Technology
Nested Atoms Model with Application to Clustering Big Population-Scale Single-Cell Data
Chakrabarti, Arhit, Ni, Yang, Jiang, Yuchao, Mallick, Bani K.
We consider the problem of clustering nested or hierarchical data, where observations are grouped and there are both group-level and observation-level variables. In our motivating OneK1K dataset, observations consist of single-cell RNA-sequencing (scRNA-seq) data from 982 individuals (groups), totaling 1.27 million cells (observations), along with individual-specific genotype data. This type of data would enable the identification of cell types and the investigation of how genetic variations among individuals influence differences in cell-type profiles. Our goal, therefore, is to jointly cluster cells and individuals to capture the heterogeneity across both levels using cell-specific gene expressions as well as individual-specific genotypes. However, existing grouped clustering methods do not incorporate group-level variables, thereby limiting their ability to capture the heterogeneity of genotypes in our motivating application. To address this, we propose the Nested Atoms Model (NAM), a new Bayesian nonparametric approach that enables the desired two-layered clustering, accounting for both group-level and observation-level variables. To scale NAM for high-dimensional data, we develop a fast variational Bayesian inference algorithm. Simulations show that NAM outperforms existing methods that ignore group-level variables. Applied to the OneK1K dataset, NAM identifies clusters of genetically similar individuals with homogeneous cell-type profiles. The resulting cell clusters align with known immune cell types based on differential gene expression, underscoring the ability of NAM to capture nested heterogeneity and provide biologically meaningful insights.
Performance of weakly-supervised electronic health record-based phenotyping methods in rare-outcome settings
Hong, Yunjing, Nelson, Jennifer C., Williamson, Brian D.
Accurately identifying patients with specific medical conditions is a key challenge when using clinical data from electronic health records. Our objective was to comprehensively assess when weakly-supervised prediction methods, which use silver-standard labels (proxy measures of the true outcome) rather than gold-standard true labels, perform well in rare-outcome settings like vaccine safety studies. We compared three methods (PheNorm, MAP, and sureLDA) that combine structured features and features derived from clinical text using natural language processing, through an extensive simulation study with data-generating mechanisms ranging from simple to complex, varying outcome rates, and varying degrees of informative silver labels. We also considered using predicted probabilities to design a chart review validation study. No single method dominated the other across all prediction performance metrics. Probability-guided sampling selected a cohort enriched for patients with more mentions of important concepts in chart notes. SureLDA, the most complex of the three algorithms we considered, often performed well in simulations. Performance depended greatly on selected tuning parameters. Care should be taken when using weakly-supervised prediction methods in rare-outcome settings, particularly if the probabilities will be used in downstream analysis, but these methods can work well when silver labels are strong predictors of true outcomes.
Regional Explanations: Bridging Local and Global Variable Importance
Amoukou, Salim I., Brunel, Nicolas J-B.
We analyze two widely used local attribution methods, Local Shapley Values and LIME, which aim to quantify the contribution of a feature value $x_i$ to a specific prediction $f(x_1, \dots, x_p)$. Despite their widespread use, we identify fundamental limitations in their ability to reliably detect locally important features, even under ideal conditions with exact computations and independent features. We argue that a sound local attribution method should not assign importance to features that neither influence the model output (e.g., features with zero coefficients in a linear model) nor exhibit statistical dependence with functionality-relevant features. We demonstrate that both Local SV and LIME violate this fundamental principle. To address this, we propose R-LOCO (Regional Leave Out COvariates), which bridges the gap between local and global explanations and provides more accurate attributions. R-LOCO segments the input space into regions with similar feature importance characteristics. It then applies global attribution methods within these regions, deriving an instance's feature contributions from its regional membership. This approach delivers more faithful local attributions while avoiding local explanation instability and preserving instance-specific detail often lost in global methods.
