Negative sampling approaches are prevalent in implicit collaborative filtering for obtaining negative labels from massive unlabeled data. As two major concerns in negative sampling, efficiency and effectiveness are still not fully achieved by recent works that use complicate structures and overlook risk of false negative instances. In this paper, we first provide a novel understanding of negative instances by empirically observing that only a few instances are potentially important for model learning, and false negatives tend to have stable predictions over many training iterations. Above findings motivate us to simplify the model by sampling from designed memory that only stores a few important candidates and, more importantly, tackle the untouched false negative problem by favouring high-variance samples stored in memory, which achieves efficient sampling of true negatives with high-quality. Empirical results on two synthetic datasets and three real-world datasets demonstrate both robustness and superiorities of our negative sampling method.

Out-of-distribution (OOD) detection has received much attention lately due to its practical importance in enhancing the safe deployment of neural networks. One of the primary challenges is that models often produce highly confident predictions on OOD data, which undermines the driving principle in OOD detection that the model should only be confident about in-distribution samples. In this work, we propose ReAct--a simple and effective technique for reducing model overconfidence on OOD data. Our method is motivated by novel analysis on internal activations of neural networks, which displays highly distinctive signature patterns for OOD distributions. Our method can generalize effectively to different network architectures and different OOD detection scores. We empirically demonstrate that ReAct achieves competitive detection performance on a comprehensive suite of benchmark datasets, and give theoretical explication for our method's efficacy. On the ImageNet benchmark, ReAct reduces the false positive rate (FPR95) by 25.05% compared to the previous best method.

Analyzing machine learning model performance stratified by patient and recording properties is becoming the accepted norm and often yields crucial insights about important model failure modes. Performing such analyses in a statistically rigorous manner is non-trivial, however. Appropriate performance metrics must be selected that allow for valid comparisons between groups of different sample sizes and base rates; metric uncertainty must be determined and multiple comparisons be corrected for, in order to assess whether any observed differences may be purely due to chance; and in the case of intersectional analyses, mechanisms must be implemented to find the most `interesting' subgroups within combinatorially many subgroup combinations. We here present a statistical toolbox that addresses these challenges and enables practitioners to easily yet rigorously assess their models for potential subgroup performance disparities. While broadly applicable, the toolbox is specifically designed for medical imaging applications. The analyses provided by the toolbox are illustrated in two case studies, one in skin lesion malignancy classification on the ISIC2020 dataset and one in chest X-ray-based disease classification on the MIMIC-CXR dataset.

Fair regression methods have the potential to mitigate societal bias concerns in health care, but there has been little work on penalized fair regression when multiple groups experience such bias. We propose a general regression framework that addresses this gap with unfairness penalties for multiple groups. Our approach is demonstrated for binary outcomes with true positive rate disparity penalties. It can be efficiently implemented through reduction to a cost-sensitive classification problem. We additionally introduce novel score functions for automatically selecting penalty weights. Our penalized fair regression methods are empirically studied in simulations, where they achieve a fairness-accuracy frontier beyond that of existing comparison methods. Finally, we apply these methods to a national multi-site primary care study of chronic kidney disease to develop a fair classifier for end-stage renal disease. There we find substantial improvements in fairness for multiple race and ethnicity groups who experience societal bias in the health care system without any appreciable loss in overall fit.

Out-of-distribution (OOD) detection is essential for determining when a supervised model encounters inputs that differ meaningfully from its training distribution. While widely studied in classification, OOD detection for regression and survival analysis remains limited due to the absence of discrete labels and the challenge of quantifying predictive uncertainty. We introduce a framework for OOD detection that is simultaneously model aware and subspace aware, and that embeds variable prioritization directly into the detection step. The method uses the fitted predictor to construct localized neighborhoods around each test case that emphasize the features driving the model's learned relationship and downweight directions that are less relevant to prediction. It produces OOD scores without relying on global distance metrics or estimating the full feature density. The framework is applicable across outcome types, and in our implementation we use random forests, where the rule structure yields transparent neighborhoods and effective scoring. Experiments on synthetic and real data benchmarks designed to isolate functional shifts show consistent improvements over existing methods. We further demonstrate the approach in an esophageal cancer survival study, where distribution shifts related to lymphadenectomy identify patterns relevant to surgical guidelines.

Identifying and comparing topological features, particularly cycles, across different topological objects remains a fundamental challenge in persistent homology and topological data analysis. This work introduces a novel framework for constructing cycle communities through two complementary approaches. First, a dendrogram-based methodology leverages merge-tree algorithms to construct hierarchical representations of homology classes from persistence intervals. The Wasserstein distance on merge trees is introduced as a metric for comparing dendrograms, establishing connections to hierarchical clustering frameworks. Through simulation studies, the discriminative power of dendrogram representations for identifying cycle communities is demonstrated. Second, an extension of Stratified Gradient Sampling simultaneously learns multiple filter functions that yield cycle barycenter functions capable of faithfully reconstructing distinct sets of cycles. The set of cycles each filter function can reconstruct constitutes cycle communities that are non-overlapping and partition the space of all cycles. Together, these approaches transform the problem of cycle matching into both a hierarchical clustering and topological optimization framework, providing principled methods to identify similar topological structures both within and across groups of topological objects.

