Sample Efficiency Matters: A Benchmark for Practical Molecular Optimization

Molecular optimization is a fundamental goal in the chemical sciences and is of central interest to drug and material design. In recent years, significant progress has been made in solving challenging problems across various aspects of computational molecular optimizations, emphasizing high validity, diversity, and, most recently, synthesizability. Despite this progress, many papers report results on trivial or self-designed tasks, bringing additional challenges to directly assessing the performance of new methods. Moreover, the sample efficiency of the optimization--the number of molecules evaluated by the oracle--is rarely discussed, despite being an essential consideration for realistic discovery applications. To fill this gap, we have created an open-source benchmark for practical molecular optimization, PMO, to facilitate the transparent and reproducible evaluation of algorithmic advances in molecular optimization. This paper thoroughly investigates the performance of 25 molecular design algorithms on 23 tasks with a particular focus on sample efficiency. Our results show that most "state-of-the-art" methods fail to outperform their predecessors under a limited oracle budget allowing 10K queries and that no existing algorithm can efficiently solve certain molecular optimization problems in this setting. We analyze the influence of the optimization algorithm choices, molecular assembly strategies, and oracle landscapes on the optimization performance to inform future algorithm development and benchmarking. PMO provides a standardized experimental setup to comprehensively evaluate and compare new molecule optimization methods with existing ones. All code can be found at https://github.com/wenhao-gao/mol_opt

Sample-efficient Multi-objective Molecular Optimization with GFlowNets

Many crucial scientific problems involve designing novel molecules with desired properties, which can be formulated as a black-box optimization problem over the discrete chemical space. In practice, multiple conflicting objectives and costly evaluations (e.g., wet-lab experiments) make the diversity of candidates paramount. Computational methods have achieved initial success but still struggle with considering diversity in both objective and search space. To fill this gap, we propose a multi-objective Bayesian optimization (MOBO) algorithm leveraging the hypernetwork-based GFlowNets (HN-GFN) as an acquisition function optimizer, with the purpose of sampling a diverse batch of candidate molecular graphs from an approximate Pareto front. Using a single preference-conditioned hypernetwork, HN-GFN learns to explore various trade-offs between objectives. We further propose a hindsight-like off-policy strategy to share high-performing molecules among different preferences in order to speed up learning for HN-GFN. We empirically illustrate that HN-GFN has adequate capacity to generalize over preferences. Moreover, experiments in various real-world MOBO settings demonstrate that our framework predominantly outperforms existing methods in terms of candidate quality and sample efficiency. The code is available at https://github.com/violet-sto/HN-GFN.Comment: NeurIPS 202

Machine Learning Guided Discovery and Design for Inertial Confinement Fusion

Inertial confinement fusion (ICF) experiments at the National Ignition Facility (NIF) and their corresponding computer simulations produce an immense amount of rich data. However, quantitatively interpreting that data remains a grand challenge. Design spaces are vast, data volumes are large, and the relationship between models and experiments may be uncertain. We propose using machine learning to aid in the design and understanding of ICF implosions by integrating simulation and experimental data into a common frame-work. We begin by illustrating an early success of this data-driven design approach which resulted in the discovery of a new class of high performing ovoid-shaped implosion simulations. The ovoids achieve robust performance from the generation of zonal flows within the hotspot, revealing physics that had not previously been observed in ICF capsules. The ovoid discovery also revealed deficiencies in common machine learning algorithms for modeling ICF data. To overcome these inadequacies, we developed a novel algorithm, deep jointly-informed neural networks (DJINN), which enables non-data scientists to quickly train neural networks on their own datasets. DJINN is routinely used for modeling data ICF data and for a variety of other applications (uncertainty quantification; climate, nuclear, and atomic physics data). We demonstrate how DJINN is used to perform parameter inference tasks for NIF data, and how transfer learning with DJINN enables us to create predictive models of direct drive experiments at the Omega laser facility. Much of this work focuses on scalar or modest-size vector data, however many ICF diagnostics produce a variety of images, spectra, and sequential data. We end with a brief exploration of sequence-to-sequence models for emulating time-dependent multiphysics systems of varying complexity. This is a first step toward incorporating multimodal time-dependent data into our analyses to better constrain our predictive models

Tuning a variational autoencoder for data accountability problem in the Mars Science Laboratory ground data system

The Mars Curiosity rover is frequently sending back engineering and science data that goes through a pipeline of systems before reaching its final destination at the mission operations center making it prone to volume loss and data corruption. A ground data system analysis (GDSA) team is charged with the monitoring of this flow of information and the detection of anomalies in that data in order to request a re-transmission when necessary. This work presents $\Delta$-MADS, a derivative-free optimization method applied for tuning the architecture and hyperparameters of a variational autoencoder trained to detect the data with missing patches in order to assist the GDSA team in their mission