Representing ontogeny through ontology: a developmental biologist's guide to the gene ontology

Abstract

Developmental biology, like many other areas of biology, has undergone a dramatic shift in the perspective from which developmental processes are viewed. Instead of focusing on the actions of a handful of genes or functional RNAs, we now consider the interactions of large functional gene networks and study how these complex systems orchestrate the unfolding of an organism, from gametes to adult. Developmental biologists are beginning to realize that understanding ontogeny on this scale requires the utilization of computational methods to capture, store and represent the knowledge we have about the underlying processes. Here we review the use of the Gene Ontology (GO) to study developmental biology. We describe the organization and structure of the GO and illustrate some of the ways we use it to capture the current understanding of many common developmental processes. We also discuss ways in which gene product annotations using the GO have been used to ask and answer developmental questions in a variety of model developmental systems. We provide suggestions as to how the GO might be used in more powerful ways to address questions about development. Our goal is to provide developmental biologists with enough background about the GO that they can begin to think about how they might use the ontology efficiently and in the most powerful ways possible.

Figure 1

A) A simple list of keywords for anatomical structures in the limbs does not provide information about how the keywords relate to one another. B) The use of a hierarchy allows a simple view of how the structures of the limbs can relate to one another. In this case the hierarchy describes parts of the limbs, but does not relate the upper parts of the forelimb and hindlimb. C) The use of a directed acyclic graph permits terms to have more than one parent and provides a robust representation of the anatomy of limbs. In this tree-view of a simplified ontology, the upper leg bone is both a part_of the upper leg and is_a hindlimb bone. The boxed “I” denotes an is_a relationship and the circled “P” denotes a part_of relationship.

Figure 2

The Gene Ontology consists of three ontologies. Molecular Function describes the biochemical activity of a gene product, such as histone kinase activity. Biological Process describes an overall biological objective, such as seed germination (image obtained from http://etc.usf.edu/clipart/49400/49471/49471_seed_stages.htm). Cellular Component describes where in the cell a gene product is located, such as nucleus (image obtained from http://etc.usf.edu/clipart/47800/47857/47857_cell_struct.htm).

Figure 3

A partial OBO stanza displaying the term vitellogenesis. An OBO stanza is the textual description of an ontology term in the OBO format. Each term has an ID, a unique name, a textual definition that is supported by a reference, appropriate synonyms and relationships with other terms. Each term in the ontology is represented in an OBO stanza similar to this example. The definition of a term is tied to its ID. Although the string to describe a term may change, the ID of a term is stable and always represents the same biological object.

Figure 4

Rules governing relationships allow inferences to be made across the ontology. Here we show 3 rules that can be used for inference using the is_a and part_of relationships. The is_a and part_of relationships are transitive over themselves. The part_of relationship is transitive over the is_a relationship. The black arrow can be read as “therefore”.

Figure 5

This graphical representation shows cell differentiation and its part_of children. To make the graph easier to view, we have removed the is_a parents from the terms.

Figure 6

A tree-view of a portion of central nervous system development in GO and the portion of the Mouse Anatomical Dictionary for the brain. Ontology editors for both resources coordinate their efforts so that the description of anatomical structure development in GO is consistent with the structure of the anatomical dictionary. For example, diencephalon development and telencephalon development are represented as part_of forebrain development in GO and diencephalon and telencephalon are represented as part_of the forebrain in the anatomical dictionary.

Figure 7

A screen capture showing the search interface for the AmiGO tool that is provided by The Gene Ontology Consortium. The tool can be used to search for either GO terms or genes or proteins in the GO database. The results of the search are shown in the bottom panel.

Figure 8

A screen capture showing the results of a gene search using the AmiGO tool. The results can be filtered in a number of ways or can be used to link to annotations, gene information or BLAST.