A simplified metabolic network reconstruction to promote understanding and development of flux balance analysis tools

Comput Biol Med. 2019 Feb;105:64-71. doi: 10.1016/j.compbiomed.2018.12.010. Epub 2018 Dec 17.


GEnome-scale Network REconstructions (GENREs) mathematically describe metabolic reactions of an organism or a specific cell type. GENREs can be used with a number of constraint-based reconstruction and analysis (COBRA) methods to make computational predictions on how a system changes in different environments. We created a simplified GENRE (referred to as iSIM) that captures central energy metabolism with nine metabolic reactions to illustrate the use of and promote the understanding of GENREs and constraint-based methods. We demonstrate the simulation of single and double gene deletions, flux variability analysis (FVA), and test a number of metabolic tasks with the GENRE. Code to perform these analyses is provided in Python, R, and MATLAB. Finally, with iSIM as a guide, we demonstrate how inaccuracies in GENREs can limit their use in the interrogation of energy metabolism.

Keywords: Computational modeling; Flux balance analysis; Metabolic engineering; Metabolic networks; Systems biology.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Humans
  • Metabolic Flux Analysis*
  • Metabolic Networks and Pathways / physiology*
  • Models, Biological*