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TestCellSortingLiteratePaper.hpp
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TestCellSortingLiteratePaper.hpp
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#ifndef TESTCELLSORTINGLITERATEPAPER_HPP_
#define TESTCELLSORTINGLITERATEPAPER_HPP_
/*
* = Adhesion Example =
*
* On this wiki page we describe in detail the code that is used to run this example from the paper.
*
* The easiest way to visualize these simulations is with Paraview.
*
* [[EmbedYoutube(4YZp_WmBZTI)]]
*
* == Code overview ==
*
* The first thing to do is to include the necessary header files.
*/
#include <cxxtest/TestSuite.h>
// Must be included before other cell_based headers
#include "CellBasedSimulationArchiver.hpp"
#include "AbstractCellBasedWithTimingsTestSuite.hpp"
#include "CellLabel.hpp"
#include "SmartPointers.hpp"
#include "CellsGenerator.hpp"
#include "UniformG1GenerationalCellCycleModel.hpp"
#include "TransitCellProliferativeType.hpp"
#include "DifferentiatedCellProliferativeType.hpp"
#include "HeterotypicBoundaryLengthWriter.hpp"
#include "OffLatticeSimulation.hpp"
#include "VertexBasedCellPopulation.hpp"
#include "HoneycombVertexMeshGenerator.hpp"
#include "NagaiHondaDifferentialAdhesionForce.hpp"
#include "RandomMotionForce.hpp"
#include "SimpleTargetAreaModifier.hpp"
#include "MeshBasedCellPopulationWithGhostNodes.hpp"
#include "HoneycombMeshGenerator.hpp"
#include "DifferentialAdhesionGeneralisedLinearSpringForce.hpp"
#include "RandomMotionForce.hpp"
#include "OnLatticeSimulation.hpp"
#include "CellPopulationAdjacencyMatrixWriter.hpp"
#include "CaBasedCellPopulation.hpp"
#include "ShovingCaBasedDivisionRule.hpp"
#include "RandomCaSwitchingUpdateRule.hpp"
#include "DifferentialAdhesionCaSwitchingUpdateRule.hpp"
#include "PottsBasedCellPopulation.hpp"
#include "PottsMeshGenerator.hpp"
#include "VolumeConstraintPottsUpdateRule.hpp"
#include "SurfaceAreaConstraintPottsUpdateRule.hpp"
#include "AdhesionPottsUpdateRule.hpp"
#include "DifferentialAdhesionPottsUpdateRule.hpp"
#include "CellIdWriter.hpp"
#include "CellMutationStatesWriter.hpp"
#include "PetscSetupAndFinalize.hpp"
/*
* This is where you can set parameters to be used in all the simulations.
*
* The first block (commented out) are the original parameter values.
* The second block are parameters for a much shorter simulation, and are used for continuous testing with Chaste.
*/
//static const double M_TIME_TO_STEADY_STATE = 10; //10
//static const double M_TIME_FOR_SIMULATION = 100; //100
//static const double M_NUM_CELLS_ACROSS = 20; //20 // this ^2 cells
//static const double M_CELL_FLUCTUATION = 1.0;
static const double M_TIME_TO_STEADY_STATE = 10.0; //10
static const double M_TIME_FOR_SIMULATION = 11.0; //100
static const double M_NUM_CELLS_ACROSS = 20; //20 // this ^2 cells
static const double M_CELL_FLUCTUATION = 1.0;
class TestCellSortingLiteratePaper : public AbstractCellBasedWithTimingsTestSuite
{
private:
/*
* This is a helper method to randomly label cells add is used in all simulations.
*/
void RandomlyLabelCells(std::list<CellPtr>& rCells, boost::shared_ptr<AbstractCellProperty> pLabel, double labelledRatio)
{
for (std::list<CellPtr>::iterator cell_iter = rCells.begin();
cell_iter != rCells.end();
++cell_iter)
{
if (RandomNumberGenerator::Instance()->ranf() < labelledRatio)
{
(*cell_iter)->AddCellProperty(pLabel);
}
}
}
public:
/*
* == CA ==
*
* Simulate a population of cells exhibiting cell sorting using the
* Cellular Automaton model.
