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Scalable Dynamic Fuzzy Biomolecular Network Models for Large Scale Biology

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Part of the book series: Studies in Fuzziness and Soft Computing ((STUDFUZZ,volume 242))

Summary

Fuzzy logic is an effective language for models that interpret large scale, high throughput molecular biology experiments, including genomics, proteomics,metabolomics, and inhibitor screening. Two important principles apply for biological system modeling: (1) In the post-genome era, the development of novel molecular diagnostics and therapeutics requires interpreting the complex results of high-throughput multiplexed experiments, and a framework to efficiently and rapidly design hypothesis-driven experiments. (2) Biomolecular data are typically noisy and semi-quantitative, in particular because of the typical fluorescence output of high throughput experiments. Fuzzy biomolecular network models coupled with hypothesis generation strategies address these needs. In this chapter, we describe an integrated, data-driven method for extracting system models from data and generating hypotheses for experimental design. The method is based on scalable, linear relationships between nodes of a biomolecular network, representing the expression of genes, proteins, and/or metabolites. Data from high-throughput are fuzzified using a universal normalization method. Best-fitting models are generated through an evolutionary algorithm, and disagreements between plausible hypothetical network models are used as the basis for identifying experimental designs. The result is a modeling and simulation framework that can be easily integrated with text-based and graphical biological knowledge contained within existing literature and databases.

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References

  1. Arita, M., Robert, M., Tomita, M.: All systems go: launching cell simulation fueled by integrated experimental biology data. Curr. Opin. Biotech. 16, 344–349 (2005)

    Article  Google Scholar 

  2. McCutchen-Maloney, S.L., Forde, C.E.: Characterization of transcription factors by mass spectrometry and the role of seldi-ms. Mass. Spectrom. Rev. 21, 419–439 (2002)

    Article  Google Scholar 

  3. Chen, K.C., Csikasz-Nagy, A., Gyorffy, B., Val, J., Novak, B., Tyson, J.: Kinetic analysis of a molecular model of the budding yeast cell cycle. Mol. Biol. Cell. 13, 52–70 (2000)

    Google Scholar 

  4. Combs, W.E., Andrews, J.E.: Combinatorial rule explosion eliminated by a fuzzy rule configuration. IEEE Trans. Fuzzy Syst. 6, 1–11 (1998)

    Article  Google Scholar 

  5. Cutler, P.L.: Protein arrays: the current state-of-the-art. Proteomics 3, 3–18 (2003)

    Article  Google Scholar 

  6. Datta, S., Sokhansanj, B.A.: Accelerated search for biomolecular network models to interpret high-throughput experimental data. BMC Bioinformatics 8, 258 (2007)

    Article  Google Scholar 

  7. D’Haeseleer, P., Wen, X., Fuhrman, S., Somogyi, R.: Linear modeling of mrna expression levels during cns development and injury. In: Pac. Symp. Biocomp (PSB 1999), vol. 2, pp. 41–52 (1999)

    Google Scholar 

  8. Fitch, J.P., Sokhansanj, B.: Genomic engineering: moving beyond dna sequence to function. Proc. IEEE 88, 1949–1971 (2000)

    Article  Google Scholar 

  9. Friedman, N.: Inferring cellular networks using probabilistic graphical models. Science 303(5659), 799–805 (2004)

    Article  Google Scholar 

  10. Gianchandani, E.P., Brautigan, D.L., Papin, J.A.: System analyses characterize integrated functions of biochemical networks. Trends Biochem. Sci. 31, 284–291 (2006)

    Article  Google Scholar 

  11. Gipson, G.T., Tatsuoka, K.S., Sokhansanj, B.A., Ball, R.J., Connor, S.C.: Assignment of ms-based metabolomic datasets via compound interaction pair mapping. Metabolomics 4, 94–103 (2008)

