Figure 6.

Upstream Regulator Analysis of differentially expressed genes in vapers and smokers. The IPA Upstream Regulator Analysis was used to identify upstream regulators that are likely to account for the aberrant expression of genes identified in vapers and smokers. (A) The Upstream Regulator Heat Map for the top 25 upstream regulators is shown. Orange squares indicate predicted increase in regulator’s activity, whereas blue squares indicate predicted decrease in activity. Of interest, the most significant upstream regulators identified in both vapers and smokers are members of a large class of proteins known as cytokines (IL2, IL21, IL12, IFNα, IL18, etc.), which play a crucial role in innate immunity and inflammation. Based on the activation z-score, all cytokines in the list are predicted to be inhibited in both vapers and smokers, although the number of affected downstream molecules differs between the two groups. (B) Regulatory network of IL2, its targeted genes and downstream biological effects in vapers. In vapers, inhibition of IL2 is likely to lead to downregulation (indicated by blue lines) of genes (shown by green color), which in turn may lead to impaired immune response (i.e., lack of activation of T lymphocytes). (C) Regulatory network of IL2, its targeted genes and downstream biological effects in smokers. Likewise, in smokers, inhibition of IL2 is likely to disrupt normal immune functions, though the number of genes modulated by IL2 is much higher in smokers than vapers (25 vs. 6). For more indicators, please refer to the Prediction Legend.