Broad-Color: The Genome Center for the Future of All of Us - The All of Us Research Program is building a national biomedical research resource to empower and accelerate the understanding, diagnosis, and treatment of human diseases. The Broad Institute of MIT & Harvard has a 35 year track record of delivering on transformative projects in the field of genomics. Over the last two decades, Broad has sequenced the genomes of over 630,000 people (>290,000 All of Us participants). Color Health’s clinical programming brings improved risk assessment, identification, and disease management directly to large populations. Color’s genetic services laboratory (Color Dx) has sequenced and returned clinical results to >200,000 individuals, with as many as 10,000 results in a single month’s time. Together Broad and Color propose to continue to serve as a genome center and clinical validation laboratory for the All of Us Program. We propose to leverage our economies of scale to allow the program to meet all its commitments and maximize value while also delivering new and powerful data types into the hands of the scientific community, we also propose an aggressive cost reduction and cost sharing plan. We further offer a vision, for a future where additional funding is available, to accelerate the adoption of the All of Us cohort data by providing a set of cutting edge pilot and demo project proposals including innovative multiomic data generation in longitudinal studies to elucidate the interplay between exposures a participant may have had to markers in their genetic, epigenetic, or proteomic profiles. Our group brings together expertise in management of large scale genomics projects, novel assay development, interpretation of human variation, clinical validation, regulations, information security, and scientific vision. We also bring our network of scientific colleagues and collaborators for the analysis of expression, long read, and proteomic data and for future studies to further elucidate the mechanisms of complex traits and genes by environment interactions. Specifically, for this award we propose to support the core genomic assays of whole genome sequencing and genotyping at the desired scales, utilizing the same validated, secure, and compliant workflows we have used over the last 5 years. We will continue to collaborate with the Data Resource Center and across the Program to ensure the data is securely available to the research community.