WntCellCycleModel.cpp

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*/
#include "WntCellCycleModel.hpp"

#include "TransitCellProliferativeType.hpp"
#include "DifferentiatedCellProliferativeType.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()
{}

WntCellCycleModel::WntCellCycleModel(const WntCellCycleModel& rModel)
   : AbstractWntOdeBasedCellCycleModel(rModel)
{
    /*
     * Initialize only those member variables defined in this class.
     * Create the new cell-cycle model's ODE system and use the current
     * values of the state variables in mpOdeSystem as an initial condition.
     *
     * The member variables mDivideTime and mG2PhaseStartTime are
     * initialized in the AbstractOdeBasedPhaseBasedCellCycleModel
     * constructor.
     *
     * The member variables mCurrentCellCyclePhase, mG1Duration,
     * mMinimumGapDuration, mStemCellG1Duration, mTransitCellG1Duration,
     * mSDuration, mG2Duration and mMDuration are initialized in the
     * AbstractPhaseBasedCellCycleModel constructor.
     *
     * The member variables mBirthTime, mReadyToDivide and mDimension
     * are initialized in the AbstractCellCycleModel constructor.
     */
    assert(rModel.GetOdeSystem());
    double wnt_level = rModel.GetWntLevel();
    SetOdeSystem(new WntCellCycleOdeSystem(wnt_level, rModel.mpCell->GetMutationState()));
    SetStateVariables(rModel.GetOdeSystem()->rGetStateVariables());
}

AbstractCellCycleModel* WntCellCycleModel::CreateCellCycleModel()
{
    // Create a new cell-cycle model
    return new WntCellCycleModel(*this);
}

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

    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 == nullptr);
    assert(mpCell != nullptr);
    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, so just 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)