Inferring Change Points in Regression via Sample Weighting
Arpino, Gabriel, Venkataramanan, Ramji
We study the problem of identifying change points in high-dimensional generalized linear models, and propose an approach based on sample-weighted empirical risk minimization. Our method, Weighted ERM, encodes priors on the change points via weights assigned to each sample, to obtain weighted versions of standard estimators such as M-estimators and maximum-likelihood estimators. Under mild assumptions on the data, we obtain a precise asymptotic characterization of the performance of our method for general Gaussian designs, in the high-dimensional limit where the number of samples and covariate dimension grow proportionally. We show how this characterization can be used to efficiently construct a posterior distribution over change points. Numerical experiments on both simulated and real data illustrate the efficacy of Weighted ERM compared to existing approaches, demonstrating that sample weights constructed with weakly informative priors can yield accurate change point estimators. Our method is implemented as an open-source package, weightederm, available in Python and R.
Last-Iterate Convergence of Randomized Kaczmarz and SGD with Greedy Step Size
Dereziลski, Michaล, Dong, Xiaoyu
We study last-iterate convergence of SGD with greedy step size over smooth quadratics in the interpolation regime, a setting which captures the classical Randomized Kaczmarz algorithm as well as other popular iterative linear system solvers. For these methods, we show that the $t$-th iterate attains an $O(1/t^{3/4})$ convergence rate, addressing a question posed by Attia, Schliserman, Sherman, and Koren, who gave an $O(1/t^{1/2})$ guarantee for this setting. In the proof, we introduce the family of stochastic contraction processes, whose behavior can be described by the evolution of a certain deterministic eigenvalue equation, which we analyze via a careful discrete-to-continuous reduction.
fastml: Guarded Resampling Workflows for Safer Automated Machine Learning in R
Korkmaz, Selcuk, Goksuluk, Dincer, Karaismailoglu, Eda
Preprocessing leakage arises when scaling, imputation, or other data-dependent transformations are estimated before resampling, inflating apparent performance while remaining hard to detect. We present fastml, an R package that provides a single-call interface for leakage-aware machine learning through guarded resampling, where preprocessing is re-estimated inside each resample and applied to the corresponding assessment data. The package supports grouped and time-ordered resampling, blocks high-risk configurations, audits recipes for external dependencies, and includes sandboxed execution and integrated model explanation. We evaluate fastml with a Monte Carlo simulation contrasting global and fold-local normalization, a usability comparison with tidymodels under matched specifications, and survival benchmarks across datasets of different sizes. The simulation demonstrates that global preprocessing substantially inflates apparent performance relative to guarded resampling. fastml matched held-out performance obtained with tidymodels while reducing workflow orchestration, and it supported consistent benchmarking of multiple survival model classes through a unified interface.
Orthogonal machine learning for conditional odds and risk ratios
Conditional effects are commonly used measures for understanding how treatment effects vary across different groups, and are often used to target treatments/interventions to groups who benefit most. In this work we review existing methods and propose novel ones, focusing on the odds ratio (OR) and the risk ratio (RR). While estimation of the conditional average treatment effect (ATE) has been widely studied, estimators for the OR and RR lag behind, and cutting edge estimators such as those based on doubly robust transformations or orthogonal risk functions have not been generalized to these parameters. We propose such a generalization here, focusing on the DR-learner and the R-learner. We derive orthogonal risk functions for the OR and RR and show that the associated pseudo-outcomes satisfy second-order conditional-mean remainder properties analogous to the ATE case. We also evaluate estimators for the conditional ATE, OR, and RR in a comprehensive nonparametric Monte Carlo simulation study to compare them with common alternatives under hundreds of different data-generating distributions. Our numerical studies provide empirical guidance for choosing an estimator. For instance, they show that while parametric models are useful in very simple settings, the proposed nonparametric estimators significantly reduce bias and mean squared error in the more complex settings expected in the real world. We illustrate the methods in the analysis of physical activity and sleep trouble in U.S. adults using data from the National Health and Nutrition Examination Survey (NHANES). The results demonstrate that our estimators uncover substantial treatment effect heterogeneity that is obscured by traditional regression approaches and lead to improved treatment decision rules, highlighting the importance of data-adaptive methods for advancing precision health research.
