Showing 1–6 of 6 results for author: Jones, H T

Adversarial Query Synthesis via Bayesian Optimization

Authors: Jeffrey Tao, Yimeng Zeng, Haydn Thomas Jones, Natalie Maus, Osbert Bastani, Jacob R. Gardner, Ryan Marcus

Abstract: Benchmark workloads are extremely important to the database management research community, especially as more machine learning components are integrated into database systems. Here, we propose a Bayesian optimization technique to automatically search for difficult benchmark queries, significantly reducing the amount of manual effort usually required. In preliminary experiments, we show that our ap… ▽ More Benchmark workloads are extremely important to the database management research community, especially as more machine learning components are integrated into database systems. Here, we propose a Bayesian optimization technique to automatically search for difficult benchmark queries, significantly reducing the amount of manual effort usually required. In preliminary experiments, we show that our approach can generate queries with more than double the optimization headroom compared to existing benchmarks. △ Less

Submitted 2 March, 2026; originally announced March 2026.

Purely Agentic Black-Box Optimization for Biological Design

Authors: Natalie Maus, Yimeng Zeng, Haydn Thomas Jones, Yining Huang, Gaurav Ng Goel, Alden Rose, Kyurae Kim, Hyun-Su Lee, Marcelo Der Torossian Torres, Fangping Wan, Cesar de la Fuente-Nunez, Mark Yatskar, Osbert Bastani, Jacob R. Gardner

Abstract: Many key challenges in biological design-such as small-molecule drug discovery, antimicrobial peptide development, and protein engineering-can be framed as black-box optimization over vast, complex structured spaces. Existing methods rely mainly on raw structural data and struggle to exploit the rich scientific literature. While large language models (LLMs) have been added to these pipelines, they… ▽ More Many key challenges in biological design-such as small-molecule drug discovery, antimicrobial peptide development, and protein engineering-can be framed as black-box optimization over vast, complex structured spaces. Existing methods rely mainly on raw structural data and struggle to exploit the rich scientific literature. While large language models (LLMs) have been added to these pipelines, they have been confined to narrow roles within structure-centered optimizers. We instead cast biological black-box optimization as a fully agentic, language-based reasoning process. We introduce Purely Agentic BLack-box Optimization (PABLO), a hierarchical agentic system that uses scientific LLMs pretrained on chemistry and biology literature to generate and iteratively refine biological candidates. On both the standard GuacaMol molecular design and antimicrobial peptide optimization tasks, PABLO achieves state-of-the-art performance, substantially improving sample efficiency and final objective values over established baselines. Compared to prior optimization methods that incorporate LLMs, PABLO achieves competitive token usage per run despite relying on LLMs throughout the optimization loop. Beyond raw performance, the agentic formulation offers key advantages for realistic design: it naturally incorporates semantic task descriptions, retrieval-augmented domain knowledge, and complex constraints. In follow-up in vitro validation, PABLO-optimized peptides showed strong activity against drug-resistant pathogens, underscoring the practical potential of PABLO for therapeutic discovery. △ Less

Submitted 29 January, 2026; originally announced January 2026.

A Dataset for Distilling Knowledge Priors from Literature for Therapeutic Design

Authors: Haydn Thomas Jones, Natalie Maus, Josh Magnus Ludan, Maggie Ziyu Huan, Jiaming Liang, Marcelo Der Torossian Torres, Jiatao Liang, Zachary Ives, Yoseph Barash, Cesar de la Fuente-Nunez, Jacob R. Gardner, Mark Yatskar

Abstract: AI-driven discovery can greatly reduce design time and enhance new therapeutics' effectiveness. Models using simulators explore broad design spaces but risk violating implicit constraints due to a lack of experimental priors. For example, in a new analysis we performed on a diverse set of models on the GuacaMol benchmark using supervised classifiers, over 60\% of molecules proposed had high probab… ▽ More AI-driven discovery can greatly reduce design time and enhance new therapeutics' effectiveness. Models using simulators explore broad design spaces but risk violating implicit constraints due to a lack of experimental priors. For example, in a new analysis we performed on a diverse set of models on the GuacaMol benchmark using supervised classifiers, over 60\% of molecules proposed had high probability of being mutagenic. In this work, we introduce Medex, a dataset of priors for design problems extracted from literature describing compounds used in lab settings. It is constructed with LLM pipelines for discovering therapeutic entities in relevant paragraphs and summarizing information in concise fair-use facts. Medex consists of 32.3 million pairs of natural language facts, and appropriate entity representations (i.e. SMILES or refseq IDs). To demonstrate the potential of the data, we train LLM, CLIP, and LLava architectures to reason jointly about text and design targets and evaluate on tasks from the Therapeutic Data Commons (TDC). Medex is highly effective for creating models with strong priors: in supervised prediction problems that use our data as pretraining, our best models with 15M learnable parameters outperform larger 2B TxGemma on both regression and classification TDC tasks, and perform comparably to 9B models on average. Models built with Medex can be used as constraints while optimizing for novel molecules in GuacaMol, resulting in proposals that are safer and nearly as effective. We release our dataset at https://huggingface.co/datasets/medexanon/Medex, and will provide expanded versions as available literature grows. △ Less

Submitted 11 September, 2025; v1 submitted 14 August, 2025; originally announced August 2025.

