arXiv:2512.14011cs.LGq-bio.QM2025-12KDD

构建多尺度抗原呈递数据集,提升MHC-II表位预测精度。

Accelerating MHC-II Epitope Discovery via Multi-Scale Prediction in Antigen Presentation

  • 基于多源数据构建标准化的肽-MHC-II数据集,引入生物上下文信息。
  • 设计三阶段机器学习任务,覆盖结合、呈递到抗原呈递全过程。
  • 提出多尺度评估框架,为免疫治疗模型提供可复现基准。

主要组织相容性复合体II类(MHC-II)蛋白呈递的抗原表位在免疫治疗中起关键作用。然而,与计算免疫学中研究更广泛的MHC-I相比,MHC-II表位研究面临更大挑战,因其结合特异性复杂且基序模式模糊。现有MHC-II互作数据集规模小且标准化程度低。为此,我们从免疫表位数据库(IEDB)及其他公开来源构建了一个精心整理的数据集,不仅扩展并标准化了现有肽-MHC-II数据集,还引入了更具生物学背景的抗原-MHC-II数据集。基于该数据集,我们定义了三个机器学习任务:肽结合、肽呈递和抗原呈递,逐步捕捉MHC-II抗原呈递通路中的更广泛生物学过程。我们进一步采用多尺度评估框架来评测现有模型,并对多种建模方案进行系统分析,构建模块化框架。本工作为推进计算免疫治疗提供了宝贵资源,为未来基于机器学习的表位发现及免疫反应预测建模奠定基础。

原文摘要 · Abstract (English)

Antigenic epitope presented by major histocompatibility complex II (MHC-II) proteins plays an essential role in immunotherapy. However, compared to the more widely studied MHC-I in computational immunotherapy, the study of MHC-II antigenic epitope poses significantly more challenges due to its complex binding specificity and ambiguous motif patterns. Consequently, existing datasets for MHC-II interactions are smaller and less standardized than those available for MHC-I. To address these challenges, we present a well-curated dataset derived from the Immune Epitope Database (IEDB) and other public sources. It not only extends and standardizes existing peptide-MHC-II datasets, but also introduces a novel antigen-MHC-II dataset with richer biological context. Leveraging this dataset, we formulate three major machine learning (ML) tasks of peptide binding, peptide presentation, and antigen presentation, which progressively capture the broader biological processes within the MHC-II antigen presentation pathway. We further employ a multi-scale evaluation framework to benchmark existing models, along with a comprehensive analysis over various modeling designs to this problem with a modular framework. Overall, this work serves as a valuable resource for advancing computational immunotherapy, providing a foundation for future research in ML guided epitope discovery and predictive modeling of immune responses.

免疫计算MHC-II表位预测多尺度建模

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