Metagenomes encode an enormous diversity of proteins, reflecting a multiplicity of functions and activities. Exploration of this vast sequence space has been limited to a comparative analysis against reference microbial genomes and protein families derived from those genomes. Here, to examine the scale of yet untapped functional diversity beyond what is currently possible through the lens of reference genomes, a team of scientists has developed a computational approach to generate reference-free protein families from the sequence space in metagenomes. The researchers include Joel Kostka, professor and Associate Chair of Research in the School of Biological Sciences (part of the Novel Metagenome Protein Families Consortium), and Kostas T. Konstantinidis, Richard C. Tucker Professor in the School of Civil and Environmental Engineering. (This research was also covered at Berkeley Lab.)