IS THERE STRENGTH IN NUMBERS? LOOKING FOR THE BEST BACKGROUND REFERENCE IN ONTOLOGY ANALYSIS

CRISTÓBAL FRESNO; ANDREA S LLERA; MARÍA R GIROTTI; MARÍA P VALACCO; JUAN A LÓPEZ; OSVALDO L PODHAJCER; MÓNICA G BALZARINI; FEDERICO PRADA; ELMER A FERNÁNDEZ

Hinxton, Cambridge, UK

Congreso; Functional Genomics and Systems Biology 2011, Wellcome Trust; 2011

Set enrichment analysis (SEA) is used to identify enriched biological categories/terms within a high-throughput differential expression experiments. This is performed by evaluating the proportion of differentially expressed genes against a background reference (BR). However, the choice of the ?appropriate? BR is a perplexing problem and results may depend on it (particularly for proteomics studies). Hence, in order to do SEA the user has to choose a reference, usually the whole genome or the chip-gene list. Nevertheless, potentially relevant terms could be missing due to the BR choice. In this work, a visualization procedure that helps SEA interpretation is presented. The multi-reference contrast method (MRCM) combines simultaneous results from multiple BRs (the genome, the chip-gene list and a reference lead by the experimental setting). The MRCM facilitates the experimental interpretation and also helps to validate relevant terms among consensus and/or to identify potentially relevant terms by contrast. The MRCM facilitates the exploration task involved in ontology analysis on proteomic/genomic experiments, where consensus terms were found to validate main experimental hypothesis. It also allows finding new biologically relevant categories/terms (literature validated) in several various experiments. In this sense, the use of more than one reference may provide new biological insights. Non-consensus terms were automatically highlighted by the MRCM, helping its interpretation and analysis. Its utility is shown in one proteomic study and evaluated in three microarrays based experiments.