Chuang Cheng-Che, Liu Yu-Chen, Jhang Wei-En, Wei Sin-Siang, Ou Yu-Yen
Department of Computer Science and Engineering, Yuan Ze University, Chung-Li 32003, Taiwan.
Graduate Program in Biomedical Informatics, Yuan Ze University, Chung-Li 32003, Taiwan.
J Chem Inf Model. 2025 Mar 10;65(5):2685-2694. doi: 10.1021/acs.jcim.4c02144. Epub 2025 Feb 19.
Interleukin-6 (IL-6) is a critical cytokine involved in immune regulation, inflammation, and the pathogenesis of various diseases, including autoimmune disorders, cancer, and the cytokine storm associated with severe COVID-19. Identifying IL-6 inducing epitopes, the short peptide fragments that trigger IL-6 production, is crucial for developing epitope-based vaccines and immunotherapies. However, traditional methods for epitope prediction often lack accuracy and efficiency. This study presents RAG_MCNNIL6, a novel deep learning framework that integrates Retrieval-augmented generation (RAG) with multiwindow convolutional neural networks (MCNNs) for accurate and rapid prediction of IL-6 inducing epitopes. RAG_MCNNIL6 leverages ProtTrans, a state-of-the-art pretrained protein language model, to generate rich embedding representations of peptide sequences. By incorporating a RAG-based similarity retrieval and embedding augmentation strategy, RAG_MCNNIL6 effectively captures both local and global sequence patterns relevant for IL-6 induction, significantly improving prediction performance compared to existing methods. We demonstrate the superior performance of RAG_MCNNIL6 on benchmark data sets, highlighting its potential for advancing research and therapeutic development for IL-6-mediated diseases.
白细胞介素-6(IL-6)是一种关键的细胞因子,参与免疫调节、炎症以及包括自身免疫性疾病、癌症和与严重COVID-19相关的细胞因子风暴在内的各种疾病的发病机制。识别IL-6诱导表位(即触发IL-6产生的短肽片段)对于开发基于表位的疫苗和免疫疗法至关重要。然而,传统的表位预测方法往往缺乏准确性和效率。本研究提出了RAG_MCNNIL6,这是一种新颖的深度学习框架,它将检索增强生成(RAG)与多窗口卷积神经网络(MCNN)相结合,用于准确快速地预测IL-6诱导表位。RAG_MCNNIL6利用最先进的预训练蛋白质语言模型ProtTrans来生成肽序列的丰富嵌入表示。通过结合基于RAG的相似性检索和嵌入增强策略,RAG_MCNNIL6有效地捕捉了与IL-6诱导相关的局部和全局序列模式,与现有方法相比,显著提高了预测性能。我们在基准数据集上展示了RAG_MCNNIL6的卓越性能,突出了其在推进IL-6介导疾病的研究和治疗开发方面的潜力。