In this paper we define a hierarchical Bayesian model for microarray expression data collected from several studies and use it to identify genes that show differential expression between two conditions. Key features include shrinkage across both genes and studies; flexible modeling that allows for interactions between platforms and the estimated effect, and for both concordant and discordant differential expression across studies. We evaluated the performance of our model in a comprehensive fashion, using both artificial data, and a "split-sample" validation approach that provides an agnostic assessment of the model's behavior not only under the null hypothesis but also under a realistic alternative. The simulation results from the artificial data demonstrate the advantages of a Bayesian model. Compared to a more direct combination of t- or SAM-statistics, the 1-AUC values for the Bayesian model is roughly half of the corresponding values for the t- and SAM-statistics. Furthermore, the simulations provide guidelines for when the Bayesian model is most likely to be useful. Most noticeably, in small studies the Bayesian model generally Outperforms other methods when evaluated by AUC, FDR, and MDR across a range of simulation parameters, and this difference diminishes for larger sample sizes in the individual studies. The split-study validation illustrates appropriate shrinkage of the Bayesian model in the absence of platform-, sample-, and annotation-differences that otherwise complicate experimental data analyses. Finally, we fit our model to four breast cancer studies employing different technologies (cDNA and Affymetrix) to estimate differential expression in estrogen receptor positive tumors versus negative ones. Software and data for reproducing our analysis are publicly available.
Bioinformatics | Computational Biology
Scharpf, Robert B.; Tjelemeland, Hakon ; Parmigiani, Giovanni; and Nobel, Andrew B., "A BAYESIAN MODEL FOR CROSS-STUDY DIFFERENTIAL GENE EXPRESSION" (November 2007). Johns Hopkins University, Dept. of Biostatistics Working Papers. Working Paper 158.