Background: Single-cell RNA sequencing (scRNA-seq) enables gene expression profiling at cellular resolution but is inherently affected by sparsity caused by dropout events, where expressed genes are recorded as zeros due to technical limitations. These artifacts distort gene expression distributions and compromise downstream analyses. Numerous imputation methods have been proposed to recover latent transcriptional signals. These methods range from traditional statistical models to deep learning (DL)-based methods. However, their comparative performance remains unclear, as existing benchmarks evaluate only a limited subset of methods, datasets, and downstream analyses. Results: We present a comprehensive benchmark of 15 scRNA-seq imputation methods spanning 7 methodological categories, including traditional and DL-based methods. Methods are evaluated across 30 datasets from 10 experimental protocols on 6 downstream analyses. Results show that traditional methods, such as model-based, smoothing-based, and low-rank matrix-based methods, generally outperform DL-based methods, including diffusion-based, GAN-based, GNN-based, and autoencoder-based methods. In addition, strong performance in numerical gene expression recovery does not necessarily translate into improved biological interpretability in downstream analyses, including cell clustering, differential expression analysis, marker gene analysis, trajectory analysis, and cell type annotation. Furthermore, method performance varies substantially across datasets, protocols, and downstream analyses, with no single method consistently outperforming others. Conclusions: Our findings provide practical guidance for selecting imputation methods tailored to specific analytical objectives and underscore the importance of task-specific evaluation when assessing imputation performance in scRNA-seq data analysis.

We study offline-online reinforcement learning in linear mixture Markov decision processes (MDPs) under environment shift. In the offline phase, data are collected by an unknown behavior policy and may come from a mismatched environment, while in the online phase the learner interacts with the target environment. We propose an algorithm that adaptively leverages offline data. When the offline data are informative, either due to sufficient coverage or small environment shift, the algorithm provably improves over purely online learning. When the offline data are uninformative, it safely ignores them and matches the online-only performance. We establish regret upper bounds that explicitly characterize when offline data are beneficial, together with nearly matching lower bounds. Numerical experiments further corroborate our theoretical findings.

The Energy Conserving Descent (ECD) algorithm was recently proposed (De Luca & Silverstein, 2022) as a global non-convex optimization method. Unlike gradient descent, appropriately configured ECD dynamics escape strict local minima and converge to a global minimum, making it appealing for machine learning optimization. We present the first analytical study of ECD, focusing on the one-dimensional setting for this first installment. We formalize a stochastic ECD dynamics (sECD) with energy-preserving noise, as well as a quantum analog of the ECD Hamiltonian (qECD), providing the foundation for a quantum algorithm through Hamiltonian simulation. For positive double-well objectives, we compute the expected hitting time from a local to the global minimum. We prove that both sECD and qECD yield exponential speedup over respective gradient descent baselines--stochastic gradient descent and its quantization. For objectives with tall barriers, qECD achieves a further speedup over sECD.

Fine-tuning is a widely used strategy for adapting pre-trained models to new tasks, yet its methodology and theoretical properties in high-dimensional nonparametric settings with variable selection have not yet been developed. This paper introduces the fine-tuning factor augmented neural Lasso (FAN-Lasso), a transfer learning framework for high-dimensional nonparametric regression with variable selection that simultaneously handles covariate and posterior shifts. We use a low-rank factor structure to manage high-dimensional dependent covariates and propose a novel residual fine-tuning decomposition in which the target function is expressed as a transformation of a frozen source function and other variables to achieve transfer learning and nonparametric variable selection. This augmented feature from the source predictor allows for the transfer of knowledge to the target domain and reduces model complexity there. We derive minimax-optimal excess risk bounds for the fine-tuning FAN-Lasso, characterizing the precise conditions, in terms of relative sample sizes and function complexities, under which fine-tuning yields statistical acceleration over single-task learning. The proposed framework also provides a theoretical perspective on parameter-efficient fine-tuning methods. Extensive numerical experiments across diverse covariate- and posterior-shift scenarios demonstrate that the fine-tuning FAN-Lasso consistently outperforms standard baselines and achieves near-oracle performance even under severe target sample size constraints, empirically validating the derived rates.

Monitoring binomial proportions across multiple independent streams is a critical challenge in Statistical Process Control (SPC), with applications from manufacturing to cybersecurity. While EWMA charts offer sensitivity to small shifts, existing implementations rely on asymptotic variance approximations that fail during early-phase monitoring. We introduce a Cumulative Standardized Binomial EWMA (CSB-EWMA) chart that overcomes this limitation by deriving the exact time-varying variance of the EWMA statistic for binary multiple-stream data, enabling adaptive control limits that ensure statistical rigor from the first sample. Through extensive simulations, we identify optimal smoothing (λ) and limit (L) parameters to achieve target in-control average run length (ARL0) of 370 and 500. The CSB-EWMA chart demonstrates rapid shift detection across both ARL0 targets, with out-of-control average run length (ARL1) dropping to 3-7 samples for moderate shifts (δ=0.2), and exhibits exceptional robustness across different data distributions, with low ARL1 Coefficients of Variation (CV < 0.10 for small shifts) for both ARL0 = 370 and 500. This work provides practitioners with a distribution-free, sensitive, and theoretically sound tool for early change detection in binomial multiple-stream processes.

