public override void Execute(IExecutionContext context)
{
Description = PKSimConstants.Command.SetProteinTissueLocationDescription(_protein.Localization.ToString(), _localization.ToString());
var setLocationCommand = new SetExpressionLocalizationInProteinCommand(_protein, _localization, _simulationSubject, context).Run(context);
Add(setLocationCommand);
if (_localization.Is(InBloodCells))
{
AddRange(updateBloodCellsExpressionParameters(context));
}
if (_localization.Is(InVascularEndothelium))
{
AddRange(updateVascularEndotheliumExpressionParameters(context));
}
if (_localization.Is(InTissue))
{
AddRange(updateTissueExpressionParameters(context));
}
var expressionProfileUpdater = context.Resolve <IExpressionProfileUpdater>();
expressionProfileUpdater.SynchronizeAllSimulationSubjectsWithExpressionProfile(_simulationSubject);
_protein = null;
_simulationSubject = null;
//update properties from first command
this.UpdatePropertiesFrom(setLocationCommand);
}
protected override void Context()
{
_protein = new IndividualOtherProtein();
_individual = new Individual();
_context = A.Fake <IExecutionContext>();
sut = new AddMoleculeToIndividualCommand(_protein, _individual, _context);
}
protected override void Context()
{
base.Context();
_proteinToRemove = A.Fake <IndividualEnzyme>().WithName("Trlala");
sut.EditIndividual(_individual);
A.CallTo(() => _dialogCreator.MessageBoxYesNo(A <string> .Ignored, ViewResult.Yes)).Returns(ViewResult.No);
}
private void updateProteinParametersValues(IndividualProtein protein)
{
setGlobalParameterValue(protein, CoreConstants.Parameter.REL_EXP_BLOOD_CELL, CoreConstants.Compartment.BloodCells);
setGlobalParameterValue(protein, CoreConstants.Parameter.REL_EXP_PLASMA, CoreConstants.Compartment.Plasma);
setGlobalParameterValue(protein, CoreConstants.Parameter.REL_EXP_VASC_ENDO, CoreConstants.Compartment.VascularEndothelium);
foreach (var expressionContainer in _expressionContainersRetriever.AllContainersFor(_spatialStructure, protein))
{
if (expressionContainer.IsBloodCell())
{
setParameterValuesForBloodCells(protein, expressionContainer);
}
else if (expressionContainer.IsPlasma())
{
setParameterValuesForPlasma(protein, expressionContainer);
}
else if (expressionContainer.IsInterstitial())
{
setParameterValuesForInterstitial(protein, expressionContainer);
}
else if (expressionContainer.IsEndosome())
{
setParameterValuesForEndosome(protein, expressionContainer);
}
else
{
setParameterValuesForStandardContainer(protein, expressionContainer);
}
}
}
protected override void Context()
{
_protein = A.Fake <IndividualProtein>();
_context = A.Fake <IExecutionContext>();
_individual = new Individual();
_individual.AddMolecule(_protein);
sut = new RemoveMoleculeFromIndividualCommand(_protein, _individual, _context);
}
protected override void Context()
{
base.Context();
_enzyme1 = new IndividualOtherProtein().WithName("_enzyme1");
_enzyme2 = new IndividualEnzyme().WithName("_enzyme2");
sut.AddMolecule(_enzyme1);
sut.AddMolecule(_enzyme2);
}
public SetTissueLocationCommand(IndividualProtein protein, TissueLocation tissueLocation, IExecutionContext context)
{
_protein = protein;
BuildingBlockId = context.BuildingBlockIdContaining(protein);
_newTissuleLocation = tissueLocation;
ObjectType = PKSimConstants.ObjectTypes.Protein;
CommandType = PKSimConstants.Command.CommandTypeEdit;
_proteinId = _protein.Id;
context.UpdateBuildinBlockProperties(this, context.BuildingBlockContaining(protein));
}
protected override void Context()
{
base.Context();
_protein = A.Fake <IndividualProtein>();
_enzyme = A.Fake <IndividualEnzyme>();
_moleculeList.AddRange(new[] { _protein, _enzyme });
_enzymeList.Add(_enzyme);
_enzymeNode = A.Fake <ITreeNode <IndividualEnzyme> >();
A.CallTo(() => _treeNodeFactory.CreateFor(_enzyme)).Returns(_enzymeNode);
}
public ProteinExpressionDTO MapFrom(IndividualProtein protein)
{
var proteinExpressionDTO = new ProteinExpressionDTO(protein);
foreach (var enzymeExpressionContainer in protein.AllExpressionsContainers())
{
addContainerExpression(proteinExpressionDTO, protein, enzymeExpressionContainer);
}
return(proteinExpressionDTO);
