NuGO PPS1 study 1: preliminary statistical analysis

Time course experiments are aimed at characterizing the dynamic regulation of gene expression in biological systems. Data are collected at different time points to monitor the dynamic behaviour of gene expression. The NuGO PPS Mouse Study 1 investigates the development of high fat-induced insulin resistance (IR) over time in APOE*3Leiden (E3L) mice. The study consists in a series of analyses at time points, which are crucial in the development of central and peripheral IR. Affymetrix arrays have been made on critical organs. We present the results of the preliminary statistical analysis on these microarray data. We used a non-parametric approach to identify genes the expression of which changed over time, separately for three tissues: liver, muscle and white adipose tissue. We specified for each gene a basic ANOVA model, in order to check the null hypothesis that gene expression did not vary over time. We addressed the multiple tests problem calculating positive false discovery rate and q values for the F test statistics. The appropriateness of the hypothesis of homogeneous variances over time was investigated by mean of the Bartlett’s test for homoschedasticity. This is a relevant point because heteroschedasticity could be indicative of outlying behaviour of some individuals at specific time points. The necessity to use a moderated F test was evaluated. We found that a considerable part of the genes varied expression over time. For part of the genes, the variance of the response was not homogeneous over time. Response differed by tissue.