arXiv subjects

Jin-Hong Du

Publications and source records attributed to Jin-Hong Du.

At least 19 recordsLinked to original sources

arXiv2026

AI-Augmented Statistical Network Estimation with Proxy Gene Embeddings

Gene--gene networks are often observed only on a restricted target set, while modern biomedical foundation models provide proxy gene embeddings over substantially larger gene universes. To leverage externally learned representations to improve latent-structure recovery in partially observed target networks, we propose \emph{Proxy-Latent Assisted Network Estimation} (PLANE), an adaptively weighted joint network--embedding latent variable model. PLANE combines the two sources of information through the common latent positions of the target network and proxy embeddings. Under mild rank conditions, the target network enables the identification of latent positions and loading of all nodes up to an orthogonal rotation. We show that zero-order optimality analyses sharply control the weighted reconstruction loss, but are insufficient to identify the optimal weighting. To understand the network and embedding information trade-off for latent-factor recovery, we analyze blockwise Gram-normalized gradient descent and prove deterministic contraction of aligned, curvature-weighted errors up to an explicit statistical tolerance. We then specialize the weighted statistical error bound to derive the target-block error bound, yielding an optimal, data-adaptive choice of the network embedding weights. Simulations and single-cell perturbation analyses show that informative proxy embeddings improve latent recovery, network reconstruction, and imputation beyond the observed target network.

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arXiv2026

Beyond Importance: Interchange-Sobol Sensitivity Reveals Task-Specific Content Channels in Transformer Components

Mechanistic interpretability methods summarize a transformer component by a single importance score, conflating two distinct roles: a component may matter because it transports task-relevant content, or because the forward computation degrades when its contribution is removed. We introduce \emph{Interchange-Group Sobol Decomposition} (IGSD), a paired-intervention framework that compares matched activation replacement with zero ablation on the same component, estimates two Sobol-style variance indices, and uses their signed difference to separate the two roles, with intervention validity monitored by a symmetric off-manifold diagnostic $\widehat{\mathrm{ST}}>1$. In factual recall, IGSD identifies an early-layer content channel in both GPT-2 small and Qwen2.5-1.5B that standard importance methods underestimate. A controlled subject and relation donor design shows that the early channel transports relation-frame content while late attention transports subject-retrieval content, refining at head granularity to the known $\mathrm{Attn}_{L9H8}$ head. Late-layer clamping confirms that the early signal is expressed through downstream transformations rather than residual pass-through. These results show that replacement and deletion are not interchangeable controls and their divergence provides a practical statistical diagnostic for content transport in transformer components.

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arXiv2026

Disentangled Feature Importance

When predictors are statistically dependent, the appropriate definition of feature importance depends on the operational goal. Conditional-incremental measures are well-suited for feature selection, acquisition, and compression, where shared predictive information is treated as redundancy. For post-hoc interpretation, however, the goal is often to attribute predictive signals across correlated measurement channels. We introduce Disentangled Feature Importance (DFI), a population-level attribution framework for this setting. DFI maps covariates to an independent latent representation under a specified entropic optimal transport geometry, computes latent importance, and attributes it back to the original covariates through barycentric sensitivities. We show that broad conditional-incremental FI functionals target conditional incremental predictive value under squared-error loss, and therefore answer a different question from attribution of shared predictive signal under dependence. Under fixed transport cost, reference law, and regularization level, DFI defines a well-specified family of estimands. Latent scores admit a functional ANOVA interpretation, and in the Gaussian linear case, the attributed DFI recovers the classical $R^2$ decomposition for correlated regressors. We derive influence-function-based inference under nuisance-rate and smoothness conditions, and show in simulations and an HIV-1 neutralization-resistance analysis that DFI yields stable, interpretable, uncertainty-quantified attributions of shared predictive signal.

