Rapid improvements in DNA sequencing and synthesis have the potential to usher in a new era of precision medicine. To realize this vision, however, we must re-imagine the computational and storage infrastructure used to manage and extract actionable results from the massive data sets made possible by widely available advances in DNA sequencing and synthetic biology. In conjunction with the Global Alliance for Genomics and Health (GA4GH), we propose to build the Arvados platform so that a new ecosystem of clinical decision support applications will be able to navigate petabytes of global biomedical data and search millions of genomes in real-time (seconds). Our team has a proven track record of commercial success and high impact scientific research. Commercialization of this free and open-source software (FOSS) platform, which will be greatly accelerated by this grant, will permit organizations to seamlessly span on-premise & hosted cloud- operating systems and vastly simplify data-management & computation, all while facilitating compliance with institutional policies and regulatory requirements.