Prediction of gene essentiality using machine learning and genome-scale metabolic models

Lilli J. Freischem*, Mauricio Barahona, Diego A. Oyarzún*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The identification of essential genes, i.e. those that impair cell survival when deleted, requires large growth assays of knock-out strains. The complexity and cost of such experiments has triggered a growing interest in computational methods for prediction of gene essentiality. In the case of metabolic genes, Flux Balance Analysis (FBA) is widely employed to predict essentiality under the assumption that cells maximize their growth rate. However, this approach assumes that knock-out strains optimize the same objectives as the wild-type, which excludes cases in which deletions cause large physiological changes to meet other objectives for survival. Here, we resolve this limitation with a novel machine learning approach that predicts essentiality directly from wild-type flux distributions. We first project the wild-type FBA solution onto a mass flow graph, a digraph with reactions as nodes and edge weights proportional to the mass transfer between reactions, and then train binary classifiers on the connectivity of graph nodes. We demonstrate the efficacy of this approach using the most complete metabolic model of Escherichia coli, achieving near state-of-the art prediction accuracy for essential genes. Our approach suggests that wild-type FBA solutions contain enough information to predict essentiality, without the need to assume optimality of deletion strains.

Original languageEnglish
Pages (from-to)13-18
Number of pages6
Issue number23
Publication statusPublished - 1 Sept 2022
Event9th IFAC Conference on Foundations of Systems Biology in Engineering, FOSBE 2022 - Cambridge, United States
Duration: 28 Aug 202231 Aug 2022

Keywords / Materials (for Non-textual outputs)

  • flux balance analysis
  • gene essentiality
  • machine learning
  • metabolism


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