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arXiv2026

Heterogeneous Judge-Aware Ranking with Sensitivity, Disagreement, and Confidence

Pairwise comparisons from multiple judges are central to large language model evaluation and preference modeling, yet standard ranking pipelines often pool judgments into a single score vector, treating systematic judge disagreement as noise. We propose Heterogeneous Judge-Aware (HJA) ranking, a structured multi-judge ranking framework that separates consensus ranking, judge-specific sensitivity to consensus, and residual preference disagreement. HJA thereby treats ranking, judge sensitivity, and structured disagreement as separate inferential targets. We establish conditions under which this decomposition is identifiable and develop an anchored alternating algorithm that preserves the identifying geometry. For confidence quantification, we study a fixed-panel repeated-comparison regime in which the judge panel may remain fixed or modest while information grows through repeated judgments. This yields uncertainty statements for consensus and judge-specific ranking contrasts, sensitivity parameters, pairwise probabilities, and summaries of residual disagreement.Experiments on synthetic and real multi-judge comparison data show that HJA improves recovery, robustness, uncertainty calibration, and near-tie performance relative to pooled and sensitivity-only baselines. The fitted model also provides diagnostics for judge disagreement and model-affinity patterns, giving a statistically grounded framework for ranking under heterogeneous comparative judgments.

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arXiv2025

Assumption-Lean Post-Integrated Inference with Surrogate Control Outcomes

Data integration methods aim to extract low-dimensional embeddings from high-dimensional outcomes to remove unwanted variations, such as batch effects and unmeasured covariates, across heterogeneous datasets. However, multiple hypothesis testing after integration can be biased due to data-dependent processes. We introduce a robust post-integrated inference method that accounts for latent heterogeneity by utilizing control outcomes. Leveraging causal interpretations, we derive nonparametric identifiability of the direct effects using negative control outcomes. By utilizing surrogate control outcomes as an extension of negative control outcomes, we develop semiparametric inference on projected direct effect estimands, accounting for hidden mediators, confounders, and moderators. These estimands remain statistically meaningful under model misspecifications and with error-prone embeddings. We provide bias quantifications and finite-sample linear expansions with uniform concentration bounds. The proposed doubly robust estimators are consistent and efficient under minimal assumptions and potential misspecification, facilitating data-adaptive estimation with machine learning algorithms. Our proposal is evaluated using random forests through simulations and analysis of single-cell CRISPR perturbed datasets, which may contain potential unmeasured confounders.

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arXiv2025

Distance-Preserving Representations for Genomic Spatial Reconstruction

The spatial context of single-cell gene expression data is crucial for many downstream analyses, yet often remains inaccessible due to practical and technical limitations, restricting the utility of such datasets. In this paper, we propose a generic representation learning and transfer learning framework dp-VAE, capable of reconstructing the spatial coordinates associated with the provided gene expression data. Central to our approach is a distance-preserving regularizer integrated into the loss function during training, ensuring the model effectively captures and utilizes spatial context signals from reference datasets. During the inference stage, the produced latent representation of the model can be used to reconstruct or impute the spatial context of the provided gene expression by solving a constrained optimization problem. We also explore the theoretical connections between distance-preserving loss, distortion, and the bi-Lipschitz condition within generative models. Finally, we demonstrate the effectiveness of dp-VAE in different tasks involving training robustness, out-of-sample evaluation, and transfer learning inference applications by testing it over 27 publicly available datasets. This underscores its applicability to a wide range of genomics studies that were previously hindered by the absence of spatial data.

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arXiv2025

Precise Asymptotics of Bagging Regularized M-estimators

We characterize the squared prediction risk of ensemble estimators obtained through subagging (subsample bootstrap aggregating) regularized M-estimators and construct a consistent estimator for the risk. Specifically, we consider a heterogeneous collection of $M \ge 1$ regularized M-estimators, each trained with (possibly different) subsample sizes, convex differentiable losses, and convex regularizers. We operate under the proportional asymptotics regime, where the sample size $n$, feature size $p$, and subsample sizes $k_m$ for $m \in [M]$ all diverge with fixed limiting ratios $n/p$ and $k_m/n$. Key to our analysis is a new result on the joint asymptotic behavior of correlations between the estimator and residual errors on overlapping subsamples, governed through a (provably) contractive nonlinear system of equations. Of independent interest, we also establish convergence of trace functionals related to degrees of freedom in the non-ensemble setting (with $M = 1$) along the way, extending previously known cases for squared loss with ridge and lasso regularizers. When specialized to homogeneous ensembles trained with a common loss, regularizer, and subsample size, the risk characterization sheds some light on the implicit regularization effect due to the ensemble and subsample sizes $(M,k)$. For any ensemble size $M$, optimally tuning subsample size yields sample-wise monotonic risk. For the full-ensemble estimator (when $M \to \infty$), the optimal subsample size $k^\star$ tends to be in the overparameterized regime $(k^\star \le \min\{n,p\})$, when explicit regularization is vanishing. Finally, joint optimization of subsample size, ensemble size, and regularization can significantly outperform regularizer optimization alone on the full data (without any subagging).

