Use of Gene Ontology Annotation to understand the peroxisome proteome in humans

Abstract

The Gene Ontology (GO) is the de facto standard for the functional description of gene products, providing a consistent, information-rich terminology applicable across species and information repositories. The UniProt Consortium uses both manual and automatic GO annotation approaches to curate UniProt Knowledgebase (UniProtKB) entries. The selection of a protein set prioritized for manual annotation has implications for the characteristics of the information provided to users working in a specific field or interested in particular pathways or processes. In this article, we describe an organelle-focused, manual curation initiative targeting proteins from the human peroxisome. We discuss the steps taken to define the peroxisome proteome and the challenges encountered in defining the boundaries of this protein set. We illustrate with the use of examples how GO annotations now capture cell and tissue type information and the advantages that such an annotation approach provides to users. Database URL: http://www.ebi.ac.uk/GOA/ and http://www.uniprot.org.

Figure 1

A protein–protein interaction map of the human peroxisome. The peroxisome proteins and their interacting partners comprised a set of 421 proteins with a total of 408 binary interactions; peroxisomal proteins are shown as triangles and non-peroxisomal proteins as circles. Protein–protein interactions are depicted as white edges. Multiple edges between two proteins represent interactions that have been identified by more than one approach. The generic GO slim was used to identify terms in the proteome. GO terms that were common to all proteins in a cluster are shown as the cluster label.

Figure 2

Biological process GO enrichment of 88 human peroxisome proteins before the focused manual peroxisome protein annotation effort. The circles represent enriched GO terms. The size of circle is proportional to the number of proteins containing the biological process term.

Figure 3

Biological process GO enrichment of 88 human peroxisome proteins after the focused manual peroxisome protein annotation effort. The circles represent enriched GO terms. The size of circle is proportional to the number of proteins containing the biological process term. Circles with different colours represent proteins that contain an intersection of GO terms.

Figure 4

Comparison between biological processes enriched only in human peroxisome proteins (A) and those enriched only in the yeast peroxisomal protein set (B).