int main(int argc, char ** argv) {
data D;
//-------------------------
// 1. DECLARE ALL OPTIONS
//-------------------------
bpo::options_description opt_basic ("\33[33mBasic options\33[0m");
opt_basic.add_options()
("help", "Produces this help")
("silent", "Silent mode on terminal")
("seed", bpo::value< int >()->default_value(time(NULL)), "Random number seed. Useful to replicate runs.");
bpo::options_description opt_files ("\33[33mInput/Output files\33[0m");
opt_files.add_options()
("log,L", bpo::value< string >()->default_value("fastQTL_date_time_UUID.log"), "Screen output is copied in this file.")
("vcf,V", bpo::value< string >(), "Genotypes in VCF format.")
("bed,B", bpo::value< string >(), "Phenotypes in BED format.")
("cov,C", bpo::value< string >(), "Covariates in TXT format.")
("grp,G", bpo::value< string >(), "Phenotype groups in TXT format.")
("out,O", bpo::value< string >(), "Output file.");
bpo::options_description opt_exclusion ("\33[33mExclusion/Inclusion files\33[0m");
opt_exclusion.add_options()
("exclude-samples", bpo::value< string >(), "List of samples to exclude.")
("include-samples", bpo::value< string >(), "List of samples to include.")
("exclude-sites", bpo::value< string >(), "List of sites to exclude.")
("include-sites", bpo::value< string >(), "List of sites to include.")
("exclude-phenotypes", bpo::value< string >(), "List of phenotypes to exclude.")
("include-phenotypes", bpo::value< string >(), "List of phenotypes to include.")
("exclude-covariates", bpo::value< string >(), "List of covariates to exclude.")
("include-covariates", bpo::value< string >(), "List of covariates to include.");
bpo::options_description opt_parameters ("\33[33mParameters\33[0m");
opt_parameters.add_options()
("normal", "Normal transform the phenotypes.")
("window,W", bpo::value< double >()->default_value(1e6), "Cis-window size.")
("threshold,T", bpo::value< double >()->default_value(1.0), "P-value threshold used in nominal pass of association")
("maf-threshold", bpo::value< double >()->default_value(0.0), "Minor allele frequency threshold used when parsing genotypes")
("ma-sample-threshold", bpo::value< int >()->default_value(0), "Minimum number of samples carrying the minor allele; used when parsing genotypes")
("global-af-threshold", bpo::value< double >()->default_value(0.0), "AF threshold for all samples in VCF (used to filter AF in INFO field)")
("interaction-maf-threshold", bpo::value< double >()->default_value(0.0), "MAF threshold for interactions, applied to lower and upper half of samples");
bpo::options_description opt_modes ("\33[33mModes\33[0m");
opt_modes.add_options()
("permute,P", bpo::value< vector < int > >()->multitoken(), "Permutation pass to calculate corrected p-values for molecular phenotypes.")
("psequence", bpo::value< string >(), "Permutation sequence.")
("map", bpo::value< string >(), "Map best QTL candidates per molecular phenotype.")
("map-full", "Scan full cis-window to discover independent signals.")
("interaction", bpo::value< string >(), "Test for interactions with variable specified in file.")
