Abstract
Under an all or nothing hybridization model, the problem of finding a library of non-crosshybridizing DNA oligonucleotides is shown to be equivalent to finding an independent set of vertices in a graph. Individual oligonucleotides or Watson-Crick pairs are represented as vertices. Indicating a hybridization, an edge is placed between vertices (oligonucleotides or pairs) if the minimum free energy of hybridization, according to the nearest-neighbor model of duplex thermal stability, is less than some threshold value. Using this equivalence, an algorithm is implemented to find maximal libraries. Sequence designs were generated for a test of a modified PCR protocol. The results indicated that the designed structures formed as planned, and that there was little to no secondary structure present in the single-strands. In addition, simulations to find libraries of 10-mers and 20-mers were done, and the base composition of the non-crosshybridizing libraries was found to be 2/3 A-T and 1/3 G-C under high salt conditions, and closer to uniform for lower salt concentrations.
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Deaton, R., Chen, J., Bi, H., Rose, J.A. (2003). A Software Tool for Generating Non-crosshybridizing Libraries of DNA Oligonucleotides. In: Hagiya, M., Ohuchi, A. (eds) DNA Computing. DNA 2002. Lecture Notes in Computer Science, vol 2568. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-36440-4_22
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DOI: https://doi.org/10.1007/3-540-36440-4_22
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