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

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

doi:10.1186/s13326-016-0061-5

Abstract

BackgroundTo 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.MethodsBy 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.ResultsWe 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.ConclusionsAs 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.

Highlights

To address the lack of standard terminology to describe extracellular RNA data/metadata, we have launched an inter-community effort to extend the Gene Ontology (GO) with subcellular structure concepts relevant to the Extracellular RNAs (exRNAs) domain
The metadata standards build on metadata data models we previously developed during the course of the NIH Epigenome Roadmap project, International Human Epigenome Consortium (IHEC) project, and in collaboration with the ENCODE3 project, and NCBI
extracellular ribonucleic acid (ExRNA) terms and relationships added to GO Based on the option-2 proposal shown in Fig. 1, the Extracellular RNA Communication Consortium (ERCC) group worked with European Molecular Biology Laboratory (EMBL)-EBI members of the Gene Ontology Consortium (GOC) editorial team to add the proposed terms and relationships to GO

Summary

Introduction

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 annotated and queried because it will be based on a shared set of terms and relationships relevant to extracellular research. Extracellular RNAs (exRNAs) are broadly defined as RNAs that are present in the acellular portions of biofluids, such as body fluids (blood, cerebrospinal fluid, bile, lymph, vitreous humour, amniotic fluid, ascites, pleural, pericardial and peritoneal fluids, etc.), secretions (saliva, urine, sweat, tears, milk, seminal fluid, etc.), and cell and tissue culture supernatants. Export of exRNAs may be used to eliminate undesired RNAs from the originating cell. Some exRNAs might be generated in a nonspecific manner, either by living cells (e.g. by a ‘bulk flow’ process) or as a consequence of cell death (reviewed in [6])

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