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利用人工智能进行基于诱导多能干细胞的药物筛选。

Induced Pluripotent Stem Cell-Based Drug Screening by Use of Artificial Intelligence.

作者信息

Kusumoto Dai, Yuasa Shinsuke, Fukuda Keiichi

机构信息

Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Center for Preventive Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

出版信息

Pharmaceuticals (Basel). 2022 Apr 30;15(5):562. doi: 10.3390/ph15050562.

Abstract

Induced pluripotent stem cells (iPSCs) are terminally differentiated somatic cells that differentiate into various cell types. iPSCs are expected to be used for disease modeling and for developing novel treatments because differentiated cells from iPSCs can recapitulate the cellular pathology of patients with genetic mutations. However, a barrier to using iPSCs for comprehensive drug screening is the difficulty of evaluating their pathophysiology. Recently, the accuracy of image analysis has dramatically improved with the development of artificial intelligence (AI) technology. In the field of cell biology, it has become possible to estimate cell types and states by examining cellular morphology obtained from simple microscopic images. AI can evaluate disease-specific phenotypes of iPS-derived cells from label-free microscopic images; thus, AI can be utilized for disease-specific drug screening using iPSCs. In addition to image analysis, various AI-based methods can be applied to drug development, including phenotype prediction by analyzing genomic data and virtual screening by analyzing structural formulas and protein-protein interactions of compounds. In the future, combining AI methods may rapidly accelerate drug discovery using iPSCs. In this review, we explain the details of AI technology and the application of AI for iPSC-based drug screening.

摘要

诱导多能干细胞(iPSC)是终末分化的体细胞,可分化为多种细胞类型。由于iPSC分化而来的细胞能够重现基因突变患者的细胞病理学特征,因此有望用于疾病建模和开发新的治疗方法。然而,将iPSC用于全面药物筛选的一个障碍是评估其病理生理学的困难。近年来,随着人工智能(AI)技术的发展,图像分析的准确性有了显著提高。在细胞生物学领域,通过检查从简单显微镜图像中获得的细胞形态来估计细胞类型和状态已成为可能。人工智能可以从无标记显微镜图像中评估iPSC衍生细胞的疾病特异性表型;因此,人工智能可用于使用iPSC进行疾病特异性药物筛选。除了图像分析外,各种基于人工智能的方法也可应用于药物开发,包括通过分析基因组数据进行表型预测以及通过分析化合物的结构式和蛋白质-蛋白质相互作用进行虚拟筛选。未来,结合人工智能方法可能会迅速加速使用iPSC的药物发现。在这篇综述中,我们解释了人工智能技术的细节以及人工智能在基于iPSC的药物筛选中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edab/9145330/744d85aba48e/pharmaceuticals-15-00562-g001.jpg

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