title: Extending gene ontology in the context of extracellular RNA and vesicle communication.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Emergency Medicine, Yale Center for Medical Informatics, Yale University School of Medicine, New Haven, CT USA ; VA Connecticut Healthcare System, West Haven, CT USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Kei-Hoi
authors.initials: KH
authors.lastname: Cheung
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086 Australia ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Keerthikumar
authors.affiliation: European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD UK ; Gene Ontology Consortium (GOC), ᅟ, ᅟ
authors.forename: Paola
authors.initials: P
authors.lastname: Roncaglia
authors.affiliation: Bioinformatics Research Laboratory, Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Sai Lakshmi
authors.initials: SL
authors.lastname: Subramanian
authors.affiliation: Bioinformatics Research Laboratory, Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Roth
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086 Australia.
authors.forename: Monisha
authors.initials: M
authors.lastname: Samuel
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086 Australia.
authors.forename: Sushma
authors.initials: S
authors.lastname: Anand
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086 Australia.
authors.forename: Lahiru
authors.initials: L
authors.lastname: Gangoda
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ ; American Society for Exosomes and Microvesicles (ASEMV), ᅟ, ᅟ
authors.forename: Stephen
authors.initials: S
authors.lastname: Gould
authors.affiliation: Pacific Northwest Diabetes Research Institute, Seattle, WA USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Roger
authors.initials: R
authors.lastname: Alexander
authors.affiliation: Pacific Northwest Diabetes Research Institute, Seattle, WA USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: David
authors.initials: D
authors.lastname: Galas
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT USA ; Department of Computer Science, Yale University, New Haven, CT USA ; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Mark B
authors.initials: MB
authors.lastname: Gerstein
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086 Australia ; International Society for Extracellular Vesicles (ISEV), ᅟ, ᅟ
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Hill
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Robert R
authors.initials: RR
authors.lastname: Kitchen
authors.affiliation: University of Gothenburg, Gothenburg, Sweden ; International Society for Extracellular Vesicles (ISEV), ᅟ, ᅟ
authors.forename: Jan
authors.initials: J
authors.lastname: Lötvall
authors.affiliation: Mayo Clinic, Jacksonville, FL USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Tushar
authors.initials: T
authors.lastname: Patel
authors.affiliation: Division of Neuroscience and Behavior, National Institute on Drug Abuse (NIDA), Rockville, MD USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Dena C
authors.initials: DC
authors.lastname: Procaccini
authors.affiliation: University Medicine Comprehensive Cancer Center, Providence, RI USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ ; International Society for Extracellular Vesicles (ISEV), ᅟ, ᅟ
authors.forename: Peter
authors.initials: P
authors.lastname: Quesenberry
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT USA ; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Joel
authors.initials: J
authors.lastname: Rozowsky
authors.affiliation: Department of Surgery, University of California San Francisco and VA Medical Center, San Francisco, CA USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Robert L
authors.initials: RL
authors.lastname: Raffai
authors.affiliation: European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD UK ; Gene Ontology Consortium (GOC), ᅟ, ᅟ
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Shypitsyna
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Su
authors.affiliation: Institut Curie, PSL Research University, INSERM U932, Paris, France ; International Society for Extracellular Vesicles (ISEV), ᅟ, ᅟ
authors.forename: Clotilde
authors.initials: C
authors.lastname: Théry
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Kasey
authors.initials: K
authors.lastname: Vickers
authors.affiliation: Department of Biochemistry & Cell Biology, Utrecht University, Utrecht, Netherlands ; International Society for Extracellular Vesicles (ISEV), ᅟ, ᅟ
authors.forename: Marca H M
authors.initials: MH
authors.lastname: Wauben
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086 Australia ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ ; International Society for Extracellular Vesicles (ISEV), ᅟ, ᅟ
authors.forename: Suresh
authors.initials: S
authors.lastname: Mathivanan
authors.affiliation: Bioinformatics Research Laboratory, Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Milosavljevic
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, La Jolla, CA USA ; Extracellular RNA Communication Consortium (ERCC), ᅟ, ᅟ
authors.forename: Louise C
authors.initials: LC
authors.lastname: Laurent
mesh_terms: D030541:Databases, Genetic; D000067128:Extracellular Vesicles / Q000235:genetics*; D063990:Gene Ontology; D006801:Humans; D058977:Molecular Sequence Annotation; D012313:RNA / Q000235:genetics*; D064878:Web Browser
chemical_list: D012313:RNA
keywords: Atlas; Extracellular RNA; Extracellular vesicle; Faceted search; Metadata; Ontology