1. The subsystems strategy, adopted as the guiding principle of the effort [16] , centers on leveraging expert annotations to define a small set of functional roles in all genomes rather than all the functional roles in a small number of genomes. 2. The subsystem effort provided a convenient framework for the curation of a set of protein families that became known as FIGfams [22, 23] , intended to contain only isofunctional homologsthat is, each family was intended to contain only homologous proteins playing the same functional role. When errors in FiGfams are detected, the underlying subsystems are updated and then the FIGfams are regenerated to correct those errors. The rapid evolution of the FIGfam collection has made possible a number of the services described in this article. 3. Using subsystems and FIGfams as the underlying technology, the RAST server was developed and made available in 2007 [23] . Thousands of viral and prokaryotic genomes have been annotated with the RAST system, and hundreds more are being annotated each week. 4. The high-quality annotations generated by RAST together with the ability to manually modify those annotations by human experts allowed for the automatic generation of genome-scale metabolic models in the Model SEED [18, 19, 20] .