IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41392-6.html
   My bibliography  Save this article

Local flux coordination and global gene expression regulation in metabolic modeling

Author

Listed:
  • Gaoyang Li

    (Jilin University
    Tongji University)

  • Li Liu

    (Duke Kunshan University)

  • Wei Du

    (Jilin University)

  • Huansheng Cao

    (Duke Kunshan University)

Abstract

Genome-scale metabolic networks (GSMs) are fundamental systems biology representations of a cell’s entire set of stoichiometrically balanced reactions. However, such static GSMs do not incorporate the functional organization of metabolic genes and their dynamic regulation (e.g., operons and regulons). Specifically, there are numerous topologically coupled local reactions through which fluxes are coordinated; the global growth state often dynamically regulates many gene expression of metabolic reactions via global transcription factor regulators. Here, we develop a GSM reconstruction method, Decrem, by integrating locally coupled reactions and global transcriptional regulation of metabolism by cell state. Decrem produces predictions of flux and growth rates, which are highly correlated with those experimentally measured in both wild-type and mutants of three model microorganisms Escherichia coli, Saccharomyces cerevisiae, and Bacillus subtilis under various conditions. More importantly, Decrem can also explain the observed growth rates by capturing the experimentally measured flux changes between wild-types and mutants. Overall, by identifying and incorporating locally organized and regulated functional modules into GSMs, Decrem achieves accurate predictions of phenotypes and has broad applications in bioengineering, synthetic biology, and microbial pathology.

