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Clustering mutational spectra via classification likelihood and markov chain monte carlo algorithms

  • Mario MedvedovicEmail author
  • Paul Succop
  • Rakesh Shukla
  • Kathleen Dixon
Article

Abstract

We have analyzed a set of 39 mutational spectra of the supF gene that were generated by different mutagenicagents and under different experimental conditions. The clusteranalyses was performed using a newly developed clustering procedure. The clustering criterion used in the procedure was developed by applying the classification likelihood approach to multinomial observations. We also developed a Gibbs sampling-based optimization procedure that outperformed previously developed methods in a comparative simulation study The results of the cluster analysis showed that our clustering procedure was able to recreate natural grouping of the mutational spectra with respect to the characteristics of mutagenic agents used to generate them and with respect to experimental conditions applied in the process of generating spectra. These results are an important confirmation of the relevance of mutational spectra in characterizing mutagenic mechanisms of different carcinogens.

Key Words

Classification expectation maximization algorithm Cluster analysis Gibbs sampling Multinomial distribution Stochastic expectation maximization algorithm 

References

  1. Adams, W. T., and Skopek R. T. (1987), “Statistical Test for the Comparison of Samples From Mutational Spectra,” Journal of Molecular Biology, 194, 391–396.CrossRefGoogle Scholar
  2. Aitkin, M., Anderson, D., and Hinde, J. (1981), “Statistical Modeling of Data on Teaching Styles,” Journal of the Royal Statistical Society, Series A, 144, 419–461.CrossRefGoogle Scholar
  3. Bigger, C. A. H., Flickinger, A. J., St. John, J., Harvey, R. G., and Dipple, A. (1991), “Preferential Mutagenesis at GC Base Pairs by the Anti 3,4-Dihydrodiol 1,2-Epoxide of 7-Methylbenz[a]anthracene,” Molecular Carcinogenesis, 4, 176–179.CrossRefGoogle Scholar
  4. Bigger, C. A. H., Flickinger, D. J., Strandberg, J., Pataki, J., Harvey, R. G., and Dipple, A. (1990), “Mutational Specificity of the Anti 1,2-Dihydrodiol3,4-Epoxide of 5-Methylchrysene,” Carcinogenesis, 11, 2263–2265.CrossRefGoogle Scholar
  5. Bigger, C. A. H., St. John, J., Yagi, H., Jerina, D. M., and Dipple, A. (1992), “Mutagenic Specificities of Four Stereoisomeric Benzo[c]phenanthrene Dihydrodiol Epoxides,” Proceedings of the National Academy of Science, USA, 89, 368–372.CrossRefGoogle Scholar
  6. Bigger, C. A. H., Strandberg, J., Yagi, H., Jerina, D. M., and Dipple, A. (1989), “Mutagenic Specificity of a Potent Carcinogen, Benzo[c]phenanthrene (4R,3S)-Dihydrodiol (2S,1R)-Epoxide, Which Reacts With Adenine and Guanine in DNA,” Proceedings of the National Academy of Science, USA, 86, 2291–2295.CrossRefGoogle Scholar
  7. Boldt, J., Chia-Miao Mah, M., Wang, Y.-C., Smith, B. A., Beland, F. A., Maher, V. M., and McCormick, J. J. (1991), “Kinds of Mutations Found When a Shuttle Vector Containing Adducts of 1,6-Dinitropyrene Replicates in Human Cells,” Carcinogenesis, 12, 119–126.CrossRefGoogle Scholar
  8. Bredberg, A., Kraemer, K. H., and Seidman, M. M. (1986), “Restricted Ultraviolet Mutational Spectrum in a Shuttle Vector Propagated in Xeroderma Pigmentosum Cells,” Proceedings of the National Academy of Science, USA, 83, 8273–8277.CrossRefGoogle Scholar
  9. Bryant, P. G. (1991), “Large-Sample Results for Optimization-Based Clustering Methods,” Journal of Classification, 8, 31–44.zbMATHCrossRefMathSciNetGoogle Scholar
  10. Carty, M. P., El-Saleh, S., Zernik-Kobak, M., and Dixon, K. (1995), “Analysis of Mutations Induced by Replication of UV-Damaged Plasmid DNA in HeLa Cell Extracts,” Environmental and Molecular Mutagenesis, 26, 139–146.CrossRefGoogle Scholar
