Releases: Open-Systems-Pharmacology/Suite
Version 7.3.0
Downloads:
Release Notes for the Open Systems Pharmacology Suite 7.3.0
New Features
Project snapshots
PK-Sim includes various structural models together with relevant physiological and molecular databases for PBPK modeling of small and large molecules in different animal species and human populations. Relatively few inputs from the user are required to setup a complete PBPK model.
Model and/or data information stored in PK-Sim databases may change over time (e.g. in order to reflect the newest scientific findings) and be incorporated into newer PK-Sim versions. It may be of interest to the user to incorporate those changes into existing projects.
If an old project is simply opened with a new PK-Sim version, it will contain old model information, old anatomical/physiological data etc. and will not make use of improvements in the new version. The most appropriate way to incorporate the new knowledge would be to recreate, from scratch, the existing project in the new PK-Sim version.
To simplify this task, a concept of project snapshot is introduced in PK-Sim 7.3.
A project snapshot contains the minimal amount of information required to recreate the project from scratch. This includes the information on primary substance specific input parameters (e.g. molecular properties like molecular weight, lipophilicity, etc.) and required inputs (e.g. demographic characteristics) for defining the system parameters. Further, any changes made in the existing model, such as a change in liver volume, that is not a default value, will be stored in the snapshot and included in the new model once recreated from the snapshot.
Project snapshots are human-readable text files in JSON format
The following PK-Sim entities are currently supported by snapshots and will be recreated when a project is loaded from snapshot:
- All building block types (incl. observed data)
- Simulations
- Parameter Identifications
- Simulation comparisons
The following PK-Sim entities are not yet supported:
- Sensitivity Analyses
To export a project to snapshot, select File ➡️ Export to Snapshot
In this case PK-Sim will warn you. If exported anyway, the new project created from this snapshot may have some undesired deviations from the original projects, which must be corrected manually by the user.
To load a project from snapshot, select File ➡️ Load from Snapshot
Display of user defined parameters at a glance
In a simulation or building block, it might be of interest to see an overview of all parameters changed by the user.
For this, a new User Defined parameter node was introduced into PK-Sim and MoBi.
Value origin
To improve the documentation of parameter values used in PK-Sim and MoBi, the previous concept of Value description was extended to Value origin.
Value origin consists of 3 input fields:
- Source which can be one of {Database, Internet, Parameter Identification, Publication, Other, Unknown}
- Method which can be one of {Assumption, In Vitro, In Vivo, Manual Fit, Parameter Identification, Other, Unknown}
- Value description as free text
For parameters coming from the PK-Sim database, value origin is already filled.
ℹ️ Note that this is still a work in progress and value origin may be empty. ℹ️
In most cases, value origin must be manually adjusted by the user. Exceptions are:
- If the value is taken from Parameter Identification, value origin is automatically set to Parameter Identification
- If the value is manually changed by the user AND value origin comes from PK-Sim database, value origin automatically changes to Unknown
Intestinal solubility as table function of pH
Intestinal solubility can now be defined as a linear interpolation of measured (pH, Solubility) data pairs.
This can be done in the Compound building block of PK-Sim.
➡️ 
Command line interface (CLI)
CLI allows batch processing of multiple projects in PK-Sim.
To start PK-Sim CLI:
- Open windows command prompt (
cmd) and switch to PK-Sim installation folder. - Enter
PKSim.CLI --helpto show the list of available commads - Enter
PKSim.CLI <COMMAND_NAME> --help(e.g.PKSim.CLI snap --help) to show options for a command
Fixed issues and Improvements
PK-Sim and MoBi
- Proposal for unified look for PK-sim Mobi Individual/ expression/enzymes
- Optional display of “value description” and “value origin mode” in comparison
- In comparison display value and "value description" when overriding formula values
- Display Journal Page by double click on icon in Working Journal Diagram.
