ArticlePloS one2022
The choice of the objective function in flux balance analysis is crucial for predicting replicative lifespans in yeast.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 13 citations in OpenAlex.
- Flux sampling and graph neural networks for improved gene essentiality prediction in mammalian genome-scale metabolic models.NPJ systems biology and applications · 2026Article
- Metabolic Objectives and Trade-Offs: Inference and Applications.Metabolites · 2025Review
- MitoMAMMAL: a genome scale model of mammalian mitochondria predicts cardiac and BAT metabolism.Bioinformatics advances · 2025Article
- Discretised Flux Balance Analysis for Reaction-Diffusion Simulation of Single-Cell Metabolism.Bulletin of mathematical biology · 2024Article
- Flux sampling in genome-scale metabolic modeling of microbial communities.BMC bioinformatics · 2024Article
- Flux Sampling in Genome-scale Metabolic Modeling of Microbial Communities.bioRxiv : the preprint server for biology · 2023Article
- Model validation and selection in metabolic flux analysis and flux balance analysis.Biotechnology progressReview
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3 authors at 1 institution in 1 country.
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Abstract
Flux balance analysis (FBA) is a powerful tool to study genome-scale models of the cellular metabolism, based on finding the optimal flux distributions over the network. While the objective function is crucial for the outcome, its choice, even though motivated by evolutionary arguments, has not been directly connected to related measures. Here, we used an available multi-scale mathematical model of yeast replicative ageing, integrating cellular metabolism, nutrient sensing and damage accumulation, to systematically test the effect of commonly used objective functions on features of replicative ageing in budding yeast, such as the number of cell divisions and the corresponding time between divisions. The simulations confirmed that assuming maximal growth is essential for reaching realistic lifespans. The usage of the parsimonious solution or the additional maximisation of a growth-independent energy cost can improve lifespan predictions, explained by either increased respiratory activity using resources otherwise allocated to cellular growth or by enhancing antioxidative activity, specifically in early life. Our work provides a new perspective on choosing the objective function in FBA by connecting it to replicative ageing.
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