Guidelines for the functional annotation of microRNAs using the Gene Ontology.

MicroRNA regulation of developmental and cellular processes is a relatively new field of study, and the available research data have not been organized to enable its inclusion in pathway and network analysis tools. The association of gene products with terms from the Gene Ontology is an effective method to analyze functional data, but until recently there has been no substantial effort dedicated to applying Gene Ontology terms to microRNAs. Consequently, when performing functional analysis of microRNA data sets, researchers have had to rely instead on the functional annotations associated with the genes encoding microRNA targets. In consultation with experts in the field of microRNA research, we have created comprehensive recommendations for the Gene Ontology curation of microRNAs. This curation manual will enable provision of a high-quality, reliable set of functional annotations for the advancement of microRNA research. Here we describe the key aspects of the work, including development of the Gene Ontology to represent this data, standards for describing the data, and guidelines to support curators making these annotations. The full microRNA curation guidelines are available on the GO Consortium wiki (http://wiki.geneontology.org/index.php/MicroRNA_GO_annotation_manual).

Keywords

GO, analysis, annotation, biocuration, function, microRNA, Animals, Gene Silencing, Guidelines as Topic, Humans, Mice, MicroRNAs

Journal Title

RNA

Journal ISSN

1355-8382
1469-9001

Volume Title

22

Publisher

Cold Spring Harbor Laboratory

Publisher DOI

https://doi.org/10.1261/rna.055301.115

Rights

Attribution 2.0 UK: England & Wales

Sponsorship

Wellcome Trust (104967/Z/14/Z)
National Human Genome Research Institute (U41HG002659)

R.P.H. and R.C.L are supported by funding from a British Heart Foundation grant (RG/13/5/30112) and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. M.M. is a Senior Research Fellow of the British Heart Foundation (FS/13/2/29892). A.Z. is an Intermediate Fellow of the British Heart Foundation (FS/13/18/30207). D.S. is supported by a grant awarded to the Mouse Genome Database from the National Human Genome Research Institue at the US National Institutes of Health (HG-00330). P.D’E., M.G., M.O-M. are supported by grants from the US National Institutes of Health (P41 HG003751 and U54 GM114833), Ontario Research Fund, and the European Molecular Biology Laboratory. D.H. is supported by a grant awarded to the Zebrafish Information Network fromthe National Human Genome Research Institute at the US National Institutes of Health (HG002659). A.Z.K. is funded by a NIHR University College London Hospitals Biomedical Research Centre, Research Capability Funding award (RCF) (RCF123). L.M. is a Ragnar Söderberg fellow in Medicine (M-14/55), and received funding from Swedish Heart-Lung-Foundation (20120615, 20130664, 20140186). Huntley, RP 22 R.B. and D.O-S. are supported by R.B. and D.O-S. are supported by a grant awarded to The Gene Ontology Consortium (Principal Investigators: JA Blake, JM Cherry, S Lewis, PW Sternberg and P Thomas) by the National Human Genome Research Institute (NHGRI) (#U41 HG22073). V.P. and J.R.S. are supported by a grant from the National Heart, Lung, and Blood Institute on behalf of the National Institutes of Health (HL64541). K.V.A. is supported by a grant awarded to the Gene Ontology Consortium from the National Human Genome Research Institute at the US National Institutes of Health (HG002273). V.W. is supported by a Wellcome Trust grant (104967/Z/14/Z). We would like to thank Leonore Reiser and Tanya Berardini who provided guidance on the plant miRNA processing pathway. Also thanks to David Hill, Harold Drabkin, Judith Blake, Karen Christie, Donghui Li and Pascale Gaudet who contributed to discussions regarding GO curation procedures and to Lisa Matthews and Bruce May who provided helpful feedback on the manuscript. We are very grateful to Tony Sawford and Maria Martin from the European Bioinformatics Institute for access to the online GO curation tool, which is an essential component of this annotation project. Many thanks to members of the GO Editorial Office for useful discussions about the placement and definition of new GO terms. We also thank Alex Bateman and Anton Petrov for being responsive to our feedback regarding RNAcentral functionality. Author contributions: R.C.L. initiated discussions in the GO Consortium regarding miRNA curation guidelines and supervised the project, R.P.H. researched and constructed the guidelines and wrote the manuscript, R.P.H., R.C.L., D.S., R.B., P.D’E., M.G., M.O-M., D.H., V.P., J.R.S., K.V.A. and V.W. contributed to discussions regarding GO curation procedures and provided feedback on the manuscript. D.O-S. provided the expertise on definitions and placements of miRNA-related GO terms and performed the necessary updates and additions to both the GO and to the annotation extension relations used herein. M.M., A.Z., L.M. and A.Z.K. provided guidance with the scientific aspect of the guidelines and provided feedback on the manuscript.

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