Cell.cpp

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*/
 
#include "Cell.hpp"
 
#include "ApoptoticCellProperty.hpp"
#include "CellAncestor.hpp"
#include "CellId.hpp"
#include "DefaultCellProliferativeType.hpp"
#include "NullSrnModel.hpp"
#include "SmartPointers.hpp"
 
Cell::Cell(boost::shared_ptr<AbstractCellProperty> pMutationState,
           AbstractCellCycleModel* pCellCycleModel,
           AbstractSrnModel* pSrnModel,
           bool archiving,
           CellPropertyCollection cellPropertyCollection)
    : mCanDivide(false),
      mCellPropertyCollection(cellPropertyCollection),
      mpCellCycleModel(pCellCycleModel),
      mpSrnModel(pSrnModel),
      mDeathTime(DBL_MAX), // This has to be initialised for archiving
      mStartOfApoptosisTime(DBL_MAX),
      mApoptosisTime(0.25), // cell takes 15 min to fully undergo apoptosis
      mUndergoingApoptosis(false),
      mIsDead(false),
      mIsLogged(false),
      mHasSrnModel(false)
{
    if (SimulationTime::Instance()->IsStartTimeSetUp()==false)
    {
        EXCEPTION("Cell is setting up a cell-cycle model but SimulationTime has not been set up");
    }
 
    if (pCellCycleModel == nullptr)
    {
        EXCEPTION("Cell-cycle model is null");
    }
 
    mpCellCycleModel->SetCell(CellPtr(this, null_deleter()));
 
    // Create a null SRN model if none given
    if (pSrnModel == nullptr)
    {
        pSrnModel = new NullSrnModel;
        mpSrnModel = pSrnModel;
    }
    else
    {
        mHasSrnModel = true;
    }
 
    mpSrnModel->SetCell(CellPtr(this, null_deleter()));
 
    if (!mCellPropertyCollection.HasPropertyType<CellId>())
    {
        // Set cell identifier this will be called all the time unless the constructor is called through archiving
        MAKE_PTR(CellId, p_cell_id);
        p_cell_id->AssignCellId();
        mCellPropertyCollection.AddProperty(p_cell_id);
    }
 
    if (!pMutationState->IsSubType<AbstractCellMutationState>())
    {
        EXCEPTION("Attempting to create cell with a cell mutation state that is not a subtype of AbstractCellMutationState");
    }
 
    if (!mCellPropertyCollection.HasProperty(pMutationState))
    {
        mCellPropertyCollection.AddProperty(pMutationState);
    }
 
    if (!mCellPropertyCollection.HasPropertyType<CellData>())
    {
        // Add empty cell data
        MAKE_PTR(CellData, p_cell_data);
        mCellPropertyCollection.AddProperty(p_cell_data);
    }
 
    if (!mCellPropertyCollection.HasPropertyType<CellEdgeData>())
    {
        // Add empty cell edge data
        MAKE_PTR(CellEdgeData, p_cell_edge_data);
        mCellPropertyCollection.AddProperty(p_cell_edge_data);
    }
 
    /*
     * If a cell proliferative type was not passed in via the input
     * argument cellPropertyCollection (for example as in the case
     * of a daughter cell being created following division) then add
     * add a 'default' cell proliferative type to the cell property
     * collection. This ensures that the method GetCellProliferativeType()
     * always returns a valid proliferative type.
     */
    if (!mCellPropertyCollection.HasPropertyType<AbstractCellProliferativeType>())
    {
        mCellPropertyCollection.AddProperty(CellPropertyRegistry::Instance()->Get<DefaultCellProliferativeType>());
    }
 
    if (!archiving)
    {
        // Increment cell count for each cell property in mCellPropertyCollection
        for (CellPropertyCollection::Iterator property_iter = mCellPropertyCollection.Begin();
             property_iter != mCellPropertyCollection.End();
             ++property_iter)
        {
            (*property_iter)->IncrementCellCount();
        }
    }
}
 
Cell::~Cell()
{
    if (!mIsDead)
    {
        Kill();
    }
    delete mpCellCycleModel;
    delete mpSrnModel;
}
 
void Cell::SetCellProliferativeType(boost::shared_ptr<AbstractCellProperty> pProliferativeType)
{
    if (!pProliferativeType->IsSubType<AbstractCellProliferativeType>())
    {
        EXCEPTION("Attempting to give cell a cell proliferative type that is not a subtype of AbstractCellProliferativeType");
    }
 
    boost::shared_ptr<AbstractCellProliferativeType> p_old_proliferative_type = GetCellProliferativeType();
 
    p_old_proliferative_type->DecrementCellCount();
    mCellPropertyCollection.RemoveProperty(p_old_proliferative_type);
 
