BAYESIAN LATENT HIERARCHICAL MODEL FOR TRANSCRIPTOMIC META-ANALYSIS TO DETECT BIOMARKERS WITH CLUSTERED META-PATTERNS OF DIFFERENTIAL EXPRESSION SIGNALS

Ann Appl Stat. 2019 Mar;13(1):340-366. doi: 10.1214/18-AOAS1188. Epub 2019 Apr 10.

Abstract

Due to the rapid development of high-throughput experimental techniques and fast-dropping prices, many transcriptomic datasets have been generated and accumulated in the public domain. Meta-analysis combining multiple transcriptomic studies can increase the statistical power to detect disease-related biomarkers. In this paper, we introduce a Bayesian latent hierarchical model to perform transcriptomic meta-analysis. This method is capable of detecting genes that are differentially expressed (DE) in only a subset of the combined studies, and the latent variables help quantify homogeneous and heterogeneous differential expression signals across studies. A tight clustering algorithm is applied to detected biomarkers to capture differential meta-patterns that are informative to guide further biological investigation. Simulations and three examples, including a microarray dataset from metabolism-related knockout mice, an RNA-seq dataset from HIV transgenic rats, and cross-platform datasets from human breast cancer, are used to demonstrate the performance of the proposed method.

Keywords: Bayesian hierarchical model; Dirichlet process; meta-analysis; transcriptomic differential analysis.