INFRASTRUCTURE - PROJECT SUMMARY Researchers use networks to discover non-obvious relationships that lead to understanding of disease, evolution, and group behavior. Biological discoveries contribute torrents of new relationships, new kinds of relationships, and new data to our overall knowledgebase stored across many databases. Important components in this process include large biological databases containing these networks, computational methods, and specialized visualizations. New computational methods are needed to organize and extract actionable information from this knowledge base. One aim of the NRNB is to provide tools to enable and accelerate this process. The Cytoscape application is open source software available to all researchers – it combines tools to discover and load biological databases, computationally analyze them, visualize the results, and then publish them to enable collaboration with other researchers. Besides its core features, Cytoscape encourages researchers to create and publish apps that combine with Cytoscape to load novel databases, perform novel analyses, or create new and useful visualizations – all improving the speed or accuracy of the discovery process. Additionally, NRNB sponsors a high performance computing cluster housed at the San Diego Supercomputer Center on the campus of the University of California, San Diego – it enables researchers to create new techniques for the deep inspection of massive datasets (e.g., the human genome) to computationally discover new network relationships (e.g., about human disease). Currently, interesting networks are growing to exceed either Cytoscape's or the NRNB Cluster's capacity for loading or computing on them. Furthermore, new and useful computations (such as p- value computations based on random models and resampling) are often more complex than previous ones, and their running times grow much faster than the networks and data on which they operate. Finally, the pace of network biology research is often slowed by the complexity of creating and stringing multiple computations together to achieve some result. To keep pace with both the rate of information growth and the computational resources needed to extract meaningful conclusions, we will develop quantum leaps in both software and hardware infrastructure for the NRNB. Specifically, we will create a new, Internet-based computing infrastructure that combines the strengths and features of Cytoscape with the scalability of cloud-based computing using REST principles. It will enable computing on much larger networks in much less time, while greatly reducing the costs and time delays in creating new analyses and stringing them together. The Cytoscape App Store will become a central repository of both Cytoscape apps and Cyberinfrastructure services. We also propose to quadruple the memory capacity of the NRNB cluster and to tenfold increase its storage to create a new platform for state-of-the-art network investigation.