Gene expression values were obtained using the three-step Robust Multi-array Average (RMA) pre-processing method (Irizarry et al., 2003), implemented in the Affymetrix Inc. package from R/Bioconductor. We applied the ComBat method prior to analysis for adjusting data for undesirable experimental variation (or batch effect) caused by different days in which the microarrays were processed. ComBat implements an empirical Bayes approach, that is commonly used in microarray analyses due to its ability to robustly handle high-dimensional data when sample sizes are small (Johnson et al, 2007).
