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Combining Gene Expression Profiles and Drug Activity Patterns Analysis: A Relational Clustering Approach

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Journal of Mathematical Modelling and Algorithms

Abstract

The combined analysis of tissue micro array and drug response datasets has the potential of revealing valuable knowledge about various relations among gene expressions and drug activity patterns in tumor cells. However, the amount and the complexity of biological data needs appropriate data mining models in order to extract interesting patterns and useful information. The ultimate goal of this paper is to define a model which, given the gene expression profile related to a specific tumor tissue, could help in selecting a set of most responsive drugs. This is accomplished through an integrated framework based on a constraint-based clustering algorithm, called Relational K-Means, which groups cell lines using drug response information and taking into account cell-to-cell relationships derived from their gene expression profiles.

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References

  1. Amato, R., Menniti, M., Agosti, V., Boito, R., Costa, N., Bond, H.M., Barbieri, V., Tagliaferri, P., Venuta, S., Perrotti, N.: IL-2 signals through Sgk1 and inhibits proliferation and apoptosis in kidney cancer cells. J. Mol. Med. 85(7), 707–721 (2007)

    Article  Google Scholar 

  2. Basu, S., Bilenko, M., Mooney, R.J.: A probabilistic framework for semi-supervised clustering. In: Kim, W., Kohavi, R., Gehrke, J., DuMouchel, W. (eds.) Proceedings of the Tenth ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, 22–25 August 2004, Seattle, pp. 59–68. ACM, New York (2004)

    Chapter  Google Scholar 

  3. Bilenko, M., Basu, S., Mooney, R.J.: Integrating constraints and metric learning in semi-supervised clustering. In: Greiner, R., Schuurmans, D. (eds.) Proceedings of the Twenty-First International Conference on Machine Learning 2004, Alberta, pp. 81–88. ACM, New York (2004)

    Google Scholar 

  4. Buchholz, M., Biebl, A., Neee, A., Wagner, M., Iwamura, T., Leder, G., Adler, G., Gress, T.: SERPINE2 (protease nexin I) promotes extracellular matrix production and local invasion of pancreatic tumors in vivo. Cancer Res. 63, 4945–4951 (2003)

    Google Scholar 

  5. Chang, J.H., Hwang, K.B., Zhang, B.T.: Analysis of gene expression profiles and drug activity patterns by clustering and Bayesian network learning. In: Lin, S.M., Johnson, K.F. (eds.) Methods of Microarray Data Analysis II, chapter 11, pp. 169–184. Kluwer Academic, Dordrecht (2002)

    Chapter  Google Scholar 

  6. Clark, C.J., Sage, E.H.: A prototypic matricellular protein in the tumor microenvironment where there’s SPARC, there’s fire. J. Cell. Biochem. 104(3), 721–732 (2008)

    Article  Google Scholar 

  7. Cohen, J., Cohen, P., West, S.G., Aiken, L.S.: Applied Multiple Regression/Correlation Analysis for the Behavioural Science. Lawrence Erlbaum Associates, Hillsdale (2003)

    Google Scholar 

  8. Corsini, P., Lazzerini, B., Marcelloni, F.: A new fuzzy relational clustering algorithm based on the fuzzy C-means algorithm. J. Soft Comput. 9, 439–447 (2005)

    Article  Google Scholar 

  9. Dasgupta, N., Lin, S.M., Carin, L.: Modeling pharmacogenomics of the NCI-60 anticancer data set: utilizing kernel PLS to correlate the microarray data to therapeutic responses. In: Lin, S.M., Johnson, K.F. (eds.) Methods of Microarray Data Analysis II, chapter 10, pp. 151–167. Kluwer Academic, Dordrecht (2002)

    Chapter  Google Scholar 

  10. Del Rio, M., Molina, F., Bascoul-Mollevi, C., Copois, V., Bibeau, F., Chalbos, P., Bareil, C., Kramar, A., Salvetat, N., Fraslon, C., Conseiller, E., Granci, V., Leblanc, B., Pau, B., Martineau, P., Ychou, M.: Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan. J. Clin. Oncol. 25(7), 773–780 (2007)

