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Anti-senescent drug screening by deep learning-based morphology senescence scoring
Nat Commun. 2021 Jan 11;12(1):257. doi: 10.1038/s41467-020-20213-0.
Dai Kusumoto 1 2, Tomohisa Seki 3, Hiromune Sawada 1, Akira Kunitomi 4, Toshiomi Katsuki 1, Mai Kimura 1, Shogo Ito 1, Jin Komuro 1, Hisayuki Hashimoto 1 2, Keiichi Fukuda 1, Shinsuke Yuasa 5
Abstract:
...The accuracy of image classification tasks has improved owing to the establishment of convolutional neural networks (CNN). Cellular senescence is a hallmark of ageing and is important for the pathogenesis of ageing-related diseases. Furthermore, it is a potential therapeutic target. Specific molecular markers are used to identify senescent cells. Moreover senescent cells show unique morphology, which can be identified. We develop a successful morphology-based CNN system to identify senescent cells and a quantitative scoring system to evaluate the state of endothelial cells by senescence probability output from pre-trained CNN optimised for the classification of cellular senescence, Deep Learning-Based Senescence Scoring System by Morphology (Deep-SeSMo). Deep-SeSMo correctly evaluates the effects of well-known anti-senescent reagents. We screen for drugs that control cellular senescence using a kinase inhibitor library by Deep-SeSMo-based drug screening and identify four anti-senescent drugs. RNA sequence analysis reveals that these compounds commonly suppress senescent phenotypes through inhibition of the inflammatory response pathway. Thus, morphology-based CNN system can be a powerful tool for anti-senescent drug screening.
PMID: 33431893
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801636/
Tags: Drug discovery, Machine learning, senolytics