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2113 property molecule psv #2117

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merged 3 commits into from
Mar 17, 2022
Merged

2113 property molecule psv #2117

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86e097d
Ensures that the formula is using parent and not MOLECULE for #2113
msevestre Mar 15, 2022
b9e31d0
Fixes #2113 property molecule psv
msevestre Mar 15, 2022
58d3f4f
Fixes #2113 remove unecessary entries in PSV Coming from valid formula
msevestre Mar 15, 2022
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31 changes: 4 additions & 27 deletions src/Db/Diff/PKSimDB_diff.txt
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Original file line number Diff line number Diff line change
@@ -1,27 +1,4 @@
UPDATE tab_calculation_method_rates SET formula='f_int > 0 ? RC * rel_exp_org * f_exp_org_basolateral * 1 / f_int : 0' WHERE calculation_method='ExpressionParameters' AND formula_rate='InitialConcentrationInterstitial_Transporter';
CREATE TABLE tab_container_parameter_descriptor_conditions (container_id bigint NOT NULL, container_type text NOT NULL, container_name text NOT NULL, parameter_name text NOT NULL, tag text NOT NULL CONSTRAINT tab_container_parameter_descriptor_conditions_tab_tags_tag_fk REFERENCES tab_tags ON UPDATE CASCADE ON DELETE CASCADE, condition text NOT NULL CONSTRAINT tab_container_parameter_descriptor_conditions_tab_criteria_conditions_condition_fk REFERENCES tab_criteria_conditions ON UPDATE CASCADE ON DELETE CASCADE, operator TEXT DEFAULT "And" NOT NULL, CONSTRAINT tab_container_parameter_descriptor_conditions_tab_container_parameters_container_id_container_type_container_name_parameter_name_fk FOREIGN KEY (container_id, container_type, container_name, parameter_name) REFERENCES tab_container_parameters ON UPDATE CASCADE ON DELETE CASCADE);
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(1,5015,'GENERAL','PROTEIN','Fraction expressed interstitial','Interstitial','Has','And');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(2,5015,'GENERAL','PROTEIN','Fraction expressed intracellular','Intracellular','Has','And');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(3,5941,'GENERAL','TRANSPORTER','Fraction expressed at blood brain barrier','Brain','InContainer','And');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(4,5941,'GENERAL','TRANSPORTER','Fraction expressed at blood brain barrier','Plasma','Has','And');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(5,5941,'GENERAL','TRANSPORTER','Fraction expressed brain tissue','Brain','InContainer','And');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(6,5941,'GENERAL','TRANSPORTER','Fraction expressed brain tissue','Interstitial','Has','And');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(7,5015,'GENERAL','PROTEIN','Relative expression','Intracellular','Has','Or');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(8,5015,'GENERAL','PROTEIN','Relative expression','LumenSegment','Has','Or');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(9,5941,'GENERAL','TRANSPORTER','Relative expression','Intracellular','Has','Or');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(10,5941,'GENERAL','TRANSPORTER','Relative expression','LumenSegment','Has','Or');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(11,5941,'GENERAL','TRANSPORTER','Fraction expressed basolateral','Interstitial','Has','And');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(12,5941,'GENERAL','TRANSPORTER','Fraction expressed apical','Intracellular','Has','And');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(13,5941,'GENERAL','TRANSPORTER','Fraction expressed basolateral','Brain','NotInContainer','And');
INSERT INTO tab_container_parameter_descriptor_conditions(rowid,container_id,container_type,container_name,parameter_name,tag,condition,operator) VALUES(14,5941,'GENERAL','TRANSPORTER','Fraction expressed apical','Brain','NotInContainer','And');
UPDATE tab_container_parameter_rates SET formula_rate='PARAM_f_exp_interstitial' WHERE container_id=5015 AND container_type='GENERAL' AND container_name='PROTEIN' AND parameter_name='Fraction expressed interstitial' AND calculation_method='ExpressionParameters';
UPDATE tab_container_parameter_rates SET formula_rate='One_Rate' WHERE container_id=5015 AND container_type='GENERAL' AND container_name='PROTEIN' AND parameter_name='Fraction expressed intracellular' AND calculation_method='ExpressionParameters';
UPDATE tab_container_parameter_rates SET formula_rate='Zero_Rate' WHERE container_id=5015 AND container_type='GENERAL' AND container_name='PROTEIN' AND parameter_name='Relative expression' AND calculation_method='ExpressionParameters';
UPDATE tab_container_parameter_rates SET formula_rate='Zero_Rate' WHERE container_id=5941 AND container_type='GENERAL' AND container_name='TRANSPORTER' AND parameter_name='Fraction expressed apical' AND calculation_method='ExpressionParameters';
UPDATE tab_container_parameter_rates SET formula_rate='One_Rate' WHERE container_id=5941 AND container_type='GENERAL' AND container_name='TRANSPORTER' AND parameter_name='Fraction expressed at blood brain barrier' AND calculation_method='ExpressionParameters';
UPDATE tab_container_parameter_rates SET formula_rate='PARAM_f_exp_basolateral' WHERE container_id=5941 AND container_type='GENERAL' AND container_name='TRANSPORTER' AND parameter_name='Fraction expressed basolateral' AND calculation_method='ExpressionParameters';
UPDATE tab_container_parameter_rates SET formula_rate='PARAM_f_exp_brn_tissue' WHERE container_id=5941 AND container_type='GENERAL' AND container_name='TRANSPORTER' AND parameter_name='Fraction expressed brain tissue' AND calculation_method='ExpressionParameters';
UPDATE tab_container_parameter_rates SET formula_rate='Zero_Rate' WHERE container_id=5941 AND container_type='GENERAL' AND container_name='TRANSPORTER' AND parameter_name='Relative expression' AND calculation_method='ExpressionParameters';
UPDATE tab_rate_generic_parameters SET alias='f_exp_org_basolateral' WHERE calculation_method='ExpressionParameters' AND formula_rate='InitialConcentrationInterstitial_Transporter' AND path_id=139 AND parameter_name='Fraction expressed basolateral';
INSERT INTO tab_rate_generic_parameters(calculation_method,formula_rate,path_id,parameter_name,alias) VALUES('ExpressionParameters','PARAM_f_exp_bc_membrane',139,'Fraction expressed in blood cells','f_exp_bc_cell');
DELETE FROM tab_rate_generic_parameters WHERE calculation_method='ExpressionParameters' AND formula_rate='PARAM_f_exp_bc_membrane' AND path_id=240 AND parameter_name='Fraction expressed in blood cells';
INSERT INTO tab_rate_generic_parameters(calculation_method,formula_rate,path_id,parameter_name,alias) VALUES('ExpressionParameters','PARAM_f_exp_vasc_tissue_side',139,'Fraction expressed in endosomes','f_exp_vasend_endosomes');
INSERT INTO tab_rate_generic_parameters(calculation_method,formula_rate,path_id,parameter_name,alias) VALUES('ExpressionParameters','PARAM_f_exp_vasc_tissue_side',139,'Fraction expressed on plasma-side membrane of vascular endothelium','f_exp_vasend_plasma');
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.. instead of MOLECULE