    Article  Google Scholar 

  11. Dempster, A., Laird, N., Rubin, D.: Maximum likelihood from incomplete data via the EM algorithm. J. R. Stat. Soc. 39(1), 1–38 (1977)

    MATH  MathSciNet  Google Scholar 

  12. Edwards, K.M., Mnger, K.: Depletion of physiological levels of the human TID1 protein renders cancer cell lines resistant to apoptosis mediated by multiple exogenous stimuli. Oncogene 23(52), 8419–8431 (2004)

    Article  Google Scholar 

  13. Eisen, M.B., Spellman, P.T., Brown, P.O., Botstein, D.: Cluster analysis and display of genome-wide expression patterns. In: Schekman, R. (ed.) Proceedings of the National Academy of Sciences of the United States of America, vol. 1998, pp. 14863–14868 (1998)

  14. Eren, B., Sar, M., Oz, B., Dincbas, F.H.: MMP-2, TIMP-2 and CD44v6 expression in non-small-cell lung carcinomas. Ann. Acad. Med. Singap. 37(1), 32–39 (2008)

    Google Scholar 

  15. Friedman, N., Linial, M., Nachman, I., Pe’er, D.: Using Bayesian networks to analyze expression data. In: Shamir, R., Miyano, S., Istrail, S., Pevzner, P., Waterman, M. (eds.) Proceedings of the Fourth Annual International Conference on Computational Molecular Biology, 8–11 April 2000, Tokyo, pp. 127–135 (2000)

  16. Gonzalez, T.F.: Clustering to minimize the maximum inter-cluster distance. J. Theor. Comput. Sci. 38, 293–306 (1985)

    Article  MATH  Google Scholar 

  17. Graepel, T., Burger, M., Obermayer, K.: Self-organizing maps: generalizations and new optimization techniques. J. Neurocomput. 21, 173–190 (1998)

    Article  MATH  Google Scholar 

  18. Hall, M.A.: Correlation-based feature reduction for discrete and numeric class machine learning. In: Proceedings of the 17th International Conference on Machine Learning (2000)

  19. Hand, D.J., Mannila, H., Smyth, P.: Principles of Data Mining. MIT, Cambridge (2001)

    Google Scholar 

  20. Hansen, G.A., Vorum, H., Jacobsen, C., Honore, B.: Calumenin but not reticulocalbin forms a Ca2 +-dependent complex with thrombospondin-1. A potential role in haemostasis and thrombosis. Mol. Cell. Biochem. 320, 25–33 (2009)

    Article  Google Scholar 

  21. Hartemink, A.J., Gifford, D.K., Jaakkola, T.S., Young, R.A.: Using graphical models and genomic expression data to statistically validate models of genetic regulatory networks. In: Altman, R.B., Dunker, A.K., Hunker, L., Lauderdale, K., Klein, T.E.D. (eds.) Proceedings of Pacific Symposium on Biocomputing, 3–7 January 2001, Hawaii, pp. 422–433 (2001)

  22. Hwang, K.B., Cho, D.Y., Park, S.W., Kim, S.D., Zhang, B.T.: Applying machine learning techniques to analysis of gene expression data: cancer diagnosis. In: Lin, S.M., Johnson, K.F. (eds). Methods of Microarray Data Analysis, pp. 167–182. Kluwer Academic, Dordrecht (2001)

    Google Scholar 

  23. Jalilian, A., Javadi, E., Akrami, M., Fakhrzadeh, H., Heshmat, R., Rahmani, M., Bandarian, F.: Association of cys 311 ser polymorphism of paraoxonase-2 gene with the risk of coronary artery disease. Arch Iran Med. 11(5), 544–549 (2008)

    Google Scholar 

  24. Jiang, L.I., Collins, J., Davis, R., Fraser, I.D., Sternweis, P.C.: Regulation of cAMP responses by the G12/13 pathway converges on adenylyl cyclase VII. J. Biol. Chem. 283(34), 23429–23439 (2008)

