TopoNPA scores and statistics. Panels a) and b): 28-day rat inhalation study, parenchyma tissue. The two network, xenobiotic metabolism and TNF-IL1a-TLR-NF κB are perturbed across Low, Medium and High dose of cigarette smoke exposure. Panels c) and d): TNF treatment on RLAK cells. TNF-IL1a-TLR-NF κB network is perturbed in a dose and time dependent manner, while the xenobiotic network is not perturbed at any dose or time point. Panel e) The TopoNPA scores indicate an increased activation of the cell cycle processes as a function of recovery time after inhibitor washout (INH+GM vs. INH+INH). The perturbation is significant for all companion statistics at all time points. Panel f) NPA of the xenobiotic network for the comparisons of former smoker vs. never smoker (left bar) and current smoker vs. never smoker (middle bar) in GSE7895. The right bar shows the latter comparison in GSE19667. The significance at 0.05 level of the “O” and “K” statistics are indicated by ‘*o’ and ‘k*’. A grey “.o” or “k.”, indicates a P-value between 0.05 and 0.1. The significance with respect to the experimental variation is indicated by a red star or equivalently can be assessed with the confidence intervals.