Gene ontology: tool for the unification of biology. The Gene Ontology Consortium

Abstract

Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.

Fig. 1

Examples of Gene Ontology. Three examples illustrate the structure and style used by GO to represent the gene ontologies and to associate genes with nodes within an ontology. The ontologies are built from a structured, controlled vocabulary. The illustrations are the products of work in progress and are subject to change when new evidence becomes available. For simplicity, not all known gene annotations have been included in the figures. a, Biological process ontology. This section illustrates a portion of the biological process ontology describing DNA metabolism. Note that a node may have more than one parent; for example, ‘DNA ligation’ has three parents, ‘DNA-dependent DNA replication’, ‘DNA repair’ and ‘DNA recombination’. b, Molecular function ontology. The ontology is not intended to represent a reaction pathway, but instead reflects conceptual categories of gene-product function. A gene product can be associated with more than one node within an ontology, as illustrated by the MCM proteins. These proteins have been shown to bind chromatin and to possess ATP-dependent DNA helicase activity, and are annotated to both nodes. c, Cellular component ontology. The ontologies are designed for a generic eukaryotic cell, and are flexible enough to represent the known differences between diverse organisms.

Fig. 2

Correspondence between hierarchical clustering of expression microarray experiments with GO terms. The coloured matrix represents the results of clustering many microarray expression experiments. In the matrix, each row represents the yeast gene described to the right, and each column represents the expression of that gene in a particular microarray hybridization. For each gene in the matrix, the table at right lists the systematic ORF name, the standard gene name (if known), and the GO biological process, molecular function and cellular component annotations for that gene. The GO annotations suggest that this experimental expression cluster groups gene products involved in the biological process of protein folding. In contrast, the molecular function and cellular component annotations of these gene products correlate less well with the clustered expression patterns of these gene products.