Chaste  Release::2018.1
SimpleWntCellCycleModel.cpp
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35 
36 #include "SimpleWntCellCycleModel.hpp"
37 #include "Exception.hpp"
38 #include "StemCellProliferativeType.hpp"
39 #include "TransitCellProliferativeType.hpp"
40 #include "DifferentiatedCellProliferativeType.hpp"
41 #include "CellLabel.hpp"
42 #include "WildTypeCellMutationState.hpp"
43 #include "ApcOneHitCellMutationState.hpp"
44 #include "ApcTwoHitCellMutationState.hpp"
45 #include "BetaCateninOneHitCellMutationState.hpp"
46 
48  : mUseCellProliferativeTypeDependentG1Duration(false),
49  mWntStemThreshold(0.8),
50  mWntTransitThreshold(0.65),
51  mWntLabelledThreshold(0.65)
52 {
53 }
54 
57  mUseCellProliferativeTypeDependentG1Duration(rModel.mUseCellProliferativeTypeDependentG1Duration),
58  mWntStemThreshold(rModel.mWntStemThreshold),
59  mWntTransitThreshold(rModel.mWntTransitThreshold),
60  mWntLabelledThreshold(rModel.mWntLabelledThreshold)
61 {
62  /*
63  * Initialize only those member variables defined in this class.
64  *
65  * The member variables mCurrentCellCyclePhase, mG1Duration,
66  * mMinimumGapDuration, mStemCellG1Duration, mTransitCellG1Duration,
67  * mSDuration, mG2Duration and mMDuration are initialized in the
68  * AbstractPhaseBasedCellCycleModel constructor.
69  *
70  * The member variables mBirthTime, mReadyToDivide and mDimension
71  * are initialized in the AbstractCellCycleModel constructor.
72  *
73  * Note that mG1Duration and the cell's proliferative type are
74  * (re)set as soon as InitialiseDaughterCell() is called on the
75  * new cell-cycle model.
76  */
77 }
78 
80 {
81  return new SimpleWntCellCycleModel(*this);
82 }
83 
85 {
87 }
88 
89 void SimpleWntCellCycleModel::SetUseCellProliferativeTypeDependentG1Duration(bool useCellProliferativeTypeDependentG1Duration)
90 {
91  mUseCellProliferativeTypeDependentG1Duration = useCellProliferativeTypeDependentG1Duration;
92 }
93 
95 {
96  assert(mpCell != nullptr);
97 
99 
100  if (mpCell->GetCellProliferativeType()->IsType<StemCellProliferativeType>())
101  {
103  {
105  }
106  else
107  {
108  // Normally stem cells should behave just like transit cells in a Wnt simulation
110  }
111  }
112  else if (mpCell->GetCellProliferativeType()->IsType<TransitCellProliferativeType>())
113  {
115  }
116  else if (mpCell->GetCellProliferativeType()->IsType<DifferentiatedCellProliferativeType>())
117  {
118  mG1Duration = DBL_MAX;
119  }
120  else
121  {
123  }
124 
125  // Check that the normal random deviate has not returned a small or negative G1 duration
127  {
129  }
130 }
131 
133 {
134  assert(mpCell != nullptr);
135  double level = 0;
136 
137  switch (mDimension)
138  {
139  case 1:
140  {
141  const unsigned DIM = 1;
143  break;
144  }
145  case 2:
146  {
147  const unsigned DIM = 2;
149  break;
150  }
151  case 3:
152  {
153  const unsigned DIM = 3;
155  break;
156  }
157  default:
159  }
160  return level;
161 }
162 
164 {
165  WntConcentrationType wnt_type;
166  switch (mDimension)
167  {
168  case 1:
169  {
170  const unsigned DIM = 1;
172  break;
173  }
174  case 2:
175  {
176  const unsigned DIM = 2;
178  break;
179  }
180  case 3:
181  {
182  const unsigned DIM = 3;
184  break;
185  }
186  case UNSIGNED_UNSET:
187  {
188  // If you trip this you have tried to use a simulation without setting the dimension.
190  }
191  default:
193  }
194  return wnt_type;
195 }
196 
198 {
199  // The cell can divide if the Wnt concentration >= wnt_division_threshold
200  double wnt_division_threshold = DBL_MAX;
201 
202  // Set up under what level of Wnt stimulus a cell will divide
203  if (mpCell->GetMutationState()->IsType<WildTypeCellMutationState>())
204  {
205  wnt_division_threshold = mWntTransitThreshold;
206  }
207  else if (mpCell->GetMutationState()->IsType<ApcOneHitCellMutationState>())
208  {
209  // should be less than healthy values
210  wnt_division_threshold = 0.77*mWntTransitThreshold;
211  }
212  else if (mpCell->GetMutationState()->IsType<BetaCateninOneHitCellMutationState>())
213  {
214  // less than above value
215  wnt_division_threshold = 0.155*mWntTransitThreshold;
216  }
217  else if (mpCell->GetMutationState()->IsType<ApcTwoHitCellMutationState>())
218  {
219  // should be zero (no Wnt-dependence)
220  wnt_division_threshold = 0.0;
221  }
222  else
223  {
225  }
226 
227  if (mpCell->HasCellProperty<CellLabel>())
228  {
229  wnt_division_threshold = mWntLabelledThreshold;
230  }
231 
232  double wnt_level = GetWntLevel();
233  WntConcentrationType wnt_type = GetWntType();
234 
235  // Set the cell type to TransitCellProliferativeType if the Wnt stimulus exceeds wnt_division_threshold
236  if (wnt_level >= wnt_division_threshold)
237  {
238  // For a RADIAL Wnt type, override the cell type to StemCellProliferativeType if the Wnt stimulus exceeds a higher threshold
239  if ((wnt_type == RADIAL) && (wnt_level > mWntStemThreshold))
240  {
241  /*
242  * This method is usually called within a CellBasedSimulation, after the CellPopulation
243  * has called CellPropertyRegistry::TakeOwnership(). This means that were we to call
244  * CellPropertyRegistry::Instance() here when setting the CellProliferativeType, we
245  * would be creating a new CellPropertyRegistry. In this case the cell proliferative
246  * type counts, as returned by AbstractCellPopulation::GetCellProliferativeTypeCount(),
247  * would be incorrect. We must therefore access the CellProliferativeType via the cell's
248  * CellPropertyCollection.
