Standardized annotation of translated open reading frames
Jonathan M. Mudge, Jorge Ruiz‐Orera, John R. Prensner, Marie A. Brunet, Ferriol Calvet, Irwin Jungreis, José M. González, Michele Magrane, Thomas F. Martínez, Jana Felicitas Schulz, Yucheng Yang, M. Mar Albà, Julie L. Aspden, Pavel V. Baranov, Ariel Bazzini, Elspeth A. Bruford, María Martin, Lorenzo Calviello, Anne‐Ruxandra Carvunis, Jin Chen, Juan Pablo Couso, Eric W. Deutsch, Paul Flicek, Adam Frankish, Mark Gerstein, Norbert Hübner, Nicholas T. Ingolia, Manolis Kellis, Gerben Menschaert, Robert L. Moritz, Uwe Ohler, Xavier Roucou, Alan Saghatelian, Jonathan S. Weissman, Sebastiaan van Heesch
Abstract
Ribosome profiling (Ribo-seq) has extended our understanding of the translational ‘vocabulary’ of the human genome, uncovering thousands of open reading frames (ORFs) within long noncoding RNAs (lncRNAs) and presumed untranslated regions (UTRs) of protein-coding genes. However, reference gene annotation projects have been circumspect in their incorporation of these ORFs because of uncertainties about their experimental reproducibility and physiological roles. Yet, it is clear that certain ‘Ribo-seq ORFs’ make stable proteins, others mediate gene regulation, and many have medical implications. Ultimately, the absence of standardized ORF annotation has created a circular problem: while Ribo-seq ORFs remain unrecognized by reference annotation databases, this lack of recognition will thwart studies examining their roles. Here, we outline a community-led effort involving Ensembl/GENCODE, the HUGO Gene Nomenclature Committee (HGNC), UniProtKB, HUPO/HPP and PeptideAtlas to produce a standardized catalog of 7,264 human Ribo-seq ORFs; a path to bring protein-level evidence for Ribo-seq ORFs into reference annotation databases; and a roadmap to facilitate research in the global community.