The interdependent network of gene regulation and metabolism is robust where it needs to be

Abstract

The major biochemical networks of the living cell, the network of interacting genes and the network of biochemical reactions, are highly interdependent, however, they have been studied mostly as separate systems so far. In the last years an appropriate theoretical framework for studying interdependent networks has been developed in the context of statistical physics. Here we study the interdependent network of gene regulation and metabolism of the model organism Escherichia coli using the theoretical framework of interdependent networks. In particular we aim at understanding how the biological system can consolidate the conflicting tasks of reacting rapidly to (internal and external) perturbations, while being robust to minor environmental fluctuations, at the same time. For this purpose we study the network response to localized perturbations and find that the interdependent network is sensitive to gene regulatory and protein-level perturbations, yet robust against metabolic changes. This first quantitative application of the theory of interdependent networks to systems biology shows how studying network responses to localized perturbations can serve as a useful strategy for analyzing a wide range of other interdependent networks.

11 pages, 4 figures + Supplementary Material

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• A system-wide network reconstruction of gene regulation and metabolism in Escherichia coli
• Feedbacks from the metabolic network to the genetic network reveal regulatory modules in E. coli and B. subtilis
• Complexity and irreducibility of dynamics on networks of networks
• Realizing interdependent couplings as thermal or higher-order interactions
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• Network location and clustering of genetic mutations determine chronicity in a stylized model of genetic diseases