*/
void TestCaBasedMonolayerCellSorting()
{
// Create a simple 2D PottsMesh
unsigned domain_wide = 2*M_NUM_CELLS_ACROSS;
PottsMeshGenerator<2> generator(domain_wide, 0, 0, domain_wide, 0, 0);
boost::shared_ptr<PottsMesh<2> > p_mesh = generator.GetMesh();
p_mesh->Translate(-(double)domain_wide*0.5 + 0.5,-(double)domain_wide*0.5 + 0.5);
// Specify where cells lie
std::vector<unsigned> location_indices;
for (unsigned i=0; i<M_NUM_CELLS_ACROSS; i++)
{
for (unsigned j=0; j<M_NUM_CELLS_ACROSS; j++)
{
unsigned offset = (domain_wide+1) * (domain_wide-M_NUM_CELLS_ACROSS)/2;
location_indices.push_back(offset + j + i * domain_wide );
}
}
std::vector<CellPtr> cells;
MAKE_PTR(DifferentiatedCellProliferativeType, p_differentiated_type);
CellsGenerator<UniformG1GenerationalCellCycleModel, 2> cells_generator;
cells_generator.GenerateBasicRandom(cells, location_indices.size(), p_differentiated_type);
// Create cell population
CaBasedCellPopulation<2> cell_population(*p_mesh, cells, location_indices);
// Set population to output all data to results files
cell_population.AddCellWriter<CellIdWriter>();
cell_population.AddCellWriter<CellMutationStatesWriter>();
cell_population.AddPopulationWriter<HeterotypicBoundaryLengthWriter>();
cell_population.AddPopulationWriter<CellPopulationAdjacencyMatrixWriter>();
OnLatticeSimulation<2> simulator(cell_population);
simulator.SetOutputDirectory("CellSorting/Ca");
simulator.SetDt(0.01);
simulator.SetSamplingTimestepMultiple(100);
simulator.SetEndTime(M_TIME_TO_STEADY_STATE);
// Add Division Rule
boost::shared_ptr<AbstractCaBasedDivisionRule<2> > p_division_rule(new ShovingCaBasedDivisionRule<2>());
cell_population.SetCaBasedDivisionRule(p_division_rule);
// Add switching Update Rule
MAKE_PTR(DifferentialAdhesionCaSwitchingUpdateRule<2u>, p_switching_update_rule);
p_switching_update_rule->SetLabelledCellLabelledCellAdhesionEnergyParameter(0.1);
p_switching_update_rule->SetLabelledCellCellAdhesionEnergyParameter(0.2);
p_switching_update_rule->SetCellCellAdhesionEnergyParameter(0.1);
p_switching_update_rule->SetCellBoundaryAdhesionEnergyParameter(0.2);
p_switching_update_rule->SetLabelledCellBoundaryAdhesionEnergyParameter(0.4);
p_switching_update_rule->SetTemperature(0.1);
simulator.AddUpdateRule(p_switching_update_rule);
simulator.Solve();
// Now label some cells
boost::shared_ptr<AbstractCellProperty> p_state(CellPropertyRegistry::Instance()->Get<CellLabel>());
RandomlyLabelCells(simulator.rGetCellPopulation().rGetCells(), p_state, 0.5);
// modify parameters
p_switching_update_rule->SetTemperature(0.1*M_CELL_FLUCTUATION);
// Run simulation
simulator.SetEndTime(M_TIME_TO_STEADY_STATE + M_TIME_FOR_SIMULATION);
simulator.Solve();
// Check that the same number of cells
TS_ASSERT_EQUALS(simulator.rGetCellPopulation().GetNumRealCells(), M_NUM_CELLS_ACROSS*M_NUM_CELLS_ACROSS);
// Test no births or deaths
TS_ASSERT_EQUALS(simulator.GetNumBirths(), 0u);
TS_ASSERT_EQUALS(simulator.GetNumDeaths(), 0u);
}
/*
* == CP ==
*
* Simulate a population of cells exhibiting cell sorting using the
* Cellular Potts model.
