/**
* Main routine. The main logic of ProbABEL can be found here
*
* \param argc Number of command line arguments
* \param argv Vector containing the command line arguments
*
* \return 0 if all went well. Other integer numbers if an error
* occurred
*/
int main(int argc, char * argv[])
{
cmdvars input_var;
input_var.set_variables(argc, argv);
input_var.printinfo();
cout << "Reading info data...\n" << flush;
mlinfo mli(input_var.getMlinfofilename(), input_var.getMapfilename());
int nsnps = mli.nsnps;
phedata phd;
cout << "Reading phenotype data...\n" << flush;
int interaction_cox = create_phenotype(phd, input_var);
masked_matrix invvarmatrix;
if (input_var.getInverseFilename() != NULL)
{
loadInvSigma(input_var, phd, invvarmatrix);
}
gendata gtd;
cout << "Reading genotype data... " << flush;
if (!input_var.getIsFvf())
{
// TODO(maartenk): remove timing code
// make clock to time loading of the non filevector file
std::clock_t start;
start = std::clock();
// use the non-filevector input format
gtd.re_gendata(input_var.getGenfilename(), nsnps,
input_var.getNgpreds(), phd.nids_all, phd.nids,
phd.allmeasured, input_var.getSkipd(), phd.idnames);
// TODO(maartenk): remove timing code
double millisec=((std::clock() - start) / (double)(CLOCKS_PER_SEC / 1000))/1000;
cout << "done in "<< millisec<< " seconds.\n" << flush;
}
else
{
// use the filevector input format (missing second last skipd
// parameter)
gtd.re_gendata(input_var.getStrGenfilename(), nsnps,
input_var.getNgpreds(), phd.nids_all, phd.nids,
phd.allmeasured, phd.idnames);
cout << "done.\n" << flush;
}
// estimate null model
#if COXPH
coxph_data nrgd = coxph_data(phd, gtd, -1);
#else
regdata nrgd = regdata(phd, gtd, -1, input_var.isIsInteractionExcluded());
#endif
std::cout << " loaded null data..." << std::flush;
#if LOGISTIC
logistic_reg nrd = logistic_reg(nrgd);
nrd.estimate(0, 0,
input_var.getInteraction(),
input_var.getNgpreds(),
invvarmatrix,
input_var.getRobust(),
1);
#elif LINEAR
linear_reg nrd = linear_reg(nrgd);
#if DEBUG
std::cout << "[DEBUG] linear_reg nrd = linear_reg(nrgd); DONE.";
#endif
nrd.estimate(0, 0, input_var.getInteraction(),
input_var.getNgpreds(), invvarmatrix,
input_var.getRobust(), 1);
#elif COXPH
coxph_reg nrd = coxph_reg(nrgd);
nrd.estimate(nrgd, 0,
input_var.getInteraction(), input_var.getNgpreds(),
true, 1, mli, 0);
#endif
double null_loglik = nrd.loglik;
std::cout << " estimated null model...";
// end null
#if COXPH
coxph_data rgd(phd, gtd, 0);
#else
regdata rgd(phd, gtd, 0, input_var.isIsInteractionExcluded());
#endif
std::cout << " formed regression object...\n";
// Open a vector of files that will be used for output. Depending
// on the number of genomic predictors we either open 5 files (one
// for each model if we have prob data) or one (if we have dosage
// data).
std::string outfilename_str(input_var.getOutfilename());
std::vector<std::ofstream*> outfile;
// Prob data: All models output. One file per model
if (input_var.getNgpreds() == 2)
{
open_files_for_output(outfile, outfilename_str);
if (input_var.getNohead() != 1)
{
create_header(outfile, input_var, phd, interaction_cox);
}
}
else // Dosage data: Only additive model => only one output file
{
outfile.push_back(
new std::ofstream((outfilename_str + "_add.out.txt").c_str()));
if (!outfile[0]->is_open())
{
std::cerr << "Cannot open file for writing: "
<< outfilename_str
<< "\n";
exit(1);
}
if (input_var.getNohead() != 1)
{
create_header(outfile, input_var, phd, interaction_cox);
}
} // END else: we have dosage data => only one file
int maxmod = 5; // Total number of models (in random
// order: additive, recessive,
// dominant, over_dominant, 2df). Only
// with dosage data can we run all of
// them. For dosage data we can only
// run the additive model.
int start_pos, end_pos;
std::vector<std::ostringstream *> beta_sebeta;
// Han Chen
std::vector<std::ostringstream *> covvalue;
// Oct 26, 2009
std::vector<std::ostringstream *> chi2;
// Create string streams for betas, SEs, etc. These are used to
// later store the various output values that will be written to
// files.
for (int i = 0; i < maxmod; i++)
{
beta_sebeta.push_back(new std::ostringstream());
beta_sebeta[i]->precision(6);
// *beta_sebeta[i] << scientific;
// Han Chen
covvalue.push_back(new std::ostringstream());
covvalue[i]->precision(6);
// *covvalue[i] << scientific;
// Oct 26, 2009
chi2.push_back(new std::ostringstream());
chi2[i]->precision(6);
// *chi2[i] << scientific;
}
// Here we start the analysis for each SNP.
for (int csnp = 0; csnp < nsnps; csnp++)
{
rgd.update_snp(>d, csnp);
int poly = 1;
if (fabs(rgd.freq) < 1.e-16 || fabs(1. - rgd.freq) < 1.e-16)
{
poly = 0;
}
if (fabs(mli.Rsq[csnp]) < 1.e-16)
{
poly = 0;
}
// Write mlinfo information to the output file(s)
// Prob data: All models output. One file per model
if (input_var.getNgpreds() == 2)
{
for (unsigned int file = 0; file < outfile.size(); file++)
{
write_mlinfo(outfile, file, mli, csnp, input_var,
rgd.gcount, rgd.freq);
}
} else{
// Dosage data: only additive model
int file = 0;
write_mlinfo(outfile, file, mli, csnp, input_var,
rgd.gcount, rgd.freq);
maxmod = 1; // We can only calculate the additive
// model with dosage data
}
// Run regression for each model for the current SNP
for (int model = 0; model < maxmod; model++)
{
if (poly) // Allele freq is not too rare
{
#if LOGISTIC
logistic_reg rd(rgd);
#elif LINEAR
linear_reg rd(rgd);
#elif COXPH
coxph_reg rd(rgd);
#endif
#if !COXPH
if (input_var.getScore())
{
rd.score(nrd.residuals, model,
input_var.getInteraction(),
input_var.getNgpreds(),
invvarmatrix);
}
else
{
rd.estimate(0, model,
input_var.getInteraction(),
input_var.getNgpreds(),
invvarmatrix,
input_var.getRobust());
}
#else
rd.estimate(rgd, model,
input_var.getInteraction(),
input_var.getNgpreds(), true, 0, mli, csnp);
#endif
int number_of_rows_or_columns = rd.beta.nrow;
start_pos = get_start_position(input_var, model,
number_of_rows_or_columns);
// The regression coefficients for the SNPs are in the
// last rows of beta[] and sebeta[].
for (int pos = start_pos; pos < rd.beta.nrow; pos++)
{
*beta_sebeta[model] << input_var.getSep()
<< rd.beta[pos]
<< input_var.getSep()
<< rd.sebeta[pos];
// Han Chen
#if !COXPH
if (input_var.getInverseFilename() == NULL
&& !input_var.getAllcov()
&& input_var.getInteraction() != 0)
{
if (pos > start_pos)
{
if (model == 0)
{
if (input_var.getNgpreds() == 2)
{
if (pos > start_pos + 2)
{
*covvalue[model]
<< rd.covariance[pos - 3]
<< input_var.getSep()
<< rd.covariance[pos - 2];
}
} // END ngpreds=2
else
{
*covvalue[model] << rd.covariance[pos - 1];
}
} // END model == 0
else
{
*covvalue[model] << rd.covariance[pos - 1];
} // END model != 0
} // END if pos > start_pos
}
#endif
// Oct 26, 2009
} // END for(pos = start_pos; pos < rd.beta.nrow; pos++)
// calculate chi^2
// ________________________________
// cout << rd.loglik<<" "<<input_var.getNgpreds() << "\n";
if (input_var.getInverseFilename() == NULL)
{ // Only if we don't have an inv.sigma file can we use LRT
if (input_var.getScore() == 0)
{
double loglik = rd.loglik;
if (rgd.gcount != gtd.nids)
{
// If SNP data is missing we didn't
// correctly compute the null likelihood
// Recalculate null likelihood by
// stripping the SNP data column(s) from
// the X matrix in the regression object
// and run the null model estimation again
// for this SNP.
