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/*
 Genome-wide Efficient Mixed Model Association (GEMMA)
 Copyright (C) 2011-2017, Xiang Zhou

 This program is free software: you can redistribute it and/or modify
 it under the terms of the GNU General Public License as published by
 the Free Software Foundation, either version 3 of the License, or
 (at your option) any later version.

 This program is distributed in the hope that it will be useful,
 but WITHOUT ANY WARRANTY; without even the implied warranty of
 MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
 GNU General Public License for more details.

 You should have received a copy of the GNU General Public License
 along with this program. If not, see <http://www.gnu.org/licenses/>.
*/

#ifndef __MVLMM_H__
#define __MVLMM_H__

#include "gsl/gsl_vector.h"
#include "gsl/gsl_matrix.h"
#include "param.h"
#include "io.h"

using namespace std;

class MVLMM {

public:
	// IO-related parameters.
	int a_mode;	// Analysis mode: 1/2/3/4 for Frequentist tests.
	size_t d_pace;	// Display pace.

	string file_bfile;
	string file_geno;
	string file_oxford;
	string file_out;
	string path_out;

	// MVLMM-related parameters.
	double l_min;
	double l_max;
	size_t n_region;
	double logl_remle_H0, logl_mle_H0;
	vector<double> Vg_remle_null, Ve_remle_null, Vg_mle_null, Ve_mle_null;
        vector<double> VVg_remle_null, VVe_remle_null, VVg_mle_null;
        vector<double> VVe_mle_null;
        vector<double> beta_remle_null, se_beta_remle_null, beta_mle_null;
        vector<double> se_beta_mle_null;
	double p_nr;
	size_t em_iter, nr_iter;
	double em_prec, nr_prec;
	size_t crt;

	// Summary statistics.
	size_t ni_total, ni_test; // Number of individuals.
	size_t ns_total, ns_test; // Number of SNPs.
	size_t n_cvt;
	size_t n_ph;
	double time_UtX;	  // Time spent on optimization iterations.
	double time_opt;	  // Time spent on optimization iterations.

        // Indicator for individuals (phenotypes): 0 missing, 1
        // available for analysis.
	vector<int> indicator_idv;

    	// Sequence indicator for SNPs: 0 ignored because of (a) maf,
    	// (b) miss, (c) non-poly; 1 available for analysis.
	vector<int> indicator_snp;

	vector<SNPINFO> snpInfo;    // Record SNP information.

	// Not included in PARAM.
	vector<MPHSUMSTAT> sumStat; // Output SNPSummary Data.

	// Main functions
	void CopyFromParam (PARAM &cPar);
	void CopyToParam (PARAM &cPar);
	void AnalyzeBimbam (const gsl_matrix *U, const gsl_vector *eval,
			    const gsl_matrix *UtW, const gsl_matrix *UtY);
	void AnalyzePlink (const gsl_matrix *U, const gsl_vector *eval,
			   const gsl_matrix *UtW, const gsl_matrix *UtY);
	void Analyzebgen (const gsl_matrix *U, const gsl_vector *eval,
			  const gsl_matrix *UtW, const gsl_matrix *UtY);
	void AnalyzeBimbamGXE (const gsl_matrix *U, const gsl_vector *eval,
			       const gsl_matrix *UtW, const gsl_matrix *UtY,
			       const gsl_vector *env);
        void AnalyzePlinkGXE (const gsl_matrix *U, const gsl_vector *eval,
			      const gsl_matrix *UtW, const gsl_matrix *UtY,
			      const gsl_vector *env);
	void WriteFiles ();

};

void CalcMvLmmVgVeBeta (const gsl_vector *eval, const gsl_matrix *UtW,
			const gsl_matrix *UtY, const size_t em_iter,
			const size_t nr_iter, const double em_prec,
			const double nr_prec, const double l_min,
			const double l_max, const size_t n_region,
			gsl_matrix *V_g, gsl_matrix *V_e, gsl_matrix *B,
			gsl_matrix *se_B);

#endif