    Article  Google Scholar 

  25. Khan, J., Wei, J.S., Ringnr, M., Saal, L.H., Ladanyi, M., Westermann, F., Berthold, F., Schwab, M., Antonescu, C.R., Peterson, C., Meltzer, P.S.: Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks. J. Nat. Med. 7, 673–679 (2001)

    Article  Google Scholar 

  26. Kim, S., Jin, J., Kunapuli, S.P.: Akt activation in platelets depends on Gi signaling pathways. J. Biol. Chem. 279(6), 4186–4195 (2004)

    Article  Google Scholar 

  27. Kutty, R.K., Chen, S., Samuel, W., Vijayasarathy, C., Duncan, T., Tsai, J.Y., Fariss, R.N., Carper, D., Jaworski, C., Wiggert, B.: Cell density-dependent nuclear/cytoplasmic localization of NORPEG (RAI14) protein. Mol. Cell Biol. Res. Commun. 345(4), 1333–1341 (2006)

    Google Scholar 

  28. Lee, J.H., Kim, S.H., Lee, E.S., Kim, Y.S.: CD24 overexpression in cancer development and progression: a meta-analysis. Oncol. Rep. 22(5), 1149–1156 (2009)

    Google Scholar 

  29. Li, Z., Zhou, Z., Welch, D.R., Donahue, H.J.: Expressing connexin 43 in breast cancer cells reduces their metastasis to lungs. Clin. Exp. Metastasis. 25(8), 893–901 (2008)

    Article  Google Scholar 

  30. MacQueen, J.B.: Some methods for classification and analysis of multivariate observations. In: LeCam, L.M., Neyman, N. (eds.) Proceedings of the Fifth Berkeley Symposium on Mathematical Statistics and Probability, pp. 281–297. University of California Press, Berkeley (1967)

    Google Scholar 

  31. Maglott, D., Ostell, J., Pruitt, K.D., Tatusova, T.: Entrez Gene: gene-centered information at NCBI. Nucleic Acids Res. 35, D26–D31 (2007)

    Article  Google Scholar 

  32. Mikosz, C.A., Brickley, D.R., Sharkey, M.S., Moran, T.W., Conzen, S.D.: Glucocorticoid receptor-mediated protection from apoptosis is associated with induction of the serine/threonine survival kinase gene, sgk-1. J. Biol. Chem. 276, 16649–16654 (2001)

    Article  Google Scholar 

  33. Ng, C.J., Bourquard, N., Grijalva, V., Hama, S., Shih, D.M., Navab, M., Fogelman, A.M., Lusis, A.J., Young, S., Reddy, S.T.: Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower apolipoprotein-B-containing lipoproteins: anti-atherogenic role for paraoxonase-2. J. Biol. Chem. 281(40), 29491–29500 (2006)

    Article  Google Scholar 

  34. Roberts, A.N., Leighton, B., Todd, J.A., Cockburn, D., Schofield, P.N., Sutton, R., Holt, S., Boyd, Y., Day, A.J., Foot, E.A.: Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus. Proc. Natl. Acad. Sci. U.S.A. 86(24), 9662–9666 (1989)

    Article  Google Scholar 

  35. Raychaudhuri, S., Stuart, J.M., Altman, R.B.: Principal components analysis to summarize microarray experiments: application to sporulation time series. In: Altman, R.B., Dunker, A.K., Hunker, L., Lauderdale, K., Klein, T.E.D. (eds.) Proceedings of Pacific Symposium on Biocomputing, 4–9 January 2000, Hawaii, pp. 452–463 (2000)

  36. Qin, H., Shao, Q., Curtis, H., Galipeau, J., Belliveau, D.J., Wang, T., Alaoui-Jamali, M.A., Laird, D.W.: Retroviral delivery of connexin genes to human breast tumor cells inhibits in vivo tumor growth by a mechanism that is independent of significant gap junctional intercellular communication. J. Biol. Chem. 277(32), 29132–29138 (2002)

    Article  Google Scholar 

  37. Sagiv, E., Arber, N.: The novel oncogene CD24 and its arising role in the carcinogenesis of the GI tract: from research to therapy. Expert Rev. Gastroenterol. Hepatol. 2(1), 125–133 (2008)

