Creating And Using A New Cell Killer

This tutorial is automatically generated from TestCreatingAndUsingANewCellKillerTutorial.hpp at revision 409e06cb314b. Note that the code is given in full at the bottom of the page.

An example showing how to create a new cell killer and use it in a cell-based simulation

Introduction

In the crypt tutorial, we used an existing cell killer class to define how cells were sloughed off the top of a crypt. In this tutorial we show how to create a new cell killer class, and how this can be used in a cell-based simulation.

1. Including header files

As in previous cell-based Chaste tutorials, we begin by including the necessary header file and archiving headers.

#include <cxxtest/TestSuite.h>
#include "CheckpointArchiveTypes.hpp"
#include "AbstractCellBasedTestSuite.hpp"

#include <boost/archive/text_oarchive.hpp>
#include <boost/archive/text_iarchive.hpp>

The next header defines a base class for cell killers, from which the new cell killer class will inherit.

#include "AbstractCellKiller.hpp"

The next header defines a writer which outputs information on cells killed to the file removals.dat .

#include "CellRemovalLocationsWriter.hpp"

The remaining header files define classes that will be used in the cell-based simulation test. We have encountered each of these header files in previous cell-based Chaste tutorials.

#include "HoneycombMeshGenerator.hpp"
#include "FixedG1GenerationalCellCycleModel.hpp"
#include "GeneralisedLinearSpringForce.hpp"
#include "OffLatticeSimulation.hpp"
#include "CellsGenerator.hpp"
#include "SmartPointers.hpp"
//This test is always run sequentially (never in parallel)
#include "FakePetscSetup.hpp"

Defining the cell killer class

As an example, let us consider a cell killer that labels any cells in a two-dimensional cell population which lie outside the elliptical domain given in Cartesian coordinates by the equation $\left(\frac{x}{20}\right)^2 + \left(\frac{y}{10}\right)^2 < 1$. To implement this we define a new cell killer class, MyCellKiller, which inherits from AbstractCellKiller and overrides the CheckAndLabelCellsForApoptosisOrDeath() method.

Note that usually this code would be separated out into a separate declaration in a .hpp file and definition in a .cpp file.

class MyCellKiller : public AbstractCellKiller<2>
{
private:

    friend class boost::serialization::access;
    template<class Archive>
    void serialize(Archive & archive, const unsigned int version)
    {
        archive & boost::serialization::base_object<AbstractCellKiller<2> >(*this);
    }

The first public method is a default constructor, which just calls the base constructor.

public:

    MyCellKiller(AbstractCellPopulation<2>* pCellPopulation)
        : AbstractCellKiller<2>(pCellPopulation)
    {}

The second public method overrides CheckAndLabelCellsForApoptosisOrDeath(). This method iterates over all cells in the population, and calls KillCell() on any cell whose centre is located outside the ellipse $(\frac{x}{20})^2 + (\frac{y}{10})^2 < 1$.

    void CheckAndLabelCellsForApoptosisOrDeath()
    {
        for (AbstractCellPopulation<2>::Iterator cell_iter = this->mpCellPopulation->Begin();
            cell_iter != this->mpCellPopulation->End();
            ++cell_iter)
        {
            c_vector<double, 2> location;
            location = this->mpCellPopulation->GetLocationOfCellCentre(*cell_iter);

            if (pow(location[0]/20, 2) + pow(location[1]/10, 2) > 1.0)
            {

This line marks the cell as killed and stores removal information for use by by the cell writers if the writer CellRemovalLocationsWriter is included.

                this->mpCellPopulation->KillCell(*cell_iter, "MyCellKiller");
            }
        }
    }

The final public method overrides OutputCellKillerParameters(). This method outputs any member variables to a specified results file rParamsFile. In our case, there are no parameters, so we simply call the method on the base class. Nonetheless, we still need to override the method, since it is pure virtual in the base class.

    void OutputCellKillerParameters(out_stream& rParamsFile)
    {
        AbstractCellKiller<2>::OutputCellKillerParameters(rParamsFile);
    }
};

As mentioned in Creating And Using A New Cell Cycle Model, we need to include the next block of code to be able to archive the cell killer object in a cell-based simulation, and to obtain a unique identifier for our new cell killer for writing results to file.