}
public SetProteinIntracellularVascularEndoLocationCommand(IndividualProtein protein, IntracellularVascularEndoLocation newVascularEndoLocation, IExecutionContext context)
{
_protein = protein;
_newVascularEndoLocation = newVascularEndoLocation;
BuildingBlockId = context.BuildingBlockIdContaining(protein);
ObjectType = PKSimConstants.ObjectTypes.Protein;
CommandType = PKSimConstants.Command.CommandTypeEdit;
_proteinId = _protein.Id;
context.UpdateBuildinBlockProperties(this, context.BuildingBlockContaining(_protein));
}
public ProteinExpressionDTO MapFrom(IndividualProtein protein)
{
var proteinExpressionDTO = new ProteinExpressionDTO(protein);
foreach (var enzymeExpressionContainer in protein.GetChildren <IMoleculeExpressionContainer>())
{
addContainerExpression(proteinExpressionDTO, protein, enzymeExpressionContainer);
}
return(proteinExpressionDTO);
}
protected override void Context()
{
base.Context();
_selectedOntogeny = new DatabaseOntogeny();
_individual = A.Fake <Individual>();
_protein = A.Fake <IndividualProtein>();
_command = A.Fake <IPKSimCommand>();
A.CallTo(() => _ontogenyTask.SetOntogenyForMolecule(_protein, _selectedOntogeny, _individual)).Returns(_command);
sut.Edit(_protein, _individual);
}
protected override void Context()
{
base.Context();
_command = A.Fake <IPKSimCommand>();
_proteinToRemove = A.Fake <IndividualEnzyme>().WithName("Trlala");
_proteinType = "toto";
A.CallTo(() => _moleculeExpressionTask.RemoveMoleculeFrom(_proteinToRemove, _individual)).Returns(_command);
A.CallTo(() => _dialogCreator.MessageBoxYesNo(A <string> .Ignored, ViewResult.Yes)).Returns(ViewResult.Yes);
A.CallTo(() => _entityTask.TypeFor(_proteinToRemove)).Returns(_proteinType);
sut.EditIndividual(_individual);
}
public IndividualProteinDTO MapFrom(IndividualProtein protein, ISimulationSubject simulationSubject)
{
var dto = new IndividualProteinDTO(protein);
simulationSubject.AllMoleculeContainersFor(protein)
.SelectMany(x => x.AllParameters())
.Union(protein.AllGlobalExpressionParameters)
.MapAllUsing(_expressionContainerMapper)
.Each(dto.AddExpressionParameter);
return(dto);
}
protected override void Context()
{
_protein = new IndividualOtherProtein();
_population = new RandomPopulation {
new AdvancedParameterCollection()
};
_population.Settings = new RandomPopulationSettings {
BaseIndividual = new Individual()
};
_context = A.Fake <IExecutionContext>();
sut = new AddMoleculeToPopulationCommand(_protein, _population, _context);
}
public SetExpressionLocalizationCommand(
IndividualProtein protein,
Localization localization,
ISimulationSubject simulationSubject,
IExecutionContext context)
{
_protein = protein;
_simulationSubject = simulationSubject;
_localization = localization;
ObjectType = PKSimConstants.ObjectTypes.Protein;
CommandType = PKSimConstants.Command.CommandTypeEdit;
context.UpdateBuildingBlockPropertiesInCommand(this, context.BuildingBlockContaining(protein));
}
protected override void Context()
{
_protein = new IndividualOtherProtein().WithName("CYP3A4");
_context = A.Fake <IExecutionContext>();
_organism = new Organism();
_liver = new Organ().WithName("liver").WithParentContainer(_organism);
_localMoleculeContainer = new Container().WithName(_protein.Name).WithParentContainer(_liver);
_individual = new Individual {
_organism
};
_individual.AddMolecule(_protein);
sut = new RemoveMoleculeFromIndividualCommand(_protein, _individual, _context);
}
protected override void Context()
{
_context = A.Fake <IExecutionContext>();
var expressionProfile = DomainHelperForSpecs.CreateExpressionProfile <IndividualEnzyme>();
(_molecule, _) = expressionProfile;
_protein = _molecule.DowncastTo <IndividualProtein>();
_result = new QueryExpressionResults(_expressionResults);
_simulationSubject = A.Fake <ISimulationSubject>();
sut = new EditIndividualMoleculeExpressionInSimulationSubjectFromQueryCommand(_molecule, _result, _simulationSubject);
A.CallTo(() => _simulationSubject.AllExpressionParametersFor(_molecule)).Returns(_allExpressionParameters);
}
protected override void Context()
{
_view = A.Fake <IExpressionLocalizationView>();