DELETE FROM tab_rate_generic_parameters WHERE calculation_method='ExpressionParameters' AND formula_rate='PARAM_f_exp_vasc_tissue_side' AND path_id=240 AND parameter_name='Fraction expressed in endosomes';
DELETE FROM tab_rate_generic_parameters WHERE calculation_method='ExpressionParameters' AND formula_rate='PARAM_f_exp_vasc_tissue_side' AND path_id=240 AND parameter_name='Fraction expressed on plasma-side membrane of vascular endothelium';
4 changes: 2 additions & 2 deletions src/Db/Dump/PKSimDB_dump.txt
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Expand Up @@ -91552,8 +91552,8 @@ INSERT INTO tab_rate_generic_parameters VALUES('ExpressionParameters','InitialCo
INSERT INTO tab_rate_generic_parameters VALUES('ExpressionParameters','InitialConcentrationEndosome',240,'Relative expression in vascular endothelium','rel_exp_vasend');
INSERT INTO tab_rate_generic_parameters VALUES('ExpressionParameters','InitialConcentrationEndosome',240,'Fraction expressed in endosomes','f_exp_vasend_endosomes');
INSERT INTO tab_rate_generic_parameters VALUES('ExpressionParameters','PARAM_f_exp_bc_membrane',139,'Fraction expressed in blood cells','f_exp_bc_cell');
INSERT INTO tab_rate_generic_parameters VALUES('ExpressionParameters','PARAM_f_exp_vasc_tissue_side',240,'Fraction expressed on plasma-side membrane of vascular endothelium','f_exp_vasend_plasma');
INSERT INTO tab_rate_generic_parameters VALUES('ExpressionParameters','PARAM_f_exp_vasc_tissue_side',240,'Fraction expressed in endosomes','f_exp_vasend_endosomes');
INSERT INTO tab_rate_generic_parameters VALUES('ExpressionParameters','PARAM_f_exp_vasc_tissue_side',139,'Fraction expressed on plasma-side membrane of vascular endothelium','f_exp_vasend_plasma');
INSERT INTO tab_rate_generic_parameters VALUES('ExpressionParameters','PARAM_f_exp_vasc_tissue_side',139,'Fraction expressed in endosomes','f_exp_vasend_endosomes');
INSERT INTO tab_rate_generic_parameters VALUES('ExpressionParameters','InitialConcentrationLumen',240,'Reference concentration','RC');
INSERT INTO tab_rate_generic_parameters VALUES('ExpressionParameters','InitialConcentrationLumen',139,'Relative expression','rel_exp_org');
INSERT INTO tab_rate_generic_parameters VALUES('ExpressionParameters','PARAM_f_exp_interstitial',4902,'Fraction expressed intracellular','f_exp_org_cell');
Expand Down
Binary file modified src/Db/PKSimDB.sqlite
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20 changes: 15 additions & 5 deletions src/PKSim.Core/Services/PKSimParameterStartValuesCreator.cs
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Original file line number Diff line number Diff line change
@@ -1,10 +1,11 @@
using System;
using System.Diagnostics;
using OSPSuite.Core.Domain;
using OSPSuite.Core.Domain.Builder;
using OSPSuite.Core.Domain.Formulas;
using OSPSuite.Core.Domain.Services;
using OSPSuite.Utility.Extensions;
using PKSim.Core.Model;
using PKSim.Core.Model.Extensions;
using static PKSim.Core.CoreConstants.CalculationMethod;
using IFormulaFactory = PKSim.Core.Model.IFormulaFactory;

