Gene2role: a role-based gene embedding method for comparative analysis of signed gene regulatory networks

Abstract

AbstractMotivationUnderstanding the dynamics of gene regulatory networks (GRNs) across various cellular states is crucial for deciphering the underlying mechanisms governing cell behavior and functionality. However, current comparative analytical methods, which often focus on simple topological information such as the degree of genes, are limited in their ability to fully capture the similarities and differences among the complex GRNs.ResultsWe present Gene2role, a gene embedding approach that leverages multi-hop topological information from genes within signed GRNs. Initially, we demonstrated the effectiveness of Gene2role in capturing the intricate topological nuances of genes using GRNs inferred from four distinct data sources. Then, applying Gene2role to integrated GRNs allowed us to identify genes with significant topological changes across cell types or states, offering a fresh perspective beyond traditional differential gene expression analysis. Additionally, we quantified the stability of gene modules between two cellular states by measuring the changes in the gene embeddings within these modules. In conclusion, our method augments the existing toolkit for probing the dynamic regulatory landscape, thereby opening new avenues for understanding gene behavior and interaction patterns across cellular transitions.