arXiv subjects

Barbara Engelhardt

Publications and source records attributed to Barbara Engelhardt.

10 recordsLinked to original sources

arXiv2026

Compartment-driven Gaussian processes for uncertainty quantification of pharmacokinetic exposures

Pharmacokinetic modeling is a crucial part of drug development. An important goal is to estimate patients' total and peak exposure to a drug over time, quantified by the area under the concentration--time curve (AUC) and the maximum concentration ($C_{\max}$) respectively. Such exposure assessment is essential to balance efficacy and safety in medications that offer therapeutic benefits but carry risks of toxicity, such as chemotherapy drugs. Uncertainty quantification for exposure quantities, however, remains challenging, since they are functionals of an often sparsely observed concentration--time curve with measurement errors. We propose a compartment-driven Gaussian process framework that propagates uncertainty in concentration--time curves to pharmacokinetic exposure functionals. Our approach uses pharmacokinetic compartmental models to specify a mechanistically informed prior and Gaussian processes to accommodate departures from the assumed pharmacokinetic dynamics. The framework can accommodate both individual-level and group-aggregated concentration--time data commonly seen in practice. We provide straightforward computational procedures for drawing posterior inference on AUC and $C_{\max}$. Simulations across a range of observation schemes demonstrate robustness to departures from the assumed compartmental dynamics. We apply the method to patient-level datasets on warfarin and theophylline, and aggregated data from a chemotherapy study of 5-fluorouracil and capecitabine in patients with normal or impaired hepatic function. The chemotherapy analysis quantifies drug-specific exposure differences between groups with differing liver function, with potential implications for informing dosing decisions.

stat.AP↗

arXiv2026

Intrinsic Gradient Barriers in Pushforward Deep Generative Models

Broad classes of deep generative models (DGMs) operate by learning to map a simple source distribution, such as a standard Gaussian, to a complex high-dimensional target distribution. Despite their success, DGMs often empirically struggle to accurately represent distributions with heavy tails or well-separated modes. In this work, we show that these difficulties reflect intrinsic properties of the underlying transport problem rather than particular neural network architectures or training procedures. We establish quantitative lower bounds on the gradients and Jacobians of pushforward mappings that transport log-concave source distributions to such targets. For heavy-tailed target distributions, the required gradient magnitude grows as the target develops increasingly large moments. For multimodal target distributions, the low-probability regions between well-separated modes similarly force large gradients in the transport map. We discuss how such large derivatives relate to trade-offs between expressivity and numerical stability. Our results hold under substantially weaker regularity conditions than previous analyses and remain stable under perturbations of the target distribution. Finally, we show that these obstructions can be mitigated when the goal is approximation of a given density rather than generative modeling. Specifically, we propose simple classes of bijective reparametrizations that can alleviate the difficult geometric structure and reduce the gradient burden placed on the learned generative map. Numerical experiments support our theoretical analysis.

stat.ML↗

arXiv2025

Non-Myopic Multi-Objective Bayesian Optimization

We consider the problem of finite-horizon sequential experimental design to solve multi-objective optimization (MOO) of expensive black-box objective functions. This problem arises in many real-world applications, including materials design, where we have a small resource budget to make and evaluate candidate materials in the lab. We solve this problem using the framework of Bayesian optimization (BO) and propose the first set of non-myopic methods for MOO problems. Prior work on non-myopic BO for single-objective problems relies on the Bellman optimality principle to handle the lookahead reasoning process. However, this principle does not hold for most MOO problems because the reward function needs to satisfy some conditions: scalar variable, monotonicity, and additivity. We address this challenge by using hypervolume improvement (HVI) as our scalarization approach, which allows us to use a lower-bound on the Bellman equation to approximate the finite-horizon using a batch expected hypervolume improvement (EHVI) acquisition function (AF) for MOO. Our formulation naturally allows us to use other improvement-based scalarizations and compare their efficacy to HVI. We derive three non-myopic AFs for MOBO: 1) the Nested AF, which is based on the exact computation of the lower bound, 2) the Joint AF, which is a lower bound on the nested AF, and 3) the BINOM AF, which is a fast and approximate variant based on batch multi-objective acquisition functions. Our experiments on multiple diverse real-world MO problems demonstrate that our non-myopic AFs substantially improve performance over the existing myopic AFs for MOBO.

cs.LG↗

arXiv2025

Sample Efficient Preference Alignment in LLMs via Active Exploration

Preference-based feedback is important for many applications in machine learning where evaluation of a reward function is not feasible. Notable recent examples arise in preference alignment for large language models, including in reinforcement learning from human feedback (RLHF) and direct preference optimization (DPO). For many applications of preference alignment, the cost of acquiring human feedback can be substantial. In this work, we take advantage of the fact that one can often choose contexts at which to obtain human feedback to most efficiently identify a good policy, and formalize the setting as an active contextual dueling bandit problem. We propose an active exploration algorithm to efficiently select the data and provide theoretical proof that it has a polynomial worst-case regret bound. We extend the setting and methodology for practical use in preference alignment of large language models. We provide two extensions, an online and an offline approach. Our method outperforms the baselines with limited samples of human preferences on several language models and four real-world datasets including two new datasets that we contribute to the literature.

cs.LG↗

arXiv2024

Active Learning for Derivative-Based Global Sensitivity Analysis with Gaussian Processes