#if !COXPH
regdata new_rgd = rgd;
#else
coxph_data new_rgd = rgd;
#endif
new_rgd.remove_snp_from_X();
#ifdef LINEAR
linear_reg new_null_rd(new_rgd);
#elif LOGISTIC
logistic_reg new_null_rd(new_rgd);
#endif
#if !COXPH
new_null_rd.estimate(0,
model,
input_var.getInteraction(),
input_var.getNgpreds(),
invvarmatrix,
input_var.getRobust(), 1);
#else
coxph_reg new_null_rd(new_rgd);
new_null_rd.estimate(new_rgd,
model,
input_var.getInteraction(),
input_var.getNgpreds(),
true, 1, mli, csnp);
#endif
*chi2[model] << 2. * (loglik - new_null_rd.loglik);
}
else
{
// No missing SNP data, we can compute the LRT
*chi2[model] << 2. * (loglik - null_loglik);
}
} else{
// We want score test output
*chi2[model] << rd.chi2_score;
}
} // END if( inv.sigma == NULL )
else if (input_var.getInverseFilename() != NULL)
{
// We can't use the LRT here, because mmscore is a
// REML method. Therefore go for the Wald test
if (input_var.getNgpreds() == 2 && model == 0)
{
/* For the 2df model we can't simply use the
* Wald statistic. This can be fixed using the
* equation just below Eq.(4) in the ProbABEL
* paper. TODO LCK
*/
*chi2[model] << "NaN";
}
else
{
double Z = rd.beta[start_pos] / rd.sebeta[start_pos];
*chi2[model] << Z * Z;
}
}
} // END first part of if(poly); allele not too rare
else
{ // SNP is rare: beta, sebeta, chi2 = NaN
int number_of_rows_or_columns = rgd.X.ncol;
start_pos = get_start_position(input_var, model,
number_of_rows_or_columns);
if (input_var.getInteraction() != 0 && !input_var.getAllcov()
&& input_var.getNgpreds() != 2)
{
start_pos++;
}
if (input_var.getNgpreds() == 0)
{
end_pos = rgd.X.ncol;
} else{
end_pos = rgd.X.ncol - 1;
}
if (input_var.getInteraction() != 0)
{
end_pos++;
}
for (int pos = start_pos; pos <= end_pos; pos++)
{
*beta_sebeta[model] << input_var.getSep()
<< "NaN"
<< input_var.getSep()
<< "NaN";
}
if (input_var.getNgpreds() == 2)
{
// Han Chen
#if !COXPH
if (!input_var.getAllcov()
&& input_var.getInteraction() != 0)
{
if (model == 0)
{
*covvalue[model] << "NaN"
<< input_var.getSep()
<< "NaN";
} else{
*covvalue[model] << "NaN";
}
}
#endif
// Oct 26, 2009
*chi2[model] << "NaN";
} else{
// ngpreds==1 (and SNP is rare)
if (input_var.getInverseFilename() == NULL)
{
// Han Chen
#if !COXPH
if (!input_var.getAllcov()
&& input_var.getInteraction() != 0)
{
*covvalue[model] << "NaN";
}
#endif
// Oct 26, 2009
} // END if getInverseFilename == NULL
*chi2[model] << "NaN";
} // END ngpreds == 1 (and SNP is rare)
} // END else: SNP is rare
} // END of model cycle
// Start writing beta's, se_beta's etc. to file
if (input_var.getNgpreds() == 2)
{
for (int model = 0; model < maxmod; model++)
{
*outfile[model] << beta_sebeta[model]->str()
<< input_var.getSep();
#if !COXPH
if (!input_var.getAllcov() && input_var.getInteraction() != 0)
{
*outfile[model] << covvalue[model]->str()
<< input_var.getSep();
}
#endif
*outfile[model] << chi2[model]->str()
<< "\n";
} // END for loop over all models
}
else // Dose data: only additive model. Only one output file
{
*outfile[0] << beta_sebeta[0]->str() << input_var.getSep();
#if !COXPH
if (!input_var.getAllcov() && input_var.getInteraction() != 0)
{
*outfile[0] << covvalue[0]->str() << input_var.getSep();
}
#endif
*outfile[0] << chi2[0]->str() << "\n";
} // End ngpreds == 1 when writing output files
// Clean chi2 and other streams
for (int model = 0; model < maxmod; model++)
{
beta_sebeta[model]->str("");
// Han Chen
covvalue[model]->str("");
// Oct 26, 2009
chi2[model]->str("");
}
update_progress_to_cmd_line(csnp, nsnps);
} // END for loop over all SNPs
// We're almost done. All computations have finished, time to
// clean up.
std::cout << setprecision(2) << fixed;
std::cout << "\b\b\b\b\b\b\b\b\b" << 100.;
std::cout << "%... done\n";
// Close output files
for (unsigned int i = 0; i < outfile.size(); i++)
{
outfile[i]->close();
delete outfile[i];
}
// delete gtd;
// Clean up a couple of vectors
std::vector<std::ostringstream *>::iterator it = beta_sebeta.begin();
while (it != beta_sebeta.end())
{
delete *it;
++it;
}
it = covvalue.begin();
while (it != covvalue.end())
{
delete *it;
++it;
}
it = chi2.begin();
while (it != chi2.end())
{
delete *it;
++it;
}
return (0);
}
int main(int argc, char * argv [])
{
int next_option;
const char * const short_options = "p:i:d:m:n:c:o:s:t:g:a:erlh:b:vu";
//b - interaction parameter
const struct option long_options [] =
{
{"pheno", 1, NULL, 'p'},
{"info", 1, NULL, 'i'},
{"dose", 1, NULL, 'd'},
{"map", 1, NULL, 'm'},
{"nids", 1, NULL, 'n'},
{"chrom", 1, NULL, 'c'},
{"out", 1, NULL, 'o'},
{"skipd", 1, NULL, 's'},
{"ntraits",1, NULL, 't'},
{"ngpreds",1, NULL, 'g'},
{"separat",1, NULL, 'a'},
{"score", 0, NULL, 'r'},
{"no-head",0, NULL, 'e'},
{"allcov", 0, NULL, 'l'},
{"help", 0, NULL, 'h'},
{"interaction", 1, NULL, 'b'},
{"interaction_only", 1, NULL, 'k'},
{"mmscore", 1, NULL, 'v'},
{"robust", 0, NULL, 'u'},
{NULL , 0, NULL, 0 }
};
char * program_name = argv[0];
char *phefilename = NULL;
char *mlinfofilename = NULL;
char *genfilename = NULL;
char *mapfilename = NULL;
char *outfilename = NULL;
char *inverse_filename = NULL;
string sep = " ";
int nohead=0;
int score=0;
int npeople=-1;
int ngpreds=1;
int interaction=0;
int interaction_excluded=0;
int robust = 0;
string chrom = "-1";
int neco[] = {0,0,0};
bool iscox=false;
#if COXPH
int noutcomes = 2;
iscox=true;
#else
int noutcomes = 1;
#endif
int skipd = 2;
int allcov = 0;
do
{
next_option = getopt_long(argc,argv,short_options,long_options,NULL);
switch (next_option)
{
case 'h': print_help(program_name,0);
case 'p':
phefilename = optarg;
neco[0]=1;
break;
case 'i':
mlinfofilename = optarg;
neco[1]=1;
break;
case 'd':
genfilename = optarg;
neco[2]=1;
break;
case 'm':
mapfilename = optarg;
break;
case 'n':
npeople = atoi(optarg);
break;
case 'c':
chrom = optarg;
break;
case 'o':
outfilename = optarg;
break;
case 's':
skipd = atoi(optarg);
break;
case 't':
noutcomes = atoi(optarg);
break;
case 'g':
ngpreds = atoi(optarg);
break;
case 'a':
sep = optarg;
break;
case 'e':
nohead=1;
break;
case 'r':
score=1;
break;
case 'l':
allcov=1;
break;
case 'b':
interaction=atoi(optarg);
break;
case 'k':
interaction_excluded=atoi(optarg);
break;
case 'v':
inverse_filename=optarg;
break;
case 'u':
robust=1;
break;
case '?': print_usage(program_name,1);
case -1 : break;
default: abort();
}
}
while (next_option != -1);
fprintf(stdout,
"ProbABEL v. %s (%s) (C) Yurii Aulchenko, Maksim Struchalin, EMCR, and others\n\n",
VERSION, DATE);
if (neco[0]!=1 || neco[1]!=1 || neco[2]!=1)
{
print_usage(program_name,1);
}
fprintf(stdout,"Options in effect:\n");
fprintf(stdout,"\t --pheno = %s\n",phefilename);
fprintf(stdout,"\t --info = %s\n",mlinfofilename);
fprintf(stdout,"\t --dose = %s\n",genfilename);
fprintf(stdout,"\t --ntraits = %d\n",noutcomes);
fprintf(stdout,"\t --ngpreds = %d\n",ngpreds);