- Allow navigation to next and previous Journal Page from the Journal Page View
- Allow attachments of general files to a Journal Page
- When attaching a Parameter Identification to a Journal Page, the used simulations should be stored automatically
- Categorial Parameter Identification: AllTheSame Category not selected upon reload
PK-Sim
- Cloning a simulation destroys Persistable-property
- Parameter identification with multi start values does not show the random start values
- Import Population from File error
- Import pkml simulation back to PK-Sim: relative expressions are gone
- Protocol comparison does not work
- Renaming of Parameter Identification via PI tab context menu not possible
- Create Simmodel-XML from PKML in Matlab interface
- Wrong default value in "Scale Individual" function
- Allow multiselect when importing templates from template database
- When importing a csv file using tab as separator, a warning that the format is old is displayed which is not accurate
- Favorite parameters that should not be variable should be ignored in PI when creating a PI automatically
- Cannot create report of a population simulation
- Add protocol parameters to Population user defined variability
- Population simulation window: Name of statistics for display not properly shown after (de)selection
- Integrate new ontogeny data for AGP
- Hidden parameter with a value changed by the user (IsFixedValue = true) should be shown
- Adding new metabolization process - metabolite selection ignored
- Error - Administration protocol creation
MoBi
- Add an option to disable Circular Reference Check
- Changing parameter Volume of protein container in MoBi does not result in changed value being displayed in comparison view
- Chart editor - many data points and scrolling
- [PSV und MSV difference. Instead of Absent and present the value of the present value should be shown](htt...
Version 7.2.2
Downloads:
Release Notes for the Open Systems Pharmacology Suite 7.2.2
Fixed issues and Improvements
PK-Sim and MoBi
PK-Sim
Installation Validator
Version 7.2.1
Downloads:
Release Notes for the Open Systems Pharmacology Suite 7.2.1
New Features
Dosage per Body Surface Area
Body surface area-based dosing is now available in PK-Sim.
Body surface area can be calculated via. either Mosteller or Du Bois, Du Bois formula.
Pregnancy population
Based on a recent literature review on anatomical and physiological changes during pregnancy, a pregnancy population PBPK model was built (s. articles by André Dallmann et al.).
In the figure below, a summary of the pregnancy-induced changes in mean organ volumes (A) and maternal organ blood flows (B) from gestational week 2 to gestational week 40 where term pregnancy is reached are illustrated. The first 2 weeks preceding conception at the beginning of gestational week 3 are lightened.
Ready to use pregnancy models
11 recently published physiologically-based whole-body models for Pregnant Women are available in the Pregnancy-Models repository
Major improvement of chart performance
In some cases (e.g. adding large amount of observed data sets simultaneously) chart performance was not optimal. In the current version the overall chart performance was significantly increased.
Individuals within Populations
The population analysis plots were improved to:
- Identify individuals within a population analysis (e.g. individuals associated with the percentiles displayed)
- Extract specific individuals from a population for follow-up analyses
Example: identify individuals in a Box-Whisker plot of a population simulation
Example: extract individuals from a Box-Whisker plot in a population simulation
Example: extract individuals from a population building block
Parameter Identification: Fixed parameters
It is now possible to fix parameter values during parameter identification
Draft watermark support
Now it is possible to clearly identify preliminary version of plots when using "Copy to clipboard" action.
(Experimental) Portable versions of PK-Sim and MoBi
Starting with 7.2 release of the OSP Suite it is possible to use PK-Sim and MoBi as portable versions without installation. These portable versions can also be used parallel to another versions of the OSP Suite.
How to use portable versions
- Download and extract PK-Sim 7.2 portable and MoBi 7.2 portable
- Some additional windows components might be required (in the most cases those are already installed as part of windows update or with other applications):
- Microsoft .NET Framework 4.5.2
If you are not sure: just start PK-Sim portable or MoBi portable. If you become error messages: this component is not installed on your system. - Microsoft Visual C++ 2015 redistributable (x86)
If you are not sure: just start PK-Sim portable or MoBi portable and try to run any simulation. If you become error messages: this component is not installed on your system. - Also if you would like to use pdf reports in PK-Sim and MoBi (and you don't have any previous OSP Suite version installed): you must install Miktex
- In PK-Sim: go to Utilities => Options => Application and enter the path to the MoBi.exe
- In MoBi: go to Utilities => Options => Application and enter the path to the PK-Sim.exe
Fixed issues and Improvements
PK-Sim and MoBi
- Selected Parameters of Sensitivity Analysis are not shown in Alphabetical order
- Parameter identification: Maximum number of iterations = 0 does not behave as designed
- Graph editor can't remember µg/l as Unit for Y Axis
- Export to excel from the chart does not use the curve name
- Parameter Identification: Allow copying values from the results tab
- Unit conversion for Da is wrong
- Export Parameter Identification to MatLab creates outdated code
- "Time Profile" plots obtainable after "Parameter Identification" are missing lines
- Feedback User Training: Bug #1: PI match observed output data
PK-Sim
- Exception when optimizing relative expression and transferring to simulation
- Expression in zonated/unzonated livers
- Curve name does not contain simulation name after cloning
- Preview of PK Parameters looks strange in time profile analysis wizard
- Simulation comparison does not show differences in RHS formula of parameters
- It should not be possible to remove observed data that are used in a comparison
- Create Formulation: Plot bottom is hidden
- Population age limit
- Export units for population parameters
MoBi
- Load Container From Template does not work
- Exception when creating new table formula
- Cannot export ODE system
- Error pops up when deleting molecule in reaction building block
- SBML importing failure
- Diagram conversion from older version done each time
MoBi Toolbox for Matlab
MoBi Toolbox for R
Installation Validator
Version 7.2.0
Downloads:
Release Notes for the Open Systems Pharmacology Suite 7.2.0
New Features
Dosage per Body Surface Area
Body surface area-based dosing is now available in PK-Sim.
