S-scores are normally distributed with a mean of 0 and a standard deviation of 1 [27]. For 2-tailed tests, p-values for each probe-set were calculated as twice the probability of obtaining an S-score at least as large as the absolute value of the observed S-score. Statistical significance of a given probe-set's ethanol response across BXD strains was assessed using Fisher's combined probability test [29]. An R implementation of Fisher's method, available as part of the MADAM package [30], was used to combine the S-score transformed p-values. This process was then repeated for 1,000 random permutations of the observed S-score expression matrix, so that empirical p-values could be obtained by comparing observed results to the permutation distribution. Finally, to correct for multiple testing, q-values were generated from the empirical p-values [31]. Probe-sets with q-values≤0.05 were considered to be significantly ethanol-responsive.
