Abstract
We present a new approach to identify the locations of critical DNA or RNA sequence signals which couples large-scale synthesis with sophisticated designs employing combinatorial group testing and balanced Gray codes. Experiments in polio and adenovirus demonstrate the efficiency and generality of this procedure. In this paper, we give a new class of consecutive positive group testing designs, which offer a better tradeoff of cost, resolution, and robustness than previous designs for signal search.
Let n denote the number of distinct regions in a sequence, and d the maximum number of consecutive positives regions which can occur. We propose a design which improves on the consecutive-positive group testing designs of Colbourn. Our design completely identifies the boundaries of the positive region using t tests, where t≈log2(1.27n/d)+0.5log2(log2(1.5n/d))+d.
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Balding, D.J., Torney, D.C.: The design of pooling experiments for screening a clone map. Fungal Genet. Biol. 21(3), 302–307 (1997)
Bhat, G., Savage, C.: Balanced gray codes. Electron. J. Comb. 3, R25 (1996)
Bruno, W.J., Knill, E., Balding, D.J., Bruce, D.C., Doggett, N.A., Sawhill, W.W., Stallings, R.L., Whittaker, C.C., Torney, D.C.: Efficient pooling designs for library screening. Genomics 26(1), 21–30 (1995)
Bugl, H., Danner, J.P., Molinari, R.J., Mulligan, J.T., Park, H.-O., Reichert, B., Roth, D.A., Wagner, R., Budowle, B., Scripp, R.M., Smith, J.A.L., Steele, S.J., Church, G., Endy, D.: DNA synthesis and biological security. Nat. Biotechnol. 25, 627–629 (2007)
Colbourn, C.J.: Group testing for consecutive positives. Ann. Comb. 3(1), 37–41 (1999)
Coleman, J.R., Papamichial, D., Futcher, B., Skiena, S., Mueller, S., Wimmer, E.: Virus attenuation by genome-scale changes in codon-pair bias. Science 320, 1784–1787 (2008)
Czar, M.J., Anderson, J.C., Bader, J.S., Peccoud, J.: Gene synthesis demystified. Trends Biotechnol. 27(2), 63–72 (2009)
Du, D., Hwang, F.: Combinatorial Group Testing and Its Applications. World Scientific, Singapore (2000)
Du, D., Hwang, F.: Pooling Designs and Nonadaptive Group Testing: Important Tools for DNA Sequencing. World Scientific, Singapore (2006)
D’yachkov, A.G., Macula, A.J. Jr., Rykov, V.V.: New constructions of superimposed codes. IEEE Trans. Inf. Theory 46(1), 284–290 (2000)
D’yachkov, A.G., Rykov, V.V.: Bounds on the length of disjunctive codes. Probl. Pereda. Inf. 18(3), 7–13 (1982)
D’yachkov, A.G., Rykov, V.V., Rashad, A.M.: Superimposed distance codes. Probl. Control Inf. Theory 18(4), 237–250 (1989)
Eppstein, D., Goodrich, M.T., Hirschberg, D.S.: Improved combinatorial group testing algorithms for real-world problem sizes. SIAM J. Comput. 36(5), 1360–1375 (2006)
Gibson, D.G., Glass, J.I., Lartigue, C., Noskov, V.N., Chuang, R.-Y., Algire, M.A., Benders, G.A., Montague, M.G., Ma, L., Moodie, M.M., Merryman, C., Vashee, S., Krishnakumar, R., Assad-Garcia, N., Andrews-Pfannkoch, C., Denisova, E.A., Young, L., Qi, Z.-Q., Segall-Shapiro, T.H., Calvey, C.H., Parmar, P.P., Hutchison, C.A., Smith, H.O., Venter, J.C.: Creation of a bacterial cell controlled by a chemically synthesized genome. Science 329(5987), 52–56 (2010)
Gray, F.: Pulse code communication. US Patent 2632058 March 17, 1953
Kautz, W., Singleton, R.: Nonrandom binary superimposed codes. IEEE Trans. Inf. Theory 10(4), 363–377 (1964)
Knuth, D.: The Art of Computer Programming, Volume 4 Fascicle 3: Generating All Combinations and Partitions. Addison-Wesley, Reading (2005)
Lin, Y.-L., Ward, C., Jain, B., Skiena, S.: Constructing Orthogonal de Bruijn Sequences. LNCS, vol. 6844, pp. 595–606. Springer, Berlin (2011)
Macula, A.J.: A simple construction of d-disjunct matrices with certain constant weights. Discrete Math. 162(1), 311–312 (1996). doi:10.1038/nbt.1636
Mueller, S., Coleman, R., Papamichail, D., Ward, C., Nimnual, A., Futcher, B., Skiena, S., Wimmer, E.: Live attenuated influenza vaccines by computer-aided rational design. Nat. Biotechnol. 28 (2010)
Müller, M., Jimbo, M.: Consecutive positive detectable matrices and group testing for consecutive positives. Discrete Math. 279(1–3), 369–381 (2004)
Müller, M., Jimbo, M.: Cyclic sequences of k-subsets with distinct consecutive unions. Discrete Math. 308(2–3), 457–464 (2008)
Pemmaraju, S., Skiena, S.: Computational Discrete Mathematics: Combinatorics and Graph Theory with Mathematica. Cambridge University Press, New York (2003)
Savage, C.: A survey of combinatorial gray codes. SIAM Rev. 39, 605–629 (1997)
Schlaghoff, J., Triesch, E.: Improved results for competitive group testing. Comb. Probab. Comput. 14(1–2), 191–202 (2005)
Shields, I., Shields, B.J., Savage, C.D.: An update on the middle levels problem. Discrete Math. 309(17), 5271–5277 (2009)
Shimada, M., Amano, K.: A note on the middle levels conjecture. (2009). Arxiv preprint. arXiv:0912.4564
Sitaraman, V., Hearing, P., Ward, C., Gnatenko, D., Wimmer, E., Skiena, S., Bahou, W.: Computationally designed adeno-associated virus (AAV) Rep 78 is efficiently maintained within an adenovirus vector. Proc. Natl. Acad. Sci. 108(34), 14294–14299 (2011)
Skiena, S.: Redesigning viral genomes. IEEE Comput. 45(3), 47–53 (2012)
Song, Y., Liu, Y., Ward, C., Mueller, S., Futcher, B., Skiena, S., Paul, A., Wimmer, E.: Identification of cis-acting elements in the coding sequence of the poliovirus RNA polymerase using computer generated designs and synthetic DNA synthesis. Proc. Natl. Acad. Sci. 109(36), 14301–14307 (2012)
Wilf, H.: Combinatorial Algorithms: An Update. SIAM, Philadelphia (1989)
Acknowledgements
We would like to thank our experimental collaborators in Wadie Bahou and Eckard Wimmer’s groups, and Ian Shields for providing the middle level Hamiltonian cycles which were used to create our group testing designs. This work was partially supported by NIH Grant AI075219 and NSF Grants DBI-1060572 and IIS-1017181.
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Lin, YL., Ward, C. & Skiena, S. Synthetic Sequence Design for Signal Location Search. Algorithmica 67, 368–383 (2013). https://doi.org/10.1007/s00453-013-9760-9
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DOI: https://doi.org/10.1007/s00453-013-9760-9