Detecting Strong Signals in Gene Perturbation Experiments: An Adaptive Approach With Power Guarantee and FDR Control

• 成果类型: Article
• 署名作者: Guan, Leying; Chen, Xi; Wong, Wing Hung
• 署名单位: Stanford University; Stanford University
• 刊物名称: JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
• ISSN/ISSBN: 0162-1459
• DOI: 10.1080/01621459.2019.1635484
• 发表日期: 2020
• 页码: 1747-1755
• 关键词: empirical bayes analysis; self-renewal; stem-cells; transcriptional network; expression; pluripotency

摘要

The perturbation of a transcription factor should affect the expression levels of its direct targets. However, not all genes showing changes in expression are direct targets. To increase the chance of detecting direct targets, we propose a modified two-group model where the null group corresponds to genes which are not direct targets, but can have small nonzero effects. We model the behavior of genes from the null set by a Gaussian distribution with unknown variance . To estimate , we focus on a simple estimation approach, the iterated empirical Bayes estimation. We conduct a detailed analysis of the properties of the iterated EB estimate and provide theoretical guarantee of its good performance under mild conditions. We provide simulations comparing the new modeling approach with existing methods, and the new approach shows more stable and better performance under different situations. We also apply it to a real dataset from gene knock-down experiments and obtained better results compared with the original two-group model testing for nonzero effects.