Structure-based and ligand-based computational drug design have traditionally relied on disjoint data sources and modeling assumptions, limiting their joint use at scale. In this work, we introduce Contrastive Geometric Learning for Unified Computational Drug Design (ConGLUDe), a single contrastive geometric model that unifies structure- and ligand-based training. ConGLUDe couples a geometric protein encoder that produces whole-protein representations and implicit embeddings of predicted binding sites with a fast ligand encoder, removing the need for pre-defined pockets. By aligning ligands with both global protein representations and multiple candidate binding sites through contrastive learning, ConGLUDe supports ligand-conditioned pocket prediction in addition to virtual screening and target fishing, while being trained jointly on protein-ligand complexes and large-scale bioactivity data. Across diverse benchmarks, ConGLUDe achieves state-of-the-art zero-shot virtual screening performance in settings where no binding pocket information is provided as input, substantially outperforms existing methods on a challenging target fishing task, and demonstrates competitive ligand-conditioned pocket selection. These results highlight the advantages of unified structure-ligand training and position ConGLUDe as a step toward general-purpose foundation models for drug discovery.

The graphical Lasso (GLASSO) is a widely used algorithm for learning high-dimensional undirected Gaussian graphical models (GGM). Given i.i.d. observations from a multivariate normal distribution, GLASSO estimates the precision matrix by maximizing the log-likelihood with an \ell_1-penalty on the off-diagonal entries. However, selecting an optimal regularization parameter λin this unsupervised setting remains a significant challenge. A well-known issue is that existing methods, such as out-of-sample likelihood maximization, select a single global λand do not account for heterogeneity in variable scaling or partial variances. Standardizing the data to unit variances, although a common workaround, has been shown to negatively affect graph recovery. Addressing the problem of nodewise adaptive tuning in graph estimation is crucial for applications like computational neuroscience, where brain networks are constructed from highly heterogeneous, region-specific fMRI data. In this work, we develop Locally Adaptive Regularization for Graph Estimation (LARGE), an approach to adaptively learn nodewise tuning parameters to improve graph estimation and selection. In each block coordinate descent step of GLASSO, we augment the nodewise Lasso regression to jointly estimate the regression coefficients and error variance, which in turn guides the adaptive learning of nodewise penalties. In simulations, LARGE consistently outperforms benchmark methods in graph recovery, demonstrates greater stability across replications, and achieves the best estimation accuracy in the most difficult simulation settings. We demonstrate the practical utility of our method by estimating brain functional connectivity from a real fMRI data set.

Granger causality (GC) [15] is a time series causal discovery framework that uses predictive modeling to identify the underlying causal structure of a time series system. Relying on the assumption that cause precedes effect, GC assesses whether including the lagged information from one time series in the autoregressive model of a second time series enhances its predictions. This improvement indicates a predictive relationship between the time series variables, where one time series provides supplemental information about the future of another time series, thereby signifying the presence of a (Granger) causal relationship. GC requires only observational data, and has been used for time series causal discovery across diverse domains, including climate science [33], political and social sciences [17], econometrics [4], and biological systems studies [13]. The original formulation of GC requires several assumptions to be satisfied for causal identifiability. In regards to the candidate time series system, it is assumed that the time series variables are stationary, and that all variables are observed (absence of latent confounders). GC was initially proposed for bivariate time series systems, but was generalised for the multivariate setting to accommodate the assumption that all relevant variables are included in the analysis [15]. Additional assumptions are made with regard to the types of causal relationships that can be identified within the time series system. GC cannot estimate a causal relationship between time series at an instantaneous time point, relying on the relationship between the lags and predicted values to determine a GC relationship.

We study the Bandit Clustering (BC) problem under the fixed confidence setting, where the objective is to group a collection of data sequences (arms) into clusters through sequential sampling from adaptively selected arms at each time step while ensuring a fixed error probability at the stopping time. We consider a setting where arms in a cluster may have different distributions. Unlike existing results in this setting, which assume Gaussian-distributed arms, we study a broader class of vector-parametric distributions that satisfy mild regularity conditions. Existing asymptotically optimal BC algorithms require solving an optimization problem as part of their sampling rule at each step, which is computationally costly. We propose an Efficient Bandit Clustering algorithm (EBC), which, instead of solving the full optimization problem, takes a single step toward the optimal value at each time step, making it computationally efficient while remaining asymptotically optimal. We also propose a heuristic variant of EBC, called EBC-H, which further simplifies the sampling rule, with arm selection based on quantities computed as part of the stopping rule. We highlight the computational efficiency of EBC and EBC-H by comparing their per-sample run time with that of existing algorithms. The asymptotic optimality of EBC is supported through simulations on the synthetic datasets. Through simulations on both synthetic and real-world datasets, we show the performance gain of EBC and EBC-H over existing approaches.

Horseshoe mixtures-of-experts (HS-MoE) models provide a Bayesian framework for sparse expert selection in mixture-of-experts architectures. We combine the horseshoe prior's adaptive global-local shrinkage with input-dependent gating, yielding data-adaptive sparsity in expert usage. Our primary methodological contribution is a particle learning algorithm for sequential inference, in which the filter is propagated forward in time while tracking only sufficient statistics. We also discuss how HS-MoE relates to modern mixture-of-experts layers in large language models, which are deployed under extreme sparsity constraints (e.g., activating a small number of experts per token out of a large pool).

