Cross-product extensions of the Gene Ontology

Abstract

The Gene Ontology (GO) consists of nearly 30,000 classes for describing the activities and locations of gene products. Manual maintenance of ontology of this size is a considerable effort, and errors and inconsistencies inevitably arise. Reasoners can be used to assist with ontology development, automatically placing classes in a subsumption hierarchy based on their properties. However, the historic lack of computable definitions within the GO has prevented the user of these tools. In this paper, we present preliminary results of an ongoing effort to normalize the GO by explicitly stating the definitions of compositional classes in a form that can be used by reasoners. These definitions are partitioned into mutually exclusive cross-product sets, many of which reference other OBO Foundry candidate ontologies for chemical entities, proteins, biological qualities and anatomical entities. Using these logical definitions we are gradually beginning to automate many aspects of ontology development, detecting errors and filling in missing relationships. These definitions also enhance the GO by weaving it into the fabric of a wider collection of interoperating ontologies, increasing opportunities for data integration and enhancing genomic analyses.

Figure 1

Using logical definitions to infer placement in hierarchy. Boxes denote classes, and edges denote relationships between classes. is_a relations are depicted as [I], regulates links as [R]. Bold text denotes the class has a logical definition in the regulation subset of BP x BP. The highlighted link between ‘regulation of peptide secretion’ and ‘regulation of peptide transport’ is inferred by the reasoner based on the logical definitions and the relationship between ‘peptide secretion’ and ‘peptide transport’. This is an example of a relationship that was previously missing in GO.