Active Protein Network Analysis Reveals Coordinated Modules and Critical Proteins Involving Extracellular Electron Transfer Process

Background: Traditional differential expression analysis typically identifies genes with varying expression levels and uses them to construct networks. However, this approach often fails to capture changes in gene interactions that occur at constant gene expression levels. Objectives: To address this limitation, this study investigated the dynamics of protein interactions through active networks under various conditions, focusing on Shewanella oneidensis MR-1, a model electroactive microorganism. Methods: We constructed both condition-specific and time-course active protein networks using gene expression and protein interaction data from S. oneidensis MR-1. Results: Our analysis revealed several functional modules that were active and well-coordinated under different extracellular electron transfer (EET) conditions. Notably, despite ongoing environmental changes, the dynamics of protein interactions in these networks primarily revolved around two central proteins, SO_0225 and SO_2402. These proteins play crucial roles in coordinating interaction dynamics under oxygen-limited conditions. Additionally, our time-course network analysis elucidated the activation stages of the classical Mtr pathway. Conclusions: This article highlights the dynamic reorganization of protein interaction networks in S. Oneidensis MR-1 under varying EET conditions. These findings provide insights into how electroactive bacteria dynamically regulate protein interactions to optimize electron transfer pathways in response to environmental changes.