("report-best-only", bpo::bool_switch()->default_value(false), "Report best variant only (nominal mode)");
bpo::options_description opt_parallel ("\33[33mParallelization\33[0m");
opt_parallel.add_options()
("chunk,K", bpo::value< vector < int > >()->multitoken(), "Specify which chunk needs to be processed")
("commands", bpo::value< vector < string > >()->multitoken(), "Generates all commands")
("region,R", bpo::value< string >(), "Region of interest.");
bpo::options_description descriptions;
descriptions.add(opt_basic).add(opt_files).add(opt_exclusion).add(opt_parameters).add(opt_modes).add(opt_parallel);
//-------------------
// 2. PARSE OPTIONS
//-------------------
bpo::variables_map options;
try {
bpo::store(bpo::command_line_parser(argc, argv).options(descriptions).run(), options);
bpo::notify(options);
} catch ( const boost::program_options::error& e ) {
cerr << "Error parsing command line :" << string(e.what()) << endl;
exit(0);
}
//-----------------------
// 3. PRINT HEADER/HELP
//-----------------------
if (! options.count("silent")) {
cout << endl;
cout << "\33[33mF\33[0mast \33[33mQTL\33[0m" << endl;
cout << " * Authors : Olivier DELANEAU, Halit ONGEN, Alfonso BUIL & Manolis DERMITZAKIS" << endl;
cout << " * Contact : [email protected]" << endl;
cout << " * Webpage : http://fastqtl.sourceforge.net/" << endl;
cout << " * Version : v2.184_gtex" << endl;
if (options.count("help")) { cout << descriptions<< endl; exit(1); }
}
//--------------
// 4. LOG FILE
//--------------
struct timeval start_time, stop_time;
gettimeofday(&start_time, 0);
START_DATE = time(0);
//localtime(&START_DATE);
//string logfile = "fastQTL_" + sutils::date2str(&START_DATE, "%d%m%Y_%Hh%Mm%Ss") + "_" + putils::getRandomID() + ".log";
if (!options["log"].defaulted()) {
if (!LOG.open(options["log"].as < string > ())) {
cerr << "Impossible to open log file[" << options["log"].as < string > () << "] check writing permissions!" << endl;
exit(1);
}
} else LOG.muteL();
if (options.count("silent")) LOG.muteC();
//------------------------
// 5. OPTIONS COMBINATIONS
//------------------------
if (!options.count("vcf")) LOG.error("Genotype data needs to be specified with --vcf [file.vcf]");
if (!options.count("bed")) LOG.error("Phenotype data needs to be specified with --bed [file.bed]");
if (!options.count("out")) LOG.error("Output needs to be specified with --out [file.out]");
int nParallel = options.count("chunk") + options.count("commands") + options.count("region");
if (nParallel != 1) LOG.error("Please, specify one of these options [--region, --chunk, --commands]");
int nMode = options.count("permute") + options.count("map");
if (nMode > 1) LOG.error("Please, specify only one of these options [--permute, --map]");
//---------------
// 6. CHECK FILES
//---------------
if (!futils::isFile(options["vcf"].as < string > ())) LOG.error(options["vcf"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (!futils::isFile(options["bed"].as < string > ())) LOG.error(options["bed"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (options.count("cov") && !futils::isFile(options["cov"].as < string > ())) LOG.error(options["cov"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (options.count("interaction") && !futils::isFile(options["interaction"].as < string > ())) LOG.error(options["interaction"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (options.count("grp") && !futils::isFile(options["grp"].as < string > ())) LOG.error(options["grp"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (options.count("map") && !futils::isFile(options["map"].as < string > ())) LOG.error(options["map"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (!futils::createFile(options["out"].as < string > ())) LOG.error(options["out"].as < string > () + " is impossible to create, check writing permissions");
//-----------------------------------
// 6. CHECK INCLUSION/EXCLUSION FILES
//-----------------------------------
