Bayesian modeling of differential gene expression.
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.
Department of Epidemiology and Public Health, Imperial College, Norfolk Place, London W2 1PG, UK. a.m.lewin@imperial.ac.uk
Alex
A
Lewin
Sylvia
S
Richardson
Clare
C
Marshall
Anne
A
Glazier
Tim
T
Aitman
D000818:Animals; D001499:Bayes Theorem; D001699:Biometry; D005189:False Positive Reactions; D020869:Gene Expression Profiling / Q000592:standards / Q000706:statistics & numerical data*; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis / Q000706:statistics & numerical data*