#01Nov 3, 2026
cs.LG
iGC: Antibody Optimization via Reinforcement Learning over a Learned Somatic Hypermutation Prior
Thao Nguyen, Robert G. Alberstein, Ewa Nowara and 10 more
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.
#02Nov 3, 2026
cs.LG
Post-Inference Model Chaining: A Problem Statement and a Model-based Bootstrap for Training End-to-End Digital Twins
Lukas Madenach, Timo Bailer, Tobias Eilert
End-to-end digital twins can be constructed by fitting separate stage models and connecting them after inference. We investigate the Frequentist prediction properties of a commonly used Monte Carlo simulation scheme that forwards complete predictive draws through such a chain when measured stage outputs contain independent normal errors, but the latent stage means are deterministic. Analytical two-stage examples show persistent asymptotic interval and coverage inflation and, with quadratic propagation, mean bias dependent on the parameters to be estimated. Simulations of four- and eight-stage linear-quadratic univariate chains with 7, 15 or 30 training runs demonstrate pronounced input-dependent distortions. A diagnostic using error-free latent training predictors shows that the effect is mainly not attributable to errors in variables, but to the MCSim approach even showing underestimation of coverage. We propose a model-based bootstrap: an initial chain forwards fitted means, bootstrap chains are refitted on fixed-center bootstrap data while forwarding their mean prediction, and a target-stage future error enters a studentized prediction root. Across the investigated scenarios, relative mean bias is substantially reduced, and coverage is closer to the nominal 90%. At sample size 30, the eight-stage bootstrap has mean width ratios of 1.16-1.42 relative to the known-parameter normal reference, compared with 4.11-4.97 for observed-to-observed MCSim. These results support improved endpoint prediction in the tested setting. Further investigations of the bootstrap scheme in the supplement for a bivariate 6-stage process show similar satisfactory results.
#03Nov 3, 2026
cs.CL
Suppressing Misaligned Behaviors in Language Models, Durably
Luxi He, Pengcheng Jiang, Jifan Zhang and 2 more
Undesired model behaviors can emerge or re-emerge at any stage of training. Once observed, how effectively can we suppress them? To study this question, we first construct two model organisms--language models deliberately trained to exhibit a specific misalignment--that differ in what triggers the behavior. The narrow-trigger organism misbehaves only when the prompt contains a specific cue: it cheats on multiple-choice questions by following a planted hint that points to a wrong answer, and behaves normally otherwise. The broad-trigger organism has no such cue: after fine-tuning on insecure code, it gives harmful responses across a wide range of open-ended prompts. We then formalize post-hoc behavioral suppression and evaluate methods along three criteria: immediate suppression of the target behavior, durability under further training, and preservation of general capability. We compare standard methods--SFT, GRPO, and gradient-ascent unlearning--along these dimensions. Building on prior work on alignment shallowness, we hypothesize that more durable suppression requires the ability to recover from a wider range of misalignment states. We introduce Prefix-Expanded Adversarial Reinforcement Learning (PEARL), a GRPO variant that augments rollouts with continuations from intermediate states sampled along cached organism trajectories. Across both organism settings and two model families (Qwen3-4B, GPT-OSS-20B), PEARL achieves strong immediate suppression while preserving task accuracy, and remains durable under further fine-tuning on either the organism's data or unrelated data. It obtains the greatest benefit when the undesirable behavior is broad and cannot be addressed through targeted SFT. Together, our framework and method offer a step toward more durable post-hoc removal of undesired behaviors.
#04Nov 3, 2026
cs.RO
GSBR: Geometric Support Behavior Regularization for Online RL
Charles Xu, Jacob Berg, Liyiming Ke and 1 more
Regularizing online reinforcement learning (RL) toward a pretrained base policy can improve sample efficiency and learning stability, but regularization that is too restrictive limits how much the policy can improve. Base policies -- typically diffusion or flow-matching models trained by imitation learning on large, diverse datasets -- capture many behaviors that are reasonable but suboptimal. Existing regularizers using such base policies are too restrictive in one of two ways: behavioral cloning regularizers pull the actor toward the full base-policy distribution, penalizing it for discarding suboptimal modes, while hard support constraints forbid improvements that lie just outside the base policy's support. We propose Geometric Support Behavior Regularization (GSBR), which penalizes actions by their distance from the base policy's support. Actions within the support incur no penalty, so the actor can concentrate on high-value modes; outside the support, where value estimates are less reliable, the penalty grows smoothly with distance while still permitting improvement when the value gained outweighs the penalty. GSBR estimates this distance from a finite set of base-policy samples, so it requires only sample access to the base policy. Across 19 tasks on four robotic benchmarks, GSBR raises the average success rate from 33% for the base policy to 95%, achieving the highest average success rate and throughput among all compared methods, with about 23% higher normalized throughput than the next-best RL method. Project website and open-source code at https://charlesxu0124.github.io/gsbr/ .
#05Nov 3, 2026
cs.CL
A Circuit for In-Context Learning
Andrew Gao, William Gao
In-context learning (ICL) lets a pretrained language model perform a task specified by demonstrations in its prompt, with no parameter updates. With arbitrary labels the model must acquire a mapping it cannot have memorized, so the learning happens within a single forward pass. Prior work found candidate parts but not how they compose. We give the composition for few-shot sentence classification with arbitrary labels in three 3-4B-parameter transformers. The model implements a key-value memory over label-token positions: each label token's residual stream encodes the label's identity, and middle-layer attention heads write into it the class of the preceding demonstration as its key. At the query, upper-layer heads match the query's class against the stored keys and copy out the matching labels. An early-layer signal encoding whether any label has repeated gates this readout; in its absence the readers attend to the start of the prompt and no label is favored. A separate set of heads suppresses the most recently seen label. Each step is established causally by activation patching, head ablations against random-head baselines, and steering with the model's own signals. A softmax model of the readout with two constants per head, fit on one prompt distribution, predicts another. The computation is conserved across the three models, the named heads alone reproduce the behaviour, and a transformer trained from scratch grows the same parts. The circuit transfers to semantic concepts and to labels with meaning, and the same parts, with a causal gate, appear from 0.6B to 8B in one family and survive instruction tuning. ICL in this setting is a gated associative lookup built from a few identifiable component types, traced causally from demonstrations to prediction.