Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300072, China; SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; Biodesign Center, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China; National Technology Innovation Center of Synthetic Biology, Tianjin 300308, China.
Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300072, China; SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
Microbiol Res. 2023 Nov;276:127485. doi: 10.1016/j.micres.2023.127485. Epub 2023 Sep 3.
Gene expression in bacteria is regulated by multiple transcription factors. Clarifying the regulation mechanism of gene expression is necessary to understand bacterial physiological activities. To further understand the structure of the transcriptional regulatory network of Corynebacterium glutamicum, we applied independent component analysis, an unsupervised machine learning algorithm, to the high-quality C. glutamicum gene expression profile which includes 263 samples from 29 independent projects. We obtained 87 robust independent regulatory modules (iModulons). These iModulons explain 76.7% of the variance in the expression profile and constitute the quantitative transcriptional regulatory network of C. glutamicum. By analyzing the constituent genes in iModulons, we identified potential targets for 20 transcription factors. We also captured the changes in iModulon activities under different growth rates and dissolved oxygen concentrations, demonstrating the ability of iModulons to comprehensively interpret transcriptional responses to environmental changes. In summary, this study provides a genome-scale quantitative transcriptional regulatory network for C. glutamicum and informs future research on complex changes in the transcriptome.
细菌中的基因表达受多个转录因子调控。阐明基因表达的调控机制对于理解细菌的生理活动是必要的。为了进一步了解谷氨酸棒杆菌转录调控网络的结构,我们应用独立成分分析(一种无监督机器学习算法)对高质量的谷氨酸棒杆菌基因表达谱进行分析,该表达谱包含 29 个独立项目中的 263 个样本。我们获得了 87 个稳健的独立调控模块(iModulons)。这些 iModulons 解释了表达谱中 76.7%的方差,构成了谷氨酸棒杆菌的定量转录调控网络。通过分析 iModulons 中的组成基因,我们确定了 20 个转录因子的潜在靶标。我们还捕捉到了不同生长速率和溶解氧浓度下 iModulon 活性的变化,证明了 iModulons 能够全面解释转录对环境变化的响应。总之,本研究为谷氨酸棒杆菌提供了一个全基因组规模的定量转录调控网络,并为未来研究转录组的复杂变化提供了信息。