Presented by: George C. Tseng, Professor and Vice Chair for Research, Department of Biostatistics, University of Pittsburgh

About the presentation: Combining p-values to integrate multiple effects is of long-standing interest in social science and biomedical research. In this paper, we focus on revisiting a classical scenario closely related to meta-analysis, which combines a relatively small (finite and fixed) number of p-values while the sample size for generating each p-value is large (asymptotically goes to infinity). We evaluate a list of traditional and recently developed modified Fisher’s methods to investigate their asymptotic efficiency and finite-sample numerical performance. The result concludes Fisher and adaptively weighted Fisher method to have top performance and complementary advantages across different proportions of true signals. Finally, we propose an ensemble method, namely Fisher ensemble, to combine the two top-performing Fisher-related methods using a robust truncated Cauchy ensemble approach. We show that Fisher ensemble achieves asymptotic Bahadur optimality and integrates the strengths of Fisher and adaptively weighted Fisher methods in simulations. We subsequently extend Fisher ensemble to a variant with emphasized power for concordant effect size directions. Three transcriptomic meta-analysis applications confirm theoretical and simulation conclusions, generate intriguing biomarker and pathway findings, and demonstrate strengths and strategy of using proposed Fisher ensemble methods.

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