Permutation-based true discovery guarantee by sum tests
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基于置换与求和检验的真实发现比例保证AI 解读 ↓
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Abstract Sum-based global tests are highly popular in multiple hypothesis testing. In this paper, we propose a general closed testing procedure for sum tests, which provides lower confidence bounds for the proportion of true discoveries (TDPs), simultaneously over all subsets of hypotheses. These simultaneous inferences come for free, i.e., without any adjustment of the α-level, whenever a global test is used. Our method allows for an exploratory approach, as simultaneity ensures control of the TDP even when the subset of interest is selected post hoc. It adapts to the unknown joint distribution of the data through permutation testing. Any sum test may be employed, depending on the desired power properties. We present an iterative shortcut for the closed testing procedure, based on the branch and bound algorithm, which converges to the full closed testing results, often after few iterations; even if it is stopped early, it controls the TDP. We compare the properties of different choices for the sum test through simulations, then we illustrate the feasibility of the method for high-dimensional data on brain imaging and genomics data.
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Population-level heterogeneity is ubiquitous in biomedical data, where differences across demographic or clinical subgroups can substantially alter risk patterns. For example, in intensive care unit (ICU) studies, the mortality risk associated with specific admission diagnoses can vary across ethnic groups. Existing approaches for detecting risk heterogeneity are often sensitive to baseline model misspecification and regularization bias, both of which commonly arise in…
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高维线性模型中基于汇总统计量的遗传力估计的一致性
In Genome-Wide Association Studies (GWAS), heritability is defined as the fraction of variance of an outcome explained by a large number of genetic predictors in a high-dimensional polygenic linear model. This work studies the asymptotic properties of the most common estimator of heritability from summary statistics called linkage disequilibrium score (LDSC) regression, together with a simpler and closely related estimator called GWAS heritability (GWASH). These estimators…
The conditional average treatment effect (CATE) is frequently estimated in clinical studies to refute a homogeneous treatment effect hypothesis. Under this regime, all patients making up the population experience identical benefit from a given treatment relative to a comparator. Uncovering heterogeneous treatment effects through inference about the CATE, however, requires that covariates truly modifying the treatment effect be reliably collected at baseline. CATE-based…
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We study the fundamental limits of convex-regularized estimation in high-dimensional linear regression with right-rotationally invariant design matrices. We show that the asymptotic risks of convex-penalized least squares estimators are lower bounded by the risk of an approximate message passing algorithm known as Bayes VAMP, and we further characterize when the lower bound is attainable. As a technical ingredient in the proof of our lower bound theorem, we characterize the…