_moleculeExpressionTask = A.Fake <IMoleculeExpressionTask <Individual> >();
_dialogCreator = A.Fake <IDialogCreator>();
sut = new ExpressionLocalizationPresenter <Individual>(_view, _moleculeExpressionTask, _dialogCreator);
_commandCollector = new PKSimMacroCommand();
sut.InitializeWith(_commandCollector);
_molecule = new IndividualEnzyme();
_individual = new Individual();
sut.Edit(_molecule, _individual);
sut.LocalizationChanged += (o, e) => _notified = true;
_command = A.Fake <IPKSimCommand>();
A.CallTo(_moleculeExpressionTask).WithReturnType <ICommand>().Returns(_command);
}
private void updateLocalizationForProtein(IndividualProtein protein, IExecutionContext context)
{
//special case for blood cells and vascular endothelium. if the value is set > 0. we need to turn on some locations programatically
var bloodCells = _queryExpressionResults.ExpressionResultFor(CoreConstants.Compartment.BLOOD_CELLS);
if (bloodCells?.RelativeExpression > 0 && !protein.InBloodCells)
{
Add(new SetExpressionLocalizationCommand(protein, Localization.BloodCellsIntracellular, _simulationSubject, context).Run(context));
}
var vascularEndothelium = _queryExpressionResults.ExpressionResultFor(CoreConstants.Compartment.VASCULAR_ENDOTHELIUM);
if (vascularEndothelium?.RelativeExpression > 0 && !protein.InVascularEndothelium)
{
Add(new SetExpressionLocalizationCommand(protein, Localization.VascEndosome, _simulationSubject, context).Run(context));
}
}
public SetExpressionLocalizationInProteinCommand(
IndividualProtein protein,
Localization localization,
ISimulationSubject simulationSubject,
IExecutionContext context, bool setAsFlag = true)
{
_protein = protein;
_simulationSubject = simulationSubject;
BuildingBlockId = context.BuildingBlockIdContaining(protein);
_newLocalization = setAsFlag ? _protein.Localization ^ localization : localization;
ObjectType = PKSimConstants.ObjectTypes.Protein;
CommandType = PKSimConstants.Command.CommandTypeEdit;
_proteinId = _protein.Id;
context.UpdateBuildingBlockPropertiesInCommand(this, context.BuildingBlockContaining(protein));
//This command is not visible. Only required to ensure that we can undo
Visible = false;
}
protected override void Context()
{
sut = new ExpressionContainersRetriever();
var objectPathFactory = new ObjectPathFactoryForSpecs();
var entityPathResolver = new EntityPathResolverForSpecs();
_liver.Add(_intLiver);
_liver.Add(_cellLiver);
_liver.Add(_plsLiver);
_liver.Add(_bcLiver);
_liver.Add(_endoLiver);
_kidney.Add(_intKidney);
_kidney.Add(_cellKidney);
_kidney.Add(_plsKidney);
_kidney.Add(_bcKidney);
_kidney.Add(_endoKidney);
_lumen.Add(_duodenum);
_organism.Add(_liver);
_organism.Add(_kidney);
_organism.Add(_lumen);
_protein = new IndividualEnzyme();
_protein.Add(new MoleculeExpressionContainer {
OrganPath = objectPathFactory.CreateObjectPathFrom(CoreConstants.Compartment.BloodCells)
}.WithName(CoreConstants.Compartment.BloodCells));
_protein.Add(new MoleculeExpressionContainer {
OrganPath = objectPathFactory.CreateObjectPathFrom(CoreConstants.Compartment.Plasma)
}.WithName(CoreConstants.Compartment.Plasma));
_protein.Add(new MoleculeExpressionContainer {
OrganPath = objectPathFactory.CreateObjectPathFrom(CoreConstants.Compartment.VascularEndothelium)
}.WithName(CoreConstants.Compartment.VascularEndothelium));
_protein.Add(new MoleculeExpressionContainer {
OrganPath = entityPathResolver.ObjectPathFor(_liver)
}.WithName(CoreConstants.Organ.Liver));
_protein.Add(new MoleculeExpressionContainer {
OrganPath = entityPathResolver.ObjectPathFor(_kidney)
}.WithName(CoreConstants.Organ.Kidney));
_protein.Add(new MoleculeExpressionContainer {
OrganPath = entityPathResolver.ObjectPathFor(_lumen), GroupName = CoreConstants.Groups.GI_LUMEN, ContainerName = _duodenum.Name
}.WithName(CoreConstants.ContainerName.LumenSegmentNameFor("Duodenum")));
}
private void setParameterValuesForInterstitial(IndividualProtein protein, IContainer expressionContainer)
{
var relExpNormPath = relExpNormPathFor(protein, expressionContainer);
var relExpPath = relExpPathFor(protein, expressionContainer);
var relExpOut = relExpOutPathFor(protein, expressionContainer);
