arXiv subjects

Zijun Gao

Publications and source records attributed to Zijun Gao.

At least 19 recordsLinked to original sources

arXiv2026

Reliable Selection of Heterogeneous Treatment Effect Estimators

We study the problem of selecting the best heterogeneous treatment effect (HTE) estimator from a collection of candidates in settings where the treatment effect is fundamentally unobserved. We cast estimator selection as a multiple testing problem and introduce a ground-truth-free procedure based on a cross-fitted, exponentially weighted test statistic. A key component of our method is a two-way sample splitting scheme that decouples nuisance estimation from weight learning and ensures the stability required for valid inference. Leveraging a stability-based central limit theorem, we establish asymptotic familywise error rate control under mild regularity conditions. Empirically, our procedure provides reliable error control while substantially reducing false selections compared with commonly used methods across ACIC 2016, IHDP, and Twins benchmarks, demonstrating that our method is feasible and powerful even without ground-truth treatment effects.

stat.ML↗

arXiv2026

Cubic-Root Gaussian Approximation under Unrestricted Covariance

For Gaussian approximation over high-dimensional rectangles under unrestricted covariance, Chernozhukov et al. (2023b) conjectured that the $n^{-1/4}$ rate, up to logarithmic factors, is near-optimal. We show that, under the coordinatewise subexponential condition with scale $B_n$ and the marginal variance lower bound condition with constant $b$ in Chernozhukov et al. (2023b), the approximation error in dimension $d$ is bounded by \begin{align*} C_b\min\left\{ 1,\, \left(\frac{B_n^2}{n}\right)^{1/3}\{\log(2dn)\}^{7/3} + \frac{B_n}{\sqrt n}\{\log(2dn)\}^{5/2} \right\}. \end{align*} In particular, for bounded $B_n$ and polynomial dimension, the new bound is $n^{-1/3}$ and therefore falsifies the polynomial-dimensional $n^{-1/4}$ near-optimality conjecture. The proof uses a two-stage interpolation and a rank-free matrix-weighted Gaussian surface bound, which may be of independent interest. The initial proof attempt was generated by ChatGPT 5.6 Pro (OpenAI) and subsequently corrected and rewritten by the authors. The machine-checked Lean formalization of the proof can be found at the GitHub repository (https://github.com/WeihanZhang2001/cubic-root-gaussian-approximation-under-unrestricted-covariance).

math.ST↗

arXiv2026

Causal Survival Forests with Negative Controls

We study heterogeneous treatment-effect (HTE) estimation in observational survival studies commonly associated with both censored outcomes and unmeasured confounding. We integrate causal survival forests (CSF) with negative controls (NC) from proximal causal inference and introduce Negative Control Causal Survival Forests (NC-CSF), a flexible nonparametric HTE learner for survival analysis. Our approach uses a loss that incorporates proxy variables and Neyman orthogonalization to train the random forest, thereby mitigating bias from unobserved confounding and gaining robustness to nuisance estimation. Through extensive simulations spanning varying levels of confounding, proxy relevance, and censoring mechanisms, we demonstrate that NC-CSF substantially reduces bias and estimation error relative to existing baselines. We further demonstrate the practical utility of our method on various clinical datasets, where it confirms several existing findings and also reveals new interpretable patterns of treatment-effect heterogeneity. To facilitate practical use, we provide an end-to-end Python implementation of NC-CSF that carefully handles implementation details such as nuisance estimation and clipping.

stat.ME↗

arXiv2026

Reliable conformal novelty detection at the decision boundary

Novelty detection via conformal $p$-values and BH procedure provides distribution-free global false discovery rate (FDR) control. We present here fundamental limits of this approach by showing that it does not produce reliable detection at the decision boundary. We study boundary false discovery rate (bFDR), the probability that the least extreme reported novelty is in fact a null observation. We first show that the support line (SL) procedure, controlling the bFDR in the continuous independent framework, fails to control the bFDR in the conformal case. We then present several modifications of the SL procedure that restore reliability at the decision boundary, by controlling the bFDR, with specific improvements in situations where many novelties are expected (adaptive procedures) and when the calibration sample is too small with respect to the test sample (subsampled procedures). Numerical experiments with both synthetic and real data support our findings and show the relevance of the new proposed approach.

