CYTOSCAPE: AN ECOSYSTEM FOR NETWORK GENOMICS PROJECT SUMMARY Cytoscape is an open source software platform for biological network analysis, visualization and modeling. It is a critical bioinformatics resource in academia and industry, with 300,000+ downloads per year and 25,000+ citations. The widespread adoption of Cytoscape is due mainly to its utility in diverse biological analyses, its sustainable open development model, and its extensible architecture, which enables anyone to add algorithmic functionality and has attracted hundreds of third-party developers. Access to network analysis tools is particularly important now, at a time when network knowledge and concepts are increasingly central to genomics research. Cytoscape is in an excellent position to address this need and serve as a hub for knowledge-based genome analysis. In this application to support Cytoscape as a U24 Genomic Community Resource, we will work towards four specific aims. First, we will maintain our longtime substantial commitment to produce Cytoscape software as a critical research resource. Second, we will complete our ongoing development of Cytoscape as an ecosystem of tools and services on the web, so that key network biology tools are more accessible to biomedical researchers and can readily access big biomedical datasets and interoperate in cloud computing environments. Immediate targets of these developments will be resources in which federal organizations are already making substantial investments, including AnVIL, BioData Catalyst and Cancer Genomic Data Commons. Third, we will work collaboratively with outside tool developers to promote a constellation of leading tools for network-based genomic analysis, including both existing and nascent approaches emerging from the data science community. Finally, we will continue to offer a rich set of Cytoscape training programs, including new material that actively guides users through analysis workflows, updating content based on input they provide. In summary, these activities will support not only production of the Cytoscape resource– they will create a next generation desktop, web and cloud-based ecosystem for using knowledge networks in genomic data science.