Bio-QuBIC: NSF QuBIC: Modeling and Manufacture of Huge DNA Oligonucleotide Libraries for Computation

Bio-QuBIC：NSF QuBIC：用于计算的大型 DNA 寡核苷酸库的建模和制造

• 批准号: 0130385
• 负责人: Russell Deaton
• 金额: $ 69.99万
• 依托单位: University of Arkansas
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0130385&HistoricalAwards=false
• 关键词: Bio; QuBIC; NSF; Modeling; Manufacture

EIA-0130385Russell J. DeatonUniversity of ArkansasTitle: Modeling and Manufacture of Huge DNA Oligonucleotide Libraries for ComputationComputing with DNA, with its advantages of massive parallelism and huge information density, promises a number of revolutionary applications, as well as the potential to solve problems beyond the capabilities of conventional computers. A critical barrier, however, is unplanned crosshybridization among oligonucleotides. In order for the computations to be reliable and efficient, and to scale to larger problems, the DNA sequences have to be designed to minimize these unplanned crosshybridizations. Though pairwise hybridization is well modeled and understood, design of such libraries is challenging because of the huge number of pairwise hybridization's, and the conflicting constraints of maximizing the library size while minimizing crosshybridization.Therefore, to overcome these limitations, huge libraries of non-crosshybridizing DNA oligonucleotides are manufactured by in vitro evolution with a PCR-based protocol that selects from a random pool those oligonucleotides that are maximally mismatched. In addition, because enumeration of all pairwise hybridization energetic in a huge library is computationally prohibitive, a statistical approach, which is based upon spin glass physics, is used to model the library. The model is the basis for a set of analysis and design tools for application to the libraries.Because of the fundamental importance of DNA hybridization in DNA computing, the modeling and manufacture of huge libraries of DNA oligonucleotides is producing foundational principles and results for the field. The size of the largest libraries of non-crosshybridizing oligonucleotides is also the limit on the size of feasible computation. The libraries are an enabling resource not only for large-scale DNA computations, but also biotechnology applications, such as reusable, universal DNA microarrays. In addition, the libraries, as well as the software tools, are available for reproduction and use by other researchers in DNA computing and biotechnology.

题目：用于计算的巨大DNA寡核苷酸库的建模和制造用DNA计算，凭借其大规模并行性和巨大信息密度的优势，承诺了许多革命性的应用，以及解决传统计算机能力之外的问题的潜力。然而，一个关键的障碍是寡核苷酸之间的计划外交叉杂交。为了使计算更加可靠和高效，并扩展到更大的问题，必须设计DNA序列以最小化这些计划外的交叉杂交。虽然两两杂交已经被很好地建模和理解，但由于大量的两两杂交，以及最大化库大小和最小化交叉杂交的冲突约束，这类库的设计是具有挑战性的。因此，为了克服这些限制，大量的非交叉杂交DNA寡核苷酸库是通过体外进化和基于pcr的方案制造的，该方案从随机池中选择最大程度不匹配的寡核苷酸。此外，由于在一个巨大的库中枚举所有成对杂化能在计算上是禁止的，因此采用了基于自旋玻璃物理的统计方法对库进行建模。该模型是一组应用于库的分析和设计工具的基础。由于DNA杂交在DNA计算中的基础重要性，DNA寡核苷酸庞大文库的建模和制造正在为该领域产生基础原理和结果。最大的非交叉杂交寡核苷酸库的大小也限制了可行计算的大小。这些文库不仅是大规模DNA计算的有利资源，而且也是生物技术应用的有利资源，例如可重复使用的通用DNA微阵列。此外，这些库以及软件工具可供DNA计算和生物技术领域的其他研究人员复制和使用。