/// <summary>
/// Expression evaluator
/// </summary>
public NoStringEvaluator(ObjectPool <Stack <InternalEvaluatorValue> > stackPool, ObjectPool <List <InternalEvaluatorValue> > argsPool, ObjectPool <ExtraTypeIdContainer> extraTypeIdContainerPool, IFormulaCache formulaCache)
{
_stackPool = stackPool;
_argsPool = argsPool;
_extraTypeIdContainerPool = extraTypeIdContainerPool;
_formulaCache = formulaCache;
}
private IFormula checkFormula(IFormulaCache formulaCache, IFormula formula)
{
if (formula.IsExplicit())
{
return(checkFormulaByType(formulaCache, (ExplicitFormula)formula, AreEqualExplicitFormula));
}
if (formula.IsBlackBox())
{
return(checkFormulaByType(formulaCache, (BlackBoxFormula)formula, AreEqualBalckBoxFormula));
}
if (formula.IsTable())
{
return(checkFormulaByType(formulaCache, (TableFormula)formula, AreEqualTableFormula));
}
if (formula.IsTableWithOffSet())
{
return(checkFormulaByType(formulaCache, (TableFormulaWithOffset)formula, AreEqualTableFormulaWithOffset));
}
if (formula.IsDynamic())
{
return(checkFormulaByType(formulaCache, (SumFormula)formula, AreEqualSumFormula));
}
return(formula);
}
private IMoleculeBuilder createFor(QuantityType moleculeType, IFormulaCache formulaCache)
{
switch (moleculeType)
{
case QuantityType.Drug:
return(_moleculeMapper.MapFrom(_flatMoleculeRepository.FindBy(QuantityType.Drug), formulaCache)
.WithIcon(ApplicationIcons.Drug.IconName));
case QuantityType.Enzyme:
case QuantityType.OtherProtein:
return(defaultProteinMoleculeFrom(moleculeType, formulaCache));
case QuantityType.Transporter:
return(defaultTransporterMoleculeFrom(formulaCache));
case QuantityType.Metabolite:
case QuantityType.Complex:
return(defaultReactionProduct(moleculeType, formulaCache));
case QuantityType.Undefined:
return(defaultFloatingNonXenobioticMolecule(moleculeType, formulaCache));
default:
throw new ArgumentOutOfRangeException(nameof(moleculeType));
}
}
protected override void Context()
{
base.Context();
_formulaCache = new FormulaCache();
_compoundFactory = IoC.Resolve <ICompoundFactory>();
_parameterAlternativeFactory = IoC.Resolve <IParameterAlternativeFactory>();
_compound = _compoundFactory.Create().WithName("Comp");
_compound.Parameter(Constants.Parameters.MOL_WEIGHT).Value = 250;
//Two simple parameters without alternatives
//one parameter defined as a constant for which an alternative was also specififed
var lipoGroup = _compound.ParameterAlternativeGroup(CoreConstants.Groups.COMPOUND_LIPOPHILICITY);
_alternativeLipo1 = _parameterAlternativeFactory.CreateAlternativeFor(lipoGroup).WithName("ALT_LIPO1").WithId("ALT_LIPO1");
_alternativeLipo1.Parameter(CoreConstants.Parameters.LIPOPHILICITY).Value = 2;
_alternativeLipo2 = _parameterAlternativeFactory.CreateAlternativeFor(lipoGroup).WithName("ALT_LIPO2").WithId("ALT_LIPO2");
_alternativeLipo2.Parameter(CoreConstants.Parameters.LIPOPHILICITY).Value = 5;
lipoGroup.AddAlternative(_alternativeLipo1);
lipoGroup.AddAlternative(_alternativeLipo2);
//one parameter defined as a formula with a default calculated alternative
var permAlternativeGroup = _compound.ParameterAlternativeGroup(CoreConstants.Groups.COMPOUND_PERMEABILITY);
//value cannot be changed by user
_alternativePerm1 = _parameterAlternativeFactory.CreateDefaultAlternativeFor(permAlternativeGroup).WithName("ALT_PERM1").WithId("ALT_PERM1");
_alternativePerm2 = _parameterAlternativeFactory.CreateAlternativeFor(permAlternativeGroup).WithName("ALT_PERM2").WithId("ALT_PERM2");
_alternativePerm2.Parameter(CoreConstants.Parameters.PERMEABILITY).Value = 10;
