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A Hopfield Neural Classifier and Its FPGA Implementation for Identification of Symmetrically Structured DNA Motifs

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Abstract

Some specialized transcription factors recognize specific DNA sequences arranged in inverted and direct repeats with a short nucleotide spacer in between. Identification of these motifs has been challenging due to their high divergence. In this paper, we describe a novel computational approach that can greatly improve the efficiency and accuracy in prediction of these DNA binding sites. A Hopfield neural classifier was designed with the flexibility of internal structure being adapted recurrently for the target motif structure. An FPGA implementation of this recurrent neural network is presented. It contains 60 neurons, and is described by the Verilog HDL modules. The circuitry was mapped onto an Alpha Data Virtex-4LX160 FPGA board. A set of 600 experimentally verified steroid hormone binding sites was used as the training set, and the developed Hopfield neural classifier has been used to identify and classify actual Hormone Response Elements. The program has been proven to be an effective tool in studying hormone-regulated gene networks.

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References

  1. B. Alberts, D. Bray, J. Lewis, M. Raff, K. Roberts and J. Watson, “Control of Gene Expression,” Mol. Biol. Cell, Garland, 1994.

  2. D. GuhaThakurta, “Computational Identification of Transcriptional Regulatory Elements in DNA Sequence,” Nucleic Acids Res, vol. 34, no. 12, 2006, pp. 3585–3598.

    Article  Google Scholar 

  3. W. W. Wasserman and A. Sandelin, “Applied Bioinformatics for the Identification of Regulatory Elements,” Nat. Rev. Genet, vol. 5, no. 4, 2004, pp. 276–287.

    Article  Google Scholar 

  4. Y. Pilpel, P. Sudarsanam and G. M. Church, “Identifying Regulatory Networks by Combinatorial Analysis of Promoter Elements”, Nat. Genet, vol. 29, no. 2, 2001, pp. 153–159.

    Article  Google Scholar 

  5. S. Jones, P. van Heyningen, H. M. Berman and J. M. Thornton, “Protein–DNA Interactions: A Structural Analysis,” J. Mol. Biol, vol. 287, no. 5, 1999, pp. 877–896.

    Article  Google Scholar 

  6. A. V. Favorov, M. S. Gelfand, A. V. Gerasimova, D. A. Ravcheev, A. A. Mironov and V. J. Makeev, “A Gibbs Sampler for Identification of Symmetrically Structured, Spaced DNA Motifs with Improved Estimation of the Signal Length,” Bioinformatics, vol. 21, no. 10, 2005, pp. 2240–2245.

    Article  Google Scholar 

  7. A. Sandelin and W. W. Wasserman, “Prediction of Nuclear Hormone Receptor Response Elements,” Mol. Endocrinol. vol. 19, no. 3, 2005, pp. 595–606.

    Article  Google Scholar 

  8. C. T. Workman and G. D. Stormo, “ANN-Spec: A Method for Discovering Transcription Factor Binding Sites with Improved Specificity”. Pac. Symp. Biocomput, 2000, pp. 467–478.

  9. J. Hawkins and M. Boden, “The Applicability of Recurrent Neural Networks for Biological Sequence Analysis,” IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol. 2, no. 3, 2005, pp. 243–253.

    Article  Google Scholar 

  10. A. Ormondi and J. Rajapakse, “FPGA Implementations of Neural Networks”, Springer, 2006.

    Google Scholar 

  11. D. Hammerstom, “A Highly Parallel Digital Architecture for Neural Network Simulation,” in VLSI for Artificial Intelligence and Neural Networks, J. D. Delgado-Frias and W. R. Moore (Eds.), Plenum, 1991.

  12. R. K. Weinstein and R. H. Lee, “Architectures for High-Performance FPGA Implementations of Neural Models,” J. Neural Eng. vol. 3, 2006, pp. 21–34.

    Article  Google Scholar 

  13. A. Upegui, C. A. Pena-Reyes, E. Sanchez, “An FPGA Platform for On-line Topology Exploration of Spiking Neural Networks,” Microprocess. Microsyst, vol. 29, no. 5, 2005, pp. 211–223.

    Article  Google Scholar 

  14. P. J. Clare, J. W. Gulley, D. Hickman, M. I. Smith, “Design and Tuning of FPGA Implementations of Neural Networks,” Proc. SPIE, vol. 3069, 1997, pp. 129–136.

    Article  Google Scholar 

  15. Y. Maeda and T. Tada, “FPGA Implementation of a Pulse Density Neural Network with Learning Ability using Simultaneous Perturbation,” IEEE Trans. Neural Netw., vol. 14, no. 3, 2003, pp. 688–695.

    Article  Google Scholar 

  16. G. Cauwenberghs, “An Analog VLSI Recurrent Neural Network Learning a Continuous-Time Trajectory,” IEEE Trans. Neural Netw., vol. 7, no. 2, 1996, pp. 346–361.

    Article  Google Scholar 

  17. J. Zhu and P. Sutton, “FPGA Implementation of Neural Networks—A Survey of a Decade of Progress. 13th International Conference on Field-Programmable Logic and Applications (FPL 2003),” 2003, pp. 1062–1066.