*/
void TestPottsMonolayerCellSorting()
{
// Create a simple 2D PottsMesh
unsigned element_size = 4;
unsigned domain_size = M_NUM_CELLS_ACROSS * element_size * 3; // Three times the initial domain size
PottsMeshGenerator<2> generator(domain_size, M_NUM_CELLS_ACROSS, element_size, domain_size, M_NUM_CELLS_ACROSS, element_size);
boost::shared_ptr<PottsMesh<2> > p_mesh = generator.GetMesh();
// Create cells
std::vector<CellPtr> cells;
MAKE_PTR(DifferentiatedCellProliferativeType, p_differentiated_type);
CellsGenerator<UniformG1GenerationalCellCycleModel, 2> cells_generator;
cells_generator.GenerateBasicRandom(cells, p_mesh->GetNumElements(), p_differentiated_type);
// Create cell population
PottsBasedCellPopulation<2> cell_population(*p_mesh, cells);
cell_population.AddCellWriter<CellIdWriter>();
cell_population.AddCellWriter<CellMutationStatesWriter>();
cell_population.AddPopulationWriter<HeterotypicBoundaryLengthWriter>();
cell_population.AddPopulationWriter<CellPopulationAdjacencyMatrixWriter>();
// Set the Temperature
cell_population.SetTemperature(0.2); //Default is 0.1
// Set up cell-based simulation and output directory
OnLatticeSimulation<2> simulator(cell_population);
simulator.SetOutputDirectory("CellSorting/Potts");
// Set time step and end time for simulation
simulator.SetDt(0.01);
simulator.SetSamplingTimestepMultiple(100);
simulator.SetEndTime(M_TIME_TO_STEADY_STATE);
// Create update rules and pass to the simulation
MAKE_PTR(VolumeConstraintPottsUpdateRule<2>, p_volume_constraint_update_rule);
p_volume_constraint_update_rule->SetMatureCellTargetVolume(16); // i.e 4x4 cells
p_volume_constraint_update_rule->SetDeformationEnergyParameter(0.1);
simulator.AddUpdateRule(p_volume_constraint_update_rule);
MAKE_PTR(SurfaceAreaConstraintPottsUpdateRule<2>, p_surface_constraint_update_rule);
p_surface_constraint_update_rule->SetMatureCellTargetSurfaceArea(16); // i.e 4x4 cells
p_surface_constraint_update_rule->SetDeformationEnergyParameter(0.01);//0.01
simulator.AddUpdateRule(p_surface_constraint_update_rule);
MAKE_PTR(DifferentialAdhesionPottsUpdateRule<2>, p_differential_adhesion_update_rule);
p_differential_adhesion_update_rule->SetLabelledCellLabelledCellAdhesionEnergyParameter(0.1);
p_differential_adhesion_update_rule->SetLabelledCellCellAdhesionEnergyParameter(0.5); // 1.0
p_differential_adhesion_update_rule->SetCellCellAdhesionEnergyParameter(0.1); //0.1
p_differential_adhesion_update_rule->SetCellBoundaryAdhesionEnergyParameter(0.2); // 1.0
p_differential_adhesion_update_rule->SetLabelledCellBoundaryAdhesionEnergyParameter(1.0); // 2.0
simulator.AddUpdateRule(p_differential_adhesion_update_rule);
// Run simulation
simulator.Solve();
// Now label some cells
boost::shared_ptr<AbstractCellProperty> p_state(CellPropertyRegistry::Instance()->Get<CellLabel>());
RandomlyLabelCells(simulator.rGetCellPopulation().rGetCells(), p_state, 0.5);
// Adjust Parameters
dynamic_cast <PottsBasedCellPopulation<2>*>(&(simulator.rGetCellPopulation()))->SetTemperature(0.2*M_CELL_FLUCTUATION);
// Run simulation
simulator.SetEndTime(M_TIME_TO_STEADY_STATE + M_TIME_FOR_SIMULATION);
simulator.Solve();
// Check that the same number of cells
TS_ASSERT_EQUALS(simulator.rGetCellPopulation().GetNumRealCells(), M_NUM_CELLS_ACROSS*M_NUM_CELLS_ACROSS);
// Test no births or deaths
TS_ASSERT_EQUALS(simulator.GetNumBirths(), 0u);
TS_ASSERT_EQUALS(simulator.GetNumDeaths(), 0u);
}
/*
* == OS ==
*
* Simulate a population of cells exhibiting cell sorting using the
* Overlapping Sphere model.
