用真实实验数据驱动的生成模型,加速科学发现中的未知设计搜索。
Large Discovery Models: Empirically-grounded Model-Based Open-Ended Search

- 结合生成模型与贝叶斯奖励预测器,实现不确定性感知的候选优化。
- 在分子、抗体和神经网络设计中分别提升2.4倍、18.2%和60%以上性能。
- 适合需要高效探索开放假设空间的科研人员,如药物和材料设计者。
科学发现常需在庞大、结构化且开放式的假设空间(如分子、蛋白序列、计算机程序)中优化昂贵的评估目标。生成模型(如大语言模型,LLMs)虽能提供丰富的先验,但其似然值和自我评估难以准确反映真实目标或校准认知不确定性,尤其对分布外的新候选。本文提出大型发现模型(LDM),一种基于实证的递归架构,将生成模型与贝叶斯非参数奖励代理模型相结合。生成模型提出并优化候选设计,代理模型预测性能并量化不确定性,生成不确定性感知的价值以指导候选生成、精炼与选择。随着每条新实验观测结果的到达,发现记忆与代理模型持续更新。我们在三种不同设计模态与目标的任务中评估了LDM:神经网络训练、抗体设计和分子优化。相比仅使用LLM反思或传统统计搜索方法,LDM在验证BPB上减少2.4倍,在结合能上降低18.2%,在分子多目标性能上提升超过60%。结果表明,LDM可作为通用发现引擎,有效搜索开放式假设空间。
原文摘要 · Abstract (English)
Scientific discovery often involves optimising expensive-to-evaluate objectives over vast, structured, and open-ended hypothesis spaces, such as molecules, protein sequences, and computer programs. Generative models such as large language models (LLMs) provide expressive priors over such spaces, but their likelihoods and self-assessments are unreliable proxies for the objectives and calibrated epistemic uncertainty, especially for novel candidates outside the observed data distribution. We introduce the Large Discovery Model (LDM), an empirically grounded recurrent architecture that couples a generative model with a Bayesian non-parametric reward surrogate model. The generative model proposes and refines candidate designs, while the surrogate predicts their performance and quantifies uncertainty, yielding an uncertainty-aware value that guides candidate generation, refinement, and selection. The discovery memory and the surrogate model are continually updated as each new experimental observation arrives. We evaluate LDM on three scenarios spanning different design modalities and objectives, including neural-network training, antibody design, and molecular optimisation. Compared to LLM-only reflection or traditional statistical search across these domains, LDM achieves a $2.4\times$ greater reduction in validation BPB, an $18.2\%$ relative decrease in binding energy, and more than $60\%$ relative gains in molecular multi-objective performance. These results suggests that LDM could serve as a general-purpose discovery engine for effective search over open-ended hypothesis spaces.
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