Interpreting experimental results using gene ontologies.
High-throughput experimental techniques, such as microarrays, produce large amounts of data and knowledge about gene expression levels. However, interpretation of these data and turning it into biologically meaningful knowledge can be challenging. Frequently the output of such an analysis is a list of significant genes or a ranked list of genes. In the case of DNA microarray studies, data analysis often leads to lists of hundreds of differentially expressed genes. Also, clustering of gene expression data may lead to clusters of tens to hundreds of genes. These data are of little use if one is not able to interpret the results in a biological context. The Gene Ontology Consortium provides a controlled vocabulary to annotate the biological knowledge we have or that is predicted for a given gene. The Gene Ontologies (GOs) are organized as a hierarchy of annotation terms that facilitate an analysis and interpretation at different levels. The top-level ontologies are molecular function, biological process, and cellular component. Several annotation databases for genes of different organisms exist. This chapter describes how to use GO in order to help biologically interpret the lists of genes resulting from high-throughput experiments. It describes some statistical methods to find significantly over- or underrepresented GO terms within a list of genes and describes some tools and how to use them in order to do such an analysis. This chapter focuses primarily on the tool GOstat (http://gostat.wehi.edu.au). Other tools exist that enable similar analyses, but are not described in detail here.
Beissbarth
Tim
T
The Walter and Eliza Hall Institute of Medical Research, Bioinformatics Group, Victoria, Australia.
D000818:Animals; D030541:Databases, Genetic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012984:Software; D009626:Terminology as Topic