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ADCNet:预测抗体药物偶联物活性的统一框架。

ADCNet: a unified framework for predicting the activity of antibody-drug conjugates.

作者信息

Chen Liye, Li Biaoshun, Chen Yihao, Lin Mujie, Zhang Shipeng, Li Chenxin, Pang Yu, Wang Ling

机构信息

Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, Joint International Research Laboratory of Synthetic Biology and Medicine, Guangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals, School of Biology and Biological Engineering, South China University of Technology, No. 382 Waihuan East Road, Higher Education Mega Center, Guangzhou 510006, China.

出版信息

Brief Bioinform. 2025 May 3;26(3). doi: 10.1093/bib/bbaf228.

Abstract

Antibody-drug conjugates (ADCs) have revolutionized the field of cancer treatment in the era of precision medicine due to their ability to precisely target cancer cells and release highly effective drugs. Nevertheless, the rational design and discovery of ADCs remain challenging because the relationship between their quintuple structures and activities is difficult to explore and understand. To address this issue, we first introduce a unified deep learning framework called ADCNet to explore such relationship and help design potential ADCs. The ADCNet highly integrates the protein representation learning language model ESM-2 and small-molecule representation learning language model functional group-based bidirectional encoder representations from transformers to achieve activity prediction through learning meaningful features from antigen and antibody protein sequences of ADC, SMILES strings of linker and payload, and drug-antibody ratio (DAR) value. Based on a carefully designed and manually tailored ADC data set, extensive evaluation results reveal that ADCNet performs best on the test set compared to baseline machine learning models across all evaluation metrics. For example, it achieves an average prediction accuracy of 87.12%, a balanced accuracy of 0.8689, and an area under receiver operating characteristic curve of 0.9293 on the test set. In addition, cross-validation, ablation experiments, and external independent testing results further prove the stability, advancement, and robustness of the ADCNet architecture. For the convenience of the community, we develop the first online platform (https://ADCNet.idruglab.cn) for the prediction of ADCs activity based on the optimal ADCNet model, and the source code is publicly available at https://github.com/idrugLab/ADCNet.

摘要

抗体药物偶联物(ADCs)在精准医学时代彻底改变了癌症治疗领域,因为它们能够精确靶向癌细胞并释放高效药物。然而,ADCs的合理设计和发现仍然具有挑战性,因为其五元结构与活性之间的关系难以探索和理解。为了解决这个问题,我们首先引入了一个名为ADCNet的统一深度学习框架来探索这种关系,并帮助设计潜在的ADCs。ADCNet高度集成了蛋白质表示学习语言模型ESM-2和小分子表示学习语言模型基于功能基团的双向编码器表示(来自Transformer),通过从ADC的抗原和抗体蛋白质序列、连接子和有效载荷的SMILES字符串以及药物-抗体比(DAR)值中学习有意义的特征来实现活性预测。基于精心设计和人工定制的ADC数据集,广泛的评估结果表明,与所有评估指标上的基线机器学习模型相比,ADCNet在测试集上表现最佳。例如,它在测试集上实现了87.12%的平均预测准确率、0.8689的平衡准确率和0.9293的受试者工作特征曲线下面积。此外,交叉验证、消融实验和外部独立测试结果进一步证明了ADCNet架构的稳定性、先进性和鲁棒性。为了方便社区使用,我们基于最优的ADCNet模型开发了第一个用于预测ADCs活性的在线平台(https://ADCNet.idruglab.cn),并且源代码可在https://github.com/idrugLab/ADCNet上公开获取。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0e0/12107246/0f9c7825281f/bbaf228f1.jpg

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