Estimation of random effects and identifying heterogeneous genes in meta-analysis of gene expression studies.

Abstract

Combining effect sizes from individual studies using random-effects meta-analysis models are commonly applied in high-dimensional gene expression data. However, unknown study heterogeneity can arise from inconsistencies in sample quality and experimental conditions. High heterogeneity of effect sizes can reduce statistical power of the models. In this study, we describe three hypothesis-testing frameworks for meta-analysis of microarray data, and review several existing meta-analytic techniques that have been used in the genomic setting. These include P-value-based methods, rank-based methods and effect-size-based methods. We then discuss limitations of some of these methods and describe random-effects-based methods in detail. We introduce two methods for estimating the inter-study variance in random-effects meta-analytic models and another method for identifying heterogeneous genes for gene expression data. We compared various methods with the standard and existing meta-analytic techniques in the genomic framework. We demonstrate our results through a series of simulations and application in Alzheimer's gene expression data.