  11. Celleux, G., and Diebolt, J. (1985), “The SEM Algorithm: A Probabilistic Teacher Algorithm Derived From the EM Algorithm for the Mixture Problem,” Computational Statistics Quarter, 2, 73–82.Google Scholar
  12. Celleux, G., and Govaert, G. (1991), “Clustering Criteria for Discrete Data and Latent Class Models,” Journal of Classification, 8, 157–176.CrossRefGoogle Scholar
  13. Celleux, G., and Govaert, G. (1992), “A Classification EM Algorithm for Clustering and Two Stochastic Versions,” Computational Statistics and Data Analysis, 14, 315–332.CrossRefMathSciNetGoogle Scholar
  14. Cohen, J. (1969), Statistical Power Analysis for the Behavioral Sciences, New York: Academic.Google Scholar
  15. Courtemanche, C., and Anderson, A. (1994), “Shuttle-Vector Mutagenesis of Aflatoxin B1 in Human Cells: Effects of Sequence Context on the supF Mutational Spectrum,” Mutation Research, 306, 143–151.Google Scholar
  16. Dempster, A. P., Laird, N. M., and Rubin, D. B. (1977), “Maximum Likelihood From Incomplete Data Via the EM Algorithm,” Journal of the Royal Statistical Society, Series B, 39, 1–38.zbMATHMathSciNetGoogle Scholar
  17. Endo, H., Schut, H. A. J., and Snydewine, E. G. (1994), “Mutagenic Specificity of 2-Amino-3-Methylimidazo[4,5-f]quinoline and 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine in the supF Shuttle Vector System,” Cancer Research, 54, 3745–3751.Google Scholar
  18. Everitt, B. S. (1993), Cluster Analysis, London: Edward Arnold.Google Scholar
  19. Feng, Z. D., and McCulloch, C. E. (1996), “Using Bootstrap Likelihood Ratios in Finite Mixture Models,” Journal of the Royal Statistical Society, Series B, 58, 609–617.zbMATHGoogle Scholar
  20. Gelfand, A. E., and Smith, A. F. M. (1990), “Sampling-Based Approaches to Calculating Marginal Densities,” Journal of the American Statistical Association, 85, 398–409.zbMATHCrossRefMathSciNetGoogle Scholar
  21. Gilks, W. R., Richardson, S., and Spiegelhalter, D. J. (1996), Markov Chain Monte Carlo in Practice, London: Chapman and Hall.zbMATHGoogle Scholar
  22. Hauser, J., Seidman, M. M., Sidur, K., and Dixon, K. (1986), “Sequence. Specificity of Point Mutations Induced During Passage of a UV-Irradiated Shuttle Vector Plasmid in Monkey Cells,” Molecular and Cellular Biology, 6, 277–285.Google Scholar
  23. Jennison, C. (1993), “Discussion on the Meeting on the Gibbs Sampler and Other Markov Chain Monte Carlo Methods,” Journal of the Royal Statistical Society, Series B, 55, 54–56.Google Scholar
  24. Keyse, S. M., Amaudruz, F., and Tyrrell, R. M. (1988), “Determination of the Spectrum of Mutations Induced by Defined-Wavelength Solar UVB (313-nm) Radiation in Mammalian Cells by Use of Shuttle Vector,” Molecular and Cellular Biology, 8, 5425–5431.Google Scholar
  25. Levy, D. D., Groopman, J. D., Lim, S. E., Seidman, M. M., and Kraemer, K. H. (1992), “Sequence Specificity of Aflatox in B 1-Induced Mutations in a Plasmid Replicated in Xeroderma Pigmentosum and DNA Repair Proficient Human Cells,” Cancer Research, 52, 5668–5673.Google Scholar
  26. Maccubbin, A. E., Mudipalli, A., Nadadur, A. A., Ersing, N., and Gurtoo, H L. (1997), “Mutations Induced in a Shuttle Vector Plasmid Exposed to Monofunctionally Activated Mitomycin C,” Environmental and Molecular Mutagenesis, 29, 143–151.CrossRefGoogle Scholar
  27. Mah, C. M. M., Maher, V. M., Thomas, H., Reid, T. M., King, C. M., and McCormick, J. J. (1989), “Mutation Induced by Aminofluorene-DNA Adducts During Replication in Human Cells,” Carcinogenesis, 10, 2321–2328.CrossRefGoogle Scholar
  28. McLachlan, J. G., and Basford, E. K. (1987), Mixture Models: Inference and Applications to Clustering, New York: Marcel Dekker.Google Scholar
  29. Page, J. E., Pataki, J., Harvey, R. G., and Dipple, A. (1996a), “Mutational Specificity of the Syn 1,2-Dihydrodiol 3,4-Epoxide of 5-Methylchrysene,” Cancer Letters, 110, 249–252.CrossRefGoogle Scholar
