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

EIA-0130385 Russell J. Deaton阿肯色大学题目：用于计算的巨大DNA寡核苷酸库的建模和制造DNA计算凭借其大规模并行和巨大信息密度的优势，有望实现许多革命性的应用，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无计划的交叉杂交。为了使计算可靠和有效，并扩展到更大的问题，DNA序列必须被设计为最小化这些无计划的交叉杂交。尽管成对杂交被很好地建模和理解，但是由于大量的成对杂交，以及最大化文库大小同时最小化交叉杂交的冲突约束，这样的文库的设计是具有挑战性的。非交叉杂交DNA寡核苷酸的巨大文库通过体外进化用PCR-基于一个协议，从随机池中选择那些最大程度错配的寡核苷酸。此外，因为在一个巨大的图书馆中的所有成对杂交能量的枚举是计算上禁止的，统计方法，这是基于自旋玻璃物理，被用来模拟库。该模型是一套分析和设计工具的基础，应用于library.Because的DNA杂交在DNA计算中的根本重要性，DNA寡核苷酸的巨大文库的建模和制造正在产生该领域的基本原则和结果。非交叉杂交寡核苷酸的最大文库的大小也是可行计算大小的限制。这些库不仅是大规模DNA计算的有利资源，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，DNA计算和生物技术领域的其他研究人员也可以复制和使用这些图书馆以及软件工具。

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.