Huazhong University of Science and Technology, Wu-han-shih, Hubei, China
DOI: 10.1007/11816102_27 Conference: Computational Intelligence and Bioinformatics, International Conference on Intelligent Computing, ICIC 2006, Kunming, China, August 16-19, 2006. Proceedings, Part III
An integrated scheme based on biochip technology for performing DNA computing is proposed here. This work is motivated by
the goal of integrating all the steps of DNA computing into one machine called DNA computing processor. The basic structure
of processor consists of making DNA micro-arrays unit, encoding DNA sequences unit, micro-reaction unit, solution extraction
unit and micro-control unit. The functions of each unit are discussed in detail, especially for the solution extraction unit,
where the optimal solution spaces are extracted. Finally, conclusions are drawn and future studies are discussed.
[Show abstract][Hide abstract] ABSTRACT: We present techniques for automating the design of computational systems built using DNA, given a set of high-level constraints on the desired behavior and performance of the system. We have developed a program called SCAN that exploits a previously implemented computational melting temperature primitive to search a 'nucleotide space' for sequences satisfying a pre-specified set of constraints, including hybridization discrimination, primer 5' end and 3' end stability, secondary structure reduction, and prevention of oligonucleotide dimer formation. The first version of SCAN utilized 24 h of computer time to search a space of over 7.5 billion unary counter designs and found only nine designs satisfying all of the pre-specified constraints. One of SCAN's designs has been implemented in the laboratory and has shown a marked improvement in performance over the products of previous attempts at manual design. We conclude with some novel ideas for improving the overall speed of the program that offer the promise of an efficient method for selecting optimal nucleotide sequences in an automated fashion.
[Show abstract][Hide abstract] ABSTRACT: We have developed an algorithm for designing multiple sequences of nucleic acids that have a uniform melting temperature between the sequence and its complement and that do not hybridize non-specifically with each other based on the minimum free energy (DeltaG (min)). Sequences that satisfy these constraints can be utilized in computations, various engineering applications such as microarrays, and nano-fabrications. Our algorithm is a random generate-and-test algorithm: it generates a candidate sequence randomly and tests whether the sequence satisfies the constraints. The novelty of our algorithm is that the filtering method uses a greedy search to calculate DeltaG (min). This effectively excludes inappropriate sequences before DeltaG (min) is calculated, thereby reducing computation time drastically when compared with an algorithm without the filtering. Experimental results in silico showed the superiority of the greedy search over the traditional approach based on the hamming distance. In addition, experimental results in vitro demonstrated that the experimental free energy (DeltaG (exp)) of 126 sequences correlated well with DeltaG (min) (|R| = 0.90) than with the hamming distance (|R| = 0.80). These results validate the rationality of a thermodynamic approach. We implemented our algorithm in a graphic user interface-based program written in Java.
Nucleic Acids Research 02/2005; 33(3):903-11. DOI:10.1093/nar/gki235 · 9.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: DNA computing often requires oligonucleotides that do not produce erroneous cross-hybridizations. By using in vitro evolution, huge libraries of non-crosshybridizing oligonucleotides might be evolved in the test tube. As a first step, a fitness function that corresponds to non-crosshybridization has to be implemented in an experimental protocol. Therefore, a modified version of PCR that selects non-crosshybridizing oligonucleotides was designed and tested. Experiments confirmed that the PCR-based protocol did amplify maximally mismatched oligonucleotides selectively over those that were more closely matched. In addition, a reaction temperature window was identified in which discrimination between matched and mismatched might be obtained. These results are a first step toward practical manufacture of very large libraries of non-crosshybridizing oligonucleotides in the test tube.
DNA Computing, 8th International Workshop on DNA Based Computers, DNA8, Sapporo, Japan, June 10-13, 2002, Revised Papers; 01/2002
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