Sampling the solution space in genome-scale metabolic networks reveals transcriptional regulation in key enzymes.

PLoS Computational Biology
Sergio BordelJens Nielsen

Abstract

Genome-scale metabolic models are available for an increasing number of organisms and can be used to define the region of feasible metabolic flux distributions. In this work we use as constraints a small set of experimental metabolic fluxes, which reduces the region of feasible metabolic states. Once the region of feasible flux distributions has been defined, a set of possible flux distributions is obtained by random sampling and the averages and standard deviations for each of the metabolic fluxes in the genome-scale model are calculated. These values allow estimation of the significance of change for each reaction rate between different conditions and comparison of it with the significance of change in gene transcription for the corresponding enzymes. The comparison of flux change and gene expression allows identification of enzymes showing a significant correlation between flux change and expression change (transcriptional regulation) as well as reactions whose flux change is likely to be driven only by changes in the metabolite concentrations (metabolic regulation). The changes due to growth on four different carbon sources and as a consequence of five gene deletions were analyzed for Saccharomyces cerevisiae. The enzymes w...Continue Reading

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Citations

Jul 18, 2014·BMC Systems Biology·Ana Conesa, Ali Mortazavi
Mar 1, 2012·Nature Reviews. Microbiology·Nathan E LewisBernhard O Palsson
May 2, 2013·BMC Systems Biology·Tobias ÖsterlundJens Nielsen
Sep 1, 2012·Science·Hojung NamBernhard O Palsson
Dec 29, 2015·Metabolic Engineering·Tadas JakočiūnasJay D Keasling
Aug 19, 2011·Biotechnology Advances·Tobias OsterlundJens Nielsen
Dec 24, 2015·Frontiers in Physiology·Xiang ZhangAlbert K Groen
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Dec 7, 2011·Journal of Internal Medicine·A Mardinoglu, J Nielsen
Mar 21, 2013·Molecular Systems Biology·Adil MardinogluJens Nielsen
Apr 1, 2011·Molecular Systems Biology·Jens Nielsen
Apr 25, 2013·Biotechnology Journal·Adil MardinogluJens Nielsen
Jan 1, 2014·Biotechnology and Bioengineering·Rodrigo Ledesma-AmaroJens Nielsen
Feb 24, 2015·Bioinformatics·Abdelmoneim Amer DesoukiMartin J Lercher
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Jun 17, 2016·Molecular Biology of the Cell·Petri-Jaan LahtveeJens Nielsen
Nov 4, 2016·Journal of Bioinformatics and Computational Biology·Fangzhou ShenZhuo Wang
May 16, 2017·PLoS Computational Biology·Siu Hung Joshua ChanCostas D Maranas
Dec 3, 2014·Seminars in Immunology·Rienk A RienksmaVitor A P Martins dos Santos
Mar 17, 2017·Annual Review of Biochemistry·Jens Nielsen
Jun 17, 2015·Integrative Biology : Quantitative Biosciences From Nano to Macro·Benjamín J Sánchez, Jens Nielsen
Aug 17, 2012·Scientific Reports·Steven M KelkFrank J Bruggeman
May 6, 2014·Nucleic Acids Research·Manuel Garcia-AlbornozJens Nielsen

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