    AddCellProperty(pProliferativeType);
}
 
boost::shared_ptr<AbstractCellProliferativeType> Cell::GetCellProliferativeType()  const
{
    CellPropertyCollection proliferative_type_collection = mCellPropertyCollection.GetPropertiesType<AbstractCellProliferativeType>();
 
    /*
     * Note: In its current form the code requires each cell to have exactly
     * one proliferative type. This is reflected in the assertion below. If a user
     * wishes to include cells with multiple proliferative types, each possible
     * combination must be created as a separate proliferative type class.
     */
    assert(proliferative_type_collection.GetSize() == 1);
 
    return boost::static_pointer_cast<AbstractCellProliferativeType>(proliferative_type_collection.GetProperty());
}
 
void Cell::SetCellCycleModel(AbstractCellCycleModel* pCellCycleModel)
{
    if (mpCellCycleModel != pCellCycleModel)
    {
        delete mpCellCycleModel;
    }
    mpCellCycleModel = pCellCycleModel;
    mpCellCycleModel->SetCell(CellPtr(this, null_deleter()));
}
 
AbstractCellCycleModel* Cell::GetCellCycleModel() const
{
    return mpCellCycleModel;
}
 
void Cell::InitialiseCellCycleModel()
{
    mpCellCycleModel->Initialise();
}
 
void Cell::SetSrnModel(AbstractSrnModel* pSrnModel)
{
    if (mpSrnModel != pSrnModel)
    {
        delete mpSrnModel;
    }
    mpSrnModel = pSrnModel;
    mpSrnModel->SetCell(CellPtr(this, null_deleter()));
    mHasSrnModel = true;
}
 
AbstractSrnModel* Cell::GetSrnModel() const
{
    return mpSrnModel;
}
 
void Cell::InitialiseSrnModel()
{
    mpSrnModel->Initialise();
}
 
double Cell::GetAge() const
{
    return mpCellCycleModel->GetAge();
}
 
double Cell::GetBirthTime() const
{
    return mpCellCycleModel->GetBirthTime();
}
 
void Cell::SetBirthTime(double birthTime)
{
    mpCellCycleModel->SetBirthTime(birthTime);
}
 
void Cell::SetMutationState(boost::shared_ptr<AbstractCellProperty> pMutationState)
{
    if (!pMutationState->IsSubType<AbstractCellMutationState>())
    {
        EXCEPTION("Attempting to give cell a cell mutation state that is not a subtype of AbstractCellMutationState");
    }
 
    boost::shared_ptr<AbstractCellMutationState> p_old_mutation_state = GetMutationState();
    p_old_mutation_state->DecrementCellCount();
    mCellPropertyCollection.RemoveProperty(p_old_mutation_state);
 
    AddCellProperty(pMutationState);
}
 
boost::shared_ptr<AbstractCellMutationState> Cell::GetMutationState() const
{
    CellPropertyCollection mutation_state_collection = mCellPropertyCollection.GetPropertiesType<AbstractCellMutationState>();
 
    /*
     * Note: In its current form the code requires each cell to have exactly
     * one mutation state. This is reflected in the assertion below. If a user
     * wishes to include cells with multiple mutation states, each possible
     * combination must be created as a separate mutation state class.
     */
    assert(mutation_state_collection.GetSize() == 1);
 
    return boost::static_pointer_cast<AbstractCellMutationState>(mutation_state_collection.GetProperty());
}
 
boost::shared_ptr<CellData> Cell::GetCellData() const
{
    CellPropertyCollection cell_data_collection = mCellPropertyCollection.GetPropertiesType<CellData>();
 
    /*
     * Note: In its current form the code requires each cell to have exactly
     * one CellData object. This is reflected in the assertion below.
     */
    assert(cell_data_collection.GetSize() <= 1);
 
    return boost::static_pointer_cast<CellData>(cell_data_collection.GetProperty());
}
 
boost::shared_ptr<CellEdgeData> Cell::GetCellEdgeData() const
{
    CellPropertyCollection collection = mCellPropertyCollection.GetPropertiesType<CellEdgeData>();
 