if (options.count("exclude-samples") && !futils::isFile(options["exclude-samples"].as < string > ())) LOG.error(options["exclude-samples"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (options.count("include-samples") && !futils::isFile(options["include-samples"].as < string > ())) LOG.error(options["include-samples"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (options.count("exclude-sites") && !futils::isFile(options["exclude-sites"].as < string > ())) LOG.error(options["exclude-sites"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (options.count("include-sites") && !futils::isFile(options["include-sites"].as < string > ())) LOG.error(options["include-sites"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (options.count("exclude-phenotypes") && !futils::isFile(options["exclude-phenotypes"].as < string > ())) LOG.error(options["exclude-phenotypes"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (options.count("include-phenotypes") && !futils::isFile(options["include-phenotypes"].as < string > ())) LOG.error(options["include-phenotypes"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (options.count("exclude-covariates") && !futils::isFile(options["exclude-covariates"].as < string > ())) LOG.error(options["exclude-covariates"].as < string > () + " is impossible to open, check file existence or reading permissions");
if (options.count("include-covariates") && !futils::isFile(options["include-covariates"].as < string > ())) LOG.error(options["include-covariates"].as < string > () + " is impossible to open, check file existence or reading permissions");
//----------------------------
// 7. CHECK METHODS/PARAMETERS
//----------------------------
if (options.count("interaction")) {
if (options.count("permute")) {
LOG.println("\nPerform permutation-based interaction analysis (used to calculate corrected p-values for MPs)");
vector < int > nPerm = options["permute"].as < vector < int > > ();
if (nPerm.size() != 1) LOG.error("Interactions only work with a fixed number of permutations!");
else {
if (nPerm[0] < 50) LOG.warning("Permutation number seems to be low, check parameters");
LOG.println(" * Perform " + sutils::int2str(nPerm[0]) + " permutations");
}
} else {
LOG.println("\nPerform nominal interaction analysis");
}
LOG.println(" * Test interaction with term from [" + options["interaction"].as < string > () + "]");
} else if (options.count("permute")) {
LOG.println("\nPerform permutation based analysis (used to calculate corrected p-values for MPs)");
vector < int > nPerm = options["permute"].as < vector < int > > ();
if (nPerm.size() > 3 || nPerm.size() < 1) LOG.error ("Option --permute takes 1, 2 or 3 arguments");
if (nPerm.size() == 1) {
if (nPerm[0] <= 0) LOG.error("Permutation number needs to be positive integer");
if (nPerm[0] < 50) LOG.warning("Permutation number seems to be low, check parameters");
LOG.println(" * Perform " + sutils::int2str(nPerm[0]) + " permutations");
} else if (nPerm.size() == 2) {
if (nPerm[0] <= 0 || nPerm[1] <= 0) LOG.error("Permutation number needs to be positive");
if (nPerm[1] <= nPerm[0]) LOG.error("For adaptive permutation scheme, arg1 needs to be smaller than arg2!");
LOG.println(" * Perform between " + sutils::int2str(nPerm[0]) + " and " + sutils::int2str(nPerm[1]) + " permutations");
} else {
if (nPerm[0] <= 0 || nPerm[1] <= 0 || nPerm[2] <= 0) LOG.error("Permutation number needs to be positive");
if (nPerm[2] <= nPerm[0]) LOG.error("For adaptive permutation scheme, arg1 needs to be smaller than arg3!");
if (nPerm[0] <= nPerm[1]) LOG.error("For adaptive permutation scheme, arg2 needs to be smaller than arg1!");
LOG.println(" * Perform between " + sutils::int2str(nPerm[0]) + " and " + sutils::int2str(nPerm[2]) + " permutations and stop when " + sutils::int2str(nPerm[1]) + " best associations are found");
}
if (options.count("grp")) LOG.println(" * Using MP groups from [" + options["grp"].as < string > () + "]");
} else if (options.count("map")) {
LOG.println("\nPerform conditional based analysis (used to map significant QTLs for MPs");
LOG.println(" * Using per MP p-value threshold from [" + options["map"].as < string > () + "]");
if (options.count("map-full")) LOG.println(" * Scanning all variants in cis and not only nominally significant ones");
} else {
LOG.println("\nPerform nominal analysis (used to get raw p-values of association)");
double threshold = options["threshold"].as < double > ();
if (threshold <= 0.0 || threshold > 1.0) LOG.error("Incorrect --threshold value : 0 < X <= 1");
LOG.println(" * Using p-value threshold = " + sutils::double2str(threshold, 10));