fprintf(stdout,"\t --interaction = %d\n",interaction);
fprintf(stdout,"\t --interaction_only = %d\n",interaction_excluded);
if (inverse_filename != NULL) fprintf(stdout,"\t --mmscore = %s\n",inverse_filename);
else fprintf(stdout,"\t --mmscore = not in output\n");
// fprintf(stdout,"\t --mmscore = %s\n",inverse_filename);
if (mapfilename != NULL) fprintf(stdout,"\t --map = %s\n",mapfilename);
else fprintf(stdout,"\t --map = not in output\n");
if (npeople>0) fprintf(stdout,"\t --nids = %d\n",npeople);
else fprintf(stdout,"\t --nids = estimated from data\n");
if (chrom != "-1") cout << "\t --chrom = " << chrom << "\n";
else cout << "\t --chrom = not in output\n";
if (outfilename != NULL ) fprintf(stdout,"\t --out = %s\n",outfilename);
else fprintf(stdout,"\t --out = regression.out.txt\n");
fprintf(stdout,"\t --skipd = %d\n",skipd);
cout << "\t --separat = \"" << sep << "\"\n";
if (score)
fprintf(stdout,"\t --score = ON\n");
else
fprintf(stdout,"\t --score = OFF\n");
if (nohead)
fprintf(stdout,"\t --nohead = ON\n");
else
fprintf(stdout,"\t --nohead = OFF\n");
if (allcov)
fprintf(stdout,"\t --allcov = ON\n");
else
fprintf(stdout,"\t --allcov = OFF\n");
if (robust)
fprintf(stdout,"\t --robust = ON\n");
else
fprintf(stdout,"\t --robust = OFF\n");
if (ngpreds!=1 && ngpreds!=2)
{
fprintf(stderr,"\n\n--ngpreds should be 1 for MLDOSE or 2 for MLPROB\n");
exit(1);
}
if(interaction_excluded != 0)
{
interaction = interaction_excluded; //ups
is_interaction_excluded = true;
}
#if COXPH
if (score)
{
fprintf(stderr,"\n\nOption --score is implemented for linear and logistic models only\n");
exit(1);
}
#endif
// if (allcov && ngpreds>1)
// {
// fprintf(stdout,"\n\nWARNING: --allcov allowed only for 1 predictor (MLDOSE)\n");
// allcov = 0;
// }
mlinfo mli(mlinfofilename,mapfilename);
int nsnps = mli.nsnps;
phedata phd(phefilename,noutcomes,npeople, interaction, iscox);
int interaction_cox = interaction;
#if COXPH
interaction_cox--;
#endif
if(interaction < 0 || interaction > phd.ncov || interaction_cox > phd.ncov)
{
std::cerr << "error: Interaction parameter is out of range (ineraction="<<interaction<<") \n";
exit(1);
}
//interaction--;
// if(inverse_filename != NULL && phd.ncov > 1)
// {
// std::cerr<<"Error: In mmscore you can not use any covariates. You phenotype file must conatin id column and trait (residuals) only\n";
// exit(1);
// }
// if(inverse_filename != NULL && (allcov == 1 || score == 1 || interaction != 0 || ngpreds==2))
// {
// std::cerr<<"Error: In mmscore you can use additive model without any inetractions only\n";
// exit(1);
// }
mematrix<double> invvarmatrix;
#if LOGISTIC
if(inverse_filename != NULL) {std::cerr<<"ERROR: mmscore is forbidden for logistic regression\n";exit(1);}
#endif
#if COXPH
if(inverse_filename != NULL) {std::cerr<<"ERROR: mmscore is forbidden for cox regression\n";exit(1);}
if (robust) {
//std::cerr<<"ERROR: robust standard errors not implemented for Cox regression (drop us e-mail if you really need that)\n";exit(1);
cout << "Robust standard errors implemented for Cox regression\n";
}
#endif
if(inverse_filename != NULL)
{
std::cout<<"you are runing mmscore...\n";
}
std::cout << "Reading data ...";
if(inverse_filename != NULL)
{
InvSigma inv(inverse_filename, &phd);
invvarmatrix = inv.get_matrix();
double par=1.; //var(phd.Y)*phd.nids/(phd.nids-phd.ncov-1);
invvarmatrix = invvarmatrix*par;
// matrix.print();
}
std::cout.flush();
gendata gtd(genfilename,nsnps,ngpreds,phd.nids_all,phd.nids,phd.allmeasured,skipd,phd.idnames);
// estimate null model
double null_loglik=0.;
#if COXPH
coxph_data nrgd(phd,gtd,-1);
#else
regdata nrgd(phd,gtd,-1);
#endif
#if LOGISTIC
logistic_reg nrd(nrgd);
nrd.estimate(nrgd,0,MAXITER,EPS,CHOLTOL,0, interaction, ngpreds, invvarmatrix, robust, 1);
#elif LINEAR
linear_reg nrd(nrgd);
nrd.estimate(nrgd,0,CHOLTOL,0, interaction, ngpreds, invvarmatrix, robust, 1);
#elif COXPH
coxph_reg nrd(nrgd);
nrd.estimate(nrgd,0,MAXITER,EPS,CHOLTOL,0, interaction, ngpreds, 1, robust);
#endif
null_loglik = nrd.loglik;
// end null
#if COXPH
coxph_data rgd(phd,gtd,0);
#else
regdata rgd(phd,gtd,0);
#endif
std::cout << " done\n";
std::cout.flush();
//________________________________________________________________
//Maksim, 9 Jan, 2009
if (outfilename==NULL)
{
outfilename="regression";
}
std::string outfilename_str(outfilename);
std::vector<std::ofstream*> outfile;
if (nohead!=1)
{
if(ngpreds==2) //All models output. One file per each model
{
// open a file for output
//_____________________
for(int i=0 ; i<5 ; i++)
{
outfile.push_back(new std::ofstream());
}
outfile[0]->open((outfilename_str+"_2df.out.txt").c_str());
outfile[1]->open((outfilename_str+"_add.out.txt").c_str());
outfile[2]->open((outfilename_str+"_domin.out.txt").c_str());
outfile[3]->open((outfilename_str+"_recess.out.txt").c_str());
outfile[4]->open((outfilename_str+"_over_domin.out.txt").c_str());
if (!outfile[0]->is_open()) {std::cerr << "Can not open file for writing: " << outfilename_str+"_2df.out.txt" << "\n"; exit(1);}
if (!outfile[1]->is_open()) {std::cerr << "Can not open file for writing: " << outfilename_str+"_add.out.txt" << "\n"; exit(1);}
if (!outfile[2]->is_open()) {std::cerr << "Can not open file for writing: " << outfilename_str+"_domin.out.txt" << "\n"; exit(1);}
if (!outfile[3]->is_open()) {std::cerr << "Can not open file for writing: " << outfilename_str+"_recess.out.txt" << "\n"; exit(1);}
if (!outfile[4]->is_open()) {std::cerr << "Can not open file for writing: " << outfilename_str+"_over_domin.out.txt" << "\n"; exit(1);}
//_____________________
//Header
//_____________________
for(int i=0 ; i<outfile.size() ; i++)
{
(*outfile[i]) << "name" << sep << "A1" << sep << "A2" << sep << "Freq1" << sep << "MAF" << sep << "Quality" << sep << "Rsq"
<< sep << "n" << sep << "Mean_predictor_allele";
if (chrom != "-1") (*outfile[i]) << sep << "chrom";
if (mapfilename != NULL) (*outfile[i]) << sep << "position";
}
//_____________________
if(allcov) //All covariates in output
{
for (int file=0; file<outfile.size() ; file++)
for (int i =0; i<phd.n_model_terms-1;i++)
*outfile[file] << sep << "beta_" << phd.model_terms[i] << sep << "sebeta_" << phd.model_terms[i];
}
*outfile[0] << sep << "beta_SNP_A1A2" << sep << "beta_SNP_A1A1" << sep << "sebeta_SNP_A1A2" << sep << "sebeta_SNP_A1A1";
*outfile[1] << sep << "beta_SNP_addA1" << sep << "sebeta_SNP_addA1";
*outfile[2] << sep << "beta_SNP_domA1" << sep << "sebeta_SNP_domA1";
*outfile[3] << sep << "beta_SNP_recA1" << sep << "sebeta_SNP_recA1";
*outfile[4] << sep << "beta_SNP_odom" << sep << "sebeta_SNP_odom";
if(interaction != 0)
{
//Han Chen
*outfile[0] << sep << "beta_SNP_A1A2_" << phd.model_terms[interaction_cox] << sep << "sebeta_SNP_A1A2_" << phd.model_terms[interaction_cox]
<< sep << "beta_SNP_A1A1_" << phd.model_terms[interaction_cox] << sep << "sebeta_SNP_A1A1_" << phd.model_terms[interaction_cox];
// #if !COXPH
if(inverse_filename == NULL && !allcov) *outfile[0] << sep << "cov_SNP_A1A2_int_SNP_" << phd.model_terms[interaction_cox]
<< sep << "cov_SNP_A1A1_int_SNP_" << phd.model_terms[interaction_cox];
// #endif
//Oct 26, 2009
for (int file=1; file<outfile.size() ; file++)
{
*outfile[file] << sep << "beta_SNP_" << phd.model_terms[interaction_cox] << sep << "sebeta_SNP_" << phd.model_terms[interaction_cox];
//Han Chen
#if !COXPH
if(inverse_filename == NULL && !allcov) *outfile[file] << sep << "cov_SNP_int_SNP_" << phd.model_terms[interaction_cox];
#endif
//Oct 26, 2009
}
}
*outfile[0] << sep << "chi2_SNP_2df\n";
*outfile[1] << sep << "chi2_SNP_A1\n";
*outfile[2] << sep << "chi2_SNP_domA1\n";
*outfile[3] << sep << "chi2_SNP_recA1\n";
*outfile[4] << sep << "chi2_SNP_odom\n";
}
else //Only additive model. Only one output file
{
// open a file for output
//_____________________
// if (outfilename != NULL)
// {
outfile.push_back(new std::ofstream((outfilename_str+"_add.out.txt").c_str()));
// }
// else
// {
// outfilename_str="regression_add.out.txt"; outfile.push_back(new std::ofstream((outfilename_str+"_add.out.txt").c_str()));
// }
if (!outfile[0]->is_open())
{
std::cerr << "Can not open file for writing: " << outfilename_str << "\n";
exit(1);
}
//_____________________
//Header
//_____________________
*outfile[0] << "name" << sep << "A1" << sep << "A2" << sep << "Freq1" << sep << "MAF" << sep << "Quality" << sep << "Rsq"
<< sep << "n" << sep << "Mean_predictor_allele";
if (chrom != "-1") *outfile[0] << sep << "chrom";
if (mapfilename != NULL) *outfile[0] << sep << "position";
//_____________________
if(allcov) //All covariates in output
{
for (int i =0; i<phd.n_model_terms-1;i++)
*outfile[0] << sep << "beta_" << phd.model_terms[i] << sep << "sebeta_" << phd.model_terms[i];
*outfile[0] << sep << "beta_SNP_add" << sep << "sebeta_SNP_add";
}
else //Only beta, sebeta for additive model go to output file
{
*outfile[0] << sep << "beta_SNP_add" << sep << "sebeta_SNP_add";
}
if(interaction != 0) *outfile[0] << sep << "beta_SNP_" << phd.model_terms[interaction_cox] << sep << "sebeta_SNP_" << phd.model_terms[interaction_cox];
if(inverse_filename == NULL)
//Han Chen
{
// #if !COXPH
if(interaction != 0 && !allcov) *outfile[0] << sep << "cov_SNP_int_SNP_" << phd.model_terms[interaction_cox];
// #endif
*outfile[0] << sep << "chi2_SNP";
}
//Oct 26, 2009
*outfile[0] << "\n";
}
}
else
{
if(ngpreds==2) //All models output. One file per each model
{
// open a file for output
//_____________________
// if (outfilename==NULL)
// {
// outfilename_str="regression";
// }
for(int i=0 ; i<5 ; i++)
{
outfile.push_back(new std::ofstream());
}
outfile[0]->open((outfilename_str+"_2df.out.txt").c_str());
outfile[1]->open((outfilename_str+"_add.out.txt").c_str());
outfile[2]->open((outfilename_str+"_domin.out.txt").c_str());
outfile[3]->open((outfilename_str+"_recess.out.txt").c_str());
outfile[4]->open((outfilename_str+"_over_domin.out.txt").c_str());
if (!outfile[0]->is_open()) {std::cerr << "Can not open file for writing: " << outfilename_str+"_2df.out.txt" << "\n"; exit(1);}
if (!outfile[1]->is_open()) {std::cerr << "Can not open file for writing: " << outfilename_str+"_add.out.txt" << "\n"; exit(1);}
if (!outfile[2]->is_open()) {std::cerr << "Can not open file for writing: " << outfilename_str+"_domin.out.txt" << "\n"; exit(1);}
if (!outfile[3]->is_open()) {std::cerr << "Can not open file for writing: " << outfilename_str+"_recess.out.txt" << "\n"; exit(1);}
if (!outfile[4]->is_open()) {std::cerr << "Can not open file for writing: " << outfilename_str+"_over_domin.out.txt" << "\n"; exit(1);}
}
else
{
// open a file for output
//_____________________
// if (outfilename != NULL)
// {
outfile.push_back(new std::ofstream((outfilename_str+"_add.out.txt").c_str()));
// }
// else
// {
// outfilename_str="regression_add.out.txt"; outfile.push_back(new std::ofstream((outfilename_str+"_add.out.txt").c_str()));
// }
if (!outfile[0]->is_open())
{
std::cerr << "Can not open file for writing: " << outfilename_str << "\n";
exit(1);
}
}
}
//________________________________________________________________
/*
if (allcov)
{
if (score)
{
outfile << sep << "beta_mu"; // << sep << "beta_SNP_A1";
outfile << sep << "sebeta_mu"; // << sep << "sebeta_SNP_A1";
}
else
{
for (int i =0; i<phd.n_model_terms-1;i++)
outfile << sep << "beta_" << phd.model_terms[i] << sep << "sebeta_" << phd.model_terms[i];
}
if(interactio != 0) outfile << sep << "beta_SNP_" << phd.model_terms[interaction];
}
if (ngpreds==2)
{
outfile << sep << "beta_SNP_A1A2" << sep << "beta_SNP_A1A1" << sep
<< "sebeta_SNP_A1A2" << sep << "sebeta_SNP_a1A1" << sep << "chi2_SNP_2df"
<< sep << "beta_SNP_addA1" << sep << "sebeta_SNP_addA1" << sep << "chi2_SNP_addA1"
<< sep << "beta_SNP_domA1" << sep << "sebeta_SNP_domA1" << sep << "chi2_SNP_domA1"
<< sep << "beta_SNP_recA1" << sep << "sebeta_SNP_recA1" << sep << "chi2_SNP_recA1"
<< sep << "beta_SNP_odom" << sep << "sebeta_SNP_odom" << sep << "chi2_SNP_odom\n";
}
else
{
outfile << sep << "beta_SNP_add" << sep << "sebeta_SNP_add" << sep << "chi2_SNP_add\n";
}
}
*/
// exit(1);
//________________________________________________________________
//Maksim, 9 Jan, 2009
int maxmod=5;
int start_pos, end_pos;
std::vector<std::ostringstream *> beta_sebeta;
//Han Chen
std::vector<std::ostringstream *> covvalue;
//Oct 26, 2009
std::vector<std::ostringstream *> chi2;
for(int i=0 ; i<maxmod ; i++)
{
beta_sebeta.push_back(new std::ostringstream());
//Han Chen
covvalue.push_back(new std::ostringstream());
//Oct 26, 2009
chi2.push_back(new std::ostringstream());
}
for (int csnp=0;csnp<nsnps;csnp++)
{
rgd.update_snp(gtd,csnp);
double freq;
if (ngpreds==2)
freq = ((gtd.G).column_mean(csnp*2)*2.+(gtd.G).column_mean(csnp*2+1))/2.;
else
freq = (gtd.G).column_mean(csnp)/2.;
int poly = 1;
if (fabs(freq)<1.e-16 || fabs(1.-freq)<1.e-16) poly=0;
if (fabs(mli.Rsq[csnp])<1.e-16) poly=0;
if(ngpreds==2) //All models output. One file per each model
{
//Write mlinfo to output:
for(int file=0 ; file<outfile.size() ; file++)
{
*outfile[file] << mli.name[csnp] << sep << mli.A1[csnp] << sep << mli.A2[csnp] << sep
<< mli.Freq1[csnp] << sep << mli.MAF[csnp] << sep << mli.Quality[csnp] << sep << mli.Rsq[csnp] << sep
<< phd.nids << sep << freq;
if (chrom != "-1") *outfile[file] << sep << chrom;
if (mapfilename != NULL) *outfile[file] << sep << mli.map[csnp];
}
for(int model=0 ; model<maxmod ; model++)
{
if(poly)//allel freq is not to rare
{
#if LOGISTIC
logistic_reg rd(rgd);
if (score)
rd.score(nrd.residuals,rgd,0,CHOLTOL,model, interaction, ngpreds, invvarmatrix);
else
rd.estimate(rgd,0,MAXITER,EPS,CHOLTOL,model, interaction, ngpreds, invvarmatrix, robust);
#elif LINEAR
linear_reg rd(rgd);
if(score)