#include "SerializationExportWrapper.hpp"
CHASTE_CLASS_EXPORT(MyCellKiller)
#include "SerializationExportWrapperForCpp.hpp"
CHASTE_CLASS_EXPORT(MyCellKiller)

We only need to include the next block of code if we wish to be able to archive (save or load) the cell killer object in a cell-based simulation. We must define save_construct_data and load_construct_data methods, which archive the cell killer constructor input argument(s) (in this case, a CellPopulation).

namespace boost
{
    namespace serialization
    {
        template<class Archive>
        inline void save_construct_data(
            Archive & ar, const MyCellKiller * t, const unsigned int file_version)
        {
            const AbstractCellPopulation<2>* const p_cell_population = t->GetCellPopulation();
            ar << p_cell_population;
        }

        template<class Archive>
        inline void load_construct_data(
            Archive & ar, MyCellKiller * t, const unsigned int file_version)
        {
            AbstractCellPopulation<2>* p_cell_population;
            ar >> p_cell_population;

            // Invoke inplace constructor to initialise instance
            ::new(t)MyCellKiller(p_cell_population);
        }
    }
}

This completes the code for MyCellKiller. Note that usually this code would be separated out into a separate declaration in a .hpp file and definition in a .cpp file.

The Tests

We now define the test class, which inherits from AbstractCellBasedTestSuite.

class TestCreatingAndUsingANewCellKillerTutorial : public AbstractCellBasedTestSuite
{
public:

Testing the cell killer

We begin by testing that our new cell-cycle model is implemented correctly.

    void TestMyCellKiller()
    {

We use the honeycomb mesh generator to create a honeycomb mesh.

        HoneycombMeshGenerator generator(20, 20, 0);
        boost::shared_ptr<MutableMesh<2,2> > p_mesh = generator.GetMesh();

We then construct and initialise some cells, each with a FixedG1GenerationalCellCycleModel, using the helper class CellsGenerator.

        std::vector<CellPtr> cells;
        CellsGenerator<FixedG1GenerationalCellCycleModel, 2> cells_generator;
        cells_generator.GenerateBasic(cells, p_mesh->GetNumNodes());

Now that we have defined the mesh and cells, we can define the cell population. The constructor takes in the mesh and the cells vector.

        MeshBasedCellPopulation<2> cell_population(*p_mesh, cells);

We now use the cell population to construct a cell killer object.

        MyCellKiller my_cell_killer(&cell_population);

To store information about the lovations and times of the killed cells use the CellRemovalLocationsWriter

        cell_population.AddCellPopulationEventWriter<CellRemovalLocationsWriter>();

To test that we have implemented the cell killer correctly, we call the overridden method CheckAndLabelCellsForApoptosisOrDeath…

        my_cell_killer.CheckAndLabelCellsForApoptosisOrDeath();

… and check that any cell whose centre is located outside the ellipse $(\frac{x}{20})^2 + (\frac{y}{10})^2 < 1$ has indeed been labelled as dead.

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

            if (pow(x/20, 2) + pow(y/10, 2) > 1.0)
            {
                TS_ASSERT_EQUALS(cell_iter->IsDead(), true);
            }
            else
            {
                TS_ASSERT_EQUALS(cell_iter->IsDead(), false);
            }
        }

As an extra test, we now remove any dead cells and check that all remaining cells are indeed located within the ellipse.

        cell_population.RemoveDeadCells();

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

            TS_ASSERT_LESS_THAN_EQUALS(pow(x/20, 2) + pow(y/10, 2) > 1.0, 1.0);
        }

The last chunk of code provides an archiving test for the cell killer. We create an output archive, save the existing cell killer object via a pointer, then create an input archive and load the cell killer. If the cell killer had any member variables, then we would test that these were correctly initialised when the cell killer is loaded.

        OutputFileHandler handler("archive", false);
        std::string archive_filename = handler.GetOutputDirectoryFullPath() + "my_cell_killer.arch";

        {
            AbstractCellKiller<2>* const p_cell_killer = new MyCellKiller(NULL);

            std::ofstream ofs(archive_filename.c_str());
            boost::archive::text_oarchive output_arch(ofs);

            output_arch << p_cell_killer;
            delete p_cell_killer;
        }

        {
            std::ifstream ifs(archive_filename.c_str(), std::ios::binary);
            boost::archive::text_iarchive input_arch(ifs);

            AbstractCellKiller<2>* p_cell_killer;

            input_arch >> p_cell_killer;
            delete p_cell_killer;
        }
    }

Using the cell killer in a cell-based simulation

We now provide a test demonstrating how MyCellKiller can be used in a cell-based simulation.

    void TestOffLatticeSimulationWithMyCellKiller()
    {

We proceed as before, creating a mesh-based cell population.

