinfo._cols[(proid<<1)+1];
uint64_t num=pos1-pos;
string rstarget="";
if(snpproblstName)
{
iter=prb_snp.find(eqtlinfo._epi_prbID[proid]);
if(iter==prb_snp.end())
{
printf("ERROR: Bugs found.\n ");
exit(EXIT_FAILURE);
}
rstarget=iter->second;
}
for(int j=0;j<num;j++)
{
if(!snpproblstName || (snpproblstName && (rstarget==eqtlinfo._esi_rs[eqtlinfo._rowid[pos+j]])))
{
double beta=eqtlinfo._val[pos+j];
double se=eqtlinfo._val[pos+j+num];
double zsxz=beta/se;
double pxz=pchisq(zsxz*zsxz, 1);
if(pxz<=plookup)
{
out_esi_id.push_back(eqtlinfo._rowid[pos+j]);
out_epi_id.push_back(i);
out_beta.push_back(beta);
out_se.push_back(se);
out_pval.push_back(pxz);
}
}
}
}
}
string smrfile = string(outFileName)+".txt";
ofstream smr(smrfile.c_str());
if (!smr) throw ("Error: can not open the file " + smrfile + " to save!");
smr << "SNP" <<'\t'<< "Chr" <<'\t' << "BP" << '\t' << "A1" << '\t'<< "A2"<< '\t' <<"Freq"<<'\t'<< "Probe"<< '\t' << "Probe_Chr"<< '\t'<< "Probe_bp"<< '\t'<<"Gene"<<'\t'<<"Orientation"<<'\t'<<"b"<<'\t'<< "SE" << '\t'<<"p"<<'\n';
for (int i = 0;i <out_esi_id.size(); i++) {
smr<<eqtlinfo._esi_rs[out_esi_id[i]]<<'\t'<<eqtlinfo._esi_chr[out_esi_id[i]]<<'\t'<<eqtlinfo._esi_bp[out_esi_id[i]]<<'\t'<<eqtlinfo._esi_allele1[out_esi_id[i]]<<'\t'<<eqtlinfo._esi_allele2[out_esi_id[i]]<<'\t'<<((eqtlinfo._esi_freq[out_esi_id[i]]+9>1e-6)?atos(eqtlinfo._esi_freq[out_esi_id[i]]):"NA")<<'\t'<<eqtlinfo._epi_prbID[out_epi_id[i]]<<'\t'<<eqtlinfo._epi_chr[out_epi_id[i]]<<'\t'<<eqtlinfo._epi_bp[out_epi_id[i]]<<'\t'<<eqtlinfo._epi_gene[out_epi_id[i]]<<'\t'<<eqtlinfo._epi_orien[out_epi_id[i]]<<'\t'<<out_beta[i]<<'\t'<<out_se[i]<<'\t'<<out_pval[i]<< '\n';
}
smr.close();
cout<<"Extracted results of "<<out_esi_id.size()<<" SNPs have been saved in the file [" + smrfile + "]."<<endl;
}
void rm_unmatched_snp(gwasData* gdata, eqtlInfo* esdata)
{
cout<<"Checking the consistency of SNP alleles between GWAS summary data and eQTL summary data..."<<endl;
// get the common SNPs
vector<string> slctSNPs;
vector<int> id_unmatched_esd;
vector<int> id_unmatched_gwas;
vector<int> gdId;
vector<int> edId;
edId.clear();
long pre_size=esdata->_esi_include.size();
vector<string> essnp;
if(esdata->_esi_include.size()<esdata->_snpNum )
{
for(int i=0;i<esdata->_esi_include.size();i++) essnp.push_back(esdata->_esi_rs[esdata->_esi_include[i]]);
StrFunc::match_only(essnp, gdata->snpName, gdId);
if(gdId.empty()) throw("Error: no common SNPs found.");
for(int i=0;i<gdId.size();i++) slctSNPs.push_back(gdata->snpName[gdId[i]]);
}else
{
StrFunc::match_only(esdata->_esi_rs, gdata->snpName, gdId);
if(gdId.empty()) throw("Error: no common SNPs found.");
for(int i=0;i<gdId.size();i++) slctSNPs.push_back(gdata->snpName[gdId[i]]);
}
//alleles check
StrFunc::match(slctSNPs, esdata->_esi_rs, edId);
id_unmatched_esd.clear();
id_unmatched_gwas.clear();
for (int i = 0; i<edId.size(); i++)
{
string ga1, ga2, ea1, ea2, rs1, rs2;
rs1 = gdata->snpName[gdId[i]];
rs2 = esdata->_esi_rs[edId[i]];
ga1 = gdata->allele_1[gdId[i]];
ga2 = gdata->allele_2[gdId[i]];
ea1 = esdata->_esi_allele1[edId[i]];
ea2 = esdata->_esi_allele2[edId[i]];
// use the allele in eQTL summary data as the reference allele. so we won't get the whole besd into memroy
if( ea1 == ga1 && ea2 == ga2)
{
}
else if(ea1 == ga2 && ea2 == ga1)
{
gdata->byz[gdId[i]]=-gdata->byz[gdId[i]];
}else {
id_unmatched_esd.push_back(edId[i]);
id_unmatched_gwas.push_back(gdId[i]);
}
}
if(id_unmatched_esd.size()>0)
{
vector<int> tmpvec;
esdata->_esi_include.swap(tmpvec);
set_complement(id_unmatched_esd,tmpvec, esdata->_esi_include);
}
if(id_unmatched_gwas.size()>0)