  30. Page, J. E., Ross, H. L., Bigger, C. A. H., and Dipple, A. (1996b), “Mutagenic. Specificities and Adduct Distributions for 7-Bromomehylbenz[a]anthracenes,” Carcinogenesis, 17, 283–288.CrossRefGoogle Scholar
  31. Page, J. E., Szeliga, J., Amin, S., Hecht, S. S., and Dipple, A. (1995), “Mutational Spectra for 5,6-Dimethylchrysene 1,2-Dihydrodiol 3,4-Epoxides in the supF Gene of pSP189,” Chemical Research in Toxicology, 8, 143–147.CrossRefGoogle Scholar
  32. Parris, N. C., Levy, D. D., Jessee, J., and Seidman, M. M. (1994), “Proximal and Distal Effects of Sequence Context on Ultraviolet Mutational Hotspots in a Shuttle Vector Replicated in Xeroderma Cells,” Journal of Molecular Biology, 236, 491–502.CrossRefGoogle Scholar
  33. Roilides, E., Gielen, J. E., Tuteja, N., Levine, A. S., and Dixon, K. (1988), “Mutational Specificity of Benzo[a]pyrene Diolepoxide in Monkey Cells,” Mutation Research, 198, 199–206.Google Scholar
  34. Seetharam, S., Protic-Sabljic, M., Seidman, M. M., and Kraemer, K. H. (1987), “Abnormal Ultraviolet Mutagenic Spectrum in Plasmid DNA Replicated in Cultured Fibroblasts From a Patient With the Skin Cancer-Prone Disease, Xeroderma Pigmentosum,” The Journal of Clinical Investigation, 80, 1613–1617.CrossRefGoogle Scholar
  35. Seidman, M. M., Dixon, K., Razzaque, A., Zagursky, J. R., and Berman, L. M. (1985), “A Shuttle Vector Plasmid for Studying Carcinogen-Induced Point Mutations in Mammalian Cells,” Gene, 38, 233–237.CrossRefGoogle Scholar
  36. Symons, M. J. (1981), “Clustering Criteria and Multivariate Normal Mixture,” Biometrics, 37, 35–43.zbMATHCrossRefMathSciNetGoogle Scholar
  37. Szeliga, J., Lee, H., Harvey, G. R., Page, J. E., Ross, H. L., Routledge, M. N., Hilton, B. D., and Dipple, A. (1994), “Reaction With DNA and Mutagenic Specificity of Syn-Benzo[g]chrysene 11,12-Dihydrodiol13,14-Epoxide,” Chemical Research in Toxicology, 7, 420–427.CrossRefGoogle Scholar
  38. Szeliga, J., Page, J. E., Hilton, B. D., Kiselyov, A. S., Harvey, R. G., Dunayevskiy, Y. M., Vouros, P., and Dipple, A. (1995), “Characterization of DNA Adducts Formed by Anti-Benzo[g]chrysene 11,12-Dihydrodiol 13,14-Epoxide,” Chemical Research in Toxicology, 8, 1014–1019.CrossRefGoogle Scholar
  39. Van Laarhoven, P. J. M., and Aarts, E. H. L. (1987), Simulated Annealing: Theory and Applications, Dordrecht, The Netherlands: Reidel.zbMATHGoogle Scholar
  40. Yagi, T., Sato, M., Nishigori, C., and Takebe, H. (1994), “Similarity in the Molecular Profile of Mutations Induced by UV Light in Shuttle Vector Plasmids Propagated in Mouse and Human Cells” Mutagenesis, 9, 73–77.CrossRefGoogle Scholar
  41. Yagi, T., Tatsumi-Miyajima, J., Sato, M., Kraemer, K. H., and Takebe, H. (1991), “Analysis of Point Mutations in an Ultraviolet-Irradiated Shuttle Vector Plasmid Propagated in Cells From Japanese X eroderma-Pigmentosum Patients in Complementation Groups A and F,” Cancer Research, 51, 3177–3182.Google Scholar
  42. Yang, J.-L., Maher, V. M., and McCormick, J. J. (1987), “Kinds of Mutations Formed When a Shuttle Vector Containing Adducts of (±)-7 β,8α-Dihdrxy-9α-Epoxy-7,8,9,10-Tetrahydro Benzo[a]pyrene Replicates in Human Cells,” Proceedings of the National Academy of Sciences, USA, 84, 3787–3791.CrossRefGoogle Scholar
  43. Yang, J.-L., Maher, V. M., and McCormick, J. J. (1988), “Kinds and Spectrum of Mutations Induced by 1-Nitrosopyrene Adducts During Plasmid Replication in Human Cells,” Molecular and Cellular Biology, 8, 3364–3372.Google Scholar

Copyright information

© International Biometric Society 2001

Authors and Affiliations

  • Mario Medvedovic
    • 1
    Email author
  • Paul Succop
    • 1
  • Rakesh Shukla
    • 1
  • Kathleen Dixon
  1. 1.Department of Environmental HealthUniversity of Cincinnati Medical CenterCincinnati

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