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Holistic View on Cell Survival and DNA Damage: How Model-Based Data Analysis Supports Exploration of Dynamics in Biological Systems
- Source :
- Computational and Mathematical Methods in Medicine, Vol 2020 (2020), Computational and Mathematical Methods in Medicine
- Publication Year :
- 2020
- Publisher :
- Hindawi Limited, 2020.
-
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 and (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.
- Subjects :
- 10253 Department of Small Animals
DNA Repair
Computer science
Semantics (computer science)
Model parameters
030218 nuclear medicine & medical imaging
0302 clinical medicine
2604 Applied Mathematics
2400 General Immunology and Microbiology
Neoplasms
11434 Center for Clinical Studies
Tumor Stem Cell Assay
Systems Biology
Applied Mathematics
Dynamics (mechanics)
Contrast (statistics)
General Medicine
030220 oncology & carcinogenesis
Modeling and Simulation
Simulated annealing
Comet Assay
Approximate Bayesian computation
Monte Carlo Method
Algorithm
Research Article
Article Subject
Cell Survival
Computer applications to medicine. Medical informatics
R858-859.7
610 Medicine & health
Genetics and Molecular Biology
Models, Biological
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Dogs
1300 General Biochemistry, Genetics and Molecular Biology
Modelling and Simulation
Cell Line, Tumor
Calibration
Animals
Humans
Cell survival
11077 Center for Applied Biotechnology and Molecular Medicine
General Immunology and Microbiology
572: Biochemie
Radiotherapy Planning, Computer-Assisted
Computational Biology
Bayes Theorem
Mathematical Concepts
General Biochemistry
2611 Modeling and Simulation
DNA Damage
Subjects
Details
- Language :
- English
- ISSN :
- 17486718
- Volume :
- 2020
- Database :
- OpenAIRE
- Journal :
- Computational and Mathematical Methods in Medicine
- Accession number :
- edsair.doi.dedup.....dcc67ebacee8af8127c5067715f75229