stat.ME↗

arXiv2026

Statistical Inference for Generative Model Comparison

Generative models have achieved remarkable success across a range of applications, yet their evaluation still lacks principled uncertainty quantification. In this paper, we develop a method for comparing how close different generative models are to the underlying distribution of test samples. Particularly, our approach employs the Kullback-Leibler (KL) divergence to measure the distance between a generative model and the unknown test distribution, as KL requires no tuning parameters such as the kernels used by RKHS-based distances, and is the only $f$-divergence that admits a crucial cancellation to enable the uncertainty quantification. Furthermore, we extend our method to comparing conditional generative models and leverage Edgeworth expansions to address limited-data settings. On simulated datasets with known ground truth, we show that our approach realizes effective coverage rates, and has higher power compared to kernel-based methods. When applied to generative models on image and text datasets, our procedure yields conclusions consistent with benchmark metrics but with statistical confidence.

stat.ML↗

arXiv2026

Flexible Inference for Winners with Conditional Validity

Researchers often select top-performing options or winners, based on a data-driven criterion, such as treatments, models, or model features and then report effect estimates for the selected winners. Naive post-selection estimates, however, are known to suffer from the winner's curse, producing systematically overoptimistic results. We introduce a flexible conditional inference method that corrects for this overoptimism through an adaptive exponential randomization scheme. Our method achieves selection quality that closely matches that of standard top-k selection, while also yielding shorter confidence intervals than existing approaches. Furthermore, our approach applies broadly to nonparametric settings with asymptotically linear selection statistics, covering wide-ranging applications such as inference for the efficacy of the most promising treatments in clinical trials, the abilities of top-ranked models on leaderboards, and the importance of the most predictive features in a model.

stat.ME↗

arXiv2026

Exploring the Alignment of Generation and Understanding in Protein Structure Modeling

Understanding and generation are often treated as two separate paradigms in training deep neural networks, despite the fact that both are trained with closely related objectives such as denoising and masked prediction. While prior studies have shown that generative models often learn suboptimal representations for understanding tasks in vision, it is less understood whether a similar gap exists in the protein domain. In this work, we systematically investigate this question by benchmarking state-of-the-art protein generative models on widely-used protein understanding tasks, and observe that these models exhibit consistently poor performance compared to existing protein encoders. Furthermore, inspired by the Representation Alignment (REPA) framework, we propose to explicitly align generative protein diffusion models with pretrained protein understanding models during training. Experiments on the MotifBench demonstrate that representation alignment significantly improves functional protein generation, boosting the MotifBench score of Protpardelle-1c from 39.2 to 47.1, corresponding to a 20% relative improvement. Our results suggest that representation alignment provides a general and effective mechanism for bridging understanding and generation in protein structure modeling.

cs.CE↗

arXiv2026

SF-Cluster: Frustration-Guided MSA Subsampling for Alternative Protein Conformation Recovery

Deep-learning structure predictors are sensitive to their multiple sequence alignment (MSA) input, making MSA subsampling a practical route to recovering alternative conformations. Existing approaches such as AF-Cluster operate in sequence space, providing limited control over which conformational basin is sampled. We introduce SF-Cluster, which subsamples MSAs using patterns of predicted local energetic frustration, a representation largely independent of sequence similarity. Across a benchmark of 48 cases spanning fold-switching, allosteric, oligomerization-coupled, and intrinsically disordered systems, and using an AF-Cluster-style dual-reference RMSD criterion, SF-Cluster improves target-state recovery of the alternative conformation over AF-Cluster across the two-state classes, with the largest improvement observed for allosteric systems (+15.5 percentage points). The selected MSAs transfer to an architecturally distinct predictor, indicating that the conformational signal resides in MSA composition. Mechanistically, matched-depth controls show that this recovery advantage is largely explained by the effective depth of the selected subsets, which frustration-pattern selection reliably reaches. At the same time, highly frustrated residues are enriched at sites supported by deep mutational scanning and NMR two-state exchange, and frustration covariation is enriched at state-switching contacts while remaining distinct from coevolutionary coupling. Together, these results identify frustration patterns as a transferable representation for conformational prediction and position MSA subsampling as a representation-guided reweighting problem.