setParameterValuesForStandardContainer(protein, expressionContainer);
//out path now depends on protein configuration
switch (protein.TissueLocation)
{
case TissueLocation.ExtracellularMembrane:
if (protein.MembraneLocation == MembraneLocation.Apical)
{
trySetFormula(relExpOut, CoreConstants.Rate.RelExpInterstialMembraneExtracellularApical);
}
else
{
trySetFormula(relExpOut, CoreConstants.Rate.RelExpInterstialMembraneExtracellularBasolateral);
}
break;
case TissueLocation.Intracellular:
if (protein.IntracellularVascularEndoLocation == IntracellularVascularEndoLocation.Interstitial)
{
//reset value in interstitial that was set before
trySetFormula(relExpNormPath, zeroFormula());
trySetFormula(relExpPath, zeroFormula());
trySetFormula(relExpOut, CoreConstants.Rate.RelExpInterstialIntraVascEndoIsInterstitial);
}
break;
case TissueLocation.Interstitial:
trySetFormula(relExpOut, CoreConstants.Rate.RelExpInterstialForInterstitial);
break;
default:
throw new ArgumentOutOfRangeException();
}
}
private void setParameterValuesForPlasma(IndividualProtein protein, IContainer expressionContainer)
{
trySetFormula(relExpNormPathFor(protein, expressionContainer), CoreConstants.Rate.RelExpPlasmaNormGlobal);
trySetFormula(relExpPathFor(protein, expressionContainer), CoreConstants.Rate.RelExpPlasmaGlobal);
var relExpOut = relExpOutPathFor(protein, expressionContainer);
//out path now depends on protein configuration
switch (protein.TissueLocation)
{
case TissueLocation.ExtracellularMembrane:
if (protein.MembraneLocation == MembraneLocation.Apical)
{
if (expressionContainer.ParentContainer.IsBloodOrgan())
{
trySetFormula(relExpOut, CoreConstants.Rate.RelExpPlasmaMembraneExtracellularApicalBloodOrgan);
}
else
{
trySetFormula(relExpOut, CoreConstants.Rate.RelExpPlasmaMembraneExtracellularApicalTissueOrgan);
}
}
else
{
trySetFormula(relExpOut, CoreConstants.Rate.RelExpPlasmaMembraneExtracellularBasolateral);
}
break;
case TissueLocation.Intracellular:
case TissueLocation.Interstitial:
trySetFormula(relExpOut, CoreConstants.Rate.RelExpOutFromNorm);
break;
default:
throw new ArgumentOutOfRangeException();
}
}
public ICommand SetIntracellularVascularEndoLocation(IndividualProtein protein, IntracellularVascularEndoLocation vascularEndoLocation)
{
return(new SetProteinIntracellularVascularEndoLocationCommand(protein, vascularEndoLocation, _executionContext).Run(_executionContext));
}
public ICommand SetMembraneLocationFor(IndividualProtein protein, MembraneLocation membraneLocation)
{
return(new SetProteinMembraneLocationCommand(protein, membraneLocation, _executionContext).Run(_executionContext));
}
public ICommand SetTissueLocationFor(IndividualProtein protein, TissueLocation tissueLocation)
{
return(new SetTissueLocationCommand(protein, tissueLocation, _executionContext).Run(_executionContext));
}
private void addContainerExpression(ProteinExpressionDTO proteinExpressionDTO, IndividualProtein protein, MoleculeExpressionContainer moleculeExpressionContainer)
{
var expressionDTO = new ExpressionContainerDTO {
MoleculeName = protein.Name, ContainerName = moleculeExpressionContainer.Name
};
_expressionContainerDTOUpdater.UpdateProperties(expressionDTO, moleculeExpressionContainer);
proteinExpressionDTO.AddProteinExpression(expressionDTO);
}
private void setParameterValuesForBloodCells(IndividualProtein protein, IContainer expressionContainer)
{
trySetFormula(relExpNormPathFor(protein, expressionContainer), CoreConstants.Rate.RelExpBloodCellsNormGlobal);
trySetFormula(relExpPathFor(protein, expressionContainer), CoreConstants.Rate.RelExpBloodCellsGlobal);
trySetFormula(relExpOutPathFor(protein, expressionContainer), CoreConstants.Rate.RelExpOutFromNorm);
}
private void setParameterValuesForEndosome(IndividualProtein protein, IContainer expressionContainer)
{
trySetFormula(relExpNormPathFor(protein, expressionContainer), CoreConstants.Rate.RelExpVascEndoNormGlobal);
trySetFormula(relExpPathFor(protein, expressionContainer), CoreConstants.Rate.RelExpVascEndoGlobal);
trySetFormula(relExpOutPathFor(protein, expressionContainer), CoreConstants.Rate.RelExpEndosomal);
}
