TOPAS - nBio, a Monte Carlo tool for radiation biology research

该提案的目标是继续我们成功开发TOPAS-nBio， Carlo仿真工具包专门设计用于连接研究学科。TOPAS-nBio 模拟初始能量沉积事件（物理），然后遵循扩散和反应 在细胞和细胞器尺度上推断生物可观察性的化学物质（化学） （生物学）。开发的应用程序已经奠定了研究生物效应的基础， 使用机械系统生物学建模方法研究辐射对细胞器的影响。 然而，随着我们对细胞修复过程的理解不断进步，问题- 放射生物学团体提出的问题越来越复杂。这些进步， 包括各种细胞系/类型的更详细信息，DNA修复缺陷， 途径和潜在的贡献，非核细胞成分，需要考虑， 正确描述细胞对辐射损伤的反应。因此，在这份更新申请中， 我们专注于提高模拟的准确性，包括更有代表性的化学， 标准反应和向可应用于特定细胞的预测模型的过渡 类型为了进一步扩大TOPAS-nBio的覆盖范围，我们将包括微环境的变化， 在肿瘤体积中的放射效应，并朝着放射效应的机械建模方向发展。 vivo.因此，TOPAS-nBio的新发展将提供生物学结果的预测 从用于体外和体内实验的各种细胞类型的初始辐射轨道结构， 从而推动生物物理研究前沿的假设生成。TOPAS-nBio 提供了一个理想的框架，包括和测试新的效应模型，细胞系或微环境， 精神状况总的来说，TOPAS-nBio将继续执行使命，推动我们的下- 组织对辐射的基本反应。

The goal of this proposal is to continue our successful development of TOPAS-nBio, a Monte Carlo simulation toolkit specifically designed to connect research disciplines. TOPAS-nBio simulates the initial energy deposition events (physics), then follows the diffusion and reaction of chemical species (chemistry) to infer biological observables at the cell and organelle scale (biology). The developed application already lays the foundation to investigate biological ef- fects of radiation in cell organelles using a mechanistic systems biology modeling approach. However, with constant advances in our understanding of cellular repair processes, the ques- tions asked by the radiation biology community are increasing in complexity. These advances, including more detailed information of various cells lines/types, deficiencies in DNA repair pathways and potential contributions of non-nuclear cell components, need to be considered to correctly describe cell response to radiation damages. Accordingly, in this renewal application, we focus on improving the accuracy of the simulations by including more representative chem- ical reactions and transitioning towards a predictive model that can be applied to specific cell types. To further extend the reach of TOPAS-nBio, we will include changes in the microenvi- ronment across tumor volumes and move towards mechanistic modeling of radiation effects in vivo. Thus, the new developments of TOPAS-nBio will offer predictions of biological outcome from the initial radiation track structure for various cell types for in vitro and in vivo experiments, and thereby drive hypothesis generation at the forefront of bio-physical research. TOPAS-nBio provides an ideal framework to include and test new effect models, cell lines or microenviron- mental conditions. Overall, TOPAS-nBio will continue the mission to advance our under- standing of the fundamental response of tissue to radiation.