q-bio.BM↗

arXiv2026

Partial Identification under High-Dimensional Potential Outcomes and Confounders via Optimal Transport

Partial identification provides informative causal guarantees when point identification is impossible, but existing approaches based on optimal transport (OT) become computationally and statistically intractable in high-dimensional settings. This limitation is particularly severe when both potential outcomes and confounders are high-dimensional, where classical OT-based bounds suffer from the curse of dimensionality and unfavorable convergence rates. To address this challenge, we propose a novel estimator that decomposes the transport problem into a low-dimensional signal subspace and a high-dimensional residual subspace. Unlike existing projection-based methods that discard residual information, we recover the residual transport energy using the Sliced Wasserstein distance, which is computationally efficient and robust to high dimensions. We establish interpretable conditions controlling the approximation gap based on residual structure and provide a data-driven rule for signal dimension selection. Empirical results show that our estimator consistently outperforms projection-only baselines by recovering lost transport energy, yielding more informative causal bounds while remaining computationally tractable in high dimensions.

stat.ME↗

arXiv2026

Selective Randomization Inference for Adaptive Experiments

Adaptive experiments use preliminary analyses of the data to inform further course of action and are commonly used in many disciplines including medical and social sciences. Because the null hypothesis and experimental design are data-dependent, it has long been recognized that statistical inference for adaptive experiments is not straightforward. Most existing methods only apply to specific adaptive designs and rely on strong assumptions. In this work, we propose selective randomization inference as a general framework for analysing adaptive experiments. In a nutshell, our approach applies conditional post-selection inference to randomization tests. By using directed acyclic graphs to describe the data generating process, we derive a selective randomization p-value that controls the selective type-I error. As inference only relies on the randomness in the treatment assignment, no modelling assumptions or independent and identically distributed data are needed. We elaborate on conditions that render the proposed p-value computable and provide rejection sampling and MCMC algorithms to find a Monte Carlo approximation. Moreover, this article shows how to estimate and construct confidence intervals for a homogeneous treatment effect. Lastly, we demonstrate our method and compare it with other randomization tests using synthetic and real-world data.

stat.ME↗

arXiv2026

GeoCycler: Reward-Aligned 3D Diffusion for Constraint-Conditioned Cyclic Peptide Design

Cyclic peptides are attractive therapeutic modalities because their closed-ring topology can improve stability and target specificity. However, de novo cyclic peptide design remains challenging for diffusion generators, as macrocyclization requires satisfying sparse, non-smooth, and compositional geometric constraints. Existing constraint-conditioned methods largely rely on inference-time guidance, which can steer samples toward desired closures but does not directly change the learned generative distribution. We propose GeoCycler, a reward-weighted diffusion alignment framework for training conditional latent diffusion models toward macrocyclization feasibility. GeoCycler introduces a type-gated stair reward that activates distance-based shaping only when prerequisite residue or linker types are satisfied, providing dense geometric feedback while avoiding misleading signals from chemically incompatible anchors. Together with positive-only reward weighting and replay-based stabilization, GeoCycler aligns a single generator across multiple cyclization topologies. On the LNR benchmark, GeoCycler improves pass@5 closure success over strong guidance-based baselines across stapled, head-to-tail, disulfide, and bicyclic settings. In particular, it improves head-to-tail success by 20.8 percentage points over CP-Composer while maintaining comparable amino-acid and backbone-dihedral statistics. These results suggest that training-time alignment to sparse geometric constraints is a promising alternative to relying solely on post hoc sampling-time correction for cyclic peptide generation.