249  */
250  boost::shared_ptr<AbstractCellProperty> p_stem_type =
251  mpCell->rGetCellPropertyCollection().GetCellPropertyRegistry()->Get<StemCellProliferativeType>();
252  mpCell->SetCellProliferativeType(p_stem_type);
253  }
254  else
255  {
256  boost::shared_ptr<AbstractCellProperty> p_transit_type =
257  mpCell->rGetCellPropertyCollection().GetCellPropertyRegistry()->Get<TransitCellProliferativeType>();
258  mpCell->SetCellProliferativeType(p_transit_type);
259  }
260  }
261  else
262  {
263  // The cell is set to have DifferentiatedCellProliferativeType and so in G0 phase
264  boost::shared_ptr<AbstractCellProperty> p_diff_type =
265  mpCell->rGetCellPropertyCollection().GetCellPropertyRegistry()->Get<DifferentiatedCellProliferativeType>();
266  mpCell->SetCellProliferativeType(p_diff_type);
267  }
269 }
270 
272 {
273  WntConcentrationType wnt_type = GetWntType();
274 
275  if (wnt_type == RADIAL)
276  {
277  boost::shared_ptr<AbstractCellProperty> p_transit_type =
278  mpCell->rGetCellPropertyCollection().GetCellPropertyRegistry()->Get<TransitCellProliferativeType>();
279  mpCell->SetCellProliferativeType(p_transit_type);
280  }
281 
283 }
284 
286 {
287  return false;
288 }
289 
291 {
292  return mWntStemThreshold;
293 }
294 
295 void SimpleWntCellCycleModel::SetWntStemThreshold(double wntStemThreshold)
296 {
297  assert(wntStemThreshold <= 1.0);
298  assert(wntStemThreshold >= 0.0);
299  mWntStemThreshold = wntStemThreshold;
300 }
301 
303 {
304  return mWntTransitThreshold;
305 }
306 
307 void SimpleWntCellCycleModel::SetWntTransitThreshold(double wntTransitThreshold)
308 {
309  //assert(wntTransitThreshold <= 1.0);
310  //assert(wntTransitThreshold >= 0.0);
311  mWntTransitThreshold = wntTransitThreshold;
312 }
313 
315 {
316  return mWntLabelledThreshold;
317 }
318 
319 void SimpleWntCellCycleModel::SetWntLabelledThreshold(double wntLabelledThreshold)
320 {
321 // assert(wntLabelledThreshold <= 1.0);
322 // assert(wntLabelledThreshold >= 0.0);
323  mWntLabelledThreshold = wntLabelledThreshold;
324 }
325 
327 {
328  *rParamsFile << "\t\t\t<UseCellProliferativeTypeDependentG1Duration>" << mUseCellProliferativeTypeDependentG1Duration << "</UseCellProliferativeTypeDependentG1Duration>\n";
329  *rParamsFile << "\t\t\t<WntStemThreshold>" << mWntStemThreshold << "</WntStemThreshold>\n";
330  *rParamsFile << "\t\t\t<WntTransitThreshold>" << mWntTransitThreshold << "</WntTransitThreshold>\n";
331  *rParamsFile << "\t\t\t<WntLabelledThreshold>" << mWntLabelledThreshold << "</WntLabelledThreshold>\n";
332 
333  // Call method on direct parent class
335 }
336 
337 // Serialization for Boost >= 1.36
virtual void OutputCellCycleModelParameters(out_stream &rParamsFile)
double GetWntLevel(double height)
WntConcentrationType GetWntType()
virtual AbstractCellCycleModel * CreateCellCycleModel()
double NormalRandomDeviate(double mean, double stdDev)
WntConcentrationType GetType()
#define NEVER_REACHED
Definition: Exception.hpp:206
bool GetUseCellProliferativeTypeDependentG1Duration() const
void SetUseCellProliferativeTypeDependentG1Duration(bool useCellProliferativeTypeDependentG1Duration=true)
static WntConcentration * Instance()
void SetWntTransitThreshold(double wntTransitThreshold)
const unsigned UNSIGNED_UNSET
Definition: Exception.hpp:52
static RandomNumberGenerator * Instance()
void SetWntLabelledThreshold(double wntLabelledThreshold)
virtual void OutputCellCycleModelParameters(out_stream &rParamsFile)
#define CHASTE_CLASS_EXPORT(T)
void SetWntStemThreshold(double wntStemThreshold)