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

Rachael P Huntley,Lars Maegdefessel,Kimberly Van Auken,Valerie Wood,Doug Howe,David Osumi-Sutherland,Anna Zampetaki,Marija Orlic-Milacic,Victoria Petri,Dmitry Sitnikov,Ruth C Lovering,Jennifer R Smith,Marc E Gillespie,Peter D'Eustachio,Manuel Mayr,Anastasia Z Kalea,Rama Balakrishnan

doi:10.1261/rna.055301.115

Abstract

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).

Highlights

The past two decades of research have established that microRNAs play a central role in regulating the stability and expression of messenger RNAs
The GO and its associated annotations are continually evolving as biological knowledge increases and as curators focus on annotation and ontology development efforts in specific areas of biological interest (The Gene Ontology Consortium 2014)
No dedicated effort had focused on the functional curation of miRNAs, or their biogenesis, and the ontology representing gene silencing by miRNA was outdated and incomplete

Summary

Introduction

The past two decades of research have established that microRNAs (miRNAs) play a central role in regulating the stability and expression of messenger RNAs (mRNAs). Even the identification of all mRNAs that can bind a given miRNA to form a stable duplex under physiological conditions is difficult given the range of approaches used and the variable data quality. This problem is reflected in miRNA databases where targets of miRNAs can frequently be reported based on weak or nonexistent evidence. Often the cited paper does not provide a rigorous experimental validation, or the miRNA:mRNA association is based on an unsound inference from a text-mining algorithm These inaccuracies and weak inferences impede data mining and integration efforts (Kalea et al 2015)

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