FDR Control

Most anomaly detection systems output scores rather than calibrated decisions, leaving practitioners to choose thresholds heuristically and without clear statistical interpretation. Conformal anomaly detection addresses this limitation by converting anomaly scores into calibrated p-values that are valid under the statistical assumption of data exchangeability, with a growing literature extending this idea beyond that setting. We present 'nonconform', a Python package for applying conformal anomaly detection within existing machine-learning workflows, and use it as the basis for an implementation-grounded introduction to the field. The package integrates with 'scikit-learn', 'pyod', and custom anomaly detectors, and provides a unified interface for calibration, p-value generation, and false discovery rate control. It supports several conformalization strategies, ranging from simple split-conformal calibration to more data-efficient and shift-aware extensions. Through a progression from foundational concepts to advanced conformalization strategies, complemented by code examples, the paper connects the statistical ideas behind conformal anomaly detection to their practical use in 'nonconform'. Empirical results demonstrate that the implemented methods enable statistically principled anomaly detection. Together, the package and exposition aim to make core conformal anomaly detection workflows more accessible and reproducible in experimental and production-oriented settings.

Online Multiple Testing (OMT), a fundamental pillar of sequential statistical inference, traditionally evaluates the False Discovery Rate (FDR) and statistical power in isolation, obscuring the highly asymmetric costs of false positives and false negatives in modern automated pipelines. To unify this evaluation, we introduce $\textit{Weighted Regret}$. Under this metric, we prove the $\textit{Duality of Regret Conservation}$: purely deterministic procedures ensuring strict FDR control inevitably incur an $Ω(T)$ linear regret penalty, as threshold depletion during signal-sparse cold starts forces massive false negatives. Tailored for exogenous testing streams, we propose Decoupled-OMT (DOMT) as a baseline-agnostic meta-wrapper. By incorporating a history-decoupled, strictly non-negative random perturbation, DOMT rescues purely deterministic baselines from severe threshold depletion. Crucially, it preserves exact asymptotic safety in stationary environments and rigorously bounds finite-sample error inflation during cold-starts. Guaranteeing zero additional false negatives, it yields an order-optimal $Ω(\sqrt{T})$ regret reduction in bursty environments, with a derived ``Cold-Start Tax'' characterizing the exact phase transition of algorithmic superiority. Experiments validate that DOMT consistently curtails empirical weighted regret, achieving an order-optimal sublinear mitigation of threshold depletion to navigate the non-stationary Pareto frontier.

This work studies decentralized novelty detection with global false discovery rate (FDR) control across heterogeneous composite null distributions, without sharing the raw data due to privacy and bandwidth considerations. We propose a framework based on the exchange of quantized surrogate models, allowing independent agents to share low-precision representations of locally learned non-conformity score functions. We prove that evaluating data against these quantized composite scores preserves conditional exchangeability, providing rigorous finite-sample guarantees for global FDR control. Empirical studies on synthetic datasets confirm our theoretical results, demonstrating that the proposed approach maintains competitive statistical power while drastically reducing the communication cost.

Conformal selection (CS) uses calibration data to identify test inputs whose unobserved outcomes are likely to satisfy a pre-specified minimal quality requirement, while controlling the false discovery rate (FDR). Existing methods fix the target FDR level before observing data, which prevents the user from adapting the balance between number of selected test inputs and FDR to downstream needs and constraints based on the available data. For example, in genomics or neuroimaging, researchers often inspect the distribution of test statistics, and decide how aggressively to pursue candidates based on observed evidence strength and available follow-up resources. To address this limitation, we introduce post-hoc CS (PH-CS), which generates a path of candidate selection sets, each paired with a data-driven false discovery proportion (FDP) estimate. PH-CS lets the user select any operating point on this path by maximizing a user-specified utility, arbitrarily balancing selection size and FDR. Building on conformal e-variables and the e-Benjamini-Hochberg (e-BH) procedure, PH-CS is proved to provide a finite-sample post-hoc reliability guarantee whereby the ratio between estimated FDP level and true FDP is, on average, upper bounded by 1, so that the average estimated FDP is, to first order, a valid upper bound on the true FDR. PH-CS is extended to control quality defined in terms of a general risk. Experiments on synthetic and real-world datasets demonstrate that, unlike CS, PH-CS can consistently satisfy user-imposed utility constraints while producing reliable FDP estimates and maintaining competitive FDR control.

