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.

中文翻译：

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关于细胞存活和DNA损伤的整体观点：基于模型的数据分析如何支持对生物系统动力学的探索。

在这项工作中，建立了一种校准模型的方法，该模型描述了DNA损伤和修复的基本动力学。该模型可用于扩展放射治疗和热疗计划，以包括生物学效应。与“句法”模型（例如，描述分子动力学）相反，此处使用的模型描述了放射生物学的语义，从而产生了更强大的模型，但也带来了更具挑战性的校准。尝试从克隆形成的测定数据（剂量为0-6 Gy）和从6 Gy照射后6小时内获得的时间分辨彗星测定数据中进行模型校准。证明仅这两个信息源中的任何一个都不足以成功地进行模型校准，并且以整体方法组合的两个信息源对于找到可行的模型参数都是必要的。