CryptSimulation2d.cpp

/*

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*/

#include "CryptSimulation2d.hpp"
#include "WntConcentration.hpp"
#include "VanLeeuwen2009WntSwatCellCycleModelHypothesisOne.hpp"
#include "VanLeeuwen2009WntSwatCellCycleModelHypothesisTwo.hpp"
#include "SmartPointers.hpp"

CryptSimulation2d::CryptSimulation2d(AbstractCellPopulation<2>& rCellPopulation,
                                     bool deleteCellPopulationInDestructor,
                                     bool initialiseCells)
    : OffLatticeSimulation<2>(rCellPopulation,
                             deleteCellPopulationInDestructor,
                             initialiseCells),
      mWriteBetaCatenin(false),
      mUsingMeshBasedCellPopulation(false)
{
    /* Throw an exception message if not using a  MeshBasedCellPopulation or a VertexBasedCellPopulation.
     * This is to catch NodeBasedCellPopulations as AbstactOnLatticeBasedCellPopulations are caught in
     * the OffLatticeSimulation constructor.
     */
    if ( (dynamic_cast<VertexBasedCellPopulation<2>*>(&rCellPopulation) == NULL)
         &&(dynamic_cast<MeshBasedCellPopulation<2>*>(&rCellPopulation) == NULL) )
    {
        EXCEPTION("CryptSimulation2d is to be used with MeshBasedCellPopulation or VertexBasedCellPopulation (or subclasses) only");
    }

    if (dynamic_cast<MeshBasedCellPopulation<2>*>(&mrCellPopulation))
    {
        mUsingMeshBasedCellPopulation = true;
    }

    /*
     * To check if beta-catenin results will be written to file, we test if the first
     * cell has a cell-cycle model that is a subclass of AbstractVanLeeuwen2009WntSwatCellCycleModel.
     * In doing so, we assume that all cells in the simulation have the same cell cycle
     * model.
     */
    if (dynamic_cast<AbstractVanLeeuwen2009WntSwatCellCycleModel*>(mrCellPopulation.Begin()->GetCellCycleModel()))
    {
        mWriteBetaCatenin = true;
    }

    if (!mDeleteCellPopulationInDestructor)
    {
        // Pass a CryptSimulationBoundaryCondition object into mBoundaryConditions
        MAKE_PTR_ARGS(CryptSimulationBoundaryCondition<2>, p_bc, (&rCellPopulation));
        AddCellPopulationBoundaryCondition(p_bc);
    }
}

CryptSimulation2d::~CryptSimulation2d()
{
}

c_vector<double, 2> CryptSimulation2d::CalculateCellDivisionVector(CellPtr pParentCell)
{
    if (mUsingMeshBasedCellPopulation)
    {
        // Location of parent and daughter cells
        c_vector<double, 2> parent_coords = mrCellPopulation.GetLocationOfCellCentre(pParentCell);
        c_vector<double, 2> daughter_coords;

        // Get separation parameter
        double separation =
            static_cast<MeshBasedCellPopulation<2>*>(&mrCellPopulation)->GetMeinekeDivisionSeparation();

        // Make a random direction vector of the required length
        c_vector<double, 2> random_vector;

        /*
         * Pick a random direction and move the parent cell backwards by 0.5*separation
         * in that direction and return the position of the daughter cell 0.5*separation
         * forwards in that direction.
         */
        double random_angle = RandomNumberGenerator::Instance()->ranf();
        random_angle *= 2.0*M_PI;

        random_vector(0) = 0.5*separation*cos(random_angle);
        random_vector(1) = 0.5*separation*sin(random_angle);

        c_vector<double, 2> proposed_new_parent_coords = parent_coords - random_vector;
        c_vector<double, 2> proposed_new_daughter_coords = parent_coords + random_vector;

        if ((proposed_new_parent_coords(1) >= 0.0) && (proposed_new_daughter_coords(1) >= 0.0))
        {
            // We are not too close to the bottom of the cell population, so move parent
            parent_coords = proposed_new_parent_coords;
            daughter_coords = proposed_new_daughter_coords;
        }
        else
        {
            proposed_new_daughter_coords = parent_coords + 2.0*random_vector;
            while (proposed_new_daughter_coords(1) < 0.0)
            {
                random_angle = RandomNumberGenerator::Instance()->ranf();
                random_angle *= 2.0*M_PI;

                random_vector(0) = separation*cos(random_angle);
                random_vector(1) = separation*sin(random_angle);
                proposed_new_daughter_coords = parent_coords + random_vector;
            }
            daughter_coords = proposed_new_daughter_coords;
        }

        assert(daughter_coords(1) >= 0.0); // to make sure dividing cells stay in the cell population
        assert(parent_coords(1) >= 0.0);   // to make sure dividing cells stay in the cell population

        // Set the parent to use this location
        ChastePoint<2> parent_coords_point(parent_coords);

        unsigned node_index = mrCellPopulation.GetLocationIndexUsingCell(pParentCell);
        mrCellPopulation.SetNode(node_index, parent_coords_point);

        return daughter_coords;
    }
    else // using a VertexBasedCellPopulation
    {
        c_vector<double, 2> axis_of_division = zero_vector<double>(2);