    Article  Google Scholar 

  12. Gipson, G.T., Tatsuoka, K.S., Sweatman, B.C., Connor, S.C.: Weighted least-squares deconvolution method for discovery of group differences between complex biofluid 1h nmr spectra. J. Magn. Reson. 183, 269–277 (2006)

    Article  Google Scholar 

  13. Glass, L., Kauffman, S.A.: The logical analysis of continuous, nonlinear biochemical control networks. J. Theor. Biol. 39, 103–129 (1973)

    Article  Google Scholar 

  14. Griffin, T.J., Gygi, S.P., Ideker, T., Rist, B., Eng, J., Hood, L., Aebersold, R.: Complementary profiling of gene expression at the transcriptome and proteome levels in saccharomyces cerevisiae. Mol. Cell. Proteomics 1, 323–333 (2002)

    Article  Google Scholar 

  15. Grigoriev, A.: On the number of protein-protein interactions in the yeast proteome. Nucleic Acids Res. 31, 4157–4161 (2003)

    Article  Google Scholar 

  16. Holland, J.H.: Adaptation in natural and artificial systems. University of Michigan Press (1975)

    Google Scholar 

  17. Hu, X., Wu, D.D.: Data mining and predictive modeling of biomolecular network from biomedical literature and databases. IEEE/ACM Trans. Comput. Biol. Bioinform. 4, 251–263 (2007)

    Article  Google Scholar 

  18. Husmeier, D.: Sensitivity and specificity of inferring genetic regulatory interactions from microarray experiments with dynamic bayesian networks. Bioinformatics 19, 2271–2282 (2003)

    Article  Google Scholar 

  19. Jin, Y.: Fuzzy modeling of high-dimensional systems: complexity reduction and interpretability improvement. IEEE Trans. Fuzzy Syst. 8, 212–221 (2000)

    Article  Google Scholar 

  20. Laubenbacher, R., Stigler, B.: A computational algebra approach to the reverse engineering of gene regulatory networks. J. Theor. Biol. 229, 523–537 (2004)

    Article  MathSciNet  Google Scholar 

  21. Liang, S., Fuhrman, S., Somogyi, R.: REVEAL, a general reverse engineering algorithm for inference of genetic network architectures. In: Pac. Symp. Biocomp (PSB 2000), vol. 3, pp. 18–29 (2000)

    Google Scholar 

  22. Mendel, J.M.: Fuzzy logic systems for engineering: a tutorial. Proc. IEEE 83, 345–377 (1995)

    Article  Google Scholar 

  23. Michiels, S., Koscielny, S., Hill, C.: Interpretation of microarray data in cancer. Br. J. Cancer. 96, 1155–1158 (2007)

    Article  Google Scholar 

  24. Overington, J.P., Al-Lazikani, B., Hopkins, A.L.: How many drug targets are there? Nat. Rev. Drug. Disc. 5, 993–996 (2006)

    Article  Google Scholar 

  25. Paddison, P.J., Silva, J.M., Conklin, D.S., Schlabach, M., Li, M., Aruleba, S., Balija, V., O’Shaughnessy, A., Gnoj, L., Scobie, K., Chang, K., Westbrook, T., Cleary, M., Sachidanandam, R., McCombie, W.R., Elledge, S.J., Hannon, G.J.: A resource for large-scale rna-interference-based screens in mammals. Nature 428, 427–431 (2004)

    Article  Google Scholar 

  26. Perkins, T.J., Hallett, M., Glass, L.: Inferring models of gene expression dynamics. J. Theor. Biol. 230, 289–299 (2004)

    Article  MathSciNet  Google Scholar 

  27. Quong, A.A., Kercher, J.R., McCready, P.M., Quong, J.N., Sokhansanj, B.A., Fitch, J.P.: An indexed modeling and experimental strategy for biosignatures of pathogen and host. J. Franklin. Inst. 341, 157–174 (2004)

