Cytoscape is an Open Source bioinformatics environment for biological network analysis, visualization, and modeling. It has grown to become a standard resource in academia and industry, due mainly to its timeliness (it was one of the first tools for visualization of biological networks), open development model (it is still one of few such tools that is open-source), and public plug-in interface (which allows anyone to add functionality to Cytoscape and has attracted many third-party developers and industrial partners). The NIH has funded Cytoscape development since 2004 under the program "Continued Maintenance and Development of Software" (R01-GM070743). In this competitive renewal, we propose to continue to improve, maintain, and support Cytoscape along three Specific Aims. First, we will fit Cytoscape with a modular architecture using the OSGi framework (http://www.osgi.org/). OSGi will enable command-line and scripting interfaces, deployment of Cytoscape as a web-server, parallelization within cluster computing environments, and customization by different user communities. Second, we will develop a collection of new network visualization and analysis features organized around target Cytoscape workflows-i.e., sets of both novel and commonly-used operations chained together to form analysis pipelines. The new features (including new data services, a more powerful structure for network attributes, and a unified network query engine) will greatly enhance the accessibility of complex but powerful network analysis operations to a broad experimental and clinical research community, and they will enable new uses of network biology in the study of human disease. Third, we will invest significant resources in outreach, training, and community support through development of education and training programs, bolstering collaborations with existing data and tool providers, and implementation of measures to actively reach out to attract new users and collaborators. Cytoscape is an important milepost on the road to developing large-scale "circuit diagrams" of the cell. Continued support of Cytoscape will allow other laboratories to avoid reinventing the same tools, time that can instead be devoted to more complex analyses or to basic research. RELEVANCE Cytoscape has supported hundreds of publications involving biological network analysis, and major databases rely on Cytoscape for visualization and analysis of molecular interactions. Renewed funding of Cytoscape will be crucial to maintain a strong core software environment and to expand its function to meet current and future challenges such as network-based disease diagnostics and interpretation of genotypes. PUBLIC HEALTH RELEVANCE: Continued support of Cytoscape will allow NIH investigators to maintain and magnify their ongoing successful efforts to mine molecular networks for new pathways, biomarkers, and individual variations underlying disease.