rd.score(nrd.residuals,rgd,0,CHOLTOL,model, interaction, ngpreds, invvarmatrix);
else
{
// rd.mmscore(rgd,0,CHOLTOL,model, interaction, ngpreds, invvarmatrix);
rd.estimate(rgd,0,CHOLTOL,model, interaction, ngpreds, invvarmatrix, robust);
}
#elif COXPH
coxph_reg rd(rgd);
rd.estimate(rgd,0,MAXITER,EPS,CHOLTOL,model, interaction, true, ngpreds,0,robust);
#endif
if(!allcov && model==0 && interaction==0) start_pos=rd.beta.nrow-2;
else if(!allcov && model==0 && interaction!=0) start_pos=rd.beta.nrow-4;
else if(!allcov && model!=0 && interaction==0) start_pos=rd.beta.nrow-1;
else if(!allcov && model!=0 && interaction!=0) start_pos=rd.beta.nrow-2;
else start_pos=0;
for(int pos=start_pos ; pos<rd.beta.nrow ; pos++)
{
*beta_sebeta[model] << sep << rd.beta[pos] << sep << rd.sebeta[pos];
//Han Chen
// #if !COXPH
if (inverse_filename == NULL && !allcov && interaction != 0)
{
if (pos>start_pos)
{if (model==0)
{if (pos>start_pos+2)
{*covvalue[model] << rd.covariance[pos-3] << sep << rd.covariance[pos-2];}
}
else
{*covvalue[model] << rd.covariance[pos-1];}
}
}
// #endif
//Oct 26, 2009
}
//calculate chi2
//________________________________
if (score==0)
{
*chi2[model] << 2.*(rd.loglik-null_loglik);
}
else
{
*chi2[model] << rd.chi2_score;
}
//________________________________
}
else //beta, sebeta = nan
{
if(!allcov && model==0 && interaction==0) start_pos=rgd.X.ncol-2;
else if(!allcov && model==0 && interaction!=0) start_pos=rgd.X.ncol-4;
else if(!allcov && model!=0 && interaction==0) start_pos=rgd.X.ncol-1;
else if(!allcov && model!=0 && interaction!=0) start_pos=rgd.X.ncol-2;
else start_pos=0;
if(model==0) {end_pos=rgd.X.ncol;}
else {end_pos=rgd.X.ncol-1;}
if(interaction!=0) end_pos++;
for(int pos=start_pos ; pos<end_pos ; pos++)
{
*beta_sebeta[model] << sep << "nan" << sep << "nan";
}
//Han Chen
// #if !COXPH
if (!allcov && interaction !=0)
{if (model==0)
{*covvalue[model] << "nan" << sep << "nan";}
else
{*covvalue[model] << "nan";}
}
// #endif
//Oct 26, 2009
*chi2[model] << "nan";
}
}//end of moel cycle
//Han Chen
*outfile[0] << beta_sebeta[0]->str() << sep;
// #if !COXPH
if (!allcov && interaction !=0)
{
*outfile[0] << covvalue[0]->str() << sep;
}
// #endif
*outfile[0] << chi2[0]->str() << "\n";
*outfile[1] << beta_sebeta[1]->str() << sep;
// #if !COXPH
if (!allcov && interaction !=0)
{
*outfile[1] << covvalue[1]->str() << sep;
}
// #endif
*outfile[1] << chi2[1]->str() << "\n";
*outfile[2] << beta_sebeta[2]->str() << sep;
// #if !COXPH
if (!allcov && interaction !=0)
{
*outfile[2] << covvalue[2]->str() << sep;
}
// #endif
*outfile[2] << chi2[2]->str() << "\n";
*outfile[3] << beta_sebeta[3]->str() << sep;
// #if !COXPH
if (!allcov && interaction !=0)
{
*outfile[3] << covvalue[3]->str() << sep;
}
// #endif
*outfile[3] << chi2[3]->str() << "\n";
*outfile[4] << beta_sebeta[4]->str() << sep;
// #if !COXPH
if (!allcov && interaction !=0)
{
*outfile[4] << covvalue[4]->str() << sep;
}
// #endif
*outfile[4] << chi2[4]->str() << "\n";
//Oct 26, 2009
}
else //Only additive model. Only one output file
{
//Write mlinfo to output:
*outfile[0] << mli.name[csnp] << sep << mli.A1[csnp] << sep << mli.A2[csnp] << sep;
*outfile[0] << mli.Freq1[csnp] << sep << mli.MAF[csnp] << sep << mli.Quality[csnp] << sep << mli.Rsq[csnp] << sep;
*outfile[0] << phd.nids << sep << freq;
if (chrom != "-1") *outfile[0] << sep << chrom;
if (mapfilename != NULL) *outfile[0] << sep << mli.map[csnp];
int model=0;
if(poly)//allel freq is not to rare
{
#if LOGISTIC
logistic_reg rd(rgd);
if (score)
rd.score(nrd.residuals,rgd,0,CHOLTOL,model, interaction, ngpreds, invvarmatrix);
else
rd.estimate(rgd,0,MAXITER,EPS,CHOLTOL,model, interaction, ngpreds, invvarmatrix, robust);
#elif LINEAR
linear_reg rd(rgd);
if (score)
rd.score(nrd.residuals,rgd,0,CHOLTOL,model, interaction, ngpreds, invvarmatrix);
else
{
// if(inverse_filename == NULL)
// {
rd.estimate(rgd,0,CHOLTOL,model, interaction, ngpreds, invvarmatrix, robust);
// }
// else
// {
// rd.mmscore(rgd,0,CHOLTOL,model, interaction, ngpreds, invvarmatrix);
// }
}
#elif COXPH
coxph_reg rd(rgd);
rd.estimate(rgd,0,MAXITER,EPS,CHOLTOL,model, interaction, true, ngpreds,0,robust);
#endif
if(!allcov && interaction==0) start_pos=rd.beta.nrow-1;
else if(!allcov && interaction!=0) start_pos=rd.beta.nrow-2;
else start_pos=0;
for(int pos=start_pos ; pos<rd.beta.nrow ; pos++)
{
*beta_sebeta[0] << sep << rd.beta[pos] << sep << rd.sebeta[pos];
//Han Chen
// #if !COXPH
if (inverse_filename == NULL && !allcov && interaction != 0)
{if (pos>start_pos)
{*covvalue[0] << rd.covariance[pos-1];}
}
// #endif
//Oct 26, 2009
}
//calculate chi2
//________________________________
if(inverse_filename == NULL)
{
if(score==0)
{
*chi2[0] << 2.*(rd.loglik-null_loglik);
}
else
{
*chi2[0] << rd.chi2_score;
}
}
//________________________________
}
else //beta, sebeta = nan
{
if(!allcov && interaction==0) start_pos=rgd.X.ncol-1;
else if(!allcov && interaction!=0) start_pos=rgd.X.ncol-2;
else start_pos=0;
end_pos=rgd.X.ncol;
if(interaction!=0) {end_pos++;}
if(interaction!=0 && !allcov) {start_pos++;}
for(int pos=start_pos ; pos<end_pos ; pos++)
{
*beta_sebeta[0] << sep << "nan" << sep << "nan";
}
if(inverse_filename == NULL)
{
//Han Chen
// #if !COXPH
if (!allcov && interaction !=0)
{*covvalue[0] << "nan";}
// #endif
//Oct 26, 2009
*chi2[0] << "nan";
}
}
if(inverse_filename == NULL)
{
//Han Chen
*outfile[0] << beta_sebeta[0]->str() << sep;
// #if !COXPH
if (!allcov && interaction !=0)
{*outfile[0] << covvalue[0]->str() << sep;}
// #endif
*outfile[0] << chi2[model]->str() << "\n";
//Oct 26, 2009
}
else
{
*outfile[0] << beta_sebeta[0]->str() << "\n";
}
}
//clean chi2
for(int i=0 ; i<5 ; i++)
{
beta_sebeta[i]->str("");
//Han Chen
covvalue[i]->str("");
//Oct 26, 2009
chi2[i]->str("");
}
if (csnp % 1000 == 0)
{
if (csnp==0)
{
fprintf(stdout,"Analysis: %6.2f ...",100.*double(csnp)/double(nsnps));
}
else
{
fprintf(stdout,"\b\b\b\b\b\b\b\b\b\b%6.2f ...",100.*double(csnp)/double(nsnps));
}
std::cout.flush();
}
}
fprintf(stdout,"\b\b\b\b\b\b\b\b\b\b%6.2f",100.);
fprintf(stdout," ... done\n");
//________________________________________________________________
//Maksim, 9 Jan, 2009
for(int i=0 ; i<outfile.size() ; i++)
{
outfile[i]->close();
delete outfile[i];
}
return(0);
}
int main(int argc, char * argv[])
{
cmdvars input_var;
input_var.set_variables(argc, argv);
input_var.printinfo();
// if (allcov && ngpreds>1)
// {
// cout << "\n\n"
// << "WARNING: --allcov allowed only for 1 predictor (MLDOSE)\n";
// allcov = 0;
// }
mlinfo mli(input_var.getMlinfofilename(), input_var.getMapfilename());
int nsnps = mli.nsnps;
phedata phd;
int interaction_cox = create_phenotype(phd, input_var);
//interaction--;
// if (input_var.getInverseFilename()!= NULL && phd.ncov > 1)
// {
// std::cerr << "Error: In mmscore you can not use any covariates."
