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：推断、分析和干预Bane Vasiæ、David W.Galbraith和Michael W.Marcell在图森州亚利桑那大学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)修复实现，在细胞中DNA损伤被持续监测和纠正。例如，电离辐射可导致单链和双链断裂，这是最危险的损伤类型，如果不加以纠正，就会导致细胞死亡，而不准确的修复可能会导致突变。这项研究建立了严格处理遗传纠错的框架，更具体地说，用于推断活细胞的纠错编码系统，并定量和算法地描述其功能。这一框架基于纠错理论中使用的概率图形模型，以设计代码，从而能够在存在非常高的噪声水平的情况下传输信息，并确保在由故障部件组成的系统中容错和可靠地存储信息，这恰好符合DNA修复的情况。通过将实验数据与现有的基因-蛋白质和蛋白质-蛋白质相互作用知识相结合，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。这使得对纠错算法及其动力学的研究成为可能，从而产生对基因、蛋白质和诱导因子之间相互作用的正式的逻辑和因果描述，或遗传接线图。这样的接线图可以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)根据现有知识和新的实验来推断解码器，(Ii)预测差错控制系统的动力学，以及(Iii)利用外部因素控制动力学。