Through the Enabling Discovery through GEnomics (EDGE) program, the National Science Foundation (NSF) and the National Institutes for Health (NIH) support research to advance understanding of comparative and functional genomics. The EDGE program supports the development of innovative tools, technologies, resources, and infrastructure that advance biological research focused on the identification of the causal mechanisms connecting genes and phenotypes. The EDGE program also supports functional genomic research that addresses the mechanistic basis of complex traits in diverse organisms within the context (environmental, developmental, social, and/or genomic) in which they function. These goals are essential to uncovering the rules that underlie genomes-to-phenomes relationships and predict phenotype, an area relevant to Understanding the Rules of Life: Predicting Phenotype, one of the 10 Big Ideas for NSF investment. The goals also support the NHGRI priority to establish the roles and relationships of all genes and regulatory elements in pathways, networks, and phenotypes.