Multi-omics peripheral and core regions of cancer

Abstract

AbstractThousands of genes are perturbed by cancer, and these disturbances can be seen in transcriptome, methylation, somatic mutation, and copy number variation omics studies. Understanding their connectivity patterns as an omnigenic neighbourhood in a molecular interaction network (interactome) is a key step towards advancing knowledge of the molecular mechanisms underlying cancers. Here, we introduce a unified connectivity line (CLine) to pinpoint omics-specific omnigenic patterns across 15 curated cancers. Taking advantage of the universality of CLine, we distinguish the peripheral and core genes for each omics aspect. We propose a network-based framework, multi-omics periphery and core (MOPC), to combine peripheral and core genes from different omics into a button-like structure. On the basis of network proximity, we provide evidence that core genes tend to be specifically perturbed in one omics, but the peripheral genes are diversely perturbed in multiple omics. And the core of one omics is regulated by multiple omics peripheries. Finally, we take the MOPC as an omnigenic neighbourhood, describe its characteristics, and explore its relative contribution to network-based mechanisms of cancer. We were able to present how multi-omics perturbations percolate through the human interactome and contribute to an integrated periphery and core.