Fully Bayesian mixture model for differential gene expression: simulations and model checks.
We present a Bayesian hierarchical model for detecting differentially expressed genes using a mixture prior on the parameters representing differential effects. We formulate an easily interpretable 3-component mixture to classify genes as over-expressed, under-expressed and non-differentially expressed, and model gene variances as exchangeable to allow for variability between genes. We show how the proportion of differentially expressed genes, and the mixture parameters, can be estimated in a fully Bayesian way, extending previous approaches where this proportion was fixed and empirically estimated. Good estimates of the false discovery rates are also obtained. Different parametric families for the mixture components can lead to quite different classifications of genes for a given data set. Using Affymetrix data from a knock out and wildtype mice experiment, we show how predictive model checks can be used to guide the choice between possible mixture priors. These checks show that extending the mixture model to allow extra variability around zero instead of the usual point mass null fits the data better. A software package for R is available.
Lewin
Alex
A
Imperial, London. a.m.lewin@imperial.ac.uk
Bochkina
Natalia
N
Richardson
Sylvia
S
D000818:Animals; D001499:Bayes Theorem; D003198:Computer Simulation; D020869:Gene Expression Profiling; D051379:Mice; D008957:Models, Genetic