RT Journal Article
SR Electronic
T1 Unifying the global coding sequence space enables the study of genes with unknown function across biomes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.30.180448
DO 10.1101/2020.06.30.180448
A1 Chiara Vanni
A1 Matthew S. Schechter
A1 Silvia G. Acinas
A1 Albert Barberán
A1 Pier Luigi Buttigieg
A1 Emilio O. Casamayor
A1 Tom O. Delmont
A1 Carlos M. Duarte
A1 A. Murat Eren
A1 Robert D. Finn
A1 Renzo Kottmann
A1 Alex Mitchell
A1 Pablo Sanchez
A1 Kimmo Siren
A1 Martin Steinegger
A1 Frank Oliver Glöckner
A1 Antonio Fernandez-Guerra
YR 2020
UL http://biorxiv.org/content/early/2020/11/18/2020.06.30.180448.abstract
AB One of the biggest challenges in molecular biology is bridging the gap between the known and the unknown coding sequence space. This challenge is especially extreme in microbial systems, where between 40% and 60% of the predicted genes are of unknown function. Discarding this uncharacterized fraction should not be an option anymore. Here, we present a conceptual framework and a computational workflow that bridges this gap and provides a powerful strategy to contextualize the investigations of genes of unknown function. Our approach partitions the coding sequence space removing the known-unknown dichotomy, unifies genomic and metagenomic data and provides a framework to expand those investigations across environments and organisms. By analyzing 415,971,742 genes predicted from 1,749 metagenomes and 28,941 bacterial and archaeal genomes we showcase our approach and its application in ecological, evolutionary and biotechnological investigations. As a result, we put into perspective the extent of the unknown fraction, its diversity, and its relevance in genomic and environmental contexts. By identifying a target gene of unknown function for antibiotic resistance, we demonstrate how a contextualized unknown coding sequence space enables the generation of hypotheses that can be used to augment experimental data.Competing Interest StatementThe authors have declared no competing interest.