Suggested Citation

  • Gaoyang Li & Li Liu & Wei Du & Huansheng Cao, 2023. "Local flux coordination and global gene expression regulation in metabolic modeling," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41392-6
    DOI: 10.1038/s41467-023-41392-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41392-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-41392-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Aditya Vikram Pandit & Shyam Srinivasan & Radhakrishnan Mahadevan, 2017. "Redesigning metabolism based on orthogonality principles," Nature Communications, Nature, vol. 8(1), pages 1-11, August.
    2. Mattia Zampieri & Manuel Hörl & Florian Hotz & Nicola F. Müller & Uwe Sauer, 2019. "Regulatory mechanisms underlying coordination of amino acid and glucose catabolism in Escherichia coli," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    3. Hugo Dourado & Martin J. Lercher, 2020. "An analytical theory of balanced cellular growth," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    4. H. Jeong & B. Tombor & R. Albert & Z. N. Oltvai & A.-L. Barabási, 2000. "The large-scale organization of metabolic networks," Nature, Nature, vol. 407(6804), pages 651-654, October.
    5. Réka Albert & Hawoong Jeong & Albert-László Barabási, 2000. "Error and attack tolerance of complex networks," Nature, Nature, vol. 406(6794), pages 378-382, July.
    6. Ali Khodayari & Costas D. Maranas, 2016. "A genome-scale Escherichia coli kinetic metabolic model k-ecoli457 satisfying flux data for multiple mutant strains," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    7. Naveen Venayak & Axel von Kamp & Steffen Klamt & Radhakrishnan Mahadevan, 2018. "MoVE identifies metabolic valves to switch between phenotypic states," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    8. Martin Lempp & Niklas Farke & Michelle Kuntz & Sven Andreas Freibert & Roland Lill & Hannes Link, 2019. "Systematic identification of metabolites controlling gene expression in E. coli," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Laurienti, Paul J. & Joyce, Karen E. & Telesford, Qawi K. & Burdette, Jonathan H. & Hayasaka, Satoru, 2011. "Universal fractal scaling of self-organized networks," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 390(20), pages 3608-3613.
    2. Wen, Xiangxi & Tu, Congliang & Wu, Minggong, 2018. "Node importance evaluation in aviation network based on “No Return” node deletion method," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 503(C), pages 546-559.
    3. Selen Onel & Abe Zeid & Sagar Kamarthi, 2011. "The structure and analysis of nanotechnology co-author and citation networks," Scientometrics, Springer;Akadémiai Kiadó, vol. 89(1), pages 119-138, October.
    4. Hayato Goto & Hideki Takayasu & Misako Takayasu, 2017. "Estimating risk propagation between interacting firms on inter-firm complex network," PLOS ONE, Public Library of Science, vol. 12(10), pages 1-12, October.
    5. P.B., Divya & Lekha, Divya Sindhu & Johnson, T.P. & Balakrishnan, Kannan, 2022. "Vulnerability of link-weighted complex networks in central attacks and fallback strategy," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 590(C).
    6. Foti, Nicholas J. & Pauls, Scott & Rockmore, Daniel N., 2013. "Stability of the World Trade Web over time – An extinction analysis," Journal of Economic Dynamics and Control, Elsevier, vol. 37(9), pages 1889-1910.
    7. Caccioli, Fabio & Farmer, J. Doyne & Foti, Nick & Rockmore, Daniel, 2015. "Overlapping portfolios, contagion, and financial stability," Journal of Economic Dynamics and Control, Elsevier, vol. 51(C), pages 50-63.
    8. Matteo Mori & Chuankai Cheng & Brian R. Taylor & Hiroyuki Okano & Terence Hwa, 2023. "Functional decomposition of metabolism allows a system-level quantification of fluxes and protein allocation towards specific metabolic functions," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Tsuchiya, Masa & Selvarajoo, Kumar & Piras, Vincent & Tomita, Masaru & Giuliani, Alessandro, 2009. "Local and global responses in complex gene regulation networks," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 388(8), pages 1738-1746.
    10. Sun, Lanfang & Jiang, Lu & Li, Menghui & He, Dacheng, 2006. "Statistical analysis of gene regulatory networks reconstructed from gene expression data of lung cancer," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 370(2), pages 663-671.
    11. Yuji Yamamoto & Keiko Yokoyama, 2011. "Common and Unique Network Dynamics in Football Games," PLOS ONE, Public Library of Science, vol. 6(12), pages 1-6, December.
    12. LaRocca, Sarah & Guikema, Seth D., 2015. "Characterizing and predicting the robustness of power-law networks," Reliability Engineering and System Safety, Elsevier, vol. 133(C), pages 157-166.
    13. Pagani, Giuliano Andrea & Aiello, Marco, 2013. "The Power Grid as a complex network: A survey," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 392(11), pages 2688-2700.
    14. N. Foti & S. Pauls & Daniel N. Rockmore, 2011. "Stability of the World Trade Web over Time - An Extinction Analysis," Papers 1104.4380, arXiv.org, revised May 2011.
    15. John Platig & Peter J Castaldi & Dawn DeMeo & John Quackenbush, 2016. "Bipartite Community Structure of eQTLs," PLOS Computational Biology, Public Library of Science, vol. 12(9), pages 1-17, September.
    16. Biggiero, Lucio & Angelini, Pier Paolo, 2015. "Hunting scale-free properties in R&D collaboration networks: Self-organization, power-law and policy issues in the European aerospace research area," Technological Forecasting and Social Change, Elsevier, vol. 94(C), pages 21-43.
    17. Markovič, Rene & Gosak, Marko & Marhl, Marko, 2014. "Broad-scale small-world network topology induces optimal synchronization of flexible oscillators," Chaos, Solitons & Fractals, Elsevier, vol. 69(C), pages 14-21.
    18. Gong, Pulin & van Leeuwen, Cees, 2003. "Emergence of scale-free network with chaotic units," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 321(3), pages 679-688.
    19. Tachimori, Yutaka & Iwanaga, Hiroaki & Tahara, Takashi, 2013. "The networks from medical knowledge and clinical practice have small-world, scale-free, and hierarchical features," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 392(23), pages 6084-6089.
    20. Guillaume, Jean-Loup & Latapy, Matthieu, 2006. "Bipartite graphs as models of complex networks," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 371(2), pages 795-813.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41392-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.