CellTarget: a convex optimisation approach to discover cellular objectives
File(s)
Published version
Author(s)
Pereira Monteiro, Mariana
Morrissey, James
Kontoravdi, Cleo
Type
Journal Article
Abstract
Metabolic network models are widely used in systems and synthetic biology to study cellular metabolism from microbes to mammals. However, their application to mammalian cells remains limited by the scarcity of intracellular flux measurements relative to network size. As a result, mammalian metabolic models are typically underdetermined and require optimisation-based assumptions to be solved. Unlike microbial systems, mammalian cells do not generally operate under growth-maximising objectives, making objective specification particularly challenging. To address this limitation, we propose CellTarget, an algorithm for inferring cellular objectives directly from experimental flux data. CellTarget combines a convex Flux Balance Analysis (FBA) module with an error-minimisation module that iteratively adjusts objective coefficients to improve agreement between predicted and measured fluxes. Gradients are obtained via implicit differentiation of the convex FBA optimisation problem, enabling backpropagation of the inferred objective coefficients and joint optimisation of both modules. CellTarget is evaluated across producer and non-producer Chinese Hamster Ovary (CHO) cell lines, growth phases, objective dimensionalities and both reduced and genome-scale networks. Across all settings, CellTarget yields accurate forward flux predictions and outperforms a benchmark inverse FBA method. The results reveal substantial non-identifiability of cellular objectives, with predictive accuracy driven more strongly by network constraints than by objective specificity.
Date Issued
2026-06-02
Date Acceptance
2026-03-23
Citation
npj Systems Biology and Applications, 2026, 12
ISSN
2056-7189
Publisher
Nature Portfolio
Journal / Book Title
npj Systems Biology and Applications
Volume
12
Copyright Statement
© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .
License URL
Identifier
10.1038/s41540-026-00700-8
Subjects
Monteiro
M.
Morrissey
J.
Kontoravdi
C. CellTarget: a convex optimisation approach to discover cellular objectives. npj Syst Biol Appl (2026)
Publication Status
Published
Article Number
ARTN 79
Date Publish Online
2026-04-03