We consider the problem of active learning for global sensitivity analysis of expensive black-box functions. Our aim is to efficiently learn the importance of different input variables, e.g., in vehicle safety experimentation, we study the impact of the thickness of various components on safety objectives. Since function evaluations are expensive, we use active learning to prioritize experimental resources where they yield the most value. We propose novel active learning acquisition functions that directly target key quantities of derivative-based global sensitivity measures (DGSMs) under Gaussian process surrogate models. We showcase the first application of active learning directly to DGSMs, and develop tractable uncertainty reduction and information gain acquisition functions for these measures. Through comprehensive evaluation on synthetic and real-world problems, our study demonstrates how these active learning acquisition strategies substantially enhance the sample efficiency of DGSM estimation, particularly with limited evaluation budgets. Our work paves the way for more efficient and accurate sensitivity analysis in various scientific and engineering applications.

cs.LG↗

arXiv2024

Automating Transparency Mechanisms in the Judicial System Using LLMs: Opportunities and Challenges

Bringing more transparency to the judicial system for the purposes of increasing accountability often demands extensive effort from auditors who must meticulously sift through numerous disorganized legal case files to detect patterns of bias and errors. For example, the high-profile investigation into the Curtis Flowers case took seven reporters a full year to assemble evidence about the prosecutor's history of selecting racially biased juries. LLMs have the potential to automate and scale these transparency pipelines, especially given their demonstrated capabilities to extract information from unstructured documents. We discuss the opportunities and challenges of using LLMs to provide transparency in two important court processes: jury selection in criminal trials and housing eviction cases.

cs.CY↗

arXiv2024

Compositional Q-learning for electrolyte repletion with imbalanced patient sub-populations

Reinforcement learning (RL) is an effective framework for solving sequential decision-making tasks. However, applying RL methods in medical care settings is challenging in part due to heterogeneity in treatment response among patients. Some patients can be treated with standard protocols whereas others, such as those with chronic diseases, need personalized treatment planning. Traditional RL methods often fail to account for this heterogeneity, because they assume that all patients respond to the treatment in the same way (i.e., transition dynamics are shared). We introduce Compositional Fitted $Q$-iteration (CFQI), which uses a compositional task structure to represent heterogeneous treatment responses in medical care settings. A compositional task consists of several variations of the same task, each progressing in difficulty; solving simpler variants of the task can enable efficient solving of harder variants. CFQI uses a compositional $Q$-value function with separate modules for each task variant, allowing it to take advantage of shared knowledge while learning distinct policies for each variant. We validate CFQI's performance using a Cartpole environment and use CFQI to recommend electrolyte repletion for patients with and without renal disease. Our results demonstrate that CFQI is robust even in the presence of class imbalance, enabling effective information usage across patient sub-populations. CFQI exhibits great promise for clinical applications in scenarios characterized by known compositional structures.

cs.LG↗

arXiv2021

Probabilistic Contrastive Principal Component Analysis

Dimension reduction is useful for exploratory data analysis. In many applications, it is of interest to discover variation that is enriched in a "foreground" dataset relative to a "background" dataset. Recently, contrastive principal component analysis (CPCA) was proposed for this setting. However, the lack of a formal probabilistic model makes it difficult to reason about CPCA and to tune its hyperparameter. In this work, we propose probabilistic contrastive principal component analysis (PCPCA), a model-based alternative to CPCA. We discuss how to set the hyperparameter in theory and in practice, and we show several of PCPCA's advantages over CPCA, including greater interpretability, uncertainty quantification and principled inference, robustness to noise and missing data, and the ability to generate data from the model. We demonstrate PCPCA's performance through a series of simulations and case-control experiments with datasets of gene expression, protein expression, and images.

stat.ME↗

arXiv2017

AdaCluster : Adaptive Clustering for Heterogeneous Data

Clustering algorithms start with a fixed divergence, which captures the possibly asymmetric distance between a sample and a centroid. In the mixture model setting, the sample distribution plays the same role. When all attributes have the same topology and dispersion, the data are said to be homogeneous. If the prior knowledge of the distribution is inaccurate or the set of plausible distributions is large, an adaptive approach is essential. The motivation is more compelling for heterogeneous data, where the dispersion or the topology differs among attributes. We propose an adaptive approach to clustering using classes of parametrized Bregman divergences. We first show that the density of a steep exponential dispersion model (EDM) can be represented with a Bregman divergence. We then propose AdaCluster, an expectation-maximization (EM) algorithm to cluster heterogeneous data using classes of steep EDMs. We compare AdaCluster with EM for a Gaussian mixture model on synthetic data and nine UCI data sets. We also propose an adaptive hard clustering algorithm based on Generalized Method of Moments. We compare the hard clustering algorithm with k-means on the UCI data sets. We empirically verified that adaptively learning the underlying topology yields better clustering of heterogeneous data.

cs.LG↗

arXiv2016

A Divide and Conquer Strategy for High Dimensional Bayesian Factor Models

We propose a distributed computing framework, based on a divide and conquer strategy and hierarchical modeling, to accelerate posterior inference for high-dimensional Bayesian factor models. Our approach distributes the task of high-dimensional covariance matrix estimation to multiple cores, solves each subproblem separately via a latent factor model, and then combines these estimates to produce a global estimate of the covariance matrix. Existing divide and conquer methods focus exclusively on dividing the total number of observations $n$ into subsamples while keeping the dimension $p$ fixed. Our approach is novel in this regard: it includes all of the $n$ samples in each subproblem and, instead, splits the dimension $p$ into smaller subsets for each subproblem. The subproblems themselves can be challenging to solve when $p$ is large due to the dependencies across dimensions. To circumvent this issue, we specify a novel hierarchical structure on the latent factors that allows for flexible dependencies across dimensions, while still maintaining computational efficiency. Our approach is readily parallelizable and is shown to have computational efficiency of several orders of magnitude in comparison to fitting a full factor model. We report the performance of our method in synthetic examples and a genomics application.

stat.ME↗