Email updates

Keep up to date with the latest news and content from BMC Bioinformatics and BioMed Central.

Open Access Highly Accessed Research article

Investigating the effect of paralogs on microarray gene-set analysis

Andre J Faure12*, Cathal Seoighe13 and Nicola J Mulder1

Author Affiliations

1 Computational Biology Group, Department of Clinical Laboratory Sciences, University of Cape Town, Cape Town, South Africa

2 EMBL-European Bioinformatics Institute (EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

3 School of Mathematics, Statistics and Applied Mathematics, National University of Ireland Galway, Ireland

For all author emails, please log on.

BMC Bioinformatics 2011, 12:29  doi:10.1186/1471-2105-12-29

Published: 24 January 2011

Abstract

Background

In order to interpret the results obtained from a microarray experiment, researchers often shift focus from analysis of individual differentially expressed genes to analyses of sets of genes. These gene-set analysis (GSA) methods use previously accumulated biological knowledge to group genes into sets and then aim to rank these gene sets in a way that reflects their relative importance in the experimental situation in question. We suspect that the presence of paralogs affects the ability of GSA methods to accurately identify the most important sets of genes for subsequent research.

Results

We show that paralogs, which typically have high sequence identity and similar molecular functions, also exhibit high correlation in their expression patterns. We investigate this correlation as a potential confounding factor common to current GSA methods using Indygene http://www.cbio.uct.ac.za/indygene webcite, a web tool that reduces a supplied list of genes so that it includes no pairwise paralogy relationships above a specified sequence similarity threshold. We use the tool to reanalyse previously published microarray datasets and determine the potential utility of accounting for the presence of paralogs.

Conclusions

The Indygene tool efficiently removes paralogy relationships from a given dataset and we found that such a reduction, performed prior to GSA, has the ability to generate significantly different results that often represent novel and plausible biological hypotheses. This was demonstrated for three different GSA approaches when applied to the reanalysis of previously published microarray datasets and suggests that the redundancy and non-independence of paralogs is an important consideration when dealing with GSA methodologies.