The epidermal growth factor receptor (EGFR) signaling pathway is one of the most important pathways that regulate growth, survival, proliferation, and differentiation in mammalian cells. Reflecting this importance, it is one of the best‐investigated signaling systems, both experimentally and computationally, and several computational models have been developed for dynamic analysis. A map of molecular interactions of the EGFR signaling system is a valuable resource for research in this area. In this paper, we present a comprehensive pathway map of EGFR signaling and other related pathways. The map reveals that the overall architecture of the pathway is a bow‐tie (or hourglass) structure with several feedback loops. The map is created using CellDesigner software that enables us to graphically represent interactions using a well‐defined and consistent graphical notation, and to store it in Systems Biology Markup Language (SBML). Mol Syst Biol. 1: 2005.0010

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.

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction‐based models and packages that extend the core with features suited to other model types including constraint‐based models, reaction‐diffusion models, logical network models, and rule‐based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single‐cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution.