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RP62A的代谢网络:验证与干预策略

RP62A's Metabolic Network: Validation and Intervention Strategies.

作者信息

Guil Francisco, Sánchez-Cid Guillermo, García José M

机构信息

Grupo de Arquitectura y Computación Paralela, Universidad de Murcia, 30080 Murcia, Spain.

出版信息

Metabolites. 2022 Aug 28;12(9):808. doi: 10.3390/metabo12090808.

Abstract

Increasingly, systems biology is gaining relevance in basic and applied research. The combination of computational biology with wet laboratory methods produces synergy that results in an exponential increase in knowledge of biological systems. The study of microorganisms such as RP62A enables the researcher to understand better their metabolic networks, which allows the design of effective strategies to treat infections caused by this species or others. is the second most commoncause of infection in patients with joint implants, so treating its proliferation seems vital for public health. There are different approaches to the analysis of metabolic networks. Flux balance analysis (FBA) is one of the most widespread streams of research. It allows the study of large metabolic networks, the study their structural properties, the optimization of metabolic flux, and the search for intervention strategies to modify the state of the metabolic network. This work presents the validation of the RP62A metabolic network model elaborated by Díaz Calvo et al. Then, we elaborate further on the network analysis's essential reactions. The full set of essential reactions (including a previously unobserved one) was computed, and we classified them into equivalence classes. Some proposals to intervene in the network and design knock-outs by studying minimal cut sets of small length are also introduced. In particular, minimal cut sets related to the medium (including exchange reactions associated with medium metabolites) have been computed. In this sense, the unique external MCS (composed of cysteine and sulfate ion) has been found, and all hybrid MCS (based on knocking out both internal and exchange reactions) of length two have also been computed. The paper also points out the possible importance of these new intervention strategies.

摘要

系统生物学在基础研究和应用研究中的相关性日益增加。计算生物学与湿实验室方法的结合产生了协同作用,导致生物系统知识呈指数级增长。对诸如RP62A等微生物的研究使研究人员能够更好地理解它们的代谢网络,从而能够设计出有效的策略来治疗由该物种或其他物种引起的感染。RP62A是关节植入患者感染的第二大常见原因,因此治疗其增殖对公共卫生似乎至关重要。代谢网络分析有不同的方法。通量平衡分析(FBA)是最广泛的研究方向之一。它允许研究大型代谢网络、研究其结构特性、优化代谢通量,以及寻找改变代谢网络状态的干预策略。这项工作展示了由迪亚斯·卡尔沃等人构建的RP62A代谢网络模型的验证。然后,我们进一步阐述了网络分析中的关键反应。计算了全套关键反应(包括一个以前未观察到的反应),并将它们分类为等价类。还介绍了一些通过研究短长度的最小割集来干预网络并设计基因敲除的建议。特别是,计算了与培养基相关的最小割集(包括与培养基代谢物相关的交换反应)。从这个意义上说,发现了独特的外部最小割集(由半胱氨酸和硫酸根离子组成),并且还计算了所有长度为二的混合最小割集(基于敲除内部和交换反应)。本文还指出了这些新干预策略可能的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac24/9503974/1f276cc07d9a/metabolites-12-00808-g001.jpg

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