Updating Chromosome Aberration Simulator (CAS) Software

描述(由申请人提供)：在细胞周期的G0/G1期，电离辐射引起的DNA损伤的酶促修复错误会产生染色体异常，如易位和双着丝粒。染色体异常可导致严重的功能紊乱，包括细胞死亡、突变和肿瘤。放射性像差在生物剂量学、致癌风险评估和肿瘤放射治疗计划中是重要的。它们与用于表征特定肿瘤类型的异常密切相关，也与现代比较基因组学中考虑的大规模基因组重排密切相关。最近的工作表明，放射性交换型像差通常是复杂的，涉及两个以上DNA双链断裂之间的相互作用。为了充分地表征和分析复杂像差的光谱，需要计算机模拟，现在通常使用计算机模拟。由伯克利/哈佛大学的一个团队开发的开创性软件是CAS(染色体畸变模拟器)，这是一个通过蒙特卡罗、马尔科夫链计算断裂错接的基本生物物理模型的软件包，考虑了间期细胞核中的染色体几何形状。中科院开源软件已成功应用于与全球多个组织的联合工作，辐射细胞遗传学家对互联网生物信息学的想法得到了广泛支持。建议的项目如下：1)重新设计CAS，以利用早期版本的经验和象差理论的最新进展；2)使CAS作为一个开源的互联网资源更加用户友好；以及3)以各种方式扩展CAS，以跟上当前快速的实验进展，例如像差检测技术。已经为这个项目组建了一个跨学科的团队。这笔赠款将确保对辐射细胞遗传学社区重要的计算机资源保持完全最新并随时可用。

DESCRIPTION (provided by applicant): Enzymatic misrepair of DNA damage induced by ionizing radiation during the G0/G1 phase of the cell cycle produces chromosome aberrations, such as translocations and dicentrics. Chromosome aberrations can cause major disruptions of function, including cell death, mutation and neoplasia. Radiogenic aberrations are important in biodosimetry, carcinogenesis risk estimation, and tumor radiotherapy treatment planning. They are closely related to aberrations used in characterizing specific tumor types and to large-scale genome rearrangements considered in modern comparative genomics. Recent work has shown that radiogenic exchange-type aberrations are often complex, involving interactions between more than two DNA double strand breaks. To characterize and analyze spectra of complex aberrations adequately, computer simulations are needed, and are now commonly used. The pioneering software, developed by a Berkeley/Harvard team, is CAS (chromosome aberration simulator), a package implementing basic biophysical models of aberration formation via Monte Carlo, Markov chain calculations of break misrejoining, taking into account chromosome geometry in an interphase cell nucleus. The CAS open source software has been successfully applied in joint work with many groups worldwide, and broad support among radiation cytogeneticists for the idea of internet bioinformatics has been identified. The proposed project is the following: 1) reengineer CAS to take advantage of experience with earlier versions and recent progress in aberration theory; 2) make CAS more user-friendly as an open source internet resource; and 3), extend CAS in various ways to keep up with current rapid experimental advances, e.g. in aberration detection technology. An interdisciplinary team has been assembled for this project. The grant would ensure that a computer resource important to the radiation cytogenetics community is kept fully current and readily available.