False discovery rates: a new deal
By Matthew Stephens. bioRxiv, 2016
1,085 citations recorded by the source corpus.
We introduce a new Empirical Bayes approach for large-scale hypothesis testing, including estimating False Discovery Rates (FDRs), and effect sizes. This approach has two key differences from existing approaches to FDR analysis. First, it assumes that the distribution of the actual (unobserved) effects is unimodal, with a mode at 0. This “unimodal assumption” (UA), although natural in many contexts, is not usually incorporated into standard FDR analysis, and we demonstrate how incorporating it brings many benefits. Specifically, the UA facilitates efficient and robust computation – estimating the unimodal distribution involves solving a simple convex optimization problem – and enables more accurate inferences provided that it holds. Second, the method takes as its input two numbers for each test (an effect size estimate, and corresponding standard error), rather than the one number usually used (p value, or z score). When available, using two numbers instead of one helps account for variation in measurement precision across tests. It also facilitates estimation of effects, and unlike standard FDR methods our approach provides interval estimates (credible regions) for each effect in addition to measures of significance. To provide a bridge between interval estimates and significance measures we introduce the term “local false sign rate” to refer to the probability of getting the sign of an effect wrong, and argue that it is a superior measure of significance than the local FDR because it is both more generally applicable, and can be more robustly estimated. Our methods are implemented in an R package ashr available from http://github.com/stephens999/ashr.
Subfields: Statistics and Probability
View Paper: https://www.semanticscholar.org/paper/4a27761b47c79dc1cece1bf24f0de2ce93cb3262
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In Statistics and Probability
- J. K. Pritchard
- Wolfgang Huber
- Nikolaos Ignatiadis
- Yang I Li
- Evan A. Boyle
- Yuxin Zou
- Matthew Stephens
- Eleazar Eskin
Citations in the corpus
- The impact of sex on gene expression across human tissues (2020, background): “Ana Viñuela13, Stephane E. Castel7,8, Pejman Mohammadi14, François Aguet15, Yuxin Zou16, Ekaterina A. Khramtsova1,17, Andrew D. Skol1,2,18,19, Diego Garrido-Martín4, Ferran Reverter20, Andrew Brown21, Patrick Evans22, Eric R. Gamazon22,23, Anthony Payne24, Rodrigo Bonazzola1, Alvaro N. Barbeira1, An”
- Covariate powered cross‐weighted multiple testing (2017, methodology): “, as seeing the results from many tests simultaneously enables us to infer properties, such as priors and other modelling parameters, that we could never learn from a single test (Efron et al., 2001; Stephens, 2016). Arguably, the perception of multiple testing as a burden has been exacerbated by sh”
- An expanded view of complex traits: from polygenic to omnigenic (2017, methodology): “(B) Estimated fraction of SNPs associated with non-zero effects on height (Stephens, 2017) as a function of linkage disequilibrium score (i.”