蛋白质语言模型中的残基级归因无法恢复过敏原表位 / Residue-Level Attributions in Protein Language Models Do Not Recover Allergen Epitopes
1️⃣ 一句话总结
这项研究发现,当前的蛋白质过敏原预测模型虽然能准确判断蛋白质是否具有致敏性,但它们解释模型为何如此判断的归因方法(如关注特定氨基酸残基)并不能真正定位到生物学上有意义的过敏原表位,因此不能直接用于安全性评估或设计低过敏原蛋白。
Deep allergenicity classifiers are increasingly used in safety screening of novel foods, and recent protein language models have substantially improved protein-level allergenicity prediction. However, whether their explanations capture biologically meaningful information remains unclear. We introduce an epitope-grounded residue-level benchmark for quantitatively evaluating attribution faithfulness in protein allergenicity models. Across frozen ESM-2, multi-task ESM-2, and DeepPlantAllergy, protein-level classification was robust, yet classification-head explanation signals did not significantly exceed random in their residue-level alignment with annotated epitopes across AUROC, AUPRC, and Precision@k. Integrated Gradients identified residues that were functionally important to the model, but not overlapping annotated epitopes. Saturation mutagenesis further suggested classifiers may rely on physicochemical and compositional sequence features rather than epitope-specific mechanisms. Residue-level importance signals should therefore not be interpreted as immunological explanations for safety screening or hypoallergen design without quantitative validation. Code available: this https URL
蛋白质语言模型中的残基级归因无法恢复过敏原表位 / Residue-Level Attributions in Protein Language Models Do Not Recover Allergen Epitopes
这项研究发现,当前的蛋白质过敏原预测模型虽然能准确判断蛋白质是否具有致敏性,但它们解释模型为何如此判断的归因方法(如关注特定氨基酸残基)并不能真正定位到生物学上有意义的过敏原表位,因此不能直接用于安全性评估或设计低过敏原蛋白。
源自 arXiv: 2606.22181