SingleOdeWntCellCycleModel.cpp

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#include "UblasIncludes.hpp"
#include "SingleOdeWntCellCycleModel.hpp"
#include "TransitCellProliferativeType.hpp"
#include "DifferentiatedCellProliferativeType.hpp"

SingleOdeWntCellCycleModel::SingleOdeWntCellCycleModel(boost::shared_ptr<AbstractCellCycleModelOdeSolver> pOdeSolver)
    : CellCycleModelOdeHandler(DOUBLE_UNSET, pOdeSolver),
      mBetaCateninDivisionThreshold(100)// MAGIC NUMBER!
{
    if (mpOdeSolver == boost::shared_ptr<AbstractCellCycleModelOdeSolver>())
    {
#ifdef CHASTE_CVODE
        mpOdeSolver = CellCycleModelOdeSolver<SingleOdeWntCellCycleModel, CvodeAdaptor>::Instance();
        mpOdeSolver->Initialise();
        mpOdeSolver->SetMaxSteps(10000);
#else
        mpOdeSolver = CellCycleModelOdeSolver<SingleOdeWntCellCycleModel, RungeKutta4IvpOdeSolver>::Instance();
        mpOdeSolver->Initialise();
        SetDt(0.001);
#endif //CHASTE_CVODE
    }
    assert(mpOdeSolver->IsSetUp());
}

SingleOdeWntCellCycleModel::SingleOdeWntCellCycleModel(const SingleOdeWntCellCycleModel& rModel)
    : SimpleWntCellCycleModel(rModel),
      CellCycleModelOdeHandler(rModel),
      mBetaCateninDivisionThreshold(rModel.mBetaCateninDivisionThreshold)
{
    /*
     * 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 mUseCellProliferativeTypeDependentG1Duration,
     * mWntStemThreshold, mWntTransitThreshold and mWntLabelledThreshold
     * are initialized in the SimpleWntCellCycleModel 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 Mirams2010WntOdeSystem(wnt_level, rModel.mpCell->GetMutationState()));
    SetStateVariables(rModel.GetOdeSystem()->rGetStateVariables());
}

AbstractCellCycleModel* SingleOdeWntCellCycleModel::CreateCellCycleModel()
{
    return new SingleOdeWntCellCycleModel(*this);
}

void SingleOdeWntCellCycleModel::UpdateCellCyclePhase()
{
    assert(SimulationTime::Instance()->IsStartTimeSetUp());
    SolveOdeToTime(SimulationTime::Instance()->GetTime());
    ChangeCellProliferativeTypeDueToCurrentBetaCateninLevel();
    AbstractSimplePhaseBasedCellCycleModel::UpdateCellCyclePhase(); 
}

void SingleOdeWntCellCycleModel::Initialise()
{
    assert(mpOdeSystem == nullptr);
    assert(mpCell != nullptr);

    double wnt_level = this->GetWntLevel();
    mpOdeSystem = new Mirams2010WntOdeSystem(wnt_level, mpCell->GetMutationState());
    mpOdeSystem->SetStateVariables(mpOdeSystem->GetInitialConditions());

    // MAGIC NUMBER!
    //mBetaCateninDivisionThreshold = 100.0;

    // This call actually sets up the G1 phase to something sensible (random number generated)
    SimpleWntCellCycleModel::Initialise();

    SetLastTime(mBirthTime);

    ChangeCellProliferativeTypeDueToCurrentBetaCateninLevel();
}

void SingleOdeWntCellCycleModel::AdjustOdeParameters(double currentTime)
{
    // Pass this time step's Wnt stimulus into the solver as a constant over this timestep.
    mpOdeSystem->rGetStateVariables()[2] = this->GetWntLevel();

    // Use the cell's current mutation status as another input
    static_cast<Mirams2010WntOdeSystem*>(mpOdeSystem)->SetMutationState(mpCell->GetMutationState());
}

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

    if (GetBetaCateninConcentration() < GetBetaCateninDivisionThreshold())
    {
        /*
         * 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);
    }
}

double SingleOdeWntCellCycleModel::GetBetaCateninConcentration()
{
    return mpOdeSystem->rGetStateVariables()[0] + mpOdeSystem->rGetStateVariables()[1];
}

void SingleOdeWntCellCycleModel::SetBetaCateninDivisionThreshold(double betaCateninDivisionThreshold)
{
    mBetaCateninDivisionThreshold = betaCateninDivisionThreshold;
}

double SingleOdeWntCellCycleModel::GetBetaCateninDivisionThreshold()
{
    return mBetaCateninDivisionThreshold;
}

void SingleOdeWntCellCycleModel::OutputCellCycleModelParameters(out_stream& rParamsFile)
{
    // No new parameters to output, so just call method on direct parent class
    SimpleWntCellCycleModel::OutputCellCycleModelParameters(rParamsFile);
}

// Declare identifier for the serializer
#include "SerializationExportWrapperForCpp.hpp"
CHASTE_CLASS_EXPORT(SingleOdeWntCellCycleModel)
#include "CellCycleModelOdeSolverExportWrapper.hpp"
EXPORT_CELL_CYCLE_MODEL_ODE_SOLVER(SingleOdeWntCellCycleModel)