void CILDMModifiedMethod::step(const double & deltaT)
{
C_INT dim = mData.dim;
C_INT fast = 0;
C_INT slow = dim - fast;
C_INT slow2, fast2;
slow2 = dim;
fast2 = dim - slow2;
C_INT i, j;
mY_initial.resize(dim);
mJacobian_initial.resize(dim, dim);
mQ.resize(dim, dim);
mR.resize(dim, dim);
mTd.resize(dim, dim);
mTdInverse.resize(dim, dim);
mQz.resize(dim, dim);
mTd_save.resize(dim, dim);
mTdInverse_save.resize(dim, dim);
mpModel->updateSimulatedValues(mReducedModel);
// TO REMOVE : mpModel->applyAssignments();
mpModel->calculateJacobianX(mJacobian, 1e-6, 1e-12);
C_INT flag_jacob;
flag_jacob = 1; // Set flag_jacob=0 to print Jacobian
C_FLOAT64 number2conc = mpModel->getNumber2QuantityFactor() / mpModel->getCompartments()[0]->getInitialValue();
//C_FLOAT64 number2conc = 1.;
//this is an ugly hack that only makes sense if all metabs are in the same compartment
//at the moment is is the only case the algorithm deals with
CVector<C_FLOAT64> Xconc; //current state converted to concentrations
Xconc.resize(dim);
for (i = 0; i < dim; ++i)
Xconc[i] = mY[i] * number2conc;
for (i = 0; i < dim; i++)
mY_initial[i] = mY[i];
CVector<C_FLOAT64> Xconc_initial; //current state converted to concentrations
Xconc_initial.resize(dim);
for (i = 0; i < dim; ++i)
Xconc_initial[i] = mY_initial[i] * number2conc;
// save initial Jacobian before next time step
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
mJacobian_initial(i, j) = mJacobian(i, j);
// Next time step
integrationStep(deltaT);
mpModel->updateSimulatedValues(mReducedModel);
// TO REMOVE : mpModel->applyAssignments();
// Calculate Jacobian for time step control
mpModel->calculateJacobianX(mJacobian, 1e-6, 1e-12);
//CMatrix<C_FLOAT64> mTd_save;
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
{
mTd_save(i, j) = 0;
mTdInverse_save(i, j) = 0;
}
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
{
mTd(i, j) = 0;
mTdInverse(i, j) = 0;
}
/** Schur Decomposition of Jacobian (reordered).
Output: mQ - transformation matrix mR - block upper triangular matrix (with ordered eigenvalues) */
C_INT failed = 0;
C_INT info_schur = 0;
C_INT number, k;
C_INT failed_while = 0;
C_INT flag_deufl;
flag_deufl = 1;
C_FLOAT64 max = 0.;
//C_FLOAT64 max = 0;
CVector<C_FLOAT64> re;
CVector<C_FLOAT64> dxdt_relax;
CVector<C_FLOAT64> x_relax;
CVector<C_FLOAT64> x_help;
CVector<C_FLOAT64> dxdt;
CVector<C_FLOAT64> x_zero;
CVector<C_FLOAT64> dxdt_zero;
CVector<C_FLOAT64> dxdt_real;
CVector<C_FLOAT64> help;
CVector<C_INT> index;
CVector<C_INT> index_temp;
CMatrix<C_FLOAT64> orthog_prove;
orthog_prove.resize(dim, dim);
C_INT info;
CVector<C_INT> index_metab;
index_metab.resize(dim);
/** Schur transformation of Jacobian */
schur(info_schur);
if (info_schur)
{
CCopasiMessage(CCopasiMessage::WARNING,
MCTSSAMethod + 9, mTime - deltaT);
goto integration;
}
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
mTdInverse(i, j) = mQ(j, i);
C_INT flag_schur;
flag_schur = 1; // set flag_schur = 0 to print Schur decomposition of jacobian (matrices mR and transformation mQ)
mY_cons.resize(dim); // consistent initial vector for DAE
/* If complex eigenvalues */
//BUG 873
if (mR(dim - 1, dim - 1) == mR(dim - 2 , dim - 2))
if (dim == 2)
{
slow = dim;
goto integration;
}
// If positive eigenvalues
if (mR(dim - 1, dim - 1) >= 0)
{
slow = dim;
fast = 0;
CCopasiMessage(CCopasiMessage::WARNING,
MCTSSAMethod + 10, mTime - deltaT);
failed = 1;
goto integration;
}
// Iterations to determine the number of slow metabolites
while ((slow2 > 1))
{
slow2 = slow2 - 1;
fast2 = dim - slow2;
if (mR(dim - fast2, dim - fast2) >= 0)
{
failed = 1;
goto integration;
}
deuflhard_metab(slow2, info);
if (info)
{
failed_while = 1;
goto integration;
}
}
//end of iterations to determine the number of slow metabolites
/** end of the block %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% */
/** %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% */
integration:
slow = slow2;
fast = fast2;
