Reusable rule-based cell cycle model explains compartment-resolved dynamics of 16 observables in RPE-1 cells.
PLoS Comput Biol
; 20(1): e1011151, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-38190398
ABSTRACT
The mammalian cell cycle is regulated by a well-studied but complex biochemical reaction system. Computational models provide a particularly systematic and systemic description of the mechanisms governing mammalian cell cycle control. By combining both state-of-the-art multiplexed experimental methods and powerful computational tools, this work aims at improving on these models along four dimensions model structure, validation data, validation methodology and model reusability. We developed a comprehensive model structure of the full cell cycle that qualitatively explains the behaviour of human retinal pigment epithelial-1 cells. To estimate the model parameters, time courses of eight cell cycle regulators in two compartments were reconstructed from single cell snapshot measurements. After optimisation with a parallel global optimisation metaheuristic we obtained excellent agreements between simulations and measurements. The PEtab specification of the optimisation problem facilitates reuse of model, data and/or optimisation results. Future perturbation experiments will improve parameter identifiability and allow for testing model predictive power. Such a predictive model may aid in drug discovery for cell cycle-related disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Descoberta de Drogas
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article