permAlternativeGroup.AddAlternative(_alternativePerm1);
permAlternativeGroup.AddAlternative(_alternativePerm2);
}
private IMoleculeBuilder defaultTransporterMoleculeFrom(IFormulaCache formulaCache)
{
var transporter = defaultProteinMoleculeFrom(QuantityType.Transporter, formulaCache);
removeGlobalExpressionsParameterFor(transporter);
return(transporter);
}
public IFormula RateFor(RateKey rateKey, IFormulaCache formulaCache)
{
if (rateKey == null)
{
return(null);
}
//no formula cache defined. Formula should be unique by id
if (formulaCache == null)
{
return(createFormula(rateKey).WithId(_idGenerator.NewId()));
}
if (!formulaCache.Contains(rateKey))
{
var formula = createFormula(rateKey);
if (formula.IsConstant())
{
return(formula);
}
formulaCache.Add(formula);
}
return(formulaCache[rateKey]);
}
protected override void Context()
{
_formulaCache = A.Fake <IFormulaCache>();
_repository = A.Fake <IRepository <IInteractionKineticUpdaterSpecification> >();
_objectBaseFactory = A.Fake <IObjectBaseFactory>();
A.CallTo(() => _objectBaseFactory.Create <ExplicitFormula>()).ReturnsLazily(x => new ExplicitFormula());
A.CallTo(() => _repository.All()).Returns(_allKineticUpdaterSpecifications);
sut = new InteractionKineticUpdater(_repository, _objectBaseFactory);
_reaction = new ReactionBuilder();
_transporterMoleculeContainer = new TransporterMoleculeContainer();
_simulation = A.Fake <Simulation>();
_interactionProperties = new InteractionProperties();
_interactionProperties.AddInteraction(new InteractionSelection {
MoleculeName = _enzymeName, ProcessName = _processName
});
A.CallTo(() => _simulation.InteractionProperties).Returns(_interactionProperties);
_kmFactor = new PKSimParameter().WithName(CoreConstants.Parameter.KM_INTERACTION_FACTOR).WithFormula(new ExplicitFormula("1"));
_vmaxFactor = new PKSimParameter().WithName(CoreConstants.Parameter.KCAT_INTERACTION_FACTOR).WithFormula(new ExplicitFormula("1"));
_reaction.Add(_kmFactor);
_reaction.Add(_vmaxFactor);
_transporterMoleculeContainer.Add(_kmFactor);
_transporterMoleculeContainer.Add(_vmaxFactor);
}
public IParameterStartValuesBuildingBlock CreateFor(IBuildConfiguration buildConfiguration, Simulation simulation)
{
try
{
//default default parameter start values matrix
_spatialStructure = buildConfiguration.SpatialStructure;
_defaultStartValues = _parameterStartValuesCreator.CreateFrom(_spatialStructure, buildConfiguration.Molecules);
_formulaCache = _defaultStartValues.FormulaCache;
var individual = simulation.Individual;
//set the relative expression values for each protein defined in individual
foreach (var protein in individual.AllMolecules <IndividualProtein>())
{
updateProteinParametersValues(protein);
}
foreach (var transporter in individual.AllMolecules <IndividualTransporter>())
{
updateTransporterParameterValues(transporter);
}
updateSimulationParameters(simulation);
return(_defaultStartValues.WithName(simulation.Name));
}
finally
{
_spatialStructure = null;
_defaultStartValues = null;
_formulaCache = null;
}
}
private void updateDose(ISchemaItem schemaItem, IContainer targetContainer, IFormulaCache formulaCache)
{
//now that parameter have been set, we need to update the dose by hand according to the selected unit
var inputDose = schemaItem.Dose;
var dose = targetContainer.Parameter(CoreConstants.Parameters.DOSE);
var dosePerBodyWeight = targetContainer.Parameter(CoreConstants.Parameters.DOSE_PER_BODY_WEIGHT);
var dosePerBodySurfaceArea = targetContainer.Parameter(CoreConstants.Parameters.DOSE_PER_BODY_SURFACE_AREA);
if (schemaItem.DoseIsInMass())