Scientific discovery increasingly relies on AI systems to select candidates for expensive experimental validation, yet no principled, budget-aware evaluation framework exists for comparing selection strategies -- a gap intensified by large language models (LLMs), which generate plausible scientific proposals without reliable downstream evaluation. We introduce the Budget-Sensitive Discovery Score (BSDS), a formally verified metric -- 20 theorems machine-checked by the Lean 4 proof assistant -- that jointly penalizes false discoveries (lambda-weighted FDR) and excessive abstention (gamma-weighted coverage gap) at each budget level. Its budget-averaged form, the Discovery Quality Score (DQS), provides a single summary statistic that no proposer can inflate by performing well at a cherry-picked budget. As a case study, we apply BSDS/DQS to: do LLMs add marginal value to an existing ML pipeline for drug discovery candidate selection? We evaluate 39 proposers -- 11 mechanistic variants, 14 zero-shot LLM configurations, and 14 few-shot LLM configurations -- using SMILES representations on MoleculeNet HIV (41,127 compounds, 3.5% active, 1,000 bootstrap replicates) under both random and scaffold splits. Three findings emerge. First, the simple RF-based Greedy-ML proposer achieves the best DQS (-0.046), outperforming all MLP variants and LLM configurations. Second, no LLM surpasses the Greedy-ML baseline under zero-shot or few-shot evaluation on HIV or Tox21, establishing that LLMs provide no marginal value over an existing trained classifier. Third, the proposer hierarchy generalizes across five MoleculeNet benchmarks spanning 0.18%-46.2% prevalence, a non-drug AV safety domain, and a 9x7 grid of penalty parameters (tau >= 0.636, mean tau = 0.863). The framework applies to any setting where candidates are selected under budget constraints and asymmetric error costs.

High-dimensional feature selection is routinely required to balance statistical power with strict control of multiple-error metrics such as the k-Family-Wise Error Rate (k-FWER) and the False Discovery Proportion (FDP), yet some existing frameworks are confined to the narrower goal of controlling the expected False Discovery Rate (FDR) and can not exploit the group-structure of the covariates, such as Sorted L-One Penalized Estimation (SLOPE). We introduce the Group Stepdown SLOPE, a unified optimization procedure which is capable of embedding the Lehmann-Romano stepdown rules into SLOPE to achieve finite-sample guarantees under k-FWER and FDP thresholds. Specifically, we derive closed-form regularization sequences under orthogonal designs that provably bound k-FWER and FDP at user-specified levels, and extend these results to grouped settings via gk-SLOPE and gF-SLOPE, which control the analogous group-level errors gk-FWER and gFDP. For non-orthogonal general designs, we provide a calibrated data-driven sequence inspired by Gaussian approximation and Monte-Carlo correction, preserving convexity and scalability. Extensive simulations are conducted across sparse, correlated, and group-structured regimes. Empirical results corroborate our theoretical findings that the proposed methods achieve nominal error control, while yielding markedly higher power than competing stepdown procedures, thereby confirming the practical value of the theoretical advances.

Conditional independence tests (CIT) are widely used for causal discovery and feature selection. Even with false discovery rate (FDR) control procedures, they often fail to provide frequentist guarantees in practice. We highlight two common failure modes: (i) in small samples, asymptotic guarantees for many CITs can be inaccurate and even correctly specified models fail to estimate the noise levels and control the error, and (ii) when sample sizes are large but models are misspecified, unaccounted dependencies skew the test's behavior and fail to return uniform p-values under the null. We propose Empirically Calibrated Conditional Independence Tests (ECCIT), a method that measures and corrects for miscalibration. For a chosen base CIT (e.g., GCM, HRT), ECCIT optimizes an adversary that selects features and response functions to maximize a miscalibration metric. ECCIT then fits a monotone calibration map that adjusts the base-test p-values in proportion to the observed miscalibration. Across empirical benchmarks on synthetic and real data, ECCIT achieves valid FDR with higher power than existing calibration strategies while remaining test agnostic.