Least absolute shrinkage and selection operator (Lasso), a popular method for high-dimensional regression, is now used widely for estimating high-dimensional time series models such as the vector autoregression (VAR). Selecting its tuning parameter efficiently and accurately remains a challenge, despite the abundance of available methods for doing so. We propose $\mathsf{autotune}$, a strategy for Lasso to automatically tune itself by optimizing a penalized Gaussian log-likelihood alternately over regression coefficients and noise standard deviation. Using extensive simulation experiments on regression and VAR models, we show that $\mathsf{autotune}$ is faster, and provides better generalization and model selection than established alternatives in low signal-to-noise regimes. In the process, $\mathsf{autotune}$ provides a new estimator of noise standard deviation that can be used for high-dimensional inference, and a new visual diagnostic procedure for checking the sparsity assumption on regression coefficients. Finally, we demonstrate the utility of $\mathsf{autotune}$ on a real-world financial data set. An R package based on C++ is also made publicly available on Github.

We present an approach to denoising spatial transcriptomics images that is particularly effective for uncovering cell identities in the regime of ultra-low sequencing depths, and also allows for interpolation of gene expression. The method -- Spatial Transcriptomics via Adaptive Regularization and Kernels (STARK) -- augments kernel ridge regression with an incrementally adaptive graph Laplacian regularizer. In each iteration, we (1) perform kernel ridge regression with a fixed graph to update the image, and (2) update the graph based on the new image. The kernel ridge regression step involves reducing the infinite dimensional problem on a space of images to finite dimensions via a modified representer theorem. Starting with a purely spatial graph, and updating it as we improve our image makes the graph more robust to noise in low sequencing depth regimes. We show that the aforementioned approach optimizes a block-convex objective through an alternating minimization scheme wherein the sub-problems have closed form expressions that are easily computed. This perspective allows us to prove convergence of the iterates to a stationary point of this non-convex objective. Statistically, such stationary points converge to the ground truth with rate $\mathcal{O}(R^{-1/2})$ where $R$ is the number of reads. In numerical experiments on real spatial transcriptomics data, the denoising performance of STARK, evaluated in terms of label transfer accuracy, shows consistent improvement over the competing methods tested.

Binary classification is one of the oldest, most prevalent, and studied problems in machine learning. However, the metrics used to evaluate model performance have received comparatively little attention. The area under the receiver operating characteristic curve (AUROC) has long been a standard choice for model comparison. Despite its advantages, AUROC is not always ideal, particularly for problems that are invariant to local exchange of classes (LxC), a new form of metric invariance introduced in this work. To address this limitation, we propose LxCIM (LxC-invariant metric), which is not only rank-based and invariant under local exchange of classes, but also intuitive, logically consistent, and always computable, while enabling more detailed analysis through the cumulative accuracy-decision rate curve. Moreover, LxCIM exhibits clear theoretical connections to AUROC, accuracy, and the area under the accuracy-decision rate curve (AUDRC). These relationships allow for multiple complementary interpretations: as a symmetric form of AUROC, a rank-based analogue of accuracy, or a more representative and more interpretable variant of AUDRC. Finally, we demonstrate the direct applicability of LxCIM to the bivariate causal discovery problem (which exhibits invariance to local exchange of classes) and show how it addresses the acknowledged limitations of existing metrics used in this field. All code and implementation details are publicly available at github.com/tiagobrogueira/Causal-Discovery-In-Exchangeable-Data.

Autoregressive (AR) models, common in sequence generation, are limited in many biological tasks such as de novo peptide sequencing and protein modeling by their unidirectional nature, failing to capture crucial global bidirectional token dependencies. Non-Autoregressive (NAR) models offer holistic, bidirectional representations but face challenges with generative coherence and scalability. To transcend this, we propose a hybrid framework enhancing AR generation by dynamically integrating rich contextual information from non-autoregressive mechanisms. Our approach couples a shared input encoder with two decoders: a non-autoregressive one learning latent bidirectional biological features, and an AR decoder synthesizing the biological sequence by leveraging these bidirectional features. A novel cross-decoder attention module enables the AR decoder to iteratively query and integrate these bidirectional features, enriching its predictions. This synergy is cultivated via a tailored training strategy with importance annealing for balanced objectives and cross-decoder gradient blocking for stable, focused learning. Evaluations on a demanding nine-species benchmark of de novo peptide sequencing show that our model substantially surpasses AR and NAR baselines. It uniquely harmonizes AR stability with NAR contextual awareness, delivering robust, superior performance on diverse downstream data. This research advances biological sequence modeling techniques and contributes a novel architectural paradigm for augmenting AR models with enhanced bidirectional understanding for complex sequence generation. Code is available at https://github.com/BEAM-Labs/denovo.