{
vector<int> tmpvec;
gdata->_include.swap(tmpvec);
set_complement(id_unmatched_gwas,tmpvec, gdata->_include);
}
cout<<id_unmatched_esd.size()<<" SNPs failed in allele check and have been excluded. Total "<<gdata->_include.size()<<" SNPs left in GWAS summary dataset and "<<esdata->_esi_include.size()<<" SNPs left in eQTL summary dtaset."<<endl;
}
void rm_unmatched_snp(eqtlInfo* etrait, eqtlInfo* esdata)
{
vector<int> id_unmatched_esd;
vector<int> id_unmatched_etrait;
// get the common SNPs
vector<string> slctSNPs;
vector<string> cmmnSNPs;
vector<int> gdId;
vector<int> edId;
cmmnSNPs.clear();
edId.clear();
string logstr="Checking the consistency of SNP allelesbetween 2 eQTL summary datasets. ";
cout<<logstr<<endl;
vector<string> etsnp;
vector<string> essnp;
if(esdata->_esi_include.size()<esdata->_snpNum || etrait->_esi_include.size()<etrait->_snpNum)
{
for(int i=0;i<esdata->_esi_include.size();i++) essnp.push_back(esdata->_esi_rs[esdata->_esi_include[i]]);
for(int i=0;i<etrait->_esi_include.size();i++) etsnp.push_back(etrait->_esi_rs[etrait->_esi_include[i]]);
match_only(essnp, etsnp, gdId);
if(gdId.empty()) throw("Error: no SNPs in common.");
for(int i=0;i<gdId.size();i++) slctSNPs.push_back(etsnp[gdId[i]]);
}else
{
StrFunc::match_only(esdata->_esi_rs, etrait->_esi_rs, gdId);
if(gdId.empty()) throw("Error: no SNPs in common.");
for(int i=0;i<gdId.size();i++) slctSNPs.push_back(etrait->_esi_rs[gdId[i]]);
}
//alleles check
match(slctSNPs, esdata->_esi_rs, edId);
gdId.clear();
match(slctSNPs, etrait->_esi_rs, gdId);
cmmnSNPs.clear();
for (int i = 0; i<edId.size(); i++)
{
string ta1, ta2, ea1, ea2;
ta1 = etrait->_esi_allele1[gdId[i]];
ta2 = etrait->_esi_allele2[gdId[i]];
ea1 = esdata->_esi_allele1[edId[i]];
ea2 = esdata->_esi_allele2[edId[i]];
// use the allele in eQTL summary data as the reference allele. so we won't get the whole besd into memroy
if( ea1 == ta1 && ea2 == ta2)
{
}
else if(ea1 == ta2 && ea2 == ta1)
{
if(etrait->_val.size()>0)
{
int count=0;
for(int j=0;j<etrait->_rowid.size();j++)
{
if(etrait->_rowid[j]==gdId[i])
{
count++;
if(count & 1)
etrait->_val[j]=-etrait->_val[j];
}
}
}
else
{
for(int j=0;j<etrait->_include.size();j++) if( etrait->_sexz[j][gdId[i]]+9 > 1e-6 ) etrait->_bxz[j][gdId[i]]=-etrait->_bxz[j][gdId[i]];
}
}
else
{
id_unmatched_esd.push_back(edId[i]);
id_unmatched_etrait.push_back(gdId[i]);
}
}
if(id_unmatched_esd.size()>0)
{
vector<int> tmpvec;
esdata->_esi_include.swap(tmpvec);
set_complement(id_unmatched_esd,tmpvec, esdata->_esi_include);
}
if(id_unmatched_etrait.size()>0)
{
vector<int> tmpvec;
etrait->_esi_include.swap(tmpvec);
set_complement(id_unmatched_etrait,tmpvec, etrait->_esi_include);
}
cout<<id_unmatched_esd.size()<<" SNPs failed in allele check and have been excluded. Total "<<etrait->_esi_include.size()<<" SNPs left in one eQTL summary dataset and "<<esdata->_esi_include.size()<<" SNPs left in another eQTL summary dtaset."<<endl;
}
void read_gene_anno(char* geneAnnoName,vector<int> &chr, vector<string> &genename,vector<int> &start,vector<int> &end)
{
ifstream flptr;
flptr.open(geneAnnoName);
if (!flptr) throw ("Error: can not open the file [" + string(geneAnnoName) + "] to read.");
cout << "Reading gene annotation information from [" + string(geneAnnoName) + "]." << endl;
char buf[MAX_LINE_SIZE];
int lineNum(0);
while(!flptr.eof() )
{
string tmpStr;
flptr.getline(buf,MAX_LINE_SIZE);
if(buf[0]!='\0'){
istringstream iss(buf);
iss>>tmpStr; //chr
if(tmpStr=="X" || tmpStr=="x") chr.push_back(23);
else if(tmpStr=="Y" || tmpStr=="y") chr.push_back(24);
else chr.push_back(atoi(tmpStr.c_str()));
