Computational and Mathematical Methods in Medicine
Volume 2013 (2013), Article ID 568480, 9 pages
http://dx.doi.org/10.1155/2013/568480
Research Article

An Empirical Bayes Optimal Discovery Procedure Based on Semiparametric Hierarchical Mixture Models

Department of Data Science, The Institute of Statistical Mathematics, 10-3 Midori-cho, Tachikawa, Tokyo 190-8562, Japan

Received 20 December 2012; Revised 23 February 2013; Accepted 4 March 2013

Academic Editor: Su-Yun Huang

Copyright © 2013 Hisashi Noma and Shigeyuki Matsui. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Multiple testing has been widely adopted for genome-wide studies such as microarray experiments. For effective gene selection in these genome-wide studies, the optimal discovery procedure (ODP), which maximizes the number of expected true positives for each fixed number of expected false positives, was developed as a multiple testing extension of the most powerful test for a single hypothesis by Storey (Journal of the Royal Statistical Society, Series B, vol. 69, no. 3, pp. 347–368, 2007). In this paper, we develop an empirical Bayes method for implementing the ODP based on a semiparametric hierarchical mixture model using the “smoothing-by-roughening" approach. Under the semiparametric hierarchical mixture model, (i) the prior distribution can be modeled flexibly, (ii) the ODP test statistic and the posterior distribution are analytically tractable, and (iii) computations are easy to implement. In addition, we provide a significance rule based on the false discovery rate (FDR) in the empirical Bayes framework. Applications to two clinical studies are presented.