This open source Systems Pharmacology project makes formerly commercial software tools PK-Sim® and MoBi® available as freeware under the GPLv2 License. All source code is public.
Latest suite release can be found here: http://setup.open-systems-pharmacology.org
We invite everyone in the field of Systems Pharmacology, be it in academia, industry or regulatory bodies, to use the platform. Active participation of computer and modeling & simulation scientists in the further development of the modeling & simulation platform, the incorporated systems models, processes for their qualification and application etc. is encouraged and highly welcome! Please follow the community’s activities in this GitHub project.
Visit and subscribe to the Open Systems Pharmacology Project Forum to stay up-to-date with the community and receive updates on new software releases, models as well as discussions.
The Open Systems Pharmacology Suite contains different software tools and has been designed using a modular concept to allow efficient multi-scale modeling and simulation. The overall platform with its various software tools is implemented in a modular way as will be explained in more detail below. The central software tools PK-Sim® and MoBi® make use of building blocks as introduced here. While PK-Sim® is based on a whole-body concept, the focus of its counterpart, MoBi®, is at the molecular level. However, both tools extend to additional physiological scales as illustrated.
PK-Sim® is a comprehensive software tool for whole-body physiologically based pharmacokinetic modeling. It enables rapid access to all relevant anatomical and physiological parameters for humans and the most common laboratory animals (mouse, rat, minipig, dog, monkey, beagle and rabbit) that are contained in the integrated database. Moreover, access to different PBPK calculation methods to allow for fast and efficient model building and parameterization is provided. Relevant generic passive processes, such as distribution through blood flow, as well as specific active processes such as metabolization by a certain enzyme are automatically taken into account by PK-Sim®. Like most PBPK modeling tools, PK-Sim® is designed for use by non-modeling experts and only allows for minor structural model modifications. Unlike most PBPK modeling tools though, PK-Sim® offers different model structures to choose from, e.g. to account for important differences between small and large molecules. More importantly, PK-Sim® is fully compatible with the expert modeling software tool MoBi®, thereby allowing full access to all model details including the option for extensive model modifications and extensions. This way, customized systems pharmacology models may be set up to deal with the challenges of modern drug research and development.
PK-Sim® uses building blocks that are grouped into Individuals, Populations, Expression Profiles, Compounds, Formulations, Administration Protocols, Events, Observers and Observed Data. Building blocks from these groups are combined to produce a model. The advantage of building blocks is that they can be reused. For example, after having established a model for a drug after single dose intravenous administration to an animal species, just substitute the individual by a suitably parameterized virtual human population and obtain a first in man simulation model. Further substitute the formulation, to obtain a controlled-release per oral simulation model, substitute the protocol to obtain a multiple dose simulation model, or substitute the compound to obtain a simulation model for another drug.
MoBi® is a systems biology software tool for multiscale physiological modeling and simulation. Within the restrictions of ordinary differential equations, almost any kind of (biological) model can be imported or set up from scratch. Examples include in vitro dissolution testing, biochemical reaction networks, compartmental disease progression models, or PBPK models. However, the de novo development of a PBPK model, for example, is very cumbersome such that the preferred procedure is to import it from PK-Sim®. Importantly, MoBi® also allows for the combination of the described examples and thereby is a very powerful tool for modeling and simulation of multiscale physiological systems covering molecular details on the one hand and whole-body architecture on the other hand.
De novo model establishment and simulation is supported by graphical tools and building blocks to support expert users. MoBi® uses building blocks that are grouped into Molecules, Reactions, Spatial Structures, Passive Transports, Observers, Events, Molecule Start Values, Parameter Start Values and Observed Data. Building blocks out of the above-mentioned groups can be combined to generate models. The advantage of building blocks is that they can be reused. Examples:
- a different set of starting values may define a new scenario, situation, or individual.
- refine a Reaction(s) network and update it in all tissues where it should be considered.
The qualification framework enables an automated validation of various scenarios (use-cases) supported by the OSP platform. This technical framework is used, for example, to release, in full confidence, a new version of the OSP Suite by verifying automatically that an ever-growing list of scenarios is performing as expected. The qualification framework is described in detail here.
Validation and automation tools include for example:
- Installation Validator: enables "1-Click" validation of the OSP Suite installation on a target computer. The validation is performed by execution of the predefined set of simulation scenarios and comparison of the simulated results with the (validated) reference values.
- Command Line Interface (CLI): allows batch processing of multiple projects in PK-Sim and is described in Command Line Interface - CLI.
The OSP software suite provides a set of packages for the R computing environment that allow scripted workflows with the models developed in PK-Sim® and MoBi®.
- ospsuite package provides the functionality of loading, manipulating, and simulating the simulations created in PK-Sim® and MoBi®. It also offers extended workflows such as parameter sensitivity or PK-parameter calculation. The package is described in detail in R documentation.
- tlf package offers a set of functions and methods for creating standardized reporting Tables, Listings, and Figures.
- ospsuite.reportingengine for automated generation of model reports.
- ospsuite.utils provides a collection of utility functions useful for R packages in the OSP ecosystem.
- ospsuite.parameteridentification provides the functionality of performing parameter identification (i.e., fitting the model to observed data) with simulations. The package is currently under development and everyone is encouraged to contribute.
OSP Qualification Framework and R packages are not included in the main OSP Suite setup and must be installed separately. Installation instructions are provided in the documentation of the tools or on the GitHub download site.
Models created in PK-Sim® or MoBi® can be exported in PK Modeling Language (*.pkml) format and shared between the OSP tools. Internally, PKML file format is nothing more than XML with a predefined structure.
Apart from the communication and exchange via R, PK-Sim® and MoBi® have import and export functions for MS Excel®, CSV and NONMEM® that allow for the import of experimental data or the export of simulation results, for example. MoBi® has SBML import functionalities. PK-Sim can also import and export project snapshots in JSON format (s. Exporting Project to Snapshot for details).
Installing the Open Systems Pharmacology Suite with PK-Sim® and MoBi® involves following steps:
- Download the Software Setup and install it on your computer. Make sure you are provided with administrator rights; these are required!
- Download PK-Sim Gene Expression Database(s) and copy to a folder accessible for all users.
- Configure PK-Sim Gene Expression Database(s) (for details view the Open Systems Pharmacology Suite manual)
Windows 7®, Windows 8®, Windows 10®, Windows 11®, Windows Server 2008 R2®, Windows Server 2012 R2®, Windows Server 2016®, Windows Server 2019®
All Windows operating systems listed above and Linux (precompiled packages available for Ubuntu 18.04 and CentOS 7)
Minimum: 1 GHz (the faster the better!)
Minimum: 2 GB RAM (3+ GB recommended)
Minimum: 2 GB
- R® (versions 3.x / 4.x - 64bit)
Everyone interacting in the Open Systems Pharmacology community (codebases, issue trackers, chat rooms, mailing lists, etc.) is expected to follow the Open Systems Pharmacology code of conduct.
We encourage contribution to the Open Systems Pharmacology community. Before getting started, please read the contribution guidelines. If you are contributing code, please be familiar with the coding standards.
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