时间序列实验对于理解生物现象的瞬态和动态性质至关重要。这些实验,利用先进的分类和聚类算法,允许深入了解细胞过程。然而,虽然这些方法有效地识别数据中的模式和趋势,他们经常需要改进阐明这些变化背后的因果机制。建立在这个基础上,我们的研究介绍了一种用于时间因果信号建模的新算法,整合已建立的知识网络与序列基因表达数据,以阐明随着时间的推移信号转导途径。专注于大肠杆菌(E.大肠杆菌)需氧到厌氧过渡(AAT),这项研究标志着在理解生物体的代谢变化方面的重大飞跃。通过将我们的算法应用于全面的大肠杆菌调控网络和时间序列微阵列数据集,我们构建了大肠杆菌AAT的跨时间点核心信号和调控过程。通过基因表达分析,我们验证了支配这一过程的主要调控相互作用.我们确定了一种新的调控方案,其中环境响应基因,soxR和oxyR,激活毛皮,调节氮代谢调节剂fnr和nac。这种调节级联控制应力调节剂ompR和lrhA,最终影响细胞运动基因flhD,揭示了一个新颖的监管轴,阐明了AAT过程中复杂的监管动态。我们的方法,将经验数据与先验知识合并,代表了细胞信号过程建模的重大进步,对微生物生理学及其在生物技术中的应用有更深入的了解。
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 Escherichia coli\'s (E. coli) 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 E. coli regulatory network and a time-series microarray dataset, we constructed the cross-time point core signaling and regulatory processes of E. coli\'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, soxR and oxyR, activate fur, modulating the nitrogen metabolism regulators fnr and nac. This regulatory cascade controls the stress regulators ompR and lrhA, ultimately affecting the cell motility gene flhD, 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.