ArticlePLoS computational biology2022
The topology of genome-scale metabolic reconstructions unravels independent modules and high network flexibility.
Article in PLoS computational biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed.
- Metabolic set theory: a generalized model of microbial interactions.NPJ systems biology and applications · 2026Article
- TSPAN4Frontiers in immunology · 2025Article
- Building blocks needed for mechanistic modeling of bioprocesses: A critical review based on protein production by CHO cells.Metabolic engineering communications · 2024Review
- AFrontiers in cardiovascular medicine · 2024Article
- Genome-scale models as a vehicle for knowledge transfer from microbial to mammalian cell systems.Computational and structural biotechnology journal · 2023Review
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6 authors.
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Abstract
The topology of metabolic networks is recognisably modular with modules weakly connected apart from sharing a pool of currency metabolites. Here, we defined modules as sets of reversible reactions isolated from the rest of metabolism by irreversible reactions except for the exchange of currency metabolites. Our approach identifies topologically independent modules under specific conditions associated with different metabolic functions. As case studies, the E.coli iJO1366 and Human Recon 2.2 genome-scale metabolic models were split in 103 and 321 modules respectively, displaying significant correlation patterns in expression data. Finally, we addressed a fundamental question about the metabolic flexibility conferred by reversible reactions: "Of all Directed Topologies (DTs) defined by fixing directions to all reversible reactions, how many are capable of carrying flux through all reactions?". Enumeration of the DTs for iJO1366 model was performed using an efficient depth-first search algorithm, rejecting infeasible DTs based on mass-imbalanced and loopy flux patterns. We found the direction of 79% of reversible reactions must be defined before all directions in the network can be fixed, granting a high degree of flexibility.
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