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Gene print-based cell subtypes annotation of human disease across heterogeneous datasets with gPRINT

摘要Identification of disease-specific cell subtypes(DSCSs)has profound implications for understanding disease mech-anisms,preoperative diagnosis,and precision therapy.However,achieving unified annotation of DSCSs in hetero-geneous single-cell datasets remains a challenge.In this study,we developed the gPRINT algorithm(generalized approach for cell subtype identification with single cell's voicePRINT).Inspired by the principles of speech recog-nition in noisy environments,gPRINT transforms gene position and gene expression information into voiceprints based on ordered and clustered gene expression phenomena,obtaining unique"gene print"patterns for each cell.Then,we integrated neural networks to mitigate the impact of background noise on cell identity label mapping.We demonstrated the reproducibility of gPRINT across different donors,single-cell sequencing platforms,and disease subtypes,and its utility for automatic cell subtype annotation across datasets.Moreover,gPRINT achieved higher annotation accuracy of 98.37%when externally validated based on the same tissue,surpassing other algorithms.Furthermore,this approach has been applied to fibrosis-associated diseases in multiple tissues throughout the body,as well as to the annotation of fibroblast subtypes in a single tissue,tendon,where fibrosis is prevalent.We successfully achieved automatic prediction of tendinopathy-specific cell subtypes,key targets,and related drugs.In summary,gPRINT provides an automated and unified approach for identifying DSCSs across datasets,facilitating the elucidation of specific cell subtypes under different disease states and providing a powerful tool for exploring therapeutic targets in diseases.

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作者 Ruojin Yan [1] Chunmei Fan [2] Shen Gu [3] Tingzhang Wang [4] Zi Yin [5] Xiao Chen [6] 学术成果认领
作者单位 Department of Orthopedic Surgery of Sir Run Run Shaw Hospital,and Liangzhu Laboratory,Zhejiang University School of Medicine,Hangzhou 310011,China [1] Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province,Department of Clinical Medicine,School of Medicine,Hangzhou City University,Hangzhou 310015,China;Department of Sports Medicine & Orthopedic Surgery,The Second Affiliated Hospital,and Dr.Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine,Zhejiang University School of Medicine,Hangzhou 310011,China [2] School of Biomedical Sciences,Faculty of Medicine,the Chinese University of Hong Kong,Hong Kong SAR,China;Key Laboratory for Regenerative Medicine,Ministry of Education,School of Biomedical Sciences,Faculty of Medicine,the Chinese University of Hong Kong,Hong Kong SAR,China;Kunming Institute of Zoology Chinese Academy of Sciences,the Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research of Common Diseases,Hong Kong SAR,China [3] Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province,Hangzhou 310000,China [4] Department of Orthopedic Surgery of Sir Run Run Shaw Hospital,and Liangzhu Laboratory,Zhejiang University School of Medicine,Hangzhou 310011,China;Institute of Cell Biology,Zhejiang University,Hangzhou 310058,China [5] Department of Sports Medicine & Orthopedic Surgery,The Second Affiliated Hospital,and Dr.Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine,Zhejiang University School of Medicine,Hangzhou 310011,China;State Key Laboratory of Transvascular Implantation Devices,Hangzhou 310009,China [6]
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DOI 10.1093/procel/pwaf001
发布时间 2025-09-12(万方平台首次上网日期,不代表论文的发表时间)
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蛋白质与细胞

蛋白质与细胞

2025年16卷8期

685-704页

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