redGEM: Systematic reduction and analysis of genome-scale metabolic reconstructions for development of consistent core metabolic models

PLoS Comput Biol. 2017 Jul 20;13(7):e1005444. doi: 10.1371/journal.pcbi.1005444. eCollection 2017 Jul.

Abstract

Genome-scale metabolic reconstructions have proven to be valuable resources in enhancing our understanding of metabolic networks as they encapsulate all known metabolic capabilities of the organisms from genes to proteins to their functions. However the complexity of these large metabolic networks often hinders their utility in various practical applications. Although reduced models are commonly used for modeling and in integrating experimental data, they are often inconsistent across different studies and laboratories due to different criteria and detail, which can compromise transferability of the findings and also integration of experimental data from different groups. In this study, we have developed a systematic semi-automatic approach to reduce genome-scale models into core models in a consistent and logical manner focusing on the central metabolism or subsystems of interest. The method minimizes the loss of information using an approach that combines graph-based search and optimization methods. The resulting core models are shown to be able to capture key properties of the genome-scale models and preserve consistency in terms of biomass and by-product yields, flux and concentration variability and gene essentiality. The development of these "consistently-reduced" models will help to clarify and facilitate integration of different experimental data to draw new understanding that can be directly extendable to genome-scale models.

MeSH terms

  • Algorithms*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Genome / genetics*
  • Metabolic Networks and Pathways / genetics*
  • Models, Biological
  • Software*
  • Systems Biology / methods*

Grants and funding

Ecole Polytechnique Fédérale de Lausanne (EPFL), the Swiss National Science Foundation, the European Union’s Horizon 2020 research and innovation programme under grant agreement No 686070, MicroscapesX within SystemsX.ch, the Swiss Initiative for Systems Biology evaluated by the Swiss National Science Foundation, and RobustYeast within ERA net project via SystemsX.ch. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.