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

University Of Arkansas, Fayetteville AR

Investigators

Abstract

EIA-0130385 Russell J. Deaton University of Arkansas Title: Modeling and Manufacture of Huge DNA Oligonucleotide Libraries for Computation Computing 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.