Covariate adjustment is an approach to improve the precision of trial analyses by adjusting for baseline variables that are prognostic of the primary endpoint. Motivated by the SEARCH Universal HIV Test-and-Treat Trial (2013-2017), we tell our story of developing, evaluating, and implementing a machine learning-based approach for covariate adjustment. We provide the rationale for as well as the practical concerns with such an approach for estimating marginal effects. Using schematics, we illustrate our procedure: targeted machine learning estimation (TMLE) with Adaptive Pre-specification. Briefly, sample-splitting is used to data-adaptively select the combination of estimators of the outcome regression (i.e., the conditional expectation of the outcome given the trial arm and covariates) and known propensity score (i.e., the conditional probability of being randomized to the intervention given the covariates) that minimizes the cross-validated variance estimate and, thereby, maximizes empirical efficiency. We discuss our approach for evaluating finite sample performance with parametric and plasmode simulations, pre-specifying the Statistical Analysis Plan, and unblinding in real-time on video conference with our colleagues from around the world. We present the results from applying our approach in the primary, pre-specified analysis of 8 recently published trials (2022-2024). We conclude with practical recommendations and an invitation to implement our approach in the primary analysis of your next trial.

Mixture models are widely used in modeling heterogeneous data populations. A standard approach of mixture modeling is to assume that the mixture component takes a parametric kernel form, while the flexibility of the model can be obtained by using a large or possibly unbounded number of such parametric kernels. In many applications, making parametric assumptions on the latent subpopulation distributions may be unrealistic, which motivates the need for nonparametric modeling of the mixture components themselves. In this paper we study finite mixtures with nonparametric mixture components, using a Bayesian nonparametric modeling approach. In particular, it is assumed that the data population is generated according to a finite mixture of latent component distributions, where each component is endowed with a Bayesian nonparametric prior such as the Dirichlet process mixture. We present conditions under which the individual mixture component's distributions can be identified, and establish posterior contraction behavior for the data population's density, as well as densities of the latent mixture components. We develop an efficient MCMC algorithm for posterior inference and demonstrate via simulation studies and real-world data illustrations that it is possible to efficiently learn complex distributions for the latent subpopulations. In theory, the posterior contraction rate of the component densities is nearly polynomial, which is a significant improvement over the logarithm convergence rate of estimating mixing measures via deconvolution.

We propose a robust and scalable variational Bayes (VB) framework designed to effectively handle contamination and outliers in dataset. Our approach partitions the data into $m$ disjoint subsets and formulates a joint optimization problem based on robust aggregation principles. A key insight is that the full posterior distribution is equivalent to the minimizer of the mean Kullback-Leibler (KL) divergence from the $m$-powered local posterior distributions. To enhance robustness, we replace the mean KL divergence with a min-max median formulation. The min-max formulation not only ensures consistency between the KL minimizer and the Evidence Lower Bound (ELBO) maximizer but also facilitates the establishment of improved statistical rates for the mean of variational posterior. We observe a notable discrepancy in the $m$-powered marginal log likelihood function contingent on the presence of local latent variables. To address this, we treat these two scenarios separately to guarantee the consistency of the aggregated variational posterior. Specifically, when local latent variables are present, we introduce an aggregate-and-rescale strategy. Theoretically, we provide a non-asymptotic analysis of our proposed posterior, incorporating a refined analysis of Bernstein-von Mises (BvM) theorem to accommodate a diverging number of subsets $m$. Our findings indicate that the two-stage approach yields a smaller approximation error compared to directly aggregating the $m$-powered local posteriors. Furthermore, we establish a nearly optimal statistical rate for the mean of the proposed posterior, advancing existing theories related to min-max median estimators. The efficacy of our method is demonstrated through extensive simulation studies.

Proper quantification of predictive uncertainty is essential for the use of machine learning in safety-critical applications. V arious uncertainty measures have been proposed for this purpose, typically claiming superiority over other measures. In this paper, we argue that there is no single best measure. Instead, uncertainty quantification should be tailored to the specific application. To this end, we use a flexible family of uncertainty measures that distinguishes between total, aleatoric, and epistemic uncertainty of second-order distributions. These measures can be instantiated with specific loss functions, so-called proper scoring rules, to control their characteristics, and we show that different characteristics are useful for different tasks. In particular, we show that, for the task of selective prediction, the scoring rule should ideally match the task loss. On the other hand, for out-of-distribution detection, our results confirm that mutual information, a widely used measure of epistemic uncertainty, performs best. Furthermore, in an active learning setting, epistemic uncertainty based on zero-one loss is shown to consistently outperform other uncertainty measures.

Model selection is a pivotal process in the quantitative sciences, where researchers must navigate between numerous candidate models of varying complexity. Traditional information criteria, such as the corrected Akaike Information Criterion (AICc), Bayesian Information Criterion (BIC), and Mallows's $\mathit{C_p}$, are valuable tools for identifying optimal models. However, the exponential increase in candidate models with each additional model parameter renders the evaluation of these criteria for all models -- a strategy known as exhaustive, or brute-force, searches -- computationally prohibitive. Consequently, heuristic approaches like stepwise regression are commonly employed, albeit without guarantees of finding the globally-optimal model. In this study, we challenge the prevailing notion that non-monotonicity in information criteria precludes bounds on the search space. We introduce a simple but novel bound that enables the development of branch-and-bound algorithms tailored for these non-monotonic functions. We demonstrate that our approach guarantees identification of the optimal model(s) across diverse model classes, sizes, and applications, often with orders of magnitude computational speedups. For instance, in one previously-published model selection task involving $2^{32}$ (approximately 4 billion) candidate models, our method achieves a computational speedup exceeding 6,000. These findings have broad implications for the scalability and effectiveness of model selection in complex scientific domains.