*/
void TestNodeBasedMonolayerCellSorting()
{
// Create a simple mesh
HoneycombMeshGenerator generator(M_NUM_CELLS_ACROSS, M_NUM_CELLS_ACROSS, 0);
boost::shared_ptr<TetrahedralMesh<2,2> > p_generating_mesh = generator.GetMesh();
//Extended to allow sorting for longer distances
double cut_off_length = 2.5;
// Convert this to a NodesOnlyMesh
NodesOnlyMesh<2> mesh;
mesh.ConstructNodesWithoutMesh(*p_generating_mesh, cut_off_length);
// Set up cells, one for each Node
std::vector<CellPtr> cells;
MAKE_PTR(DifferentiatedCellProliferativeType, p_differentiated_type);
CellsGenerator<UniformG1GenerationalCellCycleModel, 2> cells_generator;
cells_generator.GenerateBasicRandom(cells, mesh.GetNumNodes(), p_differentiated_type);
// Create cell population
NodeBasedCellPopulation<2> cell_population(mesh, cells);
// Set population to output all data to results files
cell_population.AddCellWriter<CellIdWriter>();
cell_population.AddCellWriter<CellMutationStatesWriter>();
cell_population.AddPopulationWriter<HeterotypicBoundaryLengthWriter>();
cell_population.AddPopulationWriter<CellPopulationAdjacencyMatrixWriter>();
// Set up cell-based simulation and output directory
OffLatticeSimulation<2> simulator(cell_population);
simulator.SetOutputDirectory("CellSorting/Node");
// Set time step and end time for simulation
simulator.SetDt(1.0/200.0);
simulator.SetSamplingTimestepMultiple(200);
simulator.SetEndTime(M_TIME_TO_STEADY_STATE);
// Create a force law and pass it to the simulation
MAKE_PTR(DifferentialAdhesionGeneralisedLinearSpringForce<2>, p_differential_adhesion_force);
p_differential_adhesion_force->SetMeinekeSpringStiffness(50.0);
p_differential_adhesion_force->SetHomotypicLabelledSpringConstantMultiplier(1.0);
p_differential_adhesion_force->SetHeterotypicSpringConstantMultiplier(0.1);
p_differential_adhesion_force->SetCutOffLength(cut_off_length);
simulator.AddForce(p_differential_adhesion_force);
// Add some noise to avoid local minimum
MAKE_PTR(RandomMotionForce<2>, p_random_force);
p_random_force->SetMovementParameter(0.05); //0.1 causes dissasociation, 0.001 is not enough
simulator.AddForce(p_random_force);
// Run simulation
simulator.Solve();
// Now label some cells
boost::shared_ptr<AbstractCellProperty> p_state(CellPropertyRegistry::Instance()->Get<CellLabel>());
RandomlyLabelCells(simulator.rGetCellPopulation().rGetCells(), p_state, 0.5);
// Adjust parameters
p_random_force->SetMovementParameter(0.05*M_CELL_FLUCTUATION); //0.1 causes dissasociation
// Run simulation
simulator.SetEndTime(M_TIME_TO_STEADY_STATE + M_TIME_FOR_SIMULATION);
simulator.Solve();
// Check that the same number of cells
TS_ASSERT_EQUALS(simulator.rGetCellPopulation().GetNumRealCells(), M_NUM_CELLS_ACROSS*M_NUM_CELLS_ACROSS);
// Test no births or deaths
TS_ASSERT_EQUALS(simulator.GetNumBirths(), 0u);
TS_ASSERT_EQUALS(simulator.GetNumDeaths(), 0u);
}
/*
* == VT ==
*
* Simulate a population of cells exhibiting cell sorting using the
* Voronoi tesselation model.
