Extending gene ontology in the context of extracellular RNA and vesicle communication

Kei-Hoi Cheung, Shivakumar Keerthikumar, Paola Roncaglia, Sai Lakshmi Subramanian, Matthew E. Roth, Monisha Samuel, Sushma Anand, Lahiru Gangoda, Stephen Gould, Roger Alexander, David Galas, Mark B. Gerstein, Andrew F. Hill, Robert R. Kitchen, Jan Lötvall, Tushar Patel, Dena C. Procaccini, Peter Quesenberry, Joel Rozowsky, Robert L. Raffai, Aleksandra Shypitsyna, Andrew I. Su, Clotilde Théry, Kasey Vickers, Marca H.M. Wauben, Suresh Mathivanan, Aleksandar Milosavljevic, Louise C. Laurent

To address the lack of standard terminology to describe extracellular RNA (exRNA) data/metadata, we have launched an inter-community effort to extend the Gene Ontology (GO) with subcellular structure concepts relevant to the exRNA domain. By extending GO in this manner, the exRNA data/metadata will be more easily annotated and queried because it will be based on a shared set of terms and relationships relevant to extracellular research. By following a consensus-building process, we have worked with several academic societies/consortia, including ERCC, ISEV, and ASEMV, to identify and approve a set of exRNA and extracellular vesicle-related terms and relationships that have been incorporated into GO. In addition, we have initiated an ongoing process of extractions of gene product annotations associated with these terms from Vesiclepedia and ExoCarta, conversion of the extracted annotations to Gene Association File (GAF) format for batch submission to GO, and curation of the submitted annotations by the GO Consortium. As a use case, we have incorporated some of the GO terms into annotations of samples from the exRNA Atlas and implemented a faceted search interface based on such annotations. We have added 7 new terms and modified 9 existing terms (along with their synonyms and relationships) to GO. Additionally, 18,695 unique coding gene products (mRNAs and proteins) and 963 unique non-coding gene products (ncRNAs) which are associated with the terms: "extracellular vesicle", "extracellular exosome", "apoptotic body", and "microvesicle" were extracted from ExoCarta and Vesiclepedia. These annotations are currently being processed for submission to GO. As an inter-community effort, we have made a substantial update to GO in the exRNA context. We have also demonstrated the utility of some of the new GO terms for sample annotation and metadata search.