Estimation and Selection in High-Dimensional Genomic Studies

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This book provides an overview of the statistical methods used in genome-wide screening of relevant genomic features or genes. Gene screening can facilitate deeper understanding of disease biology at the molecular level, possibly leading to discovery of new molecular targets for developing new treatments and developing diagnostic tests to predict patients' prognosis or response to treatment. The most common approach to such gene screening studies is to apply multiple univariate analysis based on separate statistical tests for individual genes to test the null hypothesis of no association with clinical variables. This book first provides an overview of the state of the art of such multiple testing methodologies for gene screening, including frequentist multiple tests, empirical Bayes, and full-Bayes model-based methods for controlling the family-wise error rate or false discovery rate. Optimal discovery procedures and model-based variants are also discussed. Although great endeavor has been directed toward developing multiple testing methods, there are other, more relevant and effective analyses that should be given much attention in gene screening, including gene ranking, estimation of effect sizes, and classification accuracy based on selected genes. The core contents of this book provide a framework for integrated gene screening analysis based on hierarchical mixture modeling and empirical Bayes. Within this framework effective tools for multiple testing, ranking, estimation of effect size, and classification accuracy are derived. Methods for sample size determination for gene screening studies are also provided. With this content, the book is certain to expand the existing framework of statistical analysis based on multiple testing for gene screening to one based on estimation and selection.