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].
journal_name
Stat Appl Genet Mol Biolauthors
Rossell D,Guerra R,Scott Cdoi
10.2202/1544-6115.1333subject
Has Abstractpub_date
2008-01-01 00:00:00pages
Article15issue
1eissn
2194-6302issn
1544-6115journal_volume
7pub_type
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