Independent Component Analysis Reveals the Transcriptional Regulatory Modules in USDA110.

The dynamic adaptation of bacteria to environmental changes is achieved through the coordinated expression of many genes, which constitutes a transcriptional regulatory network (TRN). USDA110 is an important model strain for the study of symbiotic nitrogen fixation (SNF), and its SNF ability largely depends on the TRN. In this study, independent component analysis was applied to 226 high-quality gene expression profiles of USDA110 microarray datasets, from which 64 iModulons were identified. Using these iModulons and their condition-specific activity levels, we (1) provided new insights into the connection between the FixLJ-FixK-FixK regulatory cascade and quorum sensing, (2) discovered the independence of the FixLJ-FixK-FixK and NifA/RpoN regulatory cascades in response to oxygen, (3) identified the FixLJ-FixK cascade as a mediator connecting the FixK-2 iModulon and the Phenylalanine iModulon, (4) described the differential activation of iModulons in USDA110 under different environmental conditions, and (5) proposed a notion of active-TRN based on the changes in iModulon activity to better illustrate the relationship between gene regulation and environmental condition. In sum, this research offered an iModulon-based TRN for USDA110, which formed a foundation for comprehensively understanding the intricate transcriptional regulation during SNF.