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

TOPAS - nBio，用于辐射生物学研究的蒙特卡罗工具

基本信息

批准号：
10331855
负责人：
Jan Patrick Oscar Schuemann
金额：
$ 50.58万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10331855
关键词：
Animal Model Animals Area Biochemical Biological Biological Models Biology Biophysics Cell Line Cell model Cells Cellular Structures Chemical Models Chemistry Communities DNA DNA Damage DNA Repair DNA Repair Pathway DNA strand break Data Deposition Development Diffusion Discipline Environment Event Foundations Funding Generations Goals Heterogeneity Human In Vitro Interdisciplinary Study Link Linux Lung Neoplasms Methods Mission Modality Modeling Monte Carlo Method Mus Neurons Organelles Outcome Performance Physics Process Psyche structure Publishing Radiation Radiation induced damage Radiation therapy Radiobiology Reaction Time Relative Biological Effectiveness Research Speed Structure Systems Biology Testing Tissues Tumor Volume Update Work base biological effect of radiation cell injury cell type chemical reaction computerized tools design dosimetry experimental study genetic information improved in vivo in vivo Model interdisciplinary approach interest model design multidisciplinary neoplastic cell open source outcome prediction pre-clinical preclinical study predictive modeling radiation effect radiation response repaired repository response simulation tool tumor tumor growth

项目摘要

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.

该提案的目标是继续我们成功开发 TOPAS-nBio（一种蒙特卡罗） Carlo 仿真工具包专门为连接研究学科而设计。 TOPAS-nBio 模拟初始能量沉积事件（物理），然后跟踪扩散和反应化学物质（化学）来推断细胞和细胞器尺度的生物可观测值（生物学）。开发的应用程序已经为研究生物效应奠定了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，问题放射生物学界提出的问题越来越复杂。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，在本次续展申请中，我们专注于通过纳入更具代表性的化学物质来提高模拟的准确性化学反应并过渡到可应用于特定细胞的预测模型类型。为了进一步扩大 TOPAS-nBio 的影响范围，我们将包括微环境的变化跨肿瘤体积的环境，并朝着放射效应的机械建模迈进体内。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迹结构，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来包含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 将继续推进我们的使命：组织对辐射的基本反应的立场。