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  5. Prediction of gene essentiality using machine learning and genome-scale metabolic models
 
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Prediction of gene essentiality using machine learning and genome-scale metabolic models
File(s)
1-s2.0-S240589632300006X-main.pdf (1.67 MB)
Published version
Author(s)
Freischem, Lilli J
Barahona, Mauricio
OyarzĂșn, Diego A
Type
Conference Paper
Abstract
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.
Date Issued
2022-08-28
Date Acceptance
2022-08-01
Citation
IFAC-PapersOnLine, 2022, 55 (23), pp.13-18
URI
http://hdl.handle.net/10044/1/106229
URL
http://dx.doi.org/10.1016/j.ifacol.2023.01.006
DOI
https://www.dx.doi.org/10.1016/j.ifacol.2023.01.006
ISSN
2405-8963
Publisher
Elsevier BV
Start Page
13
End Page
18
Journal / Book Title
IFAC-PapersOnLine
Volume
55
Issue
23
Copyright Statement
© 2023 The Author(s). IFAC (International Federation of Automatic Control). This is an open access article under the CC-BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/)
License URL
https://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
http://dx.doi.org/10.1016/j.ifacol.2023.01.006
Source
9th IFAC Conference on Foundations of Systems Biology in Engineering FOSBE 2022
Publication Status
Published
Start Date
2022-08-28
Finish Date
2022-08-31
Coverage Spatial
Cambridge, Massachusetts, USA
Date Publish Online
2023-02-07
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