Empirical Bayes methods are widely used in the analysis of microarray gene expression data in order to identify the differentially expressed genes or genes that are associated with other general phenotypes. Available methods often assume that genes are independent. However, genes are expected to function interactively and to form molecular modules to affect the phenotypes. In order to account for regulatory dependency among genes, we propose in this paper a network-constrained empirical Bayes method for analyzing genomic data in the framework of general linear models, where the dependency of genes is modeled by a discrete Markov random field model defined on a pre-defined biological network. This method provides a statistical framework for integrating the known biological network information into the analysis of genomic data. We present an iterated conditional mode algorithm for parameter estimation and for estimating the posterior probabilities using Gibbs sampling. We demonstrate the application of the proposed methods using simulations and analysis of a human brain aging microarray gene expression data set.


Bioinformatics | Computational Biology