CryptCellsGenerator.hpp

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*/

#ifndef CRYPTCELLSGENERATOR_HPP_
#define CRYPTCELLSGENERATOR_HPP_

#include <boost/mpl/integral_c.hpp>
#include <boost/type_traits/is_same.hpp>
#include <boost/mpl/if.hpp>

#include "CellsGenerator.hpp"

#include "CellPropertyRegistry.hpp"
#include "TetrahedralMesh.hpp"
#include "VertexMesh.hpp"
#include "PottsMesh.hpp"

#include "UniformG1GenerationalCellCycleModel.hpp"
#include "FixedG1GenerationalCellCycleModel.hpp"
#include "TysonNovakCellCycleModel.hpp"
#include "WntCellCycleModel.hpp"
#include "SimpleWntCellCycleModel.hpp"
#include "StochasticWntCellCycleModel.hpp"
#include "VanLeeuwen2009WntSwatCellCycleModelHypothesisOne.hpp"
#include "VanLeeuwen2009WntSwatCellCycleModelHypothesisTwo.hpp"
#include "Exception.hpp"
#include "StemCellProliferativeType.hpp"
#include "TransitCellProliferativeType.hpp"
#include "DifferentiatedCellProliferativeType.hpp"


template<class T1, class T2>
bool ClassesAreSame()
{
    using namespace boost::mpl;
    using namespace boost;
    typedef typename if_< is_same<T1, T2>, integral_c<unsigned, 1>, integral_c<unsigned, 0> >::type selector_t;
    return  (selector_t()==1);
}

template<class CELL_CYCLE_MODEL>
class CryptCellsGenerator : public CellsGenerator<CELL_CYCLE_MODEL,2>
{
public:

    void Generate(std::vector<CellPtr>& rCells,
                  AbstractMesh<2,2>* pMesh,
                  const std::vector<unsigned> locationIndices,
                  bool randomBirthTimes,
                  double y0 = 0.3,
                  double y1 = 2.0,
                  double y2 = 3.0,
                  double y3 = 4.0,
                  bool initialiseCells = false);
};

template<class CELL_CYCLE_MODEL>
void CryptCellsGenerator<CELL_CYCLE_MODEL>::Generate(
                                      std::vector<CellPtr>& rCells,
                                      AbstractMesh<2,2>* pMesh,
                                      const std::vector<unsigned> locationIndices,
                                      bool randomBirthTimes,
                                      double y0,
                                      double y1,
                                      double y2,
                                      double y3,
                                      bool initialiseCells)
{
    rCells.clear();

    RandomNumberGenerator* p_random_num_gen = RandomNumberGenerator::Instance();

    unsigned mesh_size;
    if (dynamic_cast<TetrahedralMesh<2,2>*>(pMesh))
    {
        mesh_size = pMesh->GetNumNodes();
        unsigned num_cells = locationIndices.empty() ? pMesh->GetNumNodes() : locationIndices.size();
        rCells.reserve(num_cells);
    }
    else if (dynamic_cast<PottsMesh<2>*>(pMesh))
    {
        mesh_size = static_cast<PottsMesh<2>*>(pMesh)->GetNumElements();
        rCells.reserve(mesh_size);
    }
    else
    {
        // Note the double brackets, to stop the macro thinking is has two arguments.
        assert((dynamic_cast<VertexMesh<2,2>*>(pMesh)));
        mesh_size = static_cast<VertexMesh<2,2>*>(pMesh)->GetNumElements();
        rCells.reserve(mesh_size);
    }

    boost::shared_ptr<AbstractCellProperty> p_state(CellPropertyRegistry::Instance()->Get<WildTypeCellMutationState>());

    // Loop over the mesh and populate rCells
    for (unsigned i=0; i<mesh_size; i++)
    {
        // Find the location of this cell
        double y = 0.0;
        if (dynamic_cast<TetrahedralMesh<2,2>*>(pMesh))
        {
            if (locationIndices.empty())
            {
                y = pMesh->GetNode(i)->GetPoint().rGetLocation()[1];

            }
            else if (std::find(locationIndices.begin(), locationIndices.end(), i) != locationIndices.end())
            {
                y = pMesh->GetNode(i)->GetPoint().rGetLocation()[1];
            }
        }
        else if (dynamic_cast<PottsMesh<2>*>(pMesh))
        {
            y = static_cast<PottsMesh<2>*>(pMesh)->GetCentroidOfElement(i)[1];
        }
        else
        {
            // Note the double brackets, to stop the macro thinking is has two arguments.
            assert((dynamic_cast<VertexMesh<2,2>*>(pMesh)));
            y = static_cast<VertexMesh<2,2>*>(pMesh)->GetCentroidOfElement(i)[1];
        }

        // Create a cell-cycle model and set the spatial dimension
        CELL_CYCLE_MODEL* p_cell_cycle_model = new CELL_CYCLE_MODEL;
        p_cell_cycle_model->SetDimension(2);

        double typical_transit_cycle_time = p_cell_cycle_model->GetAverageTransitCellCycleTime();
        double typical_stem_cycle_time = p_cell_cycle_model->GetAverageStemCellCycleTime();

        double birth_time = 0.0;
        if (randomBirthTimes)
        {
            birth_time = -p_random_num_gen->ranf();
        }

        // Set the cell-cycle model's generation if required
        unsigned generation = 4;
        if (y <= y0)
        {
            generation = 0;
        }
        else if (y < y1)
        {
            generation = 1;
        }
        else if (y < y2)
        {
            generation = 2;
        }
        else if (y < y3)
        {
            generation = 3;
        }
        if (dynamic_cast<AbstractSimpleGenerationalCellCycleModel*>(p_cell_cycle_model))
        {
            dynamic_cast<AbstractSimpleGenerationalCellCycleModel*>(p_cell_cycle_model)->SetGeneration(generation);
        }

        // Create a cell
        CellPtr p_cell(new Cell(p_state, p_cell_cycle_model));

        // Set the cell's proliferative type, dependent on its height up the crypt and whether it can terminally differentiate
        if (y <= y0)
        {
            p_cell->SetCellProliferativeType(CellPropertyRegistry::Instance()->Get<StemCellProliferativeType>());
        }
        else
        {
            p_cell->SetCellProliferativeType(CellPropertyRegistry::Instance()->Get<TransitCellProliferativeType>());
            if (y >= y3 && p_cell_cycle_model->CanCellTerminallyDifferentiate())
            {
                p_cell->SetCellProliferativeType(CellPropertyRegistry::Instance()->Get<DifferentiatedCellProliferativeType>());
            }
        }

        // Initialise the cell-cycle model if this is required
        if (initialiseCells)
        {
            p_cell->InitialiseCellCycleModel();
        }

        // Set the cell's birth time
        if (y <= y0)
        {
            birth_time *= typical_stem_cycle_time; // hours
        }
        else
        {
            birth_time *= typical_transit_cycle_time; // hours
        }
        p_cell->SetBirthTime(birth_time);

        if (locationIndices.empty())
        {
            rCells.push_back(p_cell);
        }
        else if (std::find(locationIndices.begin(), locationIndices.end(), i) != locationIndices.end())
        {
            rCells.push_back(p_cell);
        }
    }
}

#endif /* CRYPTCELLSGENERATOR_HPP_ */