Multilabel Classification (MLC) deals with the simultaneous classification of multiple binary labels. The task is challenging because, not only may there be arbitrarily different and complex relationships between predictor variables and each label, but associations among labels may exist even after accounting for effects of predictor variables. In this paper, we present a Bayesian additive regression tree (BART) framework to model the problem. BART is a nonparametric and flexible model structure capable of uncovering complex relationships within the data. Our adaptation, MLCBART, assumes that labels arise from thresholding an underlying numeric scale, where a multivariate normal model allows explicit estimation of the correlation structure among labels. This enables the discovery of complicated relationships in various forms and improves MLC predictive performance. Our Bayesian framework not only enables uncertainty quantification for each predicted label, but our MCMC draws produce an estimated conditional probability distribution of label combinations for any predictor values. Simulation experiments demonstrate the effectiveness of the proposed model by comparing its performance with a set of models, including the oracle model with the correct functional form. Results show that our model predicts vectors of labels more accurately than other contenders and its performance is close to the oracle model. An example highlights how the method's ability to produce measures of uncertainty on predictions provides nuanced understanding of classification results.

The Rashomon effect -- the existence of multiple, distinct models that achieve nearly equivalent predictive performance -- has emerged as a fundamental phenomenon in modern machine learning and statistics. In this paper, we explore the causes underlying the Rashomon effect, organizing them into three categories: statistical sources arising from finite samples and noise in the data-generating process; structural sources arising from non-convexity of optimization objectives and unobserved variables that create fundamental non-identifiability; and procedural sources arising from limitations of optimization algorithms and deliberate restrictions to suboptimal model classes. We synthesize insights from machine learning, statistics, and optimization literature to provide a unified framework for understanding why the multiplicity of good models arises. A key distinction emerges: statistical multiplicity diminishes with more data, structural multiplicity persists asymptotically and cannot be resolved without different data or additional assumptions, and procedural multiplicity reflects choices made by practitioners. Beyond characterizing causes, we discuss both the challenges and opportunities presented by the Rashomon effect, including implications for inference, interpretability, fairness, and decision-making under uncertainty.

Although extensive research exists in spatial modeling, few studies have addressed finite mixture model-based clustering methods for spatial data. Finite mixture models, especially Gaussian mixture models, particularly suffer from high dimensionality due to the number of free covariance parameters. This study introduces a spatial covariance constraint for Gaussian mixture models that requires only four free parameters for each component, independent of dimensionality. Using a coordinate system, the spatially constrained Gaussian mixture model enables clustering of multi-way spatial data and inference of spatial patterns. The parameter estimation is conducted by combining the expectation-maximization (EM) algorithm with the generalized least squares (GLS) estimator. Simulation studies and applications to Raman spectroscopy data are provided to demonstrate the proposed model.

Machine Learning algorithms are ubiquitous in key decision-making contexts such as justice, healthcare and finance, which has spawned a great demand for fairness in these procedures. However, the theoretical properties of such models in relation with fairness are still poorly understood, and the intuition behind the relationship between group and individual fairness is still lacking. In this paper, we provide a theoretical framework based on Sheaf Diffusion to leverage tools based on dynamical systems and homology to model fairness. Concretely, the proposed method projects input data into a bias-free space that encodes fairness constrains, resulting in fair solutions. Furthermore, we present a collection of network topologies handling different fairness metrics, leading to a unified method capable of dealing with both individual and group bias. The resulting models have a layer of interpretability in the form of closed-form expressions for their SHAP values, consolidating their place in the responsible Artificial Intelligence landscape. Finally, these intuitions are tested on a simulation study and standard fairness benchmarks, where the proposed methods achieve satisfactory results. More concretely, the paper showcases the performance of the proposed models in terms of accuracy and fairness, studying available trade-offs on the Pareto frontier, checking the effects of changing the different hyper-parameters, and delving into the interpretation of its outputs.

Explainable artificial intelligence (XAI) is concerned with producing explanations indicating the inner workings of models. For a Rashomon set of similarly performing models, explanations provide a way of disambiguating the behavior of individual models, helping select models for deployment. However explanations themselves can vary depending on the explainer used, and need to be evaluated. In the paper "Evaluating Model Explanations without Ground Truth", we proposed three principles of explanation evaluation and a new method "AXE" to evaluate the quality of feature-importance explanations. We go on to illustrate how evaluation metrics that rely on comparing model explanations against ideal ground truth explanations obscure behavioral differences within a Rashomon set. Explanation evaluation aligned with our proposed principles would highlight these differences instead, helping select models from the Rashomon set. The selection of alternate models from the Rashomon set can maintain identical predictions but mislead explainers into generating false explanations, and mislead evaluation methods into considering the false explanations to be of high quality. AXE, our proposed explanation evaluation method, can detect this adversarial fairwashing of explanations with a 100% success rate. Unlike prior explanation evaluation strategies such as those based on model sensitivity or ground truth comparison, AXE can determine when protected attributes are used to make predictions.