#include <TysonNovakCellCycleModel.hpp>

Inheritance diagram for TysonNovakCellCycleModel:

Collaboration diagram for TysonNovakCellCycleModel:

Public Member Functions
	TysonNovakCellCycleModel (boost::shared_ptr< AbstractCellCycleModelOdeSolver > pOdeSolver=boost::shared_ptr< AbstractCellCycleModelOdeSolver >())

void	Initialise ()

void	ResetForDivision ()

AbstractCellCycleModel *	CreateCellCycleModel ()

void	InitialiseDaughterCell ()

double	GetAverageTransitCellCycleTime ()

double	GetAverageStemCellCycleTime ()

bool	CanCellTerminallyDifferentiate ()

virtual void	OutputCellCycleModelParameters (out_stream &rParamsFile)

Public Member Functions inherited from AbstractOdeBasedCellCycleModel
	AbstractOdeBasedCellCycleModel (double lastTime=SimulationTime::Instance() ->GetTime(), boost::shared_ptr< AbstractCellCycleModelOdeSolver > pOdeSolver=boost::shared_ptr< AbstractCellCycleModelOdeSolver >())

virtual	~AbstractOdeBasedCellCycleModel ()

double	GetOdeStopTime ()

void	SetBirthTime (double birthTime)

virtual bool	ReadyToDivide ()

Public Member Functions inherited from AbstractCellCycleModel
	AbstractCellCycleModel ()

virtual	~AbstractCellCycleModel ()

void	SetCell (CellPtr pCell)

CellPtr	GetCell ()

void	SetDimension (unsigned dimension)

unsigned	GetDimension () const

double	GetBirthTime () const

double	GetAge ()

void	OutputCellCycleModelInfo (out_stream &rParamsFile)

Public Member Functions inherited from Identifiable
virtual	~Identifiable ()

std::string	GetIdentifier () const

Public Member Functions inherited from CellCycleModelOdeHandler
	CellCycleModelOdeHandler (double lastTime=SimulationTime::Instance() ->GetTime(), boost::shared_ptr< AbstractCellCycleModelOdeSolver > pOdeSolver=boost::shared_ptr< AbstractCellCycleModelOdeSolver >())

virtual	~CellCycleModelOdeHandler ()

AbstractOdeSystem *	GetOdeSystem () const

void	SetOdeSystem (AbstractOdeSystem *pOdeSystem)

const boost::shared_ptr < AbstractCellCycleModelOdeSolver >	GetOdeSolver () const

void	SetLastTime (double lastTime)

double	GetDt ()

void	SetDt (double timeStep)

void	SetStateVariables (const std::vector< double > &rStateVariables)

std::vector< double >	GetProteinConcentrations () const

void	SetProteinConcentrationsForTestsOnly (double lastTime, std::vector< double > proteinConcentrations)

Protected Member Functions
	TysonNovakCellCycleModel (const TysonNovakCellCycleModel &rModel)

Protected Member Functions inherited from AbstractOdeBasedCellCycleModel
	AbstractOdeBasedCellCycleModel (const AbstractOdeBasedCellCycleModel &rModel)

Protected Member Functions inherited from AbstractCellCycleModel
	AbstractCellCycleModel (const AbstractCellCycleModel &rModel)

Protected Member Functions inherited from CellCycleModelOdeHandler
	CellCycleModelOdeHandler (const CellCycleModelOdeHandler &rHandler)

bool	SolveOdeToTime (double currentTime)

virtual void	AdjustOdeParameters (double currentTime)

Private Member Functions
template<class Archive >
void	serialize (Archive &archive, const unsigned int version)

Friends
class	TestOdeBasedCellCycleModels

class	boost::serialization::access

Additional Inherited Members
Protected Attributes inherited from AbstractOdeBasedCellCycleModel
double	mDivideTime

Protected Attributes inherited from AbstractCellCycleModel
CellPtr	mpCell

double	mBirthTime

bool	mReadyToDivide

unsigned	mDimension

Protected Attributes inherited from CellCycleModelOdeHandler
double	mDt

AbstractOdeSystem *	mpOdeSystem

boost::shared_ptr < AbstractCellCycleModelOdeSolver >	mpOdeSolver

double	mLastTime

bool	mFinishedRunningOdes

Detailed Description

Tyson-Novak 2001 cell-cycle model, taken from the version at doi:10.1006/jtbi.2001.2293

Time taken to progress through the cycle is deterministic and given by an ODE system independent of external factors.

Definition at line 51 of file TysonNovakCellCycleModel.hpp.

Constructor & Destructor Documentation

TysonNovakCellCycleModel::TysonNovakCellCycleModel ( const TysonNovakCellCycleModel & rModel )

protected

Protected copy-constructor for use by CreateCellCycleModel. The only way for external code to create a copy of a cell cycle model is by calling that method, to ensure that a model of the correct subclass is created. This copy-constructor helps subclasses to ensure that all member variables are correctly copied when this happens.

This method is called by child classes to set member variables for a daughter cell upon cell division. Note that the parent cell cycle model will have had ResetForDivision() called just before CreateCellCycleModel() is called, so performing an exact copy of the parent is suitable behaviour. Any daughter-cell-specific initialisation can be done in InitialiseDaughterCell().