if ((failed == 1) || (failed_while == 1))
{
if (slow < dim)
{
fast = fast - 1;
slow = dim - fast;
if ((fast >= 1) && (mR(slow - 1, slow - 1) == mR(slow , slow)))
fast = fast - 1;
slow = dim - fast;
}
}
mSlow = slow;
if (slow == dim)
CCopasiMessage(CCopasiMessage::WARNING,
MCTSSAMethod + 11, mTime);
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
// mTdInverse(i,j) = mQ(i,j);
mTd(i, j) = mQ(i, j);
// Flag for print Tabs
mat_anal_mod(slow);
mat_anal_metab(slow);
mat_anal_mod_space(slow);
mat_anal_fast_space(slow);
// This block proves which metabolite could be considered as QSS. In development
/** Begin of the block %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% */
C_INT flag_dev;
flag_dev = 1;
if (flag_dev == 0)
{
C_INT temp;
temp = dim - 1;
// Mode Analysis to find the dominant metabolites in the modes
mat_anal_mod(temp);
//index_metab = -1, if there is no dominant metabolites in corresponding mode,
//and is equal
// to the number of dominant metabolite in opposite case
// Dominant metabolite - its contribution to the mode is larger as 70%
for (j = 0; j < dim; j++)
index_metab[j] = -1;
for (i = 0; i < dim ; i ++)
for (j = 0; j < dim; j++)
if (mVslow(dim - i - 1, j) > 70)
index_metab[i] = j;
C_FLOAT64 y_cons;
info = 0;
k = 0;
number = index_metab[k];
if (number > - 1)
newton_for_timestep(number, y_cons, info);
while (k < dim - 1)
{
if (number > -1)
{
dxdt.resize(dim);
for (j = 0; j < dim; j++)
dxdt[j] = 0.;
//CVector<C_FLOAT64> x_help;
x_help.resize(dim);
for (j = 0; j < dim; j++)
{
x_help[j] = mY_initial[j] * number2conc;
}
calculateDerivativesX(x_help.array(), dxdt.array());
info = 0;
//NEWTON: Looking for consistent initial value for DAE system
//Output: y_cons, info
newton_for_timestep(number, y_cons, info);
if (info)
{
// TODO info: newton iteration stop
}
if (info == 0)
{
// CVector<C_FLOAT64> x_relax;
x_relax.resize(dim);
for (i = 0; i < dim; i ++)
if (i == number)
x_relax[i] = y_cons;
else
x_relax[i] = x_help[i];
//CVector<C_FLOAT64> dxdt_relax;
dxdt_relax.resize(dim);
calculateDerivativesX(x_relax.array(), dxdt_relax.array());
//CVector<C_FLOAT64> re;
re.resize(dim);
C_FLOAT64 eps;
eps = 1 / fabs(mR(dim - k - 1 , dim - k - 1));
// stop criterion for slow reaction modes
for (i = 0; i < dim; i++)
{
if (i == number)
re[i] = 0;
else
{
re[i] = fabs(dxdt_relax[i] - dxdt[i]);
re[i] = re[i] * eps;
}
}
//C_FLOAT64 max = 0.;
for (i = 0; i < dim; i++)
if (max < re[i])
max = re[i];
if (max >= mDtol)
info = 1;
else
info = 0;
}
}
k = k + 1;
number = index_metab[k];
max = 0;
}
}
/** end of the of block %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% */
/** %%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% */
mpModel->updateSimulatedValues(mReducedModel);
// TO REMOVE : mpModel->applyAssignments();
// Calculate Jacobian for time step control
mpModel->calculateJacobianX(mJacobian, 1e-6, 1e-12);
// new entry for every entry contains the current data of currently step
setVectors(slow);
// set the stepcounter
mCurrentStep += 1;
return;
}
void CILDMMethod::step(const double & deltaT)
{
C_INT failed_while = 0;
C_INT dim = mData.dim;
C_INT fast = 0;
C_INT slow = dim - fast;
C_INT i, j, k, info_schur = 0;
mY_initial.resize(dim);
mJacobian_initial.resize(dim, dim);
mQ.resize(dim, dim);
mR.resize(dim, dim);
mQ_desc.resize(dim, dim);
mR_desc.resize(dim, dim);
mTd.resize(dim, dim);
mTdInverse.resize(dim, dim);
mQz.resize(dim, dim);
mTd_save.resize(dim, dim);
mTdInverse_save.resize(dim, dim);
mpModel->updateSimulatedValues(mReducedModel);
// TO REMOVE : mpModel->applyAssignments();
mpModel->calculateJacobianX(mJacobian, 1e-6, 1e-12);
C_INT flag_jacob;
flag_jacob = 1; // Set flag_jacob=0 to printing Jacobian
// To get the reduced Stoichiometry Matrix;
CMatrix<C_FLOAT64> Stoichiom;
Stoichiom = mpModel -> getRedStoi();
// const CCopasiVector< CReaction > & reacs = copasiModel->getReactions();
C_INT32 reacs_size = mpModel -> getRedStoi().size();
reacs_size = reacs_size / dim; //TODO what is this?
