A guide to best practices for Gene Ontology (GO) manual annotation

Abstract

The Gene Ontology Consortium (GOC) is a community-based bioinformatics project that classifies gene product function through the use of structured controlled vocabularies. A fundamental application of the Gene Ontology (GO) is in the creation of gene product annotations, evidence-based associations between GO definitions and experimental or sequence-based analysis. Currently, the GOC disseminates 126 million annotations covering >374,000 species including all the kingdoms of life. This number includes two classes of GO annotations: those created manually by experienced biocurators reviewing the literature or by examination of biological data (1.1 million annotations covering 2226 species) and those generated computationally via automated methods. As manual annotations are often used to propagate functional predictions between related proteins within and between genomes, it is critical to provide accurate consistent manual annotations. Toward this goal, we present here the conventions defined by the GOC for the creation of manual annotation. This guide represents the best practices for manual annotation as established by the GOC project over the past 12 years. We hope this guide will encourage research communities to annotate gene products of their interest to enhance the corpus of GO annotations available to all. DATABASE URL: http://www.geneontology.org.

Figure 1.

GO Term ‘leukotriene-A4 hydrolase activity’ [GO:0004463], one of the terms mentioned in the main text of the article, as seen in AmiGO (16, http://amigo.geneontology.org). (a) Graphical view of the ontology structure showing the most granular term ‘leukotriene-A4 hydrolase activity’ [GO:0004463] at the bottom (highlighted in red), and all its parent terms leading up to the root node (‘molecular_function’ [GO:0003674]) at the top. Each box representing a GO term includes the GO identifier, and the blue line connecting the terms represent the ontological relationship ‘is_a’ (implying that a child term is a subtype of the parent term). (b) Alternate text display for viewing the ontology structure. ‘leukotriene-A4 hydrolase activity’ [GO:0004463] is highlighted in red. Each child term is indented from its parent to indicate the depth of the tree. Apart from the GOID and GO term, each row includes other pieces of information that are important to understand the ontology and the annotations to each term. Starting from the left end of the row, the + sign indicates that there are child terms for that node and clicking on the + sign opens the browser to display the child terms. Next the small icon ‘i’ indicates the term is related to its parent by an is–a relationship (explained above). At the right end of the row in brackets is the total number of gene products annotated to that term and all its child terms. (c) Term information relevant to making an annotation is highlighted in red, which includes the GOID, Aspect of the ontology (Molecular Function), Synonyms and Definition of the term.

Figure 2.

GO Evidence code decision tree describing the process of choosing an evidence code. This flow chart is meant to orient the biocurator on the different categories of evidence codes and does not include the complete definitions of the evidence codes (Table 2). This chart will aid the biocurator to evaluate the reported method or results and map them to an appropriate evidence code; the biocurator should consult the detailed evidence code documentation available online from http://www.geneontology.org/GO.evidence.shtml.