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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 __BSLMM_H__
#define __BSLMM_H__
#include <gsl/gsl_randist.h>
// #include <gsl/gsl_rng.h>
#include <map>
#include <vector>
#include "param.h"
using namespace std;
class BSLMM {
public:
// IO-related parameters.
int a_mode;
size_t d_pace;
string file_bfile;
string file_geno;
string file_out;
string path_out;
// LMM-related parameters.
double l_min;
double l_max;
size_t n_region;
double pve_null;
double pheno_mean;
// BSLMM MCMC-related parameters
double h_min, h_max, h_scale; // Priors for h.
double rho_min, rho_max, rho_scale; // Priors for rho.
double logp_min, logp_max, logp_scale; // Priors for log(pi).
size_t s_min, s_max; // Min. & max. number of gammas.
size_t w_step; // Number of warm up/burn in
// iterations.
size_t s_step; // Num. sampling iterations.
size_t r_pace; // Record pace.
size_t w_pace; // Write pace.
size_t n_accept; // Number of acceptances.
size_t n_mh; // Number of MH steps per iter.
double geo_mean; // Mean of geometric dist.
// long int randseed;
gsl_rng *gsl_r; // Track randomizer state
double trace_G;
HYPBSLMM cHyp_initial;
// Summary statistics.
size_t ni_total, ns_total; // Number of total individuals and SNPs
size_t ni_test, ns_test; // Num. individuals & SNPs used in analysis.
size_t n_cvt; // Number of covariates.
double time_UtZ;
double time_Omega; // Time spent on optimization iterations.
// Time spent on constructing the proposal distribution for
// gamma (i.e. lmm or lm analysis).
double time_Proposal;
// 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;
// Record SNP information.
vector<SNPINFO> snpInfo;
// Not included in PARAM.
// gsl_rng *gsl_r;
gsl_ran_discrete_t *gsl_t;
map<size_t, size_t> mapRank2pos;
// Main functions.
void CopyFromParam(PARAM &cPar);
void CopyToParam(PARAM &cPar);
void RidgeR(const gsl_matrix *U, const gsl_matrix *UtX, const gsl_vector *Uty,
const gsl_vector *eval, const double lambda);
void MCMC(const gsl_matrix *U, const gsl_matrix *UtX, const gsl_vector *Uty,
const gsl_vector *K_eval, const gsl_vector *y);
void WriteLog();
void WriteLR();
void WriteBV(const gsl_vector *bv);
void WriteParam(vector<pair<double, double>> &beta_g, const gsl_vector *alpha,
const size_t w);
void WriteParam(const gsl_vector *alpha);
void WriteResult(const int flag, const gsl_matrix *Result_hyp,
const gsl_matrix *Result_gamma, const size_t w_col);
// Subfunctions inside MCMC.
void CalcPgamma(double *p_gammar);
double CalcPveLM(const gsl_matrix *UtXgamma, const gsl_vector *Uty,
const double sigma_a2);
void InitialMCMC(const gsl_matrix *UtX, const gsl_vector *Uty,
vector<size_t> &rank_old, class HYPBSLMM &cHyp,
vector<pair<size_t, double>> &pos_loglr);
double CalcPosterior(const gsl_vector *Uty, const gsl_vector *K_eval,
gsl_vector *Utu, gsl_vector *alpha_prime,
class HYPBSLMM &cHyp);
double CalcPosterior(const gsl_matrix *UtXgamma, const gsl_vector *Uty,
const gsl_vector *K_eval, gsl_vector *UtXb,
gsl_vector *Utu, gsl_vector *alpha_prime,
gsl_vector *beta, class HYPBSLMM &cHyp);
void CalcCC_PVEnZ(const gsl_matrix *U, const gsl_vector *Utu,
gsl_vector *z_hat, class HYPBSLMM &cHyp);
void CalcCC_PVEnZ(const gsl_matrix *U, const gsl_vector *UtXb,
const gsl_vector *Utu, gsl_vector *z_hat,
class HYPBSLMM &cHyp);
double CalcREMLE(const gsl_matrix *Utw, const gsl_vector *Uty,
const gsl_vector *K_eval);
// Calculate the maximum marginal likelihood ratio for each
// analyzed SNPs with gemma, use it to rank SNPs.
double CalcLR(const gsl_matrix *U, const gsl_matrix *UtX,
const gsl_vector *Uty, const gsl_vector *K_eval,
vector<pair<size_t, double>> &loglr_sort);
void SampleZ(const gsl_vector *y, const gsl_vector *z_hat, gsl_vector *z);
double ProposeHnRho(const class HYPBSLMM &cHyp_old, class HYPBSLMM &cHyp_new,
const size_t &repeat);
double ProposePi(const class HYPBSLMM &cHyp_old, class HYPBSLMM &cHyp_new,
const size_t &repeat);
double ProposeGamma(const vector<size_t> &rank_old, vector<size_t> &rank_new,
const double *p_gamma, const class HYPBSLMM &cHyp_old,
class HYPBSLMM &cHyp_new, const size_t &repeat);
void SetXgamma(gsl_matrix *Xgamma, const gsl_matrix *X, vector<size_t> &rank);
void CalcXtX(const gsl_matrix *X_new, const gsl_vector *y,
const size_t s_size, gsl_matrix *XtX_new, gsl_vector *Xty_new);
void SetXgamma(const gsl_matrix *X, const gsl_matrix *X_old,
const gsl_matrix *XtX_old, const gsl_vector *Xty_old,
const gsl_vector *y, const vector<size_t> &rank_old,
const vector<size_t> &rank_new, gsl_matrix *X_new,
gsl_matrix *XtX_new, gsl_vector *Xty_new);
double CalcPosterior(const double yty, class HYPBSLMM &cHyp);
double CalcPosterior(const gsl_matrix *Xgamma, const gsl_matrix *XtX,
const gsl_vector *Xty, const double yty,
const size_t s_size, gsl_vector *Xb, gsl_vector *beta,
class HYPBSLMM &cHyp);
void CalcCC_PVEnZ(gsl_vector *z_hat, class HYPBSLMM &cHyp);
void CalcCC_PVEnZ(const gsl_vector *Xb, gsl_vector *z_hat,
class HYPBSLMM &cHyp);
void MCMC(const gsl_matrix *X, const gsl_vector *y);
};
#endif
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