Trans-dimensional Bayesian model averaging for $^{13}$C-based metabolic flux analysis: Evidence-based flux inference under structural model uncertainty
Fuente:
arXiv
Guardado en:
| Autores principales: | , , , |
|---|---|
| Formato: | Preprint |
| Publicado: |
2026
|
| Materias: | |
| Acceso en línea: | |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| _version_ | 1866918531664183296 |
|---|---|
| author | Jadebeck, Johann F. Stratmann, Anton Beyß, Martin Nöh, Katharina |
| author_facet | Jadebeck, Johann F. Stratmann, Anton Beyß, Martin Nöh, Katharina |
| contents | Accurate quantification of intracellular metabolic fluxes is central to systems biology and biotechnology. Flux estimation relies on biochemical network models, with $^{13}$C metabolic flux analysis (MFA) being the state-of-the-art approach. However, isotope labeling data are often insufficient to uniquely support a single network formulation. In such cases, flux estimates become model-dependent, highlighting the need for methods that explicitly account for structural uncertainty. Bayesian model averaging (BMA) provides a principled framework for this purpose, but its application to $^{13}$C-MFA has so far been restricted to uncertainty in reaction bidirectionality within fixed network topologies. We introduce a scalable Bayesian inference framework for $^{13}$C-MFA, Bayesian model set averaging, that applies BMA to encompass uncertainty in reactions and pathways. Our approach combines reversible jump Markov chain Monte Carlo for trans-dimensional exploration of model spaces with diffusive nested sampling for robust estimation of model evidences, enabling averaging over large families of metabolic network models. Using illustrative and application-scale synthetic case studies, we demonstrate that the method yields robust flux estimates, reveals when multiple network configurations are statistically indistinguishable, and recovers data-supported model structures. Importantly, rather than committing to a single model, the framework manages structural uncertainty: under limited data, competing models are retained, whereas increasing data informativeness improved model and flux recovery. The approach scales to billions of model variants, providing a practical foundation for uncertainty- and misspecification-aware quantitative flux inference in $^{13}$C-MFA. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2605_25079 |
| institution | arXiv |
| publishDate | 2026 |
| record_format | arxiv |
| spellingShingle | Trans-dimensional Bayesian model averaging for $^{13}$C-based metabolic flux analysis: Evidence-based flux inference under structural model uncertainty Jadebeck, Johann F. Stratmann, Anton Beyß, Martin Nöh, Katharina Quantitative Methods Applications Computation Methodology Accurate quantification of intracellular metabolic fluxes is central to systems biology and biotechnology. Flux estimation relies on biochemical network models, with $^{13}$C metabolic flux analysis (MFA) being the state-of-the-art approach. However, isotope labeling data are often insufficient to uniquely support a single network formulation. In such cases, flux estimates become model-dependent, highlighting the need for methods that explicitly account for structural uncertainty. Bayesian model averaging (BMA) provides a principled framework for this purpose, but its application to $^{13}$C-MFA has so far been restricted to uncertainty in reaction bidirectionality within fixed network topologies. We introduce a scalable Bayesian inference framework for $^{13}$C-MFA, Bayesian model set averaging, that applies BMA to encompass uncertainty in reactions and pathways. Our approach combines reversible jump Markov chain Monte Carlo for trans-dimensional exploration of model spaces with diffusive nested sampling for robust estimation of model evidences, enabling averaging over large families of metabolic network models. Using illustrative and application-scale synthetic case studies, we demonstrate that the method yields robust flux estimates, reveals when multiple network configurations are statistically indistinguishable, and recovers data-supported model structures. Importantly, rather than committing to a single model, the framework manages structural uncertainty: under limited data, competing models are retained, whereas increasing data informativeness improved model and flux recovery. The approach scales to billions of model variants, providing a practical foundation for uncertainty- and misspecification-aware quantitative flux inference in $^{13}$C-MFA. |
| title | Trans-dimensional Bayesian model averaging for $^{13}$C-based metabolic flux analysis: Evidence-based flux inference under structural model uncertainty |
| topic | Quantitative Methods Applications Computation Methodology |
| url | https://arxiv.org/abs/2605.25079 |