A powerful Bayesian meta-analysis method to integrate multiple gene set enrichment studies

摘要

Motivation: Much research effort has been devoted to the identification of enriched gene sets for microarray experiments. However, identified gene sets are often found to be inconsistent among independent studies. This is probably owing to the noisy data of microarray experiments coupled with small sample sizes of individual studies. Therefore, combining information from multiple studies is likely to improve the detection of truly enriched gene classes. As more and more data become available, it calls for statistical methods to integrate information from multiple studies, also known as meta-analysis, to improve the power of identifying enriched gene sets. Results: We propose a Bayesian model that provides a coherent framework for joint modeling of both gene set information and gene expression data from multiple studies, to improve the detection of enriched gene sets by leveraging information from different sources available. One distinct feature of our method is that it directly models the gene expression data, instead of using summary statistics, when synthesizing studies. Besides, the proposed model is flexible and offers an appropriate treatment of between-study heterogeneities that frequently arise in the meta-analysis of microarray experiments. We show that under our Bayesian model, the full posterior conditionals all have known distributions, which greatly facilitates the MCMC computation. Simulation results show that the proposed method can improve the power of gene set enrichment meta-analysis, as opposed to existing methods developed by Shen and Tseng (2010, Bioinformatics, 26, 1316-1323), and it is not sensitive to mild or moderate deviations from the distributional assumption for gene expression data. We illustrate the proposed method through an application of combining eight lung cancer datasets for gene set enrichment analysis, which demonstrates the usefulness of the method.