Interpreting chromosome aberration spectra.
Interpreting chromosome aberration spectra.
复制标题
解释染色体畸变光谱。
DOI：
10.1089/cmb.2006.0127
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Sachs,Rainer
中科院分区：
文献类型：
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作者：
Levy,Dan;Reeder,Christopher;Loucas,Bradford;Hlatky,Lynn;Chen,Allen;Cornforth,Michael;Sachs,Rainer
电离辐射可以通过在多个位置破坏DNA的两条链来破坏细胞，基本上是将染色体切成碎片。细胞具有修复这种断裂的酶机制;然而，这些机制是不完善的，并且在交换过程中，可能产生大规模的基因组重排，称为染色体畸变。染色体畸变在杀死细胞、癌变过程中、表征修复/错误修复途径、回顾性辐射生物剂量测定以及许多其他方面都很重要。DNA染色技术如mFISH（荧光原位杂交）提供了一种通过检查观察到的最终模式来分析畸变光谱的方法。不幸的是，mFISH观察到的最终模式通常不能唯一地确定潜在的交换过程。此外，绘画协议中的分辨率限制有时会导致明显不完整的最终图案。在这里，我们描述了一个算法，系统地发现交换过程与任何观察到的最终模式一致。该算法使用像差多重图，一种数学形式主义，连接像差形成的各个方面。通过对一致多重图空间的测量，我们将展示如何从mFISH实验数据生成模型特定的畸变过程分布。该方法通过互联网上免费提供的软件实现。作为一个示例应用程序，我们将这些算法应用到畸变数据集，获得交换周期大小的分布，用于测量畸变的复杂性。估计复杂性，反过来，有助于表明如何破坏的畸变，并可能有助于识别辐射类型的回顾性生物剂量测定。
Ionizing radiation can damage cells by breaking both strands of DNA in multiple locations, essentially cutting chromosomes into pieces. The cell has enzymatic mechanisms to repair such breaks; however, these mechanisms are imperfect and, in an exchange process, may produce a large-scale rearrangement of the genome, called a chromosome aberration. Chromosome aberrations are important in killing cells, during carcinogenesis, in characterizing repair/misrepair pathways, in retrospective radiation biodosimetry, and in a number of other ways. DNA staining techniques such as mFISH (multicolor fluorescent in situ hybridization) provide a means for analyzing aberration spectra by examining observed final patterns. Unfortunately, an mFISH observed final pattern often does not uniquely determine the underlying exchange process. Further, resolution limitations in the painting protocol sometimes lead to apparently incomplete final patterns. We here describe an algorithm for systematically finding exchange processes consistent with any observed final pattern. This algorithm uses aberration multigraphs, a mathematical formalism that links the various aspects of aberration formation. By applying a measure to the space of consistent multigraphs, we will show how to generate model-specific distributions of aberration processes from mFISH experimental data. The approach is implemented by software freely available over the internet. As a sample application, we apply these algorithms to an aberration data set, obtaining a distribution of exchange cycle sizes, which serves to measure aberration complexity. Estimating complexity, in turn, helps indicate how damaging the aberrations are and may facilitate identification of radiation type in retrospective biodosimetry.