Fig. 1.

Flow chart of three‐step study design. In the epigenomic analysis step, we performed a two‐phase strategy to screen and validate epigenome‐wide G × G interactions. In the transcriptomic analysis step, we firstly conducted a gene annotation and again performed a two‐phase study to evaluate and validate those interactions at transcriptional level. In the trans‐omics analysis step, we explored the trans‐omics regulatory relationships and evaluated indirect effect of epigenetic G × G interactions on NSCLC survival mediated through transcriptional G × G interactions, and followed by a series of in silico analyses for potential biological functions.