Large Scale Multi-Task Bayesian Optimization with Large Language Models

Authors: Yimeng Zeng, Natalie Maus, Haydn Thomas Jones, Jeffrey Tao, Fangping Wan, Marcelo Der Torossian Torres, Cesar de la Fuente-Nunez, Ryan Marcus, Osbert Bastani, Jacob R. Gardner

Abstract: In multi-task Bayesian optimization, the goal is to leverage experience from optimizing existing tasks to improve the efficiency of optimizing new ones. While approaches using multi-task Gaussian processes or deep kernel transfer exist, the performance improvement is marginal when scaling beyond a moderate number of tasks. We introduce a novel approach leveraging large language models (LLMs) to le… ▽ More In multi-task Bayesian optimization, the goal is to leverage experience from optimizing existing tasks to improve the efficiency of optimizing new ones. While approaches using multi-task Gaussian processes or deep kernel transfer exist, the performance improvement is marginal when scaling beyond a moderate number of tasks. We introduce a novel approach leveraging large language models (LLMs) to learn from, and improve upon, previous optimization trajectories, scaling to approximately 1500 distinct tasks. Specifically, we propose a feedback loop in which an LLM is fine-tuned on the high quality solutions to specific tasks found by Bayesian optimization (BO). This LLM is then used to generate initialization points for future BO searches for new tasks. The trajectories of these new searches provide additional training data for fine-tuning the LLM, completing the loop. We evaluate our method on two distinct domains: database query optimization and antimicrobial peptide design. Results demonstrate that our approach creates a positive feedback loop, where the LLM's generated initializations gradually improve, leading to better optimization performance. As this feedback loop continues, we find that the LLM is eventually able to generate solutions to new tasks in just a few shots that are better than the solutions produced by "from scratch" by Bayesian optimization while simultaneously requiring significantly fewer oracle calls. △ Less

Submitted 12 June, 2025; v1 submitted 11 March, 2025; originally announced March 2025.

Covering Multiple Objectives with a Small Set of Solutions Using Bayesian Optimization

Authors: Natalie Maus, Kyurae Kim, Yimeng Zeng, Haydn Thomas Jones, Fangping Wan, Marcelo Der Torossian Torres, Cesar de la Fuente-Nunez, Jacob R. Gardner

Abstract: In multi-objective black-box optimization, the goal is typically to find solutions that optimize a set of $T$ black-box objective functions, $f_1, \ldots f_T$, simultaneously. Traditional approaches often seek a single Pareto-optimal set that balances trade-offs among all objectives. In contrast, we consider a problem setting that departs from this paradigm: finding a small set of $K < T$ solution… ▽ More In multi-objective black-box optimization, the goal is typically to find solutions that optimize a set of $T$ black-box objective functions, $f_1, \ldots f_T$, simultaneously. Traditional approaches often seek a single Pareto-optimal set that balances trade-offs among all objectives. In contrast, we consider a problem setting that departs from this paradigm: finding a small set of $K < T$ solutions, that collectively "cover" the $T$ objectives. A set of solutions is defined as "covering" if, for each objective $f_1, \ldots f_T$, there is at least one good solution. A motivating example for this problem setting occurs in drug design. For example, we may have $T$ pathogens and aim to identify a set of $K < T$ antibiotics such that at least one antibiotic can be used to treat each pathogen. This problem, known as coverage optimization, has yet to be tackled with the Bayesian optimization (BO) framework. To fill this void, we develop Multi-Objective Coverage Bayesian Optimization (MOCOBO), a BO algorithm for solving coverage optimization. Our approach is based on a new acquisition function reminiscent of expected improvement in the vanilla BO setup. We demonstrate the performance of our method on high-dimensional black-box optimization tasks, including applications in peptide and molecular design. Results show that the coverage of the $K < T$ solutions found by MOCOBO matches or nearly matches the coverage of $T$ solutions obtained by optimizing each objective individually. Furthermore, in in vitro experiments, the peptides found by MOCOBO exhibited high potency against drug-resistant pathogens, further demonstrating the potential of MOCOBO for drug discovery. All of our code is publicly available at the following link: https://github.com/nataliemaus/mocobo. △ Less

Submitted 27 October, 2025; v1 submitted 31 January, 2025; originally announced January 2025.

Local Latent Space Bayesian Optimization over Structured Inputs

Authors: Natalie Maus, Haydn T. Jones, Juston S. Moore, Matt J. Kusner, John Bradshaw, Jacob R. Gardner

Abstract: Bayesian optimization over the latent spaces of deep autoencoder models (DAEs) has recently emerged as a promising new approach for optimizing challenging black-box functions over structured, discrete, hard-to-enumerate search spaces (e.g., molecules). Here the DAE dramatically simplifies the search space by mapping inputs into a continuous latent space where familiar Bayesian optimization tools c… ▽ More Bayesian optimization over the latent spaces of deep autoencoder models (DAEs) has recently emerged as a promising new approach for optimizing challenging black-box functions over structured, discrete, hard-to-enumerate search spaces (e.g., molecules). Here the DAE dramatically simplifies the search space by mapping inputs into a continuous latent space where familiar Bayesian optimization tools can be more readily applied. Despite this simplification, the latent space typically remains high-dimensional. Thus, even with a well-suited latent space, these approaches do not necessarily provide a complete solution, but may rather shift the structured optimization problem to a high-dimensional one. In this paper, we propose LOL-BO, which adapts the notion of trust regions explored in recent work on high-dimensional Bayesian optimization to the structured setting. By reformulating the encoder to function as both an encoder for the DAE globally and as a deep kernel for the surrogate model within a trust region, we better align the notion of local optimization in the latent space with local optimization in the input space. LOL-BO achieves as much as 20 times improvement over state-of-the-art latent space Bayesian optimization methods across six real-world benchmarks, demonstrating that improvement in optimization strategies is as important as developing better DAE models. △ Less

Submitted 22 February, 2023; v1 submitted 27 January, 2022; originally announced January 2022.