Bayesian Modeling of Differential Gene Expression
Article first published online: 19 JUL 2005
Volume 62, Issue 1, pages 10–18, March 2006
How to Cite
Lewin, A., Richardson, S., Marshall, C., Glazier, A. and Aitman, T. (2006), Bayesian Modeling of Differential Gene Expression. Biometrics, 62: 10–18. doi: 10.1111/j.1541-0420.2005.00394.x
- Issue published online: 19 JUL 2005
- Article first published online: 19 JUL 2005
- Received October 2003. Revised February 2005. Accepted March 2005.
- Bayesian analysis;
- Differential expression;
- Hierarchical model;
- Model checks;
Summary We present a Bayesian hierarchical model for detecting differentially expressing genes that includes simultaneous estimation of array effects, and show how to use the output for choosing lists of genes for further investigation. We give empirical evidence that expression-level dependent array effects are needed, and explore different nonlinear functions as part of our model-based approach to normalization. The model includes gene-specific variances but imposes some necessary shrinkage through a hierarchical structure. Model criticism via posterior predictive checks is discussed. Modeling the array effects (normalization) simultaneously with differential expression gives fewer false positive results. To choose a list of genes, we propose to combine various criteria (for instance, fold change and overall expression) into a single indicator variable for each gene. The posterior distribution of these variables is used to pick the list of genes, thereby taking into account uncertainty in parameter estimates. In an application to mouse knockout data, Gene Ontology annotations over- and underrepresented among the genes on the chosen list are consistent with biological expectations.