cs.CE↗

arXiv2026

Simultaneous false discovery rate control in location families

When testing a number of statistical hypotheses using data from location families, it is often useful to control the false discovery rate (FDR) not just for hypotheses of the null values but also of other parameter values that are deemed practically insignificant. Here we consider FDR as a curve indexed by the location parameter and suggest a simple generalization of the Benjamini-Hochberg procedure that controls the FDR curve below any user-specified level. As a corollary of our main result, we show that the standard Benjamini-Hochberg procedure -- designed to control the FDR at the null -- also provides simultaneous control of the whole FDR curve for free. We further demonstrate the implications of our results and some practical considerations with a numerical example.

stat.ME↗

arXiv2026

CA-DEL: An Open Multi-Target, Multi-Modal Benchmark for Learning from DNA-Encoded Library Screens

The success of machine learning in drug discovery hinges on learning the relationship between a chemical structure and its biological activity. While DNA-Encoded Library (DEL) technology can generate the massive datasets required for this task, its primary signal -- sequencing read counts -- is an indirect and often noisy proxy for true molecular binding affinity. To address the scarcity of public benchmarks for developing robust models that can overcome this data challenge, we introduce CA-DEL, a multi-dimensional public benchmark featuring screens against three homologous carbonic anhydrase isoforms. While recent benchmarks like KinDEL have introduced 3D poses for kinase targets, CA-DEL distinguishes itself by focusing on the selectivity challenge among homologous Carbonic Anhydrase isoforms (CAII, CAIX, CAXII). Unlike benchmarks relying solely on noisy enrichment scores, CA-DEL integrates a rigorous validation set of experimentally determined binding affinities ($K_i$) from ChEMBL, establishing a critical Sim-to-Real evaluation paradigm: training on noisy DEL screens and testing on high-fidelity biophysical data.

q-bio.BM↗

arXiv2026

CORE: Concept-Oriented Reinforcement for Bridging the Definition-Application Gap in Mathematical Reasoning

Large language models (LLMs) often solve challenging math exercises yet fail to apply the concept right when the problem requires genuine understanding. Popular Reinforcement Learning with Verifiable Rewards (RLVR) pipelines reinforce final answers but provide little fine-grained conceptual signal, so models improve at pattern reuse rather than conceptual applications. We introduce CORE (Concept-Oriented REinforcement), an RL training framework that turns explicit concepts into a controllable supervision signal. Starting from a high-quality, low-contamination textbook resource that links verifiable exercises to concise concept descriptions, we run a sanity probe showing LLMs can restate definitions but fail concept-linked quizzes, quantifying the conceptual reasoning gap. CORE then (i) synthesizes concept-aligned quizzes, (ii) injects brief concept snippets during rollouts to elicit concept-primed trajectories, and (iii) reinforces conceptual reasoning via trajectory replacement after group failures, a lightweight forward-KL constraint that aligns unguided with concept-primed policies, or standard GRPO directly on concept-aligned quizzes. Across several models, CORE delivers consistent gains over vanilla and SFT baselines on both in-domain concept-exercise suites and diverse out-of-domain math benchmarks. CORE unifies direct training on concept-aligned quizzes and concept-injected rollouts under outcome regularization. It provides fine-grained conceptual supervision that bridges problem-solving competence and genuine conceptual reasoning, while remaining algorithm- and verifier-agnostic.

cs.AI↗

arXiv2026

Estimation and Inference for Causal Explainability

Understanding how much each variable contributes to an outcome is a central question across disciplines. A causal view of explainability is favorable for its ability in uncovering underlying mechanisms and generalizing to new contexts. Based on a family of causal explainability quantities, we develop methods for their estimation and inference. In particular, we construct a one-step correction estimator using semi-parametric efficiency theory, which explicitly leverages the independence structure of variables to reduce the asymptotic variance. For a null hypothesis on the boundary, i.e., zero explainability, we show its equivalence to Fisher's sharp null, which motivates a randomization-based inference procedure. Finally, we illustrate the empirical efficacy of our approach through simulations as well as an immigration experiment dataset, where we investigate how features and their interactions shape public opinion toward admitting immigrants.