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arXiv2025

Causal Inference for Genomic Data with Multiple Heterogeneous Outcomes

With the evolution of single-cell RNA sequencing techniques into a standard approach in genomics, it has become possible to conduct cohort-level causal inferences based on single-cell-level measurements. However, the individual gene expression levels of interest are not directly observable; instead, only repeated proxy measurements from each individual's cells are available, providing a derived outcome to estimate the underlying outcome for each of many genes. In this paper, we propose a generic semiparametric inference framework for doubly robust estimation with multiple derived outcomes, which also encompasses the usual setting of multiple outcomes when the response of each unit is available. To reliably quantify the causal effects of heterogeneous outcomes, we specialize the analysis to standardized average treatment effects and quantile treatment effects. Through this, we demonstrate the use of the semiparametric inferential results for doubly robust estimators derived from both Von Mises expansions and estimating equations. A multiple testing procedure based on Gaussian multiplier bootstrap is tailored for doubly robust estimators to control the false discovery exceedance rate. Applications in single-cell CRISPR perturbation analysis and individual-level differential expression analysis demonstrate the utility of the proposed methods and offer insights into the usage of different estimands for causal inference in genomics.

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arXiv2025

Network-based Neighborhood regression

Given the ubiquity of modularity in biological systems, module-level regulation analysis is vital for understanding biological systems across various levels and their dynamics. Current statistical analysis on biological modules predominantly focuses on either detecting the functional modules in biological networks or sub-group regression on the biological features without using the network data. This paper proposes a novel network-based neighborhood regression framework whose regression functions depend on both the global community-level information and local connectivity structures among entities. An efficient community-wise least square optimization approach is developed to uncover the strength of regulation among the network modules while enabling asymptotic inference. With random graph theory, we derive non-asymptotic estimation error bounds for the proposed estimator, achieving exact minimax optimality. Unlike the root-n consistency typical in canonical linear regression, our model exhibits linear consistency in the number of nodes n, highlighting the advantage of incorporating neighborhood information. The effectiveness of the proposed framework is further supported by extensive numerical experiments. Application to whole-exome sequencing and RNA-sequencing Autism datasets demonstrates the usage of the proposed method in identifying the association between the gene modules of genetic variations and the gene modules of genomic differential expressions.

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arXiv2025

Simultaneous inference for generalized linear models with unmeasured confounders

Tens of thousands of simultaneous hypothesis tests are routinely performed in genomic studies to identify differentially expressed genes. However, due to unmeasured confounders, many standard statistical approaches may be substantially biased. This paper investigates the large-scale hypothesis testing problem for multivariate generalized linear models in the presence of confounding effects. Under arbitrary confounding mechanisms, we propose a unified statistical estimation and inference framework that harnesses orthogonal structures and integrates linear projections into three key stages. It begins by disentangling marginal and uncorrelated confounding effects to recover the latent coefficients. Subsequently, latent factors and primary effects are jointly estimated through lasso-type optimization. Finally, we incorporate projected and weighted bias-correction steps for hypothesis testing. Theoretically, we establish the identification conditions of various effects and non-asymptotic error bounds. We show effective Type-I error control of asymptotic $z$-tests as sample and response sizes approach infinity. Numerical experiments demonstrate that the proposed method controls the false discovery rate by the Benjamini-Hochberg procedure and is more powerful than alternative methods. By comparing single-cell RNA-seq counts from two groups of samples, we demonstrate the suitability of adjusting confounding effects when significant covariates are absent from the model.