{
//we have to create a constant value for the dose parameter
dose.Formula = _formulaFactory.ValueFor(inputDose.Value, _dimensionRepository.Mass);
updateDoseParameter(inputDose, dose, dosePerBodyWeight, dosePerBodySurfaceArea);
}
else if (schemaItem.DoseIsPerBodyWeight())
{
dose.Formula = _formulaFactory.DoseFromDosePerBodyWeightFor(formulaCache);
updateDoseParameter(inputDose, dosePerBodyWeight, dose, dosePerBodySurfaceArea);
}
else if (schemaItem.DoseIsPerBodySurfaceArea())
{
dose.Formula = _formulaFactory.DoseFromDosePerBodySurfaceAreaFor(formulaCache);
updateDoseParameter(inputDose, dosePerBodySurfaceArea, dose, dosePerBodyWeight);
}
}
public void Convert(IMoleculeStartValue moleculeStartValue, IFormulaCache formulaCache)
{
if (!conversionRequired(moleculeStartValue))
{
return;
}
moleculeStartValue.Dimension = _concentrationDimension;
moleculeStartValue.DisplayUnit = _displayUnitRetriever.PreferredUnitFor(moleculeStartValue);
if (moleculeStartValue.Formula.IsExplicit())
{
convertExplicitFormula(moleculeStartValue.Formula, _concentrationDimension);
return;
}
var startValue = moleculeStartValue.StartValue.GetValueOrDefault(0);
if (startValue == 0)
{
return;
}
moleculeStartValue.Formula = createConcentrationFormulaFromConstantValue(startValue, moleculeStartValue.Path.ToPathString(), formulaCache);
}
private void updateInteractionFactor(IContainer processParameterContainer, string compoundName,
IEnumerable <IInteractionKineticUpdaterSpecification> allUpdatingKinetics,
IFormulaCache formulaCache,
string parameterName, Func <IParameter, string> createFormulaAction)
{
var interactionFactor = processParameterContainer.Parameter(parameterName);
if (!allUpdatingKinetics.Any() || interactionFactor == null)
{
return;
}
var formulaName = CoreConstants.CompositeNameFor(processParameterContainer.Name, compoundName, parameterName);
if (formulaCache.FindByName(formulaName) is ExplicitFormula formula)
{
interactionFactor.Formula = formula;
return;
}
formula = _objectBaseFactory.Create <ExplicitFormula>()
.WithName(formulaName)
.WithDimension(interactionFactor.Dimension);
interactionFactor.Formula = formula;
formula.FormulaString = createFormulaAction(interactionFactor);
formulaCache.Add(formula);
}
public FlatEventChangedObjectToEventAssignmentBuilderMapper(IObjectBaseFactory objectBaseFactory, IFormulaFactory formulaFactory,
IFlatObjectPathToObjectPathMapper objectPathMapper)
{
_objectBaseFactory = objectBaseFactory;
_formulaFactory = formulaFactory;
_objectPathMapper = objectPathMapper;
_formulaCache = new FormulaCache();
}
/// <summary>
/// Add start formula for the drug molecule. Will be created in the root application container
/// </summary>
private void addDrugStartFormula(IApplicationBuilder applicationBuilder, IFormulaCache formulaCache)
{
var applicationMoleculeBuilder = _objectBaseFactory.Create <IApplicationMoleculeBuilder>().WithName(applicationBuilder.Name);
applicationMoleculeBuilder.RelativeContainerPath = _objectPathFactory.CreateObjectPathFrom(ObjectPath.PARENT_CONTAINER, applicationBuilder.Name);
applicationMoleculeBuilder.Formula = _formulaFactory.DrugMassFormulaFor(formulaCache);
applicationBuilder.AddMolecule(applicationMoleculeBuilder);
}
protected override void Context()
{
base.Context();
_exisitingFormula = A.Fake <IFormula>().WithId(CoreConstants.Formula.Concentration);
_formulaCache = new FormulaCache {
_exisitingFormula
};
}
public IFormula RHSRateFor(ParameterRateMetaData parameterRateDefinition, IFormulaCache formulaCache)
{
if (string.IsNullOrEmpty(parameterRateDefinition.RHSRate))
