Thereafter, to reach a smaller and tractable set of hits to validate experimentally, we took advantage of testing each compound at four concentrations. Specifically, we used self-organizing maps analysis to cluster hit compounds by shape of the dose-response curve. The significance of change from dose to dose (0.24 to 1.2, 1.2 to 6, and 6 to 30) was also analyzed using linear models and moderated F-statistics as implemented in the limma package [57] in Bioconductor [55] . The concentration-response curves for each compound were then visually inspected, using scatter plots generated in TIBCO Spotfire DecisionSite (TIBCO, Palo Alto, CA), with respect to the shape of the curve and reproducibility between replicates. Compounds showing an erratic concentrationresponse (e.g. increase, then decrease, and increase again in ISRE activity with increasing concentration) were rejected. Compounds with a consistent increase or decrease in response with increasing drug concentration or good efficacy at any concentration were included for further validation. This approach led to selection of 64 compounds for further validation, including compounds with the 20 highest z-scores.