        HoneycombMeshGenerator generator(20, 20, 0);
        boost::shared_ptr<MutableMesh<2,2> > p_mesh = generator.GetMesh();

        std::vector<CellPtr> cells;
        CellsGenerator<FixedG1GenerationalCellCycleModel, 2> cells_generator;
        cells_generator.GenerateBasic(cells, p_mesh->GetNumNodes());

        MeshBasedCellPopulation<2> cell_population(*p_mesh, cells);

We now use the cell population to construct a cell killer object. This object must be added to the cell-based simulation as a boost::shared_ptr, so we make use of the macro MAKE_PTR_ARG (defined in the header SmartPointers.hpp).

        MAKE_PTR_ARGS(MyCellKiller, p_killer, (&cell_population));

We then pass in the cell population into an OffLatticeSimulation, and set the output directory and end time.

        OffLatticeSimulation<2> simulator(cell_population);
        simulator.SetOutputDirectory("TestOffLatticeSimulationWithMyCellKiller");
        simulator.SetEndTime(1.0);

We create a force law and pass it to the OffLatticeSimulation.

        MAKE_PTR(GeneralisedLinearSpringForce<2>, p_linear_force);
        p_linear_force->SetCutOffLength(3);
        simulator.AddForce(p_linear_force);

We now pass the cell killer into the cell-based simulation.

        simulator.AddCellKiller(p_killer);

To run the simulation, we call Solve().

        simulator.Solve();
    }
};

When you visualize the results with

java Visualize2dCentreCells $CHASTE_TEST_OUTPUT/TestOffLatticeSimulationWithMyCellKiller/results_from_time_0

you should see that once cells move out of the ellipse they are removed from the simulation.

Full code

#include <cxxtest/TestSuite.h>
#include "CheckpointArchiveTypes.hpp"
#include "AbstractCellBasedTestSuite.hpp"

#include <boost/archive/text_oarchive.hpp>
#include <boost/archive/text_iarchive.hpp>

#include "AbstractCellKiller.hpp"

#include "CellRemovalLocationsWriter.hpp"

#include "HoneycombMeshGenerator.hpp"
#include "FixedG1GenerationalCellCycleModel.hpp"
#include "GeneralisedLinearSpringForce.hpp"
#include "OffLatticeSimulation.hpp"
#include "CellsGenerator.hpp"
#include "SmartPointers.hpp"
//This test is always run sequentially (never in parallel)
#include "FakePetscSetup.hpp"

class MyCellKiller : public AbstractCellKiller<2>
{
private:

    friend class boost::serialization::access;
    template<class Archive>
    void serialize(Archive & archive, const unsigned int version)
    {
        archive & boost::serialization::base_object<AbstractCellKiller<2> >(*this);
    }

public:

    MyCellKiller(AbstractCellPopulation<2>* pCellPopulation)
        : AbstractCellKiller<2>(pCellPopulation)
    {}

    void CheckAndLabelCellsForApoptosisOrDeath()
    {
        for (AbstractCellPopulation<2>::Iterator cell_iter = this->mpCellPopulation->Begin();
            cell_iter != this->mpCellPopulation->End();
            ++cell_iter)
        {
            c_vector<double, 2> location;
            location = this->mpCellPopulation->GetLocationOfCellCentre(*cell_iter);

            if (pow(location[0]/20, 2) + pow(location[1]/10, 2) > 1.0)
            {
                this->mpCellPopulation->KillCell(*cell_iter, "MyCellKiller");
            }
        }
    }

    void OutputCellKillerParameters(out_stream& rParamsFile)
    {
        AbstractCellKiller<2>::OutputCellKillerParameters(rParamsFile);
    }
};

