A Causal Regulation Modeling Algorithm for Temporal Events with Application to Escherichia coli 's Aerobic to Anaerobic Transition

• Published in: International journal of molecular sciences Vol. 25; no. 11
• Main Authors: Chen, Yigang, Mao, Runbo, Xu, Jiatong, Huang, Yixian, Xu, Jingyi, Cui, Shidong, Zhu, Zihao, Ji, Xiang, Huang, Shenghan, Huang, Yanzhe, Huang, Hsi-Yuan, Yen, Shih-Chung, Lin, Yang-Chi-Duang, Huang, Hsien-Da
• Format: Journal Article
• Language: English
• Published: Switzerland 22.05.2024
• Subjects: Aerobiosis; Algorithms; Anaerobiosis - genetics; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Gene Expression Profiling - methods; Gene Expression Regulation, Bacterial; Gene Regulatory Networks; Models, Biological; Signal Transduction - genetics; temporal transcriptomics; aerobic-to-anaerobic transition; biological modeling; Escherichia coli; causal signaling model
• ISSN: 1422-0067

Time-series experiments are crucial for understanding the transient and dynamic nature of biological phenomena. These experiments, leveraging advanced classification and clustering algorithms, allow for a deep dive into the cellular processes. However, while these approaches effectively identify patterns and trends within data, they often need to improve in elucidating the causal mechanisms behind these changes. Building on this foundation, our study introduces a novel algorithm for temporal causal signaling modeling, integrating established knowledge networks with sequential gene expression data to elucidate signal transduction pathways over time. Focusing on s ( ) aerobic to anaerobic transition (AAT), this research marks a significant leap in understanding the organism's metabolic shifts. By applying our algorithm to a comprehensive regulatory network and a time-series microarray dataset, we constructed the cross-time point core signaling and regulatory processes of 's AAT. Through gene expression analysis, we validated the primary regulatory interactions governing this process. We identified a novel regulatory scheme wherein environmentally responsive genes, and , activate , modulating the nitrogen metabolism regulators fnr and nac. This regulatory cascade controls the stress regulators and , ultimately affecting the cell motility gene , unveiling a novel regulatory axis that elucidates the complex regulatory dynamics during the AAT process. Our approach, merging empirical data with prior knowledge, represents a significant advance in modeling cellular signaling processes, offering a deeper understanding of microbial physiology and its applications in biotechnology.