title: 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 ideal 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 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 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 has flexibility to handle all possible study-specific differential patterns. It improves detection of differential expression and overcomes the barrier of exponential model complexity.
authors.affiliation: Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USADepartment of Statistics, The Chinese University of Hong Kong, Shatin NT, Hong Kong.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Center for Regenerative Medicine, Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Tenzen
authors.affiliation: Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA hji@jhu.edu.
authors.forename: Hongkai
authors.initials: H
authors.lastname: Ji
mesh_terms: D000818:Animals; D003627:Data Interpretation, Statistical; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D051379:Mice; D046228:Microarray Analysis / Q000379:methods*; D008957:Models, Genetic
keywords: Bayes hierarchical model; Correlation motif; EM algorithm; Microarray; Multiple datasets