Multi-layer network modelling of genomic and transcriptomic data to investigate the response to checkpoint inhibitors in NSCLC

Recent innovations and developments in molecular biology and biotechnology have made it possible to acquire and store large omics datasets. In particular genomics, transcriptomics and the study of their relationship represent the key elements to understand how genotype influences phenotype. In this work we investigate the potential of multi-layer network modeling in integrating genomic and transcriptomic data of 152 advanced non-small cell lung cancer (NSCLC) patients treated with anti-PD-(L)1 therapy. For the transcriptomic layer, we performed differential expression and differential co-expression analyses in order to identify a subset of key genes in differentiating responder patients from non-responders. Adding to the genomic-transcriptomic model other three layers related to immune, myeloid and curated immunotherapy-based literature signatures we obtained a 5-layer Patient Similarity Network. The application of Similarity Network Fusion algorithm revealed a statistically significant stratification of patients (p-value ≤ 0.05) which allows the identification of two clusters characterized by patients responding and not responding to immunotherapy.