The impact of focused Gene Ontology curation of specific mammalian systems

Abstract

The Gene Ontology (GO) resource provides dynamic controlled vocabularies to provide an information-rich resource to aid in the consistent description of the functional attributes and subcellular locations of gene products from all taxonomic groups (www.geneontology.org). System-focused projects, such as the Renal and Cardiovascular GO Annotation Initiatives, aim to provide detailed GO data for proteins implicated in specific organ development and function. Such projects support the rapid evaluation of new experimental data and aid in the generation of novel biological insights to help alleviate human disease. This paper describes the improvement of GO data for renal and cardiovascular research communities and demonstrates that the cardiovascular-focused GO annotations, created over the past three years, have led to an evident improvement of microarray interpretation. The reanalysis of cardiovascular microarray datasets confirms the need to continue to improve the annotation of the human proteome.

Availability: GO ANNOTATION DATA IS FREELY AVAILABLE FROM: ftp://ftp.geneontology.org/pub/go/gene-associations/

Figure 1. Distribution of GO term specificity by annotation source.

Accumulative frequency of the distribution of GO terms applied in human annotations. Manual annotations created by the Cardiovascular and Renal Initiative, compared to those created by annotation groups without a system focused approach. Mann Whitney U confirms that the median granularity of GO terms used in human protein annotation by the Cardiovascular and Renal Initiatives is 8.0 (inter quartile range 6–10), compared to a median granularity of 7.0 (inter quartile range 5–9), for the GO terms used by other groups manually annotating to the human proteome (P<0.0001).

Figure 2. AmiGO ‘Tree View’ image of part of the kidney developmental process ontology.

The ‘tree view’ in AmiGO (http://amigo.geneontology.org) showing the GO term parents of GO:0003337 ‘mesenchymal to epithelial transition involved in metanephros morphogenesis’. The most specific twelve GO terms (shaded) were amongst the 470 new terms created following the kidney development ontology workshop. The numbers in brackets indicate the number of human proteins annotated to the GO term, or one of its child terms (07^th October 2011). [I] is_a parent-child relationship, ‘P’ part_of parent-child relationship.

Figure 3. QuickGO term display.

QuickGO (www.ebi.ac.uk/QuickGO) ancestor chart showing information for GO:0006935 ‘chemotaxis’ and its ‘is_a’ parent relationships within the hierarchical directed acyclic graph. The GO terms ‘chemotaxis’, ‘locomotion’ and ‘response to stimulus’ are highlighted to illustrate their parent-child relationships. The child term details are displayed for the GO term ‘chemotaxis’.