Cost-effective Screening for Differentially Expressed Genes in Microarray Experiments Based on Normal Mixtures
DOI:
https://doi.org/10.17713/ajs.v32i3.458Abstract
Microarray experiments allow the monitoring of expression levels for thousands of genes simultaneously. Based on data obtained from the co-hybridization of two mRNA samples, a frequent goal is to find out which genes are differentially expressed. For this purpose, we propose to estimate the distribution of popular test statistics by a mixture of normal distributions. These statistics are calculated for each gene separately. A Bayes classifier is then used to decide upon differential expression. The cut-off for the classifier is chosen according to the number of false positives and negatives when applied to realistic data generating models. In particular, we generate data from a mixture model and from an Empirical Bayes model. By comparing the numbers of false decisions for various test statistics in the context of the considered models, we investigate which of the statistics are particularly suitable with our approach.
References
D. Bozinov and J. Rahnenführer. Unsupervised technique for robust target separation and analysis of dna microarray spots through adaptive pixel clustering. Bioinformatics, 18
(5):747–756, 2002.
L. Devroye, L. Györfi, and G. Lugosi. A probabilistic theory of pattern recognition. Springer, Berlin, 1996.
S. Dudoit, Y.H. Yang, T.P. Speed, and M.J. Callow. Statistical methods for identifying differentially expressed genes in replicated cdna microarray experiments. Statistica
Sinica, 12(1):111–139, 2000.
B. Efron, R. Tibshirani, V. Goss, and G. Chu. Microarrays and their use in a comparative experiment. J. Amer. Statist. Assoc., 96:1151–1160, 2001.
I. Lönnstedt and T. Speed. Replicated microarray data. Statistica Sinica, 12:31–46, 2002.
G. McLachlan and D. Peel. Finite Mixture Models. Wiley, New York, 2000.
M.A. Newton, C.M. Kendziorski, C.S. Richmond, F.R. Blattner, and K.W. Tsui. On differential variability of expression ratios: Improving statistical inference about gene expression changes from microarray data. Journal of Computational Biology, 8:37–52, 2001.
W. Pan. A comparative review of statistical methods for discovering differentially expressed genes in replicated microarray experiments. Bioinformatics, 12:546–554, 2002.
V. Tusher, R. Tibshirani, and G. Chu. Significance analysis of microarrays applied to the ionizing radiation response. PNAS, 98:5116–5124, 2001.
Y.H. Yang, M. Buckley, S. Dudoit, and T. Speed. Comparison of methods for image analysis on cdna microarray data. Journal of Computational and Graphical Statistics, 11:108–136, 2002.
Y.H. Yang, S. Dudoit, P. Luu, and T. Speed. Normalization for cdna microarray data. In SPIE BiOS 2001. San Jose, California, 2001.
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