    /*
     * Note: In its current form the code requires each cell to have exactly
     * one CellEdgeData object. This is reflected in the assertion below.
     */
    assert(collection.GetSize() <= 1);
 
    return boost::static_pointer_cast<CellEdgeData>(collection.GetProperty());
}
 
bool Cell::HasCellVecData() const
{
    return mCellPropertyCollection.HasPropertyType<CellVecData>();
}
 
boost::shared_ptr<CellVecData> Cell::GetCellVecData() const
{
    assert(HasCellVecData());
 
    CellPropertyCollection cell_data_collection = mCellPropertyCollection.GetPropertiesType<CellVecData>();
 
    /*
     * Note: In its current form the code requires each cell to have exactly
     * one CellVecData object. This is reflected in the assertion below.
     */
    assert(cell_data_collection.GetSize() <= 1);
 
    return boost::static_pointer_cast<CellVecData>(cell_data_collection.GetProperty());
}
 
CellPropertyCollection& Cell::rGetCellPropertyCollection()
{
    return mCellPropertyCollection;
}
 
const CellPropertyCollection& Cell::rGetCellPropertyCollection() const
{
    return mCellPropertyCollection;
}
 
void Cell::AddCellProperty(const boost::shared_ptr<AbstractCellProperty>& rProperty)
{
    // Note: if the cell already has the specified property, no action is taken
    if (!mCellPropertyCollection.HasProperty(rProperty))
    {
        mCellPropertyCollection.AddProperty(rProperty);
        rProperty->IncrementCellCount();
    }
}
 
void Cell::SetLogged()
{
    mIsLogged = true;
}
 
bool Cell::IsLogged()
{
    return mIsLogged;
}
 
void Cell::StartApoptosis(bool setDeathTime)
{
    assert(!IsDead());
 
    if (mUndergoingApoptosis)
    {
        EXCEPTION("StartApoptosis() called when already undergoing apoptosis");
    }
    mUndergoingApoptosis = true;
    mStartOfApoptosisTime = SimulationTime::Instance()->GetTime();
    if (setDeathTime)
    {
        mDeathTime = mStartOfApoptosisTime + mApoptosisTime;
    }
    else
    {
        mDeathTime = DBL_MAX;
    }
    AddCellProperty(mCellPropertyCollection.GetCellPropertyRegistry()->Get<ApoptoticCellProperty>());
}
 
bool Cell::HasApoptosisBegun() const
{
    return mUndergoingApoptosis;
}
 
double Cell::GetStartOfApoptosisTime() const
{
    return mStartOfApoptosisTime;
}
 
double Cell::GetApoptosisTime() const
{
    return mApoptosisTime;
}
 
void Cell::SetApoptosisTime(double apoptosisTime)
{
    assert(apoptosisTime > 0.0);
    mApoptosisTime = apoptosisTime;
}
 
double Cell::GetTimeUntilDeath() const
{
    if (!mUndergoingApoptosis || mDeathTime==DBL_MAX)
    {
        EXCEPTION("Shouldn't be checking time until apoptosis as it isn't set");
    }
 
    return mDeathTime - SimulationTime::Instance()->GetTime();
}
 
bool Cell::IsDead()
{
    if (mUndergoingApoptosis && !mIsDead)
    {
        double sloppy_death_time = mDeathTime - DBL_EPSILON * mApoptosisTime;
        if (SimulationTime::Instance()->GetTime() >= sloppy_death_time )
        {
            this->Kill();
        }
    }
    return mIsDead;
}
 
void Cell::Kill()
{
    // Decrement cell count for each cell property in mCellPropertyCollection
    for (CellPropertyCollection::Iterator property_iter = mCellPropertyCollection.Begin();
         property_iter != mCellPropertyCollection.End();
         ++property_iter)
    {
        (*property_iter)->DecrementCellCount();
    }
    mIsDead = true;
}
 
void Cell::SetAncestor(boost::shared_ptr<AbstractCellProperty> pCellAncestor)
{
    if (!pCellAncestor->IsSubType<CellAncestor>())
    {
        EXCEPTION("Attempting to give cell a cell ancestor which is not a CellAncestor");
    }
 
