//
// File: GTR.h
// Created by: Julien Dutheil
// Created on: Tue Oct 25 10:17 2005
//

/*
Copyright or © or Copr. CNRS, (November 16, 2004)

This software is a computer program whose purpose is to provide classes
for phylogenetic data analysis.

This software is governed by the CeCILL  license under French law and
abiding by the rules of distribution of free software.  You can  use, 
modify and/ or redistribute the software under the terms of the CeCILL
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*/

#ifndef _GTR_H_
#define _GTR_H_

#include "NucleotideSubstitutionModel.h"
#include "../AbstractSubstitutionModel.h"

#include <Bpp/Numeric/Constraints.h>

// From SeqLib:
#include <Bpp/Seq/Alphabet/NucleicAlphabet.h>

namespace bpp
{

/**
 * @brief The General Time-Reversible substitution model for nucleotides.
 *
 * This model is sometimes called the REV model, following Yang (1994), see references.
 * It was used in Lanave et al (1984), described in Tavare et al. 1886 and Rodriguez et al. 1990.
 * It is the most general reversible one, it has 6 substitution rates and 4 frequency
 * parameters.
 * We used the parametrization proposed by Yang (1994):
 * \f[
 * S = \begin{pmatrix}
 * \cdots & d & f & b \\ 
 * d & \cdots & e & a \\ 
 * f & e & \cdots & c \\ 
 * b & a & c & \cdots \\ 
 * \end{pmatrix}
 * \f]
 * \f[
 * \pi = \left(\pi_A, \pi_C, \pi_G, \pi_T\right)
 * \f]
 * This models hence includes nine parameters, five relative rates \f$a, b, c, d, e\f$
 * and four frequencies \f$\pi_A, \pi_C, \pi_G, \pi_T\f$.
 * These four frequencies are not independent parameters, since they have the constraint to
 * sum to 1.
 * We use instead a different parametrization to remove this constraint:
 * \f[
 * \begin{cases}
 * \theta = \pi_C + \pi_G\\
 * \theta_1 = \frac{\pi_A}{1 - \theta} = \frac{\pi_A}{\pi_A + \pi_T}\\
 * \theta_2 = \frac{\pi_G}{\theta} = \frac{\pi_G}{\pi_C + \pi_G}\\
 * \end{cases}
 * \Longleftrightarrow
 * \begin{cases}
 * \pi_A = \theta_1 (1 - \theta)\\
 * \pi_C = (1 - \theta_2) \theta\\
 * \pi_G = \theta_2 \theta\\
 * \pi_T = (1 - \theta_1)(1 - \theta).
 * \end{cases}
 * \f]
 * These parameters can also be measured from the data and not optimized.
 *
 * Normalization: we set \f$f\f$ to 1, and scale the matrix so that \f$\sum_i Q_{i,i}\pi_i = -1\f$.
 * Parameters \f$a,b,c,d,e\f$ are hence relative rates.
 * \f[
 * S = \frac{1}{P}\begin{pmatrix}
 * \frac{-b\pi_T-\pi_G-d\pi_C}{\pi_A} & d & 1 & b \\ 
 * d & \frac{-a\pi_T-e\pi_G-d\pi_A}{\pi_C} & e & a \\ 
 * 1 & e & \frac{-c\pi_T-e\pi_C-\pi_A}{\pi_G} & c \\ 
 * b & a & c & \frac{-c\pi_G-a\pi_C-b\pi_A}{\pi_T} \\ 
 * \end{pmatrix}
 * \f]
 * with \f{eqnarray*}
 * P &=& \pi_A(d\pi_C+ \pi_G+b\pi_T)\\
 *   &+& \pi_C(d\pi_A+e\pi_G+a\pi_T)\\
 *   &+& \pi_G( \pi_A+e\pi_C+c\pi_T)\\
 *   &+& \pi_T(b\pi_A+a\pi_C+c\pi_G)\\
 *   &=& 2*(a*\pi_C*\pi_T+b*\pi_A*\pi_T+c*\pi_G*\pi_T+d*\pi_A*\pi_C+e*\pi_C*\pi_G+\pi_A*\pi_G)
 * \f}
 *
 * The normalized generator is obtained by taking the dot product of \f$S\f$ and \f$\pi\f$:
 * \f[
 * Q = S . \pi = \frac{1}{P}\begin{pmatrix}
 * -b\pi_T-\pi_G-d\pi_C & d\pi_C & \pi_G & b\pi_T \\ 
 * d\pi_A & -a\pi_T-e\pi_G-d\pi_A & e\pi_G & a\pi_T \\ 
 * \pi_A & e\pi_C & -c\pi_T-e\pi_C-\pi_A & c\pi_T \\ 
 * b\pi_A & a\pi_C & c\pi_G & -c\pi_G-a\pi_C-b\pi_A \\ 
 * \end{pmatrix}
 * \f]
 *
 * For now, the generator of this model is diagonalized numericaly.
 * See AbstractSubstitutionModel for details of how the porbabilities are computed.
 *
 * The parameters are named \c "a", \c "b", \c "c", \c "d", \c "e", \c "theta", \c "theta1", and \c "theta2"
 * and their values may be retrieve with the command 
 * \code
 * getParameterValue("a")
 * \endcode
 * for instance.
 * 
 * Reference:
 * - Yang Z (1994), Journal_ Of Molecular Evolution_ 39(1) 105-11.
 * - Lanave C, Preparata G, Saccone C and Serio G (1984), Journal_ Of Molecular Evolution_ 20 86-93.
 * - Tavaré S (1986), Lect_. Math. Life Sci._ 17 57-86.
 * - Rodriguez F (1990, Journal_ Of Theoretical Biology_ 142(4) 485-501.
 */
class GTR:
  public AbstractReversibleNucleotideSubstitutionModel
{
  protected:
    double a_, b_, c_, d_, e_, piA_, piC_, piG_, piT_, theta_, theta1_, theta2_, p_;

  public:
    GTR(
      const NucleicAlphabet * alpha,
      double a = 1.,
      double b = 1.,
      double c = 1.,
      double d = 1.,
      double e = 1.,
      double piA = 0.25,
      double piC = 0.25,
      double piG = 0.25,
      double piT = 0.25);
  
    virtual ~GTR() {}

    GTR* clone() const { return new GTR(*this); }

  public:
    std::string getName() const { return "GTR"; }
  
  void updateMatrices();


  /**
   * @brief This method is redefined to actualize the corresponding parameters piA, piT, piG and piC too.
   */

  void setFreq(std::map<int,double>& freqs);
};

} //end of namespace bpp.

#endif  //_GTR_H_

