提出可解释的TCR-pMHC结合预测模型,让算法决策过程透明可查。
TCR-EML: Explainable Model Layers for TCR-pMHC Prediction
- 设计原型层模拟已知结合机制,直接嵌入蛋白质语言模型中
- 在大规模数据集上达到与黑箱模型相当的预测准确率
- 解释能力优于现有方法,适合免疫治疗研发人员使用
T细胞受体(TCR)识别肽段-MHC复合物是适应性免疫的核心,对疫苗设计、癌症免疫治疗和自身免疫病具有重要意义。尽管机器学习显著提升了TCR-pMHC结合预测性能,但主流方法多为无法解释的黑箱变压器模型。后处理解释方法虽能分析输入影响,却无法显式建模生化机制(如已知结合区域)。我们提出可解释模型层(TCR-EML),可嵌入蛋白质语言模型以实现TCR-pMHC建模。该方法采用源自已知结合机制的氨基酸残基接触原型层,实现高质量预测解释。在大规模数据集上的实验表明其具备竞争性预测精度与泛化能力;在TCR-XAI基准测试中,解释性能显著优于现有方法。
原文摘要 · Abstract (English)
T cell receptor (TCR) recognition of peptide-MHC (pMHC) complexes is a central component of adaptive immunity, with implications for vaccine design, cancer immunotherapy, and autoimmune disease. While recent advances in machine learning have improved prediction of TCR-pMHC binding, the most effective approaches are black-box transformer models that cannot provide a rationale for predictions. Post-hoc explanation methods can provide insight with respect to the input but do not explicitly model biochemical mechanisms (e.g. known binding regions), as in TCR-pMHC binding. ``Explain-by-design'' models (i.e., with architectural components that can be examined directly after training) have been explored in other domains, but have not been used for TCR-pMHC binding. We propose explainable model layers (TCR-EML) that can be incorporated into protein-language model backbones for TCR-pMHC modeling. Our approach uses prototype layers for amino acid residue contacts drawn from known TCR-pMHC binding mechanisms, enabling high-quality explanations for predicted TCR-pMHC binding. Experiments of our proposed method on large-scale datasets demonstrate competitive predictive accuracy and generalization, and evaluation on the TCR-XAI benchmark demonstrates improved explainability compared with existing approaches.
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