Accurate Ranking of Differentially Expressed Genes by a Distribution-Free Shrinkage Approach

High-dimensional case-control analysis is encountered in many different settings in genomics. In order to rank genes accordingly, many different scores have been proposed, ranging from ad hoc modifications of the ordinary t statistic to complicated hierarchical Bayesian models.Here, we introduce the shrinkage t statistic that is based on a novel and model-free shrinkage estimate of the variance vector across genes. This is derived in a quasi-empirical Bayes setting. The new rank score is fully automatic and requires no specification of parameters or distributions. It is computationally inexpensive and can be written analytically in closed form.Using a series of synthetic and three real expression data we studied the quality of gene rankings produced by the shrinkage t statistic. The new score consistently leads to highly accurate rankings for the complete range of investigated data sets and all considered scenarios for across-gene variance structures.