Xinyan Zhao, Yi-Ching Tang, Victor J Cantu, Junseok Lee, Adam E Stogsdill, Ibraheem M Hamdi, Ashwin Kumar Ramesh, Zhiqiang An 等 10 位作者
Computational antibody design requires benchmarks that measure functional binding rather than similarity to natural sequences. Here we present AbBiBench, which treats the antibody--antigen complex as the evaluation unit and harmonizes 216,560 experimental measurements spanning 13 antibodies and 9 antigens. We compare 20 computational approaches without task-specific training or fine-tuning. The analyses show that global structure-conditioned inverse folding yields the strongest and most consistent affinity rankings, whereas antibody-specific fine-tuning does not consistently improve performance. Across models, rankings are more useful for prioritizing likely affinity gains than for excluding weak variants. In a subsequent case study, multi-objective evaluation of model-generated F045-092 CDR-H3 variants for H1N1 binding revealed a trade-off between predicted binding potential and evolutionary sequence plausibility; all 21 selected candidates produced H1-reactive ELISA signals. AbBiBench provides an open framework for developing and evaluating function-aware antibody design methods.
With the growing use of language models (LMs) in clinical environments, there is an immediate need to evaluate the accuracy and safety of LM-generated medical text. Currently, such evaluation relies solely on manual physician review. However, detecting errors in LM-generated text is challenging because 1) manual review is costly and 2) expert-composed reference outputs are often unavailable in real-world settings. While the "LLM-as-a-judge" paradigm offers scalable evaluation, even frontier LMs can miss subtle but clinically significant errors. We propose MedVAL, a novel, self-supervised, data-efficient distillation method that leverages synthetic data to train evaluator LMs to assess whether LM-generated medical outputs are factually consistent with inputs, without requiring physician labels or reference outputs. To evaluate LM performance, we introduce MedVAL-Bench, a dataset of 840 physician-annotated outputs across 6 diverse medical tasks capturing real-world challenges. Across 10 state-of-the-art LMs spanning open-source and proprietary models, MedVAL distillation significantly improves (p < 0.001) alignment with physicians across seen and unseen tasks, increasing average F1 scores from 66% to 83%. Despite strong baseline performance, MedVAL improves the best-performing proprietary LM (GPT-4o) by 8% without training on physician-labeled data, demonstrating a performance statistically non-inferior to a single human expert on a subset annotated by multiple physicians (p < 0.001). To support a scalable, risk-aware pathway towards clinical integration, we open-source: 1) Codebase (https://github.com/StanfordMIMI/MedVAL), 2) MedVAL-Bench (https://huggingface.co/datasets/stanfordmimi/MedVAL-Bench), 3) MedVAL-4B (https://huggingface.co/stanfordmimi/MedVAL-4B). Our benchmark provides evidence of LMs approaching expert-level ability in validating AI-generated medical text.