    Article  MATH  MathSciNet  Google Scholar 

  28. Rangel, C., Angus, J., Ghahramani, Z., Lioumi, M., Sotheran, E., Gaiba, A.: Modeling t-cell activation using gene expression profiling and state-space models. Bioinformatics 20, 1361–1372 (2004)

    Article  Google Scholar 

  29. Rosales, R.A., Fill, M., Escobar, A.L.: Calcium regulation of single ryanodine receptor channel gating analyzed using hmm/mcmc statistical methods. J. Gen. Physiol. 121, 533–553 (2004)

    Article  Google Scholar 

  30. Schliep, A., Schonhuth, A., Steinhoff, C.: Using hidden markov models to analyze gene expression time course data. Bioinformatics 19, i255–i263 (2003)

    Article  Google Scholar 

  31. Shmulevich, I., Dougherty, E.R., Kim, S., Zhang, W.: Probabilistic boolean networks: a rule-based uncertainty model for gene regulatory networks. Bioinformatics 18, 261–274 (2002)

    Article  Google Scholar 

  32. Sokhansanj, B.A., Fitch, J.P.: URC fuzzy modeling and simulation of gene regulation. In: Conf. Proc. IEEE Eng. Med. Biol. Soc., vol. 3, pp. 2918–2921 (2001)

    Google Scholar 

  33. Sokhansanj, B.A., Fitch, J.P., Quong, J.N., Quong, A.A.: Linear fuzzy gene network models obtained from microarray data by exhaustive search. BMC Bioinformatics 5, 108 (2004)

    Article  Google Scholar 

  34. Sokhansanj, B.A., Rodrigue, G.R., Fitch, J.P., Wilson III, D.M.: A quantitative model of human dna base excision repair. i. mechanistic insights. Nucleic Acids Res 30, 1817–1825 (2002)

    Article  Google Scholar 

  35. Spellman, P.T., Sherlock, G., Zhang, M.Q., Iyer, V.R., Anders, K., Eisen, M.B., Brown, P.O., Botstein, D., Fucher, B.: Comprehensive identification of cell cycle-regulated genes of the yeast saccharomyces cerevisiae by microarray hybridization. Mol. Biol. Cell. 9, 3273–3297 (1998)

    Google Scholar 

  36. Tegner, J., Yeung, M.K.S., Hasty, J., Collins, J.J.: Reverse engineering gene networks: integrating genetic perturbations with dynamical modeling. Proc. Nat. Acad. Sci. USA 99, 6163–6168 (2000)

    Google Scholar 

  37. Weinschenk, J.J., Marks, R.J.I., Combs, W.E.: Layered urc fuzzy systems: a novel link between fuzzy systems and neural networks. In: Proc. 2003 Intl. Joint Conf. Neural Net, pp. 2995–3000 (2003)

    Google Scholar 

  38. Whitfield, M.L., Sherlock, G., Saldanha, A.J., Murray, J.I., Ball, C.A., Alexander, K.E., Matese, J.C., Perou, C.M., Hurt, M.M., Brown, P.O., Botstein, D.: Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol. Biol. Cell 13, 1977–2000 (2002)

    Article  Google Scholar 

  39. Yeung, M.K.S., Tegner, J., Collins, J.J.: Reverse engineering gene networks using signular value decomposition and robust recognition. Proc. Nat. Acad. Sci. USA 100, 5944–5949 (2002)

    Google Scholar 

  40. Zadeh, L.A.: Fuzzy sets. Information and Control 8, 338–352 (1965)

    Article  MATH  MathSciNet  Google Scholar 

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Sokhansanj, B.A., Datta, S., Hu, X. (2009). Scalable Dynamic Fuzzy Biomolecular Network Models for Large Scale Biology. In: Jin, Y., Wang, L. (eds) Fuzzy Systems in Bioinformatics and Computational Biology. Studies in Fuzziness and Soft Computing, vol 242. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-89968-6_12

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  • DOI: https://doi.org/10.1007/978-3-540-89968-6_12

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-89967-9

  • Online ISBN: 978-3-540-89968-6

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