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A Bayesian mixture model for differential gene expression

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  • Kim‐Anh Do
  • Peter Müller
  • Feng Tang

Abstract

Summary. We propose model‐based inference for differential gene expression, using a nonparametric Bayesian probability model for the distribution of gene intensities under various conditions. The probability model is a mixture of normal distributions. The resulting inference is similar to a popular empirical Bayes approach that is used for the same inference problem. The use of fully model‐based inference mitigates some of the necessary limitations of the empirical Bayes method. We argue that inference is no more difficult than posterior simulation in traditional nonparametric mixture‐of‐normal models. The approach proposed is motivated by a microarray experiment that was carried out to identify genes that are differentially expressed between normal tissue and colon cancer tissue samples. Additionally, we carried out a small simulation study to verify the methods proposed. In the motivating case‐studies we show how the nonparametric Bayes approach facilitates the evaluation of posterior expected false discovery rates. We also show how inference can proceed even in the absence of a null sample of known non‐differentially expressed scores. This highlights the difference from alternative empirical Bayes approaches that are based on plug‐in estimates.

Suggested Citation

  • Kim‐Anh Do & Peter Müller & Feng Tang, 2005. "A Bayesian mixture model for differential gene expression," Journal of the Royal Statistical Society Series C, Royal Statistical Society, vol. 54(3), pages 627-644, June.
  • Handle: RePEc:bla:jorssc:v:54:y:2005:i:3:p:627-644
    DOI: 10.1111/j.1467-9876.2005.05593.x
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    Cited by:

    1. E. M. Conlon & B. L. Postier & B. A. Methe & K. P. Nevin & D. R. Lovley, 2009. "Hierarchical Bayesian meta-analysis models for cross-platform microarray studies," Journal of Applied Statistics, Taylor & Francis Journals, vol. 36(10), pages 1067-1085.
    2. Rossell David & Guerra Rudy & Scott Clayton, 2008. "Semi-Parametric Differential Expression Analysis via Partial Mixture Estimation," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 7(1), pages 1-29, April.
    3. Jing Cao & Song Zhang, 2014. "A Bayesian extension of the hypergeometric test for functional enrichment analysis," Biometrics, The International Biometric Society, vol. 70(1), pages 84-94, March.
    4. Wang Chamont & Gevertz Jana L., 2016. "Finding causative genes from high-dimensional data: an appraisal of statistical and machine learning approaches," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 15(4), pages 321-347, August.
    5. Shotwell Matthew S & Slate Elizabeth H, 2010. "Bayesian Modeling of Footrace Finishing Times," Journal of Quantitative Analysis in Sports, De Gruyter, vol. 6(3), pages 1-21, July.
    6. Vinícius Diniz Mayrink & Flávio B. Gonçalves, 2020. "Identifying atypically expressed chromosome regions using RNA-Seq data," Statistical Methods & Applications, Springer;Società Italiana di Statistica, vol. 29(3), pages 619-649, September.
    7. Francesco Denti & Michele Guindani & Fabrizio Leisen & Antonio Lijoi & William Duncan Wadsworth & Marina Vannucci, 2021. "Two‐group Poisson‐Dirichlet mixtures for multiple testing," Biometrics, The International Biometric Society, vol. 77(2), pages 622-633, June.
    8. Mark A. van de Wiel & Kyung In Kim, 2007. "Estimating the False Discovery Rate Using Nonparametric Deconvolution," Biometrics, The International Biometric Society, vol. 63(3), pages 806-815, September.
    9. Richard F. MacLehose & David B. Dunson, 2010. "Bayesian Semiparametric Multiple Shrinkage," Biometrics, The International Biometric Society, vol. 66(2), pages 455-462, June.
    10. Wang, Xia & Shojaie, Ali & Zou, Jian, 2019. "Bayesian hidden Markov models for dependent large-scale multiple testing," Computational Statistics & Data Analysis, Elsevier, vol. 136(C), pages 123-136.
    11. Vinícius Diniz Mayrink & Flávio Bambirra Gonçalves, 2017. "A Bayesian hidden Markov mixture model to detect overexpressed chromosome regions," Journal of the Royal Statistical Society Series C, Royal Statistical Society, vol. 66(2), pages 387-412, February.
    12. Dickhaus Thorsten, 2015. "Simultaneous Bayesian analysis of contingency tables in genetic association studies," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 14(4), pages 347-360, August.
    13. Muir, W.M. & Rosa, G.J.M. & Pittendrigh, B.R. & Xu, Z. & Rider, S.D. & Fountain, M. & Ogas, J., 2009. "A mixture model approach for the analysis of small exploratory microarray experiments," Computational Statistics & Data Analysis, Elsevier, vol. 53(5), pages 1566-1576, March.
    14. Michele Guindani & Wesley O. Johnson, 2018. "More nonparametric Bayesian inference in applications," Statistical Methods & Applications, Springer;Società Italiana di Statistica, vol. 27(2), pages 239-251, June.
    15. Hong, Zhaoping & Lian, Heng, 2012. "BOPA: A Bayesian hierarchical model for outlier expression detection," Computational Statistics & Data Analysis, Elsevier, vol. 56(12), pages 4146-4156.
    16. Barrientos, Andrés F. & Canale, Antonio, 2021. "A Bayesian goodness-of-fit test for regression," Computational Statistics & Data Analysis, Elsevier, vol. 155(C).
    17. Bing Han & Siddhartha R. Dalal & Daniel F. McCaffrey, 2012. "Simultaneous One-Sided Tests With Application to Education Evaluation Systems," Journal of Educational and Behavioral Statistics, , vol. 37(1), pages 114-136, February.
    18. Scott, James G., 2012. "Benchmarking historical corporate performance," Computational Statistics & Data Analysis, Elsevier, vol. 56(6), pages 1795-1807.
    19. Elisa C. J. Maria & Isabel Salazar & Luis Sanz & Miguel A. Gómez-Villegas, 2020. "Using Copula to Model Dependence When Testing Multiple Hypotheses in DNA Microarray Experiments: A Bayesian Approximation," Mathematics, MDPI, vol. 8(9), pages 1-22, September.
    20. Han, Bing & Dalal, Siddhartha R., 2012. "A Bernstein-type estimator for decreasing density with application to p-value adjustments," Computational Statistics & Data Analysis, Elsevier, vol. 56(2), pages 427-437.
    21. Bickel David R., 2008. "Correcting the Estimated Level of Differential Expression for Gene Selection Bias: Application to a Microarray Study," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 7(1), pages 1-27, March.
    22. Canale, Antonio & Lijoi, Antonio & Nipoti, Bernardo & Prünster, Igor, 2023. "Inner spike and slab Bayesian nonparametric models," Econometrics and Statistics, Elsevier, vol. 27(C), pages 120-135.
    23. David I. Ohlssen & Linda D. Sharples & David J. Spiegelhalter, 2007. "A hierarchical modelling framework for identifying unusual performance in health care providers," Journal of the Royal Statistical Society Series A, Royal Statistical Society, vol. 170(4), pages 865-890, October.
    24. Salas-Gonzalez, Diego & Kuruoglu, Ercan E. & Ruiz, Diego P., 2009. "A heavy-tailed empirical Bayes method for replicated microarray data," Computational Statistics & Data Analysis, Elsevier, vol. 53(5), pages 1535-1546, March.
    25. Cipolli III, William & Hanson, Timothy & McLain, Alexander C., 2016. "Bayesian nonparametric multiple testing," Computational Statistics & Data Analysis, Elsevier, vol. 101(C), pages 64-79.

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