DETECTING MULTIPLE REPLICATING SIGNALS USING ADAPTIVE FILTERING PROCEDURES

• Published in: The Annals of statistics Vol. 50; no. 4; p. 1890
• Main Authors: Wang, Jingshu, Gui, Lin, Su, Weijie J, Sabatti, Chiara, Owen, Art B
• Format: Journal Article
• Language: English
• Published: United States 01.08.2022
• Subjects: meta-analysis; composite null; high-throughput experiments; Simultaneous signals; multiple hypotheses testing
• ISSN: 0090-5364
• DOI: 10.1214/21-AOS2139

Replicability is a fundamental quality of scientific discoveries: we are interested in those signals that are detectable in different laboratories, different populations, across time etc. Unlike meta-analysis which accounts for experimental variability but does not guarantee replicability, testing a partial conjunction (PC) null aims specifically to identify the signals that are discovered in multiple studies. In many contemporary applications, for example, comparing multiple high-throughput genetic experiments, a large number of PC nulls need to be tested simultaneously, calling for a multiple comparisons correction. However, standard multiple testing adjustments on the PC -values can be severely conservative, especially when is large and the signals are sparse. We introduce AdaFilter, a new multiple testing procedure that increases power by adaptively filtering out unlikely candidates of PC nulls. We prove that AdaFilter can control FWER and FDR as long as data across studies are independent, and has much higher power than other existing methods. We illustrate the application of AdaFilter with three examples: microarray studies of Duchenne muscular dystrophy, single-cell RNA sequencing of T cells in lung cancer tumors and GWAS for metabolomics.