Body surface area can be calculated via. either Mosteller or Du Bois, Du Bois formula.
Pregnancy population
Based on a recent literature review on anatomical and physiological changes during pregnancy, a pregnancy population PBPK model was built (s. articles by André Dallmann et al.).
In the figure below, a summary of the pregnancy-induced changes in mean organ volumes (A) and maternal organ blood flows (B) from gestational week 2 to gestational week 40 where term pregnancy is reached are illustrated. The first 2 weeks preceding conception at the beginning of gestational week 3 are lightened.
Ready to use pregnancy models
11 recently published physiologically-based whole-body models for Pregnant Women are available in the Pregnancy-Models repository
Major improvement of chart performance
In some cases (e.g. adding large amount of observed data sets simultaneously) chart performance was not optimal. In the current version the overall chart performance was significantly increased.
Individuals within Populations
The population analysis plots were improved to:
- Identify individuals within a population analysis (e.g. individuals associated with the percentiles displayed)
- Extract specific individuals from a population for follow-up analyses
Example: identify individuals in a Box-Whisker plot of a population simulation
Example: extract individuals from a Box-Whisker plot in a population simulation
Example: extract individuals from a population building block
Parameter Identification: Fixed parameters
It is now possible to fix parameter values during parameter identification
Draft watermark support
Now it is possible to clearly identify preliminary version of plots when using "Copy to clipboard" action.
(Experimental) Portable versions of PK-Sim and MoBi
Starting with 7.2 release of the OSP Suite it is possible to use PK-Sim and MoBi as portable versions without installation. These portable versions can also be used parallel to another versions of the OSP Suite.
How to use portable versions
- Download and extract PK-Sim 7.2 portable and MoBi 7.2 portable
- Some additional windows components might be required (in the most cases those are already installed as part of windows update or with other applications):
- Microsoft .NET Framework 4.5.2
If you are not sure: just start PK-Sim portable or MoBi portable. If you become error messages: this component is not installed on your system. - Microsoft Visual C++ 2015 redistributable (x86)
If you are not sure: just start PK-Sim portable or MoBi portable and try to run any simulation. If you become error messages: this component is not installed on your system. - Also if you would like to use pdf reports in PK-Sim and MoBi (and you don't have any previous OSP Suite version installed): you must install Miktex
- In PK-Sim: go to Utilities => Options => Application and enter the path to the MoBi.exe
- In MoBi: go to Utilities => Options => Application and enter the path to the PK-Sim.exe
Fixed issues and Improvements
PK-Sim and MoBi
- Selected Parameters of Sensitivity Analysis are not shown in Alphabetical order
- Parameter identification: Maximum number of iterations = 0 does not behave as designed
- Graph editor can't remember µg/l as Unit for Y Axis
- Export to excel from the chart does not use the curve name
- Parameter Identification: Allow copying values from the results tab
- Unit conversion for Da is wrong
- Export Parameter Identification to MatLab creates outdated code
- "Time Profile" plots obtainable after "Parameter Identification" are missing lines
- Feedback User Training: Bug #1: PI match observed output data
PK-Sim
- Exception when optimizing relative expression and transferring to simulation
- Expression in zonated/unzonated livers
- Curve name does not contain simulation name after cloning
- Preview of PK Parameters looks strange in time profile analysis wizard
- Simulation comparison does not show differences in RHS formula of parameters
- It should not be possible to remove observed data that are used in a comparison
- Create Formulation: Plot bottom is hidden
- Population age limit
- Export units for population parameters
MoBi
- Load Container From Template does not work
- Exception when creating new table formula
- Cannot export ODE system
- Error pops up when deleting molecule in reaction building block
- SBML importing failure
- Diagram conversion from older version done each time
MoBi Toolbox for Matlab
MoBi Toolbox for R
Installation Validator
Version 7.1.0
Downloads:
Release Notes for the Open Systems Pharmacology Suite 7.1.0
New Features
Elderly ICRP Population
New elderly ICRP data integrated (based on the publication http://dx.doi.org/10.1007/s40262-016-0422-3).