// << " You phenotype file must conatin id column and "
// << "trait (residuals) only\n";
// exit(1);
// }
// if (input_var.getInverseFilename()!= NULL &&
// (allcov == 1 || score == 1
// || input_var.getInteraction()!= 0
// || ngpreds==2))
// {
// std::cerr << "Error: In mmscore you can use additive model "
// << "without any inetractions only\n";
// exit(1);
// }
masked_matrix invvarmatrix;
/*
* now should be possible... delete this part later when everything works
#if LOGISTIC
if (input_var.getInverseFilename()!= NULL)
{
std::cerr << "ERROR: mmscore is forbidden for logistic regression\n";
exit(1);
}
#endif
*/
std::cout << "Reading data ..." << std::flush;
if (input_var.getInverseFilename() != NULL)
{
loadInvSigma(input_var, phd, invvarmatrix);
}
gendata gtd;
if (!input_var.getIsFvf())
// use the non-filevector input format
gtd.re_gendata(input_var.getGenfilename(), nsnps,
input_var.getNgpreds(), phd.nids_all, phd.nids,
phd.allmeasured, input_var.getSkipd(), phd.idnames);
else
// use the filevector input format (missing second last skipd
// parameter)
gtd.re_gendata(input_var.getStrGenfilename(), nsnps,
input_var.getNgpreds(), phd.nids_all, phd.nids,
phd.allmeasured, phd.idnames);
std::cout << " loaded genotypic data ..." << std::flush;
/**
if (input_var.getIsFvf())
gendata gtd(str_genfilename, nsnps, input_var.getNgpreds(),
phd.nids_all, phd.allmeasured, phd.idnames);
else
gendata gtd(input_var.getGenfilename(), nsnps,
input_var.getNgpreds(), phd.nids_all, phd.nids,
phd.allmeasured, skipd, phd.idnames);
**/
// estimate null model
#if COXPH
coxph_data nrgd = coxph_data(phd, gtd, -1);
#else
regdata nrgd = regdata(phd, gtd, -1, input_var.isIsInteractionExcluded());
#endif
std::cout << " loaded null data ..." << std::flush;
#if LOGISTIC
logistic_reg nrd = logistic_reg(nrgd);
nrd.estimate(nrgd, 0, MAXITER, EPS, CHOLTOL, 0,
input_var.getInteraction(), input_var.getNgpreds(),
invvarmatrix, input_var.getRobust(), 1);
#elif LINEAR
linear_reg nrd = linear_reg(nrgd);
#if DEBUG
std::cout << "[DEBUG] linear_reg nrd = linear_reg(nrgd); DONE.";
#endif
nrd.estimate(nrgd, 0, CHOLTOL, 0, input_var.getInteraction(),
input_var.getNgpreds(), invvarmatrix, input_var.getRobust(), 1);
#elif COXPH
coxph_reg nrd(nrgd);
nrd.estimate(nrgd, 0, MAXITER, EPS, CHOLTOL, 0,
input_var.getInteraction(), input_var.getNgpreds(), 1);
#endif
std::cout << " estimated null model ...";
// end null
#if COXPH
coxph_data rgd(phd, gtd, 0);
#else
regdata rgd(phd, gtd, 0, input_var.isIsInteractionExcluded());
#endif
std::cout << " formed regression object ...";
std::cout << " done\n" << std::flush;
//________________________________________________________________
//Maksim, 9 Jan, 2009
std::string outfilename_str(input_var.getOutfilename());
std::vector<std::ofstream*> outfile;
//All models output.One file per each model
if (input_var.getNgpreds() == 2)
{
open_files_for_output(outfile, outfilename_str);
if (input_var.getNohead() != 1)
{
create_header_1(outfile, input_var, phd, interaction_cox);
}
}
else //Only additive model. Only one output file
{
outfile.push_back(
new std::ofstream((outfilename_str + "_add.out.txt").c_str()));
if (!outfile[0]->is_open())
{
std::cerr << "Cannot open file for writing: " << outfilename_str
<< "\n";
exit(1);
}
if (input_var.getNohead() != 1)
{
create_header2(outfile, input_var, phd, interaction_cox);
}
}
//________________________________________________________________
/*
if (input_var.getAllcov())
{
if (score)
{
outfile << input_var.getSep() << "beta_mu"; // << input_var.getSep() << "beta_SNP_A1";
outfile << input_var.getSep() << "sebeta_mu"; // << input_var.getSep() << "sebeta_SNP_A1";
}
else
{
for (int i =0; i<phd.n_model_terms-1;i++)
outfile << input_var.getSep() << "beta_" << phd.model_terms[i] << input_var.getSep() << "sebeta_" << phd.model_terms[i];
}
if(interactio != 0) outfile << input_var.getSep() << "beta_SNP_" << phd.model_terms[interaction];
}
if (input_var.getNgpreds()==2)
{
outfile << input_var.getSep() << "beta_SNP_A1A2"
<< input_var.getSep() << "beta_SNP_A1A1"
<< input_var.getSep() << "sebeta_SNP_A1A2"
<< input_var.getSep() << "sebeta_SNP_a1A1"
<< input_var.getSep() << "chi2_SNP_2df"
<< input_var.getSep() << "beta_SNP_addA1"
<< input_var.getSep() << "sebeta_SNP_addA1"
<< input_var.getSep() << "chi2_SNP_addA1"
<< input_var.getSep() << "beta_SNP_domA1"
<< input_var.getSep() << "sebeta_SNP_domA1"
<< input_var.getSep() << "chi2_SNP_domA1"
<< input_var.getSep() << "beta_SNP_recA1"
<< input_var.getSep() << "sebeta_SNP_recA1"
<< input_var.getSep() << "chi2_SNP_recA1"
<< input_var.getSep() << "beta_SNP_odom"
<< input_var.getSep() << "sebeta_SNP_odom"
<< input_var.getSep() << "chi2_SNP_odom\n";
}
else
{
outfile << input_var.getSep() << "beta_SNP_add"
<< input_var.getSep() << "sebeta_SNP_add"
<< input_var.getSep() << "chi2_SNP_add\n";
}
*/
// exit(1);
//________________________________________________________________
//Maksim, 9 Jan, 2009
int maxmod = 5;
int start_pos, end_pos;
std::vector<std::ostringstream *> beta_sebeta;
//Han Chen
std::vector<std::ostringstream *> covvalue;
//Oct 26, 2009
std::vector<std::ostringstream *> chi2;
for (int i = 0; i < maxmod; i++)
{
beta_sebeta.push_back(new std::ostringstream());
//Han Chen
covvalue.push_back(new std::ostringstream());
//Oct 26, 2009
chi2.push_back(new std::ostringstream());
}
for (int csnp = 0; csnp < nsnps; csnp++)
{
rgd.update_snp(gtd, csnp);
double freq = 0.;
int gcount = 0;
float snpdata1[gtd.nids];
float snpdata2[gtd.nids];
if (input_var.getNgpreds() == 2)
{
//freq = ((gtd.G).column_mean(csnp*2)*2. +
// (gtd.G).column_mean(csnp*2+1))/2.;
gtd.get_var(csnp * 2, snpdata1);
gtd.get_var(csnp * 2 + 1, snpdata2);
for (unsigned int ii = 0; ii < gtd.nids; ii++)
if (!isnan(snpdata1[ii]) && !isnan(snpdata2[ii]))
{
gcount++;
freq += snpdata1[ii] + snpdata2[ii] * 0.5;
}
}
