Fig. 4.

Smoking-sensitive AJC-associated molecular pathways. a IPA-based canonical pathways enriched among AJC-associated genes (smoking-sensitive genes negatively correlating with the I_AJC with r < −0.5). The ordinate indicates the degree of enrichment (percent of AJC-associated genes belonging to the pathway; orange boxes) and shows −log P values of enrichment. The axonal guidance pathway (enrichment 3.3%; P < 0.01) was excluded as being specific to neuronal signaling. b Spearman correlation (ρ) analysis of the PTEN gene normalized expression in the SAE of healthy smokers with the I_AJC. c STRING 8.2-based model of relationships between smoking-responsive physiological AJC-encoding genes and selected AJC-related genes correlating with the I_AJC with r < −0.5. Each circle corresponds to an individual gene with the size proportional to the degree of correlation (r) with the I_AJC, and the color corresponding to the clusters in which the genes were grouped based on known protein–protein interactions (Markov clustering); the form of the lines reflects the confidence of the association from thick (most confident) to dashed (least confident)