{
return(null);
}
return(RateFor(parameterRateDefinition.CalculationMethod, parameterRateDefinition.RHSRate, formulaCache));
}
protected override void Context()
{
_dimensionRepository = A.Fake <IDimensionFactory>();
_dataRepositoryTask = A.Fake <IDataRepositoryTask>();
A.CallTo(() => _dimensionRepository.NoDimension).Returns(new Dimension());
_objectBaseFactory = new ObjectBaseFactoryForSpecs(_dimensionRepository);
_objectToClone = createEntityToClone();
_formulaCache = new FormulaCache();
sut = new CloneManagerForBuildingBlock(_objectBaseFactory, _dataRepositoryTask);
}
public IParameter CreateConcentrationParameterIn(IFormulaCache formulaCache)
{
var parameter = CreateFor(CoreConstants.Parameter.CONCENTRATION, PKSimBuildingBlockType.Simulation);
parameter.BuildMode = ParameterBuildMode.Local;
parameter.Info.Visible = false;
parameter.Formula = _formulaFactory.ConcentrationFormulaFor(formulaCache);
parameter.Dimension = _dimensionRepository.MolarConcentration;
return(parameter);
}
public IMoleculeBuilder Create(QuantityType moleculeType, IFormulaCache formulaCache)
{
var moleculeBuilder = createFor(moleculeType, formulaCache);
moleculeBuilder.Dimension = _dimensionRepository.Amount;
moleculeBuilder.DefaultStartFormula.Dimension = _dimensionRepository.Amount;
addFormulaToCacheIfNecessary(moleculeBuilder.DefaultStartFormula, formulaCache);
addConcentrationParmeterTo(moleculeBuilder, formulaCache);
return(moleculeBuilder);
}
public void Convert(IReactionBuilder reaction, IFormulaCache formulaCache)
{
if (!conversionRequired(reaction))
{
return;
}
reaction.Dimension = _concentrationPerTimeDimension;
convertExplicitFormula(reaction.Formula, _concentrationPerTimeDimension);
}
public T Clone <T>(T objectToClone, IFormulaCache formulaCache) where T : class, IObjectBase
{
if (formulaCache == null)
{
throw new ArgumentNullException(Error.NullFormulaCachePassedToClone);
}
FormulaCache = formulaCache;
return(Clone(objectToClone));
}
public IParameter CreateConcentrationParameter(IFormulaCache formulaCache)
{
var concentrationFormula = _formulaFactory.ConcentrationFormulaFor(formulaCache);
var molarConcentrationDimension = _dimensionFactory.Dimension(Constants.Dimension.MOLAR_CONCENTRATION);
var concentrationParameter = CreateParameter(Constants.Parameters.CONCENTRATION, dimension: molarConcentrationDimension, formula: concentrationFormula)
.WithMode(ParameterBuildMode.Local);
concentrationParameter.Info.ReadOnly = true;
return(concentrationParameter);
}
protected override void Context()
{
base.Context();
_buildingBlockToAddTo = A.Fake <IBuildingBlock>();
_formulaCache = new FormulaCache();
A.CallTo(() => _buildingBlockToAddTo.FormulaCache).Returns(_formulaCache);
_totalyNewObject = new MoleculeBuilder().WithName("New");
_newFormula = A.Fake <ExplicitFormula>().WithName("New Formula").WithDimension(A.Fake <IDimension>()).WithFormulaString("1+1").WithId("1");
_newFormula.ObjectPaths = new IFormulaUsablePath[0];
_totalyNewObject.DefaultStartFormula = _newFormula;
}
protected override void Context()
{
base.Context();
_buildingBlockToAddTo = A.Fake <IBuildingBlock>();
_formulaCache = new FormulaCache();
A.CallTo(() => _buildingBlockToAddTo.FormulaCache).Returns(_formulaCache);
_totalyNewObject = new Parameter().WithName("New");
_newFormula = A.Fake <ExplicitFormula>().WithName("New Formula").WithDimension(A.Fake <IDimension>()).WithFormulaString("1+1").WithId("1");
_newFormula.ObjectPaths = new IFormulaUsablePath[0];
_totalyNewObject.Formula = _newFormula;
