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A flexible approximate likelihood ratio test for detecting differential expression in microarray data

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  • Hossain, Ahmed
  • Beyene, Joseph
  • Willan, Andrew R.
  • Hu, Pingzhao

Abstract

Identifying differentially expressed genes in microarray data has been studied extensively and several methods have been proposed. Most popular methods in the study of gene expression microarray data analysis rely on normal distribution assumption and are based on a Wald statistic. These methods may be inefficient when expression levels follow a skewed distribution. To deal with possible violations of the normality assumption, we propose a method based on Generalized Logistic Distribution of Type II (GLDII). The motivation behind this distributional assumption is to allow longer tails than normal distribution. This is important in analyzing gene expression data since extreme values are common in such experiments. The shape parameter for GLDII allows flexibility in modeling a wide range of distributions. To simplify the computational complexity involved in carrying out Likelihood Ratio (LR) tests for several thousands of genes, an Approximate LR Test (ALRT) is proposed. We also generalize the two-class ALRT method to multi-class microarray data. The performance of the ALRT method under the GLDII assumption is compared to methods based on Wald-type statistics using simulation. The results from the simulations show that our method performs quite well compared to the significance analysis of microarrays (SAM) approach using standardized Wilcoxon rank statistics and the empirical Bayes (E-B) t-statistics. Our method is also less sensitive to extreme values. We illustrate our method using two publicly available gene expression data sets.

Suggested Citation

  • Hossain, Ahmed & Beyene, Joseph & Willan, Andrew R. & Hu, Pingzhao, 2009. "A flexible approximate likelihood ratio test for detecting differential expression in microarray data," Computational Statistics & Data Analysis, Elsevier, vol. 53(10), pages 3685-3695, August.
  • Handle: RePEc:eee:csdana:v:53:y:2009:i:10:p:3685-3695
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    References listed on IDEAS

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    1. Dudoit Sandrine & van der Laan Mark J. & Pollard Katherine S., 2004. "Multiple Testing. Part I. Single-Step Procedures for Control of General Type I Error Rates," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 3(1), pages 1-71, June.
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    3. Sandrine Dudoit & Mark van der Laan & Katherine Pollard, 2004. "Multiple Testing. Part I. Single-Step Procedures for Control of General Type I Error Rates," U.C. Berkeley Division of Biostatistics Working Paper Series 1137, Berkeley Electronic Press.
    4. Geman Donald & d'Avignon Christian & Naiman Daniel Q. & Winslow Raimond L., 2004. "Classifying Gene Expression Profiles from Pairwise mRNA Comparisons," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 3(1), pages 1-22, August.
    5. Smyth Gordon K, 2004. "Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 3(1), pages 1-28, February.
    6. Dudoit S. & Fridlyand J. & Speed T. P, 2002. "Comparison of Discrimination Methods for the Classification of Tumors Using Gene Expression Data," Journal of the American Statistical Association, American Statistical Association, vol. 97, pages 77-87, March.
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    Cited by:

    1. Ahmed Hossain & Joseph Beyene, 2015. "Application of skew-normal distribution for detecting differential expression to microRNA data," Journal of Applied Statistics, Taylor & Francis Journals, vol. 42(3), pages 477-491, March.

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