Abstract
cDNA microarray is a high throughput technology for gene expression analysis. Differing from conventional molecular approaches, which detect molecular targets on a one-by-one basis, cDNA microarray monitors gene expressions of living organisms on a global scale. However, the signal detected by a microarray assay contains a significant amount of noise. Certain types of noise are introduced by the systematic variations that are hardly avoidable by experimental approaches. Significant biological information can only be recognized after the original or raw data sets of microarray assay have been effectively processed. We report here our progress in establishing a Neural Network Normalization (N3) approach to cDNA microarray data processing. With the strong learning ability of the artificial neural network, the trained N3 algorithm is capable of the detection and suppression of systematic variations during microarray data processing and has plasticity in handling both linear and non-linear microarray data sets. The potential of this system in signal processing for other types of biochips, including nucleic acid and non-nucleic acid-based biochips, is yet to be explored.
Similar content being viewed by others
References
T.R. Golub, D.K. Slonim, P. Tamayo, C. Huard, M. Gaasenbeek, J.P. Mesirov, H. Coller, M.L. Loh, J.R. Downing, M.A. Caligiuri, C.D. Bloom, and E.S. Lander, “Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring,” Science, vol. 286, 1999, pp. 531–537.
M. Schena, D. Shalon, R.W. Davis, and P.O. Brown, “Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray,” Science, vol. 270, 1995, pp. 467–470.
E.S. Lander, “Array of Hope,” Nature Genetics (Suppl.),vol. 21, 1999, pp. 3–4.
Y.D. Chen, E.R. Dougherty, and M.L. Bittner, “Ratio-Based Decisions and the Quantitative Analysis of cDNA Microarray Images,” Journal of Biomedical Optics,vol. 2, 1997, pp. 354–374.
V.G. Cheung, M. Morley, F. Aguilar, A. Massimi, R. Kucherlapti, and G. Childs, “Making and Reading Microarrays,” Nature Genetics Supplement,vol. 21, 1999, pp. 15–19.
M. Bittner, P. Meltzer, Y. Chen, et al., “Molecular Classification of Cutaneous Malignant Melanoma by Gene Expression Profiling,” Letters to Nature,vol. 403, 2000, pp. 536–540.
M.Schena, DNAMicroarrays: APractical Approach, ed. Oxford University Press, 1999.
M. Schena, Microarray Biochip Technology, ed. Eaton, 2000.
H.B. Yue, P.S. Eastman, B. Wang, et al., “An Evaluation of the Performance of cDNA Microarrays for Dectecting Changes in Global mRNA Expression,” Nucleic Acids Research,vol. 29, 2001, pp. e41–e41.
J. Schuchhardt, D. Beule, A. Malik, et al., “Normalization Strategies for cDNA Microarrays,” Nucleic Acids Research,vol. 28, 2000, pp. e47–e47.
C.J. Friddle, T. Koga, E.M. Rubin, and J. Bristow, “Expression Profiling Reveals Distinct Sets of Genes Altered During Induction and Regression of Cardiac Hypertrophy,” Proc. Natl. Acad. Sci.,vol. 97, 2000, pp. 6745–6750.
T. Galitski, A.J. Saldanha, C.A. Styles, E.S. Lander, and G.R. Fink, “Ploidy Regulation of Gene Expression,” Science,vol. 285, 1999, pp. 251–254.
M.B. Eisen, P.T. Spellman, P.O. Brown, and D. Botstein, “Cluster Analysis and Display of Genome-Wide Expression Patterns,” Proc. Natl. Acad. Sci., 1998, pp. 14863–14868.
D.T. Ross, U. Scherf, M.B. Eisen, et al., “Systematic Variation in Gene Expression Patterns in Human Cancer Cell Lines,” Nature Genetics (Suppl.), vol. 24, 2000, pp. 227–234.
M.K. Kerr, M. Martin, and G.A. Churchill, “Analysis of Variance for Gene Expression Microarray Data,” J. Comput. Biol.,vol. 7, 2000, pp. 819–837.
M.K. Kerr and G.A. Churchill, “Experimental Design for Gene Expression Microarrays,” Technical Report, The Jackson Laboratory, http://www.jax.org/research/churchill/pubs/index.html, p. 2000.
T. Kepler, L. Crosby, and K.T. Morgan, “Normalization and Analysis of DNA Microarray Data by Self-Consistency and Local Regression,” Genome Biol.,vol. 3, pp. research0037.1–0037.12, 2002.
C. Deng, A.L. Wang, D.N. Wang, and P.S. Zhang, “A Nonlinear Global Optimization Approach for Normalizing cDNAMicroarray Data,” presented at DIMACS Workshop on Analysis of Gene Expression Data, Piscataway, NJ, 2001.
C. Deng, P.S. Zhang, A.L. Wang, B.J. Trummer, and D.N. Wang, “Normalization of cDNAMicroarray Data by Using Neural Networks,” Proceedings of the 2002 International Joint Conference on Neural Networks, Hawaii, USA, 2002.
G.C. Tseng, M.K. Oh, L. Rohlin, J.C. Liao, and W.H. Wong, “Issues in cDNA Microarray Analysis: Quality Filtering, Channel Normalization, Models of Variations and Assessment of Gene Effects,” Nucleic Acids Res.,vol. 29, 2001, pp. 2549–2557.
I.V. Yang, E. Chen, J.P. Hasseman, W. Liang, B.C. Frank, S. Wang, V. Sharov, A.I. Saeed, J. White, J. Li, N.H. Lee, T.J. Yeatman, and J. Quackenbush, “Within the Fold: Assessing Differential Expression Measures and Reproducibility in Microarray Assays,” Genome Biol.,vol. 3, 2002, p. research0062.
S. Capaldi, R.C. Getts, and S.D. Jayasena, “A Signal Amplification Through Nucleotide Extension and Excision on a Dendritic DNA Platform,” Nucl. Acids Res.,vol. 28, 2000, p. 21e.
J.T.L. Irwin, W. Sandberg, Craig L. Fancourt, Jose C. Principe, Shigeru Katagiri, and S. Haykin, Nonlinear Dynamical Systems: Feedforward Neural Network Perspectives,vol., ed.
S. Haykin, Neural Networks: A Comprehensive Foundation Second Edition,vol., ed. Prentice Hall, 1999.
R. Rojas, Neural Networks: A Systematic Introduction,vol., ed. Berlin Heidelberg: Springer-Verlag, 1996.
D.E. Rumelhart, G.E. Hinton, and R.J. Williams, Chap. 8: Learning Internal Representations,vol., ed. MIT Press, 1986.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Deng, C., Wang, D. Neural Network Normalization (N3) to Uncover the Differential Signal of cDNA Microarrays. The Journal of VLSI Signal Processing-Systems for Signal, Image, and Video Technology 38, 227–236 (2004). https://doi.org/10.1023/B:VLSI.0000042489.45944.64
Published:
Issue Date:
DOI: https://doi.org/10.1023/B:VLSI.0000042489.45944.64