Chromosome structure modeling tools and their evaluation in bacteria.

The three-dimensional (3D) structure of bacterial chromosomes is crucial for understanding chromosome function. With the growing availability of high-throughput chromosome conformation capture (3C/Hi-C) data, the 3D structure reconstruction algorithms have become powerful tools to study bacterial chromosome structure and function. It is highly desired to have a recommendation on the chromosome structure reconstruction tools to facilitate the prokaryotic 3D genomics. In this work, we review existing chromosome 3D structure reconstruction algorithms and classify them based on their underlying computational models into two categories: constraint-based modeling and thermodynamics-based modeling. We briefly compare these algorithms utilizing 3C/Hi-C datasets and fluorescence microscopy data obtained from Escherichia coli and Caulobacter crescentus, as well as simulated datasets. We discuss current challenges in the 3D reconstruction algorithms for bacterial chromosomes, primarily focusing on software usability. Finally, we briefly prospect future research directions for bacterial chromosome structure reconstruction algorithms.

Independent Component Analysis Reveals the Transcriptional Regulatory Modules in Bradyrhizobium diazoefficiens 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). Bradyrhizobium diazoefficiens 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 B. diazoefficiens 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-FixK2-FixK1 regulatory cascade and quorum sensing, (2) discovered the independence of the FixLJ-FixK2-FixK1 and NifA/RpoN regulatory cascades in response to oxygen, (3) identified the FixLJ-FixK2 cascade as a mediator connecting the FixK2-2 iModulon and the Phenylalanine iModulon, (4) described the differential activation of iModulons in B. diazoefficiens 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 B. diazoefficiens USDA110, which formed a foundation for comprehensively understanding the intricate transcriptional regulation during SNF.