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arXiv2025

Augmented Doubly Robust Post-Imputation Inference for Proteomic Data

Quantitative measurements produced by mass spectrometry proteomics experiments offer a direct way to explore the role of proteins in molecular mechanisms. However, analysis of such data is challenging due to the large proportion of missing values. A common strategy to address this issue is to utilize an imputed dataset, which often introduces systematic bias into downstream analyses if the imputation errors are ignored. In this paper, we propose a statistical framework inspired by doubly robust estimators that offers valid and efficient inference for proteomic data. Our framework combines powerful machine learning tools, such as variational autoencoders, to augment the imputation quality with high-dimensional peptide data, and a parametric model to estimate the propensity score for debiasing imputed outcomes. Our estimator is compatible with the double machine learning framework and has provable properties. In application to both single-cell and bulk-cell proteomic data our method utilizes the imputed data to gain additional, meaningful discoveries and yet maintains good control of false positives.

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arXiv2024

Revisiting Optimism and Model Complexity in the Wake of Overparameterized Machine Learning

Common practice in modern machine learning involves fitting a large number of parameters relative to the number of observations. These overparameterized models can exhibit surprising generalization behavior, e.g., ``double descent'' in the prediction error curve when plotted against the raw number of model parameters, or another simplistic notion of complexity. In this paper, we revisit model complexity from first principles, by first reinterpreting and then extending the classical statistical concept of (effective) degrees of freedom. Whereas the classical definition is connected to fixed-X prediction error (in which prediction error is defined by averaging over the same, nonrandom covariate points as those used during training), our extension of degrees of freedom is connected to random-X prediction error (in which prediction error is averaged over a new, random sample from the covariate distribution). The random-X setting more naturally embodies modern machine learning problems, where highly complex models, even those complex enough to interpolate the training data, can still lead to desirable generalization performance under appropriate conditions. We demonstrate the utility of our proposed complexity measures through a mix of conceptual arguments, theory, and experiments, and illustrate how they can be used to interpret and compare arbitrary prediction models.

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arXiv2024

Implicit Regularization Paths of Weighted Neural Representations

We study the implicit regularization effects induced by (observation) weighting of pretrained features. For weight and feature matrices of bounded operator norms that are infinitesimally free with respect to (normalized) trace functionals, we derive equivalence paths connecting different weighting matrices and ridge regularization levels. Specifically, we show that ridge estimators trained on weighted features along the same path are asymptotically equivalent when evaluated against test vectors of bounded norms. These paths can be interpreted as matching the effective degrees of freedom of ridge estimators fitted with weighted features. For the special case of subsampling without replacement, our results apply to independently sampled random features and kernel features and confirm recent conjectures (Conjectures 7 and 8) of the authors on the existence of such paths in Patil et al. We also present an additive risk decomposition for ensembles of weighted estimators and show that the risks are equivalent along the paths when the ensemble size goes to infinity. As a practical consequence of the path equivalences, we develop an efficient cross-validation method for tuning and apply it to subsampled pretrained representations across several models (e.g., ResNet-50) and datasets (e.g., CIFAR-100).

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arXiv2024

Corrected generalized cross-validation for finite ensembles of penalized estimators

Generalized cross-validation (GCV) is a widely-used method for estimating the squared out-of-sample prediction risk that employs a scalar degrees of freedom adjustment (in a multiplicative sense) to the squared training error. In this paper, we examine the consistency of GCV for estimating the prediction risk of arbitrary ensembles of penalized least-squares estimators. We show that GCV is inconsistent for any finite ensemble of size greater than one. Towards repairing this shortcoming, we identify a correction that involves an additional scalar correction (in an additive sense) based on degrees of freedom adjusted training errors from each ensemble component. The proposed estimator (termed CGCV) maintains the computational advantages of GCV and requires neither sample splitting, model refitting, or out-of-bag risk estimation. The estimator stems from a finer inspection of the ensemble risk decomposition and two intermediate risk estimators for the components in this decomposition. We provide a non-asymptotic analysis of the CGCV and the two intermediate risk estimators for ensembles of convex penalized estimators under Gaussian features and a linear response model. Furthermore, in the special case of ridge regression, we extend the analysis to general feature and response distributions using random matrix theory, which establishes model-free uniform consistency of CGCV.

