论文标题
一种新的标准DNA损伤(SDD)数据格式
A new Standard DNA damage (SDD) data format
论文作者
论文摘要
在过去的几十年中,我们对辐射引起的细胞损伤的理解大大改善。尽管取得了这种进步,但仍有许多障碍可以充分理解辐射如何与生物学相关的细胞成分相互作用以形成可观察到的终点。一个障碍是不同研究小组成员在直接比较结果时面临的困难。已经开发了多个蒙特卡洛代码以模拟DNA量表的损伤诱导,同时各组开发了描述具有不同细节水平的DNA修复过程的模型。这些维修模型与其开发中采用的损坏模型本质上相关,因此很难在建模链的任何一部分中脱离系统效应。建模链通常由轨道结构组成的物理相互作用蒙特卡洛模拟,从而直接损害了DNA。然后对化学物种的生产和初始反应进行模拟,从而导致间接损害。 DNA损伤诱导后,DNA修复模型将模拟损伤模式与生物模型结合在一起,以确定损伤的生物学后果。我们提出了一种新的标准数据格式,用于DNA损伤,以统一损伤诱导模拟与细胞修复过程的生物建模之间的界面。这样的标准极大地促进了模型的比较,提供了一个理想的环境来取消模型假设并确定持久的基本机制。通过模型间比较,该统一标准有可能极大地促进我们对辐射引起的DNA损伤的潜在机制以及可观察到的生物学作用的理解。
Our understanding of radiation induced cellular damage has greatly improved over the past decades. Despite this progress, there are still many obstacles to fully understanding how radiation interacts with biologically relevant cellular components to form observable endpoints. One hurdle is the difficulty faced by members of different research groups in directly comparing results. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modelling chain. The modelling chain typically consists of track structure Monte Carlo simulations of the physics interactions creating direct damages to the DNA; followed by simulations of the production and initial reactions of chemical species causing indirect damages. After the DNA damage induction, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. We propose a new Standard data format for DNA Damage to unify the interface between the simulation of damage induction and the biological modelling of cell repair processes. Such a standard greatly facilitates inter model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation induced DNA damage and the resulting observable biological effects.