Antibody lead optimization is inherently a multi-objective challenge in drug discovery. Achieving a balance between different drug-like properties is crucial for the development of viable candidates, and this search becomes exponentially challenging as desired properties grow. The ever-growing zoo of sophisticated in silico tools for predicting antibody properties calls for an efficient joint optimization procedure to overcome resource-intensive sequential filtering pipelines. We present BOAT, a versatile Bayesian optimization framework for multi-property antibody engineering. Our `plug-and-play' framework couples uncertainty-aware surrogate modeling with a genetic algorithm to jointly optimize various predicted antibody traits while enabling efficient exploration of sequence space. Through systematic benchmarking against genetic algorithms and newer generative learning approaches, we demonstrate competitive performance with state-of-the-art methods for multi-objective protein optimization. We identify clear regimes where surrogate-driven optimization outperforms expensive generative approaches and establish practical limits imposed by sequence dimensionality and oracle costs.

We present mlr3mbo, a comprehensive and modular toolbox for Bayesian optimization in R. mlr3mbo supports single- and multi-objective optimization, multi-point proposals, batch and asynchronous parallelization, input and output transformations, and robust error handling. While it can be used for many standard Bayesian optimization variants in applied settings, researchers can also construct custom BO algorithms from its flexible building blocks. In addition to an introduction to the software, its design principles, and its building blocks, the paper presents two extensive empirical evaluations of the software on the surrogate-based benchmark suite YAHPO Gym. To identify robust default configurations for both numeric and mixed-hierarchical optimization regimes, and to gain further insights into the respective impacts of individual settings, we run a coordinate descent search over the mlr3mbo configuration space and analyze its results. Furthermore, we demonstrate that mlr3mbo achieves state-of-the-art performance by benchmarking it against a wide range of optimizers, including HEBO, SMAC3, Ax, and Optuna.

The use of transfer learning within Bayesian optimization addresses the disadvantages of the so-called \textit{cold start} problem by using source data to aid in the optimization of a target problem. We present a method that leverages an ensemble of surrogate models using transfer learning and integrates it in a constrained Bayesian optimization framework. We identify challenges particular to aircraft design optimization related to heterogeneous design variables and constraints. We propose the use of a partial-least-squares dimension reduction algorithm to address design space heterogeneity, and a \textit{meta} data surrogate selection method to address constraint heterogeneity. Numerical benchmark problems and an aircraft conceptual design optimization problem are used to demonstrate the proposed methods. Results show significant improvement in convergence in early optimization iterations compared to standard Bayesian optimization, with improved prediction accuracy for both objective and constraint surrogate models.

Preference-based many-objective optimization faces two obstacles: an expanding space of trade-offs and heterogeneous, context-dependent human value structures. Towards this, we propose a Bayesian framework that learns a small set of latent preference archetypes rather than assuming a single fixed utility function, modelling them as components of a Dirichlet-process mixture with uncertainty over both archetypes and their weights. To query efficiently, we designing hybrid queries that target information about (i) mode identity and (ii) within-mode trade-offs. Under mild assumptions, we provide a simple regret guarantee for the resulting mixture-aware Bayesian optimization procedure. Empirically, our method outperforms standard baselines on synthetic and real-world many-objective benchmarks, and mixture-aware diagnostics reveal structure that regret alone fails to capture.

Constrained optimization in high-dimensional black-box settings is difficult due to expensive evaluations, the lack of gradient information, and complex feasibility regions. In this work, we propose a Bayesian optimization method that combines a penalty formulation, a surrogate model, and a trust region strategy. The constrained problem is converted to an unconstrained form by penalizing constraint violations, which provides a unified modeling framework. A trust region restricts the search to a local region around the current best solution, which improves stability and efficiency in high dimensions. Within this region, we use the Expected Improvement acquisition function to select evaluation points by balancing improvement and uncertainty. The proposed Trust Region method integrates penalty-based constraint handling with local surrogate modeling. This combination enables efficient exploration of feasible regions while maintaining sample efficiency. We compare the proposed method with state-of-the-art methods on synthetic and real-world high-dimensional constrained optimization problems. The results show that the method identifies high-quality feasible solutions with fewer evaluations and maintains stable performance across different settings.

We present the first general purpose framework for marginal maximum a posteriori estimation of probabilistic program variables.

There is rapidly growing interest in using Bayesian optimization to tune model and inference hyperparameters for machine learning algorithms that take a long time to run. For example, Spearmint is a popular software package for selecting the optimal number of layers and learning rate in neural networks. But given that there is uncertainty about which hyperparameters give the best predictive performance, and given that fitting a model for each choice of hyperparameters is costly, it is arguably wasteful to throw away all but the best result, as per Bayesian optimization. A related issue is the danger of overfitting the validation data when optimizing many hyperparameters. In this paper, we consider an alternative approach that uses more samples from the hyperparameter selection procedure to average over the uncertainty in model hyperparameters. The resulting approach, empirical Bayes for hyperparameter averaging (EB-Hyp) predicts held-out data better than Bayesian optimization in two experiments on latent Dirichlet allocation and deep latent Gaussian models. EB-Hyp suggests a simpler approach to evaluating and deploying machine learning algorithms that does not require a separate validation data set and hyperparameter selection procedure.

Bayesian optimization is a prominent method for optimizing expensive to evaluate black-box functions that is prominently applied to tuning the hyperparameters of machine learning algorithms. Despite its successes, the prototypical Bayesian optimization approach - using Gaussian process models - does not scale well to either many hyperparameters or many function evaluations. Attacking this lack of scalability and flexibility is thus one of the key challenges of the field. We present a general approach for using flexible parametric models (neural networks) for Bayesian optimization, staying as close to a truly Bayesian treatment as possible. We obtain scalability through stochastic gradient Hamiltonian Monte Carlo, whose robustness we improve via a scale adaptation.

Gaussian Process bandit optimization has emerged as a powerful tool for optimizing noisy black box functions. One example in machine learning is hyper-parameter optimization where each evaluation of the target function may require training a model which may involve days or even weeks of computation. Most methods for this so-called "Bayesian optimization" only allow sequential exploration of the parameter space. However, it is often desirable to propose batches or sets of parameter values to explore simultaneously, especially when there are large parallel processing facilities at our disposal. Batch methods require modeling the interaction between the different evaluations in the batch, which can be expensive in complex scenarios. In this paper, we propose a new approach for parallelizing Bayesian optimization by modeling the diversity of a batch via Determinantal point processes (DPPs) whose kernels are learned automatically. This allows us to generalize a previous result as well as prove better regret bounds based on DPP sampling. Our experiments on a variety of synthetic and real-world robotics and hyper-parameter optimization tasks indicate that our DPP-based methods, especially those based on DPP sampling, outperform state-of-the-art methods.

Despite the success of kernel-based nonparametric methods, kernel selection still requires considerable expertise, and is often described as a "black art." We present a sophisticated method for automatically searching for an appropriate kernel from an infinite space of potential choices. Previous efforts in this direction have focused on traversing a kernel grammar, only examining the data via computation of marginal likelihood. Our proposed search method is based on Bayesian optimization in model space, where we reason about model evidence as a function to be maximized. We explicitly reason about the data distribution and how it induces similarity between potential model choices in terms of the explanations they can offer for observed data. In this light, we construct a novel kernel between models to explain a given dataset. Our method is capable of finding a model that explains a given dataset well without any human assistance, often with fewer computations of model evidence than previous approaches, a claim we demonstrate empirically.