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arXiv2024

Optimal Ridge Regularization for Out-of-Distribution Prediction

We study the behavior of optimal ridge regularization and optimal ridge risk for out-of-distribution prediction, where the test distribution deviates arbitrarily from the train distribution. We establish general conditions that determine the sign of the optimal regularization level under covariate and regression shifts. These conditions capture the alignment between the covariance and signal structures in the train and test data and reveal stark differences compared to the in-distribution setting. For example, a negative regularization level can be optimal under covariate shift or regression shift, even when the training features are isotropic or the design is underparameterized. Furthermore, we prove that the optimally-tuned risk is monotonic in the data aspect ratio, even in the out-of-distribution setting and when optimizing over negative regularization levels. In general, our results do not make any modeling assumptions for the train or the test distributions, except for moment bounds, and allow for arbitrary shifts and the widest possible range of (negative) regularization levels.

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arXiv2023

Extrapolated cross-validation for randomized ensembles

Ensemble methods such as bagging and random forests are ubiquitous in various fields, from finance to genomics. Despite their prevalence, the question of the efficient tuning of ensemble parameters has received relatively little attention. This paper introduces a cross-validation method, ECV (Extrapolated Cross-Validation), for tuning the ensemble and subsample sizes in randomized ensembles. Our method builds on two primary ingredients: initial estimators for small ensemble sizes using out-of-bag errors and a novel risk extrapolation technique that leverages the structure of prediction risk decomposition. By establishing uniform consistency of our risk extrapolation technique over ensemble and subsample sizes, we show that ECV yields $δ$-optimal (with respect to the oracle-tuned risk) ensembles for squared prediction risk. Our theory accommodates general ensemble predictors, only requires mild moment assumptions, and allows for high-dimensional regimes where the feature dimension grows with the sample size. As a practical case study, we employ ECV to predict surface protein abundances from gene expressions in single-cell multiomics using random forests. In comparison to sample-split cross-validation and $K$-fold cross-validation, ECV achieves higher accuracy avoiding sample splitting. At the same time, its computational cost is considerably lower owing to the use of the risk extrapolation technique. Additional numerical results validate the finite-sample accuracy of ECV for several common ensemble predictors under a computational constraint on the maximum ensemble size.

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arXiv2023

Bagging in overparameterized learning: Risk characterization and risk monotonization

Bagging is a commonly used ensemble technique in statistics and machine learning to improve the performance of prediction procedures. In this paper, we study the prediction risk of variants of bagged predictors under the proportional asymptotics regime, in which the ratio of the number of features to the number of observations converges to a constant. Specifically, we propose a general strategy to analyze the prediction risk under squared error loss of bagged predictors using classical results on simple random sampling. Specializing the strategy, we derive the exact asymptotic risk of the bagged ridge and ridgeless predictors with an arbitrary number of bags under a well-specified linear model with arbitrary feature covariance matrices and signal vectors. Furthermore, we prescribe a generic cross-validation procedure to select the optimal subsample size for bagging and discuss its utility to eliminate the non-monotonic behavior of the limiting risk in the sample size (i.e., double or multiple descents). In demonstrating the proposed procedure for bagged ridge and ridgeless predictors, we thoroughly investigate the oracle properties of the optimal subsample size and provide an in-depth comparison between different bagging variants.

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arXiv2023

Generalized equivalences between subsampling and ridge regularization

We establish precise structural and risk equivalences between subsampling and ridge regularization for ensemble ridge estimators. Specifically, we prove that linear and quadratic functionals of subsample ridge estimators, when fitted with different ridge regularization levels $λ$ and subsample aspect ratios $ψ$, are asymptotically equivalent along specific paths in the $(λ,ψ)$-plane (where $ψ$ is the ratio of the feature dimension to the subsample size). Our results only require bounded moment assumptions on feature and response distributions and allow for arbitrary joint distributions. Furthermore, we provide a data-dependent method to determine the equivalent paths of $(λ,ψ)$. An indirect implication of our equivalences is that optimally tuned ridge regression exhibits a monotonic prediction risk in the data aspect ratio. This resolves a recent open problem raised by Nakkiran et al. for general data distributions under proportional asymptotics, assuming a mild regularity condition that maintains regression hardness through linearized signal-to-noise ratios.

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