TY - JOUR
T1 - Control of fluxes in metabolic networks
AU - Basler, Georg
AU - Nikoloski, Zoran
AU - Larhlimi, Abdelhalim
AU - Barabási, Albert László
AU - Liu, Yang Yu
N1 - Publisher Copyright:
© 2016 Basler et al.
PY - 2016/7
Y1 - 2016/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84976905638&partnerID=8YFLogxK
U2 - 10.1101/gr.202648.115
DO - 10.1101/gr.202648.115
M3 - Article
C2 - 27197218
AN - SCOPUS:84976905638
SN - 1088-9051
VL - 26
SP - 956
EP - 968
JO - Genome Research
JF - Genome Research
IS - 7
ER -