Joint Analysis of Differential Gene Expression in Multiple Studies using Correlation Motifs

Abstract

The standard methods for detecting differential gene expression are mostly designed for analyzing a single gene expression experiment. When data from multiple related gene expression studies are available, separately analyzing each study is not an ideal strategy as it may fail to detect important genes with consistent but relatively weak differential signals in multiple studies. Jointly modeling all data allows one to borrow information across studies to improve the analysis. However, a simple concordance model, in which each gene is assumed to be differential in either all studies or none of the studies, is incapable of handling genes with study-specific differential expression. In contrast, a model that naively enumerates and analyzes all possible differential patterns across all studies can deal with study-specificity and allow information pooling, but the complexity of its parameter space grows exponentially as the number of studies increases. Here we propose a "correlation motif" approach to address this dilemma. This approach automatically searches for a small number of latent probability vectors called "correlation motifs" to capture the major correlation patterns among multiple studies. The motifs provide the basis for sharing information among studies and genes. The approach improves detection of differential expression and overcomes the barrier of exponentially growing parameter space. It is capable of handling all possible study-specific differential patterns in a large number of studies. The advantages of this new approach over existing methods are illustrated using both simulated and real data.