Case-Guided Sequential Assay Planning in Drug Discovery

Tianchi Chen, Jan Bíma, Otto Ritter, Sean L. Wu, Bingjia Yang, Xiang Yu

Keywords: Model-Based Reinforcement Learning, Drug Discovery, Sequential Experimental Design, Simulator-Free Methods.

TL;DR: Our paper introduces a reinforcement learning framework that plans scientific experiments by treating similar historical data as an implicit simulator, enabling effective planning where explicit models are unavailable

Abstract: Optimally sequencing experimental assays in drug discovery is a high-stakes planning problem under severe uncertainty and resource constraints. A primary obstacle for standard reinforcement learning (RL) is the absence of an explicit environment simulator or transition data $(s, a, s')$; planning must rely solely on a static database of historical outcomes. We introduce the Implicit Bayesian Markov Decision Process (IBMDP), a model-based RL framework designed for such simulator-free settings. IBMDP constructs a case-guided implicit model of transition dynamics by forming a nonparametric belief distribution using similar historical outcomes. This mechanism enables Bayesian belief updating as evidence accumulates and employs ensemble MCTS planning to generate stable policies that balance information gain toward desired outcomes with resource efficiency. We validate IBMDP through comprehensive experiments. On a real-world central nervous system (CNS) drug discovery task, IBMDP reduced resource consumption by up to 92\% compared to established heuristics while maintaining decision confidence. To rigorously assess decision quality, we also benchmarked IBMDP in a synthetic environment with a computable optimal policy. Our framework achieves significantly higher alignment with this optimal policy than a deterministic value iteration alternative that uses the same similarity-based model, demonstrating the superiority of our ensemble planner. IBMDP offers a practical solution for sequential experimental design in data-rich but simulator-poor domains.

Primary Area: applications to physical sciences (physics, chemistry, biology, etc.)

Submission Number: 8343