Representing kidney development using the gene ontology

Abstract

Gene Ontology (GO) provides dynamic controlled vocabularies to aid in the description of the functional biological attributes and subcellular locations of gene products from all taxonomic groups (www.geneontology.org). Here we describe collaboration between the renal biomedical research community and the GO Consortium to improve the quality and quantity of GO terms describing renal development. In the associated annotation activity, the new and revised terms were associated with gene products involved in renal development and function. This project resulted in a total of 522 GO terms being added to the ontology and the creation of approximately 9,600 kidney-related GO term associations to 940 UniProt Knowledgebase (UniProtKB) entries, covering 66 taxonomic groups. We demonstrate the impact of these improvements on the interpretation of GO term analyses performed on genes differentially expressed in kidney glomeruli affected by diabetic nephropathy. In summary, we have produced a resource that can be utilized in the interpretation of data from small- and large-scale experiments investigating molecular mechanisms of kidney function and development and thereby help towards alleviating renal disease.

Figure 1. An OBO-Edit ‘Ontology Tree Editor’ view showing the 21 Gene Ontology terms representing renal development before the expansion in this area of the ontology.

There were 18 GO terms directly under the ‘kidney development’ node and 3 terms representing morphogenesis of the insect renal system, the Malpighian tubule (using the Gene Ontology file from November 18^th 2009). The [−] icon beside each term denotes no further child terms; (P) denotes a part_of relationship; (I) denotes an is_a relationship.

Figure 2. An OBO-Edit ‘Ontology Tree Editor’ view demonstrating the improved Gene Ontology representing ‘kidney development’ after a focused expansion.

The Gene Ontology representing kidney development was enriched after a focused expansion with an additional 522 new terms, and as an example (using the Gene Ontology file from March 19^th 2012) the expanded node of the ‘pronephros development’ term shows it’s immediate child terms. The [+] icon beside each term denotes that there are further child terms that can be viewed; the [−] icon denotes no further child terms; (P) denotes a part_of relationship; (I) denotes an is_a relationship; (R) denotes a regulates relationship.

Figure 3. An OBO-Edit ‘Ontology Tree Editor’ view representing similarities in tubule structures and grouped terms describing the development of different types of renal tubules.

Similarities are observed in GO terms representing tubule structures and terms are grouped together describing the development of different types of renal tubules including the Malpighian tubule of insects (using the Gene Ontology file from March 19^th 2012). The [+] icon beside a term denotes that the node is expandable and has further child/grandchild terms; the [−] icon denotes no further child terms; (P) denotes a part_of relationship; (I) denotes an is_a relationship.

Figure 4. An OBO-Edit ‘Ontology Tree Editor’ view showing the relationship and position of the new GO term ‘branching involved in ureteric bud morphogenesis’.

By placing the new term ‘branching involved in ureteric bud morphogenesis’ as a sub-type of ‘morphogenesis of a branching structure’, it puts the renal branching into the context of other types of branching morphogenesis within the Gene Ontology (using the Gene Ontology file from March 19^th 2012). The [+] icon beside each term denotes that there are further child terms that can be viewed; the [−] icon denotes no further child terms; (P) denotes a part_of relationship; (I) denotes an is_a relationship.