TY - JOUR
T1 - Extending gene ontology in the context of extracellular RNA and vesicle communication
AU - Cheung, Kei Hoi
AU - Keerthikumar, Shivakumar
AU - Roncaglia, Paola
AU - Subramanian, Sai Lakshmi
AU - Roth, Matthew E.
AU - Samuel, Monisha
AU - Anand, Sushma
AU - Gangoda, Lahiru
AU - Gould, Stephen
AU - Alexander, Roger
AU - Galas, David
AU - Gerstein, Mark B.
AU - Hill, Andrew F.
AU - Kitchen, Robert R.
AU - Lötvall, Jan
AU - Patel, Tushar
AU - Procaccini, Dena C.
AU - Quesenberry, Peter
AU - Rozowsky, Joel
AU - Raffai, Robert L.
AU - Shypitsyna, Aleksandra
AU - Su, Andrew I.
AU - Théry, Clotilde
AU - Vickers, Kasey
AU - Wauben, Marca H.M.
AU - Mathivanan, Suresh
AU - Milosavljevic, Aleksandar
AU - Laurent, Louise C.
N1 - Funding Information:
This work was supported in part by the NIH Common Fund, through the Office of Strategic Coordination and the Office of the NIH Director (AM: U54DA036134, LCL: UH2TR000906 and U01HL126494, TP: UH3TR000884, and RR: U19CA179512). Paola Roncaglia and Aleksandra Shypitsyna are funded by the Gene Ontology Consortium (P41 grant from the National Human Genome Research Institute (NHGRI), grant 5U41HG002273-14). Aleksandra Shypitsyna is also funded from the European Molecular Biology Laboratory (EMBL). We would like to give special thanks to Dena C. Procaccini for coordinating meetings and conference calls facilitating discussion and collaboration as part of the manuscript writing. We would like to thank Tony Sawford (Protein Function Development team, EMBL-EBI) for running the set of ExoCarta and Vesiclepedia annotations through the validation pipeline for inclusion in the GOA database. We would also like to thank Xandra O. Breakefield for her insights and comments. Finally we would like to acknowledge the community support offered by the following Consortiums: Extracellular RNA Communication (ERC) Consortium, Gene Ontology Consortium (GOC), and International Society for Extracellular Vesicles (ISEV), and American Society for Exosomes and Microvesicles (ASEMV).
Funding Information:
Therefore, investigators are currently forced to make a choice between these competing definitions, the first being practical but mechanistically barren, while the latter being impractical but mechanistically appealing. Unfortunately, there is as yet no unambiguous way to distinguish between vesicles that bud from the plasma membrane versus those that bud at the endosome membrane based on either biophysical properties or molecular content. This lack of standard nomenclatures creates i) a problem for individual researchers to annotate/share their data in an unambiguous manner and ii) a barrier to productive interactions with the broader research community, most prominently the biomedical, genomics, and computational biology communities. To address such issues, we initiated our metadata standard efforts within the Metadata Working Group (MWG) of the Extracellular RNA Communication Consortium (ERCC) funded by the National Institutes of Health (NIH). As part of these efforts, MWG matched metadata terms to existing biomedical ontologies and identified the exRNA-relevant terms that were absent from major ontologies such as the Gene Ontology (GO).
Publisher Copyright:
© 2016 Cheung et al.
PY - 2016/4/12
Y1 - 2016/4/12
N2 - 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.
AB - 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.
KW - Atlas
KW - Extracellular RNA
KW - Extracellular vesicle
KW - Faceted search
KW - Metadata
KW - Ontology
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U2 - 10.1186/s13326-016-0061-5
DO - 10.1186/s13326-016-0061-5
M3 - Article
C2 - 27076901
AN - SCOPUS:84992107664
SN - 2041-1480
VL - 7
JO - Journal of Biomedical Semantics
JF - Journal of Biomedical Semantics
IS - 1
M1 - 19
ER -