        // We don't need to prescribe how 'stem' cells divide if Wnt is present
        bool is_wnt_included = WntConcentration<2>::Instance()->IsWntSetUp();
        if (!is_wnt_included)
        {
            WntConcentration<2>::Destroy();
            if (pParentCell->GetCellProliferativeType() == STEM)
            {
                axis_of_division(0) = 1.0;
                axis_of_division(1) = 0.0;
            }
        }
        return axis_of_division;
    }
}

void CryptSimulation2d::SetupWriteBetaCatenin()
{
    OutputFileHandler output_file_handler(this->mSimulationOutputDirectory + "/", false);
    mVizBetaCateninResultsFile = output_file_handler.OpenOutputFile("results.vizbetacatenin");
    *mpVizSetupFile << "BetaCatenin\n";
}

void CryptSimulation2d::WriteBetaCatenin(double time)
{
    *mVizBetaCateninResultsFile <<  time << "\t";

    for (AbstractCellPopulation<2>::Iterator cell_iter = mrCellPopulation.Begin();
         cell_iter != mrCellPopulation.End();
         ++cell_iter)
    {
        unsigned global_index = mrCellPopulation.GetLocationIndexUsingCell(*cell_iter);
        double x = mrCellPopulation.GetLocationOfCellCentre(*cell_iter)[0];
        double y = mrCellPopulation.GetLocationOfCellCentre(*cell_iter)[1];

        // We should only be calling this code block if mWriteBetaCatenin has been set to true in the constructor
        assert(mWriteBetaCatenin);

        AbstractVanLeeuwen2009WntSwatCellCycleModel* p_model = dynamic_cast<AbstractVanLeeuwen2009WntSwatCellCycleModel*>(cell_iter->GetCellCycleModel());
        double b_cat_membrane = p_model->GetMembraneBoundBetaCateninLevel();
        double b_cat_cytoplasm = p_model->GetCytoplasmicBetaCateninLevel();
        double b_cat_nuclear = p_model->GetNuclearBetaCateninLevel();

        *mVizBetaCateninResultsFile << global_index << " " << x << " " << y << " " << b_cat_membrane << " " << b_cat_cytoplasm << " " << b_cat_nuclear << " ";
    }

    *mVizBetaCateninResultsFile << "\n";
}

void CryptSimulation2d::SetupSolve()
{
    // First call method on base class
    OffLatticeSimulation<2>::SetupSolve();

    /*
     * If there are any cells in the simulation, and mWriteBetaCatenin has been set
     * to true in the constructor, then set up the beta-catenin results file and
     * write the initial conditions to file.
     */
    bool any_cells_present = (mrCellPopulation.Begin() != mrCellPopulation.End());
    if (any_cells_present && mWriteBetaCatenin)
    {
        SetupWriteBetaCatenin();
        double current_time = SimulationTime::Instance()->GetTime();
        WriteBetaCatenin(current_time);
    }
}

void CryptSimulation2d::UpdateAtEndOfTimeStep()
{
    SimulationTime* p_time = SimulationTime::Instance();

    if ((p_time->GetTimeStepsElapsed()+1)%mSamplingTimestepMultiple == 0)
    {
        /*
         * If there are any cells in the simulation, and mWriteBetaCatenin has been set
         * to true in the constructor, then set up the beta-catenin results file and
         * write the initial conditions to file.
         */
        bool any_cells_present = (mrCellPopulation.Begin() != mrCellPopulation.End());
        if (any_cells_present && mWriteBetaCatenin)
        {
            double time_next_step = p_time->GetTime() + p_time->GetTimeStep();
            WriteBetaCatenin(time_next_step);
        }
    }
}

void CryptSimulation2d::UpdateAtEndOfSolve()
{
    // First call method on base class
    OffLatticeSimulation<2>::UpdateAtEndOfSolve();

    /*
     * If there are any cells in the simulation, and mWriteBetaCatenin has been set
     * to true in the constructor, then close the beta-catenin results file.
     */
    bool any_cells_present = (mrCellPopulation.Begin() != mrCellPopulation.End());
    if (any_cells_present && mWriteBetaCatenin)
    {
        mVizBetaCateninResultsFile->close();
    }
}

void CryptSimulation2d::UseJiggledBottomCells()
{
    // The CryptSimulationBoundaryCondition object is the first element of mBoundaryConditions
    boost::static_pointer_cast<CryptSimulationBoundaryCondition<2> >(mBoundaryConditions[0])->SetUseJiggledBottomCells(true);
}

void CryptSimulation2d::SetBottomCellAncestors()
{
    /*
     * We use a different height threshold depending on which type of cell
     * population we are using, a MeshBasedCellPopulationWithGhostNodes or
     * a VertexBasedCellPopulation.
     */
    double threshold_height = 1.0;
    if (mUsingMeshBasedCellPopulation)
    {
        threshold_height = 0.5;
    }

    unsigned index = 0;
    for (AbstractCellPopulation<2>::Iterator cell_iter = mrCellPopulation.Begin();
         cell_iter != mrCellPopulation.End();
         ++cell_iter)
    {
        if (mrCellPopulation.GetLocationOfCellCentre(*cell_iter)[1] < threshold_height)
        {
            MAKE_PTR_ARGS(CellAncestor, p_cell_ancestor, (index++));
            cell_iter->SetAncestor(p_cell_ancestor);
        }
    }
}

void CryptSimulation2d::OutputSimulationParameters(out_stream& rParamsFile)
{
    double width = mrCellPopulation.GetWidth(0);
    bool use_jiggled_bottom_cells = boost::static_pointer_cast<CryptSimulationBoundaryCondition<2> >(mBoundaryConditions[0])->GetUseJiggledBottomCells();

    *rParamsFile << "\t\t<CryptCircumference>" << width << "</CryptCircumference>\n";
    *rParamsFile << "\t\t<UseJiggledBottomCells>" << use_jiggled_bottom_cells << "</UseJiggledBottomCells>\n";

    // Call method on direct parent class
    OffLatticeSimulation<2>::OutputSimulationParameters(rParamsFile);
}

// Serialization for Boost >= 1.36
#include "SerializationExportWrapperForCpp.hpp"
CHASTE_CLASS_EXPORT(CryptSimulation2d)