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());
}

AbstractCellCycleModel* SingleOdeWntCellCycleModel::CreateCellCycleModel()
{
    // Create a new cell-cycle model
    SingleOdeWntCellCycleModel* p_model = new SingleOdeWntCellCycleModel(this->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->SetUseCellProliferativeTypeDependentG1Duration(mUseCellProliferativeTypeDependentG1Duration);
    p_model->SetWntStemThreshold(mWntStemThreshold);
    p_model->SetWntTransitThreshold(mWntTransitThreshold);
    p_model->SetWntLabelledThreshold(mWntLabelledThreshold);
    p_model->SetLastTime(mLastTime);
    p_model->SetBetaCateninDivisionThreshold(mBetaCateninDivisionThreshold);

    /*
     * 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 = this->GetWntLevel();
    p_model->SetOdeSystem(new Mirams2010WntOdeSystem(wnt_level, mpCell->GetMutationState()));
    p_model->SetStateVariables(mpOdeSystem->rGetStateVariables());

    return p_model;
}

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

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

    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 != NULL);
    assert(mpCell != NULL);

    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

    // 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)