    Article  Google Scholar 

  38. Sato Y, Chen Z, Miyazaki K.. Strong suppression of tumor growth by insulin-like growth factor-binding protein-related protein 1/tumor-derived cell adhesion factor/mac25. Cancer Sci. 98(7), 1055–1063 (2007)

    Article  Google Scholar 

  39. Scanlan, M.J., Gordan, J.D., Williamson, B., Stockert, E., Bander, N.H., Jongeneel, V., Gure, A.O., Jger, D., Jger, E., Knuth, A., Chen, Y.T., Old, L.J.: Antigens recognized by autologous antibody in patients with renal-cell carcinoma. Int. J. Cancer 83(4), 456–464 (1999)

    Article  Google Scholar 

  40. Scherf, U., Ross, D.T., Waltham, M., Smith, L.H., Lee, J.K., Tanabe, L., Kohn, K.W., Reinhold, W.C., Myers, T.G., Andrews, D.T., Scudiero, D.A., Eisen, M.B., Sausville, E.A., Pommier, Y., Botstein, D., Brown, P.O., Weinstein, J.N.: A gene expression database for the molecular pharmacology of cancer. J. Nat. Genet. 66, 236–244 (2000)

    Article  Google Scholar 

  41. Slomnicki, L.P., Nawrot, B., Leniak, W.: S100A6 binds p53 and affects its activity. Int. J. Biochem. Cell. Biol. 41(4), 784–790 (2009)

    Article  Google Scholar 

  42. Sneath, P., Sokal, R.: Numerical Taxonomy: the Principles and Practice of Numerical Classification. Freeman, San Francisco (1973)

    MATH  Google Scholar 

  43. Staunton, J.E., Slonim, D.K., Coller, H.A., Tamayo, P., Angelo, M.J., Park, J., Scherf, U., Lee, J.K., Reinhold, W.O., Weinstein, J.N., Mesirov, J.P., Lander, E.S., Golub, T.R.: Chemosensitivity prediction by transcriptional profiling. Proc. Natl. Acad. Sci. U.S.A. 98, 10787–10792 (2001)

    Article  Google Scholar 

  44. Toler, C.R., Taylor, D.D., Gercel-Taylor, C.: Loss of communication in ovarian cancer. Am. J. Obstet. Gynecol. 194(5), 27–31 (2006)

    Article  Google Scholar 

  45. Wagstaff, K., Cardie, C., Rogers, S., Schroedl, S.: Constrained K-Means clustering with background knowledge. In: Brodley, C.E., Danyluk, A.P. (eds.) Proceedings of the Eighteenth International Conference on Machine Learning, 28 June–1 July 2001, Williamstown, Massachusetts, pp. 577–584 (2001)

  46. Yap, L.F., Jenei, V., Robinson, C.M., Moutasim, K., Benn, T.M., Threadgold, S.P., Lopes, V., Wei, W., Thomas, G.J., Paterson, I.C.: Upregulation of Eps8 in oral squamous cell carcinoma promotes cell migration and invasion through integrin-dependent Rac1 activation. Oncogene 28, 2524–2534 (2009). doi:10.1038/onc.2009.105

    Article  Google Scholar 

  47. Yap, L.F., Jenei, V., Robinson, C.M., Moutasim, K., Benn, T.M., Threadgold, S.P., Lopes, V., Wei, W., Thomas, G.J., Paterson, I.C.: Upregulation of Eps8 in oral squamous cell carcinoma promotes cell migration and invasion through integrin-dependent Rac1 activation. Oncogene 28(27), 2524–2534 (2009)

    Article  Google Scholar 

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Fersini, E., Messina, E., Archetti, F. et al. Combining Gene Expression Profiles and Drug Activity Patterns Analysis: A Relational Clustering Approach. J Math Model Algor 9, 275–289 (2010). https://doi.org/10.1007/s10852-010-9140-2

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  • DOI: https://doi.org/10.1007/s10852-010-9140-2

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