Comprehensive, knowledge-driven database extension to encompass the full course of healthy aging from young adulthood through to the age of 100 years. The elderly PBPK platform combined with age-related information on pathway or target abundance changes can be applied to develop novel treatment strategies. Such a database allows a diversification of age- and/or disease-related physiological alterations.
Enhanced Protein Model
The current parameterization of the model replaces the generic protein PBPK model available in PK-Sim since version 4.2. The new parameterization includes the following changes:
- The lymph and fluid recirculation flow rates of the organs are re-fitted and are now proportional to the plasma flow and the lymph flow of the respective organs.
- The properties of the vascular endothelium of bone have now the standard values for continuous endothelium. This improves the distribution behavior for antibodies in humans.
- Drug uptake into the endosomal space occurs now only from plasma. Also, the drug-FcRn complex is recycled only to plasma. This prevents net extravasation via the endosome. With this parameterization, there is a clear separation for the mechanism of extravasation (described by the two-pore model) and endosomal clearance/FcRn mediated recycling.
- New literature values are used for the hydraulic conductivity of some organs.
A publication in a peer reviewed journals is in preparation.
The new parameterization affects the building blocks for individuals/populations and for compounds. Existing building blocks and simulations within projects created with version 7.0 or previous remain as they are, i.e. the old parameterization is kept.
Rabbit
A rabbit model was included that can be employed in preclinical development and applications in environmental risk assessments. The rabbit PBPK model was developed and evaluated with available literature data. Model predictions involve scenarios of both intravenous (i.v.) and oral (p.o.) administrations of small and large compounds.
A publication in a peer reviewed journals is in preparation.
New Installation Validator Tool
A validation of the Open Systems Pharmacology Suite installation is performed to ensure that the Suite works fully as intended when installed in the computing environment.
The key functionalities are tested through comparison of reference simulation outputs with locally calculated simulation outputs for a set of predefined test simulations.
The validation report will include:
- overall validation result (Valid/Invalid)
- validation result for every test simulation (Valid/Invalid)
- summary of the deviations for every Invalid simulation (numerical values and comparison plots)
- information about installed software versions and local computing environment
- selected comparison plots for every Valid simulation
Fixed issues and Improvements
PK-Sim and MoBi
- Parameter Identification: Export Parameter values and Error values after PI-run
- Parameter Identification: Excel export of results
- Parameter Identification: "Stop" only works with long delay
- Memory usage reduced
- Add selected observed data into the active plot of the active simulation
- Crash when starting observed data import and clicking cancel right away
- No close confirmation dialog after changing Parameter Identification settings
- Data import: "Dimensionless" is missing
- Error bars are shown even when the corresponding data set is un-checked
- Cannot start sensitivity analysis or parameter identification via F5 if any simulation is opened
- Parameter Identification returns wrong results in log scale if any observed data is 0 and removeLLOQMode=Never
- While Parameter Identification calculates Jacobian/Sensitivity, Visual Feedback is not update properly
PK-Sim
- NHANES population needs update
- Display total GFR
- PK-Analysis changes
- Ontogeny after Individual update
- Box whisker X-grouping throws exception
- GET Variability in Population is not set
- Simulation and corresponding confidence interval invisible after saving/reopening a model
- Strange behavior if brain influx transporter is built in PK-sim
- Wrong name for receptor occupancy output
- Grid lines visible by default even though they are unchecked in the axis properties
- Removing simulation referenced by unloaded Sensitivity Analysis crashes when the analysis is loaded
- Renaming simulation may not update Parameter Identification if it is not loaded
- Editing meta data/Renaming of Observed Data does not change some hidden name
- LLOQ wrongly used in Parameter Identification if observed data was imported in mass unit
- PK Analysis are only exported to pdf in default unit
- Removing output from population analysis should remove corresponding curves
- Recreating aging simulations produces changed PSV in the simulation
- Default mapping Inhibition/Induction
- Development of Simulation without formulation is possible and crashes
- Wrong path for association rate used in some FcRn reactions
- AUC_norm and Cmax_norm for multiple doses not calculated correctly
- Error after multiple Data imports
- Working Journal path should be saved as relative to project instead of absolute
- Working Journal tables appear to have different format rules when pasted vs. when inserted (as a new table)
- Chart X-Axis range wrong after setting Side margins enabled
- Copying images from Journal Page to PowerPoint does not work
- AUC_tDlast_to_inf instead of AUC_tlastD-1_tDlast should be used for AUC Ratio
- Name of the observed data building block not updated when renamed
- Parameter Identification parameter bounds not checked
- Updating Particles dissolution formulation from a Building Block does not work if particle size distribution was changed
- Population Simulation Time Profile figure automatically resets zoom after restart PK-SIM
- Add fu to two pores rate equation for the "TwoPoresTransportLink"
MoBi
Version 7.0.0
Downloads:
Release Notes for the Open Systems Pharmacology Suite 7.0.0
Software Suite
Open Systems Pharmacology Suite (formerly known as Systems Biology Software Suite) is now distributed under GNU GENERAL PUBLIC LICENSE v2 plus clarifying addendum.