    // You can only set ancestors once
    CellPropertyCollection ancestor_collection = mCellPropertyCollection.GetPropertiesType<CellAncestor>();
    if (ancestor_collection.GetSize() == 0)
    {
        AddCellProperty(pCellAncestor);
    }
    else
    {
        // Overwrite the CellAncestor
        RemoveCellProperty<CellAncestor>();
        AddCellProperty(pCellAncestor);
    }
}
 
unsigned Cell::GetAncestor() const
{
    CellPropertyCollection ancestor_collection = mCellPropertyCollection.GetPropertiesType<CellAncestor>();
 
    assert(ancestor_collection.GetSize() <= 1);
    if (ancestor_collection.GetSize() == 0)
    {
        return UNSIGNED_UNSET;
    }
 
    boost::shared_ptr<CellAncestor> p_ancestor = boost::static_pointer_cast<CellAncestor>(ancestor_collection.GetProperty());
 
    return p_ancestor->GetAncestor();
}
 
unsigned Cell::GetCellId() const
{
    CellPropertyCollection cell_id_collection = mCellPropertyCollection.GetPropertiesType<CellId>();
 
    assert(cell_id_collection.GetSize() == 1);
 
    boost::shared_ptr<CellId> p_cell_id = boost::static_pointer_cast<CellId>(cell_id_collection.GetProperty());
 
    return p_cell_id->GetCellId();
}
 
bool Cell::ReadyToDivide()
{
    assert(!IsDead());
    if (mUndergoingApoptosis || HasCellProperty<ApoptoticCellProperty>())
    {
        return false;
    }
 
    // NOTE - we run the SRN model here first before the CCM
    mpSrnModel->SimulateToCurrentTime();
 
    // This in turn runs any simulations within the CCM through ReadyToDivide();
    mCanDivide = mpCellCycleModel->ReadyToDivide();
 
    return mCanDivide;
}
 
CellPtr Cell::Divide()
{
    // Check we're allowed to divide
    assert(!IsDead());
    assert(mCanDivide);
    mCanDivide = false;
 
    // Reset properties of parent cell
    mpCellCycleModel->ResetForDivision();
    mpSrnModel->ResetForDivision();
 
    // Create copy of cell property collection to modify for daughter cell
    CellPropertyCollection daughter_property_collection = mCellPropertyCollection;
 
    // Remove the CellId from the daughter cell, as a new one will be assigned in the constructor
    daughter_property_collection.RemoveProperty<CellId>();
 
    // Copy all cell data (note we create a new object not just copying the pointer)
    assert(daughter_property_collection.HasPropertyType<CellData>());
 
    // Get the existing copy of the cell data and remove it from the daughter cell
    boost::shared_ptr<CellData> p_cell_data = GetCellData();
    daughter_property_collection.RemoveProperty(p_cell_data);
 
    // Create a new cell data object using the copy constructor and add this to the daughter cell
    MAKE_PTR_ARGS(CellData, p_daughter_cell_data, (*p_cell_data));
    daughter_property_collection.AddProperty(p_daughter_cell_data);
 
    // Get the existing copy of the cell edge data and remove it from the daughter cell
    boost::shared_ptr<CellEdgeData> p_cell_edge_data = GetCellEdgeData();
    daughter_property_collection.RemoveProperty(p_cell_edge_data);
 
    // Create a new cell edge data object using the copy constructor and add this to the daughter cell
    MAKE_PTR_ARGS(CellEdgeData, p_daughter_cell_edge_data, (*p_cell_edge_data));
    daughter_property_collection.AddProperty(p_daughter_cell_edge_data);
 
    // Copy all cell Vec data (note we create a new object not just copying the pointer)
    if (daughter_property_collection.HasPropertyType<CellVecData>())
    {
        // Get the existing copy of the cell data and remove it from the daughter cell
        boost::shared_ptr<CellVecData> p_cell_vec_data = GetCellVecData();
        daughter_property_collection.RemoveProperty(p_cell_vec_data);
 
        // Create a new cell data object using the copy constructor and add this to the daughter cell
        MAKE_PTR_ARGS(CellVecData, p_daughter_cell_vec_data, (*p_cell_vec_data));
        daughter_property_collection.AddProperty(p_daughter_cell_vec_data);
    }
 
    // Create daughter cell with modified cell property collection
    CellPtr p_new_cell(new Cell(GetMutationState(), mpCellCycleModel->CreateCellCycleModel(), mpSrnModel->CreateSrnModel(), false, daughter_property_collection));
 
    // Initialise properties of daughter cell
    p_new_cell->GetCellCycleModel()->InitialiseDaughterCell();
    p_new_cell->GetSrnModel()->InitialiseDaughterCell();
 
    // Set the daughter cell to inherit the apoptosis time of the parent cell
    p_new_cell->SetApoptosisTime(mApoptosisTime);
 
    return p_new_cell;
}
 
bool Cell::HasSrnModel() const
{
    return mHasSrnModel;
}