Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, Queensland, Australia.
ARC Training Centre for Biopharmaceutical Innovation (CBI), Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, Queensland, Australia.
PLoS Comput Biol. 2022 Jun 27;18(6):e1010203. doi: 10.1371/journal.pcbi.1010203. eCollection 2022 Jun.
The topology of metabolic networks is recognisably modular with modules weakly connected apart from sharing a pool of currency metabolites. Here, we defined modules as sets of reversible reactions isolated from the rest of metabolism by irreversible reactions except for the exchange of currency metabolites. Our approach identifies topologically independent modules under specific conditions associated with different metabolic functions. As case studies, the E.coli iJO1366 and Human Recon 2.2 genome-scale metabolic models were split in 103 and 321 modules respectively, displaying significant correlation patterns in expression data. Finally, we addressed a fundamental question about the metabolic flexibility conferred by reversible reactions: "Of all Directed Topologies (DTs) defined by fixing directions to all reversible reactions, how many are capable of carrying flux through all reactions?". Enumeration of the DTs for iJO1366 model was performed using an efficient depth-first search algorithm, rejecting infeasible DTs based on mass-imbalanced and loopy flux patterns. We found the direction of 79% of reversible reactions must be defined before all directions in the network can be fixed, granting a high degree of flexibility.
代谢网络的拓扑结构具有明显的模块性，模块之间的连接较弱，除了共享货币代谢物池外。在这里，我们将模块定义为可逆反应的集合，这些反应通过不可逆反应与代谢的其余部分隔离，除了货币代谢物的交换。我们的方法在与不同代谢功能相关的特定条件下识别拓扑上独立的模块。作为案例研究，将 E.coli iJO1366 和 Human Recon 2.2 基因组规模的代谢模型分别划分为 103 和 321 个模块，在表达数据中显示出显著的相关模式。最后，我们解决了关于可逆反应赋予的代谢灵活性的一个基本问题：“在所有可逆反应的方向固定的所有有向拓扑 (DT) 中，有多少能够通过所有反应传递通量？”。使用有效的深度优先搜索算法对 iJO1366 模型的 DTs 进行了枚举，根据质量不平衡和循环通量模式拒绝不可行的 DTs。我们发现，在网络中的所有方向都可以固定之前，必须先定义 79%的可逆反应的方向，从而赋予高度的灵活性。