Expand Down Expand Up @@ -78,9 +79,9 @@ private bool isChangedSimulationParameter(IParameter parameter)

private void updateMoleculeParametersValues(IndividualMolecule molecule, Individual individual, Simulation simulation)
{
var allProteinParameters = individual.AllMoleculeParametersFor(molecule);
var allMoleculeParameters = individual.AllMoleculeParametersFor(molecule);
var modelConfiguration = simulation.ModelConfiguration;
allProteinParameters.Each(p => setParameter(p, modelConfiguration.ModelName == CoreConstants.Model.FOUR_COMP));
allMoleculeParameters.Each(p => setParameter(p, modelConfiguration.ModelName == CoreConstants.Model.FOUR_COMP));
}

private void setParameter(IParameter parameter, bool isSmallMolecule)
Expand All @@ -89,13 +90,16 @@ private void setParameter(IParameter parameter, bool isSmallMolecule)
if (parameter.HasAncestorNamed(CoreConstants.Compartment.ENDOSOME) && isSmallMolecule)
return;

var parameterStartValue = getOrCreateStartValueFor(parameter);
//We do not generate value for this parameter by default. Exit
var parameterStartValue = getStartValueFor(parameter);
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We were adding entries for formula that are the same everywhere. Not generated by default in Core and it should not be added here either

if (parameterStartValue == null)
return;

if (parameter.Formula.IsExplicit())
{
var formula = _formulaFactory.RateFor(EXPRESSION_PARAMETERS, parameter.Formula.Name, _defaultStartValues.FormulaCache);
parameterStartValue.Formula = formula;
//There if a formula, make sure we use it. We set this flag to false to ensure that the formula will not be replaced with a constant formula
//There is a formula, make sure we use it. We set this flag to false to ensure that the formula will not be replaced with a constant formula
parameterStartValue.OverrideFormulaWithValue = false;
}

