基于含噪声密度聚类算法的质子辐射诱导的DNA集簇性损伤研究

Study of clustered damage in DNA after proton irradiation based on density-based spatial clustering of applications with noise algorithm

以原子级几何模型模拟脱氧核糖核酸(DNA)分子损伤的遍历算法目前存在着计算时间长、收敛速度慢、计算设备要求高等缺点,因此本文提出一种基于能量沉积点和羟自由基(·OH)位置信息的含噪声密度聚类(DBSCAN)算法,该算法结合概率统计方法,能快速地得到DNA链断裂产额,帮助进一步研究DNA集簇性损伤的变化规律。首先,课题组依托放射生物学蒙特卡罗模拟软件Geant4-DNA,模拟质子和次级粒子在细胞核中的输运以及它们对水分子电离激发的过程,获得粒子能量沉积点和羟自由基的位置信息。然后在简化的细胞核几何模型中,利用损伤发生概率函数计算得到DNA损伤点的空间分布数据集,确定损伤点密度,由DSBCAN算法计算DNA单链断裂(SSB)和双链断裂(DSB)产额。最后分析DNA链断裂产额随传能线密度(LET)值变化的趋势,总结出不同损伤簇的变化规律。实验结果表明,与遍历算法相比,本文新算法模拟速度快且模拟精度高,模拟结果同其他实验和模拟方法相比较,具备良好的一致性。实现了在分子水平上快速获得质子辐射致DNA集簇性损伤更为精细的信息,为辐射生物损伤机制的研究提供了一种重要和有力的研究手段。

The deoxyribonucleic acid (DNA) molecule damage simulations with an atom level geometric model use the traversal algorithm that has the disadvantages of quite time-consuming, slow convergence and high-performance computer requirement. Therefore, this work presents a density-based spatial clustering of applications with noise (DBSCAN) clustering algorithm based on the spatial distributions of energy depositions and hydroxyl radicals ( OH). The algorithm with probability and statistics can quickly get the DNA strand break yields and help to study the variation pattern of the clustered DNA damage. Firstly, we simulated the transportation of protons and secondary particles through the nucleus, as well as the ionization and excitation of water molecules by using Geant4-DNA that is the Monte Carlo simulation toolkit for radiobiology, and got the distributions of energy depositions and hydroxyl radicals. Then we used the damage probability functions to get the spatial distribution dataset of DNA damage points in a simplified geometric model. The DBSCAN clustering algorithm based on damage points density was used to determine the single-strand break (SSB) yield and double-strand break (DSB) yield. Finally, we analyzed the DNA strand break yield variation trend with particle linear energy transfer (LET) and summarized the variation pattern of damage clusters. The simulation results show that the new algorithm has a faster simulation speed than the traversal algorithm and a good precision result. The simulation results have consistency when compared to other experiments and simulations. This work achieves more precise information on clustered DNA damage induced by proton radiation at the molecular level with high speed, so that it provides an essential and powerful research method for the study of radiation biological damage mechanism.