Understanding flux switching in metabolic networks through an analysis of synthetic lethals.
Journal
NPJ systems biology and applications
ISSN: 2056-7189
Titre abrégé: NPJ Syst Biol Appl
Pays: England
ID NLM: 101677786
Informations de publication
Date de publication:
17 Sep 2024
17 Sep 2024
Historique:
received:
19
03
2024
accepted:
17
08
2024
medline:
18
9
2024
pubmed:
18
9
2024
entrez:
17
9
2024
Statut:
epublish
Résumé
Biological systems are robust and redundant. The redundancy can manifest as alternative metabolic pathways. Synthetic double lethals are pairs of reactions that, when deleted simultaneously, abrogate cell growth. However, removing one reaction allows the rerouting of metabolites through alternative pathways. Little is known about these hidden linkages between pathways. Understanding them in the context of pathogens is useful for therapeutic innovations. We propose a constraint-based optimisation approach to identify inter-dependencies between metabolic pathways. It minimises rerouting between two reaction deletions, corresponding to a synthetic lethal pair, and outputs the set of reactions vital for metabolic rewiring, known as the synthetic lethal cluster. We depict the results for different pathogens and show that the reactions span across metabolic modules, illustrating the complexity of metabolism. Finally, we demonstrate how the two classes of synthetic lethals play a role in metabolic networks and influence the different properties of a synthetic lethal cluster.
Identifiants
pubmed: 39289347
doi: 10.1038/s41540-024-00426-5
pii: 10.1038/s41540-024-00426-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104Informations de copyright
© 2024. The Author(s).
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