Longitudinal analysis of gene expression profiles using functional mixed-effects models

In many longitudinal microarray studies, the gene expression levels in a random sample are observed repeatedly over time under two or more conditions. The resulting time courses are generally very short, high-dimensional, and may have missing values. Moreover, for every gene, a certain amount of variability in the temporal profiles, among biological replicates, is generally observed. We propose a functional mixed-effects model for estimating the temporal pattern of each gene, which is assumed to be a smooth function. A statistical test based on the distance between the fitted curves is then carried out to detect differential expression. A simulation procedure for assessing the statistical power of our model is also suggested. We evaluate the model performance using both simulations and a real data set investigating the human host response to BCG exposure.