  18. M. Hagan, H. Demuth and M. Beale, “Neural Network Design,” PSW Publishing Company, 1996.

    Google Scholar 

  19. S. Haykin, “Neural Networks: A Comprehensive Foundation,” Prentice Hall, New Jersey, 1999.

    MATH  Google Scholar 

  20. J. J. Hopfield, “Neural Networks and Physical Systems with Emergent Collective Computational Abilities”, Proc. Natl. Acad. Sci. U.S.A., vol. 79, no. 8, 1982, pp. 2554–2558.

    Article  MathSciNet  Google Scholar 

  21. J. H. Li, A. Michel and W. Porod, “Analysis and Synthesis of a Class of Neural Networks: Linear Systems Operating On A Closed Hypercube,” IEEE Trans. Circuits. Syst., vol. 36, no. 11, 1989, pp. 1405–1422.

    Article  MATH  MathSciNet  Google Scholar 

  22. J. K. Richer, B. M. Jacobsen, N. G. Manning, M. G. Abel, D. M. Wolf and K. B. Horwitz, “Differential Gene Regulation by the Two Progesterone Receptor Isoforms in Human Breast Cancer Cells,” J. Biol. Chem, vol. 277, no. 7, 2002, pp. 5209–5218.

    Article  Google Scholar 

  23. J. C. Leo, S. M. Wang, C. H. Guo, S. E. Aw, Y. Zhao, L. M. Li, K. M. Hui and V. C. Lin, “Gene Regulation Profile Reveals Consistent Anticancer Properties of Progesterone in Hormone-Independent Breast Cancer Cells Transfected With Progesterone Receptor,” Int. J. Cancer, vol. 117, no. 4, 2005, pp. 561–568.

    Article  Google Scholar 

  24. W. Xu, “Nuclear Receptor Coactivators: The Key To Unlock Chromatin,” Biochem. Cell. Biol., vol. 83, no. 4, 2005, pp. 418–428.

    Article  Google Scholar 

  25. R. M. Evans, “The Steroid and Thyroid Hormone Receptor Superfamily,” Science, vol. 240, no. 4854, 1988, pp. 889–895.

    Article  Google Scholar 

  26. C. C. Nelson, S. C. Hendy, R. J. Shukin, H. Cheng, N. Bruchovsky, B. F. Koop and P. S. Rennie, “Determinants of DNA Sequence Specificity of the Androgen, Progesterone, and Glucocorticoid Receptors: Evidence for Differential Steroid Receptor Response Elements,” Mol. Endocrinol., vol. 13, no. 12, 1999, pp. 2090–2107.

    Article  Google Scholar 

  27. H. Gronemeyer, “Control of Transcription Activation by Steroid Hormone Receptors,” FASEB J., vol. 6, no. 8, 1992, pp. 2524–2529.

    Google Scholar 

  28. M. Stepanova, F. Lin and V. Lin, “Establishing a Statistic Model for Recognition of Steroid Hormone Response Elements,” Comput. Biol. Chem., vol. 30, no. 5, 2006, pp. 339–347.

    Article  MATH  Google Scholar 

  29. V. G. Thackray, B. A. Lieberman and S. K. Nordeen, “Differential Gene Induction by Glucocorticoid and Progesterone Receptors,” J. Steroid Biochem. Mol. Biol., vol. 66, no. 4, 1998, pp. 171–178.

    Article  Google Scholar 

  30. B. A.Lieberman, B. J. Bona, D. P. Edwards and S. K. Nordeen, “The Constitution of a Progesterone Response Element,” Mol. Endocrinol., vol. 7, no. 4, 1993, pp. 515–527.

    Article  Google Scholar 

  31. K. J. Reid, S. C. Hendy, J. Saito, P. Sorensen and C. C. Nelson, “Two Classes of Androgen Receptor Elements Mediate Cooperativity Through Allosteric Interactions,” J. Biol. Chem., vol. 276, no. 4, 2001, pp. 2943–2952.

    Article  Google Scholar 

  32. M. Stepanova, F. Lin and V. C. Lin, “In Silico Modeling of Hormone Response Elements,” BMC Bioinformatics, vol. 7, no. S4, 2006, p. 27.

    Article  Google Scholar 

  33. I. Lee, “Data Mining Coupled Conceptual Spaces for Intelligent Agents in Data-Rich Environments,” Lect. Notes Comput. Sci., vol. 3684, pp. 42–48.

    Article  Google Scholar 

  34. A. E. Maris, M. R. Sawaya, M. Kaczor-Grzeskowiak, M. R. Jarvis, S. M. Bearson, M. L. Kopka, I. Schroder, R. P. Gunsalus et al., “Dimerization Allows DNA Target Site Recognition by the NarL Response Regulator,” Nat. Struct. Biol., vol. 9, no. 10, 2002, pp. 771–778.

    Article  Google Scholar 

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Correspondence to Maria Stepanova.

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Stepanova, M., Lin, F. & Lin, V.CL. A Hopfield Neural Classifier and Its FPGA Implementation for Identification of Symmetrically Structured DNA Motifs. J VLSI Sign Process Syst Sign Im 48, 239–254 (2007). https://doi.org/10.1007/s11265-007-0068-3

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  • DOI: https://doi.org/10.1007/s11265-007-0068-3

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