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Ghim, Cheol-Min
Physical Biology & Biological Physics
Research Interests
  • Control of complex networks, Stochastic fluctuations in a cell, Biochemical information processing, Human microbiome, Ecological inference, Nonequilibrium active system

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Lethality and synthetic lethality in the genome-wide metabolic network of Escherichia coli

Cited 33 times inthomson ciCited 34 times inthomson ci
Title
Lethality and synthetic lethality in the genome-wide metabolic network of Escherichia coli
Author
Ghim, Cheol-MinGoh, KIKahng, B
Issue Date
2005-12
Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Citation
JOURNAL OF THEORETICAL BIOLOGY, v.237, no.4, pp.401 - 411
Abstract
Recent genomic analyses on the cellular metabolic network show that reaction flux across enzymes are diverse and exhibit power-law behavior in its distribution. While intuition might suggest that the reactions with larger fluxes are more likely to be lethal under the blockade of its catalysing gene products or gene knockouts, we find, by in silico flux analysis, that the lethality rarely has correlations with the flux level owing to the widespread backup pathways innate in the genome-wide metabolism of Escherichia coli. Lethal reactions, of which the deletion generates cascading failure of following reactions up to the biomass reaction, are identified in terms of the Boolean network scheme as well as the flux balance analysis. The avalanche size of a reaction, defined as the number of subsequently blocked reactions after its removal, turns out to be a useful measure of lethality. As a means to elucidate phenotypic robustness to a single deletion, we investigate synthetic lethality in reaction level, where simultaneous deletion of a pair of nonlethal reactions leads to the failure of the biomass reaction. Synthetic lethals identified via flux balance and Boolean scheme are consistently shown to act in parallel pathways, working in such a way that the backup machinery is compromised.
URI
https://scholarworks.unist.ac.kr/handle/201301/7114
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=27744585668
DOI
10.1016/j.jtbi.2005.04.025
ISSN
0022-5193
Appears in Collections:
PHY_Journal Papers
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