CellDesigner 3.5: A Versatile Modeling Tool for Biochemical Networks

Understanding of the logic and dynamics of gene-regulatory and biochemical networks is a major challenge of systems biology. To facilitate this research topic, we have developed a modeling/simulating tool called CellDesigner. CellDesigner primarily has capabilities to visualize, model, and simulate gene-regulatory and biochemical networks. Two major characteristics embedded in CellDesigner boost its usability to create/import/export models: 1) solidly defined and comprehensive graphical representation (systems biology graphical notation) of network models and 2) systems biology markup language (SBML) as a model-describing basis, which function as intertool media to import/export SBML-based models. In addition, since its initial release in 2004, we have extended various capabilities of CellDesigner. For example, we integrated other systems biology workbench enabled simulation/analysis software packages. CellDesigner also supports simulation and parameter search, supported by integration with SBML ODE Solver, enabling users to simulate through our sophisticated graphical user interface. Users can also browse and modify existing models by referring to existing databases directly through CellDesigner. Those extended functions empower CellDesigner as not only a modeling/simulating tool but also an integrated analysis suite. CellDesigner is implemented in Java and thus supports various platforms (i.e., Windows, Linux, and MacOS X). CellDesigner is freely available via our Web site.

I. Introduction

Systems biology is characterized by synergistic integration of theory, computational modeling, and experiments [1]. Identification of the logic and dynamics of gene-regulatory and biochemical networks is a major challenge of systems biology. from the view of computational modeling, a model is used to understand the dynamics of biological phenomena. the model consists of molecules and reactions that represents gene regulatory and biochemical network (such as transcription, translation, protein–protein interaction, enzymatic reaction, etc.), and contains a mathematical equation for each reaction. So that the model contains mathematical equations inside, it would be possible to simulate the dynamics of the model and compare the simulation results with their experiments; even more, it would be possible to tune the parameters in the model to fit with the experimental results. This workflow is important to understand unknown function or structure of biological phenomena, so development of software infrastructure to support this workflow is essential for systems biology research. While the software infrastructure is one of the most crucial components in systems biology research, there has been almost no common infrastructure or standard to enable integration of computational resources. for example, researchers built their model with their specific application or inside their simulator as a source code so that it was difficult to port their model to be used on other applications. Since there was no gold-standard software for systems biology research, at that time, researchers had to use multiple applications to solve their problem. They had to switch their software to run simulations, analyze the model, and fit parameters with their experimental results. To solve this problem, the Systems Biology Markup Language ¹

http://www.sbml.org.

(SBML) [2], [3] and the Systems Biology Workbench ²

http://sys-bio.org.

(SBW) have been developed [4]. SBML is an open, Extensible Markup Language (XML)-based format for representing biochemical reaction networks, which enables researchers to share their model between different software applications, while SBW is a modular, broker-based message-passing framework for simplified intercommunication between applications. Rapid acceptance of this standard is proved by the fact that more than 110 simulation and analysis software packages already support SBML or are in the process of supporting the standard.