Title: Identifying informative biological markers in high-dimensional genomic data and clinical trials
Description: Technological and biological advances allow researchers and clinicians to measure an increasingly vast diversity of biological markers. This paper describes methods for identifying markers with the most potential to further our understanding of disease processes and improve patient care. We first consider the problem of selecting differentially expressed genes in comparative microarray experiments. Optimality theory is developed for multiple hypothesis testing in this setting and illustrated though simulations and applications to real data. The proposed methods are shown to outperform existing methods by exploiting strong patterns in the data that are generally ignored. We also separately consider the problem of using multiple biomarkers to identify patients experiencing differential treatment efficacy in randomized clinical trials. Multiple markers are related to patient-specific treatment effects in a regression framework. If the regression model is correct, it describes patient subgroups with the most extreme differences in treatment efficacy and provides optimal treatment assignment rules. However even if the regression model is mis-specified, it provides a well-behaved treatment efficacy score, whose clinical value can be assessed nonparametrically. The proposed methods are illustrated through application to a large randomized trial in cardiovascular medicine.