stat.ME↗

arXiv2026

Bi-TEAM: A Unified Cross-Scale Representation Learning Framework for Chemically Modified Biomolecules

Representation learning for protein biochemical space faces a difficult trade-off: protein language models excel at capturing long-range biological semantics but often miss fine-grained chemical details. Conversely, chemical language models encode atomic information but lack broader sequence context. To address this, we introduce Bi-TEAM (Bi-gated Residual Space Modification), a general framework that injects localized chemical variation into global protein contexts. By ensuring robustness against perturbations such as non-canonical amino acids, post-translational modifications (PTMs), and topological constraints, Bi-TEAM uncovers functional chemical dependencies often missed by evolutionary baselines. Mechanistically, Bi-TEAM maps non-canonical residues to their natural counterparts and injects atomic-level data via a bi-gated residual fusion mechanism. Crucially, this process uses modification-aware prompts to ensure that local structural changes influence global functional representations without requiring alphabet expansion. We evaluated Bi-TEAM on ten datasets spanning chemically modified peptides, PTMs, and natural proteins. The model consistently outperformed state-of-the-art baselines, achieving up to a 66 percent improvement in Matthews correlation coefficient (MCC) on scaffold-similarity splits and a 350 percent increase in hemolysis prediction accuracy. Furthermore, when deployed as an oracle for generative modeling, Bi-TEAM nearly quadrupled the success rate for designing cell-penetrating cyclic peptides. By unifying biological semantics with chemical precision, Bi-TEAM provides a versatile foundation for machine learning driven exploration of peptide and protein biochemical space.

q-bio.BM↗

arXiv2026

A Decade-Long Increasing Mid-Infrared Luminosity in Galaxy NGC6447: a Turning-On Candidate of Active Galactic Nucleus

It is widely expected that the obscured accretion stage can be the initial turning-on stage of active galactic nuclei from quiescent galaxies. We present mid-infrared light curves of NGC 6447 in 3.5$μ$m and 4.6 $μ$m bands observed by WISE/NEOWISE, which show an almost monotonic increasing trend of 1.2 mag over 14 years. The optical light curve from ASAS-SN during the same period is consistent with a constant showing no variability. The mid-infrared color evolution shows that the galaxy transitioned into an active galactic nucleus (AGN) in 2018. The SPHEREx spectrum reveals an increasing continuum resembling warm to hot dust emission from an AGN. NuSTAR detected an X-ray source with a 2-30 keV luminosity of $8.4\times10^{41}$ ergs/s at the lower boundary of AGN X-ray emission range, and a factor of >7 variability in one year compared to the Swift upper limit. NGC 6447 was classified as a quiescent galaxy in the literature. The multi-wavelength timing and spectral properties of NGC 6447 are consistent with the expected AGN turning on event, where the obscuring material around the AGN central engine is gradually dispersed, revealing the central engine. This example shows that long-term infrared variability can be a powerful tool to find similar sources. Based on the sample selection statistics, we estimate the duration of the episodes of AGN accretion (duty cycle) signified by the turning-on event as $10^4$-$10^6$ yr.

astro-ph.GA↗

arXiv2026

Statistical Inference in Causal Partial Identification with Smooth Densities

Many causal quantities are only partially identifiable due to the inherent missingness of potential outcomes, and the associated partial identification (PI) sets can be obtained by solving an optimal transport (OT) problem. Covariates often provide additional information about the potential outcomes and thus yield tighter PI sets, which can be obtained via conditional optimal transport (COT). However, COT-based PI set estimators are susceptible to the curse of dimensionality in the covariates and outcomes, which precludes the asymptotic normality and hinders statistical inference. In this paper, we exploit smoothness in the marginal densities of covariates and potential outcomes and develop a wavelet-based primal method for COT with multivariate outcomes and covariates. Moreover, for quadratic cost functions, we establish a stability result for COT and prove asymptotic normality of the proposed estimator. This characterization of the asymptotic distribution enables valid statistical inference for the partial identification set. Empirically, we validate the estimation and inference performance of our approach through numerical experiments in comparison with existing benchmarks.

math.ST↗