Comparative network-based analysis of toll-like receptor agonist, L-pampo signaling pathways in immune and cancer cells

Toll-like receptors (TLRs) are critical immune components to stimulate immune responses against various infections. Recently, TLR agonists have emerged as a promising way to activate anti-tumor immunity. L-pampo, a TLR1/2 and TLR3 agonist, induces robust humoral and cellular immune responses but also causes cancer cell death. In this study, we investigated the L-pampo-induced signal pathways in immune and cancer cells and how they interact with TLRs and cancer-related pathways. First, we constructed a template network with differentially expressed genes and influential genes using the weighted gene co-expression network analysis (WGCNA). Next, we obtained perturbed modules using the same method and extracted core subnetworks from the modules by running Walktrap. Finally, we attempted to link the core subnetworks for reconstructing major molecular signals regarding the response to L-pampo utilizing a shortest path finding algorithm, TOPAS. Our analysis revealed that the key molecular processes were PI3K-AKT, JAK-STAT, and oxidative phosphorylation (OXPHOS) with reactive oxygen species (ROS) in immune and cancer cells. Notably, the OXPHOS process may be the crucial regulator for the differential responses of L-pampo between cancer cells of different tissue types. Our computational approaches can be applied to similar research for inferring underlying molecular mechanisms using complex gene expression profiles.