/* the vector mY is the current state of the system*/
C_FLOAT64 number2conc = 1.; //= mpModel->getNumber2QuantityFactor()
// / mpModel->getCompartments()[0]->getInitialValue();
//this is an ugly hack that only makes sense if all metabs are in the same compartment
//at the moment is is the only case the algorithm deals with
CVector<C_FLOAT64> Xconc; //current state converted to concentrations
Xconc.resize(dim);
for (i = 0; i < dim; ++i)
Xconc[i] = mY[i] * number2conc;
for (i = 0; i < dim; i++)
mY_initial[i] = mY[i];
CVector<C_FLOAT64> Xconc_initial; //current state converted to concentrations
Xconc_initial.resize(dim);
for (i = 0; i < dim; ++i)
Xconc_initial[i] = mY_initial[i] * number2conc;
// save initial Jacobian before next time step
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
mJacobian_initial(i, j) = mJacobian(i, j);
// Next time step
integrationStep(deltaT);
mpModel->updateSimulatedValues(mReducedModel);
// TO REMOVE : mpModel->applyAssignments();
// Calculate Jacobian for time step control
mpModel->calculateJacobianX(mJacobian, 1e-6, 1e-12);
#ifdef ILDMDEBUG
if (flag_jacob == 0)
{
std::cout << "Jacobian_next:" << std::endl;
std::cout << mJacobian << std::endl;
}
#endif
// to be removed
CMatrix<C_FLOAT64> Jacobian_for_test;
Jacobian_for_test.resize(dim, dim);
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
Jacobian_for_test(i, j) = mJacobian_initial(i, j);
// save initial Jacobian before next time step
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
mJacobian_initial(i, j) = mJacobian(i, j);
schur(info_schur);
#ifdef ILDMDEBUG
std::cout << "Eigenvalues of next Jacobian" << std::endl;
for (i = 0; i < dim; i++)
std::cout << mR(i, i) << std::endl;
#endif
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
mJacobian_initial(i, j) = Jacobian_for_test(i, j);
//end to be removed
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
{
mTd_save(i, j) = 0;
mTdInverse_save(i, j) = 0;
}
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
{
mTd(i, j) = 0;
mTdInverse(i, j) = 0;
}
/** Schur Decomposition of Jacobian (reordered).
