Improved Lower Bounds for Constant GC-Content DNA Codes

The design of large libraries of oligonucleotides having constant GC-content and satisfying Hamming distance constraints between oligonucleotides and their Watson-Crick complements is important in reducing hybridization errors in DNA computing, DNA microarray technologies, and molecular bar coding. Various techniques have been studied for the construction of such oligonucleotide libraries, ranging from algorithmic constructions via stochastic local search to theoretical constructions via coding theory. We introduce a new stochastic local search method which yields improvements up to more than one third of the benchmark lower bounds of Gaborit and King (2005) for n-mer oligonucleotide libraries when n <= 14. We also found several optimal libraries by computing maximum cliques on certain graphs.Comment: 4 page

Paradigms for computational nucleic acid design

The design of DNA and RNA sequences is critical for many endeavors, from DNA nanotechnology, to PCR‐based applications, to DNA hybridization arrays. Results in the literature rely on a wide variety of design criteria adapted to the particular requirements of each application. Using an extensively studied thermodynamic model, we perform a detailed study of several criteria for designing sequences intended to adopt a target secondary structure. We conclude that superior design methods should explicitly implement both a positive design paradigm (optimize affinity for the target structure) and a negative design paradigm (optimize specificity for the target structure). The commonly used approaches of sequence symmetry minimization and minimum free‐energy satisfaction primarily implement negative design and can be strengthened by introducing a positive design component. Surprisingly, our findings hold for a wide range of secondary structures and are robust to modest perturbation of the thermodynamic parameters used for evaluating sequence quality, suggesting the feasibility and ongoing utility of a unified approach to nucleic acid design as parameter sets are refined further. Finally, we observe that designing for thermodynamic stability does not determine folding kinetics, emphasizing the opportunity for extending design criteria to target kinetic features of the energy landscape

Deterministic Polynomial-Time Algorithms for Designing Short DNA Words

Designing short DNA words is a problem of constructing a set (i.e., code) of n DNA strings (i.e., words) with the minimum length such that the Hamming distance between each pair of words is at least k and the n words satisfy a set of additional constraints. This problem has applications in, e.g., DNA self-assembly and DNA arrays. Previous works include those that extended results from coding theory to obtain bounds on code and word sizes for biologically motivated constraints and those that applied heuristic local searches, genetic algorithms, and randomized algorithms. In particular, Kao, Sanghi, and Schweller (2009) developed polynomial-time randomized algorithms to construct n DNA words of length within a multiplicative constant of the smallest possible word length (e.g., 9 max{log n, k}) that satisfy various sets of constraints with high probability. In this paper, we give deterministic polynomial-time algorithms to construct DNA words based on derandomization techniques. Our algorithms can construct n DNA words of shorter length (e.g., 2.1 log n + 6.28 k) and satisfy the same sets of constraints as the words constructed by the algorithms of Kao et al. Furthermore, we extend these new algorithms to construct words that satisfy a larger set of constraints for which the algorithms of Kao et al. do not work.Comment: 27 page

Bounds for DNA codes with constant GC-content

We derive theoretical upper and lower bounds on the maximum size of DNA codes of length n with constant GC-content w and minimum Hamming distance d, both with and without the additional constraint that the minimum Hamming distance between any codeword and the reverse-complement of any codeword be at least d. We also explicitly construct codes that are larger than the best previously-published codes for many choices of the parameters n, d and w.Comment: 13 pages, no figures; a few references added and typos correcte

Dagstuhl Reports : Volume 1, Issue 2, February 2011

Online Privacy: Towards Informational Self-Determination on the Internet (Dagstuhl Perspectives Workshop 11061) : Simone Fischer-Hübner, Chris Hoofnagle, Kai Rannenberg, Michael Waidner, Ioannis Krontiris and Michael Marhöfer Self-Repairing Programs (Dagstuhl Seminar 11062) : Mauro Pezzé, Martin C. Rinard, Westley Weimer and Andreas Zeller Theory and Applications of Graph Searching Problems (Dagstuhl Seminar 11071) : Fedor V. Fomin, Pierre Fraigniaud, Stephan Kreutzer and Dimitrios M. Thilikos Combinatorial and Algorithmic Aspects of Sequence Processing (Dagstuhl Seminar 11081) : Maxime Crochemore, Lila Kari, Mehryar Mohri and Dirk Nowotka Packing and Scheduling Algorithms for Information and Communication Services (Dagstuhl Seminar 11091) Klaus Jansen, Claire Mathieu, Hadas Shachnai and Neal E. Youn

Thermodynamically based DNA strand design

We describe a new algorithm for design of strand sets, for use in DNA computations or universal microarrays. Our algorithm can design sets that satisfy any of several thermodynamic and combinatorial constraints, which aim to maximize desired hybridizations between strands and their complements, while minimizing undesired cross-hybridizations. To heuristically search for good strand sets, our algorithm uses a conflict-driven stochastic local search approach, which is known to be effective in solving comparable search problems. The PairFold program of Andronescu et al. [M. Andronescu, Z. C. Zhang and A. Condon (2005) J. Mol. Biol., 345, 987–1001; M. Andronescu, R. Aguirre-Hernandez, A. Condon, and H. Hoos (2003) Nucleic Acids Res., 31, 3416–3422.] is used to calculate the minimum free energy of hybridization between two mismatched strands. We describe new thermodynamic measures of the quality of strand sets. With respect to these measures of quality, our algorithm consistently finds, within reasonable time, sets that are significantly better than previously published sets in the literature