Identification of Differentially Expressed Genes for Time-Course Microarray Data Based on Modified RM ANOVA

The regulation of gene expression is a dynamic process, hence it is of vital interest to identify and characterize changes in gene expression over time. We present here a general statistical method for detecting changes in microarray expression over time within a single biological group and is based on repeated measures (RM) ANOVA. In this method, unlike the classical F-statistic, statistical significance is determined taking into account the time dependency of the microarray data. A correction factor for this RM F-statistic is introduced leading to a higher sensitivity as well as high specificity. We investigate the two approaches that exist in the literature for calculating the p-values using resampling techniques of gene-wise p-values and pooled p-values. It is shown that the pooled p-values method compared to the method of the gene-wise p-values is more powerful, and computationally less expensive, and hence is applied along with the introduced correction factor to various synthetic data sets and a real data set. These results show that the proposed technique outperforms the current methods. The real data set results are consistent with the existing knowledge concerning the presence of the genes. The algorithms presented are implemented in R and are freely available upon request.