PK-Sim and MoBi
Calculation of time profile confidence intervals as output of parameter identification. Three different types of confidence intervals are supported:
- Confidence Interval: Corresponds to the model error, which is based on the uncertainty of estimated parameters. This uncertainty is based on an estimation of the difference between the mean value of used observed data compared with the mean value of the (unknown) total data.
- Visual Predictive Check Interval: Corresponds to the uncertainty based on the data error. The data error is the standard deviation of the distribution of the used observed data.
- Prediction Interval: Corresponds to the combination of the model error and the data error. It shows how much future measured data are expected to differ from the model predictions.
Sensitivity of PK-Parameters (AUC, CMax, …) vs. simulation parameters.
Because PBPK models can be complex and contain numerous input parameters, it would be useful to know which input parameters have the most impact on the output curves. The Sensitivity Analysis tool provides an answer to this question.
For a chosen simulation, the relative impact of selected - or all - input parameters on the PK parameters of the output curves is calculated and displayed. In addition, the input parameters can be ranked by their impact on a certain PK parameter of an output. Results of Sensitivity Analysis can be shown as:
- Sensitivity table:
- Ranking of most sensitive simulation parameters. Most sensitive parameters comprise all parameters that contribute to 90% of total sensitivity.
Fixed issues and Improvements
PK-Sim and MoBi
- 46-7335 Graphical display of Parameter Identification results should match log/lin selection
- 47-8156 Default Visual Feedback Height little bit to small
- 46-7325 Only log plots in Parameter Identification
- 47-8190 Parameter Identification: Weights should all be >=0
- 47-8185 Covariance matrix and Correlation Matrix should only be calculated for residuals with weight >0
- 46-7339 Applying default templates to PI charts always hides the Simulation column in data browser
- 46-7332 Parameter Identification aborted - "Do you really want to import the identified parameters?" shows only "OK"
- 47-8196 NaN in observed data should be ignored in Parameter Identification
- 47-8173 Crash showing Covariance/Correlation matrix after removing identification parameters
- 47-8176 PI Analysis charts: After rerun of Parameter Identification Chart settings/options are reset to default
- 47-8312 PI Analysis charts: Concentration outputs not shown in mass units
PK-Sim
- 47-7496 Enable output of concentration/amount in feces
- 47-8227 Error exporting PK parameter table from comparison plot of individual simulations
- 47-8148 Population Simulation Time Profile figures sometimes show too many observed data sets
- 47-8079 Observed data "Amount in Urine/Feces" cannot be mapped to observers
- 47-6533 "Plasma protein scale factor" is not variable in a population
- 47-8199 “Export PK-Analysis” missing in ribbon for export of population simulation
- 47-8195 PI finishes but PK-Sim does not notice that project has changed when closing
- 47-8287 Specific binding reaction uses wrong concentration if fraction unbound defined in compound is <1
MoBi
- 46-7319 Using Ctrl/C on an empty parameter list crashes MoBi
- 46-7323 Re-creating (or deleting) simulation produces error in Parameter Identification
- 46-7328 Simulation Diagram is messed up after update from Building Block
- 46-7260 After Update of Building Block in Simulation from Building Blocks Symbols remain partly red
- 46-7333 Change of "GFR Fraction" in Simulation not committable to Passive Transports Building Block
MoBi Toolbox for Matlab
- 26-5517 Unicode problems in SaveSimulationToXML
- 26-5516 Error in getPKParametersForConcentration when calculating Vd or Vss for multiple individuals
- 26-5503 XML file is saved encrypted
- 47-8296 Ontogenies cannot be set in MoBi Toolbox for Matlab