A Multitask Active Learning Framework with Probabilistic Modeling for Multi-Species Acute Toxicity Prediction.

Predicting acute toxicity across species is essential for early-stage drug safety evaluation. While recent efforts have primarily focused on improving predictive accuracy, they often fail to address two critical issues: the substantial divergence in toxicity mechanisms among different species, and the inherent noise present in experimental data. To bridge this gap, we introduce a Probabilistic Multitask Active Learning (PMAL) framework for multi-species acute toxicity prediction. Our framework integrates two key modules: a Probabilistic Multitask Learning (PML) component which jointly models the predictive distributions of multiple toxicity endpoints from a probabilistic viewpoint, and an Uncertainty-based Active Learning (UAL) component which strategically selects the most informative compounds for experimental annotation based on predictive uncertainty. Empirical evaluations demonstrate that PMAL surpasses state-of-the-art methods and is capable of providing well-calibrated uncertainty estimates for small molecules across diverse toxicity endpoints. Beyond advancing multi-species toxicity prediction, the core design principles of PMAL offer a generalizable paradigm for learning in noisy multi-task environments.