#include "SerializationExportWrapper.hpp"
CHASTE_CLASS_EXPORT(MyCellKiller)
#include "SerializationExportWrapperForCpp.hpp"
CHASTE_CLASS_EXPORT(MyCellKiller)

namespace boost
{
    namespace serialization
    {
        template<class Archive>
        inline void save_construct_data(
            Archive & ar, const MyCellKiller * t, const unsigned int file_version)
        {
            const AbstractCellPopulation<2>* const p_cell_population = t->GetCellPopulation();
            ar << p_cell_population;
        }

        template<class Archive>
        inline void load_construct_data(
            Archive & ar, MyCellKiller * t, const unsigned int file_version)
        {
            AbstractCellPopulation<2>* p_cell_population;
            ar >> p_cell_population;

            // Invoke inplace constructor to initialise instance
            ::new(t)MyCellKiller(p_cell_population);
        }
    }
}

class TestCreatingAndUsingANewCellKillerTutorial : public AbstractCellBasedTestSuite
{
public:

    void TestMyCellKiller()
    {
        HoneycombMeshGenerator generator(20, 20, 0);
        boost::shared_ptr<MutableMesh<2,2> > p_mesh = generator.GetMesh();

        std::vector<CellPtr> cells;
        CellsGenerator<FixedG1GenerationalCellCycleModel, 2> cells_generator;
        cells_generator.GenerateBasic(cells, p_mesh->GetNumNodes());

        MeshBasedCellPopulation<2> cell_population(*p_mesh, cells);

        MyCellKiller my_cell_killer(&cell_population);

        cell_population.AddCellPopulationEventWriter<CellRemovalLocationsWriter>();

        my_cell_killer.CheckAndLabelCellsForApoptosisOrDeath();

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

            if (pow(x/20, 2) + pow(y/10, 2) > 1.0)
            {
                TS_ASSERT_EQUALS(cell_iter->IsDead(), true);
            }
            else
            {
                TS_ASSERT_EQUALS(cell_iter->IsDead(), false);
            }
        }

        cell_population.RemoveDeadCells();

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

            TS_ASSERT_LESS_THAN_EQUALS(pow(x/20, 2) + pow(y/10, 2) > 1.0, 1.0);
        }

        OutputFileHandler handler("archive", false);
        std::string archive_filename = handler.GetOutputDirectoryFullPath() + "my_cell_killer.arch";

        {
            AbstractCellKiller<2>* const p_cell_killer = new MyCellKiller(NULL);

            std::ofstream ofs(archive_filename.c_str());
            boost::archive::text_oarchive output_arch(ofs);

            output_arch << p_cell_killer;
            delete p_cell_killer;
        }

        {
            std::ifstream ifs(archive_filename.c_str(), std::ios::binary);
            boost::archive::text_iarchive input_arch(ifs);

            AbstractCellKiller<2>* p_cell_killer;

            input_arch >> p_cell_killer;
            delete p_cell_killer;
        }
    }

    void TestOffLatticeSimulationWithMyCellKiller()
    {
        HoneycombMeshGenerator generator(20, 20, 0);
        boost::shared_ptr<MutableMesh<2,2> > p_mesh = generator.GetMesh();

        std::vector<CellPtr> cells;
        CellsGenerator<FixedG1GenerationalCellCycleModel, 2> cells_generator;
        cells_generator.GenerateBasic(cells, p_mesh->GetNumNodes());

        MeshBasedCellPopulation<2> cell_population(*p_mesh, cells);

        MAKE_PTR_ARGS(MyCellKiller, p_killer, (&cell_population));

        OffLatticeSimulation<2> simulator(cell_population);
        simulator.SetOutputDirectory("TestOffLatticeSimulationWithMyCellKiller");
        simulator.SetEndTime(1.0);

        MAKE_PTR(GeneralisedLinearSpringForce<2>, p_linear_force);
        p_linear_force->SetCutOffLength(3);
        simulator.AddForce(p_linear_force);

        simulator.AddCellKiller(p_killer);

        simulator.Solve();
    }
};

Creating And Using A New Cell Cycle Model

Creating And Using A New Cell Mutation State

Creating And Using A New Cell Killer

An example showing how to create a new cell killer and use it in a cell-based simulation#

Introduction#

1. Including header files#

Defining the cell killer class#

The Tests#

Testing the cell killer#

Using the cell killer in a cell-based simulation#

Full code#