Owen11CaBasedDivisionRule.cpp

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#include "Owen11CaBasedDivisionRule.hpp"
#include "RandomNumberGenerator.hpp"
#include "BaseUnits.hpp"
#include "CancerCellMutationState.hpp"
#include "QuiescentCancerCellMutationState.hpp"

template<unsigned SPACE_DIM>
Owen11CaBasedDivisionRule<SPACE_DIM>::Owen11CaBasedDivisionRule()
    : AbstractCaBasedDivisionRule<SPACE_DIM>(),
      mpVesselNetwork(),
      mpRegularGrid(),
      mReferenceLengthScale(BaseUnits::Instance()->GetReferenceLengthScale()),
      mCancerCellCarryingCapacity(2)
{
}

template<unsigned SPACE_DIM>
Owen11CaBasedDivisionRule<SPACE_DIM>::~Owen11CaBasedDivisionRule()
{
}

template<unsigned SPACE_DIM>
bool Owen11CaBasedDivisionRule<SPACE_DIM>::IsRoomToDivide(CellPtr pParentCell, CaBasedCellPopulation<SPACE_DIM>& rCellPopulation)
{
    bool is_room = false;

    if(mpVesselNetwork and SPACE_DIM>1)
    {
        if(!mpRegularGrid)
        {
            EXCEPTION("A regular grid is required for determining vessel based lattice occupancy");
        }
    }

    // Get node index corresponding to this cell
    unsigned node_index = rCellPopulation.GetLocationIndexUsingCell(pParentCell);

    // Check if we can divide into self
    unsigned num_cells_at_site = 0;
    if(mpVesselNetwork and SPACE_DIM>1)
    {
        if(mpRegularGrid->IsSegmentAtLatticeSite(node_index, false))
        {
            num_cells_at_site = 1;
        }
    }
    num_cells_at_site += rCellPopulation.GetCellsUsingLocationIndex(node_index).size();
    if(pParentCell->GetMutationState()->IsType<CancerCellMutationState>() ||
            pParentCell->GetMutationState()->IsType<QuiescentCancerCellMutationState>())
    {
        if(num_cells_at_site<mCancerCellCarryingCapacity)
        {
            return true;
        }
    }
    else
    {
        if(num_cells_at_site<1)
        {
            return true;
        }
    }

    // Get the set of neighbouring node indices
    std::set<unsigned> neighbouring_node_indices = static_cast<PottsMesh<SPACE_DIM>*>(&(rCellPopulation.rGetMesh()))->GetMooreNeighbouringNodeIndices(node_index);

    // Iterate through the neighbours to see if there are any available sites
    for (std::set<unsigned>::iterator neighbour_iter = neighbouring_node_indices.begin();
         neighbour_iter != neighbouring_node_indices.end();
         ++neighbour_iter)
    {
        num_cells_at_site = 0;

        if(mpVesselNetwork and SPACE_DIM>1)
        {
            if(mpRegularGrid->IsSegmentAtLatticeSite(*neighbour_iter, false))
            {
                num_cells_at_site = 1;
            }
        }

        num_cells_at_site += rCellPopulation.GetCellsUsingLocationIndex(*neighbour_iter).size();
        if(pParentCell->GetMutationState()->IsType<CancerCellMutationState>() ||
                pParentCell->GetMutationState()->IsType<QuiescentCancerCellMutationState>())
        {
            if(num_cells_at_site<mCancerCellCarryingCapacity)
            {
                return true;
            }
        }
        else
        {
            if(num_cells_at_site<1)
            {
                return true;
            }
        }
    }

    return is_room;
}

template<>
bool Owen11CaBasedDivisionRule<1>::IsRoomToDivide(CellPtr pParentCell, CaBasedCellPopulation<1>& rCellPopulation)
{
    EXCEPTION("This division rule is not supported in 1D");
    return false;
}

template<unsigned SPACE_DIM>
unsigned Owen11CaBasedDivisionRule<SPACE_DIM>::CalculateDaughterNodeIndex(CellPtr pNewCell,
                                                                          CellPtr pParentCell,
                                                                          CaBasedCellPopulation<SPACE_DIM>& rCellPopulation)
{
    if (!IsRoomToDivide(pParentCell,rCellPopulation))
    {
        EXCEPTION("Trying to divide when there is no room to divide, check your division rule");
    }

    if(mpVesselNetwork and SPACE_DIM>1)
    {
        if(!mpRegularGrid)
        {
            EXCEPTION("A regular grid is required for determining vessel based lattice occupancy");
        }
    }

    // Get node index corresponding to the parent cell
    unsigned parent_node_index = rCellPopulation.GetLocationIndexUsingCell(pParentCell);

    // Check if we can divide into own location, cancer cells only
    if(pParentCell->GetMutationState()->IsType<CancerCellMutationState>() ||
            pParentCell->GetMutationState()->IsType<QuiescentCancerCellMutationState>())
    {
        unsigned num_cells_at_site = 0;
        if(mpVesselNetwork and SPACE_DIM>1)
        {
            if(mpRegularGrid->IsSegmentAtLatticeSite(parent_node_index, false))
            {
                num_cells_at_site = 1;
            }
        }
        num_cells_at_site += rCellPopulation.GetCellsUsingLocationIndex(parent_node_index).size();
        if(num_cells_at_site<mCancerCellCarryingCapacity)
        {
            return parent_node_index;
        }
    }

