Covariate Adaptive False Discovery Rate Control With Applications to Omics-Wide Multiple Testing
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Abstract: Conventional multiple testing procedures often assume hypotheses for different features are exchangeable. However, in many scientific applications, additional covariate information regarding the patterns of signals and nulls are available. In this paper, we introduce an FDR control procedure in large-scale inference problem that can incorporate covariate information. We develop a fast algorithm to implement the proposed procedure and prove its asymptotic validity even when the underlying model is misspecified and the p-values are weakly dependent (e.g., strong mixing). Extensive simulations are conducted to study the finite sample performance of the proposed method and we demonstrate that the new approach improves over the state-of-the-art approaches by being flexible, robust, powerful and computationally efficient. We finally apply the method to several omics datasets arising from genomics studies with the aim to identify omics features associated with some clinical and biological phenotypes. We show that the method is overall the most powerful among competing methods, especially when the signal is sparse. The proposed Covariate Adaptive Multiple Testing procedure is implemented in the R package CAMT.
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Cites work
- A Direct Approach to False Discovery Rates
- A Uniform Law of Large Numbers for Dependent and Heterogeneous Data Processes
- AdaPT: an interactive procedure for multiple testing with side information
- Controlling the false discovery rate via knockoffs
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- False Discovery Control in Large-Scale Spatial Multiple Testing
- False discovery control with p-value weighting
- False discovery rate control with groups
- Genomic Control for Association Studies
- scientific article; zbMATH DE number 720689 (Why is no real title available?)
- Maximum Likelihood Estimation of Misspecified Models
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- Weighted mining of massive collections of P-values by convex optimization
Cited in
(18)- Confounder adjustment in multiple hypothesis testing
- Semiparametric covariate-modulated local false discovery rate for genome-wide association studies
- Optimal false discovery rate control for large scale multiple testing with auxiliary information
- Unsupervised empirical Bayesian multiple testing with external covariates
- Covariate-adjusted multiple testing in genome-wide association studies via factorial hidden Markov models
- False discovery rate control for high dimensional networks of quantile associations conditioning on covariates
- AdaPT: an interactive procedure for multiple testing with side information
- Covariate-assisted ranking and screening for large-scale two-sample inference
- Multiple Testing and Data Adaptive Regression: An Application to HIV-1 Sequence Data.
- FDR control for linear log-contrast models with high-dimensional compositional covariates
- False discovery rate control for lesion-symptom mapping with heterogeneous data via weighted p-values
- Joint mirror procedure: controlling false discovery rate for identifying simultaneous signals
- Large-scale multiple testing of composite null hypotheses under heteroskedasticity
- A note on e-values and multiple testing
- NAPA: neighborhood-assisted and posterior-adjusted two-sample inference
- STRAW: structure-adaptive weighting procedure for large-scale spatial multiple testing
- Powerful spatial multiple testing via borrowing neighboring information
- Feature selection in omics prediction problems using cat scores and false nondiscovery rate control
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