Gene identification using true discovery rate degree of association sets and estimates corrected for regression to...

Analyses intended to identify genes with expression that is associated with some clinical outcome or state are often based on ranked p-values from tests of point null hypotheses of no association. Van de Wiel and Kim take the innovative approach of testing the interval null hypotheses that the degree of association for a gene is less than some value of interest against the alternative that it is greater. Combining this idea with the false discovery rate controlling methods of Storey, Taylor and Siegmund gives a computationally simple way to identify true discovery rate degree of association (TDRDA) sets of genes among which a specified proportion are expected to have an absolute association of a specified degree or more. This leads to a gene ranking method that uses the maximum lower bound degree of association for which each gene belongs to a TDRDA set. Estimates of each gene's actual degree of association with approximate correction for 'selection bias' due to regression to the mean (RM) can be derived using simple bivariate normal theory and Efron and Tibshirani's empirical Bayes approach. For a given data set, all possible TDRDA sets can be displayed along with the gene ranking and the RM-corrected estimates of degree of association in a concise graphical summary.