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A common goal of microarray and related high-throughput genomic experiments is to identify genes that vary across biological condition. Most often this is accomplished by identifying genes with changes in mean expression level, so called differentially expressed (DE) genes, and a number of effective methods for identifying DE genes have been developed. Although useful, these approaches do not accommodate other types of differential regulation. An important example concerns differential coexpression (DC). Investigations of this class of genes are hampered by the large cardinality of the space to be interrogated as well as by influential outliers. As a result, existing DC approaches are often underpowered, exceedingly prone to false discoveries, and/or computationally intractable for even a moderately large number of pairs. To address this, an empirical Bayesian approach for identifying DC gene pairs is developed. The approach provides a false discovery rate controlled list of significant DC gene pairs without sacrificing power. It is applicable within a single study as well as across multiple studies. Computations are greatly facilitated by a modification to the expectation-maximization algorithm and a procedural heuristic. Simulations suggest that the proposed approach outperforms existing methods in far less computational time; and case study results suggest that the approach will likely prove to be a useful complement to current DE methods in high-throughput genomic studies., (© 2011, The International Biometric Society.)

Although both clustering and identification of differentially expressed genes are equally essential in most microarray studies, the two tasks are often conducted without regard to each other. This is clearly not the most efficient way of extracting information. The main aim of this article is to develop a coherent statistical method that can simultaneously cluster and detect differentially expressed genes. Through information sharing between the two tasks, the proposed approach gives more sensible clustering among genes and is more sensitive in identifying differentially expressed genes. The improvement over existing methods is illustrated in both our simulation results and a case study.