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Identifiability analysis for models of the translation kinetics after mRNA transfection.

J. Math. Biol. 84:56 (2022)
Verlagsversion Postprint Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Mechanistic models are a powerful tool to gain insights into biological processes. The parameters of such models, e.g. kinetic rate constants, usually cannot be measured directly but need to be inferred from experimental data. In this article, we study dynamical models of the translation kinetics after mRNA transfection and analyze their parameter identifiability. That is, whether parameters can be uniquely determined from perfect or realistic data in theory and practice. Previous studies have considered ordinary differential equation (ODE) models of the process, and here we formulate a stochastic differential equation (SDE) model. For both model types, we consider structural identifiability based on the model equations and practical identifiability based on simulated as well as experimental data and find that the SDE model provides better parameter identifiability than the ODE model. Moreover, our analysis shows that even for those parameters of the ODE model that are considered to be identifiable, the obtained estimates are sometimes unreliable. Overall, our study clearly demonstrates the relevance of considering different modeling approaches and that stochastic models can provide more reliable and informative results.
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icb_biostatistics icb_biostats
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Chemical Langevin Equation ; Differential Equation Models ; Itô Diffusion Process ; Parameter Identifiability ; Stochastic Modeling ; Mrna Transfection
Sprache englisch
Veröffentlichungsjahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 0303-6812
e-ISSN 1432-1416
Quellenangaben Band: 84, Heft: 7, Seiten: , Artikelnummer: 56 Supplement: ,
Verlag Springer
Begutachtungsstatus Peer reviewed
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503800-001
G-553800-001
Förderungen Helmholtz-Gemeinschaft
Deutsche Forschungsgemeinschaft
PubMed ID 35577967
Erfassungsdatum 2022-06-20