Biostatistics Advance Access originally published online on January 22, 2007
Biostatistics 2007 8(4):744-755; doi:10.1093/biostatistics/kxm002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A moment-based method for estimating the proportion of true null hypotheses and its application to microarray gene expression data
Department of Statistics and Biostatistics Center, The George Washington University, Washington, DC 20052, USA
ylai{at}gwu.edu
Due to advances in experimental technologies, it is feasible to collect measurements for a large number of variables. When these variables are simultaneously screened by a statistical test, it is necessary to consider the adjustment for multiple hypothesis testing. The false discovery rate has been proposed and widely used to address this issue. A related problem is the estimation of the proportion of true null hypotheses. The long-standing difficulty to this problem is the identifiability of the nonparametric model. In this study, we propose a moment-based method coupled with sample splitting for estimating this proportion. If the p values from the alternative hypothesis are homogeneously distributed, then the proposed method will solve the identifiability and give its optimal performances. When the p values from the alternative hypothesis are heterogeneously distributed, we propose to approximate this mixture distribution so that the identifiability can be achieved. Theoretical aspects of the approximation error are discussed. The proposed estimation method is completely nonparametric and simple with an explicit formula. Simulation studies show the favorable performances of the proposed method when it is compared to the other existing methods. Two microarray gene expression data sets are considered for applications.
Keywords: Microarray; Moment estimator; Proportion of true null hypothesis
Received August 4, 2006; revised January 5, 2007; accepted for publication January 17, 2007.