Drug Discovery Today  Volume 15, Numbers 9/10  May 2010 REVIEWS Biochemical modeling with Systems Biology Graphical Notation Andreas Jansson 1,2 and Mats Jirstrand 1 1 Fraunhofer-Chalmers Centre, Chalmers Science Park, 412 88 Go ¨ teborg, Sweden 2 Infofusion, Systems Biology Research Centre, University of Sko ¨vde, Box 408, Sko ¨ vde, Sweden The Systems Biology Graphical Notation (SBGN) is an emerging standard for graphical notation developed by an international systems biology community. Standardized graphical notation is crucial for efficient and accurate communication of biological knowledge between researchers with various backgrounds in the expanding field of systems biology. Here, we highlight SBGN from a practical point of view and describe how the user can build and simulate SBGN models from a simple drag-and-drop graphical user interface in PathwayLab. Introduction Biochemical reaction networks or pathways have been used for decades in biology and medicine to graphically describe cellular processes. The aim of these maps ranges from sketches of quali- tative findings to very accurate descriptions of molecular mechan- isms; hence, the amount of effort necessary to transform these graphical formalisms to mathematical models that can be vali- dated by experimental data varies a lot. Recent advances in experi- mental techniques and the increasing amount of data have triggered a shift of focus in many biological fields from an entity-oriented view to a systems approach (i.e. from the study of parts in isolation to the study of how they interact and their functional roles). Mathematical models are indispensable tools in this work, and there is a need for software tools that support mathematical modeling, computational analysis, and documen- tation. The scientific area known as ‘systems biology’ has drawn increasing attention from the systems and control community, which is natural because the subject applies systems and control methodologies and techniques to biological problems. Systems biology makes complex systems understandable by combining experimental data with a theoretical approach that enables com- puter simulations [1–3]. Such computer simulations can be done in many different types of software packages, and the Systems Biology Markup Language (SBML) [4] has been a crucial step in systems biology to enable exchanging models between different software tools. SBML is an open standard for encoding biological models in XML-based format, which facilitates the establishment of public model libraries such as BioModels Database and JWS Online [5,6]. A published model from such a library can easily be simulated by others using a software tool that supports SBML, even though the original model was implemented in different software. CellML is another XML-based markup language [7] that aims to address similar goals as SBML. The Biological Pathway Exchange standard, BioPAX, focus on the representation of biochemical networks and information about their constituents. However, it does not support kinetic modeling (i.e. mathematical reaction rate laws etc) so BioPAX models cannot be simulated. SBML and CellML on the other hand have their main focus on kinetic modeling and have a less detailed way of representing information about the networks and their elements. One of the greatest challenges in systems biology is to encourage scientists to use similar standards for graphical representation. This is a vital step for systems biologists that come from different backgrounds. If, for example, a biologist and a mathematician use the same graphical notation for building models, this would increase their ability to communicate. A first attempt by Kurt Kohn to create a unified visual notation for biological pathways was his Molecular Interaction Map, which is a notation for defin- ing symbols and syntax to describe molecular interactions [8]. Kohn’s work has been followed by alternative notations and extensions [9–12]. From an initiative by Hiroaki Kitano, an inter- national meeting was held in Tokyo in 2006 to investigate the feasibility of a unified graphical notation for systems biology. A result of the meeting was an initial proposal constituting the basis Reviews  INFORMATICS Corresponding author:. Jirstrand, M. (mats.jirstrand@fcc.chalmers.se) 1359-6446/06/$ - see front matter ß 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.drudis.2010.02.012 www.drugdiscoverytoday.com 365