}
if (options["seed"].as < int > () < 0) LOG.error("Random number generator needs a positive seed value");
else srand(options["seed"].as < int > ());
LOG.println(" * Random number generator is seeded with " + sutils::int2str(options["seed"].as < int > ()));
if (options["window"].as < double > () <= 0) LOG.error ("Incorrect value for option --window (null or negative value)");
if (options["window"].as < double > () > 1e9) LOG.error ("Cis-window cannot be larger than 1e9bp");
LOG.println(" * Considering variants within " + sutils::double2str(options["window"].as < double > ()) + " bp of the MPs");
D.cis_window = options["window"].as < double > ();
D.maf_threshold = options["maf-threshold"].as < double > ();
if (D.maf_threshold < 0.0 || D.maf_threshold >= 0.5) LOG.error("Incorrect --maf-threshold value : 0 <= X < 0.5");
LOG.println(" * Using minor allele frequency threshold = " + sutils::double2str(D.maf_threshold, 4));
D.ma_sample_threshold = options["ma-sample-threshold"].as < int > ();
if (D.ma_sample_threshold < 0) LOG.error("Incorrect --ma-sample-threshold : 0 <= X");
LOG.println(" * Using minor allele sample threshold = " + sutils::int2str(D.ma_sample_threshold));
D.global_af_threshold = options["global-af-threshold"].as < double > ();
if (D.global_af_threshold < 0.0 || D.global_af_threshold >= 0.5) LOG.error("Incorrect --global-af-threshold value : 0 <= X < 0.5");
LOG.println(" * Using INFO field AF threshold = " + sutils::double2str(D.global_af_threshold, 4));
D.interaction_maf_threshold = options["interaction-maf-threshold"].as < double > ();
if (D.interaction_maf_threshold < 0.0 || D.interaction_maf_threshold >= 0.5) LOG.error("Incorrect --interaction-maf-threshold : 0 <= X < 0.5");
LOG.println(" * Applying interaction MAF AF threshold = " + sutils::double2str(D.interaction_maf_threshold, 4));
if (options.count("chunk")) {
vector < int > nChunk = options["chunk"].as < vector < int > > ();
if (nChunk.size() != 2) LOG.error ("--chunk needs 2 integer arguments");
if (nChunk[0] > nChunk[1]) LOG.error ("arg1 for --chunk needs to be smaller or equal to arg2");
LOG.println (" * Chunk processed " + sutils::int2str(nChunk[0]) + " / " + sutils::int2str(nChunk[1]));
} else if (options.count("commands")) {
vector < string > nCommands = options["commands"].as < vector < string > > ();
if (nCommands.size() != 2) LOG.error ("--commands needs 2 arguments");
LOG.println (" * " + nCommands[0] + " commands output in [" + nCommands[1] +"]");
} else LOG.println (" * Focus on region [" + options["region"].as < string > () +"]");
//--------------------------------
// 7. READ EXCLUDE / INCLUDE FILES
//--------------------------------
if (options.count("exclude-samples")) D.readSamplesToExclude(options["exclude-samples"].as < string > ());
if (options.count("include-samples")) D.readSamplesToInclude(options["include-samples"].as < string > ());
if (options.count("exclude-sites")) D.readGenotypesToExclude(options["exclude-sites"].as < string > ());
if (options.count("include-sites")) D.readGenotypesToInclude(options["include-sites"].as < string > ());
if (options.count("exclude-phenotypes")) D.readPhenotypesToExclude(options["exclude-phenotypes"].as < string > ());
if (options.count("include-phenotypes")) D.readPhenotypesToInclude(options["include-phenotypes"].as < string > ());
if (options.count("exclude-covariates")) D.readCovariatesToExclude(options["exclude-covariates"].as < string > ());
if (options.count("include-covariates")) D.readCovariatesToInclude(options["include-covariates"].as < string > ());
if (options.count("commands")) {
//---------------------
// 8. GENERATE COMMANDS
//---------------------
int nChunks = atoi(options["commands"].as < vector < string > > ()[0].c_str());
D.scanPhenotypes(options["bed"].as < string > ());
if (options.count("grp")) D.readGroups(options["grp"].as < string > ()); // need to read this before determining chunks (clusterizePhenotypes)
D.clusterizePhenotypes(nChunks);
D.writeCommands(options["commands"].as < vector < string > > ()[1], nChunks, argc, argv);
} else {
//--------------
// 9. SET REGION
//--------------
if (options.count("chunk")) {
D.scanPhenotypes(options["bed"].as < string > ());
if (options.count("grp")) D.readGroups(options["grp"].as < string > ()); // need to read this before determining chunks (clusterizePhenotypes)
D.clusterizePhenotypes(options["chunk"].as < vector < int > > ()[1]);
D.setPhenotypeRegion(options["chunk"].as < vector < int > > ()[0] - 1);
D.clear();
} else if (!D.setPhenotypeRegion(options["region"].as < string > ())) LOG.error("Impossible to interpret region [" + options["region"].as < string > () + "]");
D.deduceGenotypeRegion(options["window"].as < double > ());
//---------------
// 10. READ FILES
//---------------
D.readPhenotypes(options["bed"].as < string > ());
if (options.count("interaction")) D.readInteractions(options["interaction"].as < string > ()); // used by optional MAF filter, read first
D.readGenotypesVCF(options["vcf"].as < string > ());
if (options.count("cov")) D.readCovariates(options["cov"].as < string > ());
if (options.count("map")) D.readThresholds(options["map"].as < string > ());
if (options.count("grp")) D.readGroups(options["grp"].as < string > ()); // read groups again, this time limited to phenotypes
//------------------------
// 11. INITIALIZE ANALYSIS
//------------------------
D.imputeGenotypes();
D.imputePhenotypes();
if (options.count("normal")) D.normalTranformPhenotypes();
D.initResidualizer();
//-----------------
// 12. RUN ANALYSIS
//-----------------
if (options.count("interaction")) {
if (options.count("permute")) {
D.runPermutationInteraction(options["out"].as < string > (), options["permute"].as < vector < int > > ()[0]);
} else if (options["report-best-only"].as<bool>()) {
D.runNominalInteractionBest(options["out"].as < string > ());
} else {
D.runNominalInteraction(options["out"].as < string > (), options["threshold"].as < double > ());
}
} else if (options.count("permute") && options.count("grp"))
D.runPermutationPerGroup(options["out"].as < string > (), options["permute"].as < vector < int > > ());
else if (options.count("permute")) {
if (options.count("psequence")) D.runPermutation(options["out"].as < string > (), options["psequence"].as < string > ());
else D.runPermutation(options["out"].as < string > (), options["permute"].as < vector < int > > ());
} else if (options.count("map")) {
D.runMapping(options["out"].as < string > (), options.count("map-full"));
} else if (options["report-best-only"].as<bool>()) {
D.runNominalBest(options["out"].as < string > ());
} else {
D.runNominal(options["out"].as < string > (), options["threshold"].as < double > ());
}
}
//----------------
// 13. TERMINATION
//----------------
D.clear();
gettimeofday(&stop_time, 0);
int n_seconds = (int)floor(stop_time.tv_sec - start_time.tv_sec);
LOG.println("\nRunning time: " + sutils::int2str(n_seconds) + " seconds");
if (!options["log"].defaulted()) LOG.close();
}
void trans_main(vector < string > & argv) {
trans_data D;
//-------------------------
// 1. DECLARE ALL OPTIONS
//-------------------------
D.declareBasicOptions(); //Mandatory
boost::program_options::options_description opt_files ("\x1B[32mI/O\33[0m");
opt_files.add_options()
("vcf", boost::program_options::value< string >(), "Genotypes in VCF/BCF format.")
("bed", boost::program_options::value< string >(), "Phenotypes in BED format.")
("cov", boost::program_options::value< string >(), "Covariates in TXT format.")
("out", boost::program_options::value< string >(), "Output file.");
boost::program_options::options_description opt_parameters ("\x1B[32mParameters\33[0m");
opt_parameters.add_options()
("normal", "Quantile normalize phenotype data.")
("window", boost::program_options::value< double >()->default_value(5e6, "5e6"), "Cis-window of variants to be excluded.")
("threshold", boost::program_options::value< double >()->default_value(1e-5, "1e-5"), "P-value threshold below which hits are reported.")
("bins", boost::program_options::value< unsigned int >()->default_value(1000), "Number of bins to use to categorize all p-values above --threshold.");
boost::program_options::options_description opt_modes ("\x1B[32mAnalysis type\33[0m");
opt_modes.add_options()
("nominal", "MODE1: NOMINAL PASS [Pvalues are not adjusted].")
("adjust", boost::program_options::value< string >(), "MODE2: ADJUSTED PASS [Pvalues are adjusted].")
("permute", "MODE3: PERMUTATION PASS [Permute all phenotypes once].")
