PROJECT SUMMARY Genomic sequencing of tumor samples is now a routine component of cancer care, providing unprecedented insight into cancer initiation, progression, and treatment effects. Additionally, novel molecular profiling and imaging techniques are gaining traction, generating ever more data. Ensuring that these data sets are easily accessible and interpretable to scientists and clinicians is of vital importance. Towards this end, we seek to evolve and expand the capabilities of the cBioPortal for Cancer Genomics, a unique platform that enables interactive exploratory analysis of large-scale cancer genomic data. The cBioPortal is the most widely used and most highly cited tool within the cancer genomics community. The public site, with data from 325 cancer studies, is accessed by >34,000 unique users each month. The cBioPortal instance that supports AACR Project GENIE, a multi-institutional data sharing initiative, now hosts genomic profiles from >120,000 tumors. Since the software is available under an open source license, >65 cancer centers and pharmaceutical companies have institutional installations of cBioPortal to analyze their own data. Multiple institutions are making contributions to the software, including the five that are part of this application (Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, Princess Margaret Cancer Centre, and Children’s Hospital of Philadelphia). To ensure that this vital resource continues to aid the cancer research community and to keep pace with the rapidly advancing fields of cancer genomics and precision cancer medicine, including the continuing increase in the number of profiled tumor samples, we propose to actively sustain and evolve the cBioPortal platform. Specifically, we plan to make improvements across the entire cBioPortal software architecture (Aim 1); this includes significant changes to address key performance bottlenecks, a new API capable of supporting federated queries, a new App Store, and improvements to our cloud infrastructure and data pipelines. We will also support several new molecular data types, add two entirely new cBioPortal views, develop new features for precision oncology, and improve general usability (Aim 2). We propose to continue funding a group of core developers across five institutions, expand the base of code contributors, and continue to collaborate with The Hyve to support biotech and pharmaceutical companies (Aim 3). Finally, to maximize use in the scientific community, we plan to continue to improve community outreach, user support, and training (Aim 4). These improvements will be necessary to ensure that cBioPortal continues to provide an essential service for cancer research and development of new biomarkers and drugs, especially as more cancer centers are using the cBioPortal as part of their precision medicine programs, and as pharmaceutical companies are using it for internal research. We expect that, over the nex...