Smoothing Gene Expression Data with Network Information Improves Consistency of Regulated Genes

Dørum Guro, Snipen Lars, Solheim Margrete and Saebo Solve

Statistical Applications in Genetics and Molecular Biology, 2011, vol. 10, issue 1, 1-26

Abstract: Gene set analysis methods have become a widely used tool for including prior biological knowledge in the statistical analysis of gene expression data. Advantages of these methods include increased sensitivity, easier interpretation and more conformity in the results. However, gene set methods do not employ all the available information about gene relations. Genes are arranged in complex networks where the network distances contain detailed information about inter-gene dependencies. We propose a method that uses gene networks to smooth gene expression data with the aim of reducing the number of false positives and identify important subnetworks. Gene dependencies are extracted from the network topology and are used to smooth genewise test statistics. To find the optimal degree of smoothing, we propose using a criterion that considers the correlation between the network and the data. The network smoothing is shown to improve the ability to identify important genes in simulated data. Applied to a real data set, the smoothing accentuates parts of the network with a high density of differentially expressed genes.

Keywords: differentially expressed genes; gene network; gene set analysis; microarray data analysis; enrichment analysis (search for similar items in EconPapers)
Date: 2011
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DOI: 10.2202/1544-6115.1618

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