PreProPath: An Uncertainty-Aware Algorithm for Identifying Predictable Profitable Pathways in Biochemical Networks

Ehsan Ullah, Mark Walker, Kyongbum Lee, Soha Hassoun

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Pathway analysis is a powerful approach to enable rational design or redesign of biochemical networks for optimizing metabolic engineering and synthetic biology objectives such as production of desired chemicals or biomolecules from specific nutrients. While experimental methods can be quite successful, computational approaches can enhance discovery and guide experimentation by efficiently exploring very large design spaces. We present a computational algorithm, Predictably Profitable Path (PreProPath), to identify target pathways best suited for engineering modifications. The algorithm utilizes uncertainties about the metabolic networks operating state inherent in the underdetermined linear equations representing the stoichiometric model. Flux Variability Analysis is used to determine the operational flux range. PreProPath identifies a path that is predictable in behavior, exhibiting small flux ranges, and profitable, containing the least restrictive flux-limiting reaction in the network. The algorithm is computationally efficient because it does not require enumeration of pathways. The results of case studies show that PreProPath can efficiently analyze variances in metabolic states and model uncertainties to suggest pathway engineering strategies that have been previously supported by experimental data.

Original languageEnglish
Article number7027828
Pages (from-to)1405-1415
Number of pages11
JournalIEEE/ACM Transactions on Computational Biology and Bioinformatics
Volume12
Issue number6
DOIs
Publication statusPublished - 1 Nov 2015
Externally publishedYes

Keywords

  • Flux balance analysis
  • flux variability analysis
  • metabolic networks
  • uncertainty

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