Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
PLoS One. 2007 Sep 12;2(9):e881. doi: 10.1371/journal.pone.0000881.
Several types of networks, such as transcriptional, metabolic or protein-protein interaction networks of various organisms have been constructed, that have provided a variety of insights into metabolism and regulation. Here, we seek to exploit the reaction-based networks of three organisms for comparative genomics. We use concepts from spectral graph theory to systematically determine how differences in basic metabolism of organisms are reflected at the systems level and in the overall topological structures of their metabolic networks.
METHODOLOGY/PRINCIPAL FINDINGS: Metabolome-based reaction networks of Mycobacterium tuberculosis, Mycobacterium leprae and Escherichia coli have been constructed based on the KEGG LIGAND database, followed by graph spectral analysis of the network to identify hubs as well as the sub-clustering of reactions. The shortest and alternate paths in the reaction networks have also been examined. Sub-cluster profiling demonstrates that reactions of the mycolic acid pathway in mycobacteria form a tightly connected sub-cluster. Identification of hubs reveals reactions involving glutamate to be central to mycobacterial metabolism, and pyruvate to be at the centre of the E. coli metabolome. The analysis of shortest paths between reactions has revealed several paths that are shorter than well established pathways.
We conclude that severe downsizing of the leprae genome has not significantly altered the global structure of its reaction network but has reduced the total number of alternate paths between its reactions while keeping the shortest paths between them intact. The hubs in the mycobacterial networks that are absent in the human metabolome can be explored as potential drug targets. This work demonstrates the usefulness of constructing metabolome based networks of organisms and the feasibility of their analyses through graph spectral methods. The insights obtained from such studies provide a broad overview of the similarities and differences between organisms, taking comparative genomics studies to a higher dimension.
已经构建了几种类型的网络，例如各种生物体的转录、代谢或蛋白质-蛋白质相互作用网络，这些网络为代谢和调控提供了多种见解。在这里，我们试图利用三种生物体的基于反应的网络进行比较基因组学研究。我们使用谱图理论中的概念系统地确定生物体的基本代谢差异如何在系统水平以及在其代谢网络的整体拓扑结构中反映出来。
方法/主要发现：根据 KEGG LIGAND 数据库，构建了结核分枝杆菌、麻风分枝杆菌和大肠杆菌的基于代谢组的反应网络，然后对网络进行图谱分析，以识别枢纽以及反应的子聚类。还检查了反应网络中的最短和替代路径。子聚类分析表明，分枝杆菌中的分枝酸途径的反应形成了一个紧密连接的子聚类。枢纽的识别表明，涉及谷氨酸的反应是分枝杆菌代谢的核心，而丙酮酸是大肠杆菌代谢组的中心。反应之间最短路径的分析揭示了一些比已建立的途径更短的路径。
我们的结论是，麻风分枝杆菌基因组的严重缩小并没有显著改变其反应网络的全局结构，但减少了其反应之间的替代路径总数，同时保持了它们之间的最短路径不变。在人类代谢组中不存在的分枝杆菌网络中的枢纽可以作为潜在的药物靶点进行探索。这项工作证明了构建生物体基于代谢组的网络并通过图谱方法对其进行分析的有效性。从这些研究中获得的见解提供了生物体之间相似性和差异性的广泛概述，将比较基因组学研究提升到了更高的维度。