Expand Down Expand Up @@ -124,5 +128,11 @@ private IParameterStartValue getOrCreateStartValueFor(IParameter parameter)

return parameterStartValue;
}

private IParameterStartValue getStartValueFor(IParameter parameter)
{
var parameterPath = _entityPathResolver.ObjectPathFor(parameter);
return _defaultStartValues[parameterPath];
}
}
}
50 changes: 46 additions & 4 deletions tests/PKSim.Tests/IntegrationTests/PKSimParameterStartValuesCreatorSpecs.cs
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Original file line number Diff line number Diff line change
@@ -1,12 +1,16 @@
using System.Linq;
using OSPSuite.BDDHelper;
using OSPSuite.BDDHelper.Extensions;
using OSPSuite.Utility.Container;
using PKSim.Core.Services;
using PKSim.Infrastructure;
using OSPSuite.Core.Domain;
using OSPSuite.Core.Domain.Builder;
using OSPSuite.Core.Domain.Services;
using OSPSuite.Utility.Container;
using OSPSuite.Utility.Extensions;
using PKSim.Core.Model;
using PKSim.Core.Repositories;
using PKSim.Core.Services;
using PKSim.Infrastructure;
using PKSim.Infrastructure.ProjectConverter;

namespace PKSim.IntegrationTests
{
Expand All @@ -16,13 +20,39 @@ public class When_creating_a_parameter_start_value_building_block_for_a_simulati
private IEntityPathResolver _entityPathResolver;
private IObjectPath _parameterPath;
private IParameterStartValuesBuildingBlock _psv;
private Individual _individual;
private Compound _compound;
private Protocol _protocol;
private IndividualMolecule _enzyme;
private PartialProcess _metabolizationProcess;

public override void GlobalContext()
{
base.GlobalContext();
_buildConfigurationTask = IoC.Resolve<IBuildConfigurationTask>();
_entityPathResolver = IoC.Resolve<IEntityPathResolver>();
_simulation = DomainFactoryForSpecs.CreateDefaultSimulation();
var enzymeFactory = IoC.Resolve<IIndividualEnzymeFactory>();
var compoundProcessRepository = IoC.Resolve<ICompoundProcessRepository>();
var cloneManager = IoC.Resolve<ICloneManager>();
_compound = DomainFactoryForSpecs.CreateStandardCompound();
_individual = DomainFactoryForSpecs.CreateStandardIndividual();
_protocol = DomainFactoryForSpecs.CreateStandardIVBolusProtocol();
_enzyme = enzymeFactory.AddMoleculeTo(_individual, "CYP").DowncastTo<IndividualEnzyme>();
_metabolizationProcess = cloneManager.Clone(compoundProcessRepository
.ProcessByName(CoreConstantsForSpecs.Process.METABOLIZATION_SPECIFIC_FIRST_ORDER).DowncastTo<PartialProcess>());
_metabolizationProcess.Name = "My Partial Process";
_metabolizationProcess.Parameter(ConverterConstants.Parameters.CLspec).Value = 15;
_compound.AddProcess(_metabolizationProcess);

_simulation = DomainFactoryForSpecs.CreateModelLessSimulationWith(_individual, _compound, _protocol)
.DowncastTo<IndividualSimulation>();

_simulation.CompoundPropertiesList.First()
.Processes
.MetabolizationSelection
.AddPartialProcessSelection(new EnzymaticProcessSelection {ProcessName = _metabolizationProcess.Name, MoleculeName = _enzyme.Name});

DomainFactoryForSpecs.AddModelToSimulation(_simulation);
}

protected override void Because()
Expand All @@ -40,5 +70,17 @@ public void should_have_created_one_entry_for_the_changed_parameter_in_the_param
_psv[_parameterPath].ShouldNotBeNull();
_psv[_parameterPath].StartValue.ShouldBeEqualTo(10);
}

[Observation]
public void should_have_not_created_entries_for_property_parameter_of_the_enzyme()
{
var propertyParameters = _enzyme.AllParameters().Where(x => x.BuildMode == ParameterBuildMode.Property).ToList();
propertyParameters.Count.ShouldBeGreaterThan(0);
propertyParameters.Each(x =>
{
var parameterPath = _entityPathResolver.ObjectPathFor(x);
_psv[parameterPath].ShouldBeNull();
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do not add entries for property parameters (they should be excluded from psv)

});
}
}
}