else
{
// freq = (gtd.G).column_mean(csnp)/2.;
gtd.get_var(csnp, snpdata1);
for (unsigned int ii = 0; ii < gtd.nids; ii++)
if (!isnan(snpdata1[ii]))
{
gcount++;
freq += snpdata1[ii] * 0.5;
}
}
freq /= static_cast<double>(gcount);
int poly = 1;
if (fabs(freq) < 1.e-16 || fabs(1. - freq) < 1.e-16)
poly = 0;
if (fabs(mli.Rsq[csnp]) < 1.e-16)
poly = 0;
//All models output. One file per each model
if (input_var.getNgpreds() == 2)
{
//Write mlinfo to output:
for (unsigned int file = 0; file < outfile.size(); file++)
{
*outfile[file] << mli.name[csnp]
<< input_var.getSep() << mli.A1[csnp]
<< input_var.getSep() << mli.A2[csnp]
<< input_var.getSep() << mli.Freq1[csnp]
<< input_var.getSep() << mli.MAF[csnp]
<< input_var.getSep() << mli.Quality[csnp]
<< input_var.getSep() << mli.Rsq[csnp]
<< input_var.getSep() << gcount
<< input_var.getSep() << freq;
if (input_var.getChrom() != "-1")
*outfile[file] << input_var.getSep()
<< input_var.getChrom();
if (input_var.getMapfilename() != NULL)
*outfile[file] << input_var.getSep() << mli.map[csnp];
}
for (int model = 0; model < maxmod; model++)
{
if (poly) //allel freq is not to rare
{
#if LOGISTIC
logistic_reg rd(rgd);
if (input_var.getScore())
rd.score(nrd.residuals, rgd, 0, CHOLTOL, model,
input_var.getInteraction(),
input_var.getNgpreds(),
invvarmatrix);
else
rd.estimate(rgd, 0, MAXITER, EPS, CHOLTOL, model,
input_var.getInteraction(),
input_var.getNgpreds(),
invvarmatrix,
input_var.getRobust());
#elif LINEAR
linear_reg rd(rgd);
if (input_var.getScore())
rd.score(nrd.residuals, rgd, 0, CHOLTOL, model,
input_var.getInteraction(),
input_var.getNgpreds(),
invvarmatrix);
else
{
// rd.mmscore(rgd,0,CHOLTOL,model,input_var.getInteraction(), input_var.getNgpreds(), invvarmatrix);
rd.estimate(rgd, 0, CHOLTOL, model,
input_var.getInteraction(),
input_var.getNgpreds(), invvarmatrix,
input_var.getRobust());
}
#elif COXPH
coxph_reg rd(rgd);
rd.estimate(rgd, 0, MAXITER, EPS, CHOLTOL, model,
input_var.getInteraction(), true,
input_var.getNgpreds());
#endif
if (!input_var.getAllcov() && model == 0
&& input_var.getInteraction() == 0)
start_pos = rd.beta.nrow - 2;
else if (!input_var.getAllcov() && model == 0
&& input_var.getInteraction() != 0)
start_pos = rd.beta.nrow - 4;
else if (!input_var.getAllcov() && model != 0
&& input_var.getInteraction() == 0)
start_pos = rd.beta.nrow - 1;
else if (!input_var.getAllcov() && model != 0
&& input_var.getInteraction() != 0)
start_pos = rd.beta.nrow - 2;
else
start_pos = 0;
for (int pos = start_pos; pos < rd.beta.nrow; pos++)
{
*beta_sebeta[model] << input_var.getSep()
<< rd.beta[pos]
<< input_var.getSep()
<< rd.sebeta[pos];
//Han Chen
#if !COXPH
if (input_var.getInverseFilename() == NULL
&& !input_var.getAllcov()
&& input_var.getInteraction() != 0)
{
if (pos > start_pos)
{
if (model == 0)
{
if (pos > start_pos + 2)
{
*covvalue[model]
<< rd.covariance[pos - 3]
<< input_var.getSep()
<< rd.covariance[pos - 2];
}
}
else
{
*covvalue[model] << rd.covariance[pos - 1];
}
}
}
#endif
//Oct 26, 2009
}
//calculate chi2
//________________________________
if (input_var.getScore() == 0)
{
//*chi2[model] << 2.*(rd.loglik-null_loglik);
*chi2[model] << rd.loglik;
}
else
{
//*chi2[model] << rd.chi2_score;
*chi2[model] << "nan";
}
//________________________________
}
else //beta, sebeta = nan
{
if (!input_var.getAllcov() && model == 0
&& input_var.getInteraction() == 0)
start_pos = rgd.X.ncol - 2;
else if (!input_var.getAllcov() && model == 0
&& input_var.getInteraction() != 0)
start_pos = rgd.X.ncol - 4;
else if (!input_var.getAllcov() && model != 0
&& input_var.getInteraction() == 0)
start_pos = rgd.X.ncol - 1;
else if (!input_var.getAllcov() && model != 0
&& input_var.getInteraction() != 0)
start_pos = rgd.X.ncol - 2;
else
start_pos = 0;
if (model == 0)
{
end_pos = rgd.X.ncol;
}
else
{
end_pos = rgd.X.ncol - 1;
}
if (input_var.getInteraction() != 0)
end_pos++;
for (int pos = start_pos; pos < end_pos; pos++)
{
*beta_sebeta[model] << input_var.getSep() << "nan"
<< input_var.getSep() << "nan";
}
//Han Chen
#if !COXPH
if (!input_var.getAllcov()
&& input_var.getInteraction() != 0)
{
if (model == 0)
{
*covvalue[model] << "nan"
<< input_var.getSep() << "nan";
}
else
{
*covvalue[model] << "nan";
}
}
#endif
//Oct 26, 2009
*chi2[model] << "nan";
}
} //end of model cycle
//Han Chen
*outfile[0] << beta_sebeta[0]->str() << input_var.getSep();
#if !COXPH
if (!input_var.getAllcov() && input_var.getInteraction() != 0)
{
*outfile[0] << covvalue[0]->str() << input_var.getSep();
}
#endif
*outfile[0] << chi2[0]->str() << "\n";
*outfile[1] << beta_sebeta[1]->str() << input_var.getSep();
#if !COXPH
if (!input_var.getAllcov() && input_var.getInteraction() != 0)
{
*outfile[1] << covvalue[1]->str() << input_var.getSep();
}
#endif
*outfile[1] << chi2[1]->str() << "\n";
*outfile[2] << beta_sebeta[2]->str() << input_var.getSep();
#if !COXPH
if (!input_var.getAllcov() && input_var.getInteraction() != 0)
{
*outfile[2] << covvalue[2]->str() << input_var.getSep();
}
#endif
*outfile[2] << chi2[2]->str() << "\n";
*outfile[3] << beta_sebeta[3]->str() << input_var.getSep();
#if !COXPH
if (!input_var.getAllcov() && input_var.getInteraction() != 0)
{
*outfile[3] << covvalue[3]->str() << input_var.getSep();
}
#endif
*outfile[3] << chi2[3]->str() << "\n";
*outfile[4] << beta_sebeta[4]->str() << input_var.getSep();
#if !COXPH
if (!input_var.getAllcov() && input_var.getInteraction() != 0)
{
*outfile[4] << covvalue[4]->str() << input_var.getSep();
}
#endif
*outfile[4] << chi2[4]->str() << "\n";
//Oct 26, 2009
}
else //Only additive model. Only one output file
{
//Write mlinfo to output:
*outfile[0] << mli.name[csnp]
<< input_var.getSep() << mli.A1[csnp]
<< input_var.getSep() << mli.A2[csnp]
<< input_var.getSep();
*outfile[0] << mli.Freq1[csnp]
<< input_var.getSep() << mli.MAF[csnp]
<< input_var.getSep() << mli.Quality[csnp]