*/
void TestMeshBasedWithGhostsMonolayerCellSorting()
{
// Create a simple mesh
unsigned num_ghosts = 20;
HoneycombMeshGenerator generator(M_NUM_CELLS_ACROSS, M_NUM_CELLS_ACROSS, num_ghosts);
boost::shared_ptr<MutableMesh<2,2> > p_mesh = generator.GetMesh();
// Set up cells, one for each non ghost Node
std::vector<unsigned> location_indices = generator.GetCellLocationIndices();
std::vector<CellPtr> cells;
MAKE_PTR(DifferentiatedCellProliferativeType, p_differentiated_type);
CellsGenerator<UniformG1GenerationalCellCycleModel, 2> cells_generator;
cells_generator.GenerateBasicRandom(cells, location_indices.size(), p_differentiated_type);
// Create cell population
MeshBasedCellPopulationWithGhostNodes<2> cell_population(*p_mesh, cells, location_indices);
cell_population.AddPopulationWriter<CellPopulationAdjacencyMatrixWriter>();
// Set population to output all data to results files
cell_population.AddCellWriter<CellIdWriter>();
cell_population.AddCellWriter<CellMutationStatesWriter>();
cell_population.AddPopulationWriter<HeterotypicBoundaryLengthWriter>();
// Set up cell-based simulation and output directory
OffLatticeSimulation<2> simulator(cell_population);
simulator.SetOutputDirectory("CellSorting/Mesh");
// Set time step and end time for simulation
simulator.SetDt(1.0/200.0);
simulator.SetSamplingTimestepMultiple(200);
simulator.SetEndTime(M_TIME_TO_STEADY_STATE);
// Create a force law and pass it to the simulation
MAKE_PTR(DifferentialAdhesionGeneralisedLinearSpringForce<2>, p_differential_adhesion_force);
p_differential_adhesion_force->SetMeinekeSpringStiffness(50.0);
p_differential_adhesion_force->SetHomotypicLabelledSpringConstantMultiplier(1.0);
p_differential_adhesion_force->SetHeterotypicSpringConstantMultiplier(0.1);
simulator.AddForce(p_differential_adhesion_force);
// Add some noise to avoid local minimum
MAKE_PTR(RandomMotionForce<2>, p_random_force);
p_random_force->SetMovementParameter(0.1);
simulator.AddForce(p_random_force);
// Run simulation
simulator.Solve();
// Now label some cells
boost::shared_ptr<AbstractCellProperty> p_state(CellPropertyRegistry::Instance()->Get<CellLabel>());
RandomlyLabelCells(simulator.rGetCellPopulation().rGetCells(), p_state, 0.5);
// Adjust parameters
p_random_force->SetMovementParameter(0.1*M_CELL_FLUCTUATION); //0.1 causes dissasociation
// Run simulation
simulator.SetEndTime(M_TIME_TO_STEADY_STATE + M_TIME_FOR_SIMULATION);
simulator.Solve();
// Check that the same number of cells
TS_ASSERT_EQUALS(simulator.rGetCellPopulation().GetNumRealCells(), M_NUM_CELLS_ACROSS*M_NUM_CELLS_ACROSS);
// Test no births or deaths
TS_ASSERT_EQUALS(simulator.GetNumBirths(), 0u);
TS_ASSERT_EQUALS(simulator.GetNumDeaths(), 0u);
}
/*
* == VM ==
*
* Simulate a population of cells exhibiting cell sorting using the
* Cell Vertex model.
