PertMind: Eliciting Emergent Biological Reasoning in LLM via Reinforcement Learning on Cellular Perturbation Data

Large language models can describe mechanisms, yet scalable post-training still depends on costly, manually curated biological reasoning traces. Here we show that cellular perturbation atlases can instead become reinforcement-learning environments, where measured gene responses provide computable rewards for biological reasoning. We introduce PertMind, which combines trusted-trajectory supervised initialization with gene-, pathway-, and format-level reinforcement signals. Trained only on forward perturbation-response prediction, PertMind improved response inference in unseen cellular contexts while retaining general language capabilities. It also transferred without task-specific post-training to reverse perturbation identification, double-perturbation reasoning, phenotypic-screen prioritization, and biological-process interpretation. PertMind further generated biological profiles that supported competitive gene, cell, and donor representations across multiscale downstream tasks. These results support the hypothesis that reinforcement on experimental endpoints can concentrate reusable biological strategies already accessible to pretrained models. More broadly, perturbation-derived reinforcement learning offers a scalable route for transforming expanding experimental atlases into training environments for general-purpose biological reasoning.

AbLWR:A Context-Aware Listwise Ranking Framework for Antibody-Antigen Binding Affinity Prediction via Positive-Unlabeled Learning

Accurate prediction of antibody-antigen binding affinity is fundamental to therapeutic design, yet remains constrained by severe label sparsity and the complexity of antigenic variations. In this paper, we propose AbLWR (Antibody-antigen binding affinity List-Wise Ranking), a novel framework that reformulates the conventional affinity regression task as a listwise ranking problem. To mitigate label sparsity, AbLWR incorporates a PU (Positive-Unlabeled) learning mechanism leveraging a dual-level contrastive objective and meta-optimized label refinement to learn robust representations. Furthermore, we address antigenic variation by employing a homologous antigen sampling strategy where Multi-Head Self-Attention (MHSA) explicitly models inter-sample relationships within training lists to capture subtle affinity nuances. Extensive experiments demonstrate that AbLWR significantly outperforms state-of-the-art baselines, improving the Precision@1 (P@1) by over 10$\%$ in randomized cross-validation experiments. Notably, case studies on Influenza and IL-33 validate its practical utility, demonstrating robust ranking consistency in distinguishing subtle viral mutations and efficiently prioritizing top-tier candidates for wet-lab screening.