    // Otherwise check neighbours
    PottsMesh<SPACE_DIM>* static_cast_mesh = static_cast<PottsMesh<SPACE_DIM>*>(&(rCellPopulation.rGetMesh()));

    // Get the set of neighbouring node indices
    std::set<unsigned> neighbouring_node_indices = static_cast_mesh->GetMooreNeighbouringNodeIndices(parent_node_index);
    unsigned num_neighbours = neighbouring_node_indices.size();

    // Each node must have at least one neighbour
    assert(!neighbouring_node_indices.empty());

    std::vector<double> neighbouring_node_propensities;
    std::vector<unsigned> neighbouring_node_indices_vector;

    double total_propensity = 0.0;

    // Select neighbour at random
    for (std::set<unsigned>::iterator neighbour_iter = neighbouring_node_indices.begin();
         neighbour_iter != neighbouring_node_indices.end();
         ++neighbour_iter)
    {
        neighbouring_node_indices_vector.push_back(*neighbour_iter);

        // Simplify the Owen model a little, assume division propensity is independent of oxygen
        double propensity_dividing_into_neighbour = 0.0;
        unsigned num_cells_at_site = 0;
        if(mpVesselNetwork and SPACE_DIM>1)
        {
            if(mpRegularGrid->IsSegmentAtLatticeSite(*neighbour_iter, false))
            {
                num_cells_at_site = 1;
            }
        }
        num_cells_at_site += rCellPopulation.GetCellsUsingLocationIndex(*neighbour_iter).size();
        if(pParentCell->GetMutationState()->IsType<CancerCellMutationState>() ||
                pParentCell->GetMutationState()->IsType<QuiescentCancerCellMutationState>())
        {
            if(num_cells_at_site<mCancerCellCarryingCapacity)
            {
                propensity_dividing_into_neighbour = 1.0;
            }
        }
        else
        {
            if(num_cells_at_site<1)
            {
                propensity_dividing_into_neighbour = 1.0;
            }
        }

        neighbouring_node_propensities.push_back(propensity_dividing_into_neighbour);
        total_propensity += propensity_dividing_into_neighbour;
    }
    assert(total_propensity > 0); // If this trips the cell can't divide, so we need to include this in the IsSiteAvailable() method

    for (unsigned i=0; i<num_neighbours; i++)
    {
        neighbouring_node_propensities[i] /= total_propensity;
    }

    // Sample random number to specify which move to make
    RandomNumberGenerator* p_gen = RandomNumberGenerator::Instance();
    double random_number = p_gen->ranf();

    double total_probability = 0.0;
    unsigned daughter_node_index = UNSIGNED_UNSET;

    unsigned counter;
    for (counter=0; counter < num_neighbours; counter++)
    {
        total_probability += neighbouring_node_propensities[counter];
        if (total_probability >= random_number)
        {
            // Divide the parent cell to this neighbour location
            daughter_node_index = neighbouring_node_indices_vector[counter];
            break;
        }
    }
    // This loop should always break as sum(neighbouring_node_propensities) = 1

    assert(daughter_node_index != UNSIGNED_UNSET);
    assert(daughter_node_index < static_cast_mesh->GetNumNodes());

    return daughter_node_index;
}

template<>
unsigned Owen11CaBasedDivisionRule<1>::CalculateDaughterNodeIndex(CellPtr pNewCell,
                                                                          CellPtr pParentCell,
                                                                          CaBasedCellPopulation<1>& rCellPopulation)
{
    EXCEPTION("This division rule is not supported in 1D");
    return 0;
}

template<unsigned SPACE_DIM>
void Owen11CaBasedDivisionRule<SPACE_DIM>::SetVesselNetwork(boost::shared_ptr<VesselNetwork<SPACE_DIM> > pVesselNetwork)
{
    mpVesselNetwork = pVesselNetwork;
}

template<unsigned SPACE_DIM>
void Owen11CaBasedDivisionRule<SPACE_DIM>::SetReferenceLengthScale(units::quantity<unit::length> referenceLengthScale)
{
    mReferenceLengthScale = referenceLengthScale;
}

template<unsigned SPACE_DIM>
void Owen11CaBasedDivisionRule<SPACE_DIM>::SetRegularGrid(boost::shared_ptr<RegularGrid<SPACE_DIM> > pRegularGrid)
{
    mpRegularGrid = pRegularGrid;
}

// Explicit instantiation
template class Owen11CaBasedDivisionRule<2>;
template class Owen11CaBasedDivisionRule<3>;

// Serialization for Boost >= 1.36
#include "SerializationExportWrapperForCpp.hpp"
EXPORT_TEMPLATE_CLASS_SAME_DIMS(Owen11CaBasedDivisionRule)