AbstractVanLeeuwen2009WntSwatCellCycleModel.cpp

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#include "UblasIncludes.hpp"
#include "AbstractVanLeeuwen2009WntSwatCellCycleModel.hpp"
#include "TransitCellProliferativeType.hpp"
#include "DifferentiatedCellProliferativeType.hpp"

AbstractVanLeeuwen2009WntSwatCellCycleModel::AbstractVanLeeuwen2009WntSwatCellCycleModel(boost::shared_ptr<AbstractCellCycleModelOdeSolver> pOdeSolver)
   : AbstractWntOdeBasedCellCycleModel(pOdeSolver)
{
}

AbstractVanLeeuwen2009WntSwatCellCycleModel::AbstractVanLeeuwen2009WntSwatCellCycleModel(const AbstractVanLeeuwen2009WntSwatCellCycleModel& rModel)
   : AbstractWntOdeBasedCellCycleModel(rModel)
{
    /*
     * 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.
     */
}

void AbstractVanLeeuwen2009WntSwatCellCycleModel::ChangeCellProliferativeTypeDueToCurrentBetaCateninLevel()
{
    assert(mpOdeSystem != nullptr);
    assert(mpCell != nullptr);
    double beta_catenin_level =   mpOdeSystem->rGetStateVariables()[16]
                                + mpOdeSystem->rGetStateVariables()[17]
                                + mpOdeSystem->rGetStateVariables()[18]
                                + mpOdeSystem->rGetStateVariables()[19];

    // For mitogenic stimulus of 1/25.0 in Wnt equations
    if (beta_catenin_level < 10.188)
    {
        /*
         * 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 AbstractVanLeeuwen2009WntSwatCellCycleModel::Initialise()
{
    assert(mpOdeSystem == nullptr);
    assert(mpCell != nullptr);

    double wnt_level = GetWntLevel();

    InitialiseOdeSystem(wnt_level, mpCell->GetMutationState());

    mpOdeSystem->SetStateVariables(mpOdeSystem->GetInitialConditions());

    ChangeCellProliferativeTypeDueToCurrentBetaCateninLevel();
}

void AbstractVanLeeuwen2009WntSwatCellCycleModel::AdjustOdeParameters(double currentTime)
{
    // Pass this time step's Wnt stimulus into the solver as a constant over this timestep.
    mpOdeSystem->rGetStateVariables()[21] = GetWntLevel();

    // Use the cell's current mutation status as another input
    static_cast<VanLeeuwen2009WntSwatCellCycleOdeSystem*>(mpOdeSystem)->SetMutationState(mpCell->GetMutationState());
}

double AbstractVanLeeuwen2009WntSwatCellCycleModel::GetMembraneBoundBetaCateninLevel()
{
    return mpOdeSystem->rGetStateVariables()[13] + mpOdeSystem->rGetStateVariables()[14];
}

double AbstractVanLeeuwen2009WntSwatCellCycleModel::GetCytoplasmicBetaCateninLevel()
{
    return  mpOdeSystem->rGetStateVariables()[7] + mpOdeSystem->rGetStateVariables()[8]
          + mpOdeSystem->rGetStateVariables()[9] + mpOdeSystem->rGetStateVariables()[10]
          + mpOdeSystem->rGetStateVariables()[11];
}

double AbstractVanLeeuwen2009WntSwatCellCycleModel::GetNuclearBetaCateninLevel()
{
    return mpOdeSystem->rGetStateVariables()[16] +
           mpOdeSystem->rGetStateVariables()[17] +
           mpOdeSystem->rGetStateVariables()[18] +
           mpOdeSystem->rGetStateVariables()[19];
}

void AbstractVanLeeuwen2009WntSwatCellCycleModel::OutputCellCycleModelParameters(out_stream& rParamsFile)
{
    // No new parameters to output, so just call method on direct parent class
    AbstractWntOdeBasedCellCycleModel::OutputCellCycleModelParameters(rParamsFile);
}