*/
void TestVertexMonolayerCellSorting()
{
// Create a simple 2D MutableVertexMesh
HoneycombVertexMeshGenerator generator(M_NUM_CELLS_ACROSS, M_NUM_CELLS_ACROSS);
boost::shared_ptr<MutableVertexMesh<2,2> > p_mesh = generator.GetMesh();
p_mesh->SetCellRearrangementThreshold(0.1);
// Slows things down but can use a larger timestep and diffusion forces
//p_mesh->SetCheckForInternalIntersections(true);
// Set up cells, one for each VertexElement
std::vector<CellPtr> cells;
boost::shared_ptr<AbstractCellProperty> p_cell_type(CellPropertyRegistry::Instance()->Get<DifferentiatedCellProliferativeType>());
CellsGenerator<UniformG1GenerationalCellCycleModel, 2> cells_generator;
cells_generator.GenerateBasicRandom(cells, p_mesh->GetNumElements(), p_cell_type);
for (unsigned i=0; i<cells.size(); i++)
{
// Set a target area rather than setting a growth modifier. (the modifiers don't work correctly as making very long G1 phases)
cells[i]->GetCellData()->SetItem("target area", 1.0);
}
// Create cell population
VertexBasedCellPopulation<2> cell_population(*p_mesh, cells);
// Set population to output all data to results files
cell_population.AddCellWriter<CellIdWriter>();
cell_population.AddCellWriter<CellMutationStatesWriter>();
cell_population.AddPopulationWriter<HeterotypicBoundaryLengthWriter>();
cell_population.AddPopulationWriter<CellPopulationAdjacencyMatrixWriter>();
// Set up cell-based simulation and output directory
OffLatticeSimulation<2> simulator(cell_population);
simulator.SetOutputDirectory("CellSorting/Vertex");
// Set time step and end time for simulation
simulator.SetDt(1.0/200.0);
simulator.SetSamplingTimestepMultiple(200);
simulator.SetEndTime(M_TIME_TO_STEADY_STATE);
// Set up force law and pass it to the simulation
MAKE_PTR(NagaiHondaDifferentialAdhesionForce<2>, p_force);
p_force->SetNagaiHondaDeformationEnergyParameter(50.0);
p_force->SetNagaiHondaMembraneSurfaceEnergyParameter(1.0);
p_force->SetNagaiHondaCellCellAdhesionEnergyParameter(1.0);
p_force->SetNagaiHondaLabelledCellCellAdhesionEnergyParameter(2.0);
p_force->SetNagaiHondaLabelledCellLabelledCellAdhesionEnergyParameter(1.0);
p_force->SetNagaiHondaCellBoundaryAdhesionEnergyParameter(10.0);
p_force->SetNagaiHondaLabelledCellBoundaryAdhesionEnergyParameter(20.0);
simulator.AddForce(p_force);
// Add some noise to avoid local minimum
MAKE_PTR(RandomMotionForce<2>, p_random_force);
p_random_force->SetMovementParameter(0.1);
simulator.AddForce(p_random_force);
// Run simulation
simulator.Solve();
// Now label some cells
boost::shared_ptr<AbstractCellProperty> p_state(CellPropertyRegistry::Instance()->Get<CellLabel>());
RandomlyLabelCells(simulator.rGetCellPopulation().rGetCells(), p_state, 0.5);
// Adjust parameters
p_random_force->SetMovementParameter(0.1*M_CELL_FLUCTUATION);
// Run simulation
simulator.SetEndTime(M_TIME_TO_STEADY_STATE + M_TIME_FOR_SIMULATION);
simulator.Solve();
// Check that the same number of cells
TS_ASSERT_EQUALS(simulator.rGetCellPopulation().GetNumRealCells(), M_NUM_CELLS_ACROSS*M_NUM_CELLS_ACROSS);
// Test no births or deaths
TS_ASSERT_EQUALS(simulator.GetNumBirths(), 0u);
TS_ASSERT_EQUALS(simulator.GetNumDeaths(), 0u);
}
};
#endif /* TESTCELLSORTINGLITERATEPAPER_HPP_ */