Scientific discovery relies on large-scale hypothesis testing. However, the capacity to identify true discoveries while controlling false discovery faces major challenges: obtaining relevant reference data (the null distribution) is resource-intensive, leaving finite-data uncertainty, and the procedure should account for the inherent structure in the hypothesis space, when such structure exists. Here, we present a framework for controlling the false discovery rate both when each hypothesis is evidenced only by a finite count of null draws, leaving its p-value uncertain, and when the hypothesis space carries arbitrary structure, requiring only that the structure be represented through a suitable reproducing kernel. We present two decision rules that are both robust to structural mis-specification, yet offer a distinct trade-off between exact FDR control and statistical power. The first rule guarantees exact FDR control; the second maximizes power by adapting mirror-statistic control into count space, utilizing an analytical framework to assess FDR control when exact mirror symmetry is relaxed. Furthermore, the tractability gained by the RKHS framework allows us to directly investigate finite-data uncertainties, which we leverage to suggest a policy for the efficient allocation of null distribution samples.

This paper addresses structured out-of-distribution (OOD) testing in high-stakes machine learning applications. Traditional conformal methods rely on joint exchangeability, making it difficult to incorporate auxiliary information such as spatiotemporal or grouping structures. To overcome this limitation, we propose the structure-adaptive conformal q-value (SCQ), a significance index that integrates individual test evidence with structural patterns. We also develop pseudo-score-guided transductive automated model selection (P-TAMS), which adapts conformalized model selection to structured OOD testing across a toolbox of candidate models. Together, SCQ and P-TAMS form a unified framework under pairwise exchangeability, providing finite-sample error-rate control, improved power, and enhanced interpretability. Experiments on simulated and real data demonstrate that the proposed approach controls the false discovery rate and performs well across diverse settings.

The Benjamini-Hochberg (BH) procedure is widely used to control the false detection rate (FDR) in multiple testing.

Instead, we apply powerful machine learning models for one-class (Moya et al., 1993) or

Controlling the false discovery rate (FDR) in high-dimensional variable selection requires balancing rigorous error control with statistical power. Existing methods with provable guarantees are often overly conservative, creating a persistent gap between the realized false discovery proportion (FDP) and the target FDR level. We introduce a learning-augmented enhancement of the T-Rex Selector framework that narrows this gap. Our approach replaces the analytical FDP estimator with a neural network trained solely on diverse synthetic datasets, enabling a substantially tighter and more accurate approximation of the FDP. This refinement allows the procedure to operate much closer to the desired FDR level, thereby increasing discovery power while maintaining effective approximate control. Through extensive simulations and a challenging synthetic genome-wide association study (GWAS), we demonstrate that our method achieves superior detection of true variables compared to existing approaches.

Identifying truly predictive covariates while strictly controlling false discoveries remains a fundamental challenge in nonlinear, highly correlated, and low signal-to-noise regimes, where deep learning based feature selection methods are most attractive. We propose Group Regularization Importance Persistence in 2 Dimensions (GRIP2), a deep knockoff feature importance statistic that integrates first-layer feature activity over a two-dimensional regularization surface controlling both sparsity strength and sparsification geometry. To approximate this surface integral in a single training run, we introduce efficient block-stochastic sampling, which aggregates feature activity magnitudes across diverse regularization regimes along the optimization trajectory. The resulting statistics are antisymmetric by construction, ensuring finite-sample FDR control. In extensive experiments on synthetic and semi-real data, GRIP2 demonstrates improved robustness to feature correlation and noise level: in high correlation and low signal-to-noise ratio regimes where standard deep learning based feature selectors may struggle, our method retains high power and stability. Finally, on real-world HIV drug resistance data, GRIP2 recovers known resistance-associated mutations with power better than established linear baselines, confirming its reliability in practice.