Output: mQ - transformation matrix mR - block upper triangular matrix (with ordered eigenvalues) */
C_INT failed = 0;
// C_INT info_schur = 0;
schur(info_schur); // TO DO : move the test to the TSSAMethod
if (info_schur)
{
CCopasiMessage(CCopasiMessage::WARNING,
MCTSSAMethod + 5, mTime - deltaT);
goto integration;
}
C_INT flag_schur;
flag_schur = 0;
#ifdef ILDMDEBUG
std::cout << "Eigenvalues of initial Jacobian" << std::endl;
for (i = 0; i < dim; i++)
std::cout << mR(i, i) << std::endl;
if (flag_schur == 1)
{
std::cout << "Schur Decomposition" << std::endl;
std::cout << "mR - block upper triangular matrix :" << std::endl;
std::cout << mR << std::endl;
}
#endif
/* If complex eigenvalues */
//BUG 873
if (mR(dim - 1, dim - 1) == mR(dim - 2 , dim - 2))
if (dim == 2)
{
slow = dim;
goto integration;
}
// No reduction if the smallest eigenvalue is positive
if (mR(dim - 1, dim - 1) >= 0)
{
slow = dim;
fast = 0;
CCopasiMessage(CCopasiMessage::WARNING,
MCTSSAMethod + 6, mTime - deltaT);
failed = 1;
goto integration;
}
// C_INT number, k;
/** Classical ILDM iterations. The number of slow variables is decreased until the Deuflhard criterium holds */
/* do START slow iterations */
while (slow > 1)
{
fast = fast + 1;
slow = dim - fast;
if (fast < dim - 1)
if (mR(slow, slow) == mR(slow - 1 , slow - 1))
fast = fast + 1;
slow = dim - fast;
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
{
mTd_save(i, j) = mTd(i, j);
mTdInverse_save(i, j) = mTdInverse(i, j);
}
C_INT info = 0;
failed_while = 0;
if (slow == 0)
{
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
{
mTdInverse(i, j) = mQ(j, i);
mTd(i, j) = mQ(i, j);
mQz(i, j) = mR(i, j);
}
}
else
{
/** Solution of Sylvester equation for given slow, mQ,mR
Output: mTd, mTdinverse and mQz (mQz is used later for newton iterations) */
sylvester(slow, info);
if (info)
{
CCopasiMessage(CCopasiMessage::WARNING,
MCTSSAMethod + 7, slow, mTime - deltaT);
failed_while = 1;
goto integration;
}
}
/* Check real parts of eigenvalues of Jacobian */
for (i = slow ; i < dim; i++)
if (mR(i , i) >= 0)
{
failed_while = 1;
goto integration;
}
if (fast > 0)
mEPS = 1 / fabs(mR(slow , slow));
mCfast.resize(fast);
/** Deuflhard Iteration: Prove Deuflhard criteria, find consistent initial value for DAE
output: info - if Deuflhard is satisfied for this slow;
transformation matrices mTd and mTdinverse */
info = 0;
C_INT help;
help = 0;
deuflhard(slow, info);
help = help + 1;
failed_while = 0;
if (info)
{
failed_while = 1;
goto integration;
}
}
/** end of iterations to find the number of slow modes */
integration:
if ((failed == 1) || (failed_while == 1))
{
if (slow < dim)
{
fast = fast - 1;
slow = dim - fast;
if ((fast >= 1) && (mR(slow - 1, slow - 1) == mR(slow , slow)))
fast = fast - 1;
slow = dim - fast;
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
{
mTd(i, j) = mTd_save(i, j);
mTdInverse(i, j) = mTdInverse_save(i, j);
}
}
}
mSlow = slow;
if (slow == dim)
CCopasiMessage(CCopasiMessage::WARNING,
MCTSSAMethod + 8, mTime);
// test for orthogonality of the slow space
C_INT flag_orthog = 1;
if (flag_orthog == 0)
{
CMatrix<C_FLOAT64> orthog_prove;
orthog_prove.resize(dim, dim);
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
orthog_prove(i, j) = orthog(i, j);
}
C_INT flag_develop;
flag_develop = 0; //1;
if (flag_develop == 0)
{
C_INT info_schur_desc = 0;
/** Schur Decomposition of Jacobian (with another sorting: from fast to slow).
Output: mQ_desc - transformation matrix
mR_desc - block upper triangular matrix (with ordered eigenvalues) */
schur_desc(info_schur_desc);
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
{
mTd_save(i, j) = mTd(i, j);
mTdInverse_save(i, j) = mTdInverse(i, j);
}
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
{
mTdInverse(i, j) = mQ_desc(j, i);
mTd(i, j) = mQ_desc(i, j);
}
C_INT slow_desc;
slow_desc = fast;
