Yang Shengjie, Xue Jiaqi, Li Ziqi, Zhang Shiqing, Zhang Zhang, Huang Zhifeng, Yung Ken Kin Lam, Lai King Wai Chiu
Department of Biomedical Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Kowloon, Hong Kong SAR, China.
JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, College of Pharmacy, Jinan University, 601 West Huangpu Road, Tianhe, Guangzhou, 510632, China.
Adv Sci (Weinh). 2025 Mar;12(12):e2404166. doi: 10.1002/advs.202404166. Epub 2024 Dec 31.
The patch clamp technique is a fundamental tool for investigating ion channel dynamics and electrophysiological properties. This study proposes the first artificial intelligence framework for characterizing multiple ion channel kinetics of whole-cell recordings. The framework integrates machine learning for anomaly detection and deep learning for multi-class classification. The anomaly detection excludes recordings that are incompatible with ion channel behavior. The multi-class classification combined a 1D convolutional neural network, bidirectional long short-term memory, and an attention mechanism to capture the spatiotemporal patterns of the recordings. The framework achieves an accuracy of 97.58% in classifying 124 test datasets into six categories based on ion channel kinetics. The utility of the novel framework is demonstrated in two applications: Alzheimer's disease drug screening and nanomatrix-induced neuronal differentiation. In drug screening, the framework illustrates the inhibitory effects of memantine on endogenous channels, and antagonistic interactions among potassium, magnesium, and calcium ion channels. For nanomatrix-induced differentiation, the classifier indicates the effects of differentiation conditions on sodium and potassium channels associated with action potentials, validating the functional properties of differentiated neurons for Parkinson's disease treatment. The proposed framework is promising for enhancing the efficiency and accuracy of ion channel kinetics analysis in electrophysiological research.
膜片钳技术是研究离子通道动力学和电生理特性的基本工具。本研究提出了首个用于表征全细胞记录中多种离子通道动力学的人工智能框架。该框架将用于异常检测的机器学习和用于多类分类的深度学习相结合。异常检测排除了与离子通道行为不兼容的记录。多类分类结合了一维卷积神经网络、双向长短期记忆和注意力机制,以捕捉记录的时空模式。该框架在根据离子通道动力学将124个测试数据集分为六类时,准确率达到了97.58%。在两项应用中证明了该新型框架的实用性:阿尔茨海默病药物筛选和纳米基质诱导的神经元分化。在药物筛选中,该框架阐明了美金刚对内源性通道的抑制作用,以及钾、镁和钙离子通道之间的拮抗相互作用。对于纳米基质诱导的分化,分类器表明分化条件对与动作电位相关的钠和钾通道的影响,验证了分化神经元用于帕金森病治疗的功能特性。所提出的框架有望提高电生理研究中离子通道动力学分析的效率和准确性。
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