TF08: Error Correction Algorithms for DNA Repair: Inference, Analysis, and Intervention

TF08：DNA 修复纠错算法：推理、分析和干预

• 批准号: 0830245
• 负责人: Bane Vasic
• 金额: $ 30万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0830245&HistoricalAwards=false
• 关键词: TF08; Error; Correction; Algorithms; DNA

TF: Error Correction Algorithms for DNA Repair: Inference, Analysis, and InterventionBane Vasiæ, David W. Galbraith, and Michael W. MarcellinThe University of Arizona, TucsonMaintaining integrity of genetic material is vital to the survival of species, and is achieved through deoxyribonucleic acid (DNA) repair, a process in the cell in which DNA-damage is continually monitored and corrected. For example, ionizing radiation can induce single and double strand breaks, the most dangerous type of damage, which if uncorrected leads to cell death, while inaccurate repair can be mutagenic. This research establishes a framework for rigorous treatment of genetic error correction, or more specifically, for inferring the error correction coding system of the living cell and describing its functionality quantitatively and algorithmically. This framework is based on probabilistic graphical models that are used in error correction theory to design codes enabling transmission of information in the presence of very high noise levels and ensuring fault-tolerance and reliable storage of information in systems built of faulty components, which precisely corresponds to the DNA-repair scenario. By combining experimental data with existing knowledge of gene-protein and protein-protein interactions, the investigators are creating global functional interaction networks of genes involved in DNA repair. This enables a study of the error correction algorithms and their dynamics, resulting in a formal logical and causal description of interaction among genes, proteins and inducible factors, or a genetic wiring diagram. Such a wiring diagram can be viewed as a digital logic circuit of a genetic decoder. The investigators study the decoder structure and behavior, and more particularly: (i) inferring the decoder from the existing knowledge and new experiments, (ii) predicting the dynamics of the error control system, and (iii) controlling the dynamics using external factors.

TF：DNA修复的纠错算法：推理，分析和干预。Galbraith和Michael W.保持遗传物质的完整性对物种的生存至关重要，并通过脱氧核糖核酸（DNA）修复来实现，这是细胞中持续监测和纠正DNA损伤的过程。 例如，电离辐射可以诱导单链和双链断裂，这是最危险的损伤类型，如果不纠正会导致细胞死亡，而不准确的修复可能会引起突变。 这项研究建立了一个框架，严格处理遗传纠错，或更具体地说，推断活细胞的纠错编码系统，并定量和算法描述其功能。 这个框架是基于概率图形模型，用于纠错理论设计代码，使信息的传输在非常高的噪声水平，并确保容错和可靠的信息存储在系统中建立的故障组件，这正好对应于DNA修复的情况。通过将实验数据与基因-蛋白质和蛋白质-蛋白质相互作用的现有知识相结合，研究人员正在创建参与DNA修复的基因的全球功能相互作用网络。 这使得研究的纠错算法和它们的动力学，从而在一个正式的逻辑和因果关系的描述基因，蛋白质和诱导因子之间的相互作用，或遗传布线图。这样的布线图可以被看作是遗传解码器的数字逻辑电路。 研究人员研究解码器的结构和行为，更具体地说：（i）从现有知识和新实验中推断解码器，（ii）预测错误控制系统的动态，以及（iii）使用外部因素控制动态。