Deep Learning for Sequential Decision Making under Uncertainty: Foundations, Frameworks, and Frontiers
Artificial intelligence (AI) is moving increasingly beyond prediction to support decisions in complex, uncertain, and dynamic environments. This shift creates a natural intersection with operations research and management sciences (OR/MS), which have long offered conceptual and methodological foundations for sequential decision-making under uncertainty. At the same time, recent advances in deep learning, including feedforward neural networks, LSTMs, transformers, and deep reinforcement learning, have expanded the scope of data-driven modeling and opened new possibilities for large-scale decision systems. This tutorial presents an OR/MS-centered perspective on deep learning for sequential decision-making under uncertainty. Its central premise is that deep learning is valuable not as a replacement for optimization, but as a complement to it. Deep learning brings adaptability and scalable approximation, whereas OR/MS provides the structural rigor needed to represent constraints, recourse, and uncertainty. The tutorial reviews key decision-making foundations, connects them to the major neural architectures in modern AI, and discusses leading approaches to integrating learning and optimization. It also highlights emerging impact in domains such as supply chains, healthcare and epidemic response, agriculture, energy, and autonomous operations. More broadly, it frames these developments as part of a wider transition from predictive AI toward decision-capable AI and highlights the role of OR/MS in shaping the next generation of integrated learning--optimization systems.
DDO-RM for LLM Preference Optimization: A Minimal Held-Out Benchmark against DPO
Zhang, Tiantian, Zuo, Jierui, Wang, Wenping
This paper reorganizes the current manuscript around the DPO versus DDO-RM preference-optimization project and focuses on two parts: the algorithmic view and the preliminary held-out benchmark. The benchmark asks a narrow question: even in a minimal pairwise chosen-versus-rejected setting, can a reward-guided decision-distribution update outperform a direct pairwise objective? We compare Direct Preference Optimization (DPO) against DDO-RM on EleutherAI/pythia-410m using HuggingFaceH4/ultrafeedback\_binarized, evaluate on the held-out test\_prefs split, and report results for seeds 42, 13, and 3407. Algorithmically, DDO-RM treats each prompt as a finite decision problem over candidate responses. Instead of optimizing only a binary chosen-rejected relation, it forms a policy distribution over candidates, centers reward-model scores under that distribution, and distills a reward-guided target distribution back into the policy. In the current public benchmark, DDO-RM improves mean pair accuracy from 0.5238 to 0.5602, AUC from 0.5315 to 0.5382, and mean margin from 0.1377 to 0.5353 relative to DPO. These are encouraging but still preliminary results: the study covers one model family, one dataset, one held-out evaluation split, and three seeds.
Cross-Spectral Witness for Hidden Nonequilibrium Beyond the Scalar Ceiling
Partial observation is a pervasive obstacle in nonequilibrium physics: coarse graining may absorb hidden forcing into an apparently equilibrium-like reduced description, so a driven system can look reversible through the only variables one can measure. For scalar Gaussian observables of linear stochastic systems, no time-irreversibility statistic can detect the underlying drive. The Lucente--Crisanti ceiling constrains what one channel carries; what two channels carry is a different question, with a sharp closed-form answer. Two simultaneously observed channels retain an off-diagonal cross-spectral sector inaccessible to any scalar reduction; under channel-separable multiplicative structure the observed-channel response factors cancel identically, leaving a closed-form cross-spectral witness controlled only by the hidden spectrum, the loadings, and the innovation scales, strictly positive at every nonzero cross-coupling including at exact timescale coalescence where every scalar reduction is blind. Within general CSM this certifies shared hidden-sector drive; under the additional one-way coupling assumption the witness identifies the total entropy production rate at leading order with a square-root scaling.