Throughout this work we adopted the term biomarker to refer to a metagene together with associated score that quantifies it in each brain tissue sample. The biomarker score for each sample was calculated as the mean expression levels of the comprising gene probes or as the arithmetic difference between the means in the positive and negative arms of the metagene when both arms were specified.where I/I 0 is normalized intensity of the metagene probes. To produce a robust score, all samples have to be normalized to the same reference. The reference intensity I 0 for each gene corresponded to the average intensity in the cohort. Importantly, averaging genes that correlate with each other produced a measure that is more accurate than individual genes. For all metagenes identified in this work, the biomarker score represented a quantitative measure of a particular disease aspect in each brain sample. To evaluate the performance of the biomarker score as a classifier between diseased and normal samples, we used the area under the curve for the receiver operating characteristic (AUROC) [30].