("sample", boost::program_options::value< unsigned int >(), "MODE4: PERMUTATION PASS [Permute randomly chosen phenotypes multiple times].");
boost::program_options::options_description opt_parallel ("\x1B[32mParallelization\33[0m");
opt_parallel.add_options()
("chunk", boost::program_options::value< vector < int > >()->multitoken(), "Specify which chunk needs to be processed");
D.option_descriptions.add(opt_files).add(opt_parameters).add(opt_modes).add(opt_parallel);
//-------------------
// 2. PARSE OPTIONS
//-------------------
try {
boost::program_options::store(boost::program_options::command_line_parser(argv).options(D.option_descriptions).run(), D.options);
boost::program_options::notify(D.options);
} catch ( const boost::program_options::error& e ) {
cerr << "Error parsing [trans] command line :" << string(e.what()) << endl;
exit(0);
}
//---------------------
// 3. PRINT HELP/HEADER
//---------------------
vrb.ctitle("MAPPING QTL IN TRANS");
if (D.options.count("help")) {
cout << D.option_descriptions << endl;
exit(EXIT_SUCCESS);
}
//-----------------
// 4. COMMON CHECKS
//-----------------
if (!D.options.count("vcf")) vrb.error("Genotype data needs to be specified with --vcf [file.vcf]");
if (!D.options.count("bed")) vrb.error("Phenotype data needs to be specified with --bed [file.bed]");
if (!D.options.count("out")) vrb.error("Output needs to be specified with --out [file.out]");
int nMode = D.options.count("nominal") + D.options.count("adjust") + D.options.count("permute") + D.options.count("sample");
if (nMode != 1) vrb.error("Please, specify only one of these options [--nominal, --adjust, --permute, --sample]");
if (D.options.count("chunk") && D.options.count("sample")) vrb.error("--chunk cannot be combined with --sample");
//---------
// 5. MODES
//---------
//MODE1: NOMINAL PASS NON ADJUSTED
if (D.options.count("nominal")) {
D.mode = TRANS_MODE1;
vrb.bullet("TASK: Perform a full nominal pass, do not adjust p-values");
}
//MODE2: NOMINAL PASS ADJUSTED
if (D.options.count("adjust")) {
D.mode = TRANS_MODE2;
vrb.bullet("TASK: Test and adjust p-values using [" + D.options["adjust"].as < string > () +"]");
}
//MODE3: PERMUTATION PASS
if (D.options.count("permute")) {
D.mode = TRANS_MODE3;
vrb.bullet("TASK: Permute all phenotype once and test");
}
//MODE4: PERMUTATION PASS
if (D.options.count("sample")) {
D.mode = TRANS_MODE4;
vrb.bullet("TASK: Permute randomly chosen phenotypes " + stb.str(D.options["sample"].as < unsigned int > ()) + " times and test");
}
//--------------
// 6. SET PARAMS
//--------------
if (D.options["window"].as < double > () <= 0 || D.options["window"].as < double > () > 1e9) vrb.error ("Incorrect cis-window size");
vrb.bullet("Cis-window size is " + stb.str((int)D.options["window"].as < double > ()) + " bp");
D.cis_window = D.options["window"].as < double > ();
if (D.options.count("chunk")) {
vector < int > nChunk = D.options["chunk"].as < vector < int > > ();
if (nChunk.size() != 2 || nChunk[0] > nChunk[1]) vrb.error("Incorrect --chunk arguments!");
vrb.bullet("Chunk = [" + stb.str(nChunk[0]) + "/" + stb.str(nChunk[1]) + "]");
}
D.n_bins = D.options["bins"].as < unsigned int > ();
vrb.bullet("#bins = " + stb.str(D.n_bins));
vrb.bullet("threshold = " + stb.str(D.options["threshold"].as < double > ()));
D.processBasicOptions();
if (D.options.count("chunk")) {
D.scanPhenotypes(D.options["bed"].as < string > ());
D.setPhenotypeLines(D.options["chunk"].as < vector < int > > ()[0], D.options["chunk"].as < vector < int > > ()[1]);
D.clear();
}
//---------------------------
// 7. READ FILES & INITIALIZE
//---------------------------
//D.processBasicOptions();
D.readSampleFromVCF(D.options["vcf"].as < string > ());
D.checkSampleInBED(D.options["bed"].as < string > ());
if (D.options.count("cov")) D.checkSampleInCOV(D.options["cov"].as < string > ());
D.readPhenotypes(D.options["bed"].as < string > ());
D.imputePhenotypes();
if (D.options.count("cov")) {
D.readCovariates(D.options["cov"].as < string > ());
D.residualizePhenotypes();
}
if (D.options.count("normal")) D.normalTranformPhenotypes();
if (D.options.count("permute")) D.shufflePhenotypes();
if (D.options.count("sample")) D.samplePhenotypes(D.options["sample"].as < unsigned int > ());
if (D.options.count("adjust")) D.buildNullDistribution(D.options["adjust"].as < string > ());
D.getCorrelationThreshold(D.options["threshold"].as < double > ());
D.normalizePhenotypes();
//----------------
// 8. RUN ANALYSIS
//----------------
D.runTransPass(D.options["vcf"].as < string > (), D.options["out"].as < string > ());
}
