Control of fluxes in metabolic networks

Georg Basler, Zoran Nikoloski, Abdelhalim Larhlimi, Albert László Barabási, Yang Yu Liu

Research output: Contribution to journalArticlepeer-review

Abstract (may include machine translation)

Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life.We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism.

Original languageEnglish
Pages (from-to)956-968
Number of pages13
JournalGenome Research
Volume26
Issue number7
DOIs
StatePublished - Jul 2016
Externally publishedYes

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