Alarcon2004OxygenBasedCellCycleOdeSystem::Alarcon2004OxygenBasedCellCycleOdeSystem(double oxygenConcentration,
bool isLabelled,
std::vector<double> stateVariables)
: AbstractOdeSystem(6),
mOxygenConcentration(oxygenConcentration),
mIsLabelled(isLabelled)
{
mpSystemInfo.reset(new CellwiseOdeSystemInformation<Alarcon2004OxygenBasedCellCycleOdeSystem>);
/**
* State variables
*
* 0. x = Cdh1-APC complexes
* 1. y = cyclin-CDK
* 2. z = p27
* 3. m = mass
* 4. u = RBNP
* 5. oxygenConcentration
*/
Init(); // set up parameters
// Parameter values are taken from the Alarcon et al. (2004) paper
if (mIsLabelled) // labelled "cancer" cells
{
ma1 = 0.04;
mc1 = 0.007;
mxThreshold = 0.004;
myThreshold = 0.05;
}
else // normal cells
{
ma1 = 0.05;
mc1 = 0.1;
mxThreshold = 0.004;
myThreshold = 0.2;
}
// Cell-specific initial conditions
SetDefaultInitialCondition(3, 0.5*mMstar);
SetDefaultInitialCondition(5, oxygenConcentration);
if (stateVariables != std::vector<double>())
{
SetStateVariables(stateVariables);
}
}
Mirams2010WntOdeSystem::Mirams2010WntOdeSystem(double wntLevel,
boost::shared_ptr<AbstractCellMutationState> pMutationState,
std::vector<double> stateVariables)
: AbstractOdeSystem(3),
mpMutationState(pMutationState),
mWntLevel(wntLevel)
{
mpSystemInfo.reset(new CellwiseOdeSystemInformation<Mirams2010WntOdeSystem>);
/**
* State variables.
*
* 0. b1 = Beta-Catenin (1st allele's copy)
* 1. b2 = Beta-Catenin (2nd allele's copy)
* 2. wntLevel
*/
Init(); // set up parameter values
// Set up rough guesses for the initial steady states in this Wnt conc.
double b1 = 0;
double b2 = 0;
b1 = (mA/2.0) / (((wntLevel + mB)/(mC*wntLevel + mD)) + mF);
if (!mpMutationState)
{
// No mutations specified
}
else if (mpMutationState->IsType<BetaCateninOneHitCellMutationState>())
{
b2 = (mA/2.0)/mF;
}
else
{
b2 = (mA/2.0) / (((wntLevel + mB)/(mC*wntLevel + mD)) + mF);
}
SetDefaultInitialCondition(0, b1);
SetDefaultInitialCondition(1, b2);
SetDefaultInitialCondition(2, wntLevel);
if (stateVariables != std::vector<double>())
{
SetStateVariables(stateVariables);
}
}
WntCellCycleOdeSystem::WntCellCycleOdeSystem(double wntLevel,
boost::shared_ptr<AbstractCellMutationState> pMutationState,
std::vector<double> stateVariables)
: AbstractOdeSystem(9),
mpMutationState(pMutationState),
mWntLevel(wntLevel)
{
mpSystemInfo.reset(new CellwiseOdeSystemInformation<WntCellCycleOdeSystem>);
/**
* State variables.
*
* 0. r = pRb
* 1. e = E2F1 (This is the S-phase indicator)
* 2. i = CycD (inactive)
* 3. j = CycD (active)
* 4. p = pRb-p
* 5. c = APC (Active)
* 6. b1 = Beta-Catenin (1st allele's copy)
* 7. b2 = Beta-Catenin (2nd allele's copy)
* 8. wntLevel
*/
Init(); // set up parameter values
// Set up a Wnt signalling pathway in a steady state
double destruction_level = ma5d/(ma4d*wntLevel+ma5d);
double beta_cat_level_1 = -1.0;
double beta_cat_level_2 = -1.0;
if (!mpMutationState)
{
// No mutations specified
}
else if (mpMutationState && mpMutationState->IsType<ApcOneHitCellMutationState>())
{
// APC +/- : only half are active
beta_cat_level_1 = 0.5*ma2d/(ma2d+0.5*ma3d*destruction_level);
beta_cat_level_2 = 0.5*ma2d/(ma2d+0.5*ma3d*destruction_level);
}
else if (mpMutationState && mpMutationState->IsType<ApcTwoHitCellMutationState>())
{
// APC -/-
destruction_level = 0.0; // no active destruction complex
beta_cat_level_1 = 0.5; // fully active beta-catenin
beta_cat_level_2 = 0.5; // fully active beta-catenin
}
else if (mpMutationState && mpMutationState->IsType<BetaCateninOneHitCellMutationState>())
{
// Beta-cat delta 45
beta_cat_level_1 = 0.5*ma2d/(ma2d+ma3d*destruction_level);
beta_cat_level_2 = 0.5;
}
else
{
// healthy cells
beta_cat_level_1 = 0.5*ma2d/(ma2d+ma3d*destruction_level);
beta_cat_level_2 = 0.5*ma2d/(ma2d+ma3d*destruction_level);
}
// Cell-specific initial conditions
SetDefaultInitialCondition(5, destruction_level);
SetDefaultInitialCondition(6, beta_cat_level_1);
SetDefaultInitialCondition(7, beta_cat_level_2);
SetDefaultInitialCondition(8, wntLevel);
if (stateVariables != std::vector<double>())
{
SetStateVariables(stateVariables);
}
}