Eissing, Thomas (1); Hobe, Martin (2); Ince, Ibrahim (1); Solodenko, Juri (1); Teutonico, Donato (1); Wendl, Thomas (1)
(1) Bayer Technology Services, Leverkusen, Germany, (2) Bayer Pharma, Wuppertal, Germany
The Bayer Computational Systems Biology Software Suite contains different software tools and has been designed using a modular concept to allow efficient multi-scale modeling and simulation [1]. The central software tools are PK-Sim® and MoBi®. While PK-Sim® is focused on whole-body physiologically-based pharmacokinetic (PBPK) modeling, MoBi® provides a flexible modeling environment fully compatible with PK-Sim®, for model customization or extension including pharmacodynamic or systems pharmacology modeling.
PK-Sim® is a comprehensive software tool for whole-body PBPK modeling of small and large molecules. It enables rapid access to all relevant anatomical, physiological, and molecular parameters for humans (age-dependent) and the most common laboratory animals (mouse, rat, minipig, dog, and monkey) that are contained in the integrated database. Moreover, easy access to different PBPK calculation methods and template building blocks allows for fast and efficient model building and parameterization. Relevant passive processes for drug absorption, distribution, metabolization and elimination (ADME) are automatically taken into account by PK-Sim®. Specific active processes such as metabolization by a certain enzyme, transport, or target binding can be conveniently added. For a large set of enzymes, transporters and other proteins, information on expression profiles and ontogeny information is contained in the software database. Different models can be combined to allow parent-metabolite or drug-drug interaction (DDI) modeling. In order to facilitate DDI modeling, a growing number of predefined templates for interaction partner substances are integrated. PK-Sim® is designed for use by non-modeling experts and only allows for minor structural model modifications.
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 biochemical reaction networks, compartmental disease progression models, or PBPK models, e.g. imported 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 multiple physiological scales and systems covering molecular details on the one hand and whole-body architecture on the other hand.
Apart from the two central graphical user interface (GUI) based software tools PK-Sim® and MoBi®, the software platform has a common core, import and export options including SBML and MS Excel®, as well as interfaces to the general computing environments MATLAB® and R. The toolboxes can be used to access and modify model parameters as well as to execute simulations and retrieve results. That way, the toolboxes can be used to script or code batch simulations, analysis tasks, visualizations or customized workflows to any complexity.
Optimization-based parameter identification or population simulations can be conveniently performed using integrated guided workflows. Tracking and roll-back features embedded in an automated project history, model comparison functions as well as a project journal for additional documentation allow for full traceability and transparency.
In summary, the software platform with its core components PK-Sim® and MoBi® provides a very flexible, comprehensive and transparent systems pharmacology modeling and simulation environment to challenge the consistency of data and allow for the integration and translation of knowledge to support modern drug research and development [2].
References:
[1] Eissing T. et al. A computational system biology software platform for the multiscale modeling and simulation: integrating whole-body physiology, disease biology, and molecular reaction networks. Front. Physio. (2011)
[2] www.systems-biology.com
Reference: PAGE 25 () Abstr 6072 [www.page-meeting.org/?abstract=6072]
Poster: Software Demonstration