<< input_var.getSep() << mli.Rsq[csnp]
<< input_var.getSep();
*outfile[0] << gcount << input_var.getSep() << freq;
if (input_var.getChrom() != "-1")
*outfile[0] << input_var.getSep() << input_var.getChrom();
if (input_var.getMapfilename() != NULL)
*outfile[0] << input_var.getSep() << mli.map[csnp];
int model = 0;
if (poly) //allel freq is not to rare
{
#if LOGISTIC
logistic_reg rd(rgd);
if (input_var.getScore())
rd.score(nrd.residuals, rgd, 0, CHOLTOL, model,
input_var.getInteraction(),
input_var.getNgpreds(),
invvarmatrix);
else
rd.estimate(rgd, 0, MAXITER, EPS, CHOLTOL, model,
input_var.getInteraction(),
input_var.getNgpreds(),
invvarmatrix,
input_var.getRobust());
#elif LINEAR
//cout << (rgd.get_unmasked_data()).nids << " 1\n";
#if DEBUG
rgd.X.print();
rgd.Y.print();
#endif
linear_reg rd(rgd);
#if DEBUG
rgd.X.print();
rgd.Y.print();
#endif
//cout << (rgd.get_unmasked_data()).nids << " 2\n";
if (input_var.getScore())
{
#if DEBUG
cout << "input_var.getScore/n";
nrd.residuals.print();
cout << CHOLTOL << " <-CHOLTOL\n";
cout << model << " <-model\n";
cout << input_var.getInteraction()
<< " <-input_var.getInteraction()\n";
cout << input_var.getNgpreds()
<< " <-input_var.getNgpreds()\n";
invvarmatrix.print();
#endif
rd.score(nrd.residuals, rgd, 0, CHOLTOL, model,
input_var.getInteraction(),
input_var.getNgpreds(),
invvarmatrix);
#if DEBUG
rd.beta.print();
cout << rd.chi2_score << " <-chi2_scoren\n";
rd.covariance.print();
rd.residuals.print();
rd.sebeta.print();
cout << rd.loglik << " <-logliken\n";
cout << rd.sigma2 << " <-sigma2\n";
#endif
}
else
{
// if(input_var.getInverseFilename()== NULL)
// {
// cout << (rgd.get_unmasked_data()).nids << " 3\n";
#if DEBUG
cout << "rd.estimate\n";
cout << CHOLTOL << " <-CHOLTOL\n";
cout << model << " <-model\n";
cout << input_var.getInteraction()
<< " <-input_var.getInteraction()\n";
cout << input_var.getNgpreds()
<< " <-input_var.getNgpreds()\n";
cout << input_var.getRobust()
<< " <-input_var.getRobust()\n";
cout << "start invarmatrix\n";
invvarmatrix.print();
cout << "end invarmatrix\n";
cout << rgd.is_interaction_excluded
<< " <-rgd.is_interaction_excluded\n";
#endif
rd.estimate(rgd, 0, CHOLTOL, model,
input_var.getInteraction(),
input_var.getNgpreds(),
invvarmatrix,
input_var.getRobust());
#if DEBUG
cout << "rd.beta\n";
rd.beta.print();
cout << rd.chi2_score << " <-chi2_scoren\n";
cout << "rd.covariance\n";
rd.covariance.print();
cout << "rd.residuals\n";
rd.residuals.print();
cout << "rd.sebeta\n";
rd.sebeta.print();
cout << rd.loglik << " <-logliken\n";
cout << rd.sigma2 << " <-sigma2\n";
#endif
//cout << (rgd.get_unmasked_data()).nids << " 4\n";
//}
//else
//{
// rd.mmscore(rgd, 0, CHOLTOL, model,
// input_var.getInteraction(),
// input_var.getNgpreds(), invvarmatrix);
//}
}
#elif COXPH
coxph_reg rd(rgd);
rd.estimate(rgd, 0, MAXITER, EPS, CHOLTOL, model,
input_var.getInteraction(), true,
input_var.getNgpreds());
#endif
if (!input_var.getAllcov() && input_var.getInteraction() == 0)
{
start_pos = rd.beta.nrow - 1;
}
else if (!input_var.getAllcov()
&& input_var.getInteraction() != 0)
{
start_pos = rd.beta.nrow - 2;
}
else
{
start_pos = 0;
}
#if DEBUG
cout << " start_pos;" << start_pos << "\n";
#endif
for (int pos = start_pos; pos < rd.beta.nrow; pos++)
{
*beta_sebeta[0] << input_var.getSep() << rd.beta[pos]
<< input_var.getSep() << rd.sebeta[pos];
//Han Chen
#if !COXPH
if (input_var.getInverseFilename() == NULL
&& !input_var.getAllcov()
&& input_var.getInteraction() != 0)
{
if (pos > start_pos)
{
*covvalue[0] << rd.covariance[pos - 1];
}
}
#endif
//Oct 26, 2009
}
//calculate chi2
//________________________________
if (input_var.getInverseFilename() == NULL)
{
#if DEBUG
cout << " inverse_filename == NULL" << "\n";
#endif
if (input_var.getScore() == 0)
{
*chi2[0] << rd.loglik; //2.*(rd.loglik-null_loglik);
}
else
{
*chi2[0] << "nan"; //rd.chi2_score;
}
}
//________________________________
}
else //beta, sebeta = nan
{
if (!input_var.getAllcov() && input_var.getInteraction() == 0)
start_pos = rgd.X.ncol - 1;
else if (!input_var.getAllcov()
&& input_var.getInteraction() != 0)
start_pos = rgd.X.ncol - 2;
else
start_pos = 0;
end_pos = rgd.X.ncol;
if (input_var.getInteraction() != 0)
{
end_pos++;
}
if (input_var.getInteraction() != 0 && !input_var.getAllcov())
{
start_pos++;
}
for (int pos = start_pos; pos < end_pos; pos++)
{
*beta_sebeta[0] << input_var.getSep() << "nan"
<< input_var.getSep() << "nan";
}
if (input_var.getInverseFilename() == NULL)
{
//Han Chen
#if !COXPH
if (!input_var.getAllcov()
&& input_var.getInteraction() != 0)
{
*covvalue[0] << "nan";
}
#endif
//Oct 26, 2009
*chi2[0] << "nan";
}
}
if (input_var.getInverseFilename() == NULL)
{
//Han Chen
*outfile[0] << beta_sebeta[0]->str() << input_var.getSep();
#if !COXPH
if (!input_var.getAllcov() && input_var.getInteraction() != 0)
{
*outfile[0] << covvalue[0]->str() << input_var.getSep();
}
#endif
*outfile[0] << chi2[model]->str() << "\n";
//Oct 26, 2009
}
else
{
*outfile[0] << beta_sebeta[0]->str() << "\n";
#if DEBUG
cout << "Se beta" << beta_sebeta[0] << "\n";
#endif
}
}
//clean chi2
for (int i = 0; i < 5; i++)
{
beta_sebeta[i]->str("");
//Han Chen
covvalue[i]->str("");
//Oct 26, 2009
chi2[i]->str("");
}
update_progress_to_cmd_line(csnp, nsnps);
}
std::cout << "\b\b\b\b\b\b\b\b\b" << 100.;
std::cout << "%... done\n";
//________________________________________________________________
//Maksim, 9 Jan, 2009
for (unsigned int i = 0; i < outfile.size(); i++)
{
outfile[i]->close();
delete outfile[i];
}
//delete gtd;
// Clean up a couple of vectors
std::vector<std::ostringstream *>::iterator it = beta_sebeta.begin();
while (it != beta_sebeta.end())
{
delete *it;
++it;
}
it = covvalue.begin();
while (it != covvalue.end())
{
delete *it;
++it;
}
it = chi2.begin();
while (it != chi2.end())
{
delete *it;
++it;
}
return (0);
}