We decompose the Kullback--Leibler generalization error (GE) -- the expected KL divergence from the data distribution to the trained model -- of unsupervised learning into three non-negative components: model error, data bias, and variance. The decomposition is exact for any e-flat model class and follows from two identities of information geometry: the generalized Pythagorean theorem and a dual e-mixture variance identity. As an analytically tractable demonstration, we apply the framework to $ε$-PCA, a regularized principal component analysis in which the empirical covariance is truncated at rank $N_K$ and discarded directions are pinned at a fixed noise floor $ε$. Although rank-constrained $ε$-PCA is not itself e-flat, it admits a technical reformulation with the same total GE on isotropic Gaussian data, under which each component of the decomposition takes closed form. The optimal rank emerges as the cutoff $λ_{\mathrm{cut}}^{*} = ε$ -- the model retains exactly those empirical eigenvalues exceeding the noise floor -- with the cutoff reflecting a marginal-rate balance between model-error gain and data-bias cost. A boundary comparison further yields a three-regime phase diagram -- retain-all, interior, and collapse -- separated by the lower Marchenko--Pastur edge and an analytically computable collapse threshold $ε_{*}(α)$, where $α$ is the dimension-to-sample-size ratio. All claims are verified numerically.

This paper studies Graphical SLOPE for precision matrix estimation, with emphasis on its ability to recover both sparsity and clusters of edges with equal or similar strength. In a fixed-dimensional regime, we establish that the root-$n$ scaled estimation error converges to the unique minimizer of a strictly convex optimization problem defined through the directional derivative of the SLOPE penalty. We also establish convergence of the induced SLOPE pattern, thereby obtaining an asymptotic characterization of the clustering structure selected by the estimator. A comparison with GLASSO shows that the grouping property of SLOPE can substantially improve estimation accuracy when the precision matrix exhibits structured edge patterns. To assess the effect of departures from Gaussianity, we then analyze Gaussian-loss precision matrix estimation under elliptical distributions. In this setting, we derive the limiting distribution and quantify the inflation in variability induced by heavy tails relative to the Gaussian benchmark. We also study TSLOPE, based on the multivariate $t$-loss, and derive its limiting distribution. The results show that TSLOPE offers clear advantages over GSLOPE under heavy-tailed data-generating mechanisms. Simulation evidence suggests that these qualitative conclusions persist in high-dimensional settings, and an empirical application shows that SLOPE-based estimators, especially TSLOPE, can uncover economically meaningful clustered dependence structures.

High-dimensional and complex discrete distributions often exhibit multimodal behavior due to inherent discontinuities, posing significant challenges for sampling. Gradient-based discrete samplers, while effective, frequently become trapped in local modes when confronted with rugged or disconnected energy landscapes. This limits their ability to achieve adequate mixing and convergence in high-dimensional multimodal discrete spaces. To address these challenges, we propose \emph{Hyperbolic Secant-squared Gibbs-Sampling (HiSS)}, a novel family of sampling algorithms that integrates a \emph{Metropolis-within-Gibbs} framework to enhance mixing efficiency. HiSS leverages a logistic convolution kernel to couple the discrete sampling variable with the continuous auxiliary variable in a joint distribution. This design allows the auxiliary variable to encapsulate the true target distribution while facilitating easy transitions between distant and disconnected modes. We provide theoretical guarantees of convergence and demonstrate empirically that HiSS outperforms many popular alternatives on a wide variety of tasks, including Ising models, binary neural networks, and combinatorial optimization.

In recent years, the widespreadavailability of large-scale, high-dimensionaldatasets has driven significant interest in clustering algorithms that are both computationally efficient and robust to distributional shifts and outliers. The classical clustering method, K-means, can be seen as an application of the Lloyd-Max quantization algorithm, in which the distribution being quantized is the empirical distribution of the points to be clustered. This empirical distribution generally differs from the true underlying distribution, especially when the number of points to be clustered is small. This induces a distributional shift, which can also arise in many real-world settings, such as image segmentation, biological data analysis, and sensor networks, due to noise variations, sensor inaccuracies, or environmental changes. Distributional shifts can severely impact the performance of clustering algorithms, leading to degraded cluster assignments and unreliable downstream analysis. The field of clustering has a rich history. One of the most popular algorithms in this field is theK-means (KM) algorithm, introduced by [1], which computes centroids by iteratively updating the conditional mean of the data in the Voronoi regions induced by the centroids. However, standardK-means is sensitive to initialization and, in general, converges only to a local minimum.

Data leakage remains a recurrent source of optimistic bias in biomedical machine learning studies. Standard row-wise cross-validation and globally estimated preprocessing steps are often inappropriate for data with repeated measurements, study-level heterogeneity, batch effects, or temporal dependencies. This paper describes bioLeak, an R package for constructing leakage-aware resampling workflows and for auditing fitted models for common leakage mechanisms. The package provides leakage-aware split construction, train-fold-only preprocessing, cross-validated model fitting, nested hyperparameter tuning, post hoc leakage audits, and HTML reporting. The implementation supports binary classification, multiclass classification, regression, and survival analysis, with task-specific metrics and S4 containers for splits, fits, audits, and inflation summaries. The simulation artifacts show how apparent performance changes under controlled leakage mechanisms, and the case study illustrates how guarded and leaky pipelines can yield materially different conclusions on multi-study transcriptomic data. The emphasis throughout is on software design, reproducible workflows, and interpretation of diagnostic output.