mat_anal_fast_space(slow_desc);
mat_anal_mod_space(slow_desc);
CVector<C_FLOAT64> Reac_slow_space_orth;
Reac_slow_space_orth.resize(reacs_size);
for (i = 0; i < reacs_size; i ++)
{
Reac_slow_space_orth[i] = 0;
for (j = 0; j < dim; j++)
{
Reac_slow_space_orth[i] = Reac_slow_space_orth[i] + mVfast_space[j] * Stoichiom(j, i);
}
}
for (i = 0; i < dim; i++)
for (j = 0; j < dim; j++)
{
mTd(i, j) = mTd_save(i, j);
mTdInverse(i, j) = mTdInverse_save(i, j);
}
}
// end of test
// Post Analysis
mat_anal_mod(slow);
mat_anal_metab(slow);
mat_anal_mod_space(slow);
mat_anal_fast_space(slow);
/** This part corresponds to the investigation of fast and slow reactions. In development at
the moment. To activate the calculations take flag_develop = 0;
*/
if (flag_develop == 0)
{
CMatrix<C_FLOAT64> Slow_react_contr;
Slow_react_contr.resize(dim, reacs_size);
CMatrix<C_FLOAT64> Mode_react_contr;
Mode_react_contr.resize(dim, reacs_size);
CVector<C_FLOAT64> Reac_slow_space;
Reac_slow_space.resize(reacs_size);
CVector<C_FLOAT64> Reac_fast_space;
Reac_fast_space.resize(reacs_size);
mReacSlowSpace.resize(reacs_size); //NEW TAB
for (i = 0; i < dim; i ++)
for (j = 0; j < reacs_size; j++)
{
Slow_react_contr(i, j) = 0;
for (k = 0; k < dim; k++)
Slow_react_contr(i, j) = Slow_react_contr(i, j) + mVslow(i, k) * Stoichiom(k, j);
}
CVector<C_FLOAT64> denom_mode;
denom_mode.resize(dim);
for (j = 0; j < dim; j++)
denom_mode[j] = 0;
for (i = 0; i < dim; i++)
for (j = 0; j < reacs_size; j++)
denom_mode[i] = denom_mode[i] + fabs(Slow_react_contr(i, j));
for (i = 0; i < dim; i++)
for (j = 0; j < reacs_size; j++)
{
if (denom_mode[i] == 0)
Mode_react_contr(i, j) = 0;
else
Mode_react_contr(i, j) = (Slow_react_contr(i, j)) / denom_mode[i] * 100;
}
CVector<C_FLOAT64> denom_reac;
denom_reac.resize(reacs_size);
for (j = 0; j < reacs_size; j++)
denom_reac[j] = 0;
for (i = 0; i < reacs_size; i++)
for (j = 0; j < dim; j++)
denom_reac[i] = denom_reac[i] + fabs(Slow_react_contr(j, i));
for (i = 0; i < reacs_size; i++)
for (j = 0; j < dim; j++)
{
if (denom_reac[i] == 0)
Slow_react_contr(j, i) = 0;
else
Slow_react_contr(j, i) = (Slow_react_contr(j , i)) / denom_reac[i] * 100;
}
for (i = 0; i < reacs_size; i ++)
{
Reac_slow_space[i] = 0;
for (j = 0; j < dim; j++)
{
Reac_slow_space[i] = Reac_slow_space[i] + mVslow_space[j] * Stoichiom(j, i);
}
}
C_FLOAT64 length;
length = 0;
for (i = 0; i < reacs_size; i++)
length = length + fabs(Reac_slow_space[i]);
for (i = 0; i < reacs_size; i++)
if (length > 0)
mReacSlowSpace[i] = Reac_slow_space[i] / length * 100;
else
mReacSlowSpace[i] = 0;
for (i = 0; i < reacs_size; i ++)
{
Reac_fast_space[i] = 0;
for (j = 0; j < dim; j++)
Reac_fast_space[i] = Reac_fast_space[i] + mVfast_space[j] * Stoichiom(j, i);
}
length = 0;
for (i = 0; i < reacs_size; i++)
length = length + fabs(Reac_fast_space[i]);
for (i = 0; i < reacs_size; i++)
if (length > 0)
Reac_fast_space[i] = Reac_fast_space[i] / length * 100;
else
Reac_fast_space[i] = 0;
#ifdef ILDMDEBUG
std::cout << "**********************************************************" << std::endl;
std::cout << "**********************************************************" << std::endl;
std::cout << std::endl;
std::cout << std::endl;
#endif
mTMP1.resize(reacs_size, dim);
mTMP2.resize(reacs_size, dim);
mTMP3.resize(reacs_size, 1);
for (i = 0; i < dim; i++)
for (j = 0; j < reacs_size; j++)
{
mTMP1(j, i) = Mode_react_contr(i, j);
mTMP2(j, i) = Slow_react_contr(i, j);
}
for (j = 0; j < reacs_size; j++)
mTMP3(j, 0) = Reac_fast_space[j];
}
// End of reaction analysis
mpModel->updateSimulatedValues(mReducedModel);
// TO REMOVE : mpModel->applyAssignments();
// Calculate Jacobian for time step control
mpModel->calculateJacobianX(mJacobian, 1e-6, 1e-12);
// new entry for every entry contains the current data of currently step
setVectors(slow);
// set the stepcounter
mCurrentStep += 1;
return;
}
