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

EIA-0130385拉塞尔·J·迪顿阿肯色大学题：用于计算的巨大DNA寡核苷酸文库的建模和制造DNA计算具有大规模并行性和巨大的信息密度的优势，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的意外交叉杂交。为了使计算可靠和有效，并扩大到更大的问题，DNA序列的设计必须尽量减少这些计划外的交叉杂交。尽管配对杂交被很好地模拟和理解，但由于大量的配对杂交，以及在最小化交叉杂交的同时最大化文库大小的相互冲突的限制，这种文库的设计是具有挑战性的。因此，为了克服这些限制，通过基于PCR的技术从随机池中选择最大失配的寡核苷酸来制造巨大的非交叉杂交DNA寡核苷酸文库。此外，由于在一个巨大的库中列举所有两两杂交的能量在计算上是令人望而却步的，因此基于自旋玻璃物理的统计方法被用来对库进行建模。该模型是一套用于文库的分析和设计工具的基础。由于DNA杂交在DNA计算中的根本重要性，对巨大的DNA寡核苷酸文库的建模和制造正在产生该领域的基本原理和结果。最大的非交叉杂交寡核苷酸文库的大小也是可行计算的大小的限制。这些文库不仅是大规模DNA计算的使能资源，也是生物技术应用的使能资源，例如可重复使用的、通用的DNA微阵列。此外，这些文库以及软件工具可供复制和供DNA计算和生物技术领域的其他研究人员使用。

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.