Coupling Fluxes, Enzymes, and Regulation in Genome-Scale Metabolic Models

Methods Mol Biol. 2018;1716:337-351. doi: 10.1007/978-1-4939-7528-0_15.


Genome-scale models have expanded beyond their metabolic origins. Multiple modeling frameworks are required to combine metabolism with enzymatic networks, transcription, translation, and regulation. Mathematical programming offers a powerful set of tools for tackling these "multi-modality" models, although special attention must be paid to the connections between modeling types. This chapter reviews common methods for combining metabolic and discrete logical models into a single mathematical programming framework. Best practices, caveats, and recommendations are presented for the most commonly used software packages. Methods for troubleshooting large sets of logical rules are also discussed.

Keywords: Boolean networks; Constraint-based modeling; Flux balance analysis; MILP; Metabolic modeling; Mixed-integer programming; Transcriptional regulation.

Publication types

  • Review

MeSH terms

  • Computational Biology / methods*
  • Gene Expression Regulation
  • Genome
  • Metabolic Networks and Pathways*
  • Models, Biological
  • Software