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Publication type: Article in scientific journal
Type of review: Peer review (publication)
Title: Holistic view on cell survival and DNA damage : how model-based data analysis supports exploration of dynamics in biological systems
Authors: Weyland, Mathias S.
Thumser-Henner, Pauline
Nytko, Katarzyna J.
Rohrer Bley, Carla
Ulzega, Simone
Petri-Fink, Alke
Lattuada, Marco
Füchslin, Rudolf Marcel
Scheidegger, Stephan
et. al: No
DOI: 10.1155/2020/5972594
Published in: Computational and Mathematical Methods in Medicine
Volume(Issue): 2020
Issue Date: 15-Sep-2020
Publisher / Ed. Institution: Hindawi
ISSN: 1748-670X
Language: English
Subject (DDC): 572: Biochemistry
Abstract: In this work, a method is established to calibrate a model that describes the basic dynamics of DNA damage and repair. The model can be used to extend planning for radiotherapy and hyperthermia in order to include the biological effects. In contrast to ``syntactic'' models (e.g. describing molecular kinetics), the model used here describes radiobiological semantics, resulting in a more powerful model but also in a far more challenging calibration. Model calibration is attempted from clonogenic assay data (doses of 0 -- 6 Gy) and from time-resolved comet assay data obtained within 6~h after irradiation with 6~Gy. It is demonstrated that either of those two sources of information alone is insufficient for successful model calibration, and that both sources of information combined in a holistic approach are necessary to find viable model parameters. Approximate Bayesian Computation (ABC) with simulated annealing is used for parameter search, revealing two aspects that are beneficial to resolving the calibration problem: (1) assessing posterior parameter distributions instead of point-estimates; (2) combining calibration runs from different assays by joining posterior distributions instead of running a single calibration run with a combined, computationally very expensive objective function.
Fulltext version: Published version
License (according to publishing contract): CC BY 4.0: Attribution 4.0 International
Departement: School of Engineering
Life Sciences and Facility Management
Organisational Unit: Institute of Applied Mathematics and Physics (IAMP)
Institute of Computational Life Sciences (ICLS)
Published as part of the ZHAW project: Dynamic Thermal Dosimetric Concept for Evaluating Synergistic Effect of Combined Hyperthermia-Radiotherapy (RT-HT)
Appears in collections:Publikationen School of Engineering

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