iss>>tmpStr; // start
start.push_back(atoi(tmpStr.c_str()));
iss>>tmpStr; // end
end.push_back(atoi(tmpStr.c_str()));
iss>>tmpStr; // gene
genename.push_back(tmpStr.c_str());
lineNum++;
}
}
cout << lineNum << " gene annotation infomation to be included from [" + string(geneAnnoName) + "]." << endl;
flptr.close();
}
void read_gene_anno_strand(char* geneAnnoName,vector<int> &chr, vector<string> &genename,vector<int> &start,vector<int> &end, vector<string> &strand)
{
ifstream flptr;
flptr.open(geneAnnoName);
if (!flptr) throw ("Error: can not open the file [" + string(geneAnnoName) + "] to read.");
cout << "Reading gene annotation information from [" + string(geneAnnoName) + "]." << endl;
char buf[MAX_LINE_SIZE];
int lineNum(0);
vector<string> vs_buf;
int col_num = -9;
while(!flptr.eof() )
{
string tmpStr;
flptr.getline(buf,MAX_LINE_SIZE);
if(buf[0]!='\0'){
vs_buf.clear();
int tmpnum = split_string(buf, vs_buf, ", \t\n");
if(tmpnum!=4 && tmpnum!=5) {
printf("ERROR: column number is not correct in row %d!\n", lineNum+2);
exit(EXIT_FAILURE);
}
if(col_num==-9)
{
col_num=tmpnum;
} else {
if(col_num!=tmpnum)
{
printf("ERROR: column number is not correct in row %d!\n", lineNum+2);
exit(EXIT_FAILURE);
}
}
int tmpchr;
if(vs_buf[0]=="X" || vs_buf[0]=="x") tmpchr=23;
else if(vs_buf[0]=="Y" || vs_buf[0]=="y") tmpchr=24;
else tmpchr=atoi(vs_buf[0].c_str());
chr.push_back(tmpchr);
start.push_back(atoi(vs_buf[1].c_str()));
end.push_back(atoi(vs_buf[2].c_str()));
genename.push_back(vs_buf[3].c_str());
if(col_num==5) strand.push_back(vs_buf[4].c_str());
lineNum++;
}
}
cout << lineNum << " gene annotation infomation to be included from [" + string(geneAnnoName) + "]." << endl;
flptr.close();
}
void plot(char* outFileName, char* bFileName,char* gwasFileName, char* eqtlFileName, double maf,char* indilstName, char* snplstName,char* problstName,bool bFlag,double p_hetero,double ld_top,int m_hetero , char* indilst2remove, char* snplst2exclde, char* problst2exclde,double p_smr, char* refSNP, bool heidioffFlag, int cis_itvl, char* genelistName, int chr,int prbchr, char* prbname, char* fromprbname, char* toprbname,int prbWind,int fromprbkb, int toprbkb,bool prbwindFlag, char* genename,int snpchr, char* snprs, char* fromsnprs, char* tosnprs,int snpWind,int fromsnpkb, int tosnpkb,bool snpwindFlag,bool cis_flag, char* geneAnnoName)
{
setNbThreads(thread_num);
if(!prbwindFlag) throw("Error: please input probe window by the flag --probe-wind.");
if(!heidioffFlag && bFileName == NULL ) throw("Error: please input Plink file by the flag --bfile.");
if(gwasFileName==NULL) throw("Error: please input GWAS summary data by the flag --gwas-summary.");
if(eqtlFileName==NULL) throw("Error: please input eQTL summary data by the flag --eqtl-summary.");
if(geneAnnoName==NULL) throw("Error: please input gene annotation file by the flag --gene-list.");
vector<int> gene_anno_chr;
vector<string> gene_anno_genename;
vector<int> gene_anno_start;
vector<int> gene_anno_end;
read_gene_anno(geneAnnoName,gene_anno_chr, gene_anno_genename,gene_anno_start,gene_anno_end);
map<string, int> gene_anno_map;
map<string, int>::iterator iter;
for(int i=0;i<gene_anno_genename.size();i++) gene_anno_map.insert(pair<string,int>(gene_anno_genename[i], i));
eqtlInfo prbhead;
read_epifile(&prbhead, string(eqtlFileName)+".epi");
if(problstName != NULL || genelistName != NULL)
{
if(problstName != NULL) extract_prob(&prbhead, problstName);
if(genelistName != NULL) extract_prob_by_gene(&prbhead, genelistName);
}
else if(prbname!=NULL)
{
extract_eqtl_single_probe(&prbhead, prbname);