Adaptive behavior in volatile environments requires agents to deploy different value-control regimes across latent contexts, but representing separate preferences, policy biases, and action confidence for every situation is intractable. We introduce value profiles: a small set of reusable bundles of value-related parameters--outcome preferences, policy priors, and policy precision--that are assigned to hidden states in the generative model. As posterior beliefs over states evolve trial-by-trial, effective control parameters emerge through belief-weighted mixing, enabling state-conditional strategy recruitment without maintaining independent parameters for each situation. We evaluate this framework in probabilistic reversal learning, comparing static precision, entropy-coupled dynamic precision, and profile-based models using cross-validated log-likelihood and information criteria. Model comparison using AIC favors the profile-based model over simpler alternatives ( 100-point differences), with consistent parameter recovery demonstrating structural identifiability even when context must be inferred from noisy observations. Model-based inference suggests that, in this task, adaptive control operates primarily through policy prior modulation rather than policy precision modulation, with gradual belief-driven profile recruitment confirming state-conditional rather than merely uncertainty-driven control. Overall, reusable value profiles provide a tractable computational account of belief-conditioned value control in volatile environments, providing a reusable, mode-like representational scheme for behavioral flexibility that yields testable signatures of belief-conditioned control.

For four decades statistical physics has been providing a framework to analyse neural networks. A long-standing question remained on its capacity to tackle deep learning models capturing rich feature learning effects, thus going beyond the narrow networks or kernel methods analysed until now. We positively answer through the study of the supervised learning of a multi-layer perceptron. Importantly, (i) its width scales as the input dimension, making it more prone to feature learning than ultra wide networks, and more expressive than narrow ones or ones with fixed embedding layers; and (ii) we focus on the challenging interpolation regime where the number of trainable parameters and data are comparable, which forces the model to adapt to the task. We consider the matched teacher-student setting. Therefore, we provide the fundamental limits of learning random deep neural network targets and identify the sufficient statistics describing what is learnt by an optimally trained network as the data budget increases. A rich phenomenology emerges with various learning transitions. With enough data, optimal performance is attained through the model's "specialisation" towards the target, but it can be hard to reach for training algorithms which get attracted by sub-optimal solutions predicted by the theory. Specialisation occurs inhomogeneously across layers, propagating from shallow towards deep ones, but also across neurons in each layer. Furthermore, deeper targets are harder to learn. Despite its simplicity, the Bayes-optimal setting provides insights on how the depth, non-linearity and finite (proportional) width influence neural networks in the feature learning regime that are potentially relevant in much more general settings.

The property of learning-curve monotonicity, highlighted in a recent series of work by Loog, Mey and Viering, describes algorithms which only improve in average performance given more data, for any underlying data distribution within a given family. We establish the first nontrivial monotonicity guarantees for the maximum likelihood estimator in a variety of well-specified parametric settings. For sequential prediction with log loss, we show monotonicity (in fact complete monotonicity) of the forward KL divergence for Gaussian vectors with unknown covariance and either known or unknown mean, as well as for Gamma variables with unknown scale parameter. The Gaussian setting was explicitly highlighted as open in the aforementioned works, even in dimension 1. Finally we observe that for reverse KL divergence, a folklore trick yields monotonicity for very general exponential families. All results in this paper were derived by variants of GPT-5.2 Pro. Humans did not provide any proof strategies or intermediate arguments, but only prompted the model to continue developing additional results, and verified and transcribed its proofs.

Topology identification and inference of processes evolving over graphs arise in timely applications involving brain, transportation, financial, power, as well as social and information networks. This chapter provides an overview of graph topology identification and statistical inference methods for multidimensional relational data. Approaches for undirected links connecting graph nodes are outlined, going all the way from correlation metrics to covariance selection, and revealing ties with smooth signal priors. To account for directional (possibly causal) relations among nodal variables and address the limitations of linear time-invariant models in handling dynamic as well as nonlinear dependencies, a principled framework is surveyed to capture these complexities through judiciously selected kernels from a prescribed dictionary. Generalizations are also described via structural equations and vector autoregressions that can exploit attributes such as low rank, sparsity, acyclicity, and smoothness to model dynamic processes over possibly time-evolving topologies. It is argued that this approach supports both batch and online learning algorithms with convergence rate guarantees, is amenable to tensor (that is, multi-way array) formulations as well as decompositions that are well-suited for multidimensional network data, and can seamlessly leverage high-order statistical information.

Causal discovery methods have traditionally been developed under two distinct regimes: independent and identically distributed (i.i.d.) and timeseries data, each governed by separate modelling assumptions. In this paper, we argue that the i.i.d. setting can and should be reframed in terms of exchangeability, a strictly more general symmetry principle. We present the implications of this reframing, alongside two core arguments: (1) a conceptual argument, based on extending the dependency of experimental causal inference on exchangeability to causal discovery; and (2) an empirical argument, showing that many existing i.i.d. causal-discovery methods are predicated on exchangeability assumptions, and that the sole extensive widely-used real-world "i.i.d." benchmark (the Tübingen dataset) consists mainly of exchangeable (and not i.i.d.) examples. Building on this insight, we introduce a novel synthetic dataset that enforces only the exchangeability assumption, without imposing the stronger i.i.d. assumption. We show that our exchangeable synthetic dataset mirrors the statistical structure of the real-world "i.i.d." dataset more closely than all other i.i.d. synthetic datasets. Furthermore, we demonstrate the predictive capability of this dataset by proposing a neural-network-based causal-discovery algorithm trained exclusively on our synthetic dataset, and which performs similarly to other state-of-the-art i.i.d. methods on the real-world benchmark.