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Semi-parametric differential expression analysis via partial mixture estimation
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Rossell, David, Guerra, Rudy and Scott, Clayton (2008) Semi-parametric differential expression analysis via partial mixture estimation. Statistical Applications in Genetics and Molecular Biology, Volume 7 (Number 1). doi:10.2202/1544-6115.1333 ISSN 1544-6115.
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Official URL: http://dx.doi.org/10.2202/1544-6115.1333
Abstract
We develop an approach for microarray differential expression analysis, i.e. identifying genes whose expression levels differ between two or more groups. Current approaches to inference rely either on full parametric assumptions or on permutation-based techniques for sampling under the null distribution. In some situations, however, a full parametric model cannot be justified, or the sample size per group is too small for permutation methods to be valid. We propose a semi-parametric framework based on partial mixture estimation which only requires a parametric assumption for the null (equally expressed) distribution and can handle small sample sizes where permutation methods break down. We develop two novel improvements of Scott's minimum integrated square error criterion for partial mixture estimation [Scott, 2004a,b]. As a side benefit, we obtain interpretable and closed-form estimates for the proportion of EE genes. Pseudo-Bayesian and frequentist procedures for controlling the false discovery rate are given. Results from simulations and real datasets indicate that our approach can provide substantial advantages for small sample sizes over the SAM method of Tusher et al. [2001], the empirical Bayes procedure of Efron and Tibshirani [2002], the mixture of normals of Pan et al. [2003] and a t-test with p-value adjustment [Dudoit et al., 2003] to control the FDR [Benjamini and Hochberg, 1995].
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Statistics | ||||
Journal or Publication Title: | Statistical Applications in Genetics and Molecular Biology | ||||
Publisher: | Walter de Gruyter GmbH & Co. KG | ||||
ISSN: | 1544-6115 | ||||
Official Date: | 28 April 2008 | ||||
Dates: |
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Volume: | Volume 7 | ||||
Number: | Number 1 | ||||
DOI: | 10.2202/1544-6115.1333 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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