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

这项提议的目标是继续我们成功开发的Topas-nBio，一种 专门为连接研究学科而设计的卡洛模拟工具包。Topas-nBio 模拟初始能量沉积事件(物理)，然后跟踪扩散和反应 在细胞和细胞器尺度上推断生物可观察性的化学物种(化学) (生物学)。所开发的应用程序已经为研究生物效应奠定了基础。 用机械系统生物学建模方法研究细胞器中的辐射效应。 然而，随着我们对细胞修复过程理解的不断进步，QUES- 辐射生物界提出的要求越来越复杂。这些进步， 包括各种细胞系/类型、DNA修复缺陷的更详细信息 需要考虑非核细胞成分的途径和潜在贡献 正确描述细胞对辐射损伤的反应。因此，在这份续签申请中， 我们致力于通过纳入更具代表性的化学成分来提高模拟的准确性。 化学反应和向可应用于特定细胞的预测模型过渡 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- 跨肿瘤体积的辐射环境并转向放射效应的机制模拟 活着。因此，Topas-nBio的新发展将提供对生物结果的预测 从用于体外和体内实验的各种细胞类型的初始辐射轨迹结构， 从而在生物物理学研究的前沿推动假说的产生。Topas-nBio 提供一个理想的框架来包括和测试新的效应模型、细胞系或微环境- 精神状况。总体而言，Topas-nBio将继续推进我们的Under- 组织对辐射的基本反应的立场。

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.