Improvements to cardiovascular gene ontology

Abstract

Gene Ontology (GO) provides a controlled vocabulary to describe the attributes of genes and gene products in any organism. Although one might initially wonder what relevance a 'controlled vocabulary' might have for cardiovascular science, such a resource is proving highly useful for researchers investigating complex cardiovascular disease phenotypes as well as those interpreting results from high-throughput methodologies. GO enables the current functional knowledge of individual genes to be used to annotate genomic or proteomic datasets. In this way, the GO data provides a very effective way of linking biological knowledge with the analysis of the large datasets of post-genomics research. Consequently, users of high-throughput methodologies such as expression arrays or proteomics will be the main beneficiaries of such annotation sets. However, as GO annotations increase in quality and quantity, groups using small-scale approaches will gradually begin to benefit too. For example, genome wide association scans for coronary heart disease are identifying novel genes, with previously unknown connections to cardiovascular processes, and the comprehensive annotation of these novel genes might provide clues to their cardiovascular link. At least 4000 genes, to date, have been implicated in cardiovascular processes and an initiative is underway to focus on annotating these genes for the benefit of the cardiovascular community. In this article we review the current uses of Gene Ontology annotation to highlight why Gene Ontology should be of interest to all those involved in cardiovascular research.

Fig. 1

Protein record page of the QuickGO browser, showing all annotations for the human CDKN2B protein (www.ebi.ac.uk/ego/GProtein?ac=P42772). The QuickGO protein record page displays a short summary for the chosen UniProtKB protein accession number, together with associated GO annotations. Descriptions about the information in each column are provided in green call-outs, red arrows and circles show some of the additional information hyperlinked to this protein record. In the QuickGO GO term ancestor chart the term ‘cytoplasm’ is shown to be a child of the broader parent term intracellular part. The GO term ‘cytoplasm’ was associated with the CDKN2B record based on the direct assay ‘immunofluorescent staining’ and given the evidence code ‘IDA’, an acronym for ‘inferred from direct assay’ (text in the abstract highlighted yellow). 17 different evidence codes can be used to categorise the type of evidence available to support the annotation, one of which (IEA) is use to indicate an ‘electronic’ source for the annotation, the remaining 16 are all used for manually curated annotations. For further information about the use of evidence codes see www.geneontology.org/GO.evidence.shtml and for an explanation about how some of these annotations are made, see the Annotation Tutorial at EBI (www.ebi.ac.uk/GOA/annotationexample.html). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)

Fig. 2

Protein record page of the QuickGO browser, showing the manual annotations for the human TNF protein (www.ebi.ac.uk/ego/GProtein?ac=P01375). TNF is described in over 55,000 publications, however the annotations currently associated with human TNF have been extracted from only 15 of these publications. A review of these annotations by scientists working on TNF could increase the number and quality of annotations associated with this gene.