iGC: Antibody Optimization via Reinforcement Learning over a Learned Somatic Hypermutation Prior
Thao Nguyen, Robert G. Alberstein, Ewa Nowara, Homa MohammadiPeyhani, Holly R. Steach, Sarah A. Robinson, Yuval Shechter, Donald W. Lee 等 13 位作者
AI 速览：iGC 是一个两阶段强化学习框架，先学习体细胞超突变先验，再在抗原特异性亲和力优化中结合 KL 正则与奖励税元梯度，以兼顾生物学合理的突变与结合优化。
Antibody affinity maturation is a natural optimization process in which B cells acquire mutations through somatic hypermutation (SHM), undergo selection for improved antigen binding, and iteratively evolve toward higher affinity. Computationally modeling this process requires capturing both biologically plausible mutations and antigen-specific selection. However, existing mutation models do not directly optimize binding, while affinity optimization often neglects realistic mutation trajectories. We introduce iGC (in silico Germinal Centers), a two-stage reinforcement learning (RL) framework for antigen-specific antibody optimization. Stage 1 learns an SHM mutation prior from parent-child pairs in B-cell lineage trees and adapts it to a target affinity-maturation dataset. Stage 2 initializes an RL policy from this prior and optimizes antigen binding with Kullback-Leibler (KL) regularization toward the frozen prior. To prevent reward exploitation, including repetitive high-reward substitutions and structurally tolerated framework mutations, we introduce a Reward-Tax Meta-Gradient objective. RewardNet smooths the affinity landscape, while TaxNet penalizes reward overexploitation, jointly defining a learned meta-reward for policy optimization. We evaluate iGC on mutation prediction, SHM consistency, affinity optimization, and mutation diversity. The mutation prior more than doubles the strongest baseline in mutation-site prediction. Following RL optimization, iGC maintains SHM sequence structure. It also achieves a strong exploration-exploitation balance, yielding competitive reward-diversity products across candidate-selection cutoffs. These results demonstrate that iGC integrates biologically plausible mutation generation with antigen-specific affinity selection, providing an in silico framework for iterative antibody affinity maturation.
Louis Bradshaw, Irmak Bukey, Daniel Chenyu Lin, John Thickstun, Chris Donahue
Multimodal language models continue to improve on broad music understanding benchmarks, but which musical features can they perceive and reason about? We investigate this question by introducing PianoBench, a benchmark that tasks language models with reasoning about musical performances across congruent acoustic and symbolic input representations. PianoBench is derived from our new multimodal, training-scale dataset comprising more than 20,000 hours of interleaved transcripts of music and spoken musical commentary from instructional piano videos. Open-weight audio-language models achieve at most 52.8% accuracy on PianoBench, and at best only modestly outperform their accuracy on a no-audio control. In contrast, frontier models using chain of thought achieve up to 93.2% accuracy when provided transcripts of music as text, exposing a gap between perceiving musical features from audio and reasoning about musical events when they are given explicitly. We then test whether mid-training on interleaved musical instruction can improve question answering without chain of thought, raising Qwen 3.5 9B Base's zero-shot accuracy on PianoBench with music transcripts from 42.8% to 56.0% after instruction tuning. These experiments suggest that instructional videos may represent an overlooked source of multimodal supervision for music. Available: https://gclef-cmu.org/pianobench.
Large language model agents automate web penetration testing through observation-action loops, enabling defenders to influence decisions with deceptive decoy observations. Advanced agents can recognize and bypass static decoys, then refocus on real targets. We propose AgentSnare, a trajectory-adaptive deception system that expands a decoy environment alongside exploration. For online deployment, ShadowOS combines an LLM-driven decoy constructor with a virtual kernel. Conditioned on exploration, it generates decoy artifacts that the kernel materializes and handles consistently across interactions, sustaining long-horizon exploration. Because deploying a powerful LLM for decoy construction is costly and slow, we train a small LLM using an offline adversarial interaction-simulation framework. It synthesizes multi-round trajectories by generating candidates and retaining those that sustain simulated interactions. Across 15 CVE-Bench web applications and four attacker models, AgentSnare absorbs 49.9% of tool calls to delay attacks, retains 57.2% of post-entry actions in the decoy to divert trajectories, and grounds 89.5% of completion reports in decoy evidence to defuse threats; across 60 attacker-CVE pairs, no real target is exploited at pass@3.