Parameters

rModel the cell cycle model to copy.

Definition at line 61 of file TysonNovakCellCycleModel.cpp.

References CellCycleModelOdeHandler::GetOdeSystem(), AbstractParameterisedSystem< VECTOR >::rGetStateVariables(), CellCycleModelOdeHandler::SetOdeSystem(), and CellCycleModelOdeHandler::SetStateVariables().

Referenced by CreateCellCycleModel().

TysonNovakCellCycleModel::TysonNovakCellCycleModel ( boost::shared_ptr< AbstractCellCycleModelOdeSolver > pOdeSolver = boost::shared_ptr<AbstractCellCycleModelOdeSolver>() )

Default constructor.

Parameters

pOdeSolver An optional pointer to a cell-cycle model ODE solver object (allows the use of different ODE solvers)

Definition at line 40 of file TysonNovakCellCycleModel.cpp.

References CellCycleModelOdeSolver< CELL_CYCLE_MODEL, ODE_SOLVER >::Instance(), CellCycleModelOdeHandler::mpOdeSolver, and CellCycleModelOdeHandler::SetDt().

Member Function Documentation

bool TysonNovakCellCycleModel::CanCellTerminallyDifferentiate ( )

virtual

Overridden CanCellTerminallyDifferentiate() method.

Returns: whether cell can terminally differentiate

Reimplemented from AbstractCellCycleModel.

Definition at line 151 of file TysonNovakCellCycleModel.cpp.

AbstractCellCycleModel * TysonNovakCellCycleModel::CreateCellCycleModel ( )

virtual

Overridden builder method to create new copies of this cell-cycle model.

Returns: new cell-cycle model

Implements AbstractCellCycleModel.

Definition at line 136 of file TysonNovakCellCycleModel.cpp.

References TysonNovakCellCycleModel().

double TysonNovakCellCycleModel::GetAverageStemCellCycleTime ( )

virtual

Overridden GetAverageStemCellCycleTime() method.

Returns: time

Implements AbstractCellCycleModel.

Definition at line 146 of file TysonNovakCellCycleModel.cpp.

double TysonNovakCellCycleModel::GetAverageTransitCellCycleTime ( )

virtual

Overridden GetAverageTransitCellCycleTime() method.

Returns: time

Implements AbstractCellCycleModel.

Definition at line 141 of file TysonNovakCellCycleModel.cpp.

void TysonNovakCellCycleModel::Initialise ( void )

virtual

Initialise the cell-cycle model at the start of a simulation.

This method will be called precisely once per cell set up in the initial cell population. It is not called on cell division; use ResetForDivision(), CreateCellCycleModel() and InitialiseDaughterCell() for that.

By the time this is called, a CellPopulation will have been set up, so the model can know where its cell is located in space. If relevant to the simulation, any singletons will also have been initialised.

Reimplemented from AbstractCellCycleModel.

Definition at line 83 of file TysonNovakCellCycleModel.cpp.

References AbstractParameterisedSystem< VECTOR >::GetInitialConditions(), AbstractCellCycleModel::Initialise(), CellCycleModelOdeHandler::mpOdeSystem, and AbstractParameterisedSystem< VECTOR >::SetStateVariables().

void TysonNovakCellCycleModel::InitialiseDaughterCell ( )

virtual

If the daughter cell type is stem, change it to transit.

Reimplemented from AbstractCellCycleModel.

Definition at line 117 of file TysonNovakCellCycleModel.cpp.

References AbstractCellCycleModel::mpCell.

void TysonNovakCellCycleModel::OutputCellCycleModelParameters ( out_stream & rParamsFile )

virtual

Overridden OutputCellCycleModelParameters() method.

Parameters

rParamsFile the file stream to which the parameters are output

Reimplemented from AbstractOdeBasedCellCycleModel.

Definition at line 156 of file TysonNovakCellCycleModel.cpp.

References AbstractOdeBasedCellCycleModel::OutputCellCycleModelParameters().

void TysonNovakCellCycleModel::ResetForDivision ( )

virtual

Reset cell-cycle model by calling AbstractOdeBasedCellCycleModelWithStoppingEvent::ResetForDivision() and setting initial conditions for protein concentrations.

This model needs the protein concentrations and phase resetting to G0/G1.

In theory, the solution to the Tyson-Novak equations should exhibit stable oscillations, and we only need to halve the mass of the cell each period.

However, the backward Euler solver used to solve the equations currently returns a solution that diverges after long times, so we must reset the initial conditions each period.

When running with CVODE however we can use the halving the mass of the cell method.

Reimplemented from AbstractOdeBasedCellCycleModel.

Definition at line 92 of file TysonNovakCellCycleModel.cpp.

References AbstractParameterisedSystem< VECTOR >::GetInitialConditions(), CellCycleModelOdeHandler::mpOdeSystem, AbstractOdeBasedCellCycleModel::ResetForDivision(), AbstractParameterisedSystem< VECTOR >::rGetStateVariables(), and AbstractParameterisedSystem< VECTOR >::SetStateVariables().

template<class Archive >