Over the past two decades, the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a DOE Office of Science User Facility at Lawrence Berkeley National Laboratory, has transitioned from a high-throughput genome sequencing center to a national user facility that provides researchers around the world with access to sequencing and computational analysis capabilities on projects relevant to the DOE missions of energy and environmental challenges. Along with advances in sequencing technologies and capacities, JGI has developed capabilities such as single-cell genomics, synthetic biology, and metabolomics to move beyond generating a DNA sequence to understanding gene functions for a myriad of applications.