A.CallTo(() => _objectBaseRepository.ContainsObjectWithId(A <string> ._)).Returns(false);
}
protected override void Context()
{
base.Context();
_rateKey = new RateKey("CM1", "Rate1");
_formulaCache = new FormulaCache();
A.CallTo(() => _rateFormulaRepository.FormulaFor(_rateKey)).Returns("Time * 2");
A.CallTo(() => _objectBaseFactory.Create <ExplicitFormula>()).Returns(new ExplicitFormula());
A.CallTo(() => _rateObjectPathsRepository.ObjectPathsFor(_rateKey)).Returns(
new List <IFormulaUsablePath>());
}
protected override void Context()
{
base.Context();
_formulaCache = A.Fake <IFormulaCache>();
_parameterRateDefinition = new ParameterRateMetaData();
_parameterRateDefinition.ParameterName = "Tralal";
_rateFormula = A.Fake <IFormula>();
_parameter = A.Fake <IParameter>();
A.CallTo(() => _formulaFactory.RateFor(_parameterRateDefinition, _formulaCache)).Returns(_rateFormula);
A.CallTo(() => _objectBaseFactory.CreateParameter()).Returns(_parameter);
A.CallTo(() => _dimensionRepository.DimensionByName(_parameterRateDefinition.Dimension)).Returns(_dimension);
}
private IMoleculeBuilder defaultReactionProduct(QuantityType moleculeType, IFormulaCache formulaCache)
{
var metabolite = _objectBaseFactory.Create <IMoleculeBuilder>();
addDrugParametersTo(metabolite, formulaCache);
metabolite.QuantityType = moleculeType;
metabolite.Name = moleculeType.ToString();
metabolite.DefaultStartFormula = _objectBaseFactory.Create <ConstantFormula>().WithValue(0);
metabolite.IsFloating = false;
metabolite.IsXenobiotic = true;
return(metabolite);
}
/// <summary>
/// add the given formula to the cache only if
/// 1- the formula is not constant (constant formula are not registered in cache)
/// 2- the formula was not registered already.
/// </summary>
/// <param name="formula">formula to add</param>
/// <param name="formulaCache">formula cache</param>
private void addFormulaToCacheIfNecessary(IFormula formula, IFormulaCache formulaCache)
{
if (formula.IsConstant())
{
return;
}
if (formulaCache.Contains(formula.Id))
{
return;
}
formulaCache.Add(formula);
}
protected override void Context()
{
base.Context();
_formulaCache = A.Fake <IFormulaCache>();
_pkSimTransport = new PKSimTransport {
Formula = A.Fake <IFormula>()
};
_process = new SystemicProcess {
InternalName = "Proc", Name = "BLA BLA"
};
A.CallTo(() => _simulationActiveProcessRepository.ProcessFor <PKSimTransport>(_process.InternalName)).Returns(_pkSimTransport);
A.CallTo(() => _cloneManager.Clone(_pkSimTransport)).Returns(_pkSimTransport);
}
public IMoleculeBuilder MapFrom(FlatMolecule flatMolecule, IFormulaCache formulaCache)
{
var molecule = _objectBaseFactory.Create <IMoleculeBuilder>();
molecule.Name = flatMolecule.Id;
molecule.IsFloating = flatMolecule.IsFloating;
molecule.QuantityType = flatMolecule.MoleculeType;
molecule.DefaultStartFormula = _formulaFactory.RateFor(flatMolecule, new FormulaCache());
_parameterContainerTask.AddMoleculeParametersTo(molecule, formulaCache);
return(molecule);
}
protected override void Context()
{
base.Context();
_formulaCache = new FormulaCache();
_protein = A.Fake <IMoleculeBuilder>().WithName("CYP3A4");
var reaction = new ReactionBuilder {
Formula = new ExplicitFormula().WithName("ABC")
};
reaction.Formula.AddObjectPath(new FormulaUsablePath(CoreConstants.KeyWords.Protein, "P1").WithAlias("P1"));
reaction.Formula.AddObjectPath(new FormulaUsablePath(CoreConstants.KeyWords.Reaction, "R1").WithAlias("R1"));
_template = A.Fake <IReactionBuilder>().WithName(CoreConstants.Reaction.TURNOVER);
A.CallTo(() => _cloneManager.Clone(_template)).Returns(reaction);
}