WntCellCycleModel.cpp

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*/
#include "WntCellCycleModel.hpp"

WntCellCycleModel::WntCellCycleModel(boost::shared_ptr<AbstractCellCycleModelOdeSolver> pOdeSolver)
    : AbstractWntOdeBasedCellCycleModel(pOdeSolver)
{
    if (!mpOdeSolver)
    {
#ifdef CHASTE_CVODE
        mpOdeSolver = CellCycleModelOdeSolver<WntCellCycleModel, CvodeAdaptor>::Instance();
        mpOdeSolver->Initialise();
        // Chaste solvers always check for stopping events, CVODE needs to be instructed to do so
        mpOdeSolver->CheckForStoppingEvents();
        mpOdeSolver->SetMaxSteps(10000);
#else
        mpOdeSolver = CellCycleModelOdeSolver<WntCellCycleModel, RungeKutta4IvpOdeSolver>::Instance();
        mpOdeSolver->Initialise();
#endif //CHASTE_CVODE
    }
}

WntCellCycleModel::~WntCellCycleModel()
{}

AbstractCellCycleModel* WntCellCycleModel::CreateCellCycleModel()
{
    // Create a new cell-cycle model
    WntCellCycleModel* p_model = new WntCellCycleModel(mpOdeSolver);

    /*
     * Set each member variable of the new cell-cycle model that inherits
     * its value from the parent.
     *
     * Note 1: some of the new cell-cycle model's member variables (namely
     * mBirthTime, mCurrentCellCyclePhase, mReadyToDivide, mDt, mpOdeSolver)
     * will already have been correctly initialized in its constructor.
     *
     * Note 2: one or more of the new cell-cycle model's member variables
     * may be set/overwritten as soon as InitialiseDaughterCell() is called on
     * the new cell-cycle model.
     */
    p_model->SetBirthTime(mBirthTime);
    p_model->SetDimension(mDimension);
    p_model->SetMinimumGapDuration(mMinimumGapDuration);
    p_model->SetStemCellG1Duration(mStemCellG1Duration);
    p_model->SetTransitCellG1Duration(mTransitCellG1Duration);
    p_model->SetSDuration(mSDuration);
    p_model->SetG2Duration(mG2Duration);
    p_model->SetMDuration(mMDuration);
    p_model->SetDivideTime(mDivideTime);
    p_model->SetFinishedRunningOdes(mFinishedRunningOdes);
    p_model->SetG2PhaseStartTime(mG2PhaseStartTime);
    p_model->SetLastTime(mLastTime);

    /*
     * Create the new cell-cycle model's ODE system and use the current values
     * of the state variables in mpOdeSystem as an initial condition.
     */
    assert(mpOdeSystem);
    double wnt_level = GetWntLevel();
    p_model->SetOdeSystem(new WntCellCycleOdeSystem(wnt_level, mpCell->GetMutationState()));
    p_model->SetStateVariables(mpOdeSystem->rGetStateVariables());

    return p_model;
}

void WntCellCycleModel::ChangeCellProliferativeTypeDueToCurrentBetaCateninLevel()
{
    assert(mpOdeSystem != NULL);
    assert(mpCell != NULL);

    double beta_catenin_level = mpOdeSystem->rGetStateVariables()[6] + mpOdeSystem->rGetStateVariables()[7];

    // For mitogenic stimulus of 6x10^-4 in Wnt equations
    if (beta_catenin_level < 0.4127)
    {
        /*
         * This method is usually called within a CellBasedSimulation, after the CellPopulation
         * has called CellPropertyRegistry::TakeOwnership(). This means that were we to call
         * CellPropertyRegistry::Instance() here when setting the CellProliferativeType, we
         * would be creating a new CellPropertyRegistry. In this case the cell proliferative
         * type counts, as returned by AbstractCellPopulation::GetCellProliferativeTypeCount(),
         * would be incorrect. We must therefore access the CellProliferativeType via the cell's
         * CellPropertyCollection.
         */
        boost::shared_ptr<AbstractCellProperty> p_diff_type =
            mpCell->rGetCellPropertyCollection().GetCellPropertyRegistry()->Get<DifferentiatedCellProliferativeType>();
        mpCell->SetCellProliferativeType(p_diff_type);
    }
    else
    {
        boost::shared_ptr<AbstractCellProperty> p_transit_type =
            mpCell->rGetCellPropertyCollection().GetCellPropertyRegistry()->Get<TransitCellProliferativeType>();
        mpCell->SetCellProliferativeType(p_transit_type);
    }
}

void WntCellCycleModel::Initialise()
{
    assert(mpOdeSystem == NULL);
    assert(mpCell != NULL);
    double wnt_level = GetWntLevel();

    mpOdeSystem = new WntCellCycleOdeSystem(wnt_level, mpCell->GetMutationState());
    mpOdeSystem->SetStateVariables(mpOdeSystem->GetInitialConditions());

    ChangeCellProliferativeTypeDueToCurrentBetaCateninLevel();
}

void WntCellCycleModel::AdjustOdeParameters(double currentTime)
{
    double wnt_level = GetWntLevel();

    // Pass this time step's Wnt stimulus into the solver as a constant over this timestep.
    mpOdeSystem->rGetStateVariables()[8] = wnt_level;

    // Use the cell's current mutation status as another input
    static_cast<WntCellCycleOdeSystem*>(mpOdeSystem)->SetMutationState(mpCell->GetMutationState());
}

void WntCellCycleModel::OutputCellCycleModelParameters(out_stream& rParamsFile)
{
    // No new parameters to output

    // Call method on direct parent class
    AbstractWntOdeBasedCellCycleModel::OutputCellCycleModelParameters(rParamsFile);
}

// Serialization for Boost >= 1.36
#include "SerializationExportWrapperForCpp.hpp"
CHASTE_CLASS_EXPORT(WntCellCycleModel)
#include "CellCycleModelOdeSolverExportWrapper.hpp"
EXPORT_CELL_CYCLE_MODEL_ODE_SOLVER(WntCellCycleModel)