Multiple hypothesis testing with false discovery rate (FDR) control is a fundamental problem in statistical inference, with broad applications in genomics, drug screening, and outlier detection. In many such settings, researchers may have access not only to real experimental observations but also to auxiliary or synthetic data -- from past, related experiments or generated by generative models -- that can provide additional evidence about the hypotheses of interest. We introduce SynthBH, a synthetic-powered multiple testing procedure that safely leverages such synthetic data. We prove that SynthBH guarantees finite-sample, distribution-free FDR control under a mild PRDS-type positive dependence condition, without requiring the pooled-data p-values to be valid under the null. The proposed method adapts to the (unknown) quality of the synthetic data: it enhances the sample efficiency and may boost the power when synthetic data are of high quality, while controlling the FDR at a user-specified level regardless of their quality. We demonstrate the empirical performance of SynthBH on tabular outlier detection benchmarks and on genomic analyses of drug-cancer sensitivity associations, and further study its properties through controlled experiments on simulated data.

We develop a flexible feature selection framework based on deep neural networks that approximately controls the false discovery rate (FDR), a measure of Type-I error. The method applies to architectures whose first layer is fully connected. From the second layer onward, it accommodates multilayer perceptrons (MLPs) of arbitrary width and depth, convolutional and recurrent networks, attention mechanisms, residual connections, and dropout. The procedure also accommodates stochastic gradient descent with data-independent initializations and learning rates. To the best of our knowledge, this is the first work to provide a theoretical guarantee of FDR control for feature selection within such a general deep learning setting. Our analysis is built upon a multi-index data-generating model and an asymptotic regime in which the feature dimension $n$ diverges faster than the latent dimension $q^{*}$, while the sample size, the number of training iterations, the network depth, and hidden layer widths are left unrestricted. Under this setting, we show that each coordinate of the gradient-based feature-importance vector admits a marginal normal approximation, thereby supporting the validity of asymptotic FDR control. As a theoretical limitation, we assume $\mathbf{B}$-right orthogonal invariance of the design matrix, and we discuss broader generalizations. We also present numerical experiments that underscore the theoretical findings.

AI-Scientist systems risk manufacturing spurious discoveries through uncontrolled multiple testing. We present a functional architecture that enforces statistical rigor at two levels: a Haskell embedded domain-specific language (the Research monad) that makes it impossible to test a hypothesis without updating the error budget, and a declarative scaffold, backed by an OS-level sandbox, that makes validation data physically absent from the environment in which LLM-generated code runs. We ground the design in a machine-checked Lean4 formalization of LORD++ online false-discovery-rate (FDR) control: we derive its error budget and prove both marginal and full FDR control, then close the gap to the implementation by verifying the budget's wealth invariant over IEEE754 arithmetic in SPARK/Ada. To our knowledge this is the first verified chain from theorem to floating-point implementation for an online FDR procedure. In simulation, the architecture holds the false discovery rate near 1% against a 5% target, where a naive approach reaches 41%. In end-to-end case studies, a valid test avoids the false discoveries a flawed one produces, yet still finds real effects when the data allow. An adversarial evaluation confirms that generated code cannot read the held-out data even when given its exact path.

We study data-driven score construction in conformal selection, which uses conformal p-values and multiple testing to select "interesting" instances with large unobserved labels from a pool of unlabeled data, while controlling the FDR in finite sample. While existing solutions require the score function to be constructed independent of the calibration and test data, it is desirable to select or construct powerful conformity score in a data-driven manner and to leverage all labeled data for score training when presented with many score choices and limited labeled data. We propose Optimized Conformal Selection (OptCS), a general framework that allows valid multiple testing after flexible data-driven score construction. We introduce general conditions under which OptCS constructs valid conformal p-values despite substantial data reuse and handles complex p-value dependencies to maintain finite-sample FDR control. We instantiate this general recipe to propose three FDR-controlling procedures, each optimizing the models differently: (i) selecting a powerful score function among multiple candidates, (ii) training the score with all labeled data without sample splitting, and (iii) combining full-sample training and model selection. We demonstrate the efficacy of our methods via simulation studies and real applications in drug discovery and large language models.

Many important tasks of large-scale recommender systems can be naturally cast as testing multiple linear forms for noisy matrix completion. These problems, however, present unique challenges because of the subtle bias-and-variance tradeoff of and an intricate dependence among the estimated entries induced by the low-rank structure. In this paper, we develop a general approach to overcome these difficulties by introducing new statistics for individual tests with sharp asymptotics both marginally and jointly, and utilizing them to control the false discovery rate (FDR) via a data splitting and symmetric aggregation scheme. We show that valid FDR control can be achieved with guaranteed power under nearly optimal sample size requirements using the proposed methodology. Extensive numerical simulations and real data examples are also presented to further illustrate its practical merits.